WO2003102159A2 - Novel proteins and nucleic acids encoding same - Google Patents

Novel proteins and nucleic acids encoding same Download PDF

Info

Publication number
WO2003102159A2
WO2003102159A2 PCT/US2003/017573 US0317573W WO03102159A2 WO 2003102159 A2 WO2003102159 A2 WO 2003102159A2 US 0317573 W US0317573 W US 0317573W WO 03102159 A2 WO03102159 A2 WO 03102159A2
Authority
WO
WIPO (PCT)
Prior art keywords
novx
polypeptide
nucleic acid
cell
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2003/017573
Other languages
French (fr)
Other versions
WO2003102159A3 (en
Inventor
John P. Ii Alsobrook
David W. Anderson
Jason C. Baumgartner
Constance Berghs
Ferenc L. Boldog
Catherine E. Burgess
Stacie J. Casman
Elina Catterton
Mohanraj Dhanabal
Shlomit R. Edinger
Karen Ellerman
Seth Ettenberg
Esha A. Gangolli
Valerie L. Gerlach
Linda Gorman
William M. Grosse
Erik Gunther
Xiaojia Guo
Vladimir Y. Gusev
John L. Herrmann
Weizhen Ji
Ramesh Kekuda
Nikolai V. Khramtsov
William J. Larochelle
Li Li
Hongping Liang
Kenneth Low
John R. Macdougall
Timothy Maclachlan
Uriel M. Malyankar
Kelly Mcqueeney
Amanda J. Mezick
Charles E. Miller
Isabelle Millet
Muralidhara Padigaru
Meera Patturajan
John A. Peyman
Xiaozhong Qian
Luca Rastelli
Daniel K. Rieger
Mark E. Rothenberg
Suresh G. Shenoy
Richard A. Shimkets
Glennda Smithson
Kimberly A. Spytek
David J. Stone
Sujatha Sukumaran
Edward S. Szekeres, Jr.
Corine A. M. Vernet
Edward Z. Voss
Adam R. Wolenc
Mei Zhong
Haihong Zhong
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CuraGen Corp
Original Assignee
CuraGen Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CuraGen Corp filed Critical CuraGen Corp
Priority to EP03817179A priority Critical patent/EP1590480A2/en
Priority to CA002488539A priority patent/CA2488539A1/en
Priority to AU2003256263A priority patent/AU2003256263A1/en
Publication of WO2003102159A2 publication Critical patent/WO2003102159A2/en
Anticipated expiration legal-status Critical
Publication of WO2003102159A3 publication Critical patent/WO2003102159A3/en
Ceased legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Definitions

  • the present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.
  • Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are extremely highly balanced to achieve the preservation and propagation of the cells.
  • the regulation of the biochemical and physiological processes involves intricate signaling pathways.
  • signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells.
  • Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors.
  • Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue.
  • the target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced.
  • Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid.
  • the second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect.
  • Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor.
  • the autocrine effector binds to receptors on the same cell, or on identical neighboring cells.
  • the binding process then elicits the characteristic biochemical or physiological effect.
  • Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.
  • pathological conditions involve dysregulation of expression of important effector proteins.
  • the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors.
  • the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors.
  • a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture.
  • Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.
  • Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states.
  • Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target.
  • the target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes.
  • Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.
  • the invention includes nucleic acid sequences and the novel polypeptides they encode.
  • the novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides.
  • NOVX nucleic acid
  • NOVX represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566
  • polypeptide sequences which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566.
  • the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid.
  • a variant of a mature form of a NOVX amino acid sequence wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed.
  • the amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.
  • the invention also includes fragments of any of these.
  • the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.
  • NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence.
  • allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence.
  • NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution.
  • the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample.
  • the method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample.
  • the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject.
  • This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
  • the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide.
  • the agent is a cellular receptor or a downstream effector.
  • the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide.
  • the method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.
  • the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide.
  • This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide.
  • This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide.
  • the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene.
  • the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.
  • the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.
  • the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.
  • the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.
  • the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.
  • the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566, or a complement of the nucleotide sequence.
  • the invention provides a vector or a cell expressing a NOVX nucleotide sequence.
  • the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.
  • the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed.
  • the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.
  • the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed.
  • the invention includes the complement ofany of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant.
  • the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.
  • the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.
  • the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed.
  • the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.
  • the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence.
  • the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.
  • the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample.
  • the method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample.
  • the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.
  • the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject.
  • the method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
  • Fig. Dl Alignment of CG55806-04 (SEQ ID NO:748), CG55806-02 (SEQ ID NO:752), and 1PFX (SEQ ID NO: 1476).
  • Fig. D2 Structure of porcine factor IXa (1PFX).
  • Fig. El Data showing effect on cell growth by knockdown of CG59693-01.
  • Fig. E2 Data showing effect on cell growth by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (48 hr).
  • Fig. E3 Data showing effect on cell viability by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (48 hr).
  • Fig. E4 Data showing effect on cell growth by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (72 hr).
  • Fig. E5 Data showing effect on cell viability by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (72 hr).
  • Fig. E6 Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Gemcitabine.
  • Fig. E7 Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Daunorubicin.
  • Fig. E8 Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Etoposide.
  • Fig. E9 Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Etoposide.
  • Fig. E9 Data showing effect on cell growth by knockdown of CG59693-01 by
  • the present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds.
  • the sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.
  • Table A indicates the homology of NOVX polypeptides to known protein families.
  • nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.
  • Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to, e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hype ⁇ lasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic pu ⁇ ura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn'
  • NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts.
  • the various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.
  • NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.
  • the NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.
  • the NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g., detection of a variety of cancers. SNP analysis for each NOVX, if applicable, is presented in Example D.
  • NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts.
  • the various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.
  • the NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes.
  • NOVX genes based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.
  • the NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool.
  • nucleic acid or protein diagnostic and/or prognostic marker serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.
  • the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residue
  • the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566, in which any amino acid specified in the chosen sequence is changed
  • the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l , wherein n is an integer between 1 and 566 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence
  • nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX rnRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules.
  • nucleic acid molecule is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof.
  • the nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.
  • a NOVX nucleic acid can encode a mature NOVX polypeptide.
  • a "mature" form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein.
  • the naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the co ⁇ esponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein.
  • the product "mature" form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises.
  • Examples of such processing steps leading to a "mature" form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence.
  • a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine would have residues 2 through N remaining after removal of the N-terminal methionine.
  • a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+l to residue N remaining.
  • a "mature" form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation.
  • a mature polypeptide or protein may result from the operation of only one of these processes, or a combination ofany of them.
  • probe refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.
  • isolated nucleic acid molecule is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid.
  • an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5'- and 3'-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived.
  • the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.).
  • an "isolated" nucleic acid molecule such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.
  • a nucleic acid molecule of the invention e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n-l , wherein n is an integer between 1 and 566, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein.
  • NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2 nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989; and Ausubel, et al, (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993.)
  • a nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques.
  • nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis.
  • oligonucleotides co ⁇ esponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.
  • oligonucleotide refers to a series of linked nucleotide residues.
  • a short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue.
  • Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length.
  • an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2 «- 1 , wherein n is an integer between 1 and 566, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.
  • an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide).
  • binding means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like.
  • a physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.
  • a “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.
  • a full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the co ⁇ esponding full-length cDNA extend in the 5' direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the co ⁇ esponding full-length cDNA extend in the 3' direction of the disclosed sequence.
  • a “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution.
  • An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g., they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type.
  • a “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.
  • Derivatives and analogs may be full length or other than full length.
  • Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, ⁇ 0%, or 95% identity (with a prefe ⁇ ed identity of ⁇ O-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g., Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993, and below.
  • a "homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above.
  • Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes.
  • homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms.
  • homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein.
  • a homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein.
  • Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2/ ⁇ -l , wherein n is an integer between 1 and 566, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.
  • a NOVX polypeptide is encoded by the open reading frame ("ORF") of a NOVX nucleic acid.
  • An ORF co ⁇ esponds to a nucleotide sequence that could potentially be translated into a polypeptide.
  • a stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon.
  • An ORF that represents the coding sequence for a full protein begins with an ATG "start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA.
  • an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both.
  • a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.
  • the nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g., from other tissues, as well as NOVX homologues from other vertebrates.
  • the probe/primer typically comprises substantially purified oligonucleotide.
  • the oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566; or an anti-sense strand nucleotide sequence of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566; or of a naturally occurring mutant of SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566.
  • Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins.
  • the probe has a detectable label attached, e.g., the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor.
  • Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.
  • a polypeptide having a biologically-active portion of a NOVX polypeptide refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency.
  • a nucleic acid fragment encoding a "biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.
  • nucleic Acid and Polypeptide Variants The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566.
  • an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2 «, wherein n is an integer between 1 and 566.
  • DNA sequence polymo ⁇ hisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population).
  • Such genetic polymo ⁇ hism in the NOVX genes may exist among individuals within a population due to natural allelic variation.
  • the terms "gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein.
  • Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymo ⁇ hisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.
  • nucleic acid molecules encoding NOVX proteins from other species and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566, are intended to be within the scope of the invention.
  • Nucleic acid molecules co ⁇ esponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.
  • an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566.
  • the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length.
  • an isolated nucleic acid molecule of the invention hybridizes to the coding region.
  • the term "hybridizes under stringent conditions" is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.
  • Homologs i.e., nucleic acids encoding NOVX proteins derived from species other than human
  • other related sequences e.g., paralogs
  • stringent hybridization conditions refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium.
  • Tm thermal melting point
  • stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30 °C for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60 °C for longer probes, primers and oligonucleotides.
  • Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide. Stringent conditions are known to those skilled in the art and can be found in
  • the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other.
  • a non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6X SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65°C, followed by one or more washes in 0.2X SSC, 0.01% BSA at 50°C.
  • An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566, co ⁇ esponds to a naturally-occurring nucleic acid molecule.
  • a "naturally-occurring" nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).
  • a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2M-1 , wherein n is an integer between 1 and 566, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided.
  • moderate stringency hybridization conditions are hybridization in 6X SSC, 5X Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55 °C, followed by one or more washes in IX SSC, 0.1% SDS at 37 °C.
  • Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.
  • low stringency hybridization conditions are hybridization in 35% formamide, 5X SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40°C, followed by one or more washes in 2X SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50°C.
  • Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations).
  • nucleotide sequences of SEQ ID NO:2w-l wherein n is an integer between 1 and 566, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein.
  • nucleotide substitutions leading to amino acid substitutions at "non-essential" amino acid residues can be made in the sequence of SEQ ID NO:2w, wherein n is an integer between 1 and 566.
  • non-essential amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an "essential" amino acid residue is required for such biological activity.
  • amino acid residues that are conserved among the NOVX proteins of the invention are not particularly amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.
  • nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity.
  • NOVX proteins differ in amino acid sequence from SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566, yet retain biological activity.
  • the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2 «, wherein n is an integer between 1 and 566.
  • the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2 «, wherein n is an integer between 1 and 566; more preferably at least about 70% homologous to SEQ ID NO:2 ⁇ ., wherein n is an integer between 1 and 566; still more preferably at least about ⁇ 0% homologous to SEQ ID NO:2 «, wherein n is an integer between 1 and 566; even more preferably at least about 90% homologous to SEQ ID NO:2 » wherein n is an integer between 1 and 566; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 566.
  • An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2 «, wherein n is an integer between 1 and 566, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.
  • Mutations can be introduced any one of SEQ ID NO:2H-1 , wherein n is an integer between 1 and 566, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis.
  • conservative amino acid substitutions are made at one or more non-essential amino acid residues.
  • a "conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art.
  • amino acids with basic side chains e.g., lysine, arginine, histidine
  • acidic side chains e.g., aspartic acid, glutamic acid
  • uncharged polar side chains e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine
  • nonpolar side chains e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan
  • beta-branched side chains e.g., threonine, valine, isoleucine
  • aromatic side chains e.g., tyrosine, phenylalanine, tryptophan, histidine
  • a non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family.
  • mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity.
  • mutagenesis of a nucleic acid of SEQ ID NO:2 «-l wherein n is an integer between 1 and 566
  • the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.
  • amino acid families may also be determined based on side chain interactions.
  • Substituted amino acids may be fully conserved "strong” residues or fully conserved “weak” residues.
  • the "strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other.
  • the "weak" group of conserved residues may be any one of the following: CSA, ATN, SAG, ST ⁇ K, STPA, SG ⁇ D, S ⁇ DEQK, ⁇ DEQHK, ⁇ EQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.
  • a mutant ⁇ OVX protein can be assayed for (i) the ability to form protein:protein interactions with other ⁇ OVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant ⁇ OVX protein and a ⁇ OVX ligand; or (iii) the ability of a mutant ⁇ OVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g., avidin proteins).
  • a mutant ⁇ OVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release). Interfering RNA
  • NOVX gene expression can be attenuated by RNA interference.
  • RNA interference One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5' untranslated (UT) region, the ORF, or the 3' UT region.
  • siRNA short interfering RNA
  • Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene.
  • upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.
  • NOVX gene expression is silenced using short interfering RNA.
  • a NOVX polynucleotide according to the invention includes a siRNA polynucleotide.
  • a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence.
  • siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3' overhang.
  • sequence of the 2-nt 3' overhang makes an additional small contribution to the specificity of siRNA target recognition.
  • the nucleotides in the 3' overhang are ribonucleotides.
  • the nucleotides in the 3' overhang are deoxyribonucleotides. Using 2'-deoxyribonucleotides in the 3' overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.
  • a contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands.
  • An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3' of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5' of the cloned DNA).
  • the sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene.
  • two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct.
  • cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes.
  • a hai ⁇ in RNAi product is homologous to all or a portion of the target gene.
  • a hai ⁇ in RNAi product is a siRNA.
  • the regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.
  • siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA HI .
  • a vector system is the GeneSuppressor RNA Interference kit (commercially available from Imgenex).
  • the U6 and HI promoters are members of the type III class of Pol III promoters.
  • the +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for HI promoters is adenosine.
  • the termination signal for these promoters is defined by five consecutive thymidines.
  • the transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3' UU overhang in the expressed siRNA, which is similar to the 3' overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21 -nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.
  • a siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.
  • siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER.
  • DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex.
  • siRNP siRNAs/protein complex
  • RISC RNA-induced silencing complex
  • RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.
  • a NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon.
  • 5' or 3' UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites.
  • UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex.
  • An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6 ⁇ 77-88. Hence, consideration should be taken to accommodate SNPs, polymo ⁇ hisms, allelic variants or species-specific variations when targeting a desired gene.
  • a complete NOVX siRNA experiment includes the proper negative control.
  • a negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.
  • Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect.
  • expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide.
  • NOVX siRNA duplexes e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide.
  • Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.
  • a targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT).
  • a desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21).
  • the sequence of the NOVX sense siRNA co ⁇ esponds to (NI 9)TT or N21 , respectively. In the latter case, conversion of the 3' end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3' overhangs.
  • Symmetric 3' overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes & Dev. 15: 188-200, inco ⁇ orated by reference herein in its entirely.
  • the modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.
  • the NOVX target mRNA does not contain a suitable AA(N21) sequence
  • the sequence of the sense strand and antisense strand may still be synthesized as 5' (N19)TT, as it is believed that the sequence of the 3'-most nucleotide of the antisense siRNA does not contribute to specificity.
  • the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, inco ⁇ orated by reference in its entirety.
  • Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen).
  • An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes.
  • approximately 0.84 ⁇ g of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence.
  • the choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type.
  • the efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells.
  • the time and the manner of formation of siRNA-liposome complexes are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing.
  • the efficiency of transfection needs to be carefully examined for each new cell line to be used.
  • Prefe ⁇ ed cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human.
  • the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.
  • transfection of 0.84 ⁇ g single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 ⁇ g antisense siRNA has a weak silencing effect when compared to 0.84 ⁇ g of duplex siRNAs.
  • Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes.
  • targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a
  • CMV-driven EGFP-expression plasmid e.g., commercially available from Clontech.
  • a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression.
  • Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.
  • a knock-down phenotype may become apparent after 1 to 3 days, or even later.
  • depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transfe ⁇ ed to a fresh 24-well plate for re-transfection.
  • RNA RNA
  • RNA reverse transcribed using a target-specific primer
  • RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell.
  • transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.
  • An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or abe ⁇ ant NOVX expression or activity.
  • the NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above.
  • the NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above.
  • a NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues.
  • the present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation.
  • a specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.
  • a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like.
  • a subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state.
  • the NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product.
  • NOVX siRNA's are administered to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described.
  • This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX " ) phenotype in the treated subject sample.
  • NOVX " phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.
  • a NOVX siRNA is used in therapy.
  • Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.
  • Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors.
  • the sense and antisense RNA are about 500 bases in length each.
  • the produced ssRNA and asRNA (0.5 ⁇ M) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C for 1 min then cooled and annealed at room temperature for 12 to 16 h.
  • the RNAs are precipitated and resuspended in lysis buffer (below).
  • RNAs are elecfrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).
  • Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30° C for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double sfranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.
  • the double stranded RNA is internally radiolabeled with a 32 P-ATP. Reactions are stopped by the addition of 2X-proteinase-K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined. The band of double stranded RNA, about 21-23 bps, is eluded.
  • RNAs are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak CI 8 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).
  • RNAs (20 ⁇ M) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 90° C followed by 1 h at 37° C.
  • annealing buffer 100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate
  • a cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3 X 105 cells/ml) and transfe ⁇ ed to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3' ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used.
  • siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.
  • the above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression.
  • In vivo suppression may be performed using the same siRNA using well known in-vivo transfection or gene therapy transfection techniques.
  • Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2 «-l , wherein n is an integer between 1 and 566, or fragments, analogs or derivatives thereof.
  • An "antisense" nucleic acid comprises a nucleotide sequence that is complementary to a "sense" nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence).
  • antisense nucleic acid molecules comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof.
  • an antisense nucleic acid molecule is antisense to a "coding region" of the coding strand of a nucleotide sequence encoding a NOVX protein.
  • coding region refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues.
  • the antisense nucleic acid molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence encoding the NOVX protein.
  • noncoding region refers to 5' and 3' sequences that flank the coding region that are not translated into amino acids (i.e., also refe ⁇ ed to as 5' and 3' untranslated regions).
  • antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing.
  • the antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA.
  • the antisense oligonucleotide can be complementary to the region su ⁇ ounding the translation start site of NOVX mRNA.
  • An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length.
  • An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art.
  • an antisense nucleic acid e.g., an antisense oligonucleotide
  • an antisense nucleic acid can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used).
  • modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1 -methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiourour
  • the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).
  • the antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation).
  • the hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix.
  • An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site.
  • antisense nucleic acid molecules can be modified to target selected cells and then administered systemically.
  • antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens).
  • the antisense nucleic acid molecules can also be delivered to cells using the vectors described herein.
  • vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are prefe ⁇ ed.
  • the antisense nucleic acid molecule of the invention is an ⁇ -anomeric nucleic acid molecule.
  • An ⁇ -anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual ⁇ -units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641.
  • the antisense nucleic acid molecule can also comprise a 2'-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15:
  • RNA-DNA analogue See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.
  • Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
  • an antisense nucleic acid of the invention is a ribozyme.
  • Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region.
  • ribozymes e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334: 585-591
  • a ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566).
  • a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Patent 4,987,071 to Cech, et al. and U.S. Patent 5,116,742 to Cech, et al.
  • NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Barrel et al., (1993) Science 261 :1411-1418.
  • NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells.
  • nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid e.g., the NOVX promoter and/or enhancers
  • the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule.
  • the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23.
  • peptide nucleic acids refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained.
  • the neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength.
  • the synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al, 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.
  • PNAs of NOVX can be used in therapeutic and diagnostic applications.
  • PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation a ⁇ est or inhibiting replication.
  • PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., Si nucleases (See, Hyrup, et al, 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al, 1996, supra; Perry-O'Keefe, et al, 1996. supra).
  • PNA directed PCR clamping as artificial restriction enzymes when used in combination with other enzymes, e.g., Si nucleases (See, Hyrup, et al, 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al, 1996, supra; Perry-O'Keefe, et al, 1996. supra).
  • PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art.
  • PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA.
  • Such chimeras allow DNA recognition enzymes (e.g. , RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity.
  • PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra).
  • the synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al, 1996. supra and Finn, et al, 1996. Nucl Acids Res 24: 3357-3363.
  • a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5'-(4-methoxytrityl)-amino-5'-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5' end of DNA. See, e.g., Mag, et al, 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5' PNA segment and a 3' DNA segment. See, e.g., Finn, et al, 1996. supra.
  • chimeric molecules can be synthesized with a 5' DNA segment and a 3' PNA segment. See, e.g., Petersen, et al, 1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.
  • the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al, 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al, 19 ⁇ 7. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO8 ⁇ /09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134).
  • other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al, 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556
  • oligonucleotides can be modified with hybridization-triggered cleavage agents (see, e.g., Krol, et al, 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549).
  • the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.
  • a polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the co ⁇ esponding residues shown in any one of SEQ ID NO:2«, wherein n is an integer between 1 and 566, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.
  • a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence.
  • Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.
  • One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies.
  • native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques.
  • NOVX proteins are produced by recombinant DNA techniques.
  • a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.
  • an “isolated” or “purified” polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized.
  • the language “substantially free of cellular material” includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced.
  • the language "substantially free of cellular material” includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also refe ⁇ ed to herein as a "contaminating protein"), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins.
  • non-NOVX proteins also refe ⁇ ed to herein as a "contaminating protein”
  • the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.
  • the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein.
  • the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.
  • Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2 «, wherein n is an integer between 1 and 566) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein.
  • biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein.
  • a biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.
  • biologically-active portions in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.
  • the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
  • the NOVX protein is substantially homologous to SEQ ID NO:2 «, wherein n is an integer between 1 and 566, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 566, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below.
  • the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2 «, wherein n is an integer between 1 and 566, and retains the functional activity of the NOVX proteins of SEQ ID NO:2w, wherein n is an integer between 1 and 566.
  • the sequences are aligned for optimal comparison pu ⁇ oses (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence).
  • the amino acid residues or nucleotides at co ⁇ esponding amino acid positions or nucleotide positions are then compared.
  • a position in the first sequence is occupied by the same amino acid residue or nucleotide as the co ⁇ esponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid "homology” is equivalent to amino acid or nucleic acid "identity").
  • the nucleic acid sequence homology may be determined as the degree of identity between two sequences.
  • the homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. J Mol Biol 48: 443-453.
  • the coding region of the analogous nucleic acid sequences refe ⁇ ed to above exhibits a degree of identity preferably of at least 70%, 75%, ⁇ 0%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566.
  • sequence identity refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison.
  • percentage of sequence identity is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity.
  • substantially identical denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.
  • NOVX chimeric or fusion proteins As used herein, a NOVX "chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide.
  • An "NOVX polypeptide” refers to a polypeptide having an amino acid sequence co ⁇ esponding to a NOVX protein of SEQ ID NO:2 «, wherein n is an integer between 1 and 566, whereas a "non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence co ⁇ esponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism.
  • a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein.
  • a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein.
  • a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein.
  • the term "operatively-linked" is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another.
  • the non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.
  • the fusion protein is a GST-NO VX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences.
  • GST glutthione S-transferase
  • the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus.
  • NOVX a heterologous signal sequence at its N-terminus.
  • expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.
  • the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family.
  • the NOVX-immunoglobulin fusion proteins of the invention can be inco ⁇ orated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo.
  • the NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand.
  • NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.
  • a NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation.
  • the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers.
  • PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992).
  • anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence
  • expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide).
  • a NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.
  • NOVX Agonists and Antagonists The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists.
  • Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein).
  • An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein.
  • An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein.
  • treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.
  • Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g. , truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity.
  • a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library.
  • a variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein.
  • a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein.
  • methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector.
  • degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences.
  • Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al, 1984. Annu. Rev. Biochem. 53: 323; Itakura, et al, 1984. Science 198: 1056; Ike, et al, 1983. Nucl. Acids Res. 11 : 477. Polypeptide Libraries
  • libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein.
  • a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with Si nuclease, and li gating the resulting fragment library into an expression vector.
  • expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.
  • Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, et al, 1993. Protein Engineering 6:327-331.
  • Anti-NOVX Antibodies Included in the invention are antibodies to NOVX proteins, or fragments of
  • antibody refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (lg) molecules, i.e., molecules that contain an antigen-binding site that specifically binds (immunoreacts with) an antigen.
  • immunoglobulin (lg) molecules i.e., molecules that contain an antigen-binding site that specifically binds (immunoreacts with) an antigen.
  • Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, F a b, F a b' and ⁇ . 2 fragments, and an F ab expression library.
  • antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule.
  • the light chain may be a kappa chain or a lambda chain.
  • Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.
  • An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecif ⁇ cally bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation.
  • the full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens.
  • An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 566, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope.
  • the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues.
  • Prefe ⁇ ed epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.
  • At least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region.
  • a hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production.
  • hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat.
  • epitope includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor.
  • Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three-dimensional structural characteristics, as well as specific charge characteristics.
  • a NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope.
  • An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (K D ) is ⁇ 1 ⁇ M, preferably ⁇ 100 nM, more preferably ⁇ 10 nM, and most preferably ⁇ 100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.
  • K D equilibrium binding constant
  • a protein of the invention may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.
  • Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, inco ⁇ orated herein by reference). Some of these antibodies are discussed below.
  • an appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein.
  • the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized.
  • immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor.
  • the preparation can further include an adjuvant.
  • adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinifrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents.
  • Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
  • the polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen that is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Engineer, published by The Engineer, Inc., Philadelphia PA, Vol. 14, No. 8 (April 17, 2000), pp. 25-28).
  • MAb monoclonal antibody
  • CDRs complementarity determining regions
  • Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975).
  • a hybridoma method a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the lymphocytes can be immunized in vitro.
  • the immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof.
  • peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired.
  • the lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, MONOCLONAL ANTIBODIES: PRINCIPLES AND PRACTICE, Academic Press, (1986) pp. 59-103).
  • Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed.
  • the hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfiised, immortalized cells.
  • the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thy idine ("HAT medium”), which substances prevent the growth of HGPRT-deficient cells.
  • HAT medium hypoxanthine, aminopterin, and thy idine
  • Prefe ⁇ ed immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More prefe ⁇ ed immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia.
  • Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).
  • the culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen.
  • the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).
  • RIA radioimmunoassay
  • ELISA enzyme-linked immunoabsorbent assay
  • the binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.
  • the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this pu ⁇ ose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.
  • the monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • the monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567.
  • DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies).
  • the hybridoma cells of the invention serve as a prefe ⁇ ed source of such DNA.
  • the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells.
  • host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein.
  • the DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Patent No.
  • non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.
  • the antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin.
  • Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') 2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin.
  • humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences.
  • the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions co ⁇ espond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence.
  • the humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Cu ⁇ . Op. Struct. Biol., 2:593-596 (1992)).
  • Fc immunoglobulin constant region
  • Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed "human antibodies", or “fully human antibodies” herein.
  • Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).
  • Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Ban Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).
  • human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol.
  • human antibodies can be made by introducing human immunoglobulin loci into transgenic animals. For example, mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rea ⁇ angement, assembly, and antibody repertoire.
  • This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545, ⁇ 06; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison ( Nature 368, 812-13 (1994)); Fishwild et al,( Nature Biotechnology 14,
  • Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen.
  • transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen.
  • the endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome.
  • the human genes are inco ⁇ orated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications.
  • the prefe ⁇ ed embodiment of such a nonhuman animal is a mouse, and is termed the XenomouseTM as disclosed in PCT publications WO 96/33735 and WO 96/34096.
  • This animal produces B cells which secrete fully human immunoglobulins.
  • the antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies.
  • the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.
  • U.S. Patent No. 5,939,598 An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Patent No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rea ⁇ angement of the locus and to prevent formation of a transcript of a rea ⁇ anged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.
  • a method for producing an antibody of interest such as a human antibody, is disclosed in U.S. Patent No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell.
  • the hybrid cell expresses an antibody containing the heavy chain and the light chain.
  • techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Patent No. 4,946,77 ⁇ ).
  • methods can be adapted for the construction of F ab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F ab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof.
  • Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F ab ⁇ fragment produced by pepsin digestion of an antibody molecule; (ii) an F a b fragment generated by reducing the disulfide bridges of an F(ab ' ) 2 fragment; (iii) an F a b fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F v fragments.
  • Bispecific Antibodies produced by techniques known in the art including, but not limited to: (i) an F ab ⁇ fragment produced by pepsin digestion of an antibody molecule; (ii) an F a b fragment generated by reducing the disulfide bridges of an F(ab ' ) 2 fragment; (iii) an F a b fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F v fragments.
  • Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens.
  • one of the binding specificities is for an antigenic protein of the invention.
  • the second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.
  • bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture often different antibody molecules, of which only one has the co ⁇ ect bispecific structure. The purification of the co ⁇ ect molecule is usually accomplished by affinity chromatography. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).
  • Antibody variable domains with the desired binding specificities can be fused to immunoglobulin constant domain sequences.
  • the fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is prefe ⁇ ed to have the first heavy-chain constant region (CHI) containing the site necessary for light-chain binding present in at least one of the fusions.
  • CHI first heavy-chain constant region
  • the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers that are recovered from recombinant cell culture.
  • the prefe ⁇ ed interface comprises at least a part of the CH3 region of an antibody constant domain.
  • one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g., tyrosine or tryptophan).
  • Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g., alanine or threonine).
  • Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g., F(ab') 2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab') 2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation.
  • the Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives.
  • TAB thionitrobenzoate
  • One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody.
  • the bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.
  • Fab' fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies.
  • Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab') 2 molecule.
  • Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody.
  • the bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.
  • bispecific antibodies have been produced using leucine zippers. Kostelny et al, J.
  • the fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) by a linker that is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and V L domains of one fragment are forced to pair with the complementary V L and VH domains of another fragment, thereby forming two antigen-binding sites.
  • V H heavy-chain variable domain
  • V L light-chain variable domain
  • Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994). Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).
  • bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention.
  • an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g., CD2, CD3, CD28, or B7), or Fc receptors for IgG (Fc ⁇ R), such as Fc ⁇ RI (CD64), Fc ⁇ RII (CD32) and Fc ⁇ RIII (CDI 6) so as to focus cellular defense mechanisms to the cell expressing the particular antigen.
  • Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen.
  • antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA.
  • a cytotoxic agent or a radionuclide chelator such as EOTUBE, DPTA, DOTA, or TETA.
  • Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).
  • TF tissue factor
  • Heteroconjugate antibodies are also within the scope of the present invention.
  • Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089).
  • the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents.
  • immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this pu ⁇ ose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Patent No. 4,676,980.
  • cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region.
  • the homodimeric antibody thus generated can have improved intemalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 14 ⁇ : 2918-2922 (1992).
  • Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993).
  • an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).
  • the invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).
  • a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).
  • Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes.
  • a variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212 Bi, 131 1, 13I In, 90 Y, and 186 Re.
  • Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene).
  • SPDP N-succinimidyl
  • a ricin immunotoxin can be prepared as described in Vitetta et al., Science.238: 1098 ( 1987).
  • Carbon- 14-labeled l-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.
  • the antibody in another embodiment, can be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand” (e.g., avidin) that is in turn conjugated to a cytotoxic agent.
  • a "receptor” such streptavidin
  • a "ligand” e.g., avidin
  • Immunoliposomes The antibodies disclosed herein can also be formulated as immunoliposomes.
  • Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556.
  • Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and
  • PEG-derivatized phosphatidylethanolamme PEG-PE
  • Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter.
  • Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al.,_J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction.
  • a chemotherapeutic agent such as Doxorubicin is optionally contained within the liposome. See Gabizon et al, J. National Cancer Inst., 81(19): 1484 (1989).
  • methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art.
  • ELISA enzyme linked immunosorbent assay
  • selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain.
  • antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.
  • Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like).
  • antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain are utilized as pharmacologically active compounds (refe ⁇ ed to hereinafter as "Therapeutics").
  • An antibody specific for a NOVX protein of the invention can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation.
  • An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells.
  • an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein.
  • Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance.
  • detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials.
  • suitable enzymes include horseradish peroxidase, alkaline phosphatase, ⁇ -galactosidase, or acetylcholinesterase;
  • suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin;
  • suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin;
  • an example of a luminescent material includes luminol;
  • examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ,25 I, 13l I, 35 S or 3 H.
  • Antibody Therapeutics include horseradish peroxidase, alkaline phosphatase, ⁇ -galactosidase, or acetylcholinesterase;
  • Antibodies of the invention may be used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject.
  • An antibody preparation preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds.
  • the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule.
  • the receptor mediates a signal transduction pathway for which ligand is responsible.
  • the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule.
  • the target a receptor having an endogenous ligand that may be absent or defective in the disease or pathology, binds the antibody as a su ⁇ ogate effector ligand, initiating a receptor-based signal transduction event by the receptor.
  • a therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response.
  • the amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered.
  • Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.
  • Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions.
  • Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington : The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa. : 1995; Drug Abso ⁇ tion Enhancement : Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.
  • the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are prefe ⁇ ed.
  • liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is prefe ⁇ ed.
  • peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7 ⁇ 93 (1993).
  • the formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
  • the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent.
  • cytotoxic agent such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent.
  • Such molecules are suitably present in combination in amounts that are effective for the pu ⁇ ose intended.
  • the active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.
  • colloidal drug delivery systems for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules
  • sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules.
  • sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No.
  • copolymers of L-glutamic acid and ⁇ ethyl-L-glutamate non-degradable ethylene-vinyl acetate
  • degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT TM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate)
  • poly-D-(-)-3-hydroxybutyric acid While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.
  • An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label.
  • Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g. , F ab or F (ab)2 ) can be used.
  • the term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled.
  • biological sample is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term "biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo.
  • in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations.
  • In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence.
  • In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in "ELISA: Theory and Practice: Methods in Molecular Biology", Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, NJ, 1995; "Immunoassay", E. Diamandis and T.
  • analyte protein in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody.
  • the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.
  • vectors preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof.
  • vector refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked.
  • plasmid refers to a circular double stranded DNA loop into which additional DNA segments can be ligated.
  • viral vector is another type of vector, wherein additional DNA segments can be ligated into the viral genome.
  • vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors).
  • Other vectors e.g., non-episomal mammalian vectors
  • certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are refe ⁇ ed to herein as "expression vectors".
  • useful expression vectors in recombinant DNA techniques are often in the form of plasmids.
  • plasmid and "vector” can be used interchangeably as the plasmid is the most commonly used form of vector.
  • the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.
  • viral vectors e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses
  • the recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed.
  • "operably-linked" is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).
  • regulatory sequence is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc.
  • the expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).
  • the recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells.
  • NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990).
  • the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.
  • Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein.
  • Such fusion vectors typically serve three pu ⁇ oses: (/) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification.
  • a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein.
  • enzymes, and their cognate recognition sequences include Factor Xa, thrombin and enterokinase.
  • Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988.
  • GST glutathione S-transferase
  • E. coli expression vectors examples include pTrc (Amrann et al, (1988) Gene 69:301-315) and pET 1 Id (Srudier et al, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).
  • One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128.
  • Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized inE. coli (see, e.g., Wada, et al, 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.
  • the NOVX expression vector is a yeast expression vector.
  • yeast expression vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (Baldari, et al, 1987. EMBOJ. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al, 1987. Gene 54: 113-123), pYES2 (Invitrogen Co ⁇ oration, San Diego, Calif), and picZ (InVitrogen Co ⁇ , San Diego, Calif.).
  • NOVX can be expressed in insect cells using baculovirus expression vectors.
  • Baculovirus vectors available for expression of proteins in cultured insect cells include the pAc series (Smith, et al, 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31 -39).
  • a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al, 1987. EMBO J.
  • the expression vector's control functions are often provided by viral regulatory elements.
  • promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40.
  • suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al, MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.
  • the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid).
  • tissue-specific regulatory elements are known in the art.
  • suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al, 1987. Genes Dev. 1 : 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banerji, et al, 1983. Cell 33: 729-740; Queen and Baltimore, 1983.
  • neuron-specific promoters e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477
  • pancreas-specific promoters Esdlund, et al, 1985. Science 230: 912-916
  • mammary gland-specific promoters e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166.
  • promoters are also encompassed, e.g. , the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the -fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).
  • the invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA.
  • Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA.
  • the antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced.
  • a high efficiency regulatory region the activity of which can be determined by the cell type into which the vector is introduced.
  • a host cell can be any prokaryotic or eukaryotic cell.
  • NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells).
  • bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells).
  • mammalian cells such as Chinese hamster ovary cells (CHO) or COS cells.
  • Other suitable host cells are known to those skilled in the art.
  • Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques.
  • transformation and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, D ⁇ A ⁇ -dextran-mediated transfection, lipofection, or electroporation.
  • Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.
  • a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest.
  • selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate.
  • Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g.
  • a host cell of the invention such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein.
  • the invention further provides methods for producing NOVX protein using the host cells of the invention.
  • the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced.
  • the method further comprises isolating NOVX protein from the medium or the host cell.
  • a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity.
  • a "transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene.
  • Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc.
  • a transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal.
  • a "homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.
  • a transgenic animal of the invention can be created by introducing a
  • NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal.
  • the human NOVX cDNA sequences i.e., any one of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566, can be introduced as a transgene into the genome of a non-human animal.
  • a non-human homologue of the human NOVX gene such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene.
  • Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene.
  • a tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells.
  • a transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other fransgenes.
  • a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene.
  • the NOVX gene can be a human gene (e.g., the cDNA ofany one of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566), but more preferably, is a non-human homologue of a human NOVX gene.
  • a mouse homologue of human NOVX gene of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566 can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome.
  • the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also refe ⁇ ed to as a "knock out" vector).
  • the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein).
  • the altered portion of the NOVX gene is flanked at its 5'- and 3 '-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell.
  • the additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene.
  • flanking DNA both at the 5'- and 3'-termini
  • flanking DNA both at the 5'- and 3'-termini
  • Cell 51 503 for a description of homologous recombination vectors.
  • the vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al, 1992. Ce/769: 915.
  • the selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras.
  • an animal e.g., a mouse
  • a chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term.
  • Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene.
  • transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene.
  • a system is the cre/loxP recombinase system of bacteriophage PI .
  • cre/loxP recombinase system see, e.g., Lakso, et al, 1992. Proc. Natl. Acad. Sci. USA 89: 6232-6236.
  • Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al, 1991. Science 251 :1351-1355.
  • a cre loxP recombinase system is used to regulate expression of the transgene
  • animals containing transgenes encoding both the Cre recombinase and a selected protein are required.
  • Such animals can be provided through the construction of "double" transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.
  • Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al, 1997. Nature 3 ⁇ 5: 810-813.
  • a cell e.g., a somatic cell
  • the quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated.
  • the reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transfe ⁇ ed to pseudopregnant female foster animal.
  • the offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.
  • compositions suitable for administration can be inco ⁇ orated into pharmaceutical compositions suitable for administration.
  • compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carrier is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and abso ⁇ tion delaying agents, and the like, compatible with pharmaceutical administration.
  • Suitable ca ⁇ iers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is inco ⁇ orated herein by reference.
  • Prefe ⁇ ed examples of such ca ⁇ iers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used.
  • the use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be inco ⁇ orated into the compositions.
  • a pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration.
  • routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration.
  • Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose.
  • the pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide.
  • the parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.
  • compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion.
  • suitable carriers include physiological saline, bacteriostatic water, Cremophor EL (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS).
  • the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi.
  • the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof.
  • the proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants.
  • Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like.
  • isotonic agents for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition.
  • Prolonged abso ⁇ tion of the injectable compositions can be brought about by including in the composition an agent that delays abso ⁇ tion, for example, aluminum monostearate and gelatin.
  • Sterile injectable solutions can be prepared by inco ⁇ orating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization.
  • the active compound e.g., a NOVX protein or anti-NOVX antibody
  • dispersions are prepared by inco ⁇ orating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above.
  • methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.
  • Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the pu ⁇ ose of oral therapeutic administration, the active compound can be inco ⁇ orated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition.
  • the tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.
  • a binder such as microcrystalline cellulose, gum tragacanth or gelatin
  • an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch
  • a lubricant such as magnesium stearate or Sterotes
  • a glidant such as colloidal silicon dioxide
  • the compounds are delivered in the form of an aerosol spray from pressured container or dispenser that contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.
  • a suitable propellant e.g., a gas such as carbon dioxide, or a nebulizer.
  • Systemic administration can also be by transmucosal or transdermal means.
  • penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives.
  • Transmucosal administration can be accomplished through the use of nasal sprays or suppositories.
  • the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.
  • the compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.
  • the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems.
  • a controlled release formulation including implants and microencapsulated delivery systems.
  • Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Co ⁇ oration and Nova
  • Liposomal suspensions can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Patent No. 4,522,811. It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage.
  • Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.
  • the specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.
  • the nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors.
  • Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Patent No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al, 1994. Proc. Natl. Acad. Sci. USA 91 : 3054-3057).
  • the pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded.
  • the pharmaceutical preparation can include one or more cells that produce the gene delivery system.
  • the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.
  • the isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below.
  • the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or abe ⁇ ant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias.
  • the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity.
  • the invention can be used in methods to influence appetite, abso ⁇ tion of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.
  • the invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.
  • the invention provides a method (also refe ⁇ ed to herein as a "screening assay") for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity.
  • modulators i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity.
  • modulators i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression
  • the invention provides assays for screening candidate or test compounds that bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof.
  • the test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the "one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection.
  • the biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g.. Lam, 1997 ' . Anticancer Drug Design 12: 145.
  • a "small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD.
  • Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules.
  • Libraries of chemical and or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.
  • Biotechniques 13: 412-421 or on beads (Lam, 1991. Nature 354: 82- ⁇ 4), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Patent No. 5,223,409), spores (Ladner, U.S. Patent 5,233,409), plasmids (Cull, et al, 1992. Proc. Natl. Acad. Sci. USA ⁇ 9: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al, 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Patent No. 5,233,409.).
  • an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined.
  • the cell for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex.
  • test compounds can be labeled with 125 I, 35 S, 14 C, or 3 H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting.
  • test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product.
  • the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.
  • an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule.
  • a "target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule.
  • a NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention.
  • a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g., a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell.
  • the target for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.
  • Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule.
  • the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e., intracellular Ca 2+ , diacylglycerol, IP 3 , etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.
  • a cellular second messenger of the target i.e., intracellular Ca 2+ , diacylglycerol, IP 3 , etc.
  • detecting catalytic/enzymatic activity of the target an appropriate substrate detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g
  • an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above.
  • the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.
  • an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule.
  • the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.
  • the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.
  • the cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein.
  • solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton ® X-100, Triton ® X-l 14, Thesit ® , Isotridecypoly(ethylene glycol ether) n , N-dodecyl ⁇ N,N-dimethyl-3-ammonio-l -propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1 -propane sulfonate (CHAPS), or
  • non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl
  • binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes.
  • a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix.
  • GST-NO VX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, MO) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH).
  • the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra.
  • the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.
  • NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin.
  • Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, 111.), and immobilized in the wells of sfreptavidin-coated 96 well plates (Pierce Chemical).
  • antibodies reactive with NOVX protein or target molecules can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation.
  • Methods for detecting such complexes include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.
  • modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression.
  • the candidate compound when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression.
  • the level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.
  • the NOVX proteins can be used as "bait proteins" in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Patent No. 5,283,317; Zervos, et al, 1993. Cell 72: 223-232; Madura, et al, 1993. J. Biol. Chem. 26 ⁇ : 12046-12054; Bartel, et al, 1993. Biotechniques 14: 920-924; Iwabuchi, et al, 1993.
  • NOVX-binding proteins proteins that bind to or interact with NOVX
  • NOVX-binding proteins proteins that bind to or interact with NOVX
  • NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.
  • the two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4).
  • GAL-4 a known transcription factor
  • a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the "bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.
  • a reporter gene e.g., LacZ
  • the invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein. Detection Assays
  • Portions or fragments of the cDNA sequences identified herein (and the co ⁇ esponding complete gene sequences) can be used in numerous ways as polynucleotide reagents.
  • these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample.
  • Chromosome Mapping Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2 «-l, wherein n is an integer between 1 and 566, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping ofthe NOVX sequences to chromosomes is an important first step in co ⁇ elating these sequences with genes associated with disease.
  • NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis ofthe NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene co ⁇ esponding to the NOVX sequences will yield an amplified fragment.
  • Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes.
  • mammals e.g., human and mouse cells.
  • Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.
  • PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.
  • Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step.
  • Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle.
  • the chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually.
  • the FISH technique can be used with a DNA sequence as short as 500 or 600 bases.
  • clones larger than 1 ,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection.
  • 1,000 bases, and more preferably 2,000 bases will suffice to get good results at a reasonable amount of time.
  • Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents co ⁇ esponding to noncoding regions of the genes actually are prefe ⁇ ed for mapping pu ⁇ oses. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.
  • differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene can be determined. If a mutation is observed in some or all ofthe affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent ofthe particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymo ⁇ hisms.
  • the NOVX sequences ofthe invention can also be used to identify individuals from minute biological samples.
  • an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification.
  • the sequences ofthe invention are useful as additional DNA markers for RFLP ("restriction fragment length polymo ⁇ hisms," described in U.S. Patent No. 5,272,057).
  • sequences ofthe invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome.
  • NOVX sequences described herein can be used to prepare two PCR primers from the 5'- and 3'-termini ofthe sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.
  • Panels of co ⁇ esponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences.
  • the sequences ofthe invention can be used to obtain such identification sequences from individuals and from tissue.
  • the NOVX sequences ofthe invention uniquely represent portions ofthe human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much ofthe allelic variation is due to single nucleotide polymo ⁇ hisms (SNPs), which include restriction fragment length polymo ⁇ hisms (RFLPs).
  • SNPs single nucleotide polymo ⁇ hisms
  • RFLPs restriction fragment length polymo ⁇ hisms
  • each ofthe sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification pu ⁇ oses. Because greater numbers of polymo ⁇ hisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals.
  • the noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.
  • the invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) pu ⁇ oses to thereby treat an individual prophylactically.
  • diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with abe ⁇ ant NOVX expression or activity.
  • a biological sample e.g., blood, serum, cells, tissue
  • the disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.
  • the invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample.
  • Such assays can be used for prognostic or predictive pu ⁇ ose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.
  • Another aspect ofthe invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (refe ⁇ ed to herein as "pharmacogenomics").
  • Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability ofthe individual to respond to a particular agent.)
  • Yet another aspect ofthe invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.
  • agents e.g., drugs, compounds
  • An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g. , mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample.
  • a compound or an agent capable of detecting NOVX protein or nucleic acid e.g. , mRNA, genomic DNA
  • An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA.
  • the nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA.
  • n is an integer between 1 and 566
  • a portion thereof such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA.
  • An agent for detecting NOVX protein is an antibody capable of binding to
  • NOVX protein preferably an antibody with a detectable label.
  • Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab') 2 ) can be used.
  • the term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling ofthe probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling ofthe probe or antibody by reactivity with another reagent that is directly labeled.
  • Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin.
  • biological sample is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo.
  • in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations.
  • In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence.
  • In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations.
  • in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody.
  • the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.
  • the biological sample contains protein molecules from the test subject.
  • the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject.
  • a prefe ⁇ ed biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.
  • the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.
  • kits for detecting the presence of NOVX in a biological sample can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard.
  • the compound or agent can be packaged in a suitable container.
  • the kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.
  • the diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with abe ⁇ ant NOVX expression or activity.
  • the assays described herein such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity.
  • the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder.
  • the invention provides a method for identifying a disease or disorder associated with abe ⁇ ant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with abe ⁇ ant NOVX expression or activity.
  • a test sample refers to a biological sample obtained from a subject of interest.
  • a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.
  • the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity.
  • an agent e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate
  • such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder.
  • the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with abe ⁇ ant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g. , wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with abe ⁇ ant NOVX expression or
  • the methods ofthe invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by abe ⁇ ant cell proliferation and/or differentiation.
  • the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene.
  • such genetic lesions can be detected by ascertaining the existence of at least one of: (/ ' ) a deletion of one or more nucleotides from a NOVX gene; ( ⁇ ) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rea ⁇ angement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) abe ⁇ ant modification of a NOVX gene, such as of the methylation pattem of the genomic DNA, (v») the presence of a non-wild-type splicing pattem of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of
  • a prefe ⁇ ed biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.
  • any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.
  • detection ofthe lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Patent Nos. 4,6 ⁇ 3,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al, 1988. Science 241: 1077- 1080; and Nakazawa, et al, 1994. Proc. Natl. Acad. Sci. USA 91 : 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al, 1995.
  • PCR polymerase chain reaction
  • LCR ligation chain reaction
  • This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells ofthe sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification ofthe NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size ofthe amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any ofthe techniques used for detecting mutations described herein.
  • nucleic acid e.g., genomic, mRNA or both
  • Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al, 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al, 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Q ⁇ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection ofthe amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.
  • mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns.
  • sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and confrol DNA indicates mutations in the sample DNA.
  • sequence specific ribozymes see, e.g., U.S. Patent No. 5,493,531 can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.
  • genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density a ⁇ ays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al, 1996. Human Mutation 7: 244-255; Kozal, et al, 1996. Nat. Med. 2: 753-759.
  • genetic mutations in NOVX can be identified in two dimensional a ⁇ ays containing light-generated DNA probes as described in Cronin, et al, supra.
  • a first hybridization a ⁇ ay of probes can be used to scan through long stretches of DNA in a sample and confrol to identify base changes between the sequences by making linear a ⁇ ays of sequential overlapping probes. This step allows the identification of point mutations.
  • a second hybridization a ⁇ ay that allows the characterization of specific mutations by using smaller, specialized probe a ⁇ ays complementary to all variants or mutations detected.
  • Each mutation a ⁇ ay is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.
  • any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence ofthe sample NOVX with the co ⁇ esponding wild-type (control) sequence.
  • Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al, 1995.
  • Biotechniques 19: 448 including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101 ; Cohen, et al, 1996. Adv. Chromatography 36: 127-162; and Griffin, et al, 1993. Appl. Biochem. Biotechnol 38: 147-159).
  • RNA/RNA or RNA/DNA heteroduplexes Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al, 1985. Science 230: 1242.
  • the art technique of "mismatch cleavage" starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample.
  • the double-stranded duplexes are treated with an agent that cleaves single-stranded regions ofthe duplex such as which will exist due to basepair mismatches between the control and sample strands.
  • RNA/DNA duplexes can be treated with RNase and DNA DNA hybrids treated with Si nuclease to enzymatically digesting the mismatched regions.
  • either DNA/DNA or RNA DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion ofthe mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al, 198 ⁇ . Proc. Natl. Acad. Sci. USA ⁇ 5: 4397; Saleeba, et al, 1992. Methods Enzymol 217: 2 ⁇ 6-295.
  • the control DNA or RNA can be labeled for detection.
  • the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called "DNA mismatch repair" enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells.
  • DNA mismatch repair enzymes
  • the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al, 1994. Carcinogenesis 15: 1657-1662.
  • a probe based on a NOVX sequence e.g., a wild-type NOVX sequence
  • a cDNA or other DNA product from a test cell(s).
  • the duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Patent No. 5,459,039.
  • alterations in electrophoretic mobility will be used to identify mutations in NOVX genes.
  • single strand conformation polymo ⁇ hism may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al, 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature.
  • the secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change.
  • the DNA fragments may be labeled or detected with labeled probes.
  • the sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence.
  • the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g.. Keen, et al, 1991. Trends Genet. 7: 5.
  • the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE).
  • DGGE denaturing gradient gel electrophoresis
  • DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR.
  • a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265: 12753.
  • oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, et al, 1986. Nature 324: 163; Saiki, et al, 1989. Proc. Natl. Acad. Sci. USA 86: 6230.
  • Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.
  • Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al, 1989. Nucl. Acids Res. 17: 2437-2448) or at the extreme 3 '-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11 : 238).
  • amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 1991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3'-terminus ofthe 5' sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.
  • the methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.
  • any cell type or tissue preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein.
  • any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.
  • Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity can be administered to individuals to treat (prophylactically or therapeutically) disorders.
  • the disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
  • the pharmacogenomics i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug
  • the pharmacogenomics ofthe individual permits the selection of effective agents (e.g., drugs) for prophylactic or therapeutic treatments based on a consideration ofthe individual's genotype.
  • Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens.
  • the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment ofthe individual.
  • Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol, 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated.
  • G6PD glucose-6-phosphate dehydrogenase
  • the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action.
  • drug metabolizing enzymes e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19
  • NAT 2 N-acetyltransferase 2
  • CYP2D6 and CYP2C19 cytochrome pregnancy zone protein precursor enzymes
  • CYP2D6 and CYP2C19 cytochrome pregnancy zone protein precursor enzymes
  • These polymo ⁇ hisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations.
  • the gene coding for CYP2D6 is highly polymo ⁇ hic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite mo ⁇ hine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.
  • the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment ofthe individual.
  • pharmacogenetic studies can be used to apply genotyping of polymo ⁇ hic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one ofthe exemplary screening assays described herein.
  • Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX can be applied not only in basic drug screening, but also in clinical trials.
  • agents e.g., drugs, compounds
  • the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity.
  • the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity.
  • the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a "read out" or markers ofthe immune responsiveness of a particular cell.
  • genes including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified.
  • an agent e.g., compound, drug or small molecule
  • NOVX activity e.g., identified in a screening assay as described herein
  • cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder.
  • the levels of gene expression i.e.
  • a gene expression pattern can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one ofthe methods as described herein, or by measuring the levels of activity of NOVX or other genes.
  • the gene expression pattern can serve as a marker, indicative of the physiological response ofthe cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment ofthe individual with the agent.
  • the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration ofthe agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity ofthe NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity ofthe NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration ofthe agent to the subject accordingly.
  • an agent e.g
  • increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness ofthe agent.
  • decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness ofthe agent.
  • the invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with abe ⁇ ant NOVX expression or activity.
  • the disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
  • Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner.
  • Therapeutics that may be utilized include, but are not limited to: (/) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (») antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are "dysfunctional" (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to "knockout" endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989.
  • modulators i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide ofthe invention
  • modulators i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide ofthe invention
  • Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity.
  • Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner.
  • Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability. Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity ofthe expressed peptides (or mRNAs of an aforementioned peptide).
  • Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).
  • immunoassays e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.
  • hybridization assays to detect expression of mRNAs e.g., Northern assays, dot blots, in situ hybridization, and the like.
  • the invention provides a method for preventing, in a subject, a disease or condition associated with an abe ⁇ ant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity.
  • Subjects at risk for a disease that is caused or contributed to by abe ⁇ ant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein.
  • Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic ofthe NOVX abe ⁇ ancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression.
  • a NOVX agonist or NOVX antagonist agent can be used for treating the subject.
  • the appropriate agent can be determined based on screening assays described herein. The prophylactic methods ofthe invention are further discussed in the following subsections.
  • the modulatory method ofthe invention involves contacting a cell with an agent that modulates one or more ofthe activities of NOVX protein activity associated with the cell.
  • An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule.
  • the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell.
  • the agent inhibits one or more NOVX protein activity.
  • inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject).
  • the invention provides methods of treating an individual afflicted with a disease or disorder characterized by abe ⁇ ant expression or activity of a NOVX protein or nucleic acid molecule.
  • the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity.
  • an agent e.g., an agent identified by a screening assay described herein
  • the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or abe ⁇ ant NOVX expression or activity.
  • Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect.
  • a subject has a disorder characterized by abe ⁇ ant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders).
  • a gestational disease e.g., preclampsia
  • suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment ofthe affected tissue.
  • in vitro assays may be performed with representative cells ofthe type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s).
  • Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects.
  • suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects.
  • any ofthe animal model system known in the art may be used prior to administration to human subjects.
  • the NOVX nucleic acids and proteins ofthe invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders.
  • the disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
  • a cDNA encoding the NOVX protein ofthe invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof.
  • the compositions ofthe invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.
  • Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein ofthe invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed.
  • a further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties).
  • These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances ofthe invention for use in therapeutic or diagnostic methods.
  • Example A Polynucleotide and Polypeptide Sequences, and Homology Data
  • the NOVl clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table IA.
  • PSG a new signal peptide prediction method
  • N-region length 0; pos.chg 0; neg.chg 0 H-region: length 16; peak value 3.12 PSG score: -1.28
  • GvH von Heijne's method for signal seq. recognition
  • GvH score (threshold: -2.1) 0.37 possible cleavage site: between 43 and 44
  • Gavel prediction of cleavage sites for mitochondrial preseq R-2 motif at 176 CRY
  • NUCDISC discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.47
  • KDEL ER retention motif in the C-terminus : none
  • SKL peroxisomal targeting signal in the C-terminus: none
  • VAC possible vacuolar targeting motif
  • Actinin-type actin-binding motif type 1 : none type 2 : none
  • NMYR N-myristoylation pattern : none
  • Prenylation motif none memYQRL: transport motif from cell surface to Golgi: none
  • NNCN Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
  • COIL Lupas's algorithm to detect coiled-coil regions total : 0 residues
  • NOVla protein was found to have homology to the proteins shown in the BLASTP data in Table IE.
  • the NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.
  • NOV2a SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
  • NOV2b SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
  • NOV2C SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
  • NOV2a NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRK HSMASLNCIRKST
  • NOV2b NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRK HSMASLNCIRKST
  • NOV2a SEKGLNGSLQERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK
  • PRPSASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFL NOV2a TVSR DNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2b
  • TVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2d TVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2d
  • NOV2a SEQ ID NO 6
  • NOV2b SEQ ID NO 8
  • NOV2c SEQ ID NO 10
  • NOV2d SEQ ID NO 12
  • PSG a new signal peptide prediction method
  • N- region length 2 ; pos . chg 0 ; neg . chg 1 H-region : length 16 ; peak value 0 . 00 PSG score : -4 .40
  • GvH von Heijne ' s method for signal seq . recognition
  • GvH score (threshold: -2. 1) : -1. 56 possible cleavage site : between 17 and 18
  • Gavel prediction of cleavage sites for mitochondrial preseq R-2 motif at 29 VRA
  • NUCDISC discrimination of nuclear localization signals pat4 : none pat7: PKRYKGF (5) at 460 bipartite: RKWHSMASLNCIRKSTK at 341 content of basic residues: 9.5% NLS Score: 0.45
  • VAC possible vacuolar targeting motif
  • Actinin-type actin-binding motif type 1 : none type 2 : none
  • NMYR N-myristoylation pattern : none Prenylation motif: none
  • memYQRL transport motif from cell surface to Golgi: none
  • NNCN Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
  • COIL Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
  • NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.
  • the NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.
  • KLPTMPGPRVGKYLWRSPHSKGCPGAM WLLL GVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKG QESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTVSFVGSDPSQFCGQQGSPLGRPPGQREFVSSG RSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYY QAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRG GGALLGDR ILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNF SGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNA LQKRQRPEVFSDNMFCVGDETQRHS
  • NOV3a (SEQ ID NO 16) NOV3b (SEQ ID NO 18) NOV3C (SEQ ID NO 20) NOV3d (SEQ ID NO 22) NOV3e (SEQ ID NO 24) NOV3f (SEQ ID NO 26) NOV3g (SEQ ID NO 28) NOV3h (SEQ ID NO 30) NOV3i (SEQ ID NO 32) NOV3J (SEQ ID NO 34) NOV3k (SEQ ID NO 36) NOV31 (SEQ ID NO 38) NOV3m (SEQ ID NO 40) NOV3n (SEQ ID NO 42) NOV3o (SEQ ID NO 44) Further analysis ofthe NOV3a protein yielded the following properties shown in Table 3C.
  • PSG a new signal peptide prediction method
  • N-region length 9; pos . chg 2; neg.chg 0 H-region: length 3; peak value -5.40 PSG score: -9.80
  • GvH von Heijne's method for signal seq. recognition
  • GvH score (threshold: -2.1): 2.53 possible cleavage site: between 35 and 36
  • NUCDISC discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 8.4% NLS Score: -0.47
  • KKXX-like motif in the C-terminus MNGK SKL: peroxisomal targeting signal in the C-terminus: none PTS2 : 2nd peroxisomal targeting signal: none
  • VAC possible vacuolar targeting motif
  • Actinin-type actin-binding motif type 1 : none type 2 : none
  • NMYR N-myristoylation pattern : none
  • Prenylation motif none memYQRL: transport motif from cell surface to Golgi: none
  • NNCN Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7
  • COIL Lupas's algorithm to detect coiled-coil regions total: 0 residues
  • NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E.
  • AAH35220 Similar to complement 189..483 176/303 (58%) e-108 component - Homo sapiens 400..701 226/303 (74%) (Human), 705 aa.
  • NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4 A. Table 4A. NOV4 Sequence Analysis

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Hospice & Palliative Care (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Chemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention provides novel isolated polynucleotides and small molecule target polypeptides encoded by the polynucleotides. Antibodies that immunospecifically bind to a novel small molecule target polypeptide or any derivative, variant, mutant or fragment of that polypeptide, polynucleotide or antibody are disclosed, as are methods in which the small molecule target polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states. More specifically, the present invention discloses methods of using recombinantly expressed and/or endogenously expressed proteins in various screening procedures for the purpose of identifying therapeutic antibodies and therapeutic small molecules associated with diseases. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Description

NOVEL PROTEINS AND NUCLEIC ACIDS ENCODING SAME
FIELD OF THE INVENTION
The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.
TfflS PAGE INTENTIONALLY LEFT BLANK
THIS PAGE INTENTIONALLY LEFT BLANK
BACKGROUND
Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells. Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect. Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.
Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.
Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Coφoration to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions. In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.
In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.
SUMMARY OF THE INVENTION
The invention includes nucleic acid sequences and the novel polypeptides they encode. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as "NOVX" nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566. In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.
Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.
In another aspect, the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.
The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence. In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed. In another embodiment, the invention includes the complement ofany of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.
In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof. In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.
In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incoφorated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF THE FIGURES
Fig. Dl: Alignment of CG55806-04 (SEQ ID NO:748), CG55806-02 (SEQ ID NO:752), and 1PFX (SEQ ID NO: 1476).
Fig. D2: Structure of porcine factor IXa (1PFX). Fig. El : Data showing effect on cell growth by knockdown of CG59693-01.
Fig. E2: Data showing effect on cell growth by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (48 hr).
Fig. E3: Data showing effect on cell viability by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (48 hr). Fig. E4: Data showing effect on cell growth by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (72 hr).
Fig. E5: Data showing effect on cell viability by knockdown of CG59693-01 with subsequent treatment with Paclitaxel (72 hr).
Fig. E6: Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Gemcitabine.
Fig. E7: Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Daunorubicin.
Fig. E8: Data showing effect on cell growth by knockdown of CG59693-01 by AS4 antisense oligonucleotide followed by subsequent treatment with Etoposide. Fig. E9: Data showing effect on cell growth by knockdown of CG59693-01 by
AS4 antisense oligonucleotide followed by subsequent treatment with Cisplatin.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as "NOVX nucleic acids" or "NOVX polynucleotides" and the corresponding encoded polypeptides are referred to as "NOVX polypeptides" or "NOVX proteins." Unless indicated otherwise, "NOVX" is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.
TABLE A. Sequences and Corresponding SEQ DD Numbers
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
Figure imgf000020_0001
Figure imgf000021_0001
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000025_0001
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
Figure imgf000036_0001
Figure imgf000037_0001
Figure imgf000038_0001
Figure imgf000039_0001
Figure imgf000040_0001
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.
Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to, e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hypeφlasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic puφura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.
NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.
Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.
The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.
The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g., detection of a variety of cancers. SNP analysis for each NOVX, if applicable, is presented in Example D.
Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.
NOVX clones
NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong. The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders. The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.
In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).
In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 566 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement ofany of said nucleic acid molecules. In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l , wherein n is an integer between 1 and 566 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. NOVX Nucleic Acids and Polypeptides
One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX rnRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term "nucleic acid molecule" is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.
A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a "mature" form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the coπesponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product "mature" form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a "mature" form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+l to residue N remaining. Further as used herein, a "mature" form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination ofany of them.
The term "probe", as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.
The term "isolated" nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an "isolated" nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5'- and 3'-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an "isolated" nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.
A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n-l , wherein n is an integer between 1 and 566, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989; and Ausubel, et al, (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993.) A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides coπesponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.
As used herein, the term "oligonucleotide" refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2«- 1 , wherein n is an integer between 1 and 566, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.
In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2w-l , wherein n is an integer between 1 and 566, thereby forming a stable duplex.
As used herein, the term "complementary" refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term "binding" means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates. A "fragment" provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.
A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the coπesponding full-length cDNA extend in the 5' direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the coπesponding full-length cDNA extend in the 3' direction of the disclosed sequence. A "derivative" is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An "analog" is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g., they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A "homolog" is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.
Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, δ0%, or 95% identity (with a prefeπed identity of δO-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g., Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993, and below.
4δ A "homologous nucleic acid sequence" or "homologous amino acid sequence," or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2/ι-l , wherein n is an integer between 1 and 566, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.
A NOVX polypeptide is encoded by the open reading frame ("ORF") of a NOVX nucleic acid. An ORF coπesponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG "start" codon and terminates with one of the three "stop" codons, namely, TAA, TAG, or TGA. For the p poses of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.
The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g., from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566; or an anti-sense strand nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566; or of a naturally occurring mutant of SEQ ID NO:2«-l , wherein n is an integer between 1 and 566.
Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g., the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.
"A polypeptide having a biologically-active portion of a NOVX polypeptide" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a "biologically-active portion of NOVX" can be prepared by isolating a portion of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.
NOVX Nucleic Acid and Polypeptide Variants The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 566. In addition to the human NOVX nucleotide sequences of SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, it will be appreciated by those skilled in the art that DNA sequence polymoφhisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymoφhism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms "gene" and "recombinant gene" refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymoφhisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.
Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, are intended to be within the scope of the invention. Nucleic acid molecules coπesponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.
Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term "hybridizes under stringent conditions" is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.
Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.
As used herein, the phrase "stringent hybridization conditions" refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30 °C for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60 °C for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide. Stringent conditions are known to those skilled in the art and can be found in
Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6X SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65°C, followed by one or more washes in 0.2X SSC, 0.01% BSA at 50°C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, coπesponds to a naturally-occurring nucleic acid molecule. As used herein, a "naturally-occurring" nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein). In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2M-1 , wherein n is an integer between 1 and 566, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6X SSC, 5X Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55 °C, followed by one or more washes in IX SSC, 0.1% SDS at 37 °C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.
In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5X SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40°C, followed by one or more washes in 2X SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50°C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792. Conservative Mutations
In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at "non-essential" amino acid residues can be made in the sequence of SEQ ID NO:2w, wherein n is an integer between 1 and 566. A "non-essential" amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an "essential" amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are not particularly amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.
Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2«, wherein n is an integer between 1 and 566. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 566; more preferably at least about 70% homologous to SEQ ID NO:2τ., wherein n is an integer between 1 and 566; still more preferably at least about δ0% homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 566; even more preferably at least about 90% homologous to SEQ ID NO:2», wherein n is an integer between 1 and 566; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 566.
An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2«, wherein n is an integer between 1 and 566, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.
Mutations can be introduced any one of SEQ ID NO:2H-1 , wherein n is an integer between 1 and 566, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more non-essential amino acid residues. A "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.
The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved "strong" residues or fully conserved "weak" residues. The "strong" group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the "weak" group of conserved residues may be any one of the following: CSA, ATN, SAG, STΝK, STPA, SGΝD, SΝDEQK, ΝDEQHK, ΝEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code. In one embodiment, a mutant ΝOVX protein can be assayed for (i) the ability to form protein:protein interactions with other ΝOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant ΝOVX protein and a ΝOVX ligand; or (iii) the ability of a mutant ΝOVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g., avidin proteins). In yet another embodiment, a mutant ΝOVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release). Interfering RNA
In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5' untranslated (UT) region, the ORF, or the 3' UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WO01/75164, WO01/92513, WO 01/29058, WOO 1/89304, WO02/16620, and WO02/2985δ, each incoφorated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway. According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Barrel and Shaφ (1999), Genes & Dev. 13: 3191-3197, incoφorated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format. The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3' overhang. The sequence of the 2-nt 3' overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3' overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3' overhang are deoxyribonucleotides. Using 2'-deoxyribonucleotides in the 3' overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.
A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3' of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5' of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct. Finally, cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a haiφin RNAi product is homologous to all or a portion of the target gene. In another example, a haiφin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.
In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA HI . One example of a vector system is the GeneSuppressor RNA Interference kit (commercially available from Imgenex). The U6 and HI promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for HI promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3' UU overhang in the expressed siRNA, which is similar to the 3' overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21 -nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript. A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.
In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transfeπed to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.
A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon. Alternatively, 5' or 3' UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites.
UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6δ77-88. Hence, consideration should be taken to accommodate SNPs, polymoφhisms, allelic variants or species-specific variations when targeting a desired gene. In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.
Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility. A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA coπesponds to (NI 9)TT or N21 , respectively. In the latter case, conversion of the 3' end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3' overhangs. Symmetric 3' overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes & Dev. 15: 188-200, incoφorated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.
Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5' (N19)TT, as it is believed that the sequence of the 3'-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, incoφorated by reference in its entirety. Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g., inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Prefeπed cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention. For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a
CMV-driven EGFP-expression plasmid (e.g., commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.
Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transfeπed to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.
An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or abeπant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues. The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.
Where the NOVX gene function is not coπelated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA's to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX") phenotype in the treated subject sample. The NOVX" phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.
In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.
Production of RNAs
Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are elecfrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).
Lysate Preparation
Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30° C for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double sfranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.
In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a 32P-ATP. Reactions are stopped by the addition of 2X-proteinase-K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined. The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques. RNA Preparation
21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak CI 8 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).
These RNAs (20 μM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 90° C followed by 1 h at 37° C. Cell Culture
A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3 X 105 cells/ml) and transfeπed to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3' ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.
The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in-vivo transfection or gene therapy transfection techniques.
Antisense Nucleic Acids
Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2«-l , wherein n is an integer between 1 and 566, or fragments, analogs or derivatives thereof. An "antisense" nucleic acid comprises a nucleotide sequence that is complementary to a "sense" nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 566, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, are additionally provided.
In one embodiment, an antisense nucleic acid molecule is antisense to a "coding region" of the coding strand of a nucleotide sequence encoding a NOVX protein. The term "coding region" refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence encoding the NOVX protein. The term "noncoding region" refers to 5' and 3' sequences that flank the coding region that are not translated into amino acids (i.e., also refeπed to as 5' and 3' untranslated regions).
Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region suπounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used). Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1 -methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5'-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine.
Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).
The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are prefeπed. In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2'-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15:
6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.
Ribozymes and PNA Moieties
Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2«-l, wherein n is an integer between 1 and 566). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Patent 4,987,071 to Cech, et al. and U.S. Patent 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Barrel et al., (1993) Science 261 :1411-1418.
Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991. Anticancer DrugDes. 6: 569-84; Helene, et al. 1992. Ann. N.Y. Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.
In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms "peptide nucleic acids" or "PNAs" refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al, 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.
PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation aπest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., Si nucleases (See, Hyrup, et al, 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al, 1996, supra; Perry-O'Keefe, et al, 1996. supra).
In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g. , RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al, 1996. supra and Finn, et al, 1996. Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5'-(4-methoxytrityl)-amino-5'-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5' end of DNA. See, e.g., Mag, et al, 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5' PNA segment and a 3' DNA segment. See, e.g., Finn, et al, 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5' DNA segment and a 3' PNA segment. See, e.g., Petersen, et al, 1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.
In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al, 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al, 19δ7. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO8δ/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization-triggered cleavage agents (see, e.g., Krol, et al, 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.
NOVX Polypeptides A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 566. The invention also includes a mutant or variant protein any of whose residues may be changed from the coπesponding residues shown in any one of SEQ ID NO:2«, wherein n is an integer between 1 and 566, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.
In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.
One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques. An "isolated" or "purified" polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language "substantially free of cellular material" includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language "substantially free of cellular material" includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also refeπed to herein as a "contaminating protein"), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.
The language "substantially free of chemical precursors or other chemicals" includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.
Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 566) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein.
Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.
Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.
In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 566. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 566, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 566, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 566, and retains the functional activity of the NOVX proteins of SEQ ID NO:2w, wherein n is an integer between 1 and 566.
Determining Homology Between Two or More Sequences
To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison puφoses (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at coπesponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the coπesponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid "homology" is equivalent to amino acid or nucleic acid "identity").
The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. J Mol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences refeπed to above exhibits a degree of identity preferably of at least 70%, 75%, δ0%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2w-l, wherein n is an integer between 1 and 566.
The term "sequence identity" refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term "percentage of sequence identity" is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term "substantial identity" as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.
Chimeric and Fusion Proteins
The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX "chimeric protein" or "fusion protein" comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An "NOVX polypeptide" refers to a polypeptide having an amino acid sequence coπesponding to a NOVX protein of SEQ ID NO:2«, wherein n is an integer between 1 and 566, whereas a "non-NOVX polypeptide" refers to a polypeptide having an amino acid sequence coπesponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can coπespond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term "operatively-linked" is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide. In one embodiment, the fusion protein is a GST-NO VX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides.
In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.
In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incoφorated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g., promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.
A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.
NOVX Agonists and Antagonists The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.
Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g. , truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al, 1984. Annu. Rev. Biochem. 53: 323; Itakura, et al, 1984. Science 198: 1056; Ike, et al, 1983. Nucl. Acids Res. 11 : 477. Polypeptide Libraries
In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with Si nuclease, and li gating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.
Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, et al, 1993. Protein Engineering 6:327-331.
Anti-NOVX Antibodies Included in the invention are antibodies to NOVX proteins, or fragments of
NOVX proteins. The term "antibody" as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (lg) molecules, i.e., molecules that contain an antigen-binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab' and ¥^.2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgGi, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.
An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifϊcally bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 566, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Prefeπed epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.
In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol 157: 105-142, each incoφorated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.
The term "epitope" includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three-dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is <1 μM, preferably < 100 nM, more preferably < 10 nM, and most preferably < 100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.
A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components. Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, incoφorated herein by reference). Some of these antibodies are discussed below. Polyclonal Antibodies
For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinifrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen that is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia PA, Vol. 14, No. 8 (April 17, 2000), pp. 25-28).
Monoclonal Antibodies
The term "monoclonal antibody" (MAb) or "monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.
Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro. The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, MONOCLONAL ANTIBODIES: PRINCIPLES AND PRACTICE, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfiised, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thy idine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells. Prefeπed immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More prefeπed immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63). The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.
After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this puφose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.
The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography. The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a prefeπed source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Patent No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody. Humanized Antibodies
The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321 :522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science,
239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the coπesponding sequences of a human antibody. (See also U.S. Patent No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by coπesponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions coπespond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Cuπ. Op. Struct. Biol., 2:593-596 (1992)).
Human Antibodies Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed "human antibodies", or "fully human antibodies" herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Ban Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals. For example, mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene reaπangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,δ06; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison ( Nature 368, 812-13 (1994)); Fishwild et al,( Nature Biotechnology 14,
845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).
Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incoφorated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The prefeπed embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules. An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Patent No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent reaπangement of the locus and to prevent formation of a transcript of a reaπanged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.
A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Patent No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.
In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a coπelative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049. Fab Fragments and Single Chain Antibodies
According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Patent No. 4,946,77δ). In addition, methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F ab^ fragment produced by pepsin digestion of an antibody molecule; (ii) an Fab fragment generated by reducing the disulfide bridges of an F(ab')2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments. Bispecific Antibodies
Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.
Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture often different antibody molecules, of which only one has the coπect bispecific structure. The purification of the coπect molecule is usually accomplished by affinity chromatography. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).
Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is prefeπed to have the first heavy-chain constant region (CHI) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121 :210 (1986).
According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers that are recovered from recombinant cell culture. The prefeπed interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g., tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g., alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers. Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g., F(ab')2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab')2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.
Additionally, Fab' fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab')2 molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.
Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al, J.
Immunol. 148(5): 1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The "diabody" technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) by a linker that is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994). Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).
Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g., CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CDI 6) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF). Heteroconjugate Antibodies
Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this puφose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Patent No. 4,676,980.
Effector Function Engineering
It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved intemalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 14δ: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).
Immunoconj ugates
The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate). Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212Bi, 1311, 13IIn, 90Y, and 186Re.
Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science.238: 1098 ( 1987). Carbon- 14-labeled l-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.
In another embodiment, the antibody can be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" (e.g., avidin) that is in turn conjugated to a cytotoxic agent.
Immunoliposomes The antibodies disclosed herein can also be formulated as immunoliposomes.
Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556.
Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and
PEG-derivatized phosphatidylethanolamme (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al.,_J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al, J. National Cancer Inst., 81(19): 1484 (1989).
Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention
In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.
Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (refeπed to hereinafter as "Therapeutics"). An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ,25I, 13lI, 35S or 3H. Antibody Therapeutics
Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible. Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand that may be absent or defective in the disease or pathology, binds the antibody as a suπogate effector ligand, initiating a receptor-based signal transduction event by the receptor.
A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.
Pharmaceutical Compositions of Antibodies
Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington : The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa. : 1995; Drug Absoφtion Enhancement : Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.
If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are prefeπed. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is prefeπed. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7δ93 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the puφose intended.
The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.
The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes. Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT ™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. ELISA Assay
An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g. , Fab or F(ab)2) can be used. The term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term "biological sample" is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term "biological sample", therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in "ELISA: Theory and Practice: Methods in Molecular Biology", Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, NJ, 1995; "Immunoassay", E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, CA, 1996; and "Practice and Theory of Enzyme Immunoassays", P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. NOVX Recombinant Expression Vectors and Host Cells
Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are refeπed to herein as "expression vectors". In general, useful expression vectors in recombinant DNA techniques are often in the form of plasmids. In the present specification, "plasmid" and "vector" can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.
The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, "operably-linked" is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).
The term "regulatory sequence" is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).
The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase. Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three puφoses: (/) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.
Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al, (1988) Gene 69:301-315) and pET 1 Id (Srudier et al, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).
One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized inE. coli (see, e.g., Wada, et al, 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.
In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (Baldari, et al, 1987. EMBOJ. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al, 1987. Gene 54: 113-123), pYES2 (Invitrogen Coφoration, San Diego, Calif), and picZ (InVitrogen Coφ, San Diego, Calif.).
Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al, 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31 -39). In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al, 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al, MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.
In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid).
Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al, 1987. Genes Dev. 1 : 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banerji, et al, 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al, 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166).
Developmentally-regulated promoters are also encompassed, e.g. , the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the -fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).
The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al, "Antisense RNA as a molecular tool for genetic analysis," Reviews-Trends in Genetics, Vol. 1(1) 1986. Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms "host cell" and "recombinant host cell" are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.
A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.
Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DΕAΕ-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.
For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g. , cells that have incoφorated the selectable marker gene will survive, while the other cells die). A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.
Transgenic NOVX Animals The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a "transgenic animal" is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a "homologous recombinant animal" is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal. A transgenic animal of the invention can be created by introducing a
NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866; 4,870,009; and 4,873,191 ; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other fransgenes. To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA ofany one of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also refeπed to as a "knock out" vector). Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5'- and 3 '-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5'- and 3'-termini) are included in the vector. See, e.g., Thomas, et al., 1987. Cell 51 : 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al, 1992. Ce/769: 915.
The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 19δ7. In: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACΠCAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol 2: δ23-δ29; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.
In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage PI . For a description of the cre/loxP recombinase system, see, e.g., Lakso, et al, 1992. Proc. Natl. Acad. Sci. USA 89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al, 1991. Science 251 :1351-1355. If a cre loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of "double" transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.
Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al, 1997. Nature 3δ5: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter Go phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transfeπed to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.
Pharmaceutical Compositions
The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also refeπed to herein as "active compounds") of the invention, and derivatives, fragments, analogs and homologs thereof, can be incoφorated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absoφtion delaying agents, and the like, compatible with pharmaceutical administration. Suitable caπiers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incoφorated herein by reference. Prefeπed examples of such caπiers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incoφorated into the compositions. A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.
Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absoφtion of the injectable compositions can be brought about by including in the composition an agent that delays absoφtion, for example, aluminum monostearate and gelatin.
Sterile injectable solutions can be prepared by incoφorating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incoφorating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.
Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the puφose of oral therapeutic administration, the active compound can be incoφorated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.
For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser that contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer. Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art. The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.
In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Coφoration and Nova
Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Patent No. 4,522,811. It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.
The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Patent No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al, 1994. Proc. Natl. Acad. Sci. USA 91 : 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system. The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.
Screening and Detection Methods
The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or abeπant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absoφtion of nutrients and the disposition of metabolic substrates in both a positive and negative fashion. The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.
Screening Assays
The invention provides a method (also refeπed to herein as a "screening assay") for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.
In one embodiment, the invention provides assays for screening candidate or test compounds that bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the "one-bead one-compound" library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g.. Lam, 1997 '. Anticancer Drug Design 12: 145.
A "small molecule" as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.
Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al, 1993. Proc. Natl. Acad. Sci. U.S.A. 90: 6909; Erb, et al, 1994. Proc. Natl. Acad. Sci. U.S.A. 91 : 11422; Zuckermann, et al, 1994. J. Med. Chem. 37: 2678; Cho, et al, 1993. Science 261: 1303; Caπell, et al, 1994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et al, 1994. Angew. Chem. Int. Ed. Engl. 33: 2061 ; and Gallop, et al, 1994. J. Med. Chem. 37: 1233. Libraries of compounds may be presented in solution (e.g. , Houghten, 1992.
Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-δ4), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Patent No. 5,223,409), spores (Ladner, U.S. Patent 5,233,409), plasmids (Cull, et al, 1992. Proc. Natl. Acad. Sci. USA δ9: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al, 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Patent No. 5,233,409.).
In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with 125I, 35S, 14C, or 3H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.
In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a "target molecule" is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g., a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.
Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e., intracellular Ca2+, diacylglycerol, IP3, etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.
In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.
In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra. In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.
The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-l 14, Thesit®, Isotridecypoly(ethylene glycol ether)n, N-dodecyl~N,N-dimethyl-3-ammonio-l -propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1 -propane sulfonate (CHAPS), or
3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-l -propane sulfonate (CHAPSO). In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NO VX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, MO) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.
Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, 111.), and immobilized in the wells of sfreptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.
In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.
In yet another aspect of the invention, the NOVX proteins can be used as "bait proteins" in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Patent No. 5,283,317; Zervos, et al, 1993. Cell 72: 223-232; Madura, et al, 1993. J. Biol. Chem. 26δ: 12046-12054; Bartel, et al, 1993. Biotechniques 14: 920-924; Iwabuchi, et al, 1993. Oncogene 8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX ("NOVX-binding proteins" or "NOVX-bp") and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway. The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein ("prey" or "sample") is fused to a gene that codes for the activation domain of the known transcription factor. If the "bait" and the "prey" proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.
The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein. Detection Assays
Portions or fragments of the cDNA sequences identified herein (and the coπesponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.
Chromosome Mapping Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 566, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping ofthe NOVX sequences to chromosomes is an important first step in coπelating these sequences with genes associated with disease.
Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis ofthe NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene coπesponding to the NOVX sequences will yield an amplified fragment.
Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al, 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.
PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.
Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1 ,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al, HUMAN CHROMOSOMES: A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988).
Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents coπesponding to noncoding regions of the genes actually are prefeπed for mapping puφoses. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.
Once a sequence has been mapped to a precise chromosomal location, the physical position ofthe sequence on the chromosome can be coπelated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al, 1987. Nature, 325: 783-787.
Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all ofthe affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent ofthe particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymoφhisms.
Tissue Typing
The NOVX sequences ofthe invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences ofthe invention are useful as additional DNA markers for RFLP ("restriction fragment length polymoφhisms," described in U.S. Patent No. 5,272,057).
Furthermore, the sequences ofthe invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5'- and 3'-termini ofthe sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.
Panels of coπesponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences ofthe invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences ofthe invention uniquely represent portions ofthe human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much ofthe allelic variation is due to single nucleotide polymoφhisms (SNPs), which include restriction fragment length polymoφhisms (RFLPs).
Each ofthe sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification puφoses. Because greater numbers of polymoφhisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.
Predictive Medicine
The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) puφoses to thereby treat an individual prophylactically. Accordingly, one aspect ofthe invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with abeπant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive puφose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity. Another aspect ofthe invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (refeπed to herein as "pharmacogenomics"). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability ofthe individual to respond to a particular agent.)
Yet another aspect ofthe invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials. These and other agents are described in further detail in the following sections.
Diagnostic Assays
An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g. , mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays ofthe invention are described herein. An agent for detecting NOVX protein is an antibody capable of binding to
NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab')2) can be used. The term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling ofthe probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling ofthe probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term "biological sample" is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A prefeπed biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.
The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid. Prognostic Assays
The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with abeπant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with abeπant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with abeπant NOVX expression or activity. As used herein, a "test sample" refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.
Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with abeπant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g. , wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with abeπant NOVX expression or activity).
The methods ofthe invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by abeπant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (/') a deletion of one or more nucleotides from a NOVX gene; (ιϊ) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal reaπangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) abeπant modification of a NOVX gene, such as of the methylation pattem of the genomic DNA, (v») the presence of a non-wild-type splicing pattem of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A prefeπed biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.
In certain embodiments, detection ofthe lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Patent Nos. 4,6δ3,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al, 1988. Science 241: 1077- 1080; and Nakazawa, et al, 1994. Proc. Natl. Acad. Sci. USA 91 : 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al, 1995. Nucl. Acids Res. 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells ofthe sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification ofthe NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size ofthe amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any ofthe techniques used for detecting mutations described herein.
Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al, 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al, 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection ofthe amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.
In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and confrol DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Patent No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site. In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density aπays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al, 1996. Human Mutation 7: 244-255; Kozal, et al, 1996. Nat. Med. 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional aπays containing light-generated DNA probes as described in Cronin, et al, supra. Briefly, a first hybridization aπay of probes can be used to scan through long stretches of DNA in a sample and confrol to identify base changes between the sequences by making linear aπays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization aπay that allows the characterization of specific mutations by using smaller, specialized probe aπays complementary to all variants or mutations detected. Each mutation aπay is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.
In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence ofthe sample NOVX with the coπesponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al, 1995. Biotechniques 19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101 ; Cohen, et al, 1996. Adv. Chromatography 36: 127-162; and Griffin, et al, 1993. Appl. Biochem. Biotechnol 38: 147-159).
Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al, 1985. Science 230: 1242. In general, the art technique of "mismatch cleavage" starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions ofthe duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA DNA hybrids treated with Si nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion ofthe mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al, 198δ. Proc. Natl. Acad. Sci. USA δ5: 4397; Saleeba, et al, 1992. Methods Enzymol 217: 2δ6-295. In an embodiment, the control DNA or RNA can be labeled for detection.
In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called "DNA mismatch repair" enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al, 1994. Carcinogenesis 15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Patent No. 5,459,039.
In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymoφhism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al, 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g.. Keen, et al, 1991. Trends Genet. 7: 5.
In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e.g., Myers, et al, 1985. Nature 313: 495. When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265: 12753.
Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, et al, 1986. Nature 324: 163; Saiki, et al, 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.
Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al, 1989. Nucl. Acids Res. 17: 2437-2448) or at the extreme 3 '-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11 : 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e.g., Gasparini, et al, 1992. Mol. Cell Probes 6: 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 1991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3'-terminus ofthe 5' sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification. The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.
Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.
Pharmacogenomics
Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) ofthe individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration ofthe pharmacologically active drug. Thus, the pharmacogenomics ofthe individual permits the selection of effective agents (e.g., drugs) for prophylactic or therapeutic treatments based on a consideration ofthe individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment ofthe individual. Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol, 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymoφhisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.
As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymoφhisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymoφhisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymoφhic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite moφhine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.
Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment ofthe individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymoφhic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one ofthe exemplary screening assays described herein.
Monitoring of Effects During Clinical Trials
Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e.g., the ability to modulate abeπant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity. In such clinical trials, the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a "read out" or markers ofthe immune responsiveness of a particular cell.
By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e. , a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one ofthe methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response ofthe cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment ofthe individual with the agent.
In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration ofthe agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity ofthe NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity ofthe NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration ofthe agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness ofthe agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness ofthe agent. Methods of Treatment
The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with abeπant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
These methods of treatment will be discussed more fully, below.
Diseases and Disorders Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (/) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (») antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are "dysfunctional" (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to "knockout" endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989.
Science 244: 1288-1292); or (v) modulators ( i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide ofthe invention) that alter the interaction between an aforementioned peptide and its binding partner. Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability. Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity ofthe expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like). Prophylactic Methods
In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an abeπant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by abeπant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic ofthe NOVX abeπancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX abeπancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods ofthe invention are further discussed in the following subsections.
Therapeutic Methods
Another aspect ofthe invention pertains to methods of modulating NOVX expression or activity for therapeutic puφoses. The modulatory method ofthe invention involves contacting a cell with an agent that modulates one or more ofthe activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by abeπant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or abeπant NOVX expression or activity.
Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by abeπant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).
Determination of the Biological Effect of the Therapeutic In various embodiments ofthe invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment ofthe affected tissue.
In various specific embodiments, in vitro assays may be performed with representative cells ofthe type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any ofthe animal model system known in the art may be used prior to administration to human subjects. Prophylactic and Therapeutic Uses of the Compositions of the Invention
The NOVX nucleic acids and proteins ofthe invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.
As an example, a cDNA encoding the NOVX protein ofthe invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions ofthe invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.
Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein ofthe invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances ofthe invention for use in therapeutic or diagnostic methods.
The invention will be further described in the following examples, which do not limit the scope ofthe invention described in the claims.
EXAMPLES
Example A: Polynucleotide and Polypeptide Sequences, and Homology Data
Example 1.
The NOVl clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table IA.
Table IA. NOVl Sequence Analysis
NOVla, CG101340-01 SEQ ID NO: 1 1327 bp DNA Sequence IORF Start: ATG at 76 fORF Stop: TGA at 1192
GAGGTGAATGCCATGCCATGATTCTGGTGTGCTCCATGGCATCCCCAGCCTAGCTCCCAATCCCACTTi
TGGCACGATGTTAGCCAACAGCTCCTCAACCAACAGTTCTGTTCTCCCGTGTCCTGACTACCGACCTA!
CCCACCGCCTGCACTTGGTGGTCTACAGCTTGGTGCTGGCTGCCGGGCTCCCCCTCAACGCGCTAGCC CTCTGGGTCTTCCTGCGCGCGCTGCGCGTGCACTCGGTGGTGAGCGTGTACATGTGTAACCTGGCGGC CAGCGACCTGCTCTTCACCCTCTCGCTGCCCGTTCGTCTCTCCTACTACGCACTGCACCACTGGCCCT TCCCCGACCTCCTGTGCCAGACGACGGGCGCCATCTTCCAGATGAACATGTACGGCAGCTGCATCTTC CTGATGCTCATCAACGTGGACCGCTACGCCGCCATCGTGCACCCGCTGCGACTGCGCCACCTGTGGCG GCCCCGCGTGGCGCGGCTGCTCTACCTGGGCGTGTGGGCGCTCATCCTGGTGTTTGCCGTGCCCGCCG CCCGCGTGCACAGGCCCTCGCGTTGCCGCTACCGGGACCTCGAGGTGCGCCTATGCTTCGAGAGCTTC TGCGACGAGCTGTGGAAAGGCAGGCTGCTGCCCCTCGTGCTGCTGGCCGAGGCGCTGGGCTTCCTGCT GCCCCTGGCGGCGGTGGTCTACTCGTCGGGCCGAGTCTTCTGGACGCTGGCGCGCCCCGACGCCACGC AGAGCCAGCGGCGGTGGAAGACCGTGCGCCTCCTGCTGGCTAACCTCGTCATCTTCCTGCTGTGCTTC GTGCCCTACAACAGCACGCTGGCGGTCTACGGGCTGCTGCGGAGCAAGCTGGTGGCGGCCAGCGTGCC TGCCCGCGATCGCGTGCGCGGGGTGCTGATGGTGATGGTGCTGCTGGCCGGCGCCAACTGCGTGCTGG ACCCGCTGGTGTACTACTTTAGCGCCGAGGGCTTCCGCAACACCCTGCGCGGCCTGGGCACTCCGCAC CGGGCCAGGACCTCGGCCACCAACGGGACGCGGGCGGCGCTCGCGCAATCCGAAAGGTCCGCCGTCAC CACCGACGCCACCAGGCCGGATGCCGCCAGTCAGGGGCTGCTCCGACCCTCCGACTCCCACTCTCTGT CTTCCTTCACACAGTGTCCCCAGGATTCCGCCCTCTGAACACACATGCCATTGCGCTGTCCGTGCCCG ACTCCCAACGCCTCTCGTTCTGGGAGGCTTACAGGGCGTACACACAAGAAGGTGGGCTGGGCACTTGG ACCTTTGGGTGGCAATTCCAGCTTAGCAACGCAGA
NO VI a, CGI 01340-01 SEQ ID NO: 2 372 aa MW at 414δ2.1kD Protein Sequence
MLANSSSTNSSVLPCPDYRPTHRLHLWYS VLAAGLPLNALA WVFLRALRVHSWSVYMCNLAASD LFTLSLPVRLSYYA HHWPFPDLLCQTTGAI FQMNMYGSCI F M INVDRYAAI VHP R RH WRPR VARLLYLGVWALI VFAVPAARVHRPSRCRYRDLEVRLCFESFCDELWKGRLLPLVLLAEALGF LP AAVVYSSGRVFWTLARPDATQSQRRWKTVR LANLVIFLLCFVPYNSTLAVYGLLRSKLVAASVPAR DRV GVL^r\ V JIiAGANCV DPLVYYFSAEGFRNTLRG GTPHRARTSATNGTRA LAQSERSAVTTD ATRPDAASQGLLRPSDSHSLSSFTQCPQDSA
NOVlb, SNP133δ2465 of SEQ ID NO: 3 1327 bp CG101340-01 , DNA Sequence ORF Start: ATG at 76 ORF Stop: TGA at 1192
SNP Pos: 472 SNP Change: T to C
GAGGTGAATGCCATGCCATGATTCTGGTGTGCTCCATGGCATCCCCAGCCTAGCTCCCAATCCCACTT
TGGCACGATGTTAGCCAACAGCTCCTCAACCAACAGTTCTGTTCTCCCGTGTCCTGACTACCGACCTA
CCCACCGCCTGCACTTGGTGGTCTACAGCTTGGTGCTGGCTGCCGGGCTCCCCCTCAACGCGCTAGCC CTCTGGGTCTTCCTGCGCGCGCTGCGCGTGCACTCGGTGGTGAGCGTGTACATGTGTAACCTGGCGGC CAGCGACCTGCTCTTCACCCTCTCGCTGCCCGTTCGTCTCTCCTACTACGCACTGCACCACTGGCCCT TCCCCGACCTCCTGTGCCAGACGACGGGCGCCATCTTCCAGATGAACATGTACGGCAGCTGCATCTTC CTGATGCTCATCAACGTGGACCGCTACGCCGCCATCGTGCACCCGCTGCGACTGCGCCACCTGCGGCG GCCCCGCGTGGCGCGGCTGCTCTACCTGGGCGTGTGGGCGCTCATCCTGGTGTTTGCCGTGCCCGCCG CCCGCGTGCACAGGCCCTCGCGTTGCCGCTACCGGGACCTCGAGGTGCGCCTATGCTTCGAGAGCTTC TGCGACGAGCTGTGGAAAGGCAGGCTGCTGCCCCTCGTGCTGCTGGCCGAGGCGCTGGGCTTCCTGCT GCCCCTGGCGGCGGTGGTCTACTCGTCGGGCCGAGTCTTCTGGACGCTGGCGCGCCCCGACGCCACGC AGAGCCAGCGGCGGTGGAAGACCGTGCGCCTCCTGCTGGCTAACCTCGTCATCTTCCTGCTGTGCTTC GTGCCCTACAACAGCACGCTGGCGGTCTACGGGCTGCTGCGGAGCAAGCTGGTGGCGGCCAGCGTGCC TGCCCGCGATCGCGTGCGCGGGGTGCTGATGGTGATGGTGCTGCTGGCCGGCGCCAACTGCGTGCTGG ACCCGCTGGTGTACTACTTTAGCGCCGAGGGCTTCCGCAACACCCTGCGCGGCCTGGGCACTCCGCAC CGGGCCAGGACCTCGGCCACCAACGGGACGCGGGCGGCGCTCGCGCAATCCGAAAGGTCCGCCGTCAC CACCGACGCCACCAGGCCGGATGCCGCCAGTCAGGGGCTGCTCCGACCCTCCGACTCCCACTCTCTGT CTTCCTTCACACAGTGTCCCCAGGATTCCGCCCTCTGAACACACATGCCATTGCGCTGTCCGTGCCCG ACTCCCAACGCCTCTCGTTCTGGGAGGCTTACAGGGCGTACACACAAGAAGGTGGGCTGGGCACTTGG
ACCTTTGGGTGGCAATTCCAGCTTAGCAACGCAGA
NOVlb, SNP133δ2465 of SEQ ID NO: 4 372 aa MW at 41452.1kD CGI 01340-01, Protein Sequence SNP Pos: 133 SNP Change: Tφ to Arg
MLJ-NSSSTNSSV PCPDYRPTHR HLVVYS VLAAGLPLNALAL VF RA RVHSVVSVYMCN AASD L FTLSLPVR SYYALHH PFPD CQTTGAI FQM MYGSCIFLM INVDRYAAIVHPLR RHLRRPR VARLLYLGWALILVFAVPAARVHRPSRCRYRDLEWLCFESFCDELWKGRLLPLVLLAEALGFLL.PL. AAWYSSGRVF TLARPDATQSQRRWKTVRLLLANLVIFLLCFVPYNSTLAVYG LRSKLVAASVPAR DRVRGVLMVMV IΛGANC ^DPLVYYFSAEGFRNTLRGLGTPHRARTSATNGTRAALAQSERSAVTTD ATRPDAASQGLLRPSDSHSLSSFTQCPQDSAL
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table IB.
Table IB. Comparison of the NOVl protein sequences.
NOVl8a MCSLPMARYYRIKΥADQKALYTRDGQLLVGDPVADNCCAEKICILPNRGLARTKVPIFLG NOVl8b MCSLPMARYYIIKYADQKALYTRDGQLLVGDPVADNCCAEKICILPNRG ARTKVPIF G NOVl8c SYCFRIKYADQKALYTRDGQ LVGDPVADNCCAEKICI PNRG ARTKVPIFLG
NOVl8a IQGGSRC ACVETEEGPSLQLEPST PPQDVNIEELYKGGEEATRFTFFQSSSGSAFRLE NOVl8b IQGGSRCLACVETEEGPSLQ E DVNIEELYKGGEEATRFTFFQSSSGSAFRLE NOV18C IQGGSRCLACVETEEGPSLQLEPSTLPPQDVNIEELYKGGEEATRFTFFQSSSGSAFRLE
NOVl8a AAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQSW
NOVl8b AAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQSW
NOV18C AAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQSW
NOVla (SEQ ID NO: 2)
Further analysis ofthe NOVla protein yielded the following properties shown in Table IC.
Table IC. Protein Sequence Properties NOVla
SignalP analysis: Cleavage site between residues 59 and 60
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 16; peak value 3.12 PSG score: -1.28
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1) : 0.37 possible cleavage site: between 43 and 44
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 6
INTEGRAL Likelihood -4.19 Transmembrane 31 - 47
INTEGRAL Likelihood -0.16 Transmembrane 99 - 115
INTEGRAL Likelihood -7.01 Transmembrane 140 - 156
INTEGRAL Likelihood -6.90 Transmembrane 192 - 208
INTEGRAL Likelihood -7.54 Transmembrane 232 - 248
INTEGRAL Likelihood -3.82 Transmembrane 277 - 293
PERIPHERAL Likelihood 1.43 (at 56)
ALOM score: •7.54 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 38 Charge difference: 0.5 C( 2.5) - N( 2.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 4.95 Hyd Moment(95): 3.49 G content: 0 D/E content: 1 S/T content: 6 Score: -3.65
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 176 CRY|RD
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum 11.1 %.- Golgi 11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG101340-01 is end (k=9)
A search ofthe NOVla protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several l hiΛommnollnognoiuios T pYrrroktteiinncs c shnrovwu/nn i inn T Taalblilne I IfDl.
Figure imgf000141_0001
In a BLAST search of public sequence databases, the NOVla protein was found to have homology to the proteins shown in the BLASTP data in Table IE.
Figure imgf000142_0001
PFam analysis indicates that the NOVla protein contains the domains shown in the Table IF.
Table IF. Domain Analysis of NOVla
Identities/
Pfam Domain NOVla Match Region Similarities Expect Value for the Matched Region
7tm 1 39..297 87/276 (32%) 7.2e-53 196/276 (71%) Example 2.
The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.
Table 2A. NOV2 Sequence Analysis
NO V2a, CG101396-01 SEQ ID NO? 5 |3189 bp DNA Sequence ORF Start: ATG at 86 ORF Stop: TGA at 3113
CTGCACCGGGACCAGCGCCTCCCCGCTTCGCGCTGCCCTCGGCCTCGCCCCGGGCCCGGGTGGATGAG
CCGCGCGCCCGGGGGACATGGAAGCGCTGACGCTGTGGCTTCTCCCCTGGATATGCCAGTGCGTGTCG!
GTGCGGGCCGACTCCATCATCCACATCGGTGCCATCTTCGAGGAGAACGCGGCCAAGGACGACAGGGT GTTCCAGTTGGCGGTATCCGACCTGAGCCTCAACGATGACATCCTGCAGAGCGAGAAGATCACCTACT CCATCAAGGTCATCGAGGCCAACAACCCATTCCAGGCTGTGCAGGAAGCCTGTGACCTCATGACCCAG GGGATTTTGGCCTTGGTCACGTCCACTGGCTGTGCATCTGCCAATGCCCTGCAGTCCCTCACGGATGC CATGCACATCCCACACCTCTTTGTCCAGCGCAACCCGGGAGGGTCGCCACGCACCGCATGCCACCTGA ACCCCAGCCCCGATGGTGAGGCCTACACACTGGCTTCGAGACCACCCGTCCGCCTCAATGATGTCATG CTCAGGCTGGTGACGGAGCTGCGCTGGCAGAAGTTCGTCATGTTCTACGACAGCGAGTATGATATCCG TGGGCTTCAAAGCTTTCTGGACCAGGCCTCGCGGCTGGGCCTTGACGTCTCTTTACAAAAGGTGGACA AGAACATTAGCCACGTATTCACCAGCCTCTTCACCACGATGAAGACAGAGGAGCTGAATCGCTACCGG GACACGCTTCGCCGCGCCATCCTGCTGCTCAGCCCACAGGGAGCCCACTCCTTCATCAACGAGGCCGT GGAGACCAACCTGGCTTCCAAGGACAGCCACTGGGTCTTTGTGAATGAGGAAATCAGTGACCCGGAGA TCCTGGATCTGGTCCATAGTGCCCTTGGAAGGATGACCGTGGTCCGGCAAATCTTTCCGTCTGCAAAG GACAATCAGAAATGCACGAGGAACAACCACCGCATCTCCTCCCTGCTCTGCGACCCCCAGGAAGGCTA CCTCCAGATGCTGCAGATCTCCAACCTCTATCTGTATGACAGTGTTCTGATGCTGGCCAACGCCTTTC ACAGGAAGCTGGAGGACCGGAAGTGGCATAGCATGGCGAGCCTCAACTGCATACGGAAATCCACTAAG CCATGGAATGGTGGGAGGTCCATGCTGGATACCATCAAAAAGGGCCACATCACTGGCCTCACTGGGGT GATGGAGTTTCGGGAGGACAGTTCGAATCCCTATGTCCAGTTTGAAATCCTTGGCACTACCTATAGTG AGACTTTTGGCAAAGACATGCGCAAGTTGGCGACATGGGACTCAGAGAAGGGCTTGAATGGCAGCTTG CAAGAGAGGCCCATGGGCAGCCGCCTCCAAGGATTGACTCTTAAAGTGGTGACTGTCTTGGAAGAGCC TTTCGTGATGGTGGCTGAGAACATCCTAGGACAGCCCAAGCGCTACAAAGGGTTCTCCATAGATGTCC TGGATGCACTGGCCAAGGCTCTGGGCTTTAAATATGAGATTTACCAAGCCCCTGATGGCAGGTACGGT CACCAGCTCCATAACACCTCCTGGAACGGGATGATCGGGGAGCTCATCAGCAAGAGAGCAGACTTGGC CATCTCTGCCATCACCATCACCCCAGAGAGGGAGAGCGTTGTGGACTTCAGCAAGCGGTACATGGACT ATTCAGTGGGGATTCTAATTAAGAAGCCCGAGGAGAAAATCAGCATCTTCTCCCTCTTTGCTCCATTT GATTTCGCTGTGTGGGCCTGCATTGCAGCAGCCATCCCTGTGGTTGGTGTGCTGATATTTGTGTTGAA CAGGATACAGGCTGTGAGGGCTCAGAGTGCTGCCCAGCCCAGGCCGTCAGCTTCTGCCACTCTGCACA GCGCCATCTGGATTGTCTATGGAGCCTTCGTACAGCAAGGTGGCGAATCTTCCGTGAACTCCATGGCC ATGCGCATCGTGATGGGCAGCTGGTGGCTCTTCACGCTCATTGTGTGCTCCTCCTACACAGCCAACCT TGCTGCCTTCCTCACAGTGTCCAGGATGGACAACCCCATAAGGACTTTCCAGGACCTGTCCAAACAAG TGGAAATGTCTTATGGCACTGTCCGGGATTCTGCTGTATATGAGTACTTCCGAGCCAAGGGCACCAAC CCCCTGGAGCAGGACAGCACGTTTGCTGAACTCTGGCGGACCATCAGCAAGAACGGAGGGGCTGACAA CTGCGTGTCCAGTCCTTCAGAAGGCATCAGGAAGGCAAAGAAGGGGAACTACGCCTTCCTGTGGGATG TGGCCGTGGTGGAATACGCAGCCCTGACGGATGACGACTGCTCGGTGACTGTCATCGGCAACAGCATC AGCAGCAAGGGTTACGGGATTGCCCTGCAGCATGGCAGCCCCTACAGGGACCTCTTCTCCCAGAGGAT CCTGGAGCTGCAGGACACAGGGGACCTGGATGTGCTGAAGCAGAAGTGGTGGCCGCACATGGGCCGCT GTGACCTCACCAGCCATGCCAGCGCCCAGGCCGACGGCAAATCCCTCAAGCTGCACAGCTTCGCCGGG GTCTTCTGCATCCTGGCCATTGGCCTGCTCCTGGCCTGCCTGGTGGCTGCCCTGGAGTTGTGGTGGAA CAGCAACCGGTGCCACCAGGAGACCCCCAAGGAGGACAAAGAAGTGAACTTGGAGCAGGTCCACCGGC GCATGAACAGCCTCATGGATGAAGACATTGCTCACAAGCAGATTTCCCCAGCGTCGATTGAGCTCTCG GCCCTGGAGATGGGGGGCCTGGCTCCCACCCAGACCTTGGAGCCGACACGGGAGTACCAGAACACCCA GCTCTCGGTCAGCACCTTTCTGCCAGAGCAGAGCAGCCATGGCACCAGCCGGACACTCTCATCAGGGC CCAGCAGCAACCTGCCGCTGCCGCTGAGCAGCTCGGCGACCATGCCCTCCATGCAGTGCAAACACAGG TCACCCAACGGGGGGCTGTTCCGGCAGAGCCCGGTGAAGACCCCCATCCCCATGTCCTTCCAGCCCGT GCCTGGAGGCGTCCTTCCAGAGGCTCTGGACACCTCCCACGGGACCTCCATCTGACTGCGCCGCCTGC CCTCCTGCCCACCCTCCCACCCACCCGACCAGCAGAGCTTTTTAATACAAGAAAACAACAA NOV2a, CGI 01396-01 SEQ ID NO: 6 1009 aa MW at l l2129.7kD Protein Sequence
MEALTLWLLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQSEKITYSIKVIE ANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFVQRNPGGSPRTACHLNPSPDG EAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIRGLQSFLDQASRLGLDVSLQKVDKNISHV FTSLFTTMKTEELNRYRDTLRRAILLLSPQGAHSFINEAVETNLASKDSHWVFVNEEISDPEILDLVH SALGRMTWRQIFPSAKDNQKCTRNNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLED RK HSMASLNCIRKSTKPWNGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKD MRKLATVroSEKGLNGSLQERPMGSRLQGLTLKVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK ALGFKYEIYQAPDGRYGHQLHNTS NGMIGELISKRADLAISAITITPERESWDFSKRYMDYSVGIL IKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQPRPSASATLHSAIWIV YGAFVQQGGESSVNSMAMRIVMGS LFTLIVCSSYTANLAAFLTVSRMDNPIRTFQDLSKQVEMSYG TVRDSAVYEYFRAKGTNPLEQDSTFAEL RTISKNGGADNCVSSPSEGIRKAKKGNYAFL DVAWEY AALTDDDCSVTVIGNSISSKGYGIALQHGSPYRDLFSQRILELQDTGDLDVLKQKW PHMGRCDLTSH ASAQADGKSLKLHSFAGVFCILAIGLLLACLVAALEL WNSNRCHQETPKEDKEVNLEQVHRRMNSLM DEDIAHKQISPASIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLP LPLSSSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI
NOV2b, 267253224 SEQ ID NO: 7 2986 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGTACCGACTCCATCATCCACATCGGTGCCATCTTCGAGGAGAACGCGGCCAAGGACGACAGGG TGTTCCAGTTGGCGGTATCCGACCTGAGCCTCAACGATGACATCCTGCAGAGCGAGAAGATCACCTAC TCCATCAAGGTCATCGAGGCCAACAACCCATTCCAGGCTGTGCAGGAAGCCTGTGACCTCATGACCCA GGGGATTTTGGCCTTGGTCACGTCCACTGGCTGTGCATCTGCCAATGCCCTGCAGTCCCTCACGGATG CCATGCACATCCCACACCTCTTTGTCCAGCGCAACCCGGGAGGGTCGCCACGCACCGCATGCCACCTG AACCCCAGCCCCGATGGTGAGGCCTACACACTGGCTTCGAGACCACCCGTCCGCCTCAATGATGTCAT GCTCAGGCTGGTGACGGAGCTGCGCTGGCAGAAGTTCGTCATGTTCTACGACAGCGAGTATGATATCC GTGGGCTTCAAAGCTTTCTGGACCAGGCCTCGCGGCTGGGCCTTGACGTCTCTTTACAAAAGGTGGAC AAGAACATTAGCCACGTATTCACCAGCCTCTTCACCACGATGAAGACAGAGGAGCTGAATCGCTACCG GGACACGCTTCGCCGCGCCATCCTGCTGCTCAGCCCACAGGGAGCCCACTCCTTCATCAACGAGGCCG TGGAGACCAACCTGGCTTCCAAGGACAGCCACTGGGTCTTTGTGAATGAGGAAATCAGTGACCCGGAG ATCCTGGATCTGGTCCATAGTGCCCTTGGAAGGATGACCGTGGTCCGGCAAATCTTTCCGTCTGCAAA GGACAATCAGAAATGCACGAGGAACAACCACCGCATCTCCTCCCTGCTCTGCGACCCCCAGGAAGGCT ACCTCCAGATGCTGCAGATCTCCAACCTCTATCTGTATGACAGTGTTCTGATGCTGGCCAACGCCTTT CACAGGAAGCTGGAGGACCGGAAGTGGCATAGCATGGCGAGCCTCAACTGCATACGGAAATCCACTAA GCCATGGAATGGTGGGAGGTCCATGCTGGATACCATCAAAAAGGGCCACATCACTGGCCTCACTGGGG TGATGGAGTTTCGGGAGGACAGTTCGAATCCCTATGTCCAGTTTGAAATCCTTGGCACTACCTATAGT GAGACTTTTGGCAAAGACATGCGCAAGTTGGCGACATGGGACTCAGAGAAGGGCTTGAATGGCAGCTT GCAAGAGAGGCCCATGGGCAGCCGCCTCCAAGGATTGACTCTTAAAGTGGTGACTGTCTTGGAAGAGC CTTTCGTGATGGTGGCTGAGAACATCCTAGGACAGCCCAAGCGCTACAAAGGGTTCTCCATAGATGTC CTGGATGCACTGGCCAAGGCTCTGGGCTTTAAATATGAGATTTACCAAGCCCCTGATGGCAGGTACGG TCACCAGCTCCATAACACCTCCTGGAACGGGATGATCGGGGAGCTCATCAGCAAGAGAGCAGACTTGG CCATCTCTGCCATCACCATCACCCCAGAGAGGGAGAGCGTTGTGGACTTCAGCAAGCGGTACATGGAC TATTCAGTGGGGATTCTAATTAAGAAGCCCGAGGAGAAAATCAGCATCTTCTCCCTCTTTGCTCCATT TGATTTCGCTGTGTGGGCCTGCATTGCAGCAGCCATCCCTGTGGTTGGTGTGCTGATATTTGTGTTGA ACAGGATACAGGCTGTGAGGGCTCAGAGTGCTGCCCAGCCCAGGCCGTCAGCTTCTGCCACTCTGCAC AGCGCCATCTGGATTGTCTATGGAGCCTTCGTACAGCAAGGTGGCGAATCTTCCGTGAACTCCATGGC CATGCGCATCGTGATGGGCAGCTGGTGGCTCTTCACGCTCATTGTGTGCTCCTCCTACACAGCCAACC TTGCTGCCTTCCTCACAGTGTCCAGGATGGACAACCCCATAAGGACTTTCCAGGACCTGTCCAAACAA GTGGAAATGTCTTATGGCACTGTCCGGGATTCTGCTGTATATGAGTACTTCCGAGCCAAGGGCACCAA CCCCCTGGAGCAGGACAGCACGTTTGCTGAACTCTGGCGGACCATCAGCAAGAACGGAGGGGCTGACA ACTGCGTGTCCAGTCCTTCAGAAGGCATCAGGAAGGCAAAGAAGGGGAACTACGCCTTCCTGTGGGAT GTGGCCGTGGTGGAATACGCAGCCCTGACGGATGACGACTGCTCGGTGACTGTCATCGGCAACAGCAT CAGCAGCAAGGGTTACGGGATTGCCCTGCAGCATGGCAGCCCCTACAGGGACCTCTTCTCCCAGAGGA TCCTGGAGCTGCAGGACACAGGGGACCTGGATGTGCTGAAGCAGAAGTGGTGGCCGCACATGGGCCGC TGTGACCTCACCAGCCATGCCAGCGCCCAGGCCGACGGCAAATCCCTCAAGCTGCACAGCTTCGCCGG GGTCTTCTGCATCCTGGCCATTGGCCTGCTCCTGGCCTGCCTGGTGGCTGCCCTGGAGTTGTGGTGGA ACAGCAACCGGTGCCACCAGGAGACCCCCAAGGAGGACAAAGAAGTGAACTTGGAGCAGGTCCACCGG CGCATGAACAGCCTCATGGATGAAGACATTGCTCACAAGCAGATTTCCCCAGCGTCGATTGAGCTCTC GGCCCTGGAGATGGGGAGCCTGGCTCCCACCCAGACCTTGGAGCCGACACGGGAGTACCAGAACACCC AGCTCTCGGTCAGCACCTTTCTGCCAGAGCAGAGCAGCCATGGCACCAGCCGGACACTCTCATCAGGG CCCAGCAGCAACCTGCCGCTGCCGCTGAGCAGCTCGGCGACCATGCCCTCCATGCAGTGCAAACACAG GTCACCCAACGGGGGGCTGTTCCGGCAGAGCCCGGTGAAGACCCCCATCCCCATGTCCTTCCAGCCCG TGCCTGGAGGCGTCCTTCCAGAGGCTCTGGACACCTCCCACGGGACCTCCATCCTCGAGGGC
NOV2b, 267253224 SEQ ID NO: 8 995 aa MW at l l0403.5kD Protein Sequence
TGTDSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQSEKITYSIKVIEANNPFQAVQEACDLMTQ GILALVTSTGCASANALQSLTDAMHIPHLFVQRNPGGSPRTACHLNPSPDGEAYTLASRPPVRIiNDVM LRLVTELR QKFVMFYDSEYDIRGLQSFLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYR DTLRRAILLLSPQGAHSFINEAVETNLASKDSHWVFVNEEISDPEILDLVHSALGRMTWRQIFPSAK DNQKCTRNNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRKWHSMASLNCIRKSTK P NGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWDSEKGLNGSL QERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAKALGFKYEIYQAPDGRYG HQLHNTS NGMIGELISKRADLAISAITITPERESWDFSKRYMDYSVGILIKKPEEKISIFSLFAPF DFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQPRPSASATLHSAIWIVYGAFVQQGGESSVNSMA MRIVMGS LFTLIVCSSYTANLAAFLTVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTN PLEQDSTFAELWRTISKNGGADNCVSSPSEGIRKAKKGNYAFLWDVAWEYAALTDDDCSVTVIGNSI SSKGYGIALQHGSPYRDLFSQRILELQDTGDLDVLKQK WPHMGRCDLTSHASAQADGKSLKLHSFAG VFCILAIGLLLACLVAALEL WNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPASIELS ALEMGSLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLSSSATMPSMQCKHR SPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSILEG
NOV2c, 315490179 SEQ ID NO: 9 3049 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCACCATGGAAGCGCTGACGCTGTGGCTTCTCCCCTGGATATGCCAGTGCGTGTCGGTGC GGGCCGACTCCATCATCCACATTGGTGCCATCTTCGAGGAGAACGCGGCCAAGGACGACAGGGTGTTC CAGTTGGCGGTATCCGACCTGAGCCTCAACGATGACATCCTGCAGAGCGAGAAGATCACCTACTCCAT CAAGGTCATCGAGGCCAACAACCCATTCCAGGCTGTGCAGGAAGCCTGTGACCTCATGACCCAGGGGA TTTTGGCCTTGGTCACGTCCACTGGCTGTGCATCTGCCAATGCCCTGCAGTCCCTCACGGATGCCATG CACATCCCACACCTCTTTGTCCAGCGCAACCCGGGAGGGTCGCCACGCACCGCATGCCACCTGAACCC CAGCCCCGATGGTGAGGCCTACACACTGGCTTCGAGACCACCCGTCCGCCTCAATGATGTCATGCTCA GGCTGGTGACGGAGCTGCGCTGGCAGAAGTTCGTCATGTTCTACGACAGCGAGTATGATATCCGTGGG CTTCAAAGCTTTCTGGACCAGGCCTCGCGGCTGGGCCTTGACGTCTCTTTACAAAAGGTGGACAAGAA CATTAGCCACGTATTCACCAGCCTCTTCACCACGATGAAGACAGAGGAGCTGAATCGCTACCGGGACA CGCTTCGCCGCGCCATCCTGCTGCTCAGCCCACAGGGAGCCCACTCCTTCATCAACGAGGCCGTGGAG ACCAACCTGGCTTCCAAGGACAGCCACTGGGTCTTTGTGAATGAGGAAATCAGTGACCCGGAGATCCT GGATCTGGTCCATAGTGCCCTTGGAAGGATGACCGTGGTCCGGCAAATCTTTCCGTCTGCAAAGGACA ATCAGAAATGCACGAGGAACAACCACCGCATCTCCTCCCTGCTCTGCGACCCCCAGGAAGGCTACCTC CAGATGCTGCAGATCTCCAACCTCTATCTGTATGACAGTGTTCTGATGCTGGCCAACGCCTTTCACAG GAAGCTGGAGGACCGGAAGTGGCATAGCATGGCGAGCCTCAACTGCATACGGAAATCCACTAAGCCAT GGAATGGTGGGAGGTCCATGCTGGATACCATCAAAAAGGGCCACATCACTGGCCTCACTGGGGTGATG GAGTTTCGGGAGGACAGTTCGAATCCCTATGTCCAGTTTGAAATCCTTGGCACTACCTATAGTGAGAC TTTTGGCAAAGACATGCGCAAGTTGGCGACATGGGACTCAGAGAAGGGCTTGAATGGCAGCTTGCAAG AGAGGCCCATGGGCAGCCGCCTCCAAGGATTGACTCTTAAAGTGGTGACTGTCTTGGAAGAGCCTTTC GTGATGGTGGCTGAGAACATCCTAGGACAGCCCAAGCGCTACAAAGGGTTCTCCATAGATGTCCTGGA TGCACTGGCCAAGGCTCTGGGCTTTAAATATGAGATTTACCAAGCCCCTGATGGCAGGTACGGTCACC AGCTCCATAACACCTCCTGGAACGGGATGATCGGGGAGCTCATCAGCAAGAGAGCAGACTTGGCCATC TCTGCCATCACCATCACCCCAGAGAGGGAGAGCGTTGTGGACTTCAGCAAGCGGTACATGGACTATTC AGTGGGGATTCTAATTAAGAAGCCCGAGGAGAAAATCAGCATCTTCTCCCTCTTTGCTCCATTTGATT TCGCTGTGTGGGCCTGCATTGCAGCAGCCATCCCTGTGGTTGGTGTGCTGATATTTGTGTTGAACAGG ATACAGGCTGTGAGGGCTCAGAGTGCTGCCCAGCCCAGGCCGTCAGCTTCTGCCACTCTGCACAGCGC CATCTGGATTGTCTATGGAGCCTTCGTACAGCAAGGTGGCGAATCTTCCGTGAACTCCATGGCCATGC GCATCGTGATGGGCAGCTGGTGGCTCTTCACGCTCATTGTGTGCTCCTCCTACACAGCCAACCTTGCT GCCTTCCTCACAGTGTCCAGGATGGACAACCCCATAAGGACTTTCCAGGACCTGTCCAAACAAGTGGA AATGTCTTATGGCACTGTCCGGGATTCTGCTGTATATGAGTACTTCCGAGCCAAGGGCACCAACCCCC TGGAGCAGGACAGCACGTTTGCTGAACTCTGGCGGACCATCAGCAAGAACGGAGGGGCTGACAACTGC GTGTCCAGTCCTTCAGAAGGCATCAGGAAGGCAAAGAAGGGGAACTACGCCTTCCTGTGGGATGTGGC CGTGGTGGAATACGCAGCCCTGACGGATGACGACTGCTCGGTGACTGTCATCGGCAACAGCATCAGCA GCAAGGGTTACGGGATTGCCCTGCAGCATGGCAGCCCCTACAGGGACCTCTTCTCCCAGAGGATCCTG GAGCTGCAGGACACAGGGGACCTGGATGTGCTGAAGCAGAAGTGGTGGCCGCACATGGGCCGCTGTGA CCTCACCAGCCATGCCAGCGCCCAGGCCGACGGCAAATCCCTCAAGCTGCACAGCTTCGCCGGGGTCT TCTGCATCCTGGCCATTGGCCTGCTCCTGGCCTGCCTGGTGGCTGCCCTGGAGTTGTGGTGGAACAGC AACCGGTGCCACCAGGAGACCCCCAAGGAGGACAAAGAAGTGAACTTGGAGCAGGTCCACCGGCGCAT GAACAGCCTCATGGATGAAGACATTGCTCACAAGCAGATTTCCCCAGCGTCGATTGAGCTCTCGGCCC TGGAGATGGGGGGCCTGGCTCCCACCCAGACCTTGGAGCCGACACGGGAGTACCAGAACACCCAGCTC TCGGTCAGCACCTTTCTGCCAGAGCAGAGCAGCCATGGCACCAGCCGGACACTCTCATCAGGGCCCAG CAGCAACCTGCCGCTGCCGCTGAGCAGCTCGGCGACCATGCCCTCCATGCAGTGCAAACACAGGTCAC CCAACGGGGGGCTGTTCCGGCAGAGCCCGGTGAAGACCCCCATCCCCATGTCCTTCCAGCCCGTGCCT GGAGGCGTCCTTCCAGAGGCTCTGGACACCTCCCACGGGACCTCCATCCTCGAGGGC
NOV2c, 315490179 SEQ ID NO: 10 1016 aa MW at l l2775.3kD Protein Sequence
TGSTMEALTLWLLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQSEKITYSI KVIEANNPFQAVQEACDLMTQGI ALVTSTGCASANALQSLTDAMHIPHLFVQR PGGSPRTACHLNP SPDGEAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIRGLQSFLDQASRLGLDVSLQKVDKN ISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGAHSFINEAVETNLASKDSHWVFVNEEISDPEIL DLVHSALGRMTWRQIFPSAKDNQKCTRNNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHR KLEDRK HSMASLNCIRKSTKP NGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSET FGKDMRKLATWDSEKGLNGSLQERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLD ALAKALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRYMDYS VGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQPRPSASATLHSA IWIVYGAFVQQGGESSVNSMAMRIVMGSW LFTLIVCSSYTANLAAFLTVSRMDNPIRTFQDLSKQVE MSYGTVRDSAVYEYFRAKGTNPLEQDSTFAEL RTISKNGGADNCVSSPSEGIRKAKKGNYAFLWDVA WEYAALTDDDCSVTVIGNSISSKGYGIALQHGSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCD LTSHASAQADGKSLKLHSFAGVFCILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRM NSLMDEDIAHKQISPASIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPS SNLPLPLSSSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSILEG
NOV2d, CG101396-02 SEQ ID NO: 11 3094 bp DNA Sequence ORF Start: ATG at 56 ORF Stop: TAG at 3083
TGTCGACGGCGCCAGTGTGATGATATTGCAGATTCGCCTTCACCGCGGCCGCACCATGGAAGCGCTGA
CGCTGTGGCTTCTCCCCTGGATATGCCAGTGCGTGTCGGTGCGGGCCGACTCCATCATCCACATCGGT GCCATCTTCGAGGAGAACGCGGCCAAGGACGACAGGGTGTTCCAGTTGGCGGTATCCGACCTGAGCCT CAGCGATGACATCCTGCAGAGCGAGAAGATCACCTACTCCATCAAGGTCATCGAGGCCAACAACCCAT TCCAGGCTGTGCAGGAAGCCTGTGACCTCATGACCCAGGGGATTTTGGCCTTGGTCACGTCCACTGGC TGTGCATCTGCCAATGCCCTGCAGTCCCTCACGGATGCCATGCACATCCCACACCTCTTTGTCCAGCG CAACCCGGGAGGGTCGCCACGCACCGCATGCCACCTGAACCCCAGCCCCGATGGTGAGGCCTACACAC TGGCTTCGAGACCACCCGTCCGCCTCAATGATGTCATGCTCAGGCTGGTGACGGAGCTGCGCTGGCAG AAGTTCGTCATGTTCTACGACAGCGAGTATGATATCCGTGGGCTTCAAAGCTTTCTGGACCAGGCCTC GCGGCTGGGCCTTGACGTCTCTTTACAAAAGGTGGACAAGAACATTAGCCACGTATTCACCAGCCTCT TCACCACGATGAAGACAGAGGAGCTGAATCGCTACCGGGACACGCTTCGCCGCGCCATCCTGCTGCTC AGCCCACAGGGAGCCCACTCCTTCATCAACGAGGCCGTGGAGACCAACCTGGCTTCCAAGGACAGCCA CTGGGTCTTTGTGAATGAGGAAATCAGTGACCCGGAGATCCTGGATCTGGTCCATAGTGCCCTTGGAA GGATGACCGTGGTCCGGCAAATCTTTCCGTCTGCAAAGGACAATCAGAAATGCACGAGGAACAACCAC CGCATCTCCTCCCTGCTCTGCGACCCCCAGGAAGGCTACCTCCAGATGCTGCAGATCTCCAACCTCTA TCTGTATGACAGTGTTCTGATGCTGGCCAACGCCTTTCACAGGAAGCTGGAGGACCGGAAGTGGCATA GCATGGCGAGCCTCAACTGCATACGGAAATCCACTAAGCCATGGAATGGTGGGAGGTCCATGCTGGAT ACCATCAAAAAGGGCCACATCACTGGCCTCACTGGGGTGATGGAGTTTCGGGAGGACAGTTCGAATCC CTATGTCCAGTTTGAAATCCTTGGCACTACCTATAGTGAGACTTTTGGCAAAGACATGCGCAAGTTGG CGACATGGGACTCAGAGAAGGGCTTGAATGGCAGCTTGCAAGAGAGGCCCATGGGCAGCCGCCTCCAA GGATTGACTCTTAAAGTGGTGACTGTCTTGGAAGAGCCTTTCGTGATGGTGGCTGAGAACATCCTAGG ACAGCCCAAGCGCTACAAAGGGTTCTCCATAGATGTCCTGGATGCACTGGCCAAGGCTCTGGGCTTTA AATATGAGATTTACCAAGCCCCTGATGGCAGGTACGGTCACCAGCTCCATAACACCTCCTGGAACGGG ATGATCGGGGAGCTCATCAGCAAGAGAGCAGACTTGGCCATCTCTGCCATCACCATCACCCCAGAGAG GGAGAGCGTTGTGGACTTCAGCAAGCGGTACATGGACTATTCAGTGGGGATTCTAATTAAGAAGCCCG AGGAGAAAATCAGCATCTTCTCCCTCTTTGCTCCATTTGATTTCGCTGTGTGGGCCTGCATTGCAGCA GCCATCCCTGTGGTTGGTGTGCTGATATTTGTGTTGAACAGGATACAGGCTGTGAGGGCTCAGAGTGC TGCCCAGCCCAGGCCGTCAGCTTCTGCCACTCTGCACAGCGCCATCTGGATTGTCTATGGAGCCTTCG TACAGCAAGGTGGCGAATCTTCCGTGAACTCCATGGCCATGCGCATCGTGATGGGCAGCTGGTGGCTC TTCACGCTCATTGTGTGCTCCTCCTACACAGCCAACCTTGCTGCCTTCCTCACAGTGTCCAGGATGGA CAACCCCATAAGGACTTTCCAGGACCTGTCCAAACAAGTGGAAATGTCTTATGGCACTGTCCGGGATT CTGCTGTATATGAGTACTTCCGAGCCAAGGGCACCAACCCCCTGGAGCAGGACAGCACGTTTGCTGAA CTCTGGCGGACCATCAGCAAGAACGGAGGGGCTGACAACTGCGTGTCCAGTCCTTCAGAAGGCATCAG GAAGGCAAAGAAGGGGAACTACGCCTTCCTGTGGGATGTGGCCGTGGTGGAATACGCAGCCCTGACGG ATGACGACTGCTCGGTGACTGTCATCGGCAACAGCATCAGCAGCAAGGGTTACGGGATTGCCCTGCAG CATGGCAGCCCCTACAGGGACCTCTTCTCCCAGAGGATCCTGGAGCTGCAGGACACAGGGGACCTGGA TGTGCTGAAGCAGAAGTGGTGGCCGCACATGGGCCGCTGTGACCTCACCAGCCATGCCAGCGCCCAGG CCGACGGCAAATCCCTCAAGCTGCACAGCTTCGCCGGGGTCTTCTGCATCCTGGCCATTGGCCTGCTC CTGGCCTGCCTGGTGGCTGCCCTGGAGTTGTGGTGGAACAGCAACCGGTGCCACCAGGAGACCCCCAA GGAGGACAAAGAAGTGAACTTGGAGCAGGTCCACCGGCGCATGAACAGCCTCATGGATGAAGACATTG CTCACAAGCAGATTTCCCCAGCGTCGATTGAGCTCTCGGCCCTGGAGATGGGGGGCCTGGCTCCCACC CAGACCTTGGAGCCGACACGGGAGTACCAGAACACCCAGCTCTCGGTCAGCACCTTTCTGCCAGAGCA GAGCAGCCATGGCACCAGCCGGACACTCTCATCAGGGCCCAGCAGCAACCTGCCGCTGCCGCTGAGCA GCTCGGCGACCATGCCCTCCATGCAGTGCAAACACAGGTCACCCAACGGGGGGCTGTTCCGGCAGAGC CCGGTGAAGACCCCCATCCCCATGTCCTTCCAGCCCGTGCCTGGAGGCGTCCTTCCAGAGGCTCTGGA CACCTCCCACGGGACCTCCATCTAGCTCGAGGGC
NOV2d, CGI 01396-02 SEQ ID NO: 12 1009 aa MW at l l2102.6kD Protein Sequence
MEALTLWLLP ICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLSDDILQSEKITYSIKVIE ANNPFQAVQEACDLMTQGILALVTSTGCAS NALQSLTDAMHIPHLFVQRNPGGSPRTACHLNPSPDG EAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIRGLQSFLDQASRLGLDVSLQKVDKNISHV FTSLFTTMKTEELNRYRDTLRRAILLLSPQGAHSFINEAVETNLASKDSH VFVNEEISDPEILDLVH SALGRMTWRQIFPSAKDNQKCTRNNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLED RKWHSMASLNCIRKSTKP NGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKD MRKLATWDSEKGLNGSLQERPMGSRLQGLTLKWTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRYMDYSVGIL IKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQPRPSASATLHSAIWIV YGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFLTVSRMDNPIRTFQDLSKQVEMSYG TVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNGGADNCVSSPSEGIRKAKKGNYAFLWDVAVVEY AALTDDDCSVTVIGNSISSKGYGIALQHGSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSH ASAQADGKSLKLHSFAGVFCILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLM DEDIAHKQISPASIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLP LPLSSSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI
NOV2e, SNP13379211 of SEQ ID NO: 13 3189 bp CG101396-01 , DNA Sequence ORF Start: ATG at 861 ORF Stop: TGA at 31 13
SNP Pos: 3184 SNP Change: C to T
CTGCACCGGGACCAGCGCCTCCCCGCTTCGCGCTGCCCTCGGCCTCGCCCCGGGCCCGGGTGGATGAG
CCGCGCGCCCGGGGGACATGGAAGCGCTGACGCTGTGGCTTCTCCCCTGGATATGCCAGTGCGTGTCG
GTGCGGGCCGACTCCATCATCCACATCGGTGCCATCTTCGAGGAGAACGCGGCCAAGGACGACAGGGT GTTCCAGTTGGCGGTATCCGACCTGAGCCTCAACGATGACATCCTGCAGAGCGAGAAGATCACCTACT CCATCAAGGTCATCGAGGCCAACAACCCATTCCAGGCTGTGCAGGAAGCCTGTGACCTCATGACCCAG GGGATTTTGGCCTTGGTCACGTCCACTGGCTGTGCATCTGCCAATGCCCTGCAGTCCCTCACGGATGC CATGCACATCCCACACCTCTTTGTCCAGCGCAACCCGGGAGGGTCGCCACGCACCGCATGCCACCTGA ACCCCAGCCCCGATGGTGAGGCCTACACACTGGCTTCGAGACCACCCGTCCGCCTCAATGATGTCATG CTCAGGCTGGTGACGGAGCTGCGCTGGCAGAAGTTCGTCATGTTCTACGACAGCGAGTATGATATCCG TGGGCTTCAAAGCTTTCTGGACCAGGCCTCGCGGCTGGGCCTTGACGTCTCTTTACAAAAGGTGGACA AGAACATTAGCCACGTATTCACCAGCCTCTTCACCACGATGAAGACAGAGGAGCTGAATCGCTACCGG GACACGCTTCGCCGCGCCATCCTGCTGCTCAGCCCACAGGGAGCCCACTCCTTCATCAACGAGGCCGT GGAGACCAACCTGGCTTCCAAGGACAGCCACTGGGTCTTTGTGAATGAGGAAATCAGTGACCCGGAGA TCCTGGATCTGGTCCATAGTGCCCTTGGAAGGATGACCGTGGTCCGGCAAATCTTTCCGTCTGCAAAG GACAATCAGAAATGCACGAGGAACAACCACCGCATCTCCTCCCTGCTCTGCGACCCCCAGGAAGGCTA CCTCCAGATGCTGCAGATCTCCAACCTCTATCTGTATGACAGTGTTCTGATGCTGGCCAACGCCTTTC ACAGGAAGCTGGAGGACCGGAAGTGGCATAGCATGGCGAGCCTCAACTGCATACGGAAATCCACTAAG CCATGGAATGGTGGGAGGTCCATGCTGGATACCATCAAAAAGGGCCACATCACTGGCCTCACTGGGGT GATGGAGTTTCGGGAGGACAGTTCGAATCCCTATGTCCAGTTTGAAATCCTTGGCACTACCTATAGTG AGACTTTTGGCAAAGACATGCGCAAGTTGGCGACATGGGACTCAGAGAAGGGCTTGAATGGCAGCTTG CAAGAGAGGCCCATGGGCAGCCGCCTCCAAGGATTGACTCTTAAAGTGGTGACTGTCTTGGAAGAGCC TTTCGTGATGGTGGCTGAGAACATCCTAGGACAGCCCAAGCGCTACAAAGGGTTCTCCATAGATGTCC TGGATGCACTGGCCAAGGCTCTGGGCTTTAAATATGAGATTTACCAAGCCCCTGATGGCAGGTACGGT CACCAGCTCCATAACACCTCCTGGAACGGGATGATCGGGGAGCTCATCAGCAAGAGAGCAGACTTGGC CATCTCTGCCATCACCATCACCCCAGAGAGGGAGAGCGTTGTGGACTTCAGCAAGCGGTACATGGACT ATTCAGTGGGGATTCTAATTAAGAAGCCCGAGGAGAAAATCAGCATCTTCTCCCTCTTTGCTCCATTT GATTTCGCTGTGTGGGCCTGCATTGCAGCAGCCATCCCTGTGGTTGGTGTGCTGATATTTGTGTTGAA CAGGATACAGGCTGTGAGGGCTCAGAGTGCTGCCCAGCCCAGGCCGTCAGCTTCTGCCACTCTGCACA GCGCCATCTGGATTGTCTATGGAGCCTTCGTACAGCAAGGTGGCGAATCTTCCGTGAACTCCATGGCC ATGCGCATCGTGATGGGCAGCTGGTGGCTCTTCACGCTCATTGTGTGCTCCTCCTACACAGCCAACCT TGCTGCCTTCCTCACAGTGTCCAGGATGGACAACCCCATAAGGACTTTCCAGGACCTGTCCAAACAAG TGGAAATGTCTTATGGCACTGTCCGGGATTCTGCTGTATATGAGTACTTCCGAGCCAAGGGCACCAAC CCCCTGGAGCAGGACAGCACGTTTGCTGAACTCTGGCGGACCATCAGCAAGAACGGAGGGGCTGACAA CTGCGTGTCCAGTCCTTCAGAAGGCATCAGGAAGGCAAAGAAGGGGAACTACGCCTTCCTGTGGGATG TGGCCGTGGTGGAATACGCAGCCCTGACGGATGACGACTGCTCGGTGACTGTCATCGGCAACAGCATC AGCAGCAAGGGTTACGGGATTGCCCTGCAGCATGGCAGCCCCTACAGGGACCTCTTCTCCCAGAGGAT CCTGGAGCTGCAGGACACAGGGGACCTGGATGTGCTGAAGCAGAAGTGGTGGCCGCACATGGGCCGCT GTGACCTCACCAGCCATGCCAGCGCCCAGGCCGACGGCAAATCCCTCAAGCTGCACAGCTTCGCCGGG GTCTTCTGCATCCTGGCCATTGGCCTGCTCCTGGCCTGCCTGGTGGCTGCCCTGGAGTTGTGGTGGAA CAGCAACCGGTGCCACCAGGAGACCCCCAAGGAGGACAAAGAAGTGAACTTGGAGCAGGTCCACCGGC GCATGAACAGCCTCATGGATGAAGACATTGCTCACAAGCAGATTTCCCCAGCGTCGATTGAGCTCTCG GCCCTGGAGATGGGGGGCCTGGCTCCCACCCAGACCTTGGAGCCGACACGGGAGTACCAGAACACCCA GCTCTCGGTCAGCACCTTTCTGCCAGAGCAGAGCAGCCATGGCACCAGCCGGACACTCTCATCAGGGC CCAGCAGCAACCTGCCGCTGCCGCTGAGCAGCTCGGCGACCATGCCCTCCATGCAGTGCAAACACAGG TCACCCAACGGGGGGCTGTTCCGGCAGAGCCCGGTGAAGACCCCCATCCCCATGTCCTTCCAGCCCGT GCCTGGAGGCGTCCTTCCAGAGGCTCTGGACACCTCCCACGGGACCTCCATCTGACTGCGCCGCCTGC CCTCCTGCCCACCCTCCCACCCACCCGACCAGCAGAGCTTTTTAATACAAGAAAATAACAA
NOV2e, SNPl 3379211 of SEQ ID NO: 14 1009 aa MW at l l2129.7kD CG101396-01, Protein Sequence SNP Change: no change
MEALTL LLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQSEKITYSIKVIE ANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFVQRNPGGSPRTACHLNPSPDG EAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIRGLQSFLDQASRLGLDVSLQKVDKNISHV FTSLFTTMKTEELNRYRDTLRRAILLLSPQGAHSFINEAVETNLASKDSH VFVNEEISDPEILDLVH SALGRMTVVRQIFPSAKDNQKCTRNNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLED RKWHSMASLNCIRKSTKPWNGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKD MRKLATWDSEKGLNGSLQERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRYMDYSVGIL IKKPEEKISIFSLFAPFDFAV ACIAAAIPWGVLIFVLNRIQAVRAQSAAQPRPSASATLHSAI IV YGAFVQQGGESSVNSMAMRIVMGS LFTLIVCSSYTANLAAFLTVSRMDNPIRTFQDLSKQVEMSYG TVRDSAVYEYFRAKGTNPLEQDSTFAEL RTISKNGGADNCVSSPSEGIRKAKKGNYAFLWDVAWEY AALTDDDCSVTVIGNSISSKGYGIALQHGSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSH ASAQADGKSLKLHSFAGVFCILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLM DEDIAHKQISPASIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLP LPLSSSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 2B.
Table 2B. Comparison of the NOV2 protein sequences.
NOV2a - -MEALTL LLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQ N0V2b TGTDSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQ
NOV2C TGSTMEALTL LLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQ
NOV2d MEALTL LLP ICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLSDDILQ
NOV2a SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
NOV2b SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
NOV2C SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
NOV2d SEKITYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFV
NOV2a QRNPGGSPRTACHLNPSPDGEAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIR
NOV2b QRNPGGSPRTACHLNPSPDGEAYTLASRPPVRLNDVMLRLVTELR QKFVMFYDSEYDIR
NOV2C QRNPGGSPRTACHLNPSPDGEAYTLASRPPVRLNDVMLRLVTELR QKFVMFYDSEYDIR
NOV2d QRNPGGSPRTACHLNPSPDGEAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIR
NOV2a GLQSFLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGA
NOV2b GLQSFLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGA
NOV2c GLQSFLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGA
NOV2d GLQSFLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGA
NOV2a HSFINEAVETNLASKDSHWVFVNEEISDPEILDLVHSALGRMTWRQIFPSAKDNQKCTR
NOV2b HSFINEAVETNLASKDSHWVFVNEEISDPEILDLVHSALGRMTWRQIFPSAKDNQKCTR
NOV2c HSFINEAVETNLASKDSHWVFVNEEISDPEILDLVHSALGRMTWRQIFPSAKDNQKCTR
NOV2d HSFINEAVETNLASKDSH VFVNEEISDPEILDLVHSALGRMTWRQIFPSAKDNQKCTR
NOV2a NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRK HSMASLNCIRKST
NOV2b NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRK HSMASLNCIRKST
NOV2c NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRKWHSMASLNCIRKST
NOV2d NNHRISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRKWHSMASLNCIRKST
NOV2a KP NGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWD
NOV2b KPWNGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWD
NOV2c KPWNGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWD
NOV2d KPWNGGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWD
NOV2a SEKGLNGSLQERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK
NOV2b SEKGLNGSLQERPMGSRLQGLTLKWTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK
NOV2c SEKGLNGSLQERPMGSRLQGLTLKWTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK
NOV2d SEKGLNGSLQERPMGSRLQGLTLKWTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAK
NOV2a ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRY
NOV2b ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRY
NOV2c ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRY
NOV2d ALGFKYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESWDFSKRY
NOV2a MDYSVGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQ
NOV2b MDYSVGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQ
NOV2C MDYSVGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQ
NOV2d MDYSVGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPWGVLIFVLNRIQAVRAQSAAQ
NOV2a PRPSASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFL
NOV2b PRPSASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFL
NOV2C PRP.SASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFL
NOV2d PRPSASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFL NOV2a TVSR DNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2b TVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2c TVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG NOV2d TVSRMDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNG
NOV2a GADNCVSSPSEGIRKAKKGNYAFLWDVAWEYAALTDDDCSVTVIGNSISSKGYGIALQH NOV2b GADNCVSSPSEGIRKAKKGNYAFLWDVAWEYAALTDDDCSVTVIGNSISSKGYGIALQH NOV2c GADNCVSSPSEGIRKAKKGNYAFLWDVAWΕYAALTDDDCSVTVIGNSISSKGYGIALQH NOV2d GADNCVSSPSEGIRKAKKGNYAFLWDVAWEYAALTDDDCSVTVIGNSISSKGYGIALQH
NOV2a GSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSHASAQADGKSLKLHSFAGVFC NOV2b GSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSHASAQADGKSLKLHSFAGVFC NOV2c GSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSHASAQADGKSLKLHSFAGVFC NOV2d GSPYRDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSHASAQADGKSLKLHSFAGVFC
NOV2a ILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPA NOV2b ILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPA NOV2c ILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPA NOV2d ILAIGLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPA
NOV a SIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLS NOV2b SIELSALEMGSLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLS NOV2c SIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLS NOV2d SIELSALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLS
NOV2a SSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI NOV2b SSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSILEG NOV2c SSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSILEG NOV2d SSATMPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI
NOV2a (SEQ ID NO 6) NOV2b (SEQ ID NO 8) NOV2c (SEQ ID NO 10) NOV2d (SEQ ID NO 12)
Further analysis ofthe NOV2a protein yielded the following properties shown in Table 2C.
Table 2C. Protein Sequence Properties NOV2a
SignalP analysis: Cleavage site between residues 21 and 22
PSORT π analysis:
PSG : a new signal peptide prediction method
N- region : length 2 ; pos . chg 0 ; neg . chg 1 H-region : length 16 ; peak value 0 . 00 PSG score : -4 .40
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold: -2. 1) : -1. 56 possible cleavage site : between 17 and 18
>>> Seems to have no N-terminal signal peptide ALOM: Klein et al * s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 3
INTEGRAL Likelihood =-11.41 Transmembrane 567 - 583
INTEGRAL Likelihood = -0.43 Transmembrane 629 - 645
INTEGRAL Likelihood =-12.79 Transmembrane 834 - 850
PERIPHERAL Likelihood = 1.01 (at 437)
ALOM score: -12.79 (number of TMSs: 3)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 574 Charge difference: 5.0 C( 3.0) - N(-2.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 3.64 Hyd Momen (95): 6.21 G content: 0 D/E content: 2 S/T content: 2 Score: -5.86
Gavel : prediction of cleavage sites for mitochondrial preseq R-2 motif at 29 VRA|DS
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PKRYKGF (5) at 460 bipartite: RKWHSMASLNCIRKSTK at 341 content of basic residues: 9.5% NLS Score: 0.45
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none Prenylation motif: none
memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
44, .4 %: endoplasmic reticulum
22, .2 %: vacuolar
11, .1 %: Golgi
11, .1 %: nuclear
11, .1 %: mitochondrial
>> prediction for CG101396-01 is end (k=9)
A search ofthe NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.
Figure imgf000153_0001
In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.
Figure imgf000154_0001
PFam analysis indicates that the NOV2a protein contains the domains shown in the Table 2F.
Figure imgf000154_0002
Example 3.
The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.
Table 3A. NOV3 Sequence Analysis
NOV3a, CGI 02348-01 SEQ ID NO: 15 J3345 bp DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 1479
CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCCi
AAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGG CTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGAC TTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCC AAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCT CAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTTCAC AAGGGCTTTCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCT ATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGAT GGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGAC GACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCC GTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGAC AGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCT GAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCG GTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCAT GGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCA ACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAG ACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCA TCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCA AGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAA CAGGGACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG TAGGGGTTGGGGGTGGGGGGTTGGGGGAGGCAGGGAAATCCTATTCACATCACTGTTGCACCAAGCCA CTGCAAGAGAAACCCCCACCCGGCAAGCCCGCCCCATCCCAGACAGGAAGCAGAGTCCCACAGACCGC TCCTCCTCACCCTCTACCTCCCTGTGCTCATGCACTAGGCCCCGGGAAGCCTGTACATCTCAACAACT TTCGCCTTGAATGTCCTTAGAACCACCTTCCCCTACTTCATCTGTTGACACAGCTTTTATACTCACCT GTGGAAGAGTCAGCTACTCACCCGCTATTAGAGTATGGAGGAAGGGGTTTTCATTGCATTGCATTTCT GAAACATTCCTAAGACCCTTTAGTTGACCTTCAAATATTCAAGCTATTCTGCAGCTCCAAGATGCAAT TATAGAAACAGCTCCTTTTTTATTTTATGTCCTCTATATGCCAGGTGCTTCACCTGTTATTTCACTTA ATCCTCATACCATATTTGCAAAGGATGTGTTATTATCTATGTGTGACAAATGAGGAAACTGAGGCTCA GGGGATAAAGGGACTTGCCCAAGTCCCACAGCTGGTGTGTGACTGCAGAGACTGTGCTCTTCCCAGTG TGCTGCAATACTTCTCAACCCTCCTCTAACCTGCTGTGTCACCCGCTTTCCCTCCCAGCCCCCACATC CTTACCATTTTCCCTCCCTGGGAATTCCTGCTTCTGCGAAAATGGTATCCTCTAGCTCACACTTTCCT AATGGCCCCATCTCCTGCAGAAGCCAGGTGAGCCCAGCACTGGACTGAAGTTCTTGCAGACACCCCAC CTGTGCCCCTATCATCAGGGGAACTGCTCCACCTGAGAGGACCAACTCTTTAATTTTTAGTAAAACCT GAAGGTGATGGGCCGGGCGCAGTGGCTCACGCCTGTAATCCCAACACCTTAGGAGTCCGAGGTGGGTG GATCACGAGGTCAGGAGATCCAGCCCATCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATAC AAAAATTAGCCGGGCGTGGTGACACGTGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAAT CACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTAAGATCACGCCACTGCACTCCAGCCTGCGGACA GACCAAGACTTCATCCCCCCCAAAAAAAAAAGATTGGAGGTGATTTACAGTGAAAGACACAAATAAAA TACAACTGTTCAATGGAAATAGAAAATAAACACCATAAAAGAGAGAAGAGAGGTAATTTGTTAGCATC AAGAGTCAAGTTGCTATATGGTCAAAGGTTAAATTTATCTCTAAAAAATGGCAGGATTCAAAGTTGTA CATACATGTGATTACTTCTGTTTTTTACACCCACATACAGTACAAAAGATTATTAAAAATATTCCCAA AAGGCAGGTGCAATGATGCACACTTATACCCCCAGCCACTCAGGAGGCTGATGCAAGAGGATCGCTTG AGCCCAGGAGTTGAAGTCCAGCCTAAGCAACATAGTGAAACCCCATCTCCAAAAATATAATAATAATT
CTCTCAAAATACTAAACAGAGGTGGTTTTATTGATAAGATTTTGGCTGTTTGGTTTTCCACTATTCTC
TATTGGCTAAAATTTGTTTAATGAGCATGAAATGTTTTTATTTTATTTTGCTTATTTTTATGATTGCAi
AAAAATGATATGAGTTTCTCCCTGCCAAGGCAAAAAATATATATATATACCTATAAAAAAAAAAAAAAi
AAAAAAAAAAAAA
NOV3a, CGI 02348-01 SEQ ID NO: 16 487 aa MW at 53483.9kD Protein Sequence
MPGPRVWGKYLWRSPHSKGCPGAMW LLL GVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPA VQNHCQEPYYQAAA AGALTCATPGT KDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGAL LGDR ILTAAHTVYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNA LQK RQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYW DNHAHHWVATGIVS GIGCGEGYDFYTKVLSYV DWIKGVMNGKN
NOV3b, 199842645 SEQ ID NO: 17 1368 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGTTCGTCTTCCAGGACTTCGACCTGGAGTCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCACGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT
NOV3b, 199842645 SEQ ID NO: 18 456 aa MW at 49986.8kD Protein Sequence
KLCPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRFVFQDFDLESSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAKVQNHCQEPYYQATAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVT PIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGALLGDR ILTAAHTIYPKDSVSLRKNQSVNVFLGH TAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLG YVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYV DNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVDWIKGVMNGKNKL
NOV3c, 198306343 SEQ ID NO: 19 741 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCA CGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCA AGAACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAG ATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTC CCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCC TCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTT GGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGC CTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGG ATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCGT GCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTA CACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCTT
NOV3c, 198306343 SEQ ID NO: 20 247 aa MW at 27566.2kD Protein Sequence
KLTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKNSVSLRKNQSVNVFLGHTAIDE MLKLGNHPVHR WHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGF GMEMG LTTELKYSRLPVAPREACNA LQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNR AHH VATGIVSWGIGCGEGYDFYTKVLSYVDWIKGVMNGKNKL
NOV3d, 199842665 SEQ ID NO: 21 1368 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCGTCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT
NOV3d, 199842665 SEQ ID NO: 22 456 aa MW at 49918.7kD Protein Sequence
KLCPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAI VQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVT PIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGALLGDRWILTAAHTVYPKDSVSLRKNQSVNVFLGH TAIDEMLKLGNHPVHR WHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLG YVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYV VWDNHAHH VATGIVS GIGCGEGYDFYTKVLSYVDWIKGVMNGKNKL
NOV3e, 199842661 SEQ ID NO: 23 1368 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGG ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT
NOV3e, 199842661 SEQ ID NO: 24 456 aa MW at 49933.7kD Protein Sequence
KLCPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSvTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSEDKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVT PIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGH TAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLG YVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYV V DNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYVD I GVMNGKNKL
NOV3f, 199597024 SEQ ID NO: 25 1479 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTCCCACCATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCCAAAGG CTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGGCTCCG TCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCAAAGGC CAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGACTTCGA CCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAGTCTCATTCGTCGGTTCGGATCCAAGCC AGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCTCAGGG AGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTCCACAAGGG CTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAGGGGCT CTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCTATTAT CAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGATGGGGA GGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGACGACCC TCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGG GGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCAAGGACAGTGT TTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCTGAAAC TGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATAACTTT AGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCGGTCTG TCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCATGGAGA TGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCAACGCC TGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAGACGCA AAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCATCACT GGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCAAGGTG CTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCTT
NOV3f, 199597024 SEQ ID NO: 26 493 aa MW at 54164.8kD Protein Sequence
KLPTMPGPRVGKYLWRSPHSKGCPGAM WLLL GVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKG QESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTVSFVGSDPSQFCGQQGSPLGRPPGQREFVSSG RSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYY QAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRG GGALLGDR ILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNF SGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNA LQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKV LS VD IKGVMNGKNKL NOV3g, 199842653 SEQ ID NO: 27 1293 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGTCTGCGGACGGCCAGTCACCCCCATTG CCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACC AGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCAT CTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCA TAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAG AATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCC CAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCA GTGGGTTTGGCATGGAGATGGGCCGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCC AGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTG TGTCGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGG ACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTAT GACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCT T
NOV3g, 199842653 SEQ ID NO: 28 431 aa MW at 47213.7kD Protein Sequence
K CPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFT SIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVVVHPDYRQ NESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGRLTTELKYSRLPVAP REACNA LQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHH VATGIVS GIGCGEGY DFYTϊVLSYVD IKGVMNGKNKL
NOV3h, 199652830 SEQ ID NO: 29 1368 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCCGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGGAAGACAGACAGGATGGGGAAGAGGTTCTTCAGTGTATGCCTGTCTGTGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT NOV3h, 199652830 SEQ ID NO: 30 456 aa MW at 49933.7kD Protein Sequence
KLCPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGT EDRQDGEEVLQCMPVCGRPVT PIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGH TAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLG YVSGFGME GWLTTELKYSRLPVAPREACNA LQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYV V DNHAHH VATGIVS GIGCGEGYDFYTKVLSYVDWIKGVMNGKNKL
NOV3i, 199652835 SEQ ID NO: 31 1368 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCGGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGGGACACAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT
NOV3i, 199652835 SEQ ID NO: 32 456 aa MW at 49888.7kD Protein Sequence
KLCPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQ PISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVT PIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGH TAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELRHSIPLGPNVLPVCLPDNETLYRSGLLG YVSGFGMEMGWLTTELKYSRLPVAPREACNA LQKRQRPEVFSDNMFCVGDGTQRHSVCQGDSGSVYV VWDNHAHH VATGIVSWGIGCGEGYDFYTKVLSYVDWIKGVMNGKNKL
NOV3j, 198306308 SEQ ID NO: 33 387 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCGGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTTCACAAGGGCTTTCTGGCCCTCTACAAGCTT
NOV3j, 198306308 SEQ ID NO: 34 129 aa MW at l4001.5kD Protein Sequence
KLCPTRGSVIiLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTI SFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYKL
NOV3k, CGI 02348-02 SEQ ID NO: 35 387 bp DNA Sequence ORF Start: at 7 ORF Stop: at 382
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG
GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCGGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTTCACAAGGGCTTTCTGGCCCTCTACAAGCTT
NOV3k, CGI 02348-02 SEQ ID NO: 36 125 aa MW at l3518.9kD Protein Sequence
CPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISF VGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALY
NOV31, CGI 02348-03 SEQ ID NO: 37 741 bp DNA Sequence ORF Start: at 7 ORF Stop: at 736
AAGCTTACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCA
CGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCA AGAACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAG ATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTC CCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCC TCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTT GGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGC CTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGG ATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCGT GCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTA CACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCTT
NOV31, CGI 02348-03 SEQ ID NO: 38 243 aa MW at 27083.5kD Protein Sequence
TLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKNSVSLRKNQSVNVFLGHTAIDEML KLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGM EMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYW DNRAH HWVATGIVSWGIGCGEGYDFYTKVLSYVD IKGVMNGKN
NOV3m, CGI 02348-04 SEQ ID NO: 39 1293 bp DNA Sequence ORF Start: at 7 ORF Stop: at 1288
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG
GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGCTCGTCTTCCAGGACTTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCGCGGCAGCAGTCTGCGGACGGCCAGTCACCCCCATTG CCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACC AGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCAT CTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCA TAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAG AATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCC CAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCA GTGGGTTTGGCATGGAGATGGGCCGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCC AGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTG TGTCGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGG ACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTAT GACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCT NOV3m, CG102348-04 SEQ ID NO: 40 427 aa MW at 46731.0kD Protein Sequence
CPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISF VGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPI SEASRGSEAINAPGDNPAKVQNHCQEPYYQAAAAVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFTSI HGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNE SHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGRLTTELKYSRLPVAPRE ACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHH VATGIVSWGIGCGEGYDF YTKVLSYVDWIKGVMNGKN
NOV3n, CGI 02348-05 SEQ ID NO: 41 1368 bp DNA Sequence ORF Start: at 7 ORF Stop: at 1363
AAGCTTTGCCCAACCCGGGGCTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGG
GTACCCAGAGCCGTATGGCAAAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTG TGAGGTTCGTCTTCCAGGACTTCGACCTGGAGTCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATC TCATTCGTCGGTTCGGATCCAAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGG TCAGAGGGAGTTTGTATCCTCAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGA ACAAGACTGCCCACCTCCACAAGGGCTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAG CCCATCAGCGAGGCCAGCAGGGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCA GAACCACTGCCAGGAGCCCTATTATCAGGCCACGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGA CCTGGAAAGACAGACAGGATGGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACC CCCATTGCCCAGAATCAGACGACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGC CTTCACCAGTATCCACGGCCGTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCC ACACCATCTACCCCAAGGACAGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCAC ACAGCCATAGATGAGATGCTGAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTA CCGTCAGAATGAGTCCCATAACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCC TGGGCCCCAACGTCCTCCCGGTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGC TACGTCAGTGGGTTTGGCATGGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGT AGCTCCCAGGGAGGCCTGCAACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATA TGTTCTGTGTTGGGGATGAGACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTG GTATGGGACAATCATGCCCATCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGA AGGGTATGACTTCTACACCAAGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGA ATAAGCTT
NOV3n, CGI 02348-05 SEQ ID NO: 42 452 aa MW at 49504. lkD Protein Sequence
CPTRGSVLLAQELPQQLTSPGYPEPYGKGQESSTDIKAPEGFAVRFVFQDFDLESSQDCAGDSVTISF VGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPI SEASRGSEAINAPGDNPAKVQNHCQEPYYQATAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPI AQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTA IDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYV SGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYVVW DNHAHH VATGIVSWGIGCGEGYDFYTKVLSYVD IKGVMNGKN
NOV3o, CGI 02348-06 SEQ ID NO: 43 1479 bp DNA Sequence ORF Start: ATG at 13 ORF Stop: at 1474
AAGCTTCCCACCATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCCAAAGGJ
CTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGGCTCCG TCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCAAAGGC CAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGACTTCGA CCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCCAAGCC AGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCTCAGGG AGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTCCACAAGGG CTTCCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAGGGGCT CTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCTATTAT CAGGCCACGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGATGGGGA GGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGACGACCC TCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCCGTGGG GGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCATCTACCCCAAGGACAGTGT TTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCTGAAAC TGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATAACTTT AGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCGGTCTG TCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCATGGAGA TGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCAACGCC TGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAGACGCA AAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCATCACT GGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCAAGGTG CTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATAAGCTT
NOV3o, CGI 02348-06 SEQ ID NO: 44 487 aa MW at 53528.0kD Protein Sequence
MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYYQATA AGALTCATPGT KDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGAL LGDRWILTAAHTIYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMG LTTELKYSRLPVAPREACNAWLQK RQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV DWIKGVMNGKN
NOV3p, SNP 13376570 of SEQ ID NO: 45 3345 bp CGI 02348-01, DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 1479 SNP Pos: 343 SNP Change: G to A
CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCC
AAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGG CTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGAC TTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCC AAACCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCT CAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTTCAC AAGGGCTTTCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCT ATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGAT GGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGAC GACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCC GTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGAC AGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCT GAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCG GTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCAT GGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCA ACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAG ACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCA TCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCA AGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAA CAGGGACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG TAGGGGTTGGGGGTGGGGGGTTGGGGGAGGCAGGGAAATCCTATTCACATCACTGTTGCACCAAGCCA CTGCAAGAGAAACCCCCACCCGGCAAGCCCGCCCCATCCCAGACAGGAAGCAGAGTCCCACAGACCGC TCCTCCTCACCCTCTACCTCCCTGTGCTCATGCACTAGGCCCCGGGAAGCCTGTACATCTCAACAACT TTCGCCTTGAATGTCCTTAGAACCACCTTCCCCTACTTCATCTGTTGACACAGCTTTTATACTCACCT GTGGAAGAGTCAGCTACTCACCCGCTATTAGAGTATGGAGGAAGGGGTTTTCATTGCATTGCATTTCT GAAACATTCCTAAGACCCTTTAGTTGACCTTCAAATATTCAAGCTATTCTGCAGCTCCAAGATGCAAT TATAGAAACAGCTCCTTTTTTATTTTATGTCCTCTATATGCCAGGTGCTTCACCTGTTATTTCACTTA ATCCTCATACCATATTTGCAAAGGATGTGTTATTATCTATGTGTGACAAATGAGGAAACTGAGGCTCA GGGGATAAAGGGACTTGCCCAAGTCCCACAGCTGGTGTGTGACTGCAGAGACTGTGCTCTTCCCAGTG
TGCTGCAATACTTCTCAACCCTCCTCTAACCTGCTGTGTCACCCGCTTTCCCTCCCAGCCCCCACATC
CTTACCATTTTCCCTCCCTGGGAATTCCTGCTTCTGCGAAAATGGTATCCTCTAGCTCACACTTTCCT
AATGGCCCCATCTCCTGCAGAAGCCAGGTGAGCCCAGCACTGGACTGAAGTTCTTGCAGACACCCCAC
CTGTGCCCCTATCATCAGGGGAACTGCTCCACCTGAGAGGACCAACTCTTTAATTTTTAGTAAAACCT
GAAGGTGATGGGCCGGGCGCAGTGGCTCACGCCTGTAATCCCAACACCTTAGGAGTCCGAGGTGGGTG
GATCACGAGGTCAGGAGATCCAGCCCATCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATAC
AAAAATTAGCCGGGCGTGGTGACACGTGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAAT
CACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTAAGATCACGCCACTGCACTCCAGCCTGCGGACA
GACCAAGACTTCATCCCCCCCAAAAAAAAAAGATTGGAGGTGATTTACAGTGAAAGACACAAATAAAA
TACAACTGTTCAATGGAAATAGAAAATAAACACCATAAAAGAGAGAAGAGAGGTAATTTGTTAGCATC
AAGAGTCAAGTTGCTATATGGTCAAAGGTTAAATTTATCTCTAAAAAATGGCAGGATTCAAAGTTGTA
CATACATGTGATTACTTCTGTTTTTTACACCCACATACAGTACAAAAGATTATTAAAAATATTCCCAA
AAGGCAGGTGCAATGATGCACACTTATACCCCCAGCCACTCAGGAGGCTGATGCAAGAGGATCGCTTG
AGCCCAGGAGTTGAAGTCCAGCCTAAGCAACATAGTGAAACCCCATCTCCAAAAATATAATAATAATT
CTCTCAAAATACTAAACAGAGGTGGTTTTATTGATAAGATTTTGGCTGTTTGGTTTTCCACTATTCTC
TATTGGCTAAAATTTGTTTAATGAGCATGAAATGTTTTTATTTTATTTTGCTTATTTTTATGATTGCA
AAAAATGATATGAGTTTCTCCCTGCCAAGGCAAAAAATATATATATATACCTATAAAAAAAAAAAAAA
AAAAAAAAAAAAA
NOV3p, SNPl 3376570 of SEQ ID NO: 46 487 aa MW at 53510.9kD CGI 02348-01, Protein Sequence SNP Pos: 109 SNP Change: Ser to Asn
MPGPRV GKYL RSPHSKGCPGAM WLLL GVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPNQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAA AGALTCATPGT KDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGAL LGDR ILTAAHTVYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQK RQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVS GIGCGEGYDFYTKVLSYV D IKGVMNGKN
NOV3q, SNPl 3376568 of SEQ ID NO: 47 3345 bp CG102348-01, DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 1479
SNP Pos: 564 SNP Change: G to A
CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCC
AAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGG CTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGAC TTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCC AAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCT CAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTTCAC AAGGGCTTTCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACACACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCT ATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGAT GGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGAC GACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCC GTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGAC AGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCT GAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCG GTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCAT GGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCA ACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAG ACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCA TCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCA AGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAA CAGGGACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG TAGGGGTTGGGGGTGGGGGGTTGGGGGAGGCAGGGAAATCCTATTCACATCACTGTTGCACCAAGCCA CTGCAAGAGAAACCCCCACCCGGCAAGCCCGCCCCATCCCAGACAGGAAGCAGAGTCCCACAGACCGC jTCCTCCTCACCCTCTACCTCCCTGTGCTCATGCACTAGGCCCCGGGAAGCCTGTACATCTCAACAACT
TTCGCCTTGAATGTCCTTAGAACCACCTTCCCCTACTTCATCTGTTGACACAGCTTTTATACTCACCT
GTGGAAGAGTCAGCTACTCACCCGCTATTAGAGTATGGAGGAAGGGGTTTTCATTGCATTGCATTTCT jGAAACATTCCTAAGACCCTTTAGTTGACCTTCAAATATTCAAGCTATTCTGCAGCTCCAAGATGCAAT
TATAGAAACAGCTCCTTTTTTATTTTATGTCCTCTATATGCCAGGTGCTTCACCTGTTATTTCACTTA
ATCCTCATACCATATTTGCAAAGGATGTGTTATTATCTATGTGTGACAAATGAGGAAACTGAGGCTCA
GGGGATAAAGGGACTTGCCCAAGTCCCACAGCTGGTGTGTGACTGCAGAGACTGTGCTCTTCCCAGTG jTGCTGCAATACTTCTCAACCCTCCTCTAACCTGCTGTGTCACCCGCTTTCCCTCCCAGCCCCCACATC
CTTACCATTTTCCCTCCCTGGGAATTCCTGCTTCTGCGAAAATGGTATCCTCTAGCTCACACTTTCCT
IAATGGCCCCATCTCCTGCAGAAGCCAGGTGAGCCCAGCACTGGACTGAAGTTCTTGCAGACACCCCAC
CTGTGCCCCTATCATCAGGGGAACTGCTCCACCTGAGAGGACCAACTCTTTAATTTTTAGTAAAACCT
GAAGGTGATGGGCCGGGCGCAGTGGCTCACGCCTGTAATCCCAACACCTTAGGAGTCCGAGGTGGGTG
IGATCACGAGGTCAGGAGATCCAGCCCATCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATAC
AAAAATTAGCCGGGCGTGGTGACACGTGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAAT
CACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTAAGATCACGCCACTGCACTCCAGCCTGCGGACA
GACCAAGACTTCATCCCCCCCAAAAAAAAAAGATTGGAGGTGATTTACAGTGAAAGACACAAATAAAA
ITACAACTGTTCAATGGAAATAGAAAATAAACACCATAAAAGAGAGAAGAGAGGTAATTTGTTAGCATC
AAGAGTCAAGTTGCTATATGGTCAAAGGTTAAATTTATCTCTAAAAAATGGCAGGATTCAAAGTTGTA
CATACATGTGATTACTTCTGTTTTTTACACCCACATACAGTACAAAAGATTATTAAAAATATTCCCAA
AAGGCAGGTGCAATGATGCACACTTATACCCCCAGCCACTCAGGAGGCTGATGCAAGAGGATCGCTTG
AGCCCAGGAGTTGAAGTCCAGCCTAAGCAACATAGTGAAACCCCATCTCCAAAAATATAATAATAATT
CTCTCAAAATACTAAACAGAGGTGGTTTTATTGATAAGATTTTGGCTGTTTGGTTTTCCACTATTCTC
TATTGGCTAAAATTTGTTTAATGAGCATGAAATGTTTTTATTTTATTTTGCTTATTTTTATGATTGCA
AAAAATGATATGAGTTTCTCCCTGCCAAGGCAAAAAATATATATATATACCTATAAAAAAAAAAAAAA
AAAAAAAAAAAAA
NOV3q, SNP13376568 of SEQ ID NO: 48 487 aa MW at 53513.9kD
CG 102348-01 , Protein Sequence SNP Pos: 183 SNP Change: Ala to Thr
MPGPRVWGKYLWRSPHSKGCPGAMW LLL GVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINTPGDNPAKVQNHCQEPYYQAAA AGALTCATPGTWKDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGAL LGDRWILTAAHTVYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQK RQRPEVFSDN FCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV DWIKGVMNGKN
NOV3r, SNPl 3382463 of SEQ ID NO: 49 3345 bp CGI 02348-01, DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 1479
SNP Pos: 693 SNP Change: C to T
CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCC
AAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGG CTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGAC TTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCC AAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCT CAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTTCAC AAGGGCTTTCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCT ATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGAT GGGGAGGAGGTTTTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGAC GACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCC GTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGAC AGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCT GAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCG GTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCAT GGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCA ACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAG ACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCA TCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCA AGGTGCTCAGCTATGTGGACTGGATCAAGGGAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAA CAGGGACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG
TAGGGGTTGGGGGTGGGGGGTTGGGGGAGGCAGGGAAATCCTATTCACATCACTGTTGCACCAAGCCA
CTGCAAGAGAAACCCCCACCCGGCAAGCCCGCCCCATCCCAGACAGGAAGCAGAGTCCCACAGACCGC
TCCTCCTCACCCTCTACCTCCCTGTGCTCATGCACTAGGCCCCGGGAAGCCTGTACATCTCAACAACT
TTCGCCTTGAATGTCCTTAGAACCACCTTCCCCTACTTCATCTGTTGACACAGCTTTTATACTCACCT
GTGGAAGAGTCAGCTACTCACCCGCTATTAGAGTATGGAGGAAGGGGTTTTCATTGCATTGCATTTCT
GAAACATTCCTAAGACCCTTTAGTTGACCTTCAAATATTCAAGCTATTCTGCAGCTCCAAGATGCAAT
TATAGAAACAGCTCCTTTTTTATTTTATGTCCTCTATATGCCAGGTGCTTCACCTGTTATTTCACTTA
ATCCTCATACCATATTTGCAAAGGATGTGTTATTATCTATGTGTGACAAATGAGGAAACTGAGGCTCA
GGGGATAAAGGGACTTGCCCAAGTCCCACAGCTGGTGTGTGACTGCAGAGACTGTGCTCTTCCCAGTG
TGCTGCAATACTTCTCAACCCTCCTCTAACCTGCTGTGTCACCCGCTTTCCCTCCCAGCCCCCACATC
CTTACCATTTTCCCTCCCTGGGAATTCCTGCTTCTGCGAAAATGGTATCCTCTAGCTCACACTTTCCT
AATGGCCCCATCTCCTGCAGAAGCCAGGTGAGCCCAGCACTGGACTGAAGTTCTTGCAGACACCCCAC
CTGTGCCCCTATCATCAGGGGAACTGCTCCACCTGAGAGGACCAACTCTTTAATTTTTAGTAAAACCT jGAAGGTGATGGGCCGGGCGCAGTGGCTCACGCCTGTAATCCCAACACCTTAGGAGTCCGAGGTGGGTG
GATCACGAGGTCAGGAGATCCAGCCCATCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATAC
AAAAATTAGCCGGGCGTGGTGACACGTGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAAT
CACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTAAGATCACGCCACTGCACTCCAGCCTGCGGACA
GACCAAGACTTCATCCCCCCCAAAAAAAAAAGATTGGAGGTGATTTACAGTGAAAGACACAAATAAAA
TACAACTGTTCAATGGAAATAGAAAATAAACACCATAAAAGAGAGAAGAGAGGTAATTTGTTAGCATC lAAGAGTCAAGTTGCTATATGGTCAAAGGTTAAATTTATCTCTAAAAAATGGCAGGATTCAAAGTTGTA
CATACATGTGATTACTTCTGTTTTTTACACCCACATACAGTACAAAAGATTATTAAAAATATTCCCAA
AAGGCAGGTGCAATGATGCACACTTATACCCCCAGCCACTCAGGAGGCTGATGCAAGAGGATCGCTTG
AGCCCAGGAGTTGAAGTCCAGCCTAAGCAACATAGTGAAACCCCATCTCCAAAAATATAATAATAATT
CTCTCAAAATACTAAACAGAGGTGGTTTTATTGATAAGATTTTGGCTGTTTGGTTTTCCACTATTCTC
TATTGGCTAAAATTTGTTTAATGAGCATGAAATGTTTTTATTTTATTTTGCTTATTTTTATGATTGCA
AAAAATGATATGAGTTTCTCCCTGCCAAGGCAAAAAATATATATATATACCTATAAAAAAAAAAAAAA
AAAAAAAAAAAAA
NOV3r, SNPl 3382463 of SEQ ID NO: 50 487 aa MW at 53517.9kD CGI 02348-01, Protein Sequence SNP Pos: 226 SNP Change: Leu to Phe
MPGPRVWGKYLWRSPHSKGCPGAM LLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAA AGALTCATPGTWKDRQDGEEVFQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGAL LGDRWILTAAHTVYPKDSVSLRKNQSV VFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQK RQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYWWDNHAHH VATGIVSWGIGCGEGYDFYTKVLSYV DWIKGVMNGKN
NOV3s, SNPl 3374245 of SEQ ID NO: 51 3345 bp CG102348-01 , DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 1479
SNP Pos: 1459 SNP Change: G to A
CAGATGTCCAGTTCCAGATGCCTGGACCCAGAGTGTGGGGGAAATATCTCTGGAGAAGCCCTCACTCC
AAAGGCTGTCCAGGCGCAATGTGGTGGCTGCTTCTCTGGGGAGTCCTCCAGGCTTGCCCAACCCGGGG CTCCGTCCTCTTGGCCCAAGAGCTACCCCAGCAGCTGACATCCCCCGGGTACCCAGAGCCGTATGGCA AAGGCCAAGAGAGCAGCACGGACATCAAGGCTCCAGAGGGCTTTGCTGTGAGGCTCGTCTTCCAGGAC TTCGACCTGGAGCCGTCCCAGGACTGTGCAGGGGACTCTGTCACAATCTCATTCGTCGGTTCGGATCC AAGCCAGTTCTGTGGTCAGCAAGGCTCCCCTCTGGGCAGGCCCCCTGGTCAGAGGGAGTTTGTATCCT CAGGGAGGAGTTTGCGGCTGACCTTCCGCACACAGCCTTCCTCGGAGAACAAGACTGCCCACCTTCAC AAGGGCTTTCTGGCCCTCTACCAAACCGTGGCTGTGAACTATAGTCAGCCCATCAGCGAGGCCAGCAG GGGCTCTGAGGCCATCAACGCACCTGGAGACAACCCTGCCAAGGTCCAGAACCACTGCCAGGAGCCCT ATTATCAGGCCGCGGCAGCAGGGGCACTCACCTGTGCAACCCCAGGGACCTGGAAAGACAGACAGGAT GGGGAGGAGGTTCTTCAGTGTATGCCTGTCTGCGGACGGCCAGTCACCCCCATTGCCCAGAATCAGAC GACCCTCGGTTCTTCCAGAGCCAAGCTGGGCAACTTCCCCTGGCAAGCCTTCACCAGTATCCACGGCC GTGGGGGCGGGGCCCTGCTGGGGGACAGATGGATCCTCACTGCTGCCCACACCGTCTACCCCAAGGAC AGTGTTTCTCTCAGGAAGAACCAGAGTGTGAATGTGTTCTTGGGCCACACAGCCATAGATGAGATGCT GAAACTGGGGAACCACCCTGTCCACCGTGTCGTTGTGCACCCCGACTACCGTCAGAATGAGTCCCATA ACTTTAGCGGGGACATCGCCCTCCTGGAGCTGCAGCACAGCATCCCCCTGGGCCCCAACGTCCTCCCG GTCTGTCTGCCCGATAATGAGACCCTCTACCGCAGCGGCTTGTTGGGCTACGTCAGTGGGTTTGGCAT GGAGATGGGCTGGCTAACTACTGAGCTGAAGTACTCGAGGCTGCCTGTAGCTCCCAGGGAGGCCTGCA ACGCCTGGCTCCAAAAGAGACAGAGACCCGAGGTGTTTTCTGACAATATGTTCTGTGTTGGGGATGAG ACGCAAAGGCACAGTGTCTGCCAGGGGGACAGTGGCAGCGTCTATGTGGTATGGGACAATCATGCCCA TCACTGGGTGGCCACGGGCATTGTGTCCTGGGGCATAGGGTGTGGCGAAGGGTATGACTTCTACACCA AGGTGCTCAGCTATGTGGACTGGATCAAGGAAGTGATGAATGGCAAGAATTGACCCTGGGGGCTTGAA CAGGGACTGACCAGCACAGTGGAGGCCCCAGGCAACAGAGGGCCTGGAGTGAGGACTGAACACTGGGG
TAGGGGTTGGGGGTGGGGGGTTGGGGGAGGCAGGGAAATCCTATTCACATCACTGTTGCACCAAGCCA
CTGCAAGAGAAACCCCCACCCGGCAAGCCCGCCCCATCCCAGACAGGAAGCAGAGTCCCACAGACCGC
ITCCTCCTCACCCTCTACCTCCCTGTGCTCATGCACTAGGCCCCGGGAAGCCTGTACATCTCAACAACT
TTCGCCTTGAATGTCCTTAGAACCACCTTCCCCTACTTCATCTGTTGACACAGCTTTTATACTCACCT
GTGGAAGAGTCAGCTACTCACCCGCTATTAGAGTATGGAGGAAGGGGTTTTCATTGCATTGCATTTCT
GAAACATTCCTAAGACCCTTTAGTTGACCTTCAAATATTCAAGCTATTCTGCAGCTCCAAGATGCAAT
TATAGAAACAGCTCCTTTTTTATTTTATGTCCTCTATATGCCAGGTGCTTCACCTGTTATTTCACTTA
ATCCTCATACCATATTTGCAAAGGATGTGTTATTATCTATGTGTGACAAATGAGGAAACTGAGGCTCA
GGGGATAAAGGGACTTGCCCAAGTCCCACAGCTGGTGTGTGACTGCAGAGACTGTGCTCTTCCCAGTG
TGCTGCAATACTTCTCAACCCTCCTCTAACCTGCTGTGTCACCCGCTTTCCCTCCCAGCCCCCACATC
CTTACCATTTTCCCTCCCTGGGAATTCCTGCTTCTGCGAAAATGGTATCCTCTAGCTCACACTTTCCT
AATGGCCCCATCTCCTGCAGAAGCCAGGTGAGCCCAGCACTGGACTGAAGTTCTTGCAGACACCCCAC
CTGTGCCCCTATCATCAGGGGAACTGCTCCACCTGAGAGGACCAACTCTTTAATTTTTAGTAAAACCT
GAAGGTGATGGGCCGGGCGCAGTGGCTCACGCCTGTAATCCCAACACCTTAGGAGTCCGAGGTGGGTG
GATCACGAGGTCAGGAGATCCAGCCCATCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAAATAC
AAAAATTAGCCGGGCGTGGTGACACGTGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAAT
CACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTAAGATCACGCCACTGCACTCCAGCCTGCGGACA
GACCAAGACTTCATCCCCCCCAAAAAAAAAAGATTGGAGGTGATTTACAGTGAAAGACACAAATAAAA
TACAACTGTTCAATGGAAATAGAAAATAAACACCATAAAAGAGAGAAGAGAGGTAATTTGTTAGCATC lAAGAGTCAAGTTGCTATATGGTCAAAGGTTAAATTTATCTCTAAAAAATGGCAGGATTCAAAGTTGTA
CATACATGTGATTACTTCTGTTTTTTACACCCACATACAGTACAAAAGATTATTAAAAATATTCCCAA iAAGGCAGGTGCAATGATGCACACTTATACCCCCAGCCACTCAGGAGGCTGATGCAAGAGGATCGCTTG
AGCCCAGGAGTTGAAGTCCAGCCTAAGCAACATAGTGAAACCCCATCTCCAAAAATATAATAATAATT
CTCTCAAAATACTAAACAGAGGTGGTTTTATTGATAAGATTTTGGCTGTTTGGTTTTCCACTATTCTC
TATTGGCTAAAATTTGTTTAATGAGCATGAAATGTTTTTATTTTATTTTGCTTATTTTTATGATTGCA
AAAAATGATATGAGTTTCTCCCTGCCAAGGCAAAAAATATATATATATACCTATAAAAAAAAAAAAAA
AAAAAAAAAAAAA
NOV3s, SNPl 3374245 of SEQ ID NO: 52 487 aa MW at 53556.0kD CGI 02348-01, Protein Sequence SNP Pos: 481 SNP Change: Gly to Glu
MPGPRV GKYL RSPHSKGCPGAMW LLLWGVLQACPTRGSVLLAQELPQQLTSPGYPEPYGKGQESS TDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQGSPLGRPPGQREFVSSGRSLR LTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASRGSEAINAPGDNPAKVQNHCQEPYYQAAA AGALTCATPGT KDRQDGEEVLQCMPVCGRPVTPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGAL LGDRWILTAAHTVYPKDSVSLRKNQSVNVFLGHTAIDEMLKLGNHPVHRWVHPDYRQNESHNFSGDI ALLELQHSIPLGPNVLPVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKΥSRLPVAPREACNAWLQK RQRPEVFSDNMFCVGDETQRHSVCQGDSGSVYW DNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV DWIKEVMNGKN
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 3B. Table 3B. Comparison ofthe NOV3 protein sequences.
NOV3a MPGPRVWGKYL RSPHSKGCPGAM LLLWGVLQACPTRGSVLLAQELPQQLTSPG
NOV3b KLCPTRGSVLLAQELPQQLTSPG
NOV3c
NOV3d KLCPTRGSVLLAQELPQQLTSPG
NOV3e KLCPTRGSVLLAQELPQQLTSPG
NOV3f KLPTMPGPRV GKYLWRSPHSKGCPGA WLLLWGVLQACPTRGSVLLAQELPQQLTSPG
NOV3g KLCPTRGSVLLAQELPQQLTSPG
NOV3h KLCPTRGSVLLAQELPQQLTSPG
NOV3i KLCPTRGSVLLAQELPQQLTSPG
NOV3j KLCPTRGSVLLAQELPQQLTSPG
NOV3k CPTRGSVLLAQELPQQLTSPG
NOV31
NOV3m CPTRGSVLLAQELPQQLTSPG
NOV3n CPTRGSVLLAQELPQQLTSPG
NOV3o MPGPRVWGKYLWRSPHSKGCPGAMWWLLLWGVLQACPTRGSVLLAQELPQQLTSPG
NOV3a YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3b YPEPYGKGQESSTDIKAPEGFAVRFVFQDFDLESSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3C
NOV3d YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3e YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3f YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTVSFVGSDPSQFCGQQG
NOV3g YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3h YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3i YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3J YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3k YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV31
NOV3m YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3n YPEPYGKGQESSTDIKAPEGFAVRFVFQDFDLESSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3o YPEPYGKGQESSTDIKAPEGFAVRLVFQDFDLEPSQDCAGDSVTISFVGSDPSQFCGQQG
NOV3a SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3b SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3C
NOV3d SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3e SPLGRPPGQREFVSSGRSLRLTFRTQPSSEDKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3f SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3g SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3h SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3i SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3j SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYKL
NOV3k SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALY
NOV31
NOV3m SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3n SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3o SPLGRPPGQREFVSSGRSLRLTFRTQPSSENKTAHLHKGFLALYQTVAVNYSQPISEASR
NOV3a GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPV NOV3b GSEAINAPGDNPAKVQNHCQEPYYQATAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPV NOV3c NOV3d GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGT KDRQDGEEVLQCMPVCGRPV
NOV3e GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGT KDRQDGEEVLQCMPVCGRPV
NOV3f GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPV
NOV3g GSEAINAPGDNPAKVQNHCQEPYYQAAAA V- -CGRPV
NOV3h GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWEDRQDGEEVLQC PVCGRPV
NOV3i GSEAINAPGDNPAKVQNHCQEPYYQAAAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPV
NOV3j
NOV3k
NOV31
NOV3m GSEAINAPGDNPAKVQNHCQEPYYQAAAA V- -CGRPV
NOV3n GSEAINAPGDNPAKVQNHCQEPYYQATAAGALTCATPGTWKDRQDGEEVLQCMPVCGRPV
NOV3o GSEAINAPGDNPAKVQNHCQEPYYQATAAGALTCATPGT KDRQDGEEVLQC PVCGRPV
NOV3a TPIAQNQTTLGSSRAKLGNFP QAFTSIHGRGGGALLGDRWILTAAHTVYPKDSVSLRKN
NOV3b TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKN
NOV3c KLTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDR ILTAAHTIYPKNSVSLRKN
NOV3d TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTVYPKDSVSLRKN
NOV3e TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKN
NOV3 f TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKN
NOV3g TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDR ILTAAHTIYPKDSVSLRKN
NOV3h TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDR ILTAAHTIYPKDSVSLRKN
NOV3i TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDR ILTAAHTIYPKDSVSLRKN
NOV3J
NOV3k
NOV31 TLGSSRAKLGNFP QAFTSIHGRGGGALLGDRWILTAAHTIYPKNSVSLRKN
NOV3m TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKN
NOV3n TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDR ILTAAHTIYPKDSVSLRKN
NOV3o TPIAQNQTTLGSSRAKLGNFPWQAFTSIHGRGGGALLGDRWILTAAHTIYPKDSVSLRKN
NOV3a QSVNVFLGHTAIDEMLKLGNHPVHRWVHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3b QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3c QSVNVFLGHTAIDE LKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3d QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3e QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3f QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3g QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3h QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3i QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELRHSIPLGPNVL NOV3J NOV3k NOV31 QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3m QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3n QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL NOV3o QSVNVFLGHTAIDEMLKLGNHPVHRVWHPDYRQNESHNFSGDIALLELQHSIPLGPNVL
NOV3a PVCLPDNETLYRSGLLGYVSGFGMEMG LTTELKYSRLPVAPREACNA LQKRQRPEVFS
NOV3b PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNA LQKRQRPEVFS
NOV3c PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFS
NOV3d PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFS
NOV3e PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFS
NOV3f PVCLPDNETLYRSGLLGYVSGFGMEMG LTTELKYSRLPVAPREACNAWLQKRQRPEVFS
NOV3g PVCLPDNETLYRSGLLGYVSGFGMEMGRLTTELKYSRLPVAPREACNA LQKRQRPEVFS
NOV3h PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNA LQKRQRPEVFS
NOV3i PVCLPDNETLYRSGLLGYVSGFGMEMG LTTELKYSRLPVAPREACNAWLQKRQRPEVFS NOV3k NOV31 PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFS NOV3m PVCLPDNETLYRSGLLGYVSGFGMEMGRLTTELKYSRLPVAPREACNAWLQKRQRPEVFS NOV3n PVCLPDNETLYRSGLLGYVSGFGMEMGWLTTELKYSRLPVAPREACNAWLQKRQRPEVFS NOV3o PVCLPDNETLYRSGLLGYVSGFGMEMG LTTELKYSRLPVAPREACNA LQKRQRPEVFS
NOV3a DNMFCVGDETQRHSVCQGDSGSVYW DNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV NOV3b DNMFCVGDETQRHSVCQGDSGSVYW DNHAHH VATGIVSWGIGCGEGYDFYTKVLSYV NOV3c DNMFCVGDETQRHSVCQGDSGSVYWWDNRAHHWVATGIVSWGIGCGEGYDFYTKVLSYV NOV3d DNMFCVGDETQRHSVCQGDSGSVYW DNHAHH VATGIVSWGIGCGEGYDFYTKVLSYV NOV3e DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHH VATGIVSWGIGCGEGYDFYTKVLSYV NOV3f DNMFCVGDETQRHSVCQGDSGSVYW DNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV NOV3g DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHH VATGIVS GIGCGEGYDFYTKVLSYV NOV3h DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVSWGIGCGEGYDFYTKVLSYV NOV3i DNMFCVGDGTQRHSVCQGDSGSVYWWDNHAHH VATGIVSWGIGCGEGYDFYTKVLSYV NOV3J NOV3k NOV31 DNMFCVGDETQRHSVCQGDSGSVYW DNRAHHWVATGIVSWGIGCGEGYDFYTKVLSYV NOV3 DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVS GIGCGEGYDFYTKVLSYV NOV3n DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVS GIGCGEGYDFYTKVLSYV NOV3o DNMFCVGDETQRHSVCQGDSGSVYWWDNHAHHWVATGIVS GIGCGEGYDFYTKVLSYV
NOV3a DWIKGVMNGKN-- NOV3b DWIKGVMNGKNKL NOV3C DWIKGVMNGKNKL NOV3d D IKGVMNGKNKL NOV3e DWIKGVMNGKNKL NOV3f DWIKGVMNGKNKL NOV3g DWIKGVMNGKNKL NOV3h DWIKGVMNGKNKL NOV3i DWIKGVMNGKNKL NOV3J NOV3k NOV31 DWIKGVMNGKN-- NOV3m DWIKGVMNGKN-- NOV3n DWIKGVMNGKN-- NOV3o DWIKGVMNGKN--
NOV3a (SEQ ID NO 16) NOV3b (SEQ ID NO 18) NOV3C (SEQ ID NO 20) NOV3d (SEQ ID NO 22) NOV3e (SEQ ID NO 24) NOV3f (SEQ ID NO 26) NOV3g (SEQ ID NO 28) NOV3h (SEQ ID NO 30) NOV3i (SEQ ID NO 32) NOV3J (SEQ ID NO 34) NOV3k (SEQ ID NO 36) NOV31 (SEQ ID NO 38) NOV3m (SEQ ID NO 40) NOV3n (SEQ ID NO 42) NOV3o (SEQ ID NO 44) Further analysis ofthe NOV3a protein yielded the following properties shown in Table 3C.
Table 3C. Protein Sequence Properties NOV3a
SignalP analysis: Cleavage site between residues 36 and 37
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos . chg 2; neg.chg 0 H-region: length 3; peak value -5.40 PSG score: -9.80
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 2.53 possible cleavage site: between 35 and 36
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 2.97 (at 20) ALOM score: 2.97 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment(75): 7.36 Hyd Moment(95): 6.26 G content: 6 D/E content : 1 S/T content : 4 Score: -3.72
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 49 TRG|SV
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 8.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: PGPR
KKXX-like motif in the C-terminus: MNGK SKL: peroxisomal targeting signal in the C-terminus: none PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
60.9 %: mitochondrial
17.4 %: cytoplasmic
17.4 %: nuclear
4.3 %: peroxisomal
>> prediction for CG102348-01 is mit (k=23)
A search ofthe NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D.
Figure imgf000173_0001
In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E.
Table 3E. Public BLASTP Results for NOV3a
NOV3a Identities/
Protein Residues/ Similarities for Expect
Accession Protein/Organism/Length
Match the Matched Value
Number Residues Portion
Q9NZP8 Complement Cl -like 1..487 487/487 (100%) 0.0 proteinase - Homo sapiens 1..487 487/487 (100%) (Human), 487 aa.
CAC88678 Sequence 16 from Patent 1..487 485/487 (99%) 0.0 WOO 166747 - Homo sapiens 1..487 487/487 (99%) (Human), 487 aa.
Q9H804 Hypothetical protein - Homo 1..425 423/425 (99%) 0.0 sapiens (Human), 438 aa. 1..425 423/425 (99%)
AAH35220 Similar to complement 189..483 176/303 (58%) e-108 component - Homo sapiens 400..701 226/303 (74%) (Human), 705 aa.
Q8J012 Complement component 1 , r 189..483 176/303 (58%) e-108 subcomponent - Homo sapiens 144..445 226/303 (74%) (Human), 449 aa (fragment).
PFam analysis indicates that the NOV3a protein contains the domains shown in the Table 3F.
Figure imgf000174_0001
Example 4.
The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4 A. Table 4A. NOV4 Sequence Analysis
NOV4a, CG125860-02 SEQ ID NO: 53 1880 bp DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG
TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4a, CG125860-02 SEQ ID NO: 54 513 aa MW at 55531.5kD
Protein Sequence
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4b, CGI 25860-01 SEQ ID NO: 55 1787 bp DNA Sequence ORF Start: ATG at 54 ORF Stop: TAA at 1470
GCGGAACATTGCCTAGTAGACCCTGAGGCTTTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTG
GATGACCAACCCCCTATGGAGGCCCAGTATGCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGA GCCTGGAGACCAGCAGCATCCCATTTCTCAGGCGGTGTGCTGGCGTTCCATGCGACGTGGCTGTGCAG TGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTATCTGTGT CCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCTCAGAGGC CAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACAGTATCTTTCAGAATAAACAGCGAAGACT TCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCTGGTCTGCCATGAGGGCTGGAGCCCC GCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGACTCACTCACCACAAGGGAGTAAACCT CACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTCTCTCCTAGACTGGGAGGCTTCCTGG AGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAACAACTGCACTTCTGGTCAAGTTGTT TCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCCGGATAGTTGGTGGGCAGTCTGTGGC TCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTCCGGCACACGTGTGGGGGCTCTGTGC TAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAGTTTCAGGCTGGCCCGCCTGTCCAGC TGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGCCCCACCAAGGGGCTCTGGTGGAGAG GATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTACGACGTCGCCCTCCTGAGGCTCCAGA CCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCCGGCCAAGGAACAGCATTTTCCGAAG GGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTAGCCATACTTACAGCTCGGATATGCT CCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAACAGCTCTTGCGTGTACAGCGGAGCCC TCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGCTGATGCATGCCAGGGAGATAGCGGG GGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGGGGGTGGTCAGCTGGGGGCGTGGCTG CGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAGTTTCTGGACTGGATCCATGACACTG CTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTAAAGGACCTGCCCTCGAATGCAAGGA
ACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGGTGCTAGGACATATTCCCCAGAGTGA
GTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTTCTATCAGTTTAAGGATGAACTGGGT
AAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGTGTCGACCTTTGGCAAATTTCTAACT
TTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTTATATGCTATTGTTATATGCTATTAAl
ATAAGACCCGTACAATGCC
NOV4b, CG125860-01 SEQ ID NO: 56 472 aa MW at 50916.3kD Protein Sequence
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPISQAVCWRSMRRGCAVLGALGLLAGAGVGSWLL VLYLCPAASQPISGTLQDEEITLSCSEASAEEALLPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCH EGWSPALGLQICWSLGHLRLTHHKGVNLTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCT SGQWSLRCSECGARPLASRIVGGQSVAPGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRL ARLSSWRVHAGLVSHSAVRPHQGALVERIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKE QHFPKGSRCWVSGWGHTHPSHTYSSDMLQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADAC QGDSGGPLVCPDGDTWRLVGWSWGRGCAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4c, SNP13376012 of SEQ ID NO: 57 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 36 SNP Change: C to T
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGTTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC NOV4c, SNP13376012 of SEQ ID NO: 58 513 aa MW at 55531.5kD
CGI 25860-02, Protein Sequence JsNP Pos: 5 SNP Change: Leu to Leu
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4d, SNP 13376014 of SEQ ID NO: 59 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 265 SNP Change: G to A
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCAACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
IGTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4d, SNP13376014 of SEQ ID NO: 60 513 aa MW at 55503.5kD CGI 25860-02, Protein Sequence SNP Pos: 81 SNP Change: Arg to Gin
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMQRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF NOV4e, SNP 13376015 of SEQ ID NO: 61 1880 bp CG125860-02, DNA Sequence ORF Start: ATG at 24JORF Stop: TAA at 1563 SNP Pos: 827 SNP Change: T to C
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGCGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4e, SNP13376015 of SEQ ID NO: 62J513 aa [MW at 5553 L5kD CGI 25860-02, Protein Sequence SNP Pos: 268 SNP Change: Gly to Gly
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4f, SNPl 3376016 of SEQ ID NO: 63 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 830 SNP Change: G to T
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGTCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4f, SNP13376016 of SEQ ID NO: 64J513 aa JMW at 55531.5kD CG125860-02, Protein Sequence SNP Pos: 269 SNP Change: Gly to Gly
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWVVTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4g, SNPl 3376017 of SEQ ID NO: 65 1880 bp CG125860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 836 SNP Change: T to C
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCCGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4g, SNPl 3376017 of SEQ ID NO: 66 513 aa MW at 55531.5kD CG125860-02, Protein Sequence SNP Pos: 271 SNP Change: Ser to Ser
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4h, SNPl 3376011 of SEQ ID NO: 67 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 869 SNP Change: C to T
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGTGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4h, SNPl 3376011 of SEQ ID NO: 68 513 aa MW at 55531.5kD CGI 25860-02, Protein Sequence SNP Pos: 282 SNP Change: Ser to Ser
MSLMLDDQPP EAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF NOV4i, SNPl 3376018 of SEQ ID NO: 69 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 975 jSNP Change: A to G
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCGGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4i, SNP13376018 of SEQ ID NO: 70 513 aa MW at 55501.5kD CG125860-02, Protein Sequence SNP Pos: 318 SNP Change: Ser to Gly
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSGWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4j, SNP13382467 of SEQ ID NO: 71 1880 bp CG125860-02, DNA Sequence ORF Start: ATG at 24|ORF Stop: TAA at_1563 SNP Pos: 1269 SNP Change: C to T
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCTTGCTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT
CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT
GTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4j, SNPl 3382467 of SEQ ID NO: 72 513 aa MW at 55531.5kD
CGI 25860-02, Protein Sequence SNP Pos: 416 SNP Change: Leu to Leu
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RlIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLLSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOV4k, SNPl 3382466 of SEQ ID NO: 73 1880 bp CGI 25860-02, DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 1563
SNP Pos: 1272 SNP Change: C to T
TTACAACAGTGCCACTGACCCCTATGAGCCTGATGCTGGATGACCAACCCCCTATGGAGGCCCAGTAT
GCAGAGGAGGGCCCAGGACCTGGGATCTTCAGAGCAGAGCCTGGAGACCAGCAGCATCCCAGTAGGCC AGACTGGGCCATAGGGGAAATGACAGGGTGGGGACAGTGGAGGGCAATCATCCTACATTCCCCGGATC CTCCTTGGGGTCAGCCCCACATGATTGATGTTTCTCAGGCAGTGTGCTGGCGTTCCATGCGACGTGGC TGTGCAGTGCTGGGAGCCCTGGGGCTGCTGGCCGGTGCAGGTGTTGGCTCATGGCTCCTAGTGCTGTA TCTGTGTCCTGCTGCCTCTCAGCCCATTTCCGGGACCTTGCAGGATGAGGAGATAACTTTGAGCTGCT CAGAGGCCAGCGCTGAGGAAGCTCTGCTCCCTGCACTTCCCAAAACACCTGCACTTCCCAAAACAGTA TCTTTCAGAATAAACAGCGAAGACTTCTTGCTGGAAGCGCAAGTGAGGGATCAGCCACGCTGGCTCCT GGTCTGCCATGAGGGCTGGAGCCCCGCCCTGGGGCTGCAGATCTGCTGGAGCCTTGGGCATCTCAGAC TCACTCACCACAAGGGAGTAAACCTCACTGACATCAAACTCAACAGTTCCCAGGAGTTTGCTCAGCTC TCTCCTAGACTGGGAGGCTTCCTGGAGGAGGCGTGGCAGCCCAGTAGGACTACTGAGGCTGTTAGGAA CAACTGCACTTCTGGTCAAGTTGTTTCCCTCAGATGCTCTGAGTGTGGAGCGAGGCCCCTGGCTTCCC GGATAGTTGGTGGGCAGTCTGTGGCTCCTGGGCGCTGGCCGTGGCAGGCCAGCGTGGCCCTGGGCTTC CGGCACACGTGTGGGGGCTCTGTGCTAGCGCCACGCTGGGTGGTGACTGCTGCACATTGTATGCACAG TTTCAGGCTGGCCCGCCTGTCCAGCTGGCGGGTTCATGCGGGGCTGGTCAGCCACAGTGCCGTCAGGC CCCACCAAGGGGCTCTGGTGGAGAGGATTATCCCACACCCCCTCTACAGTGCCCAGAATCATGACTAC GACGTCGCCCTCCTGAGGCTCCAGACCGCTCTCAACTTCTCAGACACTGTGGGCGCTGTGTGCCTGCC GGCCAAGGAACAGCATTTTCCGAAGGGCTCGCGGTGCTGGGTGTCTGGCTGGGGCCACACCCACCCTA GCCATACTTACAGCTCGGATATGCTCCAGGACACGGTGGTGCCCCTGTTCAGCACTCAGCTCTGCAAC AGCTCTTGCGTGTACAGCGGAGCCCTCACCCCCCGCATGCTTTGCGCTGGCTACCTGGACGGAAGGGC TGATGCATGCCAGGGAGATAGCGGGGGCCCCCTAGTGTGCCCAGATGGGGACACATGGCGCCTAGTGG GGGTGGTCAGCTGGGGGCGTGGCTGCGCAGAGCCCAATCACCCAGGTGTCTACGCCAAGGTAGCTGAG TTTCTGGACTGGATCCATGACACTGCTCAGGTGAGTGTGGGGGCAGGAGTAGGGCAGGGAGATTTCTA AAGGACCTGCCCTCGAATGCAAGGAACCTTACCCCTTAGGCCCGGGCCCTGCTGGGGACTGGGGAGGG TGCTAGGACATATTCCCCAGAGTGAGTGGAGGAAGAAGTGAAGCTTAAACATGGAATCCATTGGATTT CTATCAGTTTAAGGATGAACTGGGTAAGAGTATGCCTGAGTTTGTATCCCAGATCTACCATTTCCTGT IGTCGACCTTTGGCAAATTTCTAACTTTGTTAAACCTTAATTTCCTGATAATAACCATGATGGCTACTT
ATATGCTATTGTTATATGCTATTAAATAAGACCCGTACAATGCC
NOV4k, SNPl 3382466 of SEQ ID NO: 74 513 aa MW at 55565.5kD CGI 25860-02, Protein Sequence SNP Pos: 417 SNP Change: Leu to Phe
MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPDPPWGQPHM IDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQDEEITLSCSEASAEEA LLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGWSPALGLQICWSLGHLRLTHHKGVN LTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAVRNNCTSGQWSLRCSECGARPLASRIVGGQSV APGRWPWQASVALGFRHTCGGSVLAPRWWTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVE RIIPHPLYSAQNHDYDVALLRLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDM LQDTWPLFSTQLCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRG CAEPNHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 4B.
Table 4B. Comparison ofthe NOV4 protein sequences.
NOV4a MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHPSRPDWAIGEMTGWGQWRAIILHSPD NOV4b MSLMLDDQPPMEAQYAEEGPGPGIFRAEPGDQQHP
NOVla PPWGQPHMIDVSQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQ NOV4b ISQAVCWRSMRRGCAVLGALGLLAGAGVGSWLLVLYLCPAASQPISGTLQ
NOV4a DEEITLSCSEASAEEALLPALPKTPALPKTVSFRINSEDFLLEAQVRDQPRWLLVCHEGW NOV4b DEEITLSCSEASAEEALLPALPKT VSFRINSEDFLLEAQVRDQPRWLLVCHEGW
NOVla SPALGLQICWSLGHLRLTHHKGVNLTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAV NOV4b SPALGLQICWSLGHLRLTHHKGVNLTDIKLNSSQEFAQLSPRLGGFLEEAWQPSRTTEAV
NOV4a RNNCTSGQWSLRCSECGARPLASRIVGGQSVAPGRWPWQASVALGFRHTCGGSVLAPRW NOV4b RNNCTSGQWSLRCSECGARPLASRIVGGQSVAPGRWPWQASVALGFRHTCGGSVLAPRW
NOV4a WTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVERIIPHPLYSAQNHDYDVALL NOV4b WTAAHCMHSFRLARLSSWRVHAGLVSHSAVRPHQGALVERIIPHPLYSAQNHDYDVALL
NOV4a RLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDMLQDTWPLLSTQ NOV4b RLQTALNFSDTVGAVCLPAKEQHFPKGSRCWVSGWGHTHPSHTYSSDMLQDTWPLLSTQ
NOV4a LCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRGCAEP NOV4b LCNSSCVYSGALTPRMLCAGYLDGRADACQGDSGGPLVCPDGDTWRLVGWSWGRGCAEP
NOV4a NHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF NOV4b NHPGVYAKVAEFLDWIHDTAQVSVGAGVGQGDF
NOVla (SEQ ID NO: 54) NOVlb (SEQ ID NO: 56)
Further analysis ofthe NOV4a protein yielded the following properties shown in Table 4C. Table 4C. Protein Sequence Properties NOV4a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 7; pos.chg 0; neg.chg 2 H-region: length 4; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -12.80 possible cleavage site: between 13 and 14
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -3.40 Transmembrane 89 - 105 PERIPHERAL Likelihood = 5.57 (at 173) ALOM score: -3.40 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 96 Charge difference: -8.0 C(-6.0) - N( 2.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 2 (cytoplasmic tail 1 to 89)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.83 Hyd Moment (95): 8.90 G content: 0 D/E content : 2 S/T content : 1 Score: -6.04
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pa 7: none bipartite: none content of basic residues: 7.2% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
34.8 % mitochondrial 26.1 % cytoplasmic 17.4 % Golgi
8.7 % endoplasmic reticulum
4.3 extracellular, including cell wall
4.3 % nuclear
4.3 % vesicles of secretory system
>> prediction for CG125860-02 is mit (k=23)
A search ofthe NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4D.
Figure imgf000186_0001
In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4E.
Figure imgf000187_0001
PFam analysis indicates that the NOV4a protein contains the domains shown in the Table 4F.
Figure imgf000187_0002
Example 5.
The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.
Figure imgf000188_0001
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 5B. Table 5B. Comparison of the NOV5 protein sequences.
NOV5a MEQDNTTLLTEFVLTGLTYQPEWKMPLFLVFLVIYLITIVWNLGLIALIWNDPQLHIPMY
NOV5b MEQDNTTLLTEFVLTGLTYQPE KMPLFLVFLVIYLITIVWNLGLIALIWNDPQLHIPMY
NOV5a FFLGSLAFVDAWISSTVTPKMLVNFLAKNRMISLSECMIQFFSFAFGGTTECFLLATMAY
NOV5b FFLGSLAFVDAWISSTVTPKMLVNFLAKNRMISLSECMIQFFSFAFGGTTECFLLATMAY
NOV5a DRYVAICKPLLYPVIMNNSLCIRLLAFSFLGGFLHALIHEVLIFRLTFCNSNIIHHFYCD
NOV5b DRYVAICKPLLYPVIMNNSLCIRLLAFSFLGGFLHALIHEVLIFRLTFCNSNIIHHFYCD
NOV5a IIPLFMISCTDPSINFLMVFILSGSIQVFTIVTVLNSYTFALFTILKKKSVRGVRKAFST
NOV5b IIPLFMISCTDPSINFLMVFILSGSIQVFTIVTVLNSYTFALFTILKKKSVRGVRKAFST
NOV5a CGAHLLSVSLYYGPLIFMYLRPASPQADDQDMIDSVFYTIIIPLLNPIIYSLRNKQVIDS
NOV5b CGAHLLSVSLYYGPLIFMYLRPASPQADDQDMIDSVFYTIIIPLLNPIIYSLRNKQVIDS
NOV5a FTKMVKRNV NOV5b FTKMVKRNV
NOV5a (SEQ ID NO: 76) NOV5b (SEQ ID NO: 78)
Further analysis ofthe NOV5a protein yielded the following properties shown in Table 5C.
Table 5C. Protein Sequence Properties NOV5a
SignalP analysis: Cleavage site between residues 52 and 53
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos . chg 0; neg.chg 3 H-region: length 10; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.77 possible cleavage site: between 38 and 39
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -9. .24 Transmembrane 25 - - 41
INTEGRAL Likelihood = 0, .37 Transmembrane 57 - • 73
INTEGRAL Likelihood = -2. .02 Transmembrane 142 - - 158
INTEGRAL Likelihood = -5. .79 Transmembrane 196 - 212
INTEGRAL Likelihood = -1. .70 Transmembrane 276 - 292
PERIPHERAL Likelihood = 0. .90 (at 173)
ALOM score : -9.24 (number of TMSs: 5) MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 32 Charge difference: 0.5 C(-0.5) - N(-1.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 6.20 Hyd Momen (95): 3.11 G content: 0 D/E content: 2 S/T content: 0 Score: -7.39
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 6.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: VKRN
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
33.3 %: endoplasmic reticulum
11.1 %: mitochondrial
11.1 %: Golgi
11.1 %: vacuolar
11.1 %: nuclear
11.1 %: vesicles of secretory system
11.1 %: cytoplasmic
>> prediction for CG155759-02 is end (k=9)
A search ofthe NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5D.
Figure imgf000192_0001
In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5E.
Figure imgf000193_0001
PFam analysis indicates that the NOV5a protein contains the domains shown in the Table 5F.
Figure imgf000194_0001
Example 6.
The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.
Table 6A. NOV6 Sequence Analysis
NOV6a, CGI 87667-01 SEQ ID NO: 79 2680 bp DNA Sequence ORF Start: ATG at 873 ORF Stop: TAG at 2484
GGGCAGGTGTTAAGCGATAAAGGGGGGCAGAACAAGTCTTTTATCCGGCCATTTAATTGGTCACCTTA
AGAAAGAATCCTATCTTCCCACCGCAGCTGAGAAGACACTTCTAAGAGGTACAGCTAAAAGGTGGAGG
ACTGATAGACAACTTAGAGGTTGGTTTCGGGAACGATAAAACAAGTAACGGGCTGCCCGGCCTGCGCCj
GCGGAGTCCCGAGGAGCCTGCGCTGTGCTCCTCTCGCGGTGTCTCGTCATCTCCGGGAAGACTCGGCG!
CCTGGGTCCGCGCTCTCTGGGTAAGCTTTCCGGGAAGCTTTCCCGGGAGCTCGCTGGTCCTGGCCCCAj
IGAAGCCTGCGGACCCGCCCAGGGAGGATAAGCAGCTGAAAGACCGCGCGGTGCCGCTCCGAGGCCCCGI iGGACGTGGGCCCATGGTCGGCCTGGCGCCACCTTTCCGGGGGAAGCCACGCGCACCAGGCATCGCACGj
CGGCTCTGCACCCGCGCCGCCGGACCTGAAACCCGGCGGAGGGCACACGGGGCTGCCGCTGCGGGCCC;
CGGACCAACCCATGCTTACTCCGGAGCCTGTACCGGCGCCGACGGGTCGGACCTCCCTGCGCGGTGTC
GCCCAGCGGGTTCGTGCGAAAGGCGGGGCCGACTACACGCGGTGCCGCGCCCTGAGACCGTTTATCTG
CAGTCAACGCAGCCTCCCGGCTCAGCCTGGGAAGATGCGCGAATCGGGAACCCCAGAGCGCGGTGGCT
AGACCGGGCTCCGCCGCCTCCCCCACAGCCCCTTTCCTAATCGTTCAGACGGAGCCTGGTCGACTTCG
CCGGAGACTGCCAGATCTCGTTCCTCTTCCCTGTGTCATCTTCTTAATTATAAATAATGGGGGATGAA
GATAAAAGAATTACATATGAAGATTCAGAACCATCCACAGGAATGAATTACACGCCCTCCATGCATCA AGAAGCACAGGAGGAGACAGTTATGAAGCTCAAAGGTATAGATGCAAATGAACCAACAGAAGGAAGTA TTCTTTTGAAAAGCAGTGAAAAAAAGCTACAAGAAACACCAACTGAAGCAAATCACGTACAAAGACTG AGACAAATGCTGGCTTGCCCTCCACATGGTTTACTGGACAGGGTCATAACAAATGTTACCATCATTGT TCTTCTGTGGGCTGTAGTTTGGTCAATTACTGGCAGTGAATGTCTTCCTGGAGGAAACCTATTTGGAA TTATAATCCTATTCTATTGTGCCATCATTGGTGGTAAACTTTTGGGGCTTATTAAGTTACCTACATTG CCTCCACTGCCTTCTCTTCTTGGCATGCTGCTTGCAGGGTTTCTCATCAGAAATATCCCAGTCATCAA CGATAATGTGCAGATCAAGCACAAGTGGTCTTCCTCTTTGAGAAGCATAGCCCTGTCTATCATTCTGG TTCGTGCTGGCCTTGGTCTGGATTCAAAGGCCCTGAAGAAGTTAAAGGGCGTTTGTGTAAGACTGTCC ATGGGTCCCTGTATTGTGGAGGCGTGCACATCTGCTCTTCTTGCCCATTACCTGCTGGGTTTACCATG GCAATGGGGATTTATACTGGGTTTTGTTTTAGGTGCTGTATCTCCAGCTGTTGTGGTGCCTTCAATGC TCCTTTTGCAGGGAGGAGGCTATGGTGTTGAGAAGGGTGTCCCAACCTTGCTCATGGCAGCTGGCAGC TTCGATGACATTCTGGCCATCACTGGCTTCAACACATGCTTGGGCATAGCCTTTTCCACAGGCTCTAC TGTCTTTAATGTCCTCAGAGGAGTTTTGGAGGTGGTAATTGGTGTGGCAACTGGATCTGTTCTTGGAT TTTTCATTCAGTACTTTCCAAGCCGTGACCAGGACAAACTTGTGTGTAAGAGAACATTCCTTGTGTTG GGGTTGTCTGTGCTAGCTGTGTTCAGCAGTGTGCATTTTGGTTTCCCTGGATCAGGAGGACTGTGCAC GTTGGTCATGGCTTTCCTTGCAGGCATGGGATGGACCAGCGAAAAGGCAGAGGTTGAAAAGATAATTG CAGTTGCCTGGGACATTTTTCAGCCCCTTCTTTTTGGACTAATTGGAGCAGAGGTATCTATTGCATCT CTCAGACCAGAAACTGTAGGCCTTTGTGTTGCCACCGTAGGCATTGCAGTATTGATACGAATTTTGAC TACATTTCTGATGGTGTGTTTTGCTGGTTTTAACTTAAAAGAAAAGATATTTATTTCTTTTGCATGGC TTCCAAAGGCCACAGTTCAGGCTGCAATAGGATCTGTGGCTTTGGACACAGCAAGGTCACATGGAGAG AAACAATTAGAAGACTATGGAATGGATGTGTTGACAGTGGCATTTTTGTCCATCCTCATCACAGCCCC AATTGGAAGTCTGCTTATTGGTTTACTGGGCCCCAGGCTTCTGCAGAAAGTTGAACATCAAAATAAAG ATGAAGAAGTTCAAGGAGAGACTTCTGTGCAAGTTTAGGAAGCGCGGATTCTATTACTGGAAACTTTG
GGACTGAAAGGCCAAAGCTTCTGGGCCCACCATCAACGCAGCTCCGCTTTCATTTCTTTCACATACAA
CTTTCCACATAAGATTTCATGCGGAAAAAAAAAAAAAACTCACAAAGGTTTTATACTGATAACAGTAT
ATTAAGTGTTTACTTTGTACACAGCGTC
NOV6a, CGI 87667-01 SEQ ID NO: 80 537 aa MW at 57563.3kD Protein Sequence
MGDEDKRITYEDSEPSTGMNYTPSMHQEAQEETVMKLKGIDANEPTEGSILLKSSEKKLQETPTEANH VQRLRQMLACPPHGLLDRVITNVTIIVLLWAWWSITGSECLPGGNLFGIIILFYCAIIGGKLLGLIK LPTLPPLPSLLGMLLAGFLIRNIPVINDNVQIKHKWSSSLRSIALSIILVRAGLGLDSKALKKLKGVC VRLSMGPCIVEACTSALLAHYLLGLPWQWGFILGFVLGAVSPAVWPSMLLLQGGGYGVEKGVPTLLM AAGSFDDILAITGFNTCLGIAFSTGSTVFNVLRGVLEWIGVATGSVLGFFIQYFPSRDQDKLVCKRT FLVLGLSVLAVFSSVHFGFPGSGGLCTLVMAFLAGMGWTSEKAEVEKIIAVAWDIFQPLLFGLIGAEV SIASLRPETVGLCVATVGIAVLIRILTTFLMVCFAGFNLKEKIFISFAWLPKATVQAAIGSVALDTAR SHGEKQLEDYGMDVLTVAFLSILITAPIGSLLIGLLGPRLLQKVEHQNKDEEVQGETSVQV
NOV6b, CGI 87667-02 SEQ ID NO: 81 2285 bp DNA Sequence ORF Start: ATG at 873 ORF Stop: TAA at 2235
GGGCAGGTGTTAAGCGATAAAGGGGGGCAGAACAAGTCTTTTATCCGGCCATTTAATTGGTCACCTTA
AGAAAGAATCCTATCTTCCCACCGCAGCTGAGAAGACACTTCTAAGAGGTACAGCTAAAAGGTGGAGG
ACTGATAGACAACTTAGAGGTTGGTTTCGGGAACGATAAAACAAGTAACGGGCTGCCCGGCCTGCGCC iGCGGAGTCCCGAGGAGCCTGCGCTGTGCTCCTCTCGCGGTGTCTCGTCATCTCCGGGAAGACTCGGCG
CCTGGGTCCGCGCTCTCTGGGTAAGCTTTCCGGGAAGCTTTCCCGGGAGCTCGCTGGTCCTGGCCCCA
IGAAGCCTGCGGACCCGCCCAGGGAGGATAAGCAGCTGAAAGACCGCGCGGTGCCGCTCCGAGGCCCCG
IGGACGTGGGCCCATGGTCGGCCTGGCGCCACCTTTCCGGGGGAAGCCACGCGCACCAGGCATCGCACG
CGGCTCTGCACCCGCGCCGCCGGACCTGAAACCCGGCGGAGGGCACACGGGGCTGCCGCTGCGGGCCC
CGGACCAACCCATGCTTACTCCGGAGCCTGTACCGGCGCCGACGGGTCGGACCTCCCTGCGCGGTGTC
GCCCAGCGGGTTCGTGCGAAAGGCGGGGCCGACTACACGCGGTGCCGCGCCCTGAGACCGTTTATCTG
CAGTCAACGCAGCCTCCCGGCTCAGCCTGGGAAGATGCGCGAATCGGGAACCCCAGAGCGCGGTGGCT
AGACCGGGCTCCGCCGCCTCCCCCACAGCCCCTTTCCTAATCGTTCAGACGGAGCCTGGTCGACTTCG
CCGGAGACTGCCAGATCTCGTTCCTCTTCCCTGTGTCATCTTCTTAATTATAAATAATGGGGGATGAA
GATAAAAGAATTACATATGAAGATTCAGAACCATCCACAGGAATGAATTACACGCCCTCCATGCATCA AGAAGCACAGGAGGAOACAGTTATGAAGCTCAAAGGTATAGATGCAAATGAACCAACAGAAGGAAGTA TTCTTTTGAAAAGCAGTGAAAAAAAGCTACAAGAAACACCAACTGAAGCAAATCACGTACAAAGACTG AGACAAATGCTGGCTTGCCCTCCACATGGTTTACTGGACAGGGTCATAACAAATGTTACCATCATTGT TCTTCTGTGGGCTGTAGTTTGGTCAATTACTGGCAGTGAATGTCTTCCTGGAGGAAACCTATTTGGAA TTATAATCCTATTCTATTGTGCCATCATTGGTGGTAAACTTTTGGGGCTTATTAAGTTACCTACATTG CCTCCACTGCCTTCTCTTCTTGGCATGCTGCTTGCAGGGTTTCTCATCAGAAATATCCCAGTCATCAA CGATAATGTGCAGATCAAGCACAAGTGGTCTTCCTCTTTGAGAAGCATAGCCCTGTCTATCATTCTGG TTCGTGCTGGCCTTGGTCTGGATTCAAAGGCCCTGAAGAAGTTAAAGGGCGTTTGTGTAAGACTGTCC ATGGGTCCCTGTATTGTGGAGGCGTGCACATCTGCTCTTCTTGCCCATTACCTGCTGGGTTTACCATG GCAATGGGGATTTATACTGGGTTTTGTTTTAGGTGCTGTATCTCCAGCTGTTGTGGTGCCTTCAATGC TCCTTTTGCAGGGAGGAGGCTATGGTGTTGAGAAGGGTGTCCCAACCTTGCTCATGGCAGCTGGCAGC TTCGATGACATTCTGGCCATCACTGGCTTCAACACATGCTTGGGCATAGCCTTTTCCACAGGCTCTAC TGTCTTTAATGTCCTCAGAGGAGTTTTGGAGGTGGTAATTGGTGTGGCAACTGGATCTGTTCTTGGAT TTTTCATTCAGTACTTTCCAAGCCGTGACCAGGACAAACTTGTGTGTAAGAGAACATTCCTTGTGTTG GGGTTGTCTGTGCTAGCTGTGTTCAGCAGTGTGCATTTTGGTTTCCCTGGATCAGGAGGACTGTGCAC GTTGGTCATGGCTTTCCTTGCAGGCATGGGATGGACCAGCGAAAAGGCAGAGGTTGAAAAGATAATTG CAGTTGCCTGGGACATTTTTCAGCCCCTTCTTTTTGGACTAATTGGAGCAGAGGTATCTATTGCATCT CTCAGACCAGAAACTGTAGGAAGCGCGGATTCTATTACTGGAAACTTTGGGACTGAAAGGCCAAAGCT TCTGGGCCCACCATCAACGCAGCTCCGCTTTCATTTCTTTCACATACAACTTTCCACATAAGATTTCA TGCGGAAAAAAAAAAAAAACTCACAAAGGTTTTATACTGAT
NOV6b, CGI 87667-02 SEQ ID NO: 82 454 aa MW at 48709.8kD Protein Sequence
MGDEDKRITYEDSEPSTGMNYTPSMHQEAQEETVMKLKGIDANEPTEGSILLKSSEKKLQETPTEANH VQRLRQMLACPPHGLLDRVITNVTIIVLLWAWWSITGSECLPGGNLFGIIILFYCAIIGGKLLGLIK LPTLPPLPSLLGMLLAGFLIRNIPVINDNVQIKHKWSSSLRSIALSIILVRAGLGLDSKALKKLKGVC VRLSMGPCIVEACTSALLAHYLLGLPWQWGFILGFVLGAVSPAWVPSMLLLQGGGYGVEKGVPTLLM AAGSFDDILAITGFNTCLGIAFSTGSTVFNVLRGVLEWIGVATGSVLGFFIQYFPSRDQDKLVCKRT FLVLGLSVLAVFSSVHFGFPGSGGLCTLVMAFLAGMGWTSEKAEVEKIIAVAWDIFQPLLFGLIGAEV SIASLRPETVGSADSITGNFGTERPKLLGPPSTQLRFHFFHIQLST
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 6B.
Table 6B. Comparison of the NOV6 protein sequences.
NOV6a MGDEDKRITYEDSEPSTGMNYTPSMHQEAQEETVMKLKGIDANEPTEGSILLKSSEKKLQ
NOV6b MGDEDKRITYEDSEPSTGMNYTPSMHQEAQEETVMKLKGIDANEPTEGSILLKSSEKKLQ
NOV6a ETPTEANHVQRLRQMLACPPHGLLDRVITNVTIIVLLWAWWSITGSECLPGGNLFGIII
NOV6b ETPTEANHVQRLRQMLACPPHGLLDRVITNVTIIVLLWAWWSITGSECLPGGNLFGIII
NOV6a LFYCAIIGGKLLGLIKLPTLPPLPSLLGMLLAGFLIRNIPVINDNVQIKHKWSSSLRSIA
NOV6b LFYCAIIGGKLLGLIKLPTLPPLPSLLGMLLAGFLIRNIPVINDNVQIKHKWSSSLRSIA
NOV6a LSIILVRAGLGLDSKALKKLKGVCVRLSMGPCIVEACTSALLAHYLLGLPWQWGFILGFV
NOV6b LSIILVRAGLGLDSKALKKLKGVCVRLSMGPCIVEACTSALLAHYLLGLPWQWGFILGFV
NOV6a LGAVSPAWVPSMLLLQGGGYGVEKGVPTLLMAAGSFDDILAITGFNTCLGIAFSTGSTV
NOV6b LGAVSPAVWPSMLLLQGGGYGVEKGVPTLLMAAGSFDDILAITGFNTCLGIAFSTGSTV
NOV6a FNVLRGVLEWIGVATGSVLGFFIQYFPSRDQDKLVCKRTFLVLGLSVLAVFSSVHFGFP
NOV6b FNVLRGVLEWIGVATGSVLGFFIQYFPSRDQDKLVCKRTFLVLGLSVLAVFSSVHFGFP
NOV6a GSGGLCTLVMAFLAGMGWTSEKAEVEKIIAVAWDIFQPLLFGLIGAEVSIASLRPETVGL
NOV6b GSGGLCTLVMAFLAGMGWTSEKAEVEKIIAVAWDIFQPLLFGLIGAEVSIASLRPETVGS
NOV6a CVATVGIAVLIRILTTFLMVCFAGFNLKEKIFISFAWLPKATVQAAIGSVALDTARSHGE
NOV6b ADSITGNFGTERPK- -LLG P PSTQLRFHFFHIQLST
NOV6a KQLEDYGMDVLTVAFLSILITAPIGSLLIGLLGPRLLQKVEHQNKDEEVQGETSVQV NOV6b
NOV6a (SEQ ID NO: 80) NOV6b (SEQ ID NO: 82)
Further analysis ofthe NOV6a protein yielded the following properties shown in Table 6C. Table 6C. Protein Sequence Properties NOV6a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos.chg 2; neg . chg 4 H-region: length 0; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -13.82 possible cleavage site: between 48 and 49
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative nlumber of TM£ !(s) i Eor the threshold 0 .5: 10
INTEGRAL Likelihood = -5 .20 Transmembrane 88 - 104
INTEGRAL Likelihood = -6 .10 Transmembrane 118 - 134
INTEGRAL Likelihood = -3 .13 Transmembrane 146 - 162
INTEGRAL Likelihood = -1 .06 Transmembrane 176 - 192
INTEGRAL Likelihood = -6 .26 Transmembrane 234 - 250
INTEGRAL Likelihood = -4 .09 Transmembrane 308 - 324
INTEGRAL Likelihood = -4 .94 Transmembrane 341 - 357
INTEGRAL Likelihood = -3. .19 Transmembrane 388 - 404
INTEGRAL Likelihood = -7. .91 Transmembrane 418 - 434
INTEGRAL Likelihood = -6. .69 Transmembrane 493 - 509
PERIPHERAL Likelihood = 0. .63 (at 213)
ALOM score: -7.91 (number of TMSs: 10)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 95 Charge difference: -2.5 C(-1.0) - N( 1.5) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 9.18 Hyd Moment(95): 7.68 G content: 1 D/E content : 2 S/T content : 0 Score: -6.91
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 7.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum
11.1 %: nuclear
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG187667-01 is end (k=9) A search ofthe NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6D.
Figure imgf000199_0001
In a BLAST search of public sequence databases, the NOVόa protein was found to have homology to the proteins shown in the BLASTP data in Table 6E.
Figure imgf000200_0001
PFam analysis indicates that the NOVόa protein contains the domains shown in the Table 6F.
Figure imgf000200_0002
Example 7.
The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A. Table 7A. NOV7 Sequence Analysis
NOV7a, CGI 87676-01 SEQ I NO: 83 2474 bp DNA Sequence ORF Start: ATG at 5 ORF Stop: TGA at 2270
AAAAATGAAAAAACAGAGGAAAATTCTATGGAGGAAAGGAATCCACTTAGCCTTTTCTGAGAAATGGA
ATACTGGGTTTGGAGGCTTTAAGAAGTTTTATTTTCACCAACACTTGTGCATTCTGAAAGCTAAGCTG GGAAGGCCAGTTACTTGGAATAGACAGTTGAGACATTTCCAGGGTAGAAAGAAAGCTCTTCAAATCCA GAAAACGTGGATCAAGGATGAACCCCTTTGTGCTAAGACCAAGTTCAATGTGGCTACTCAAAATGTTA GTACTTTGTCCTCTAAAGTGAAAAGAAAGGACGCTAAACACTTCATTTCCTCCTCAAAGACTCTCCTG AGACTCCAAGCAGAGAAGCTGTTGTCATCAGCAAAGAATTCTGACCATGAATACTGCAGAGAGAAAAA TCTCTTGAAGGCAGTTACTGACTTTCCATCAAATAGTGCTTTAGGTCAGGCCAATGGTCACAGACCTA GGACAGACCCACAACCTTCTGACTTTCCCATGAAGTTCAATGGGGAGAGCCAAAGTCCAGGTGAGAGT GGCACGATTGTGGTCACCTTGAACAACCATAAGAGAAAGGGCTTTTGTTACGGCTGCTGCCAAGGGCC GGAGCACCACAGGAATGGGGGACCCTTGATTCCAAAAAAGTTCCAACTTAACCAACATAGAAGGATAA AATTATCTCCTCTTATGATGTATGAGAAATTATCCATGATTAGATTTCGGTACAGGATTCTCAGATCC CAGCACTTCAGAACCAAAAGCAAGGTTTGCAAGCTAAGAAAAGCCCAGCGAAGCTGGGTACAGAAAGT CACTGGGGACCATCAAGAGACCCGTAGGGAGAACGGTGAGGGTGGCAGTTGCAGCCCATTTCCTTCCC CAGAACCTAAAGACCCTTCTTGTCGGCATCAGCCGTACTTTCCAGATATGGACAGCAGTGCTGTGGTG AAGGGGACGAACTCTCATGTGCCTGATTGCCACACTAAAGGAAGCTCTTTCTTGGGCAAGGAGCTTAG TTTAGACGAAGCATTCCCTGACCAACAGAATGGCAGTGCCACAAACGCCTGGGACCAGTCATCCTGTT CTTCTCCTAAGTGGGAGTGTACAGAGCTGATTCATGACATCCCCTTACCAGAACATCGTTCTAATACC ATGTTCATTTCAGAAACTGAAAGAGAAATTATGACTCTGGGTCAGGAAAATCAGACAAGTTCTGTCAG TGATGACAGAGTAAAACTGTCAGTGTCTGGAGCAGATACATCTGTGAGTAGCGTAGATGGGCCTGTGT CCCAAAAGGCTGTTCAAAATGAGAACTCATACCAGATGGAGGAGGATGGATCTCTCAAGCAGAGCATT CTTAGTTCTGAGTTGCTGGACCACCCTTACTGTAAAAGTCCACTGGAGGCTCCCTTGGTGTGCAGTGG ACTCAAACTAGAAAATCAAGTAGGAGGTGGAAAGAACAGTCAGAAAGCCTCTCCAGTGGATGATGAAC AGCTGTCAGTCTGTCTTTCTGGATTCCTAGATGAGGTTATGAAGAAGTATGGCAGTTTGGTTCCACTC AGTGAAAAAGAAGTCCTTGGAAGATTAAAAGATGTCTTTAATGAAGACTTTTCTAATAGAAAACCATT TATCAATAGGGAAATAACAAACTATCGGGCCAGACATCAAAAATGTAACTTCCGTATCTTCTATAATA AACACATGCTGGATATGGACGACCTGGCGACTCTGGATGGTCAGAACTGGCTGAATGACCAGGTCATT AATATGTATGGTGAGCTGATAATGGATGCAGTCCCAGACAAAGTTCACTTCTTCAACAGCTTTTTTCA TAGACAGCTGGTAACCAAAGGATATAATGGAGTAAAAAGATGGACTAAAAAGGTGGATTTGTTTAAAA AGAGTCTTCTGTTGATTCCTATTCACCTGGAAGTCCACTGGTCTCTCATTACTGTGACACTCTCTAAT CGAATTATTTCATTTTATGATTCCCAAGGCATTCATTTTAAGTTTTGTGTAGAGAATATAAGAAAGTA TTTGCTGACTGAAGCCAGAGAAAAAAATAGACCTGAATTTCTTCAGGGTTGGCAGACTGCTGTTACGA AGTGTATTCCACAACAGAAAAACGACAGTGACTGTGGAGTCTTTGTGCTCCAGTACTGCAAGTGCCTC GCCTTAGAGCAGCCTTTCCAGTTTTCACAAGAAGACATGCCCCGAGTGCGGAAGAGGATTTACAAGGA GCTATGTGAGTGCCGGCTCATGGACTGAAACTCAGCAGGGACTCTGGGAAGTCTGACCAAGTTGGAGC
AGATGGTTTGTTACTTGAATCTCCAAACACTTAGTTGAATTTTTACAGATATTTCAGATCAGTGGTGT
TGGGCCACTATTGTTACCTCAAATTTATTTTTTGCCCTTATTCATTTCTCCAGCTACCATGTACTATT
GTTTAATGTTCAGTTTGGTTTCAAAA
NO V7a, CGI 87676-01 SEQ ID NO: 84 755 aa MW at 86692.3kD Protein Sequence
MKKQRKILWRKGIHLAFSEKWNTGFGGFKKFYFHQHLCILKAKLGRPVTWNRQLRHFQGRKKALQIQK TWIKDEPLCAKTKFNVATQNVSTLSSKVKRKDAKHFISSSKTLLRLQAEKLLSSAKNSDHEYCREKNL LKAVTDFPSNSALGQANGHRPRTDPQPSDFPMKFNGESQSPGESGTIWTLNNHKRKGFCYGCCQGPE HHRNGGPLIPKKFQLNQHRRIKLSPLMMYEKLSMIRFRYRILRSQHFRTKSKVCKLRKAQRSWVQKVT GDHQETRRENGEGGSCSPFPSPEPKDPSCRHQPYFPDMDSSAWKGTNSHVPDCHTKGSSFLGKELSL DEAFPDQQNGSATNAWDQSSCSSPKWECTELIHDIPLPEHRSNTMFISETEREIMTLGQENQTSSVSD DRVKLSVSGADTSVSSVDGPVSQKAVQNENSYQMEEDGSLKQSILSSELLDHPYCKSPLEAPLVCSGL KLENQVGGGKNSQKASPVDDEQLSVCLSGFLDEVMKKYGSLVPLSEKEVLGRLKDVFNEDFSNRKPFI NREITNYRARHQKCNFRIFYNKHMLDMDDLATLDGQNWLNDQVINMYGELIMDAVPDKVHFFNSFFHR QLVTKGYNGVKRWTKKVDLFKKSLLLIPIHLEVHWSLITVTLSNRIISFYDSQGIHFKFCVENIRKYL LTEAREKNRPEFLQGWQTAVTKCIPQQKNDSDCGVFVLQYCKCLALEQPFQFSQEDMPRVRKRIYKEL CECRLMD Further analysis ofthe NOV7a protein yielded the following properties shown in Table 7B.
Table 7B. Protein Sequence Properties NOV7a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos.chg 6; neg . chg 0 H-region: length 7; peak value 0.84 PSG score: -3.56
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -10.14 possible cleavage site: between 18 and 19
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 6.31 (at 710) ALOM score: -0.06 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 3.21 Hyd Moment(95): 10.20 G content: 1 D/E content: 1 S/T content: 1 Score: -3.27
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 70 GRK|KA
NUCDISC: discrimination of nuclear localization signals pat4: HKRK (3) at 190 pat7: PRVRKRI (5) at 738 bipartite: none content of basic residues: 15.1% NLS Score: 0.15
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: KKQR none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
65.2 %: nuclear
26.1 %: mitochondrial
4.3 %: cytoplasmic
4.3 %-. peroxisomal
>> prediction for CG187676-01 is nuc (k=23)
A search ofthe NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.
Figure imgf000204_0001
In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.
Figure imgf000205_0001
PFam analysis indicates that the NOV7a protein contains the domains shown in the Table 7E. Table 7E. Domain Analysis of NOV7a
Identities/
Pfam Domain NOV7a Match Region Similarities Expect Value for the Matched Region
Peptidase_C48 563.J52 62/248 (25%) 7e-43 149/248 (60%)
Example 8.
The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.
Table 8A. NOV8 Sequence Analysis
NOV8a, CG50235-04 SEQ ID NO: 85 3120 bp DNA Sequence ORF Start: ATG at 256 ORF Stop: TGA at 2719
TAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGCi
TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG!
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCAGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA
GGCCCGCTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG!
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGAT:
GATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
TCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8a, CG50235-04 SEQ ID NO: 86 821 aa MW at 91404.2kD Protein Sequence
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
NOV8b, CG50235-01 SEQ ID NO: 87 3350 bp DNA Sequence ORF Start: ATG at 365 ORF Stop: TAG at 3341
CGCCCATTGGCTCCTCAGCCAAGCACGTACACCAAATGTCTGAACCTGCGGTTCCTCTCGTACTGAGC!
AGGATTACCATGGCAACAACACATCATCAGTAGGGTAAAACTAACCTGTCTCACGACGGTCTAAACCCj
AGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGCTTCCCGGTTGCCTCGAAGAAGACAGGG
GGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAGCAGCCCTGTGTAACCACCGAGTCCCGG!
CCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAGCTGAGCTTTCGTGCACGCAACTCCCTC
TGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGCACTTGGGGCCCTGGTGTCACTGCTGCT
GCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGCGCCCGGACGCCACCGCAGACTACTCAG AGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCATTACCACGACCCTTGCAAAGCCGCTGTC TTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCTGTTTCACATTGACAAAGCCAGAGACTG GACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTGGGCTTGAAGAGCAGGCATCTGAGAGCA GCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCTGGAAAGGATGGCCGGGAGAATACCACA CTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGACCTTCTCTCCCCGGGTCCGAAGAGCCAC AACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCCCCTACGTCATTGGAGGGAACTTCACTG GGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGGGAGAAGCACACCTGTGTGACCTTCATA GAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAGAACCTGTGGCTGTTGCTCCTATGTTGG GCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGAACTGTGACAAGTTTGGCATTGTGGCTC ACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACCCGGCCAGACAGAGACCAACATGTCACC ATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTTCTTAAAAATGGAAGCTGGGGAAGTGAG CTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACTACGCCCGGAACACCTTCTCAAGAGGAG TTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGCGTCAGGCCAACCATTGGCCAGCGCGTG CGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTACAAATGCCCAGCGTGTGGGGAGACCCT GCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAAATGGGTACCCATCTTACTCCCACTGCG TCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTAAACTTCACATCCATGGATTTGTTTAAA AGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGGTTACTGGAGAAAAGCCCCCCTTTTGGG CAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCACGGACAGCCGGCTCTGGGTGGAGTTCC GCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCGTACGAAGCTACCTGCGGGGGAGACATG AACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGATGACTACAGACCTTCCAAGGAATGTGT CTGGAGGATTACGGTTTCAGAGGGGTTTCACGTGGGACTTACCTTCCAAGCTTTTGAGATTGAAAGGC ACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGCCCCACGGAAGAGAGTGCCCTGATCGGC CACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAGCTCCAACAGACTGTGGATGAAGTTTGT GTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATTTTTTCAAGGAGGTGGATGAGTGTTCCT GGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACGCTGGGCAGCTACAAGTGTGCCTGTGAC CCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGTGGCCTGTGGCGGTTTCATTACCAAGCT GAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATCCCACAAACAAAAACTGTGTCTGGCAGG TGGTGGCCCCCACTCAGTACCGGATCTCCCTTCAGTTTGAAGTGTTTGAACTGGAAGGCAATGACGTC TGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCCCGACGCCAAGCTGCACGGCAGGTTCTG CGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACAACATGCGCGTGGAGTTCAAGTCCGACA ACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCAGATAAGGACGAGTGTGCCAAGGACAAC GGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTACCTGTGCAGGTGCAGAAACGGCTACTG GCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTGCACACAAGATCAGCAGTGTGGAGGGGA CCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGGAGGGAGTGTACCTGGAACATCTCTTCG ACTGCAGGCCACAGAGTGAAACTCACCTTTAATGAGTTTGAGATCGAGCAGCACCAGGAATGTGCCTA TGACCACCTGGAAATGTATGACGGGCCGGACAGCCTGGCCCCCATTCTGGGCCGTTTCTGCGGCAGCA AGAAACCAGACCCCACGGTGGCTTCCGGCAGCAAGTGCGGGGGCAGGCTGAAGGCTGAAGTGCAGACC AAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGAGGCCCGCTGTGACTGGGT GATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTGAGGTTGAGGAGGAGGCCG ACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCGCCCAGGCTCGGCCGCTTC TGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGATGATTCGATTCCGCACAGA TGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGTTCCAGGATGGCCTGCACA TGAAGAAATAGTGCTGAT
NOV8b, CG50235-01 SEQ ID NO: 88 992 aa MW at l l0925.6kD Protein Sequence
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPTQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL TFNEFEIEQHQECAYDHLEMYDGPDSLAPILGRFCGSKKPDPTVASGSKCGGRLKAEVQTKELYSHAQ FGDNNYPSEARCDWVIVAEDGYGVELTFRTFEVEEEADCGYDYMEAYDGYDSSAPRLGRFCGSGPLEE IYSAGDSLMIRFRTDDTINKKGFHARYTSTKFQDGLHMKK
NOV8c, CG50235-02 SEQ ID NO: 89 5006 bp DNA Sequence ORF Start: ATG at 365 ORF Stop: TAG at 3410
CGCCCATTGGCTCCTCAGCCAAGCACGTACACCAAATGTCTGAACCTGCGGTTCCTCTCGTACTGAGC
AGGATTACCATGGCAACAACACATCATCAGTAGGGTAAAACTAACCTGTCTCACGACGGTCTAAACCC
AGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGCTTCCCGGTTGCCTCGAAGAAGACAGGG
GGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAGCAGCCCTGTGTAACCACCGAGTCCCGG
CCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAGCTGAGCTTTCGTGCACGCAACTCCCTC
TGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGCACTTGGGGCCCTGGTGTCACTGCTGCT
GCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGCGCCCGGACGCCACCGCAGACTACTCAG AGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCATTACCACGACCCTTGCAAAGCCGCTGTC TTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCTGTTTCACATTGACAAAGCCAGAGACTG GACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTGGGCTTGAAGAGCAGGCATCTGAGAGCA GCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCTGGAAAGGATGGCCGGGAGAATACCACA CTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGACCTTCTCTCCCCGGGTCCGAAGAGCCAC AACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCCCCTACGTCATTGGAGGGAACTTCACTG GGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGGGAGAAGCACACCTGTGTGACCTTCATA GAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAGAACCTGTGGCTGTTGCTCCTATGTTGG GCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGAACTGTGACAAGTTTGGCATTGTGGCTC ACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACCCGGCCAGACAGAGACCAACATGTCACC ATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTTCTTAAAAATGGAAGCTGGGGAAGTGAG CTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACTACGCCCGGAACACCTTCTCAAGAGGAG TTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGCGTCAGGCCAACCATTGGCCAGCGCGTG CGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTACAAATGCCCAGCGTGTGGGGAGACCCT GCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAAATGGGTACCCATCTTACTCCCACTGCG TCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTAAACTTCACATCCATGGATTTGTTTAAA AGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGGTTACTGGAGAAAAGCCCCCCTTTTGGG CAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCACGGACAGCCGGCTCTGGGTGGAGTTCC GCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCGTACGAAGCTACCTGCGGGGGAGACATG AACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGATGACTACAGACCTTCCAAGGAATGTGT CTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTACCTTCCAAGCTTTTGAGATTGAAAGGC ACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGCCCCACGGAAGAGAGTGCCCTGATCGGC CACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAGCTCCAACAGACTGTGGATGAAGTTTGT GTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATTTTTTCAAGGAGGTGGATGAGTGTTCCT GGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACGCTGGGCAGCTACAAGTGTGCCTGTGAC CCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGTGGCCTGTGGCGGTTTCATTACCAAGCT GAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATCCCACAAACAAAAACTGTGTCTGGCAGG TGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAAGTGTTTGAACTGGAAGGCAATGACGTC TGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCCCGACGCCAAGCTGCACGGCAGGTTCTG CGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACAACATGCGCGTGGAGTTCAAGTCCGACA ACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCAGATAAGGACGAGTGTGCCAAGGACAAC GGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTACCTGTGCAGGTGCAGAAACGGCTACTG GCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTGCACACAAGATCAGCAGTGTGGAGGGGA CCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGGAGGGAGTGTACCTGGAACATCTCTTCG ACTGCAGGCCACAGAGTGAAACTCACCTTTAATGAGTTTGAGATCGAGCAGCACCAGGAATGTGCCTA TGACCACCTGGAAATGTATGACGGGCCGGACAGCCTGGCCCCCATTCTGGGCCGTTTCTGCGGCAGCA AGAAACCAGACCCCACGGTGGCTTCCGGCAGCAGTATGTTTCTCAGGTTTTATTCGGATGCCTCAGTG CAGAGGAAAGGCTTCCAGGCAGTGCACAGCACAGAGTGCGGGGGCAGGCTGAAGGCTGAAGTGCAGAC CAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGAGGCCCGCTGTGACTGGG TGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTGAGGTTGAGGAGGAGGCC GACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCGCCCAGGCTCGGCCGCTT CTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGATGATTCGATTCCGCACAG
ATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGTTCCAGGATGCCCTGCAC ATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGAATTTTTTTGTTTTGTTTTGTTTTTA ACAACAATAGCACCTTGAAAATCTGCCCTAAAACAGTGTACAGTATTTTTCTCAAACAAAAACTCAGA ATCCAGCCTTAGAGGTATATATTTGAATGAAAGTCTTGTAAGTTTGGCCAACAAGGTGGAGAAAAAAA TGTTCTTTTGCTTCTGTCTGCAATGTTGTCATTCATGAACTGTTAAAGTGTTAAAGATTAGGATTGGA GTCACTGACCATTCCGGCTATGCTTCTTCATACCATTCTCCTTGTTGTCCCTTGCTCCTATGTGGCAA AAGGTCAGCCTTGGGGTTGGCCGTTCCTCTAATCTGGACTTGCTTGCAAAGGTGCCAGGCTGTCTTCT GTCCATGTTGGGCATAAGGGATGAAAACTTGGCCGAGACTAATGTGTGGCCCACAGCTTTGGCTGGAA TCATTTTCTTTCTCTCTGCCAGGGACATGTCAACCAAGAAACCTGAAAATATGGATGGATGTCAGGAC TAAAAAAAGGCATCACAGTGAGCAGTGAGCACAGAGGGAGTTTCGAGTATAAGAATCATTGTCATGAA GTTAGGAGACCACAAAGCCATTTCTCAGAGTCATTCACTCTCCTTGTCCCTTTGGTTTCCCCCCTTCC TTAATTGCAGTGGGGGCTAAGGTATCCATTATGAATACAGCAGAACATTTGCTGGCGAGAGTCCTGTC TGCTGAGAAGACAATATTGTGGCTCGTCCTGATATTTTTTCATTCATTGACTTTGAGAAGACTCCACC TGTGCTTGGAATTCCATGGGCTTCAAAGAACATTTCTTCTTTTAGCTTTGGAGGCACTTGCCGTGGCA CACCTGGACTCCTTGACATCCAATTCAAACTGCATTTGCAAAATGTGCAAAGACCTCTTATGAGGGAC CAATTCAGGTCCCTTATGGGGTGAACACTGTTGAAGACTGGTTAATTATAAGTTATGTAAGAATCATC GCCTTGTGGAACAAGTCAATCAGTGACTAGCTTCCTGTAGCCAATCAGGTTAAAGAGGGCGTTGGTAA TTTTGTTCTGATTTAACTAGTATTCAATCACCAACTTGCAAACAGAATTCATAACACTTGGCACTTGT TCTAGAGAAGTGTAGAGGATGATGTTAACATAATTTTAGCACTTCAAGGTATAATTTAAACAGTGAGG TAGTTTTGAATGGCATTTCATTAAGGCATCTATGGGCATTATGAGCTAAAAGCTGTGGTATGTTAGCT TTAAAAGAGTATTTATGTTGGAATAATTTTTAAATAATGTTTACATAACTGTAAGTCCTGTTTGGTTG TTGTTGGACGCAGGGCGGCACATGAGTGTTTTTGGTTAGAGCCAAGATAGCTCCCATGCACCGGAATT CCTTTGGGATGAATCAGCATCATTTTAAACAAAGTATATGTAAAAGGTGAAAGGTTATATTTTTTACA GATCAGAATGTGGCACCAGAGGACTGTGTCTCATTAAAGTGATTGCTGGGAGCAAAAACTAGAATGAT ACAAAGAAAGGTCAGAGAAATGCATGGGAATATTTTTTCTTT NOV8c, CG50235-02 SEQ ID NO: 90 1015 aa MW at l l3555.5kD Protein Sequence
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL TFNEFEIEQHQECAYDHLEMYDGPDSLAPILGRFCGSKKPDPTVASGSSMFLRFYSDASVQRKGFQAV HSTECGGRLKAEVQTKELYSHAQFGDNNYPSEARCDWVIVAEDGYGVELTFRTFEVEEEADCGYDYME AYDGYDSSAPRLGRFCGSGPLEEIYSAGDSLMIRFRTDDTINKKGFHARYTSTKFQDALHMKK
NOV8d, CG50235-03 SEQ ID NO: 91 3146 bp DNA Sequence ORF Start: ATG at 227 ORF Stop: TAG at 3137
GCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGCTTCCCGGTTGCCTCGACGAAGACAGGGGG
CGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAGCAGCCCTGTGTAACCACCGAGTCCCGGCC
GGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAGCTGAGCTTTCGTGCACGCAACTCCCTCTG
CCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGCACTTGGGGCCCTGGTGTCACTGCTGCTGC
TGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGCGCCCGGACGCCACCGCAGACTACTCAGAG CTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCATTACCACGACCCTTGCAAAGCCGCTGTCTT TTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCTGTTTCACATTGACAAAGCCAGAGACTGGA CCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTGGGCTTGAAGAGCAGGCATCTGAGAGCAGC CCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCTGGAAAGGGGAGCCAGAGGGCCATTTTTAA GCAGGCCATGAGACACTGGGAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCT TTATTGTATTCAGTTACAGAACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAG GCCATATCCATTGGGAAGAACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGG GTTTTGGCATGAACACACCCGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGC CAGGTCAGGAGTATAATTTCTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGAC TTTGACAGCATCATGCACTACGCCCGGAACACCTTCTCAAGAGGAGTTTTTTTAGACACCATCCTTCC CCGTCAAGATGACAATGGCGTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAG CTCAAGCCCGGAAGCTGTACAAATGCCCAGGTCCTACTTGTGCTTTTGTTAGCCAGAAAACATCAATC TGCTTGCTACACTTCTCACCAACCTGTTCCGAGGGCTTTGGCTGGCAAAGGGCGTGTGGGGAGACCCT GCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAAATGGGTACCCATCTTACTCCCACTGCG TCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTAAACTTCACATCCATGGATTTGTTTAAA AGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGGTTACTGGAGAAAAGCCCCCCTTTTGGG CAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCACGGACAGCCGGCTCTGGGTGGAGTTCC GCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCGTACGAAGCTACCTGCGGGGGAGACATG AACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGATGACTACAGACCTTCCAAGGAATGTGT CTGGAGGATTACGGTTTCAGAGGGGTTTCACGTGGGACTTACCTTCCAAGCTTTTGAGATTGAAAGGC ACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGCCCCACGGAAGAGAGTGCCCTGATCGGC CACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAGCTCCAACAGACTGTGGATGAAGTTTGT GTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATTTTTTCAAGGAGGTGGATGAGTGTTCCT GGCCAGATCACGGCGGGTGCGAGCATCGCTGTGTGAACACGCTGGGCAGCTACAAGTGTGCCTGTGAC CCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGTGGCCTGTGGCGGTTTCATTACCAAGCT GAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATCCCACAAACAAAAACTGTGTCTGGCAGG TGGTGGCCCCCACTCAGTACCGGATCTCCCTTCAGTTTGAAGTGTTTGAACTGGAAGGCAATGACGTC TGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCCCGACGCCAAGCTGCACGGCAGGTTCTG CGGCTCTGAGACGCCGGAGGTCATCACCTCGCAGAGCAACAACATGCGCGTGGAGTTCAAGTCCGACA ACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCAGATAAGGACGAGTGTGCCAAGGACAAC GGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTACCTGTGCAGGTGCAGAAACGGCTACTG GCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTGCACACAAGATCAGCAGTGTGGAGGGGA CCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGGAGGGAGTGTACCTGGAACATCTCTTCG ACTGCAGGCCACAGAGTGAAACTCACCTTTAATGAGTTTGAGATCGAGCAGCACCAGGAATGTGCCTA TGACCACCTGGAAATGTATGACGGGCCGGACAGCCTGGCCCCCATTCTGGGCCGTTTCTGCGGTAGCA AGAAACCAGACCCCACGGTGGCTTCCGGCAGCAAGTGCGGGGGCAGGCTGAAGGCTGAAGTGCAGACC AAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGAGGCCCGCTGTGACTGGGT GATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTGAGGTTGAGGAGGAGGCCG ACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCGCCCAGGCTCGGCCGCTTC TGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGATGATTCGATTCCGCACAGA TGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGTTCCAGGATGCCCTGCACA TGAAGAAATAGTGCTGAT
NOV8d, CG50235-03 SEQ ID NO: 92 970 aa MW at l08564.0kD Protein Sequence
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKGSQRAIFKQAMRHWE KHTCVTFIERTDEESFIVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTR PDRDQHVTIIRENIQPGQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGV RPTIGQRVRLSQGDIAQARKLYKCPGPTCAFVSQKTSICLLHFSPTCSEGFGWQRACGETLQDTTGNF SAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDYVEVRDGYWRKAPLLGRFCGDKI PEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQSPNYPDDYRPSKECVWRITVSE GFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKPEDVKSSSNRLWMKFVSDGSINK AGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAADKKMCEVACGGFITKLNGTITSP GWPKEYPTNKNCVWQWAPTQYRISLQFEVFELEGNDVCKYDFVEVRSGLSPDAKLHGRFCGSETPEV ITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECVNTFGSYLCRCRNGYWLHENGHD CKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKLTFNEFEIEQHQECAYDHLEMYD GPDSLAPILGRFCGSKKPDPTVASGSKCGGRLKAEVQTKELYSHAQFGDNNYPSEARCDWVIVAEDGY GVELTFRTFEVEEEADCGYDYMEAYDGYDSSAPRLGRFCGSGPLEEIYSAGDSLMIRFRTDDTINKKG FHARYTSTKFQDALHMKK
NOV8e, SNPl 3377383 of SEQ ID NO: 93 3120 bp CG50235-04, DNA Sequence ORF Start: ATG at 256 ORF Stop: TGA at 2719
SNP Pos: 2201 SNP Change: A to G
TAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGC
TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCGGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA GGCCCGCTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGAT
GATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
TCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8e, SNPl 3377383 of SEQ ID NO: 94 821 aa JMW at 91432.3kD CG50235-04, Protein Sequence SNP Pos: 649 SNP Change: Gin to Arg
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWRWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
NOV8f, SNP 13377384 of SEQ ID NO: 95 3120 bp CG50235-04, DNA Sequence ORF Start: ATG at 256 ORF Stop: TGA at 2719
SNP Pos: 2434 SNP Change: G to A
TAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGC
TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCAGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGACCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA GGCCCGCTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGAT
GATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
TCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8f, SNPl 3377384 of SEQ ID NO: 96 821 aa MW at 91434.2kD CG50235-04, Protein Sequence SNP Pos: 727 SNP Change: Ala to Thr
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRTHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
NOV8g, SNP13377385 of SEQ ID NO: 97 3120 bp CG50235-04, DNA Sequence ORF Start: ATG at 256 ORF Stop: TGA at 2719
SNP Pos: 2751 SNP Change: T to C
TAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGC
TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCAGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATCCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA GGCCCGCTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGAT iGATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
ITCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8g, SNPl 3377385 of |SEQ ID NO: 98 821 aa MW at 91404.2kD
CG50235-04, Protein Sequence SNP Change: no change
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
NOV8h, SNPl 3377386 of SEQ ID NO: 99 3120 bp
CG50235-04, DNA Sequence jpRF Start: ATG at 256 ORF Stop: TGA at 2719
SNP Pos: 2794 SNP Change: G to A jTAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGC TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCAGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA GGCCCACTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGATTCCCTGAT
GATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
TCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8h, SNPl 3377386 of SEQ ID NO: 100 821 aa MW at 91404.2kD CG50235-04, Protein Sequence SNP Change: no change
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
NOV8i, SNPl 3377387 of SEQ ID NO: 101 3120 bp CG50235-04, DNA Sequence ORF Start: ATG at 256 ORF Stop: TGA at 2719 SNP Pos: 2983 SNP Change: A to G
ITAACCTGTCTCACGACGGTCTAAACCCAGGCAGCCTCGGCCGCCGGGCAAGTAGCTCCGAGCGGCTGC
TTCCCGGTTGCCTCGAAGAAGACAGGGGGCGCCGCGCTCCGCTTGCTCCGCGCCTGAGCCATGCCCAG
CAGCCCTGTGTAACCACCGAGTCCCGGCCGGAGCCGACCGACCCAGTGTGCGCCGTCTTTCGGCCGAG
CTGAGCTTTCGTGCACGCAACTCCCTCTGCCCCAGCCGGCCCCGCGCCACCATGCCCCGGGCGACTGC
ACTTGGGGCCCTGGTGTCACTGCTGCTGCTGCTGCCGCTGCCTCGCGGCGCCGGGGGACTCGGGGAGC GCCCGGACGCCACCGCAGACTACTCAGAGCTGGACGGCGAGGAGGGCACGGAGCAGCAGCTGGAGCAT TACCACGACCCTTGCAAAGCCGCTGTCTTTTGGGGAGACATTGCCTTAGATGAAGATGACTTGAAGCT GTTTCACATTGACAAAGCCAGAGACTGGACCAAGCAGACAGTGGGGGCAACAGGACACAGCACAGGTG GGCTTGAAGAGCAGGCATCTGAGAGCAGCCCAGACACCACAGCCATGGACACTGGCACCAAGGAAGCT GGAAAGGATGGCCGGGAGAATACCACACTCCTGCACAGCCCTGGGACCTTGCATGCCGCAGCCAAGAC CTTCTCTCCCCGGGTCCGAAGAGCCACAACCTCAAGGACAGAGAGGATATGGCCTGGAGGAGTCATCC CCTACGTCATTGGAGGGAACTTCACTGGGAGCCAGAGGGCCATTTTTAAGCAGGCCATGAGACACTGG GAGAAGCACACCTGTGTGACCTTCATAGAAAGGACGGATGAGGAAAGCTTTATTGTATTCAGTTACAG AACCTGTGGCTGTTGCTCCTATGTTGGGCGCCGAGGAGGAGGCCCACAGGCCATATCCATTGGGAAGA ACTGTGACAAGTTTGGCATTGTGGCTCACGAGCTGGGCCATGTGGTTGGGTTTTGGCATGAACACACC CGGCCAGACAGAGACCAACATGTCACCATCATCAGGGAAAACATCCAGCCAGGTCAGGAGTATAATTT CTTAAAAATGGAAGCTGGGGAAGTGAGCTCTCTGGGAGAGACATACGACTTTGACAGCATCATGCACT ACGCCCGGAACACCTTCTCAAGAGGAGTTTTCTTAGACACCATCCTTCCCCGTCAAGATGACAATGGC GTCAGGCCAACCATTGGCCAGCGCGTGCGGCTCAGTCAGGGAGACATAGCTCAAGCCCGGAAGCTGTA CAAATGCCCAGCGTGTGGGGAGACCCTGCAGGACACAACGGGAAACTTTTCTGCACCTGGTTTCCCAA ATGGGTACCCATCTTACTCCCACTGCGTCTGGAGGATCTCGGTCACCCCAGGGGAAAAGATCGTATTA AACTTCACATCCATGGATTTGTTTAAAAGCCGACTGTGCTGGTATGATTACGTGGAGGTCCGGGATGG TTACTGGAGAAAAGCCCCCCTTTTGGGCAGGTTTTGTGGCGATAAGATCCCGGAGCCCCTCGTCTCCA CGGACAGCCGGCTCTGGGTGGAGTTCCGCAGCAGCAGCAACATCTTGGGCAAGGGCTTCTTTGCAGCG TACGAAGCTACCTGCGGGGGAGACATGAACAAAGATGCCGGTCAGATTCAATCTCCCAACTATCCGGA TGACTACAGACCTTCCAAGGAATGTGTCTGGAGGATTACGGTTTCGGAGGGGTTTCACGTGGGACTTA CCTTCCAAGCTTTTGAGATTGAAAGGCACGACAGCTGTGCATATGACTACCTGGAAGTCCGGGATGGC CCCACGGAAGAGAGTGCCCTGATCGGCCACTTTTGTGGCTATGAGAAGCCGGAGGATGTGAAATCGAG CTCCAACAGACTGTGGATGAAGTTTGTGTCCGATGGCTCTATCAATAAAGCGGGCTTTGCAGCCAATT TTTTCAAGGAGGTGGATGAGTGTTCCTGGCCAGATCACGGCGGGTGCGAACATCGCTGTGTGAACACG CTGGGCAGCTACAAGTGTGCCTGTGACCCTGGCTACGAGCTGGCCGCCGATAAGAAGATGTGTGAAGT GGCCTGTGGCGGTTTCATTACCAAGCTGAATGGAACCATCACCAGCCCTGGGTGGCCGAAGGAGTATC CCACAAACAAAAACTGTGTCTGGCAGGTGGTGGCCCCCGCTCAGTACCGGATCTCCCTTCAGTTTGAA GTGTTTGAACTGGAAGGCAATGACGTCTGTAAGTACGACTTTGTAGAGGTGCGCAGCGGCCTGTCCCC CGACGCCAAGCTGCACGGCAGGTTCTGCGGCTCTGAGACGCCGGAAGTCATCACCTCGCAGAGCAACA ACATGCGCGTGGAGTTCAAGTCCGACAACACCGTCTCCAAGCGCGGCTTCAGGGCCCACTTCTTCTCA GATAAGGACGAGTGTGCCAAGGACAACGGCGGGTGTCAGCATGAGTGCGTCAACACCTTCGGGAGCTA CCTGTGCAGGTGCAGAAACGGCTACTGGCTCCACGAGAATGGGCATGACTGCAAAGAGGCTGGCTGTG CACACAAGATCAGCAGTGTGGAGGGGACCCTGGCGAGCCCCAACTGGCCTGACAAATACCCCAGCCGG AGGGAGTGTACCTGGAACATCTCTTCGACTGCAGGCCACAGAGTAAAACTCAGTGCGGGGTCAGGCTG AAGGCTGAAGTGCAGACCAAAGAGCTCTATTCCCACGCCCAGTTTGGGGACAACAACTACCCGAGCGA GGCCCGCTGTGACTGGGTGATCGTGGCAGAGGACGGCTACGGCGTGGAGCTGACATTCCGGACCTTTG
AGGTTGAGGAGGAGGCCGACTGCGGCTACGACTACATGGAAGCCTACGACGGCTACGACAGCTCAGCG
CCCAGGCTCGGCCGCTTCTGTGGCTCTGGGCCATTAGAAGAAATCTACTCTGCAGGTGGTTCCCTGAT
GATTCGATTCCGCACAGATGACACCATCAACAAGAAAGGCTTTCATGCCCGATACACCAGCACCAAGT
TCCAGGATGCCCTGCACATGAAGAAATAGTGCTGATGTTCTTGAAAGACAGAAACTGAGA
NOV8i, SNPl 3377387 of SEQ ID NO: 102 821 aa MW at 91404.2kD CG50235-04, Protein Sequence SNP Change: no change
MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAVFWGDIALD EDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAGKDGRENTTLLHSPGTL HAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIFKQAMRHWEKHTCVTFIERTDEESF IVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIVAHELGHWGFWHEHTRPDRDQHVTIIRENIQP GQEYNFLKMEAGEVSSLGETYDFDSIMHYARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIA QARKLYKCPACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIVLNFTSMDLFKSRLCWYDY VEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSNILGKGFFAAYEATCGGDMNKDAGQIQ SPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFEIERHDSCAYDYLEVRDGPTEESALIGHFCGYEKP EDVKSSSNRLWMKFVSDGSINKAGFAANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAAD KKMCEVACGGFITKLNGTITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEV RSGLSPDAKLHGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECV NTFGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTAGHRVKL SAGSG
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 8B.
Table 8B. Comparison of the NOV8 protein sequences.
NOV8a MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAV
NOV8b MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAV
NOVΘc MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAV
NOV8d MPRATALGALVSLLLLLPLPRGAGGLGERPDATADYSELDGEEGTEQQLEHYHDPCKAAV
NOV8a FWGDIALDEDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAG
NOV8b FWGDIALDEDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAG
NOV8C FWGDIALDEDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAG
NOV8d FWGDIALDEDDLKLFHIDKARDWTKQTVGATGHSTGGLEEQASESSPDTTAMDTGTKEAG
NOV8a KDGRENTTLLHSPGTLHAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIF
NOV8b KDGRENTTLLHSPGTLHAAAKTFSPRVRRATTSRTERIWPGGVIPYVIGGNFTGSQRAIF
NOV8C KDGRENTTLLHSPGTLHAAAKTFSPRVRRATTSRTERI PGGVIPYVIGGNFTGSQRAIF
NOVΘd K GSQRAIF
NOV8a KQAMRHWEKHTCVTFIERTDEESFIVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIV
NOV8b KQAMRHWEKHTCVTFIERTDEESFIVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIV
NOVΘc KQAMRHWEKHTCVTFIERTDEESFIVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIV
NOV8d KQAMRHWEKHTCVTFIERTDEESFIVFSYRTCGCCSYVGRRGGGPQAISIGKNCDKFGIV
NOV8a AHELGHWGFWHEHTRPDRDQHVTIIRENIQPGQEYNFLKMEAGEVSSLGETYDFDSIMH
NOV8b AHELGHWGFWHEHTRPDRDQHVTIIRENIQPGQEYNFLKMEAGEVSSLGETYDFDSIMH
NOV8C AHELGHWGFWHEHTRPDRDQHVTIIRENIQPGQEYNFLKMEAGEVSSLGETYDFDSIMH
NOV8d AHELGHWGFWHEHTRPDRDQHVTIIRENIQPGQEYNFLKMEAGEVSSLGETYDFDSIMH
NOV8a YARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIAQARKLYKCP
NOV8b YARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIAQARKLYKCP
NOV8C YARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIAQARKLYKCP
NOVΘd YARNTFSRGVFLDTILPRQDDNGVRPTIGQRVRLSQGDIAQARKLYKCPGPTCAFVSQKT
NOV8a ACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIV
NOV8b ACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIV
NOV8c ACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIV
NOVΘd SICLLHFSPTCSEGFGWQRACGETLQDTTGNFSAPGFPNGYPSYSHCVWRISVTPGEKIV
NOV8a LNFTSMDLFKSRLCWYDYVEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSN NOV8b LNFTSMDLFKSRLCWYDYVEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSN NOVΘc LNFTSMDLFKSRLCWYDYVEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSN NOV8d LNFTSMDLFKSRLCWYDYVEVRDGYWRKAPLLGRFCGDKIPEPLVSTDSRLWVEFRSSSN
NOV8a ILGKGFFAAYEATCGGDMNKDAGQIQSPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFE
NOVΘb ILGKGFFAAYEATCGGDMNKDAGQIQSPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFE
NOV8C ILGKGFFAAYEATCGGDMNKDAGQIQSPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFE
NOV8d ILGKGFFAAYEATCGGDMNKDAGQIQSPNYPDDYRPSKECVWRITVSEGFHVGLTFQAFE
NOV8a IERHDSCAYDYLEVRDGPTEESALIGHFCGYEKPEDVKSSSNRLWMKFVSDGSINKAGFA
NOV8b IERHDSCAYDYLEVRDGPTEESALIGHFCGYEKPEDVKSSSNRLWMKFVSDGSINKAGFA
NOV8C IERHDSCAYDYLEVRDGPTEESALIGHFCGYEKPEDVKSSSNRLWMKFVSDGSΪNKAGFA
NOV8d IERHDSCAYDYLEVRDGPTEESALIGHFCGYEKPEDVKSSSNRLWMKFVSDGSINKAGFA
NOV8a ANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAADKKMCEVACGGFITKLNGT
NOVΘb ANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAADKKMCEVACGGFITKLNGT
NOV8c ANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAADKKMCEVACGGFITKLNGT
NOV8d ANFFKEVDECSWPDHGGCEHRCVNTLGSYKCACDPGYELAADKKMCEVACGGFITKLNGT
NOV8a ITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEVRSGLSPDAKL
NOVΘb ITSPGWPKEYPTNKNCVWQWAPTQYRISLQFEVFELEGNDVCKYDFVEVRSGLSPDAKL
NOV8C ITSPGWPKEYPTNKNCVWQWAPAQYRISLQFEVFELEGNDVCKYDFVEVRSGLSPDAKL
NOV8d ITSPGWPKEYPTNKNCVWQWAPTQYRISLQFEVFELEGNDVCKYDFVEVRSGLSPDAKL
NOV8a HGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECVNT
NOV8b HGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECVNT
NOV8C HGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECVNT
NOV8d HGRFCGSETPEVITSQSNNMRVEFKSDNTVSKRGFRAHFFSDKDECAKDNGGCQHECVNT
NOV8a FGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTA
NOV8b FGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTA
NOV8c FGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTA
NOV8d FGSYLCRCRNGYWLHENGHDCKEAGCAHKISSVEGTLASPNWPDKYPSRRECTWNISSTA
NOV8a GHRVKLSAGSG
NOVΘb GHRVKLTFNEFEIEQHQECAYDHLEMYDGPDSLAPILGRFCGSKKPDPTVASGSKCGGRL
NOVΘc GHRVKLTFNEFEIEQHQECAYDHLEMYDGPDSLAPILGRFCGSKKPDPTVASGSSMFLRF
NOV8d GHRVKLTFNEFEIEQHQECAYDHLEMYDGPDSLAPILGRFCGSKKPDPTVASGSKCGGRL
NOV8a NOV8b KAEVQTKELYSHAQFGDNNYPSEARCDWVIVAEDGYGVELTFRTFEVEEEADCGYDYMEA NOV8C YSDASVQRKGFQAVHSTECGGRLKAEVQTKELYSHAQFGDNNYPSEARCDWVIVAEDGYG NOV8d KAEVQTKELYSHAQFGDNNYPSEARCDWVIVAEDGYGVELTFRTFEVEEEADCGYDYMEA
NOV8a NOV8b YDGYDSSAPRLGRFCGSGPLEEIYSAGDSLMIRFRTDDTINKKGFHARYTSTKFQDGLHM NOV8C VELTFRTFEVEEEADCGYDYMEAYDGYDSSAPRLGRFCGSGPLEEIYSAGDSLMIRFRTD NOV8d YDGYDSSAPRLGRFCGSGPLEEIYSAGDSLMIRFRTDDTINKKGFHARYTSTKFQDALHM
NOV8a
NOV8b KK
NOV8C DTINKKGFHARYTSTKFQDALHMKK
NOV8d KK
NOV8a (SEQ ID NO: 86) NOV8b (SEQ ID NO: 88) NOV8C (SEQ ID NO: 90) NOV8d (SEQ ID NO: 92)
Further analysis ofthe NOV8a protein yielded the following properties shown in Table 8C.
Table 8C. Protein Sequence Properties NOV8a
SignalP analysis: Cleavage site between residues 26 and 27
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 3; pos . chg 1; neg.chg 0 H-region: length 17; peak value 10.45 PSG score: 6.05
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 4.44 possible cleavage site: between 25 and 26
>>> Seems to have a cleavable signal peptide (1 to 25)
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 26
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 6.31 (at 203) ALOM score: 6.31 (number of TMSs: 0)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 12 Charge difference: -3.0 C(-1.0) - N( 2.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 7.80 Hyd Moment(95): 7.61 G content: 5 D/E content: 1 S/T content: 2 Score: -4.54
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 31 PRG|AG
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PRVRRAT (5) at 145 bipartite: none content of basic residues: 11.2% NLS Score: -0.04
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: XXRR-like motif in the N-terminus : PRAT none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
33.3 %: extracellular, including cell wall
22.2 %: Golgi
22.2 %: vacuolar
11.1 %: mitochondrial
11.1 %: endoplasmic reticulum
>> prediction for CG50235-04 is exc (k=9)
A search ofthe NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8D.
Figure imgf000221_0001
In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E.
Figure imgf000222_0001
PFam analysis indicates that the NOV8a protein contains the domains shown in the Table 8F.
Figure imgf000223_0001
Example 9.
The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.
Table 9A. NOV9 Sequence Ana ysis
NOV9a, CG50249-01 SEQ ID NO: 103 1953 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAA at 1930
GTCTGAGTCACAGAGATGGGCAAGATCGAGAACAACGAGAGGGTGATCCTCAATGTCGGGGGCACCCG
GCACGAAACCTACCGCAGCACCCTCAAGACCCTGCCTGGAACACGCCTGGCCCTTCTTGCCTCCTCCG AGCCCCCAGGCGACTGCTTGACCACGGCGGGCGACAAGCTGCAGCCGTCGCCGCCTCCACTGTCGCCG CCGCCGAGAGCGCCCCCGCTGTCCCCCGGGCCAGGCGGCTGCTTCGAGGGCGGCGCGGGCAACTGCAG TTCCCGCGGCGGCAGGGCCAGCGACCATCCCGGTGGCGGCCGCGAGTTCTTCTTCGACCGGCACCCGG GCGTCTTCGCCTATGTGCTCAATTACTACCGCACCGGCAAGCTGCACTGCCCCGCAGACGTGTGCGGG CCGCTCTTCGAGGAGGAGCTGGCCTTCTGGGGCATCGACGAGACCGACGTGGAGCCCTGCTGCTGGAT GACCTACCGGCAGCACCGCGACGCCGAGGAGGCGCTGGACATCTTCGAGACCCCCGACCTCATTGGCG GCGACCCCGGCGACGACGAGGACCTGGCGGCCAAGAGGCTGGGCATCGAGGACGCGGCGGGGCTCGGG GGCCCGGACGGCAAATCTGGCCGCTGGAGGAGGCTGCAGCCCCGCATGTGGGCCCTCTTCGAAGACCC CTACTCGTCCAGAGCCGCCAGGTTTATTGCTTTTGCTTCTTTATTCTTCATCCTGGTTTCAATTACAA CTTTTTGCCTGGAAACACATGAAGCTTTCAATATTGTTAAAAACAAGACAGAACCAGTCATCAATGGC ACAAGTGTTGTTCTACAGTATGAAATTGAAACGGATCCTGCCTTGACGTATGTAGAAGGAGTGTGTGT GGTGTGGTTTACTTTTGAATTTTTAGTCCGTATTGTTTTTTCACCCAATAAACTTGAATTCATCAAAA ATCTCTTGAATATCATTGACTTTGTGGCCATCCTACCTTTCTACTTAGAGGTGGGACTCAGTGGGCTG TCATCCAAAGCTGCTAAAGATGTGCTTGGCTTCCTCAGGGTGGTAAGGTTTGTGAGGATCCTGAGAAT TTTCAAGCTCACCCGCCATTTTGTAGGTCTGAGGGTGCTTGGACATACTCTTCGAGCTAGTACTAATG AATTTTTGCTGCTGATAATTTTCCTGGCTCTAGGAGTTTTGATATTTGCTACCATGATCTACTATGCC GAGAGAGTGGGAGCTCAACCTAACGACCCTTCAGCTAGTGAGCACACACAGTTCAAAAACATTCCCAT TGGGTTCTGGTGGGCTGTAGTGACCATGACTACCCTGGGTTATGGGGATATGTACCCCCAAACATGGT CAGGCATGCTGGTGGGAGCCCTGTGTGCTCTGGCTGGAGTGCTGACAATAGCCATGCCAGTGCCTGTC ATTGTCAATAATTTTGGAATGTACTACTCCTTGGCAATGGCAAAGCAGAAACTTCCAAGGAAAAGAAA GAAGCACATCCCTCCTGCTCCTCAGGCAAGCTCACCTACTTTTTGCAAGACAGAATTAAATATGGCCT GCAATAGTACACAGAGTGACACATGTCTGGGCAAAGACAATCGACTTCTGGAACATAACAGATCAGTG TTATCAGGTGACGACAGTACAGGAAGTGAGCCGCCACTATCACCCCCAGAAAGGCTCCCCATCAGACG CTCTAGTACCAGAGACAAAAACAGAAGAGGGGAAACATGTTTCCTACTGACGACAGGTGATTACACGT GTGCTTCTGATGGAGGGATCAGGAAAGGTTATGAAAAATCCCGAAGCTTAAACAACATAGCGGGCTTG GCAGGCAATGCTCTGAGGCTCTCTCCAGTAACATCACCCTACAACTCTCCTTGTCCTCTGAGGCGCTC TCGATCTCCCATCCCATCTATCTTGTAAACCAAACAACCAAACTGCATC
NOV9a, CG50249-01 SEQ ID NO: 104 638 aa MW at 70224.7kD Protein Sequence
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGDKLQPSPPPLSPPPRAP PLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEE ELAF GIDETDVEPCC MTYRQHRDAEEALDIFETPDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGK SGRWRRLQPRM ALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSWL QYEIETDPALTYVEGVCWWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAA KDVLGFLRWRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGA QPNDPSASEHTQFKNIPIGF AWTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNF GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHNRSVLSGDD STGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNAL RLSPVTSPYNSPCPLRRSRSPIPSIL
NOV9b, 207885588 SEQ ID NO: 105 1815 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AGATCTCCCACCATGGGCAAGATCGAGAACAACGAGAGGGTGATCCTCAATGTCGGGGGCACCCGGCA CGAAACCTACCGCAGCACCCTCAAGACCCTGCCTGGAACACGCCTGGCCCTTCTTGCCTCCTCCGAGC CCCCAGGCAACTGCAGTTCCCGCGGCGGCAGGGCCAGCGACCATCCCGGTGGCGGCCGCGAGTTCTTC TTCGACCGGCACCCGGGCGTCTTCGCCTATGTGCTCAATTACTACCGCACCGGCAAGCTGCACTGCCC CGCAGACGTGTGCGGGCCGCTCTTCGAGGAGGAGCTGGCCTTCTGGGGCATCGACGAGACCGACGTGG AGCCCTGCTGCTGGATGACCTACCGGCAGCACCGCGACGCCGAGGAGGCGCTGGACATCTTCGAGACC CCCGACCTCATTGGCGGCGACCCCGGCGACGACGAGGACCTGGCGGCCAAGAGGCTGGGCATCGAGGA CGCGGCGGGGCTCGGGGGCCCCGACGGCAAATCTGGCCGCTGGAGGAGGCTGCAGCCCCGCATGTGGG CCCTCTTCGAAGACCCCTACTCGTCCAGAGCCGCCAGGTTTATTGCTTTTGCTTCTTTATTCTTCATC CTGGTTTCAATTACAACTTTTTGCCTGGAAACACATGAAGCTTTCAATATTGTTAAAAACAAGACAGA ACCAGTCATCAATGGCACAAGTGTTGTTCTACAGTATGAAATTGAAACGGATCCTGCCTTGACGTATG TAGAAGGAGTGTGTGTGGTGTGGTTTACTTTTGAATTTTTAGTCCGTATTGTTTTTTCACCCAATAAA CTTGAATTCATCAAAAATCTCTTGAATATCATTGACTTTGTGGCCATCCTACCTTTCTACTTAGAGGT GGGACTCAGTGGGCTGTCATCCAAAGCTGCTAAAGATGTGCTTGGCTTCCTCAGGGTGGTAAGGTTTG TGAGGATCCTGAGAATTTTCAAGCTCACCCGCCATTTTGTAGGTCTGAGGGTGCTTGGACATACTCTT CGAGCTAGTACTAATGAATTTTTGCTGCTGATAATTTTCCTGGCTCTAGGAGTTTTGATATTTGCTAC CATGATCTACTATGCCGAGAGAGTGGGAGCTCAACCTAACGACCCTTCAGCTAGTGAGCACACACAGT TCAAAAACATTCCCATTGGGTTCTGGTGGGCTGTAGTGACCATGACTACCCTGGGTTATGAGGATACG TACCCCCAAACATGGTCAGGCATGCTGGTGGGAGCCCTGTGTGCTCTGGCTGGAGTGCTGACAATAGC CATGCCAGTGCCTGTCATTGTCAATAATTTTGGAATGTACTACTCCTTGGCAATGGCAAAGCAGAAAC TTCCAAGGAAAAGAAAGAAGCACATCCCTCCTGCTCCTCAGGCAAGCTCACCTACTTTTTGCAAGACA GAATTAAATATGGCCTGCAATAGTACACAGAGTGACACATGTCTGGGCAAAGACAATCGACTTCTGGA ACATAACAGATCAGTGTTATCAGGTGACGACAGTACAGGAAGTGAGCCGCCACTATCACCCCCAGAAA GGCTCCCCATCAGACGCTCTAGTACCAGAGACAAAAACAGAAGAGGGGAAACATGTTTCCTACTGACG ACAGGTGATTACACGTGTGCTTCTGATGGAGGGATCAGGAAAGGATATGAAAAATCCCGAAGCTTAAA CAACATAGCGGGCTTGGCAGGCAATGCTCTGAGGCTCTCTCCAGTAACATCACCCTACAACTCTCCTT GTCCTCTGAGGCGCTCTCGATCTCCCATCCCATCTATCTTGCTCGAG
NOV9b, 207885588 SEQ ID NO: 106 605 aa MW at 67228.3kD Protein Sequence
RSPTMGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGNCSSRGGRASDHPGGGREFF FDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAF GIDETDVEPCCWMTYRQHRDAEEALDIFET PDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGKSGR RRLQPRMWALFEDPYSSRAARFIAFASLFFI LVSITTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFEFLVRIVFSPNK LEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRILRIFKLTRHFVGLRVLGHTL RASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAWTMTTLGYEDT YPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKT ELNMACNSTQSDTCLGKDNRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLT TGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSILLE
NOV9c, CG50249-02 SEQ ID NO: 107 607 bp DNA Sequence ORF Start: ATG at 13 ORF Stop: at 604
AGATTTCCCACCATGGGCAAGATCGAGAACAACGAGAGGGTGATCCTCAATGTCGGGGGCACCCGGCA
CGAAACCTACCGCAGCACCCTCAAGACCCTGCCTGGAACACGCCTGGCCCTTCTTGCCTCCTCCGAGC CCCCAGGCGACTGCTTGACCACAGCGGGCAACTGCAGTTCCCGCGGCGGCAGGGCCAGCGACCATCCC GGTGGCGGCCGCGAGTTCTTCTTCGACCGGCATCCGGGCGTCTTCGCCTATGTGCTCAATTACTACCG CACCGGCAAGCTGCACTGTCCCGCAGACGTGTGCGGGCCGCTCTTCGAGGAGGAGCTGGCCTTCTGGG GCATCGACGAGACCGACGTGGAGCCCTGCTGCTGGATGACCTACCGGCAGCACCGCGACGCCGAGGAG GCGCTGGACATCTTCGAGACCCCCGACCTCATTGGCGGCGACCCCGGCGACGACGAGGACCTGGCGGC CAAGAGGCTGGGCATCGAGGACGCGGCGGGGCTCGGGGGCCCCGACGGCAAATCTGGCCGCTGGAGGA GGCTGCAGCCCCGCATGTGGGCCCTCTTCGAAGACCCCTACTCGTCCAGAGCCGCCAGGCTCG
NOV9c, CG50249-02 SEQ ID NO: 108 197 aa MW at 21779.0kD Protein Sequence
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGNCSSRGGRASDHPGGGR EFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCC MTYRQHRDAEEALDI FETPDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRM ALFEDPYSSRAAR
NOV9d, CG50249-03 SEQ ID NO: 109 1815 bp DNA Sequence ORF Start: ATG at 13 ORF Stop: at 1810
AGATCTCCCACCATGGGCAAGATCGAGAACAACGAGAGGGTGATCCTCAATGTCGGGGGCACCCGGCA
CGAAACCTACCGCAGCACCCTCAAGACCCTGCCTGGAACACGCCTGGCCCTTCTTGCCTCCTCCGAGC CCCCAGGCAACTGCAGTTCCCGCGGCGGCAGGGCCAGCGACCATCCCGGTGGCGGCCGCGAGTTCTTC TTCGACCGGCACCCGGGCGTCTTCGCCTATGTGCTCAATTACTACCGCACCGGCAAGCTGCACTGCCC CGCAGACGTGTGCGGGCCGCTCTTCGAGGAGGAGCTGGCCTTCTGGGGCATCGACGAGACCGACGTGG AGCCCTGCTGCTGGATGACCTACCGGCAGCACCGCGACGCCGAGGAGGCGCTGGACATCTTCGAGACC CCCGACCTCATTGGCGGCGACCCCGGCGACGACGAGGACCTGGCGGCCAAGAGGCTGGGCATCGAGGA CGCGGCGGGGCTCGGGGGCCCCGACGGCAAATCTGGCCGCTGGAGGAGGCTGCAGCCCCGCATGTGGG CCCTCTTCGAAGACCCCTACTCGTCCAGAGCCGCCAGGTTTATTGCTTTTGCTTCTTTATTCTTCATC CTGGTTTCAATTACAACTTTTTGCCTGGAAACACATGAAGCTTTCAATATTGTTAAAAACAAGACAGA ACCAGTCATCAATGGCACAAGTGTTGTTCTACAGTATGAAATTGAAACGGATCCTGCCTTGACGTATG TAGAAGGAGTGTGTGTGGTGTGGTTTACTTTTGAATTTTTAGTCCGTATTGTTTTTTCACCCAATAAA CTTGAATTCATCAAAAATCTCTTGAATATCATTGACTTTGTGGCCATCCTACCTTTCTACTTAGAGGT GGGACTCAGTGGGCTGTCATCCAAAGCTGCTAAAGATGTGCTTGGCTTCCTCAGGGTGGTAAGGTTTG TGAGGATCCTGAGAATTTTCAAGCTCACCCGCCATTTTGTAGGTCTGAGGGTGCTTGGACATACTCTT CGAGCTAGTACTAATGAATTTTTGCTGCTGATAATTTTCCTGGCTCTAGGAGTTTTGATATTTGCTAC CATGATCTACTATGCCGAGAGAGTGGGAGCTCAACCTAACGACCCTTCAGCTAGTGAGCACACACAGT TCAAAAACATTCCCATTGGGTTCTGGTGGGCTGTAGTGACCATGACTACCCTGGGTTATGAGGATACG TACCCCCAAACATGGTCAGGCATGCTGGTGGGAGCCCTGTGTGCTCTGGCTGGAGTGCTGACAATAGC CATGCCAGTGCCTGTCATTGTCAATAATTTTGGAATGTACTACTCCTTGGCAATGGCAAAGCAGAAAC TTCCAAGGAAAAGAAAGAAGCACATCCCTCCTGCTCCTCAGGCAAGCTCACCTACTTTTTGCAAGACA GAATTAAATATGGCCTGCAATAGTACACAGAGTGACACATGTCTGGGCAAAGACAATCGACTTCTGGA ACATAACAGATCAGTGTTATCAGGTGACGACAGTACAGGAAGTGAGCCGCCACTATCACCCCCAGAAA GGCTCCCCATCAGACGCTCTAGTACCAGAGACAAAAACAGAAGAGGGGAAACATGTTTCCTACTGACG ACAGGTGATTACACGTGTGCTTCTGATGGAGGGATCAGGAAAGGATATGAAAAATCCCGAAGCTTAAA CAACATAGCGGGCTTGGCAGGCAATGCTCTGAGGCTCTCTCCAGTAACATCACCCTACAACTCTCCTT GTCCTCTGAGGCGCTCTCGATCTCCCATCCCATCTATCTTGCTCGAG
NOV9d, CG50249-03 SEQ ID NO: 110 599 aa !MW at 66544.6kD Protein Sequence
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGNCSSRGGRASDHPGGGREFFFDRH PGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCC MTYRQHRDAEEALDIFETPDLI GGDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRMWALFEDPYSSRAARFIAFASLFFILVSI TTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFEFLVRIVFSPNKLEFI KNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRILRIFKLTRHFVGLRVLGHTLRAST NEFLLLIIFLALGVLIFATMI YAERVGAQPNDPSASEHTQFKNIPIGF WAWTMTTLGYEDTYPQT SGMLVGALCAIAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNM ACNSTQSDTCLGKDNRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDY TCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL
NOV9e, CG50249-04 SEQ ID NO: 111 3028 bp DNA Sequence ORF Start: ATG at 22 ORF Stop: TAA at 1861
AGTCATGTCTGAGTCACAGAGATGGGCAAGATCGAGAACAACGAGAGGGTGATCCTCAATGTCGGGGG
CACCCGGCACGAAACCTACCGCAGCACCCTCAAGACCCTGCCTGGAACACGCCTGGCCCTTCTTGCCT CCTCCGAGCCCCCAGGCGACTGCTTGACCACGGCGGGCGACAAGCTGCAGCCGTCGCCGCCTCCACTG TCGCCGCCGCCGAGAGCGCCCCCGCTGTCCCCCGGGCCAGGCGGCTGCTTCGAGGGCGGCGCGGGCAA CTGCAGTTCCCGCGGCGGCAGGGCCAGCGACCATCCCGGTGGCGGCCGCGAGTTCTTCTTCGACCGGC ACCCGGGCGTCTTCGCCTATGTGCTCAATTACTACCGCACCGGCAAGCTGCACTGCCCCGCAGACGTG TGCGGGCCGCTCTTCGAGGAGGAGCTGGCCTTCTGGGGCATCGACGAGACCGACGTGGAGCCCTGCTG CTGGATGACCTACCGGCAGCACCGCGACGCCGAGGAGGCGCTGGACATCTTCGAGACCCCCGACCTCA TTGGCGGCGACCCCGGCGACGACGAGGACCTGGCGGCCAAGAGGCTGGGCATCGAGGACGCGGCGGGG CTCGGGGGCCCCGACGGCAAATCTGGCCGCTGGAGGAGGCTGCAGCCCCGCATGTGGGCCCTCTTCGA AGACCCCTACTCGTCCAGAGCCGCCAGGTTTATTGCTTTTGCTTCTTTATTCTTCATCCTGGTTTCAA TTACAACTTTTTGCCTGGAAACACATGAAGCTTTCAATATTGTTAAAAACAAGACAGAACCAGTCATC AATGGCACAAGTGTTGTTCTACAGTATGAAATTGAAACGGATCCTGCCTTGACGTATGTAGAAGGAGT GTGTGTGGTGTGGTTTACTTTTGAATTTTTAGTCCGTATTGTTTTTTCACCCAATAAACTTGAATTCA TCAAAAATCTCTTGAATATCATTGACTTTGTGGCCATCCTACCTTTCTACTTAGAGGTGGGACTCAGT GGGCTGTCATCCAAAGCTGCTAAAGATGTGCTTGGCTTCCTCAGGGTGGTAAGGTTTGTGAGGATCCT GAGAATTTTCAAGCTCACCCGCCATTTTGTAGGTCTGAGGGTGCTTGGACATACTCTTCGAGCTAGTA CTAATGAATTTTTGCTGCTGATAATTTTCCTGGCTCTAGGAGTTTTGATATTTGCTACCATGATCTAC TATGCCGAGAGAGTGGGAGCTCAACCTAACGACCCTTCAGCTAGTGAGCACACACAGTTCAAAAACAT TCCCATTGGGTTCTGGTGGGCTGTAGTGACCATGACTACCCTGGGTTATGGGGATATGTACCCCCAAA CATGGTCAGGCATGCTGGTGGGAGCCCTGTGTGCTCTGGCTGGAGTGCTGACAATAGCCATGCCAGTG CCTGTCATTGTCAATAATTTTGGAATGTACTACTCCTTGGCAATGGCAAAGCAGAAACTTCCAAGGAA AAGAAAGAAGCACATCCCTCCTGCTCCTCAGGCAAGCTCACCTACTTTTTGCAAGACAGAATTAAATA TGGCCTGCAATAGTACACAGAGTGACACATGTCTGGGCAAAGACAATCGACTTCTGGAACATAACAGA TCAGTGTTATCAGGTGACGACAGTACAGGAAGTGAGCCGCCACTATCACCCCCAGAAAGGCTCCCCAT CAGACGCTCTAGTACCAGAGACAAAAACAGAAGAGGGGAAACATGTTTCCTACTGACGACAGGTGATT ACACGTGTGCTTCTGATGGAGGGATCAGGAAAGATAACTGCAAAGAGGTTGTCATTACTGGTTACACG CAAGCCGAGGCCAGATCTCTTACTTAATGACTTGGGGGAAGGCACAAAACATGAGAGAAAGTGTTGTA
CAGAATTTATCATGGATTATTGACTGCTGAGAAAGGGACAGTGGAATTTAGCCATACAAAGGACTATA
CTGGAAACAGACTTCTGCTGCTGAATGTGCCCTGATGTGACCAGGTTGCACTTGGAAGAGATCCTCCG
CGTCTTCATGAGGCACTTAAAGCTTATAAAAGAACTGCGGCTGGAACTCATCTGGTGCTCCCCATGAG
AGTGCTCTGCTTGTAGACTGGCCAGTGTCCATGAAACAACTGTAAATACCAACATGTGTGCATGGGTC,
AACAGTCTTGGCCATTTCTCATCAAAAGAAGCCAAATTCATGATCAACATCTCTGAAGTTTCAAGTAA!
GGCCCACACTTCTTTGAATTACTCTTCATGGGCCCACATTAGGTTGTGCTGTGAATTACTTAAGGCAG
TGATACTGATGTAGTATAGTTTTGTCTTAATTTCCCTTATTTCTACTTCTTTGGTTGAATCTATGAAC
TTGATTGTATAATTTTCTTATAAATTACTGATGTAATCAGCTTGTCAATTATGTTGTGAAATTGTTAG!
TATTCATTTATCAAAAATGACCTATGTTTAGTCACATATTTGTTTAGTTCTGGGAAATTGTTATAGCT
TAAATGGAACTCACCAACATTATTCATAGTTTAAGTCTTTTATCATTATTACCTCAATTATAAATATT
ACAAAAACATAATTCTGGCAATGAGAGTATTTTTTTATTCAATGATCAAGGAGCAATGTCAGTATATA
GTAGAATATCAATTAAATTATATCCTAAAATGTATATTTTGCATAAAAGAGATATTCTTTAATCAATT
ACTTTTTTGTGAGTTTTGTGGCGAATGAAGCTTGTACGTGTCTTTAAAACTGTTGTAGATGAAACTGT;
ATAAGATTTTTACATCTTGCTTAATCAATATTTTCAGAGTCTATTAGTTCCCCTGGGATTCTGAATAT
AACATATAGCCTATTATAAATCCCTGTATCGTGGACCTTTTGTGAACATTTCAAGGCGCATGCACAACl
CTTGATGATAACCAGTGGAAATGTAACTAACTGAAATGAAGAATAAAAGGCAAATGAGCTGGGGATAA!
ACTTGAATGTTATCTGATTAAATTACTCAAATTATT
NOV9e, CG50249-04 SEQ ID NO: 112 613 aa MW at 67598JkD Protein Sequence ^^
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGDKLQPSPPPLSPPPRAP PLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEE ELAFWGIDETDVEPCC MTYRQHRDAEEALDIFETPDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGK SGRWRRLQPRM ALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSWL QYEIETDPALTYVEGVCWWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAA KDVLGFLRWRFVRILRI FKLTRHFVGLRVLGHTLRASTNEFLLLI I FLALGVLI FATMI YYAERVGA QPNDPSASEHTQFKNIPIGFW AWTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNF GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHNRSVLSGDD STGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKDNCKEWITGYTQAEARSL T
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 9B.
Table 9B. Comparison of the NOV9 protein sequences.
NOV9a MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGDKLQP NOV9b RSPTMGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPG NOV9c MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTA NOV9d MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPG NOV9e MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGDKLQP
NOV9a SPPPLSPPPRAPPLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLN
NOV9b NCSSRGGRASDHPGGGREFFFDRHPGVFAYVLN
NOV9c GNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLN
NOV9d NCSSRGGRASDHPGGGREFFFDRHPGVFAYVLN
NOV9e SPPPLSPPPRAPPLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLN
NOV9a YYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIG NOV9b YYRTGKLHCPADVCGPLFEEELAF GIDETDVEPCC MTYRQHRDAEEALDIFETPDLIG NOV9C YYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCC MTYRQHRDAEEALDIFETPDLIG NOV9d YYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCC MTYRQHRDAEEALDIFETPDLIG NOV9e YYRTGKLHCPADVCGPLFEEELAF GIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIG
NOV9a GDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRM ALFEDPYSSRAARFIAFASL NOV9b GDPGDDEDLAAKRLGIEDAAGLGGPDGKSGR RRLQPRMWALFEDPYSSRAARFIAFASL NOV9C GDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRM ALFEDPYSSRAAR NOV9d GDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRMWALFEDPYSSRAARFIAFASL NOV9e GDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRM ALFEDPYSSRAARFIAFASL
NOV9a FFILVSITTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFE NOV9b FFILVSITTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFE NOV9c NOV9d FFILVSITTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFE NOV9e FFILVSITTFCLETHEAFNIVKNKTEPVINGTSWLQYEIETDPALTYVEGVCWWFTFE
NOV9a FLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRIL NOV9b FLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRIL NOV9c NOV9d FLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRIL NOV9e FLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRWRFVRIL
NOV9a RIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSAS NOV9b RlFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSAS NOV9c NOV9d RlFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSAS NOV9e RIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSAS
NOV9a EHTQFKNIPIGF WAWTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNF NOV9b EHTQFKNIPIGFWWAWTMTTLGYEDTYPQT SGMLVGALCALAGVLTIAMPVPVIVNNF NOV9c NOV9d EHTQFKNIPIGF WAWTMTTLGYEDTYPQT SGMLVGALCALAGVLTIAMPVPVIVNNF NOV9e EHTQFKNIPIGF WAWTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNF
NOV9a GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHN NOV9b GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHN NOV9c NOV9d GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHN NOV9e GMYYSLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHN
NOV9a RSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYE NOV9b RSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYE NOV9c NOV9d RSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYE NOV9e RSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKDNC
NOV9a KSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL- -
NOV9b KSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSILLE
NOV9C
NOV9d KSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL- -
NOV9e KEWITGYTQAEA SLT
NOV9a (SEQ ID NO 104)
NOV9b (SEQ ID NO 106)
NOV9C (SEQ ID NO 108)
NOV9d (SEQ ID NO 110)
NOV9e (SEQ ID NO 112)
Further analysis ofthe NOV9a protein yielded the following properties shown in Table 9C.
Table 9C. Protein Sequence Properties NOV9a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos . chg 2; neg.chg 2 H-region: length 8; peak value 4.97 PSG score: 0.57
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.54 possible cleavage site: between 46 and 47
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -6. .90 Transmembrane 230 - 246
INTEGRAL Likelihood = -3. .24 Transmembrane 287 - 303
INTEGRAL Likelihood = -2. .23 Transmembrane 314 - 330
INTEGRAL Likelihood = -0. .16 Transmembrane 343 - 359
INTEGRAL Likelihood =-13. .00 Transmembrane 382 - 398
INTEGRAL Likelihood = -7. .01 Transmembrane 451 - 467
PERIPHERAL Likelihood = 3. .61 (at 424)
ALOM score: -13.00 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 237 Charge difference: -0.5 C(-0.5) - N( 0.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 5.56 Hyd Moment(95): 3.52 G content: 1 D/E content: 2 S/T content: 0 Score: -7.90
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: PRKR (4) at 490 pat4 : RKRK (5) at 491 pat4: KRKK (5) at 492 pat4: RKKH (3) at 493 pat7: PRKRKKH (5) at 490 pat7: PLRRSRS (4) at 626 bipaitite: none content of basic residues 10.7% NLS Score: 1.37
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum 22.2 %: mitochondrial 11.1 %: nuclear
>> prediction for CG50249-01 is end (k=9)
A search ofthe NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D.
Figure imgf000231_0001
In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E.
Figure imgf000232_0001
PFam analysis indicates that the NOV9a protein contains the domains shown in the Table 9F.
Figure imgf000233_0002
Example 10.
The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.
Figure imgf000233_0001
GCAGTATGGAAGATGGGCCGTTGTCAGCGGTGCAACAGATGGGATTGGAAAAGCCTACGCTGAAGAGT TAGCAAGCCGAGGTCTCAATATAATCCTGATTAGTCGGAACGAGGAGAAGTTGCAGGTTGTTGCTAAA GACATAGCCGACACGTACAAAGTGGAAACTGATATTATAGTTGCGGACTTCAGCAGCGGTCGTGAGAT CTACCTTCCAATTCGAGAAGCCCTGAAGGACAAAGACGTTGGCATCTTGGTAAATAACGTGGGTGTGT TTTATCCCTACCCGCAGTATTTCACTCAGCTGTCCGAGGACAAGCTCTGGGACATCATAAATGTGAAC ATTGCCGCCGCTAGTTTGATGGTCCATGTTGTGTTACCGGGAATGGTGGAGAGAAAGAAAGGTGCCAT CGTCACGATCTCTTCTGGCTCCTGCTGCAAACCCACTCCTCAGCTGGCTGCATTTTCTGCTTCTAAGG CTTATTTAGACCACTTCAGCAGAGCCTTGCAATATGAATATGCCTCTAAAGGAATCTTTGTACAGAGT CTAATCCCTTTCTATGTAGCCACCAGCATGACAGCACCCAGCAACTTTCTGCACAGGTGCTCGTGGTT GGTGCCTTCGCCAAAAGTCTATGCACATCATGCTGTTTCTACTCTTGGGATTTCCAAAAGGACCACAG GATATTGGTCCCATTCTATTCAGTTTCTTTTTGCACAGTATATGCCTGAATGGCTCTGGGTGTGGGGA GCAAATATTCTCAACCGTTCACTACGTAAGGAAGCCTTATCCTGCACAGCCCTCGAGGGC
NOVl Ob, 275624102 SEQ ID NO: 116 337 aa MW at 37647.0kD Protein Sequence
TGSTMAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRLGSRADLIK QYGR AWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYKVETDIIVADFSSGREI YLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDI INVNIAAASLMVHWLPGMVERKKGAI VTI SSGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGI FVQSLI PFYVATSMTAPSNFLHRCSWL VPSPKVYAHHAVSTLGISKRTTGY SHSIQFLFAQYMPE L VWGANILNRSLRKEALSCTALEG
NOV10c, CG50307-01 SEQ ID NO: 117 1831 bp DNA Sequence ORF Start: ATG at 183 ORF Stop: TGA at 1173
ACCGGTTTGGAAGACTTTGCCGGCCTGCAGGACACATGATGACATTGGACCCACCCTCCCCAGCTCGG
AGTCTTTAACTCAGTCACATCTACGGAGTCCCTTTGGCCACATAAGATTGGCCTTAAGAGAAGGACGG
AGCCACATACTGCTGACGGCCCAGAACTGGCAGAGAGAAGGTTGCCATGGCTGCTGTTGACAGTTTCT
ACCTCTTGTACAGGGAAATCGCCAGGTCTTGCAATTGCTATATGGAAGCTCTAGCTTTGGTTGGAGCC TGGTATACGGCCAGAAAAAGCATCACTGTCATCTGTGACTTTTACAGCCTGATCAGGCTGCATTTTAT CCCCCGCCTGGGGAGCAGAGCAGACTTGATCAAGCAGTATGGAAGATGGGCCGTTGTCAGCGGTGCAA CAGATGGGATTGGAAAAGCCTACGCTGAAGAGTTAGCAAGCCGAGGTCTCAATATAATCCTGATTAGT CGGAACGAGGAGAAGTTGCAGGTTGTTGCTAAAGACATAGCCGACACGTACAAAGTGGAAACTGATAT TATAGTTGCGGACTTCAGCAGCGGTCGTGAGATCTACCTTCCAATTCGAGAAGCCCTGAAGGACAAAG ACGTTGGCATCTTGGTAAATAACGTGGGTGTGTTTTATCCCTACCCGCAGTATTTCACTCAGCTGTCC GAGGACAAGCTCTGGGACATCATAAATGTGAACATTGCCGCCGCTAGTTTGATGGTCCATGTTGTGTT ACCGGGAATGGTGGAGAGAAAGAAAGGTGCCATCGTCACGATCTCTTCTGGCTCCTGCTGCAAACCCA CTCCTCAGCTGGCTGCATTTTCTGCTTCTAAGGCTTATTTAGACCACTTCAGCAGAGCCTTGCAATAT GAATATGCCTCTAAAGGAATCTTTGTACAGAGTCTAATNCCTTTCTATGTAGCCACCAGCATGACAGC ACCCAGCAACTTTCTGCACAGGTGCTCGTGGTTGGTGCCTTCGCCAAAAGTCTATGCACATCATGCTG TTTCTACTCTTGGGATTTCCAAAAGGACCACAGGATATTGGTCCCATTCTATTCAGTTTCTTTTTGCA CAGTATATGCCTGAATGGCTCTGGGTGTGGGGAGCAAATATTCTCAACCGTTCACTACGTAAGGAAGC CTTATCCTGCACAGCCTGAGTCTGGATGGCCACTTGAGAAGTTTTGCCAACTCCTGGGAACCTCGATA
TTCTGACATTTGGAAAAACACATTTAATTTATCTCCTGTGTTTCATTGCTGATTATTCAGCATACTGT
TGATTCGTCATTTGCAAAACACACATAATACCGTCAGAGTGCTGTGAAAAACCTTAAGGGTGTGTGGA
TGGCACAGGATCAATAATGCCTGAGGCTGATTGACGACATCTACATTTCAGTGCTTTTTCCCTAAGCT
GTTTGAAAGTTACGCTTTTCTGTTGTTCTAGAGCCACAGCAGTCTAATATTGAAATATAATATGATTG
TCAGGTCTTATAATTTCAGATGTTGTTTTTTAAGGGAAATTGACCATTTCACTAGAGGAGTTGTGCTG
GTTTTTACATGTGCATCAAGGAAAGACTACTGGAAAAGTATTTATTTTGGTAACTAAGATTGCTGGCTj
ACTATTAGGGACACACTCCGGGCTGTTTGGTATAGCTCTACCTGGTTTGACTATCTGTCATGGAAATG
CTGCCTTCCACTGGTTTTTCCTTTGAGACGGGGTGTGTGCCTGGGTTGTGGGGCCCTTGGGCCCCTTT
TTTTTGGTGCCCCTTCTTCCACCCACTTTCGGCCCGCGGGCCCCCTGGCGCTCTGGGTTTCCC
NOV10c, CG50307-01 SEQ ID NO: 118 330 aa MW at 36888.2kD Protein Sequence
MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRLGSRADLIKQYGR AWSGATDGIGKAYAEELASRGLNI ILISRNEEKLQWAKDIADTYKVETDI IVADFSSGREIYLPI REALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDI INVNIAAASLMVHVVLPGMVERKKGAIVTIS SGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGIFVQSLXPFYVATSMTAPSNFLHRCSWLVPSP KVYAHHAVSTLGISKRTTGYWSHSIQFLFAQYMPEWL VWGANILNRSLRKEALSCTA NOV10d, CG50307-02 SEQ ID NO: 119 1152 bp DNA Sequence ORF Start: ATG at 97 ORF Stop: TGA at 1087
ATCTACGGAGTCCCTTTGGCCACATAAGATTGGCCTTAAGAGAAGGACGGAGCCACATACTGCTGACG
GCCCAGAACTGGCAGAGAGAAGGTTGCCATGGCTGCTGTTGACAGTTTCTACCTCTTGTACAGGGAAA:
TCGCCAGGTCTTGCAATTGCTATATGGAAGCTCTAGCTTTGGTTGGAGCCTGGTATACGGCCAGAAAA AGCATCACTGTCATCTGTGACTTTTACAGCCTGATCAGGCTGCATTTTATCCCCCGCCTGGGGAGCAG AGCAGACTTGATCAAGCAGTATGGAAGATGGGCCGTTGTCAGCGGTGCAACAGATGGGATTGGAAAAG CCTACGCTGAAGAGTTAGCAAGCCGAGGTCTCAATATAATCCTGATTAGTCGGAACGAGGAGAAGTTG CAGGTTGTTGCTAAAGACATAGCCGACACGTACAAAGTGGAAACTGATATTATAGTTGCGGACTTCAG CAGCGGTCGTGAGATCTACCTTCCAATTCGAGAAGCCCTGAAGGACAAAGACGTTGGCATCTTGGTAA ATAACGTGGGTGTGTTTTATCCCTACCCGCAGTATTTCACTCAGCTGTCCGAGGACAAGCTCTGGGAC ATCATAAATGTGAACATTGCCGCCGCTAGTTTGATGGTCCATGTTGTGTTACCGGGAATGGTGGAGAG AAAGAAAGGTGCCATCGTCACGATCTCTTCTGGCTCCTGCTGCAAACCCACTCCTCAGCTGGCTGCAT TTTCTGCTTCTAAGGCTTATTTAGACCACTTCAGCAGAGCCTTGCAATATGAATATGCCTCTAAAGGA ATCTTTGTACAGAGTCTAATCCCTTTCTATGTAGCCACCAGCATGACAGCACCCAGCAACTTTCTGCA CAGGTGCTCGTGGTTGGTGCCTTCGCCAAAAGTCTATGCACATCATGCTGTTTCTACTCTTGGGATTT CCAAAAGGACCACAGGATATTGGTCCCATTCTATTCAGTTTCTTTTTGCACAGTATATGCCTGAATGG CTCTGGGTGTGGGGAGCAAATATTCTCAACCGTTCACTACGTAAGGAAGCCTTATGCTGCACAGCCTG AGTCTGGATGGCCACTTGAGAAGTTTTGCCAACTCCTGGGAACCTCGATATTCTGACATTTGGA
NOVlOd, CG50307-02 SEQ ID NO: 120 330 aa MW at 37017.4kD Protein Sequence
MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRLGSRADLIKQYGR AWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYKVETDIIVADFSSGREIYLPI REALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDIINVNIAAASLMVHWLPGMVERKKGAIVTIS SGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGIFVQSLIPFYVATSMTAPSNFLHRCS LVPSP KVYAHHAVSTLGI SKRTTGYWSHSIQFLFAQYMPE LWV GANILNRSLRKEALCCTA
NOVl Oe, SNPl 3375811 of SEQ ID NO: 121 1162 bp CG50307-03, DNA Sequence ORF Start: ATG at 97 ORF Stop: TGA at 1087
SNP Pos: 1076 SNP Change: C to G
ATCTACGGAGTCCCTTTGGCCACATAAGATTGGCCTTAAGAGAAGGACGGAGCCACATACTGCTGACG
GCCCAGAACTGGCAGAGAGAAGGTTGCCATGGCTGCTGTTGACAGTTTCTACCTCTTGTACTGGGAAA
TCGCCAGGTCTTGCAATTGCTATATGGAAGCTCTAGCTTTGGTTGGAGCCTGGTATACGGCCAGAAAA AGCATCACTGTCATCTGTGACTTTTACAGCCTGATCAGGCTGCATTTTATCCCCCGCCTGGGGAGCAG AGCAGACTTGATCAAGCAGTATGGAAGATGGGCCGTTGTCAGCGGTGCAACAGATGGGATTGGAAAAG CCTACGCTGAAGAGTTAGCAAGCCGAGGTCTCAATATAATCCTGATTAGTCGGAACGAGGAGAAGTTG CAGGTTGTTGCTAAAGACATAGCCGACACGTACAAAGTGGAAACTGATATTATAGTTGCGGACTTCAG CAGCGGTCGTGAGATCTACCTTCCAATTCGAGAAGCCCTGAAGGACAAAGACGTTGGCATCTTGGTAA ATAACGTGGGTGTGTTTTATCCCTACCCGCAGTATTTCACTCAGCTGTCCGAGGACAAGCTCTGGGAC ATCATAAATGTGAACATTGCCGCCGCTAGTTTGATGGTCCATGTTGTGTTACCGGGAATGGTGGAGAG AAAGAAAGGTGCCATCGTCACGATCTCTTCTGGCTCCTGCTGCAAACCCACTCCTCAGCTGGCTGCAT TTTCTGCTTCTAAGGCTTATTTAGACCACTTCAGCAGAGCCTTGCAATATGAATATGCCTCTAAAGGA ATCTTTGTACAGAGTCTAATCCCTTTCTATGTAGCCACCAGCATGACAGCACCCAGCAACTTTCTGCA CAGGTGCTCGTGGTTGGTGCCTTCGCCAAAAGTCTATGCACATCATGCTGTTTCTACTCTTGGGATTT CCAAAAGGACCACAGGATATTGGTCCCATTCTATTCAGTTTCTTTTTGCACAGTATATGCCTGAATGG CTCTGGGTGTGGGGAGCAAATATTCTCAACCGTTCACTACGTAAGGAAGCCTTATGCTGCACAGCCTG AGTCTGGATGGCCACTTGAGAAGTTTTGCCAACTCCTGGGAACCTCGATATTCTGACATTTGGAAAAA CACATT
NOV10e, SNP1337581 1 of SEQ ID NO: 122 330 aa MW at 37047.4kD CG50307-03, Protein Sequence SNP Pos: 327 SNP Change: Ser to Cys
MAAVDSFYLLYWE I ARSCNCYMEALALVGAWYTARKS ITVI CDFYSLI RLHFI PRLGSRADLI KQYGR WAWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYKVETDIIVADFSSGREIYLPI REALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDI INvlvTIAAASljMVHVVLPGMVERKKGAIVTIS SGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGIFVQSLIPFYVATSMTAPSNFLHRCSWLVPSP KVYAHHAVSTLGI SKRTTGYWSHS IQFLFAQYMPEWLWVWGANI LNRSLRKEALCCTA A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 10B.
Table 10B. Comparison ofthe NOV10 protein sequences.
NOVlOa MAAVDSFYLLY EIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRL
NOVlOb TGSTMAAVDSFYLLYREIARSCNCYMEALALVGA YTARKSITVICDFYSLIRLHFIPRL
NOVlOc MAAVDSFYLLYREIARSCNCYMEALALVGA YTARKSITVICDFYSLIRLHFIPRL
NOVlOd MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRL
NOVl0a GSRADLIKQYGR AWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYK
NOVlOb GSRADLIKQYGR AWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYK
NOVlOc GSRADLIKQYGRWAWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYK
NOVlOd GSRADLIKQYGR AWSGATDGIGKAYAEELASRGLNIILISRNEEKLQWAKDIADTYK
NOVlOa VETDIIVADFSSGREIYLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDIINV
NOVlOb VETDIIVADFSSGREIYLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKL DIINV
NOVlOc VETDIIVADFSSGREIYLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDIINV
NOVlOd VETDIIVADFSSGREIYLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDIINV
NOVlOa NIAAASLMVHWLPGMVERKKGAIVTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEY
NOVlOb NIAAASLMVHWLPGMVERKKGAIVTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEY
NOVlOc NIAAASLMVHWLPGMVERKKGAIVTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEY
NOVlOd NIAAASLMVHWLPGMVERKKGAIVTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEY
NOVlOa ASKGIFVQSLIPFYVATSMTAPSNFLHRCS LVPSPKVYAHHAVSTLGISKRTTGYWSHS
NOVlOb ASKGIFVQSLIPFYVATSMTAPSNFLHRCSWLVPSPKVYAHHAVSTLGISKRTTGYWSHS
NOVlOc ASKGIFVQSLXPFYVATSMTAPSNFLHRCS LVPSPKVYAHHAVSTLGISKRTTGYWSHS
NOVlOd ASKGIFVQSLIPFYVATSMTAPSNFLHRCS LVPSPKVYAHHAVSTLGISKRTTGYWSHS
NOVlOa IQFLFAQYMPEWL VWGANILNRSLRKEALSCTA
NOVlOb IQFLFAQYMPEWL VWGANILNRSLRKEALSCTALEG
NOVlOc IQFLFAQYMPEWL V GANILNRSLRKEALSCTA
NOVlOd IQFLFAQYMPE LWVWGANILNRSLRKEALCCTA
NOVlOa (SEQ ID NO 114)
NOVlOb (SEQ ID NO 116)
NOVlOc (SEQ ID NO 118)
NOVlOd (SEQ ID NO 120)
Further analysis ofthe NOVlOa protein yielded the following properties shown in Table IOC.
Figure imgf000236_0001
PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.54 possible cleavage site: between 58 and 59
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1
Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -3.88 Transmembrane 173 - 189
PERIPHERAL Likelihood = 2.01 (at 37)
ALOM score: -3.88 (number of TMSs : 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 180 Charge difference: 4.5 C( 2.5) - N(-2.0) C > N: C-terminal side will be inside
>>> membrane topology: type lb (cytoplasmic tail 173 to 330)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 6.52 Hyd Moment(95): 5.94 G content: 0 D/E content: 2 S/T content: 1 Score: -6.71
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.0% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
34.8 % nuclear 21.7 % mitochondrial 21.7 % cytoplasmic
8.7 % vesicles of secretory system
4.3 vacuolar
4.3 % peroxisomal
4.3 % endoplasmic reticulum
>> prediction for CG50307- 03 is nuc (k=23)
A search ofthe NOVlOa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.
Figure imgf000239_0001
In a BLAST search of public sequence databases, the NOVlOa protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.
Figure imgf000240_0001
PFam analysis indicates that the NOVlOa protein contains the domains shown in the Table 10F.
Table 10F. Domain Analysis of NOVlOa
Identities/
Pfam Domain NOVlOa Match Region Similarities Expect Value for the Matched Region adh short 66..306 73/275 (27%) 8e-24 166/275 (60%)
Example 11.
The NOVl 1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11 A. Table 11 A. NOV11 Sequence Analysis
NOVl la, CG50315-01 SEQ ID NO: 123 938 bp DNA Sequence ORF Start: at 1 ORF Stop: TAG at 931
AATCTCACCAGAGTAACCGAATTCATTCTCATGGGCTTTATGGACCACCCCAAATTGGAGATTCCCCT CTTTCTGGTGTTTCTGAGTTTCTACCTAGTCACCCTTCTTGGGAATGTGGGGATGATTATGTTAATCC AAGTAGATGTCAAACTCTACACCCCAATGTACTTCTTCCTGAGCCACCTCTCCCTGCTGGATGCCTGT TACACCTCAGTCATCACCCCTCAGATCCTAGCCACATTGGCCACAGGCAAAACGGTCATCTCCTACGG CCACTGTGCTGCCCAGTTCTTTTTATTCACCATCTGTGCAGGCACAGAGTGCTTTCTGCTGGCAGTGA TGGCCTATGATCGCTATGCTGCCATTCGCAACCCACTGCTCTATACCGTGGCCATGAATCCCAGGCTC TACTGGAGCCTGGTGGTAGGAGCCTATGTCTGTGGGGTGTCAGGAGCCATCCTGCGTACCACTTGCAC CTTCACCCTCTCCTTCTGTAAGGACAATCAAATAAACTTCTTCTTCTGTGACCTCCCACCCCTGCTGA AGCTTGCCTGCAGTGACACAGCAAACATCGAGATTGTCATCATCTTCTTTGGCAATTTTGTGATTTTG GCCAATGCCTCCOTCATCCTGATTTCCTATCTGCTCATCATCAAGACCATTTTGAAAGTGAAGTCTTC AGGTGGCAGGGCCAAGACTTTCTCCACATGTGCCTCTCACATCACTGCTGTGGCCCTTTTCTTTGGAG CCCTTATCTTCATGTATCTGCAAAGTGGCTCAGGCAAATCTCTGGAGGAAGACAAAGTCGTGTCTGTC TTCTATACAGTGGTCATCCCCATGCTGAACCCTCTGATCTACAGCTTAAGAAACAAAGATGTAAAAGA CGCCTTCAGAAAGGTCGCTAGGAGACTCCAGGTGTCCCTGAGCATGTAGATTTA
NOVl la, CG50315-01 SEQ ID NO: 124 310 aa MW at 34522.7kD Protein Sequence
NLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLYTPMYFFLSHLSLLDAC YTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLAVMAYDRYAAIRNPLLYTVAMNPRL Y SLWGAYVCGVSGAILRTTCTFTLSFCKDNQINFFFCDLPPLLKLACSDTANIEIVIIFFGNFVIL ANASVILISYLLIIKTILKVKSSGGRAKTFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSV FYTWIPMLNPLIYSLRNKDVKDAFRKVARRLQVSLSM
NOVl lb, 207580272 SEQ ID NO: 125 822 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCATGATTATGTTAATCCAAGTAGATGTCAAACTCTACACCCCAATGTACTTCTTCCTGAGCCA CCTCTCCCTGCTGGATGCCTGTTACACCTCAGTCATCACCCCTCAGATCCTAGCCACATTGGCCACAG GCAAAACGGTCATCTCCTACGGCCACTGTGCTGCCCAGTTCTTTTTATTCACCATCTGTGCAGGCACA GAGTGCTTTCTGCTGGCAGTGATGGCCTATGATCGCTATGCTGCCATTCGCAACCCACTGCTCTATAC CGTGGCCATGAATCCCAGGCTCTACTGGAGCCTGGTGGTAGGAGCCTATGTCTGTGGGGTGTCAGGAG CCATCCTGCGTACCACTTGCACCTTCACCCTCTCCTTCTGTAAGGACAATCAAATAAACTTCTTCTTC TGTGACCTCCCACCCCTGCTGAAGCTTGCCTGCAGTGACACAGCAAACATCGAGATTGTCATCATCTT CTTTGGCAATTTTGTGATTTTGGCCAATGCCTCCGTCATCCTGATTTCCTATCTGCTCATCATCAAGA CCATTTTGAAAGTGAAGTCTTCAGGTGGCAGGGCCAAGACTTTCTCCACATGTGCCTCTCACATCACT GCTGTGGCCCTTTTCTTTGGAGCCCTTATCTTCATGTATCTGCAAAGTGGCTCAGGCAAATCTCTGGA GGAAGACAAAGTCGTGTCTGTCTTCTATACAGTGGTCATCCCCATGCTGAACCCTCTGATCTACAGCT TAAGAAACAAAGATGTAAAAGACGCCTTCAGAAAGGTCGCTAGGAGACTCCAGGTGTTCCTGAGCATG CTCGAG
NOVl lb, 207580272 SEQ ID NO: 126 274 aa MW at 30387.7kD Protein Sequence
GSMIMLIQVDVKLYTPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGT ECFLLAVMAYDRYAAIRNPLLYTVAMNPRLY SLWGAYVCGVSGAILRTTCTFTLSFCKDNQINFFF CDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLI IKTILKVKSSGGRAKTFSTCASHIT AVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKDVKDAFRKVARRLQVFLSM LE
NOVl lc, 314411778 SEQ ID NO: 127 964 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCACCATGGCCAAGAATAATCTCACCAGAGTAACCGAATTCATTCTCATGGGCTTTATGG ACCACCCCAAATTGGAGATTCCCCTCTTTCTGGTGTTTCTGAGTTTCTACCTAGTCACCCTTCTTGGG AATGTGGGGATGATTATGTTAATCCAAGTAGATGTCAAACTCTACACCCCAATGTACTTCTTCCTGAG CCACCTCTCCCTGCTGGATGCCTGTTACACCTCAGTCATCACCCCTCAGATCCTAGCCACATTGGCCA CAGGCAAAACGGTCATCTCCTACGGCCACTGTGCTGCCCAGTTCTTTTTATTCACCATCTGTGCAGGC ACAGAGTGCTTTCTGCTGGCAGTGATGGCCTATGATCGCTATGCTGCCATTCGCAACCCACTGCTCTA TACCGTGGCCATGAATCCCAGGCTCTGCTGGAGCCTGGTGGTAGGAGCCTATGTCTGTGGGGTGTCAG GAGCCATCCTGCGTACCACTTGCACCTTCACCCTCTCCTTCTGTAAGGACAATCAAATAAACTTCTTC TTCTGTGACCTCCCACCCCTGCTGAAGCTTGCCTGCAGTGACACAGCAAACATCGAGATTGTCATCAT CTTCTTTGGCAATTTTGTGATTTTGGCCAATGCCTCCGTCATCCTGATTTCCTATCTGCTCATCATCA AGACCATTTTGAAAGTGAAGTCTTCAGGTGGCAGGGCCAAGACTTTCTCCACATGTGCCTCTCACATC ACTGCTGTGGCCCTTTTCTTTGGAGCCCTTATCTTCATGTATCTGCAAAGTGGCTCAGGCAAATCTCT GGAGGAAGACAAAGTCGTGTCTGTCTTCTATACAGTGGTCATCCCCATGCTGAACCCTCTGATCTACA GCTTAAGAAACAAAGATGTAAAAGACGCCTTCAGAAAGGTCGCTAGGAGACTCCAGGTGTCCCTGAGC ATGCTCGAGGGC
NOVl lc, 31441 1778 SEQ ID NO: 128 321 aa MW at 35552.9kD Protein Sequence
TGSTMAKNNLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLYTPMYFFLS HLSLLDACYTSVI TPQILATLATGKTVI SYGHCAAQFFLFTI CAGTECFLLAVMAYDRYAAIRNPLLY TVAMNPRLCWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINFFFCDLPPLLKLACSDTANIEIVI I FFGNFVILANASVILISYLLIIKTILKVKSSGGRAKTFSTCASHITAVALFFGALIFMYLQSGSGKSL EEDKWSVFYTWIPMLNPLIYSLRNKDVKDAFRKVARRLQVSLSMLEG
NOVl ld, CG50315-02 SEQ ID NO: 129 968 bp DNA Sequence ORF Start: ATG at 17 ORF Stop: TAG at 959
AGTCCACATTGTCTCCATGGCCAAGAATAATCTCACCAGAGTAACCGAATTCATTCTCATGGGCTTTA
TGGACCACCCCAAATTGGAGATTCCCCTCTTTCTGGTGTTTCTGAGTTTCTACCTAGTCACCCTTCTT GGGAATGTGGGGATGATTATGTTAATCCAAGTAGATGTCAAACTCTACACCCCAATGTACTTCTTCCT GAGCCACCTCTCCCTGCTGGATGCCTGTTACACCTCAGTCATCACCCCTCAGATCCTAGCCACATTGG CCACAGGCAAAACGGTCATCTCCTACGGCCACTGTGCTGCCCAGTTCTTTTTATTCACCATCTGTGCA GGCACAGAGTGCTTTCTGCTGGCAGTGATGGCCTATGATCGCTATGCTGCCATTCGCAACCCACTGCT CTATACCGTGGCCATGAATCCCAGGCTCTGCTGGAGCCTGGTGGTAGGAGCCTATGTCTGTGGGGTGT CAGGAGCCATCCTGCGTACCACTTGCACCTTCACCCTCTCCTTCTGTAAGGACAATCAAATAAACTTC TTCTTCTGTGACCTCCCACCCCTGCTGAAGCTTGCCTGCAGTGACACAGCAAACATCGAGATTGTCAT CATCTTCTTTGGCAATTTTGTGATTTTGGCCAATGCCTCCGTCATCCTGATTTCCTATCTGCTCATCA TCAAGACCATTTTGAAAGTGAAGTCTTCAGGTGGCAGGGCCAAGACTTTCTCCACATGTGCCTCTCAC ATCACTGCTGTGGCCCTTTTCTTTGGAGCCCTTATCTTCATGTATCTGCAAAGTGGCTCAGGCAAATC TCTGGAGGAAGACAAAGTCGTGTCTGTCTTCTATACAGTGGTCATCCCCATGCTGAACCCTCTGATCT ACAGCTTAAGAAACAAAGATGTAAAAGACGCCTTCAGAAAGGTCGCTAGGAGACTCCAGGTGTCCCTG AGCATGTAGATCTAAG
NOVl Id, CG50315-02 SEQ ID NO: 130 314 aa MW at 34907.2kD Protein Sequence
MAKNNLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLYTPMYFFLSHLSL LDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLAVMAYDRYAAIRNPLLYTVAM NPRLCWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINFFFCDLPPLLKLACSDTANIEIVIIFFGN FVILANASVILISYLLI IKTILKVKSSGGRAKTFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDK WSVFYTWIPMLNPLIYSLRNKDVKDAFRKVARRLQVSLSM
NOVl le, CG50315-03 SEQ ID NO: 131 822 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: at 817
GGATCCATGATTATGTTAATCCAAGTAGATGTCAAACTCTACACCCCAATGTACTTCTTCCTGAGCCA
CCTCTCCCTGCTGGATGCCTGTTACACCTCAGTCATCACCCCTCAGATCCTAGCCACATTGGCCACAG GCAAAACGGTCATCTCCTACGGCCACTGTGCTGCCCAGTTCTTTTTATTCACCATCTGTGCAGGCACA GAGTGCTTTCTGCTGGCAGTGATGGCCTATGATCGCTATGCTGCCATTCGCAACCCACTGCTCTATAC CGTGGCCATGAATCCCAGGCTCTACTGGAGCCTGGTGGTAGGAGCCTATGTCTGTGGGGTGTCAGGAG CCATCCTGCGTACCACTTGCACCTTCACCCTCTCCTTCTGTAAGGACAATCAAATAAACTTCTTCTTC TGTGACCTCCCACCCCTGCTGAAGCTTGCCTGCAGTGACACAGCAAACATCGAGATTGTCATCATCTT CTTTGGCAATTTTGTGATTTTGGCCAATGCCTCCGTCATCCTGATTTCCTATCTGCTCATCATCAAGA CCATTTTGAAAGTGAAGTCTTCAGGTGGCAGGGCCAAGACTTTCTCCACATGTGCCTCTCACATCACT GCTGTGGCCCTTTTCTTTGGAGCCCTTATCTTCATGTATCTGCAAAGTGGCTCAGGCAAATCTCTGGA GGAAGACAAAGTCGTGTCTGTCTTCTATACAGTGGTCATCCCCATGCTGAACCCTCTGATCTACAGCT TAAGAAACAAAGATGTAAAAGACGCCTTCAGAAAGGTCGCTAGGAGACTCCAGGTGTTCCTGAGCATG CTCGAG
NOVl le, CG50315-03 SEQ ID NO: 132 270 aa MW at 30001.3kD Protein Sequence
MIMLIQVDVKLYTPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTEC FLLAVMAYDRYAAIRNPLLYTVAMNPRLYWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINFFFCD LPPLLKLACSDTANIEIVII FFGNFVILANASVILISYLLIIKTILKVKSSGGRAKTFSTCASHITAV ALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKDVKDAFRKVARRLQVFLSM
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 1 IB.
Table 11B. Comparison of the NOV11 protein sequences.
NOVlla NLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLY
NOVllb GSMIMLIQVDVKLY
NOVllc TGSTMAKNNLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLY
NOVlId MAKNNLTRVTEFILMGFMDHPKLEIPLFLVFLSFYLVTLLGNVGMIMLIQVDVKLY
NOVlle MIMLIQVDVKLY
NOVlla TPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLA
NOVllb TPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLA
NOVllc TPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLA
NOVlId TPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLA
NOVlle TPMYFFLSHLSLLDACYTSVITPQILATLATGKTVISYGHCAAQFFLFTICAGTECFLLA
NOVlla VMAYDRYAAIRNPLLYTVAMNPRLYWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINF
NOVllb VMAYDRYAAIRNPLLYTVAMNPRLY SLWGAYVCGVSGAILRTTCTFTLSFCKDNQINF
NOVllc VMAYDRYAAIRNPLLYTVAMNPRLCWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINF
NOVlId VMAYDRYAAIRNPLLYTVAMNPRLCWSLWGAYVCGVSGAILRTTCTFTLSFCKDNQINF
NOVlle VMAYDRYAAIRNPLLYTVAMNPRLY SLWGAYVCGVSGAILRTTCTFTLSFCKDNQINF
NOVlla FFCDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLIIKTILKVKSSGGRAK
NOVllb FFCDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLIIKTILKVKSSGGRAK
NOVllc FFCDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLIIKTILKVKSSGGRAK
NOVlld FFCDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLIIKTILKVKSSGGRAK
NOVlle FFCDLPPLLKLACSDTANIEIVIIFFGNFVILANASVILISYLLIIKTILKVKSSGGRAK
NOVlla TFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKD
NOVl lb TFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKD
NOVl lc TFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKD
NOVlld TFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKD
NOVlle TFSTCASHITAVALFFGALIFMYLQSGSGKSLEEDKWSVFYTWIPMLNPLIYSLRNKD
NOVlla VKDAFRKVARRLQVSLSM
NOVllb VKDAFRKVARRLQVFLSMLE-
NOV11c VKDAFRKVARRLQVSLSMLEG
NOVlld VKDAFRKVARRLQVSLSM
NOVlle VKDAFRKVARRLQVFLSM- - -
NOVlla (SEQ ID NO: 124) NOVllb (SEQ ID NO: 126) NOVllc (SEQ ID NO: 128)
NOVlld (SEQ ID NO: 130)
NOVlle (SEQ ID NO: 132)
Further analysis ofthe NOVl la protein yielded the following properties shown in Table HC.
Table 11C. Protein Sequence Properties NOVlla
SignalP analysis: Cleavage site between residues 38 and 39
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 7 ; pos . chg 1 ; neg . chg 1 H-region : length 7 ; peak value 6 .23 PSG score : 1 . 83
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1 ) : -3 . 00 possible cleavage site : between 37 and 38
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 6
INTEGRAL Likelihood -6.58 Transmembrane 21 - 37
INTEGRAL Likelihood -4.09 Transmembrane 97 - 113
INTEGRAL Likelihood -1.65 Transmembrane 138 - 154
INTEGRAL Likelihood -8.70 Transmembrane 202 - 218
INTEGRAL Likelihood -4.14 Transmembrane 240 - 256
INTEGRAL Likelihood -3.13 Transmembrane 269 - 285
PERIPHERAL Likelihood 0.85 (at 183)
ALOM score : -8.70 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 28 Charge difference: 2.0 C( 0.5) - N(-1.5) C > N: C-terminal side will be inside
>>>Caution : Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75): 1.96 Hyd Moment(95): 9.20 G content: 1 D/E content: 2 S/T content: 2 Score: -6.22
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 14 TRV|TE
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 7.7%
NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: LTRV
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
44.4 %: endoplasmic reticulum 22.2 %: vacuolar 11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG50315-01 is end (k=9)
A search ofthe NOVl la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1 ID.
Figure imgf000246_0001
In a BLAST search of public sequence databases, the NOVl la protein was found to have homology to the proteins shown in the BLASTP data in Table 1 IE.
Figure imgf000247_0001
PFam analysis indicates that the NOVl la protein contains the domains shown in the Table 1 IF.
Figure imgf000247_0002
Example 12.
The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.
Table 12A. NOV12 Sequence Analysis
NOV12a, CG50341-01 SEQ ID NO: 133 997 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TAA at 966
GGCGCTTATAATTTTGAACTATGACCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACT GAGAATTGGGTGCTCCTGAGGCTGCATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGAT GAATTTAGTCATCATTCTCCTCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCC GACATTTGTCCTTCTTAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTC GCCTCCACTGACTCCATCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGG ATCAGAGATTGGCATCCTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACT GTGAGGCTGTCATGAGCAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCC TTGGGACTCTTGTACACAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTT CTTCTGCGATGTCCCTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTG TGGCCATTGGGGTCTGTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTC TCTGCTGTGTTAAGGATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCT CATTGTTGTCACTGTGTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTT CTATTCTAGACTTGCTGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTAC TGTCTGAAGAACAAGGACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGT AATGAAAGATGACTAAAGTTGAAGATGGGAAGTACTTTTTTTGNN
NOV12a, CG50341-01 SEQ ID NO: 134 315 aa MW at 34934.2kD Protein Sequence
MTNQTQMMEFLLVRFTEN VLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFFLRHLSFLD LCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDRYAAICCPLHCEAVMSR GLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPALLKLTCSKEHAIISVSVAIGVCY AFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLV SVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDD
NOVl 2b, 169475616 SEQ ID NO: 135 819 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT AGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATC CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA CAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCT GCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTG TTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGA TATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTG TTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCT GGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGG ACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCTC GAG
NOV12b, 169475616 SEQ ID NO: 136 273 aa MW at 29857.9kD Protein Sequence
GSMILDHRLHMAMYFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGI LTAMSYDRYAAICCPLHCEAVMSRGLCVQLMALS LNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTV FLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDDL
E
NOV12c, CG50341-02 SEQ ID NO: 137 996 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TAA at 966
GGCGCTTATAATTTTGAACTATGACCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACT
GAGAATTGGGTGCTCCTGAGGCTGCATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGAT GAATTTAGTCATCATTCTCCTCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCC GACATTTGTCCTTCTTAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTC GCCTCCACTGACTCCATCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGG ATCAGAGATTGGCATCCTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACT GTGAGGCTGTCATGAGCAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCC TTGGGACTCTTGTACACAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTT CTTCTGCGATGTCCCTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTG TGGCCATTGGGGTCTGTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTC TCTGCTGTGTTAAGGATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCT CATTGTTGTCACTGTGTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTT CTATTCTAGACTTGCTGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTAC TGTCTGAAGAACAAGGACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGT AATGAAAGATGACTAAAGATTGAAGATGGGAAGTACTTTTTTTG
NOV12c, CG50341-02 SEQ ID NO: 138 315 aa MW at 34934.2kD Protein Sequence
MTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVI ILLMILDHRLHMAMYFFLRHLSFLD LCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDRYAAICCPLHCEAVMSR GLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPALLKLTCSKEHAI ISVSVAIGVCY AFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLV SVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDD
NOV12d, CG50341-03 SEQ ID NO: 139 819 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: at 814
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT
AGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATC CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA CAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCT GCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTG TTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGA TATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTG TTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCT GGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGG ACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCTC GAG
NOV12d, CG50341-03 SEQ ID NO: 140 269 aa MW at 29471.5kD Protein Sequence
MILDHRLHMAMYFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILT AMSYDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPAL LKLTCSKEHAI ISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFL VTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDD
NOV12e, CG50341-04 SEQ ID NO: 141 957 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: at 952
GGATCCATGACCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACTGAGAATTGGGTGCT
CCTGAGGCTGCATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGATGAATTTAGTCATCA TTCTCCTCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTC TTAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTC CATCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCA TCCTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATG AGCAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTA CACAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCC CTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTC TGTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAG GATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTG TGTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTG CTGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAA GGACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACC TCGAG NOV 12e, CG50341-04 SEQ ID NO: 142 315 aa MW at 34934.2kD Protein Sequence
MTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFFLRHLSFLD LCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDRYAAICCPLHCEAVMSR GLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPALLKLTCSKEHAIISVSVAIGVCY AFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLV SVFYSVAP PTLNPVI YCLKNKDI KS ALSKVLWNVRS SGVMKDD
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 12B.
Table 12B. Comparison of the NOV12 protein sequences.
NOV12a MTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFF
NOV12b GSMILDHRLHMAMYFF
NOV12C MTNQTQMMEFLLVRFTENVJVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFF
NOVl2d MILDHRLHMAMYFF NOVl2e MTNQTQMMEFLLVRFTEN VLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFF
NOV12a LRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDR
NOVl2b LRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDR
NOV12C LRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDR
NOVl2d LRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDR
NOV12e LRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDR
NOV12a YAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP
NOV12b YAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP
NOVl2c YAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP
NOV12d YAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP
NOV12e YAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP
NOV12a ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCV
NOV12b ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCV
NOV12c ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCV
NOVl2d ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCV
NOVl2e ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCV
NOV12a PHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALS
NOV12b PHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALS
NOV12C PHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALS
NOV12d PHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALS
NOV12e PHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALS
NOV12a KVLWNVRSSGVMKDD--
NOV12b KVL NVRSSGVMKDDLE
NOV12c KVLWNVRSSGVMKDD- -
NOV12d KVLWNVRSSGVMKDD--
NOV12e KVLWNVRSSGVMKDD- -
NOVl2a (SEQ ID NO 134) NOV12b (SEQ ID NO 136) NOVl2c (SEQ ID NO 138) NOV12d (SEQ ID NO: 140) NOV12e (SEQ ID NO: 142)
Further analysis ofthe NOV 12a protein yielded the following properties shown in Table 12C.
Table 12C. Protein Sequence Properties NOV12a
SignalP analysis: Cleavage site between residues 47 and 48
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 9 ; pos . chg 0 ; neg . chg 1
H-region : length 4 ; peak value 0. 00 PSG score : -4 .40
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1 ) : -3 . 11 possible cleavage site : between 36 and 37
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 5
INTEGRAL Likelihood -9.87 Transmembrane 32 - 48
INTEGRAL Likelihood -9.66 Transmembrane 90 - 106
INTEGRAL Likelihood -9.71 Transmembrane 198 - 214
INTEGRAL Likelihood -5.79 Transmembrane 239 - 255
INTEGRAL Likelihood 0.16 Transmembrane 267 - 283
PERIPHERAL Likelihood 1.11 (at 56)
ALOM score: •9.87 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 39 Charge difference: 1.0 C( 2.5) - N( 1.5) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 2.94 Hyd Moment(95): 4.71 G content: 0 D/E content: 2 S/T content: 3 Score: -5.83
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 6.7% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: VMKD
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LHALLFSLIYLTAVLMNLVIIL at 24 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
44.4 %: endoplasmic reticulum
11.1 %.- mitochondrial
11.1 %: Golgi
11.1 %: vacuolar 11 . 1 % vesicles of secretory system
11 . 1 % cytoplasmic
>> predict ion for CG50341- 31 is end (k=9)
A search ofthe NOVl 2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D.
Figure imgf000253_0001
In a BLAST search of public sequence databases, the NOV 12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E.
Figure imgf000254_0001
PFam analysis indicates that the NOV 12a protein contains the domains shown in the Table 12F.
Figure imgf000254_0002
Example 13.
The NOV 13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13 A.
Table 13 A. NOVl 3 Sequence Analysis
NOV13a, CG50365-01 SEQ ID NO: 143 828 bp DNA Sequence ORF Start: ATG at 16 lORF Stop: TAA at 802
CCACCCCGAGGGACCATGTCGAGGCTCAGCTGGGGATACCGCGAGCACAACGGTCCTATTCACTGGAA GGAATTTTTCCCTATTGCTGATGGTGATCAGCAATCTCCAATTGAGATTAAAACCAAAGAAGTGAAAT ATGACTCTTCCCTCCGACCACTTAGTATCAAGTATGACCCAAGCTCAGCTAAAATCATCAGCAACAGC GGCCATTCCTTCAATGTTGACTTTGATGACACAGAGAACAAATCAGTTCTGCGTGGTGGTCCTCTCAC TGGAAGCTACAGGTTACGGCAGGTTCACCTTCACTGGGGGTCCGCTGATGACCACGGCTCCGAGCACA TAGTAGATGGAGTGAGCTATGCTGCAGAGCTCCATGTTGTTCACTGGAATTCAGACAAATACCCCAGC TTTGTTGAGGCAGCTCATGAACCAGATGGACTGGCTGTCTTGGGAGTGTTTTTACAGGTGGGTGAACC TAATTCCCAACTGCAAAAGATTACTGACACTTTGGATTCCATTAAAGAAAAGGGTAAACAAACTCGAT TCACAAATTTTGACCTATTGTCTCTGCTTCCACCATCCTGGGACTACTGGACATATCCTGGTTCTCTT ACAGTTCCACCTCTTCTTGAGAGTGTCACATGGATTGTTTTAAAGCAACCTATAAACATCAGCTCTCA ACAGCTGGCCAAATTTCGCAGTCTCCTGTGCACAGCGGAGGGTGAAGCAGCAGCTTTTCTGGTGAGCA ATCACCGCCCACCACAGCCTCTAAAGGGCCGCAAAGTGAGAGCCTCTTTCCATTAAAAATTGTCACCA ATGAACTCCCCC
NOV13a, CG50365-01 SEQ ID NO: 144 262 aa MW at 29428.8kD Protein Sequence
MSRLSWGYREHNGPIH KEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKIISNSGHSFN VDFDDTENKSVLRGGPLTGSYRLRQVHLHWGSADDHGSEHIVDGVSYAAELHWHWNSDKYPSFVEAA HEPDGLAVLGVFLQVGEPNSQLQKITDTLDSIKEKGKQTRFTNFDLLSLLPPSWDYWTYPGSLTVPPL LESVTWIVLKQPINISSQQLAKFRSLLCTAEGEAAAFLVSNHRPPQPLKGRKVRASFH
NOVl 3b, 278019595 SEQ ID NO: 145 784 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCAGCTGGGGATACCGCGAGCACAACGGTCCTATTCACTGGAAGGAATTTTTCCCTATTG CTGATGGTGATCAGCAATCTCCAATTGAGATTAAAACCAAAGAAGTGAAATATGACTCTTCCCTCCGA CCACTTAGTATCAAGTATGACCCAAGCTCAGCTAAAATCATCAGCAACAGCGGCCATTCCTTCAATGT TGACTTTGATGACACAGAGAACAAATCAGTTCTGCGTGGTGGTCCTCTCACTGGAAGCTACAGGTTAC GGCAGGTTCACCTTCACTGGGGGTCCGCTGATGACCACGGCTCCGAGCACATAGTAGATGGAGTGAGC TATGCTGCAGAGCTCCATGTTGTTCACTGGAATTCAGACAAATACCCCAGCTTTGTTGAGGCAGCTCA TGAACCAGATGGACTGGCTGTCTTGGGAGTGTTTTTACAGATTGGTGAACCTAATTCCCAACTGCAAA AGATTACTGACACTTTGGATTCCATTAAAGAAAAGGGTAAACAAACTCGATTCACAAATTTTGACCTA TTGTCTCTGCTTCCACCATCCTGGGACTACTGGACATATCCTGGTTCTCTTACAGTTCCACCTCTTCT TGAGAGTGTCACATGGATTGTTTTAAAGCAACCTATAAACATCAGCTCTCAACAGCTGGCCAAATTTC GCAGTCTCCTGTGCACAGCGGAGGGTGAAGCAGCAGCTTTTCTGGTGAGCAATCACCGCCCACCACAG CCTCTAAAGGGCCGCAAAGTGAGAGCCCTCGAGGGC
NOV13b, 278019595 SEQ ID NO: 146 261 aa MW at 29128.4kD Protein Sequence
TGSSWGYREHNGPIH KEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKIISNSGHSFNV DFDDTENKSVLRGGPLTGSYRLRQVHLHWGSADDHGSEHIVDGVSYAAELHWHWNSDKYPSFVEAAH EPDGLAVLGVFLQIGEPNSQLQKITDTLDSIKEKGKQTRFTNFDLLSLLPPSWDYWTYPGSLTVPPLL ESVTWIVLKQPINISSQQLAKFRSLLCTAEGEAAAFLVSNHRPPQPLKGRKVRALEG
NOV13c, CG50365-02 SEQ ID NO: 147 833 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TAA at 807
ATGTCGAGGCTCAGCTGGGGATGTCGAGGCTCAGCTGGGGATACCGCGAGCACAACGGTCCTATTCAC
TGGAAGGAATTTTTCCCTATTGCTGATGGTGATCAGCAATCTCCAATTGAGATTAAAACCAAAGAAGT GAAATATGACTCTTCCCTCCGACCACTTAGTATCAAGTATGACCCAAGCTCAGCTAAAATCATCAGCA ACAGCGGCCATTCCTTCAATGTTGACTTTGATGACACAGAGAACAAATCAGTTCTGCGTGGTGGTCCT CTCACTGGAAGCTACAGGTTACGGCAGGTTCACCTTCACTGGGGGTCCGCTGATGACCACGGCTCCGA GCACATAGTAGATGGAGTGAGCTATGCTGCAGAGCTCCATGTTGTTCACTGGAATTCAGACAAATACC CCAGCTTTGTTGAGGCAGCTCATGAACCAGATGGACTGGCTGTCTTGGGAGTGTTTTTACAGATTGGT GAACCTAATTCCCAACTGCAAAAGATTACTGACACTTTGGATTCCATTAAAGAAAAGGGTAAACAAAC TCGATTCACAAATTTTGACCTATTGTCTCTGCTTCCACCATCCTGGGACTACTGGACATATCCTGGTT CTCTTACAGTTCCACCTCTTCTTGAGAGTGTCACATGGATTGTTTTAAAGCAACCTATAAACATCAGC TCTCAACAGCTGGCCAAATTTCGCAGTCTCCTGTGCACAGCGGAGGGTGAAGCAGCAGCTTTTCTGGT GAGCAATCACCGCCCACCACAGCCTCTAAAGGGCCGCAAAGTGAGAGCCTCTTTCCATTAAAAATTGT CACCAATGAACTCCCCC NOV13c, CG50365-02 SEQ ID NO: 148 262 aa MW at 29442.8kD Protein Sequence
MSRLS GYREHNGPIHWKEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKIISNSGHSFN VDFDDTENKSVLRGGPLTGSYRLRQVHLH GSADDHGSEHIVDGVSYAAELHWUWNSDKYPSFVEAA HEPDGLAVLGVFLQIGEPNSQLQKITDTLDSIKEKGKQTRFTNFDLLSLLPPS DY TYPGSLTVPPL LESVTWIVLKQPINISSQQLAKFRSLLCTAEGEAAAFLVSNHRPPQPLKGRKVRASFH
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 13B.
Table 13B. Comparison ofthe NOVl 3 protein sequences.
NOV13a MSRLS GYREHNGPIH KEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKII
NOV13b -TGSS GYREHNGPIH KEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKII
NOV13C MSRLSWGYREHNGPIH KEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKII
NOV13a SNSGHSFNVDFDDTENKSVLRGGPLTGSYRLRQVHLH GSADDHGSEHIVDGVSYAAELH
NOV13b SNSGHSFNVDFDDTENKSVLRGGPLTGSYRLRQVHLH GSADDHGSEHIVDGVSYAAELH
NOV13C SNSGHSFNVDFDDTENKSVLRGGPLTGSYRLRQVHLHWGSADDHGSEHIVDGVSYAAELH
NOVl3a WH NSDKYPSFVEAAHEPDGLAVLGVFLQVGEPNSQLQKITDTLDSIKEKGKQTRFTNF
NOV13b WH NSDKYPSFVEAAHEPDGLAVLGVFLQIGEPNSQLQKITDTLDSIKEKGKQTRFTNF
NOVl3C WH NSDKYPSFVEAAHEPDGLAVLGVFLQIGEPNSQLQKITDTLDSIKEKGKQTRFTNF
NOV13a DLLSLLPPS DYWTYPGSLTVPPLLESVTWIVLKQPINISSQQLAKFRSLLCTAEGEAAA
NOV13b DLLSLLPPSWDY TYPGSLTVPPLLESVT IVLKQPINISSQQLAKFRSLLCTAEGEAAA
NOV13C DLLSLLPPS DYWTYPGSLTVPPLLESVT IVLKQPINISSQQLAKFRSLLCTAEGEAAA
NOV13a FLVSNHRPPQPLKGRKVRASFH
NOV13b FLVSNHRPPQPLKGRKVRALEG
NOVl3c FLVSNHRPPQPLKGRKVRASFH
NOV13a (SEQ ID NO 144) NOV13b (SEQ ID NO 146) NOV13C (SEQ ID NO 148)
Further analysis ofthe NOV13a protein yielded the following properties shown in Table 13C.
Table 13C. Protein Sequence Properties NOV13a
SignalP analysis: No Known Signal Sequence Predicted
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 2; neg.chg 1 H-region: length 7; peak value -7.23 PSG score: -11.62
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -8.81 possible cleavage site: between 57 and 58
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of T S(s) .. fixed PERIPHERAL Likelihood = 2.97 (at 197) ALOM score: 2.97 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 8.62 Hyd Moment (95): 7.75 G content: 2 D/E content: 2 S/T content: 2 Score: -5.03
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 13 SRL|SW
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PLKGRKV (4) at 251 bipartite: none content of basic residues: 10.3% NLS Score: -0.13
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: SRLS
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 55.5
COIL: Lupas • s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
43.5 %: cytoplasmic 34.8 %: mitochondrial 21.7 %: nuclear
>> prediction for CG50365-01 is cyt (k=23)
A search ofthe NOVl 3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D.
Figure imgf000259_0001
In a BLAST search of public sequence databases, the NOVl 3a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.
Figure imgf000260_0001
PFam analysis indicates that the NOVl 3a protein contains the domains shown in the Table 13F.
Figure imgf000260_0002
Example 14.
The NOV 14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A. Table 14A. NOV14 Sequence Analysis
NOVl 4a, CG50367-01 SEQ ID NO: 149 2762 bp DNA Sequence ORF Start: ATG at 3 ORF Stop: TGA at 2745
CTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTC TGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGT CCTGGATGGACAACCCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGG TGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCA GGATACATAGAAACCCACTACGGCCCAGATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCA TTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCGACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGA TGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATCTGCGTCCCTGGCCACCCCGGGGCTCC AAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCA CAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAG AAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGACTCGG CACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAG GACTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCA CGCAGGACGCCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCC CACGACTCCGCGCAGCTGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGA GGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCG CAGCCACCATGGCCCATGAGATCGGCCACAGCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTG GAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTT CAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATG CCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAG TGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCC GGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCC GCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGAC GTTTACCTACTGGACGGCTCACCCTGTGCCAGGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCAC GCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGG TGGTGAACTCTGCGGGAGATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGT GCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCA CATGGTGCCAGTGGACTCTACCGTTCACCTAGATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCAC TCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGGTAGAGCCAGGCACCCAGTGTGGACCTAGA ATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGCTTCAGCGCTGCCTGACTGCCTG CCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCTGGGCTCCACCCTTCT GTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATGACACCTTC CTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGGGCCGGCCTGGCCTGGTGTTGCTA CCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCC CCAAAGATGGCCCACACAGGGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCC ACTGGACAGCCCTGGCCCCTGGCCCCAGGGGCTCCTGCTGACCATATTCACAACATTTACCCTCCACC ATTTCTCCCAGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCT CGCCTGACCCCCAAGGTGGTTCCCTTGCAGCCTGGGGCCCCAGTCCTTTAGGGGACAACATATCCTCC TCATTCTCAGCAGATCAAGTCCAGATGCCAAGATCCTGCCTCTGTGGCGAACCCTGGGGAGGCCACGT GGGAAGGAAAGAGGGCTCTAAGAGGGGAGGCCCCAGACTGGGGGAGAGGCCTGTCTGGAGCCCAGGAT CACCTGGCTGTGCTGCAGAACTGGAGAAGAGAAGCTCAGCAGAAAGGAGCTGGCATGGGGCCAACAGC AGAAAAGCAGGAGGCACGCAGAAGTGACTGGGAAGCAGGAGG
NOV14a, CG50367-01 SEQ ID NO: 150 914 aa MW at 98055.2kD Protein Sequence
MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDSWWLCTCSGM SGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVT QDANATLWAFLQWRRGLWAQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCR QAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQL GPGSHPAPEACFQV VNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEVTCRGALAL PSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSNHNCHCAPGWAPPFC DKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLA CCYRLPGAHLQRCS GCRRDPACSGP KDGPHRDHPLGGVHPMELGPTATGQP PLAPGAPADHIHNIYPPPFLPDPENSHEPSSHPEKPLPAVS PDPQGGSLAAWGPSPLGDNISSSFSADQVQMPRSCLCGEP GGHVGRKEGSKRGGPRLGERPVWSPGS PGCAAELEKRSSAERSWHGANSRKAGGTQK
NOV14b, CG50367-05 SEQ ID NO: 151 3397 bp
DNA Sequence |0RF Start: ATG at 37 ORF Stop: TGA at 2398
GCGAGCCGCTGCCTAGAGGCCGAGGAGCTCACAGCTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGAC
CCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGAC ATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAACCCTGGCGCACCGTCAGCCTG GAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCT TGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAGATGGGC AGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCC GACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAG CTATTATCTGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGG AGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGC CTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTA CATTGTGGCAGACCACACCCTGTTCTTGACTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCC TGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGACTCTGGACATTCAGGTGGCGCTGACCGGCCTG GAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACGCCAACGCCACGCTCTGGGCCTTCCT GCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGCTGCTCACGGGCCGCGCCT TCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTG AGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACAGCCT CGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGG CTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTC TTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCT CTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACC TCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTG CGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCCGCCAGGCCATGGGTGACTGTGACCTCCCTGAGTT TTGCACGGGCACCTCCTCCCACTGTCCCCCAGACGTTTACCTACTGGACGGCTCACCCTGTGCCAGGG GCAGTGGCTACTGCTGGGATGGCGCATGTCCCACGCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCT GGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAGATGCTCATGGAAACTG CGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGT GCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAGAT GGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGG CCTGGTAGAGTCAGGCACCCAGTGTGGACCTAGAATGGTTTGCAATAGCAACCATAACTGCCACTGTG CTCCAGGCTGGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTG CAGGCTGAAAACCATGACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGG GGCCGGCCTGGCCTGGTGTTGCTACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCA GAAGGGACCCTGCGTGCAGTGGCCCCAAAGATGGCCCACACAGGGACCACCCCCTGGGCGGCGTTCAC CCCATGGAGTTGGGCCCCACAGCCACTGGACAGCCCTGGCCCCTGGACCCTGAGAACTCTCATGAGCC CAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCCGACCCCCAAGCAGATCAAGTCCAGATGC CAAGATCCTGCCTCTGGTGAGAGGTAGCTCCTAAAATGAACAGATTTAAAGACAGGTGGCCACTGACA GCCACTCCAGGAACTTGAACTGCAGGGGCAGAGCCAGTGAATCACCGGACCTCCAGCACCTGCAGGCA
GCTTGGAAGTTTCTTCCCCGAGTGGAGCTTCGACCCACCCACTCCAGGAACCCAGAGCCACACTAGAA
GTTCCTGAGGGCTGGAGAACACTGCTGGGCACACTCTCCAGCTCAATAAACCATCAGTCCCAGAAGCA AAGGTCACACAGCCCCTGACCTCCCTCACCAGTGGAGGCTGGGTAGTGCTGGCCATCCCAAAAGGGCT CTGTCCTGGGAGTCTGGTGTGTCTCCTACATGCAATTTCCACGGACCCAGCTCTGTGGAGGGCATGAC TGCTGGCCAGAAGCTAGTGGTCCTGGGGCCCTATGGTTCGACTGAGTCCACACTCCCCTGCAGCCTGG CTGGCCTCTGCAAACAAACATAATTTTGGGGACCTTCCTTCCTGTTTCTTCCCACCCTGTCTTCTCCC CTAGGTGGTTCCTGAGCCCCCACCCCCAATCCCAGTGCTACACCTGAGGTTCTGGAGCTCAGAATCTG ACAGCCTCTCCCCCATTCTGTGTGTGTCGGGGGGACAGAGGGAACCATTTAAGAAAAGATACCAAAGT AGAAGTCAAAAGAAAGACATGTTGGCTATAGGCGTGGTGGCTCATGCCTATAATCCCAGCACTTTGGG AAGCCGGGGTAGGAGGATCACCAGAGGCCAGCAGGTCCACACCAGCCTGGGCAACACAGCAAGACACC GCATCTACAGAAAAATTTTAAAATTAGCTGGGCGTGGTGGTGTGTACCTGTAGGCCTAGCTGCTCAGG AGGCTGAAGCAGGAGGATCACTTGAGCCTGAGTTCAACACTGCAGTGAGCTATGGTGGCACCACTGCA CTCCAGCCTGGGTGACAGAGCAAGACCCTGTCTCTAAAATAAATTTTAAAAAGACATATTACACT NOVl 4b, CG50367-05 SEQ ID NO: 152 787 aa MW at 84713.5kD Protein Sequence
MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDSWWLCTCSGM SGLITLSRNASYYLRP PPRGSKDFSTHEIFRMEQLLT KGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVT QDANATL AFLQWRRGLWAQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCR QAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQLWGPGSHPAPEACFQV VNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEVTCRGALAL PSAQLDLLGLGLVESGTQCGPRMVCNSNHNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAM LLSVLLPLLPGAGLA CCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQP PLDPENSHEPSSHPEKPLPAVSPDPQADQVQMPRSCLW
NOV14c, CG50367-06 SEQ ID NO: 153 3351 bp DNA Sequence ORF Start: ATG at 37 ORF Stop: TGA at 1579
GCGAGCCGCTGCCTAGAGGCCGAGGAGCTCACAGCTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGAC
CCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGAC ATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAACCCTGGCGCACCGTCAGCCTG GAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCT TGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAGATGGGC AGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCC GACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAG CTATTATCTGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGG AGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGC CTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTA CATTGTGGCAGACCACACCCTGTTCTTGACTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCC TGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGACTCTGGACATTCAGGTGGCGCTGACCGGCCTG GAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACGCCAACGCCACGCTCTGGGCCTTCCT GCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGCTGCTCACGGGCCGCGCCT TCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTG AGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACAGCCT CGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGG CTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTC TTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCT CTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACC TCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTG CGCTGCCTGACGTTTACCTACTGGACGGCTCACCCTGTGCCAGGGGCAGTGGCTACTGCTGGGATGGC GCATGTCCCACGCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGC CTGTTTCCAGGTGGTGAACTCTGCGGGAGATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACT TCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTG CTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAGATGGCCAGGAAGTGACTTGTCGGGG AGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGGTAGAGCCAGGCACCCAGT GTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGCTTCAGCGCTGC CTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCTGGGC TCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACC ATGACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGGGCCGGCCTGGCC TGGTGTTGCTACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGC GTGCAGTGGCCCCAAAGATGGCCCACACAGGGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGG GCCCCACAGCCACTGGACAGCCCTGGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCT GAGAAGCCTCTGCCAGCAGTCTCGCCTGACCCCCAAGATCAAGTCCAGATGCCAAGATCCTGCCTCTG GTGAGAGGTAGCTCCTAAAATGAACAGATTTAAAGACAGGTGGCCACTGACAGCCACTCCAGGAACTT GAACTGCAGGGGCAGAGCCAGTGAATCACCGGACCTCCAGCACCTGCAGGCAGCTTGGAAGTTTCTTC CCCGAGTGGAGCTTCGACCCACCCACTCCAGGAACCCAGAGCCACATTAGAAGTTCCTGAGGGCTGGA GAACACTGCTGGGCACACTCTCCAGCTCAATAAACCATCAGTCCCAGAAGCAAAGGTCACACAGCCCC TGACCTCCCTCACCAGTGGAGGCTGGGTAGTGCTGGCCATCCCAAAAGGGCTCTGTCCTGGGAGTCTG GTGTGTCTCCTACATGCAATTTCCACGGACCCAGCTCTGTGGAGGGCATGACTGCTGGCCAGAAGCTA IGTGGTCCTGGGGCCCTATGGTTCGACTGAGTCCACACTCCCCTGGAGCCTGGCTGGCCTCTGCAAACA
AACATAATTTTGGGGACCTTCCTTCCTGTTTCTTCCCACCCTGTCTTCTCCCCTAGGTGGTTCCTGAG
CCCCCACCCCCAATCCCAGTGCTACACCTGAGGTTCTGGAGCTCAGAATCTGACAGCCTCTCCCCCAT
TCTGTGTGTGTCGGGGGGACAGAGGGAACCATTTAAGAAAAGATACCAAAGTAGAAGTCAAAAGAAAG
ACATGTTGGCTATAGGCGTGGTGGCTCATGCCTATAATCCCAGCACTTTGGGAAGCCGGGGTAGGAGG
ATCACCAGAGGCCAGCAGGTCCACACCAGCCTGGGCAACACAGCAAGACACCGCATCTACAGAAAAAT iTTTAAAATTAGCTGGGCGTGGTGGTGTGTACCTGTAGGCCTAGCTGCTCAGGAGGCTGAAGCAGGAGG
ATCACTTGAGCCTGAGTTCAACACTGCAGTGAGCTATGGTGGCACCACTGCACTCCAGCCTGGGTGAC
AGAGCAAGACCCTGTCTCT
NOVl 4c, CG50367-06 SEQ ID NO: 154 514 aa MW at 55996.3kD Protein Sequence
MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDS WLCTCSGM SGLITLSRNASYYLRP PPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVT QDANATL AFLQ RRGLWAQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLTFTYWTAHP VPGAVATAGMAHVPR SSSASSSGGLAPTQLPRPVSRW
NOV14d, CG50367-07 SEQ ID NO: 155 3139 bp DNA Sequence ORF Start: ATG at 37 ORF Stop: TGA at 1354
GCGAGCCGCTGCCTAGAGGCCGAGGAGCTCACAGCTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGAC
CCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGAC ATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAACCCTGGCGCACCGTCAGCCTG GAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCT TGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAGATGGGC AGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCC GACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAG CTATTATCTGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGG AGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGC CTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTA CATTGTGGCAGACCACACCCTGTTCTTGACTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCC TGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGACTCTGGACATTCAGGTGGCGCTGACCGGCCTG GAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACGCCAACGCCACGCTCTGGGCCTTCCT GCAGTGGCGCCGGGGACTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGCTGCTCACGACCACTCGGA GCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACAGCCTCGGCCTCAGCCACGACC CCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTGCGGCCACCGGGCAC CCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGGGGGGCGG CGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCG TGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCAC AACTGCTCGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCC GGCTGGAGCGCTGTGCCGCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCT CCCACTGTCCCCCAGACGTTTACCTACTGGACGGCTCACCCTGTGCCAGGGGCAGTGGCTACTGCTGG GATGGCGCATGTCCCACGCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCC CGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAGATGCTCATGGAAACTGCGGCCAGGACAGCGAGG GCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGTGCCAGGGTGGAAAGCCC AGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAGATGGCCAGGAAGTGACTTG TCGGGGAGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGGTAGAGCCAGGCA CCCAGTGTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGCTTCAG CGCTGCCTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGG CTGGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTG AAAACCATGACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGGGCCGGC CTGGCCTGGTGTTGCTACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGA CCCTGCGTGCAGTGGCCCCAAAGATGGCCCACACAGGGACCACCCCCTGGGCGGCGTTCACCCCATGG AGTTGGGCCCCACAGCCACTGGACAGCCCTGGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGC CACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCTGACCCCCAAGATCAAGTCCAGATGCCAAGATCCTG CCTCTGGTGAGAGGTAGCTCCTAAAATGAACAGATTTAAAGACAGGTGGCCACTGACAGCCACTCCAG GAACTTGAACTGCAGGGGCAGAGCCAGTGAATCACCGGACCTCCAGCACCTGCAGGCAGCTTGGAAGT
TTCTTCCCCGAGTGGAGCTTCGACCCACCCACTCCAGGAACCCAGAGCCACATTAGAAGTTCCTGAGG
GCTGGAGAACACTGCTGGGCACACTCTCCAGCTCAATAAACCATCAGTCCCAGAAGCAAAGGTCACAC
AGCCCCTGACCTCCCTCACCAGTGGAGGCTGGGTAGTGCTGGCCATCCCAAAAGGGCTCTGTCCTGGG
AGTCTGGTGTGTCTCCTACATGCAATTTCCACGGACCCAGCTCTGTGGAGGGCATGACTGCTGGCCAG
AAGCTAGTGGTCCTGGGGCCCTATGGTTCGACTGAGTCCACACTCCCCTGGAGCCTGGCTGGCCTCTG
CAAACAAACATAATTTTGGGGACCTTCCTTCCTGTTTCTTCCCACCCTGTCTTCTCCCCTAGGTGGTT
CCTGAGCCCCCACCCCCAATCCCAGTGCTACACCTGAGGTTCTGGAGCTCAGAATCTGACAGCCTCTC
CCCCATTCTGTGTGTGTCGGGGGGACAGAGGGAACCATTTAAGAAAAGATACCAAAGTAGAAGTCAAA
AGAAAGACATGTTGGCTATAGGCGTGGTGGCTCATGCCTATAATCCCAGCACTTTGGGAAGCCGGGGT
AGGAGGATCAC
NOV14d, CG50367-07 SEQ ID NO: 156 439 aa MW at 48163.4kD Protein Sequence
MG RPRRARGTPLLLLLLLLLL PVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDSWWLCTCSGM SGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEV TERDRSRVT QDANATLWAFLQ RRGLWAQRPHDSAQLLTTTRSSPSAPQPPWPMRSATASASATTPTAAA RLRPSP EAASWLRPPGTRFRACSAPAAAASCAPSSARGAALASPMPRTPDSRCRRRSAGTASWKRARSVTAALA RSAATSAALLTTARCARGPSAPTGTAACAAC
NOV14e, 249356906 SEQ ID NO: 157 1278 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAGA TGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCT TCCCCGACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAAT GCCAGCTATTATCTGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCG GATGGAGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGA CCAGCCTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAA CTGTACATTGTGGCAGACCACACCCTGTTCTTGACTCGGCACCGAAACTTGAACCACACCAAACAGCG TCTCCTGGAAGTCGACAACTACGTGGACCAGCTTCTCAGGACTCTGGACATTCAGGTGGCGCTGACCG GCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACGCCAACGCCACGCTCTGGGCC TTCCTGCAGTGGCGCCGGGGACTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGCTGCTCACGGGCCG CGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCTCGGGAG GCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCAC AGCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGT CATGGCTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCG CCTTCTTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCG GCGCTCTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCG CGACCTCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCT GCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCCGCCAGGCCATGGGTGACTGTGACCTCCCT GAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGACGTTTACCTACTCGAG
NOV14e, 249356906 SEQ ID NO: 158 426 aa MW at 46516.2kD Protein Sequence
KLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDSWWLCTCSGMSGLITLSRN ASYYLRPWPPRGSKDFSTHEIFRMEQLLT KGTCGHRDPGNKAGMTSLPGGPQSRGRREARRTRKYLE LYIVADHTLFLTRHRNLNHTKQRLLEVDNYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWA FLQWRRGL AQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGH SLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPP ALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCRQAMGDCDLP EFCTGTSSHCPPDVYLLE
NOV14f, CG50367-02 SEQ ID NO: 159 2705 bp DNA Sequence ORF Start: ATG at 3 ORF Stop: TGA at 2688
CTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTC TGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGT CCTGGATGGACAACCCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGG TGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCA GGATACATAGAAACCCACTACGGCCCAGATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCA TTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCGACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGA TGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATCTGCGTCCCTGGCCACCCCGGGGCTCC AAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCA CAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAG AAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGACTCGG CACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAG GACTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCA CGCAGGACGCCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCC CACGACTCCGCGCAGCTGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGA GGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCG CAGCCACCATGGCCCATGAGATCGGCCACAGCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTG GAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTT CAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATG CCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAG TGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCC GGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCC GCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGAC GTTTACCTACTGGACGGCTCACCCTGTGCCAAGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCAC GCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGG TGGTGAACTCTGCGGGAGATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGT GCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCA CATGGTGCCAGTGGACTCTACCGTTCACCTAGATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCAC TCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGGTAGAGCCAGGCACCCAGTGTGGACCTAGA ATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGCTTCAGCGCTGCCTGACTGCCTG CCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCTGGGCTCCACCCTTCT GTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATGACACCTTC CTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGCGCCGGCCTGGCCTGGTGTTGCTA CCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCC CCAAAGATGGCCCACACAGAGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCC ACTGGACAGCCCTGGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCT GCCAGCAGTCTCGCCTGACCCCCAAGGTGGTTCCCTTGCAGCCTGGGGCCCCAGTCCTTTAGGGGACA ACATATCCTCCTCATTCTCAGCAGATCAAGTCCAGATGCCAAGATCCTGCCTCTGTGGCGAACCCTGG GGAGGCCACGTGGGAAGGAAAGAGGGCTCTAAGAGGGGAGGCCCCAGACTGGGGGAGAGGCCTGTCTG GAGCCCAGGATCACCTGGCTGTGCTGCAGAACTGGAGAAGAGAAGCTCAGCAGAAAGGAGCTGGCATG GGGCCAACAGCAGAAAAGCAGGAGGCACGCAGAAGTGACTGGGAAGCAGGAGG
NOV14f, CG50367-02 SEQ ID NO: 160 895 aa MWat96021.0kD Protein Sequence
MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAΈGQELLLELEKNHRLLAPGYIETHYGPDGQPVVLAPNHTDHCHYQGRVRGFPDS VVLCTCSGM SGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVT QDANATLWAFLQWRRGLWAQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCR QAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYCWDGACPTLEQQCQQLWGPGSHPAPEACFQV VNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEV CRGALAL PSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSNHNCHCAPGWAPPFC DKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCSWGCRRDPACSGP KDGPHRDHPLGGVHPMELGPTATGQPWPLDPENSHEPSSHPEKPLPAVSPDPQGGSLAA GPSPLGDN ISSSFSADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEKRSSAERSWHG ANSRKAGGTQK
NOV14g, CG50367-03 SEQ ID NO: 161 2642 bp DNA Sequence ORF Start: ATG at 3 ORF Stop: TGA at 2625
CTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTC TGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGT CCTGGATGGACAACCCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGG TGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCA GGATACATAGAAACCCACTACGGCCCAGATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCA TTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCGACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGA TGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATCTGCGTCCCTGGCCACCCCGGGGCTCC AAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCA CAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAG AAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGACTCGG CACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAG GACTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCA CGCAGGACGCCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCC CACGACTCCGCGCAGCTGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGA GGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCG CAGCCACCATGGCCCATGAGATCGGCCACAGCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTG GAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTT CAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATG CCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAG TGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCC GGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCC GCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGAC GTTTACCTACTGGACGGCTCACCCTGTGCCAAGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCAC GCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGG TGGTGAACTCTGCGGGAGATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGT GCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCA CATGGTGCCAGTGGACTCTACCGTTCACCTAGATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCAC TCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGGTAGAGCCAGGCACCCAGTGTGGACCTAGA ATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGCTTCAGCGCTGCCTGACTGCCTG CCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCTGGGCTCCACCCTTCT GTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATGACACCTTC CTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGCGCCGGCCTGGCCTGGTGTTGCTA CCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCC CCAAAGATGGCCCACACAGAGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCC ACTGGACAGCCCTGGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCT GCCAGCAGTCTCGCCTGACCCCCAAGCAGATCAAGTCCAGATGCCAAGATCCTGCCTCTGTGGCGAAC CCTGGGGAGGCCACGTGGGAAGGAAAGAGGGCTCTAAGAGGGGAGGCCCCAGACTGGGGGAGAGGCCT GTCTGGAGCCCAGGATCACCTGGCTGTGCTGCAGAACTGGAGAAGAGAAGCTCAGCAGAAAGGAGCTG GCATGGGGCCAACAGCAGAAAAGCAGGAGGCACGCAGAAGTGACTGGGAAGCAGGAGG
NOV14g, CG50367-03 SEO ID NO: 162 874 aa MW at 94031.9kD
Protein Sequence
MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDS WLCTCSGM SGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEV TERDRSRVT QDANATLWAFLQ RRGL AQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCR QAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYC DGACPTLEQQCQQLWGPGSHPAPEACFQV VNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEVTCRGALAL PSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSNHNCHCAPG APPFC DKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCS GCRRDPACSGP KDGPHRDHPLGGVHPMELGPTATGQPWPLDPENSHEPSSHPEKPLPAVSPDPQADQVQMPRSCLCGEP GGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEKRSSAERS HGANSRKAGGTQK
NOV14h, CG50367-04 SEQ ID NO: 163 3468 bp DNA Sequence ORF Start: ATG at 37 ORF Stop: TGA at 2473
GCGAGCCGCTGCCTAGAGGCCGAGGAGCTCACAGCTATGGGCTGGAGGCCCCGGAGAGCTCGGGGGAC CCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAGTGCCAGGCGCCGGGGTGCTTCAAGGAC ATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAACCCTGGCGCACCGTCAGCCTG GAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCCAGGAGCTCCTGCT TGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAGATGGGC AGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCC GACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAG CTATTATCTGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGG AGCAGCTGCTCACCTGGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGC CTTCCTGGTGGTCCCCAGAGCAGGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTA CATTGTGGCAGACCACACCCTGTTCTTGACTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCC TGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGACTCTGGACATTCAGGTGGCGCTGACCGGCCTG GAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACGCCAACGCCACGCTCTGGGCCTTCCT GCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGCTGCTCACGGGCCGCGCCT TCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCTCGGGAGGCGTG AGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACAGCCT CGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGG CTGCGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTC TTCCGCAAGGGGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCT CTGCGGGAACGGCTTCGTGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACC TCTGCTGCTTTGCTCACAACTGCTCGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTG CGCTGCCTGCTGAAGCCGGCTGGAGCGCTGTGCCGCCAGGCCATGGGTGACTGTGACCTCCCTGAGTT TTGCACGGGCACCTCCTCCCACTGTCCCCCAGACGTTTACCTACTGGACGGCTCACCCTGTGCCAGGG GCAGTGGCTACTGCTGGGATGGCGCATGTCCCACGCTGGAGCAGCAGTGCCAGCAGCTCTGGGGGCCT GGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAGATGCTCATGGAAACTG CGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGAAGCTGCAGT GCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAGAT GGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGG CCTGGTAGAGCCAGGCACCCAGTGTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATG CCTTCCAGGAGCTTCAGCGCTGCCTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAAC TGCCACTGTGCTCCAGGCTGGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAG TGGCCCTGTGCAGGCTGAAAACCATGACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTC TGCTCCCAGGGGCCGGCCTGGCCTGGTGTTGCTACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGC TGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCCCCAAAGATGGCCCACACAGGGACCACCCCCTGGG CGGCGTTCACCCCATGGAGTTGGGCCCCACAGCCACTGGACAGCCCTGGCCCCTGGACCCTGAGAACT CTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCTGACCCCCAAGATCAAGTC CAGATGCCAAGATCCTGCCTCTGGTGAGAGGTAGCTCCTAAAATGAACAGATTTAAAGACAGGTGGCC
ACTGACAGCCACTCCAGGAACTTGAACTGCAGGGGCAGAGCCAGTGAATCACCGGACCTCCAGCACCT
GCAGGCAGCTTGGAAGTTTCTTCCCCGAGTGGAGCTTCGACCCACCCACTCCAGGAACCCAGAGCCAC
ATTAGAAGTTCCTGAGGGCTGGAGAACACTGCTGGGCACACTCTCCAGCTCAATAAACCATCAGTCCC
AGAAGCAAAGGTCACACAGCCCCTGACCTCCCTCACCAGTGGAGGCTGGGTAGTGCTGGCCATCCCAA
AAGGGCTCTGTCCTGGGAGTCTGGTGTGTCTCCTACATGCAATTTCCACGGACCCAGCTCTGTGGAGG
GCATGACTGCTGGCCAGAAGCTAGTGGTCCTGGGGCCCTATGGTTCGACTGAGTCCACACTCCCCTGG
AGCCTGGCTGGCCTCTGCAAACAAACATAATTTTGGGGACCTTCCTTCCTGTTTCTTCCCACCCTGTC
TTCTCCCCTAGGTGGTTCCTGAGCCCCCACCCCCAATCCCAGTGCTACACCTGAGGTTCTGGAGCTCA!
GAATCTGACAGCCTCTCCCCCATTCTGTGTGTGTCGGGGGGACAGAGGGAACCATTTAAGAAAAGATA!
CCAAAGTAGAAGTCAAAAGAAAGACATGTTGGCTATAGGCGTGGTGGCTCATGCCTATAATCCCAGCA
CTTTGGGAAGCCGGGGTAGGAGGATCACCAGAGGCCAGCAGGTCCACACCAGCCTGGGCAACACAGCA;
AGACACCGCATCTACAGAAAAATTTTAAAATTAGCTGGGCGTGGTGGTGTGTACCTGTAGGCCTAGCT!
GCTCAGGAGGCTGAAGCAGGAGGATCACTTGAGCCTGAGTTCAACACTGCAGTGAGCTATGGTGGCAC
CACTGCACTCCAGCCTGGGTGACAGAGCAAGACCCTGTCTCTAAAATAAATTTTAAAAAGACATATTA
NOVHh, CG50367-04 SEQ ID NO: 164 812 aa MW at 87666.9kD Protein Sequence
MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLV ALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRVRGFPDSWWLCTCSGM SGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRRE ARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVT QDANATLWAFLQWRRGLWAQRPHDSAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAA ATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNA PDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCR QAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYC DGACPTLEQQCQQL GPGSHPAPEACFQV VNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEVTCRGALAL PSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSNHNCHCAPGWAPPFC DKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCS GCRRDPACSGP KDGPHRDHPLGGVHPMELGPTATGQPWPLDPENSHEPSSHPEKPLPAVSPDPQDQVQMPRSCLW
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 14B.
Table 14B. Comparison of the NOV14 protein sequences.
NOV14a MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
NOV14b MGWRPRRARGTPLLLLLLLLLL PVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
NOV14C MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQP RTVSLEEPV
NOV14d MGWRPRRARGTPLLLLLLLLLL PVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
NOV14Θ
NOV14f MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
NOV14g MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQP RTVSLEEPV
NOV14h MG RPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
NOV14a SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14b SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14c SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14d SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14Θ KLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14f SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14g SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14h SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPWLAPNHTDHCHYQGRV
NOV14a RGFPDSWWLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLT KGTCG
NOV14b RGFPDS WLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLT KGTCG
NOV14c RGFPDSWWLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCG
NOV14d RGFPDSWWLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCG
NOV14e RGFPDSWWLCTCSGMSGLITLSRNASYYLRP PPRGSKDFSTHEIFRMEQLLTWKGTCG
NOV14f RGFPDS WLCTCSGMSGLITLSRNASYYLRP PPRGSKDFSTHEIFRMEQLLTWKGTCG
NOV14g RGFPDS WLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCG
NOV14h RGFPDS WLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLT KGTCG
NOV14a HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14b HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14C HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14d HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14e HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14f HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14g HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14h HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
NOV14a ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGLWAQRPHDSAQL
NOV14b ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQ RRGL AQRPHDSAQL
NOV14c ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQ RRGL AQRPHDSAQL
NOVl4d ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATL AFLQ RRGLWAQRPHDSAQL
NOVl4e DNYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATL AFLQWRRGL AQRPHDSAQL
NOVl4f ANYVDQLLRTLDIQVALTGLEV TERDRSRVTQDANATLWAFLQWRRGL AQRPHDSAQL
NOV14g ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGL AQRPHDSAQL NOV14h ANYVDQLLRTLDIQVALTGLEV TERDRSRVTQDANATLWAFLQ RRGLWAQRPHDSAQL
NOV14a LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOV14b LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOV14C LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOV14d LTTTRSSPSAP--QPPWPMRSATASASATTPTAAAWRLRPSPEAASWLRPPGTRFRACSA
NOV14e LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOV14f LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOVl4g LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOVl4h LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
NOV14a CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14b CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14C CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14d PAAAASCAPSSARGAALASPMPRTPDSRCRR RSAGTAS KRARSVTAALARSAA
NOVl4e CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14f CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14g CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14h CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
NOV14a GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14b GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14C GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLTFTY TAHPVPGA
NOV14d TSAALLTTARCARGPSAPTGTAACAAC
NOV14e GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14f GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14g GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14h GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKP AGA
NOV14a LCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQLWGPG
NOV14b LCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQLWGPG
NOV14C VATAGMAHVPR SSSASSSGGLAPTQLPRPVSRW
NOV14d
NOV14e LCRQAMGDCDLPEFCTGTSSHCPPDVYLLE
NOV14f LCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYC DGACPTLEQQCQQL GPG
NOV14g LCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYCWDGACPTLEQQCQQLWGPG
NOV14h LCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQLWGPG
NOV14a SHPAPEACFQWNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPV
NOVl4b SHPAPEACFQWNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPV
NOV14C
NOV14d
NOV14e
NOV14f SHPAPEACFQWNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPV
NOV14g SHPAPEACFQWNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPV
NOV14h SHPAPEACFQWNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPV
NOVl4a DSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRC
NOVl4b DSTVHLDGQEVTCRGALALPSAQLDLLGLGLVESGTQCGPRMVCN
NOVl4c
NOV14d
NOV14e
NOV14f DSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRC
NOVl g DSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRC NOV14h DSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRC
NOV14a LTACHSHGVCNSNHNCHCAPG APPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLP
NOV14b SNHNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLP
NOVl4C
NOV14d
NOV14e
NOV14f LTACHSHGVCNSNHNCHCAPG APPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLP
NOV14g LTACHSHGVCNSNHNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLP
NOV14h LTACHSHGVCNSNHNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLP
NOVl4a LLPGAGLAWCCYRLPGAHLQRCS GCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQ
NOV14b LLPGAGLAWCCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQ
NOV14C
NOV14d
NOV14Θ
NOVl4f LLPGAGLAWCCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQ
NOV14g LLPGAGLAWCCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQ
NOVl4h LLPGAGLA CCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQ
NOVl4a PWPLAPGAPADHIHNIYPPPFLPDPENSHEPSSHPEKPLPAVSPDPQGGSLAAWGPSPLG NOVl4b PWPLDP ENSHEPSSHPEKPLPAVSPDPQ NOV14C NOVl4d NOVl4e NOVl4f P PLDP- -ENSHEPSSHPEKPLPAVSPDPQGGSLAAWGPSPLG NOV14g PWPLDP- -ENSHEPSSHPEKPLPAVSPDPQ NOVl4h PWPLDP- -ENSHEPSSHPEKPLPAVSPDPQ
NOV14a DNISSSFSADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEK
NOV14b ADQVQMPRSCLW
NOV14C
NOV14d
NOV14e
NOV14f DNISSSFSADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEK
NOV14g ADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEK
NOV14h DQVQMPRSCLW
NOVl4a RSSAERSWHGANSRKAGGTQK
NOV14b
NOV14C
NOV14d
NOV14e
NOV14f RSSAERSWHGANSRKAGGTQK
NOVl4g RSSAERSWHGANSRKAGGTQK
NOV14Ϊ1
NOV14a (SEQ ID NO 150) NOV14b (SEQ ID NO 152) NOVl4C (SEQ ID NO 154) NOVl4d (SEQ ID NO 156) NOVl4e (SEQ ID NO 158) NOV14f (SEQ ID NO 160) NOVl4g (SEQ ID NO 162) NOV14h (SEQ ID NO : 164 )
Further analysis ofthe NOV 14a protein yielded the following properties shown in Table 14C.
Table 14C. Protein Sequence Properties NOV14a
SignalP analysis: Cleavage site between residues 30 and 31
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos. chg 4; neg.chg 0 H-region: length 37; peak value 11.70 PSG score: 7.30
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 5.85 possible cleavage site: between 27 and 28
>>> Seems to have a cleavable signal peptide (1 to 27)
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 28
Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -6.16 Transmembrane 702 - 718 PERIPHERAL Likelihood = 0.63 (at 126) ALOM score: -6.16 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 13 Charge difference: -5.0 C ( 0.0) - N ( 5.0) N >= C: N-terminal side will be inside
>>> membrane topology: type la (cytoplasmic tail 719 to 914)
MITDISC: discrimination of mitochondrial targeting seq R content: 4 Hyd Moment(75): 2.69 Hyd Moment(95): 8.42 G content: 6 D/E content : 1 S/T content : 2 Score: -3.80
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 19 ARG|TP
NUCDISC: discrimination of nuclear localization signals pat4: RPRR (4) at 4 pat7: PRRARGT (5) at 5 pat7: PQSRGRR (3) at 197 bipartite: none content of basic residues: 8.9% NLS Score: 0.47 KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : GWRP
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
44.4 % extracellular, including cell wall 22.2 % Golgi 22.2 % endoplasmic reticulum 11.1 % plasma membrane
>> prediction for CG50367-01 is exc (k=9) A search ofthe NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14D.
Figure imgf000274_0001
In a BLAST search of public sequence databases, the NOV 14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14E.
Figure imgf000275_0001
PFam analysis indicates that the NOVl 4a protein contains the domains shown in the Table 14F.
Figure imgf000275_0002
Example 15.
The NOV 15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.
Table 15A. NOV15 Sequence Analysis
NOV15a, CG50718-02 SEQ ID NO: 165 6881 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAA at 6859
AAAAATGTAATAAAGATGGATTTTCTTATCATTTTTCTTTTACTTTTTATTGGGACTTCAGAGACACAi
GGTAGATGTTTCCAATGTCGTTCCTGGTACTAGGTACGATATAACCATCTCTTCAATTTCTACAACAT ACACCTCACCTGTTACTAGAATAGGGGCTTCTAATGAACCAGGGCCTCCAGTCTTCCTAGCCGGGGAA AGAGTCGGATCTGCTGGGATTCTTCTGTCTTGGAATACACCACCTAATCCAAATGGAAGGATTATATC TTACATTGTCAAATATAAGGAAGTTTGTCCGTGGATGCAAACAGTATATACACAAGTCAGATCAAAGC CAGACAGTCTGGAAGTTCTTCTTACTAATCTTAATCCTGGAACAACATATGAAATTAAGGTAGCTGCT GAAAACAGTGCTGGCATTGGAGTGTTTAGTGATCCATTTCTCTTCCAAACTGCAGAAAGTGCTCCAGG AAAAGTGGTGGATTTCACAGGTGAGGCTGTCCCGTTCAGCAGTAAGCTGATGTGGTATACCTCGGCAA CCAAAAAAAAAATTACCAGCTTCAAGATTAGTGTCAAGCATAACAGAAGTGGGATAGTAGTGAAAGAA GTGTCAATCAGAGTGGAGTGCATTTTAAGTGCTTCCCTTCCTTTGCACTGCAACGAGAATAGTGAATC TTTTTTATGGAGTACAGCCAGCCCTTCTCCAACCCTTGGTAGAGTTACACCTCCATCGCGTACCACAC ATTCATCAAGCACGTTGACACAGAATGAGATCAGCTCTGTGAAAGAGCCTATCAGTTTTGTAGTGACA CACTTGAGACCTTATACAACATATCTTTTTGAAGTTTCAGCTGCTACAACTGAAGCAGGTTATATTGA TAGTACGATTGTCAGAACACCAGAATCAGTGCCTGAAGGACCACCACAAAACTGCGTAACAGGCAACA TCACAGGAAAGTCCTTTTCAATTTTATGGGACCCACCAACTATAGTAACAGGGAAATTTAGTTATAGA GTTGAATTATATGGACCATCAGCAGGTCGCATTTTGGATAACAGCACAAAAGACCTCAAGTTTGCATT CACTAACCTAACACCATTTACAATGTATGATGTCTATATTGCGGCTGAAACCAGTGCAGGGACTGGGC CCAAGTCAAATATTTCAGTATTCACTCCACCAGATGTTCCAGGGGCAGTGTTTGATTTACAACTTGCA GAGGTAGAATCCACGCAAGTAAGAATTACTTGGAAGAAACCACGACAACCAAATGGAATTATTAACCA ATACCGAGTGAAAGTGCTAGTTCCAGAGACAGGAATAATTTTGGAAAATACTTTGCTCACTGGAAATA ATGAGATAAATGACCCCATGGCTCCAGAAATTGTGAACATAGTACAGCCAATGGTAGGATTATATGAG GGTTCAGCAGAGATGTCGTCTGACCTTCACTCACTTGCTACATTTATATATAACAGCCATCCAGATAA AAACTTTCCTGCAAGGAATAGAGCTGAAGACCAGACTTCACCAGTTGTAACTACAAGGAATCAGTATA TTACTGACATTGCAGCTGAACAGCTGACTTATGTTCTTATCAGATTAAGGAGATTTTGGGCTGAGACA ATGGGGTTTTCTAGATATACAATCATGTCATCTGCAAGCAGGGACAATTTGACTTCCCCAGGCCCTTT GTCAGCCCAAAATTTCAGAGTTACACATGTTACCATAACAGAAGTATTTTTACACTGGGATCCTCCAG ATCCTGTATTTTTTCATCATTACCTTATCACTATTTTGGATGTTGAAAACCAATCCAAGAGTATTATT TTAAGGACATTAAACAGTTTGTCTCTTGTCCTTATAGGGTTAAAGAAATACACAAAATACAAAATGAG AGTGGCAGCCTCAACCCACGTTGGAGAAAGTTCTTTGTCTGAAGAAAATGACATCTTTGTGAGAACTT CAGAAGATGAACCGGAATCATCACCTCAAGATGTCGAAGTAATTGATGTTACCGCAGATGAAATAAGG TTGAAGTGGTCACCACCCGAAAAGCCCAATGGGATCATTATTGCTTATGAAGTGCTATATAAAAATAT AGATACTTTATATATGAAGAACACATCAACAACAGACATAATATTAAGGAACTTAAGACCTCACACCC TCTATAACATTTCTGTAAGGTCTTACACCAGATTTGGTCATGGCAATCAGGTATCTTCTTTACTCTCT GTAAGGACTTCGGAGTCAGTGCCTGATAGTGCACCAGAAAATATCACTTACAAAAATATTTCTTCTGG AGAGATTGAGCTATCATTCCTTCCCCCAAGTAGTCCCAATGGAATCATACAAAAATATACAATTTATC TCAAGAGAAGTAATGGAAATGAGGAAAGAACTATAAATACAACCTCTTTAACCCAAAACATTAAAGGT CTGAAGAAATATACCCAATATATCATTGAGGTGTCTGCTAGTACACTCAAAGGTGAAGGAGTTCGGAG TGCTCCCATAAGTATACTGACGGAGGAAGATGCTCCTGATTCTCCCCCTCAAGACTTCTCTGTAAAAC AGTTGTCTGGTGTCACGGTGAAGTTGTCATGGCAACCACCCCTGGAGCCAAATGGAATTATCCTTTAT TACACAGTTTATGTCTGGAGATCATCATTAAAAACTATTAATGTCACTGAAACATCATTGGAGTTATC AGATTTGGATTATAATGTTGAATACAGTGCTTATGTAACAGCTAGCACCAGATTTGGTGATGGGAAAA CAAGAAGCAATATCATTAGCTTTCAAACACCAGAGGGACCAAGCGATCCTCCCAAAGATGTTTATTAT GCAAACCTCAGTTCTTCATCAATAATTCTTTTCTGGACACCTCCTTCAAAACCTAATGGGATTATACA ATATTACTCTGTTTATTACAGAAATACTTCAGGTACTTTTATGCAGAATTTTACACTCCATGAAGTAA CCAATGACTTTGACAATATGACTGTATCCACAATTATAGATAAACTGACAATATTCAGCTACTATACA TTTTGGTTAACAGCAAGTACTTCAGTTGGAAATGGGAATAAAAGCAGTGACATCATTGAAGTATACAC AGATCAAGACGTACCTGAAGGGTTTGTTGGAAACCTGACTTACGAATCCATTTCGTCAACTGCAATAA ATGTAAGCTGGGTCCCACCGGCTCAACCAAACGGTCTAGTCTTCTACTATGTTTCACTGATCTTACAG CAGACTCCTCGCCATGTGAGACCACCTCTTGTTACATATGAGAGAAGCATATATTTTGATAATCTGGA
AAAATACACTGATTATATATTAAAAATTACTCCATCAACAGAAAAGGGATTCTCTGATACCTATACTG CCCAGCTATACATCAAGACTGAAGAAGATATCCCAGAAACTTCACCAATAATCAACACTTTTAAAAAC CTTTCCTCTACCTCAGTTCTCTTATCATGGGATCCCCCAGTAAAGCCAAATGGTGCAATAATAAGTTA TGATTTAACTTTACAAGGACCAAATGAAAATTATTCTTTCATTACTTCTGATAATTACATAATATTGG AAGAGCTTTCACCATTTACATTATATAGCTTTTTTGCTGCCGCAAGAACTAGAAAAGGACTTGGTCCT TCCAGTATTCTTTTCTTTTACACAGATGAGTCAGTGCCGTTAGCACCTCCACAAAATTTGACTTTAAT CAACTGTACTTCAGACTTTGTATGGCTGAAATGGAGCCCAAGTCCTCTTCCAGGTGGTATTGTTAAAG TATATAGTTTTAAAATTCATGAACATGAAACTGACACTATATATTATAAGAATATATCAGGATTTAAA ACTGAAGCCAAACTTGTTGGACTGGAACCAGTCAGCACCTACTCTATCCGTGTATCTGCGTTCACCAA AGTTGGAAATGGCAATCAATTTAGTAATGTAGTAAAATTCACAACCCAAGAATCAGTTCCAGATGTCG TGCAGAATATGCAGTGCATGGCAACTAGCTGGCAGTCAGTTTTAGTGAAATGGGATCCACCCAAAAAG GCAAATGGAATAATAACGCAGTATATGGTAACAGTTGAAAGGAATTCTACAAAAGTTTCTCCCCAAGA TCACATGTACACTTTCATAAAGCTTCTTGCCAATACCTCATATGTCTTTAAAGTAAGAGCTTCAACCT CAGCTGGTGAAGGTGATGAAAGCACATGCCATGTCAGCACACTACCTGAAACAGTTCCCAGTGTTCCC ACAAATATTGCTTTTTCTGATGTTCAGTCAACTAGTGCAACATTGACATGGATAAGACCTGACACTAT CCTTGGCTACTTTCAAAATTACAAAATTACCACTCAACTTCGTGCTCAAAAATGCAAAGAATGGGAAT CCGAAGAATGTGTTGAATATCAAAAAATTCAATACCTCTATGAAGCTCACTTAACTGAAGAGACAGTA TATGGATTAAAGAAATTTAGATGGTATAGATTCCAAGTGGCTGCCAGCACCAATGCTGGCTATGGCAA TGCTTCAAACTGGATTTCTACAAAAACTCTGCCTGGCCCTCCAGATGGTCCTCCTGAAAATGTTCATG TAGTAGCAACATCACCTTTTAGCATCAGCATAAGCTGGAGTGAACCTGCTGTCATTACTGGACCAACA TGTTATCTGATTGATGTCAAATCGGTAGATAATGATGAATTTAATATATCCTTCATCAAGTCAAATGA AGAAAATAAAACCATAGAAATTAAAGATTTAGAAATATTCACAAGGTATTCTGTAGTGATCACTGCAT TTACTGGGAACATTAGTGCTGCATATGTAGAAGGGAAGTCAAGTGCTGAAATGATTGTTACTACTTTA GAATCAGCCCCAAAGGACCCACCTAACAACATGACATTTCAGAAGATACCAGATGAAGTTACAAAATT TCAATTAACGTTCCTTCCTCCTTCTCAACCTAATGGAAATATCCAAGTATATCAAGCTCTGGTTTACC GAGAAGATGATCCTACTGCTGTCCAGATTCACAACCTCAGTATTATACAGAAAACCAACACATTCGTC ATTGCAATGCTAGAAGGACTAAAAGGTGGACATACATACAATATCAGTGTTTACGCAGTCAATAGTGC TGGTGCAGGTCCAAAGGTTCCGATGAGAATAACCATGGATATCAAAGCTCCAGCACGACCAAAAACCA AACCAACCCCTATTTATGATGCCACAGGAAAACTGCTTGTGACTTCAACAACAATTACAATCAGAATG CCAATATGTTACTACAGTGATGATCATGGACCAATAAAAAATGTACAAGTGCTTGTGACAGAAACAGG AGCTCAGCATGATGGAAATGTAACAAAGTGGTATGATGCATATTTTAATAAAGCAAGGCCATATTTTA CAAATGAAGGCTTTCCTAACCCTCCATGTACAGAAGGAAAGACAAAGTTTAGTGGCAATGAAGAAATC TACATCATAGGTGCTGATAATGCATGCATGATTCCTGGCAATGAAGACAAAATTTGCAATGGACCACT GAAACCAAAAAAGCAATACTTATTTAAATTTAGAGCTACAAATATTATGGGACAATTTACTGACTCTG ATTATTCTGACCCTGTTAAGACTTTAGGCGAAGGACTTTCAGAAAGAACCGTAGAGATCATTCTTTCC GTCACTTTGTGTATCCTTTCAATAATTCTCCTTGGAACAGCTATTTTTGCATTTGCAAGAATTCGACA GAAGCAGAAAGAAGGTGGCACATACTCTCCTCAGGATGCAGAAATTATTGACACTAAATTGAAGCTGG ATCAGCTCATCACAGTGGCAGACCTGGAACTGAAGGACGAGAGATTAACGCGGCCAATAAGCAAGAAA TCCTTCCTGCAACATGTTGAAGAGCTTTGCACAAACAACAACCTAAAGTTTCAAGAAGAATTTTCGGA ATTACCAAAATTTCTTCAGGATCTTTCTTCAACTGATGCTGATCTGCCTTGGAATAGAGCAAAAAACC GCTTCCCAAACATAAAACCATATAATAATAACAGAGTAAAGCTGATAGCTGACGCTAGTGTTCCAGGT TCGGATTATATTAATGCCAGCTATATTTCTGGTTATTTATGTCCAAATGAATTTATTGCTACTCAAGG TCCACTACCAGGAACAGTTGGAGATTTTTGGAGAATGGTGTGGGAAACCAGAGCAAAAACATTAGTAA TGCTAACACAGTGTTTTGAAAAAGGACGGATCAGATGCCATCAGTATTGGCCAGAGGACAACAAGCCA GTTACTGTCTTTGGAGATATAGTGATTACAAAGCTAATGGAGGATGTTCAAATAGATTGGACTATCAG GGATCTGAAAATTGAAAGGCATGGGGATTGCATGACTGTTCGACAGTGTAACTTTACTGCCTGGCCAG AGCATGGGGTTCCTGAGAACAGCGCCCCTCTAATTCACTTTGTGAAGTTGGTTCGAGCAAGCAGGGCA CATGACACCACACCTATGATTGTTCACTGCAGTGCTGGAGTTGGAAGAACTGGAGTTTTTATTGCTCT GGACCATTTAACACAACATATAAATGACCATGATTTTGTGGATATATATGGACTAGTAGCTGAACTGA
GAAGTGAAAGAATGTGCATGGTGCAGAATCTGGCACAGTATATCTTTTTACACCAGTGCATTCTGGAT CTCTTATCAAATAAGGGAAGTAATCAGCCCATCTGTTTTGTTAACTATTCAGCACTTCAGAAGATGGA CTCTTTGGACGCCATGGAAGGTGGTGATGTTGAGCTTGAATGGGAAGAAACCACTATGTAAATATTCA GACCAAAGGATAC NOVl 5a, CG50718-02 SEQ ID NO: 166 2281 aa MW at 255030.3kD Protein Sequence
MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIGASNEPGPPVFLAGERVGSA GILLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQV SKPDSLEVLLTNLNPGTTYEIKVAAENSAG IGVFSDPFLFQTAESAPGKWDFTGEAVPFSSKLMWYTSATKKKITSFKISVKHNRSGIWKEVSIRV ECILSASLPLHCNENSESFLWSTASPSPTLGRVTPPSRTTHSSSTLTQNEISSVKEPISFWTHLRPY TTYLFEVSAATTEAGYIDSTIVRTPESVPEGPPQNCVTGNITGKSFSIL DPPTIVTGKFSYRVELYG PSAGRILDNSTKDLKFAFTNLTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVEST QVRITWKKPRQPNGIINQYRVKVLVPETGIILENTLLTGNNEINDPMAPEIVNIVQPMVGLYEGSAEM SSDLHSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLTYVLIRLRRF AETMGFSR YTIMSSASRDNLTSPGPLSAQNFRVTHVTITEVFLHWDPPDPVFFHHYLITILDVENQSKSIILRTLN SLSLVLIGLKKYTKYKMRVAASTHVGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLKWSP PEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVSSLLSVRTSE SVPDSAPENITYKNISSGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTINTTSLTQNIKGLKKYT QYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGIILYYTVYV WRSSLKTINVTETSLELSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGPSDPPKDVYYANLSS SSIILFWTPPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTA STSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYYVSLILQQTPRH VRPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDIPETSPIINTFKNLSSTS VLLSWDPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFAAARTRKGLGPSSILF FYTDESVPLAPPQNLTLINCTSDFV LKWSPSPLPGGIVKVYSFKIHEHETDTIYYKNISGFKTEAKL VGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESVPDWQNMQCMATS QSVLVKWDPPKKANGII TQYMVTVERNSTKVSPQDHMYTFIKLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAF SDVQSTSATLTWIRPDTILGYFQNYKITTQLRAQKCKE ESEECVEYQKIQYLYEAHLTEETVYGLKK FRWYRFQVAASTNAGYGNASN ISTKTLPGPPDGPPENVHWATSPFSISIS SEPAVITGPTCYLID VKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEMIVTTLESAPK DPPNNMTFQKIPDEVTKFQLTFLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQKTNTFVIAMLE GLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDATGKLLVTSTTITIRMPICYY SDDHGPIKNVQVLVTETGAQHDGNVTK YDAYFNKARPYFTNEGFPNPPCTEGKTKFSGNEEI 11GA DNACMIPGNEDKICNGPLKPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERTVEIILSVTLCI LSIILLGTAIFAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLTRPISKKSFLQH VEELCTNNNLKFQEEFSELPKFLQDLSSTDADLP NRAKNRFPNIKPYNNNRVKLIADASVPGSDYIN ASYISGYLCPNEFIATQGPLPGTVGDF RMVWETRAKTLVMLTQCFEKGRIRCHQYWPEDNKPVTVFG DIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTA PEHGVPENSAPLIHFVKLVRASRAHDTTP MIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSERMCMVQNLAQYIFLHQCILDLLSNK GSNQPICFVNYSALQKMDSLDAMEGGDVELEWEETTM
NOVl 5b, CG50718-06 SEQ ID NO: 167 6900 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 6898
ATGGATTTTCTTATCATTTTTCTTTTACTTTTTATTGGGACTTCAGAGACACAGGTAGATGTTTCCAA TGTCGTTCCTGGTACTAGGTACGATATAACCATCTCTTCAATTTCTACAACATACACCTCACCTGTTA CTAGAATAGTGACAACAAATGTAACAAAACCAGGGCCTCCAGTCTTCCTAGCCGGGGAAAGAGTCGGA TCTGCTGGGATTCTTCTGTCTTGGAATACACCACCTAATCCAAATGGAAGGATTATATCTTACATTGT CAAATATAAGGAAGTTTGTCCGTGGATGCAAACAGTATATACACAAGTCAGATCAAAGCCAGACAGTC TGGAAGTTCTTCTTACTAATCTTAATCCTGGAACAACATATGAAATTAAGGTTGCTGCTGAAAACAGT GCTGGCATTGGAGTGTTTAGTGATCCATTTCTCTTCCAAACTGCAGAAAGTGCTCCAGGAAAAGTGGT GAATCTCACAGTTGAGGCCTACAACGCTTCAGCAGTTAAGCTGATTTGGTATTTACCTCGGCAACCAA ATGGCAAAATTACCAGCTTCAAGATTAGTGTCAAGCATGCCAGAAGTGGGATAGTAGTGAAAGATGTC TCAATCAGAGTAGAGGACATTTTGACTGGGAAATTGCCAGAATGCAATGAGAATAGTGAATCTTTTTT ATGGAGTACAGCCAGCCCTTCTCCAACCCTTGGTAGAGTTACACCTCCATCGCGTACCACACATTCAT CAAGCACGTTGACACAGAATGAGATCAGCTCTGTGTGGAAAGAGCCTATCAGTTTTGTAGTGACACAC TTGAGACCTTATACAACATATCTTTTTGAAGTTTCAGCTGTTACAACTGAAGCAGGTTATATTGATAG TACGATTGTCAGAACACCAGAATCAGTGCCTGAAGGACCACCACAAAACTGCGTAACAGGCAACATCA CAGGAAAGTCCTTTTCAATTTTATGGGACCCACCAACTATAGTAACAGGGAAATTTAGTTATAGAGTT GAATTATATGGACCATCAGGTCGCATTTTGGATAACAGCACAAAAGACCTCAAGTTTGCATTCACTAA CCTAACACCATTTACAATGTATGATGTCTATATTGCGGCTGAAACCAGTGCAGGGACTGGGCCCAAGT CAAATATTTCAGTATTCACTCCACCAGATGTTCCAGGGGCAGTGTTTGATTTACAACTTGCAGAGGTA GAATCCACGCAAGTAAGAATTACTTGGAAGAAACCACGACAACCAAATGGAATTATTAACCAATACCG AGTGAAAGTGCTAGTTCCAGAGACAGGAATAATTTTGGAAAATACTTTGCTCACTGGAAATAATGAGT ATATAAATGACCCCATGGCTCCAGAAATTGTGAACATAGTAGAGCCAATGGTAGGATTATATGAGGGT TCAGCAGAGATGTCGTCTGACCTTCACTCACTTGCTACATTTATATATAACAGCCATCCAGATAAAAA CTTTCCTGCAAGGAATAGAGCTGAAGACCAGACTTCACCAGTTGTAACTACAAGGAATCAGTATATTA CTGACATTGCAGCTGAACAGCTGTCTTATGTTATCAGGAGACTTGTACCTTTCACTGAGCACATGATT AGTGTATCTGCTTTCACCATCATGGGAGAAGGACCACCAACAGTTCTCAGTGTTAGGACACGTCAGCA AGTGCCAAGCTCCATTAAAATTATAAACTATAAAAATATTAGTTCTTCATCTATTTTGTTATATTGGG ATCCTCCAGAATATCCCAATGGAAAAATAACTCACTATACGATTTATGCAATGGAATTGGATACAAAC AGAGCATTCCAGATAACTACCATAGATAACAGCTTTCTCATAACAGGGTTAAAGAAATACACAAAATA CAAAATGAGAGTGGCAGCCTCAACCCACGATGGAGAAAGTTCTTTGTCTGAAGAAAATGACATCTTTG TGAGAACTTCAGAAGATGAACCGGAATCATCACCTCAAGATGTCGAAGTAATTGATGTTACCGCAGAT GAAATAAGGTTGAAGTGGTCACCACCCGAAAAGCCCAATGGGATCATTATTGCTTATGAAGTGCTATA TAAAAATATAGATACTTTATATATGAAGAACACATCAACAACAGACATAATATTAAGGAACTTAAGAC CTCACACCCTCTATAACATTTCTGTAAGGTCTTACACCAGATTTGGTCATGGCAATCAGGTATCTTCT TTACTCTCTGTAAGGACTTCGGAGACTGTGCCTGATAGTGCACCAGAAAATATCACTTACAAAAATAT TTCTTCTGGAGAGATTGAGCTATCATTCCTTCCCCCAAGTAGTCCCAATGGAATCATAAAAAAATATA CAATTTATCTCAAGAGAAGTAATGGAAATGAGGAAAGAACTATAAATACAACCTCTTTAACCCAAAAC ATTAAAGTACTGAAGAAATATACCCAATATATCATTGAGGTGTCTGCTAGTACACTGAAAGGTGAAGG AGTTCGGAGTGCTCCCATAAGTATACTGACGGAGGAAGATGCTCCTGATTCTCCCCCTCAAGACTTCT CTGTAAAACAGTTGTCTGGTGTCACGGTGAAGTTGTCATGGCAACCACCCCTGGAGCCAAATGGAATT ATCCTTTATTACACAGTTTATGTCTGGAATAGATCATCATTAAAAACTATTAATGTCACTGAAACATC ATTGGAGTTATCAGATTTGGATTATAATGTTGAATACAGTGCTTATGTAACAGCTAGCACCAGATTTG GTGATGGGAAAACAAGAAGCAATATCATTAGCTTTCAAACACCAGAGGGAGCACCAAGCGATCCTCCC AAAGATGTTTATTATGCAAACCTCAGTTCTTCATCAATAATTCTTTTCTGGACACCTCCTTCAAAACC TAATGGGATTATACAATATTACTCTGTTTATTACAGAAATACTTCAGGTACTTTTATGCAGAATTTTA CACTCCATGAAGTAACCAATGACTTTGACAATATGACTGTATCCACAATTATAGATAAACTGACAATA TTCAGCTACTATACATTTTGGTTAACAGCAAGTACTTCAGTTGGAAATGGGAATAAAAGCAGTGACAT CATTGAAGTATACACAGATCAAGACGTCCCTGAAGGGTTTGTTGGAAACCTGACTTACGAATCCATTT CGTCAACTGCAATAAATGTAAGCTGGGTCCCACCGGCTCAACCAAACGGTCTAGTCTTCTACTATGTT TCACTGATCTTACAGCAGACTCCTCGCCATGTGAGACCACCTCTTGTTACATATGAGAGAAGCATATA
TTTTGATAATCTGGAAAAATACACTGATTATATATTAAAAATTACTCCATCAACAGAAAAGGGATTCT CTGATACCTATACTGCCCAGCTATACATCAAGACTGAAGAAGATGTCCCAGAAACTTCACCAATAATC AACACTTTTAAAAACCTTTCCTCTACCTCAGTTCTCTTATCATGGGATCCCCCAGTAAAGCCAAATGG TGCAATAATAAGTTATGATTTAACTTTACAAGGACCAAATGAAAATTATTCTTTCATTACTTCTGATA ATTACATAATATTGGAAGAGCTTTCACCATTTACATTATATAGCTTTTTTGCTGCCGCAAGAACTAGA AAAGGACTTGGTCCTTCCAGTATTCTTTTCTTTTACACAGATGAGTCAGTGCCGTTAGCACCTCCACA AAATTTGACTTTAATCAACTGTACTTCAGACTTTGTATGGCTGAAATGGAGCCCAAGTCCTCTTCCAG GTGGTATTGTTAAAGTATATAGTTTTAAAATTCATGAACATGAAACTGACACTATATATTATAAGAAT ATATCAGGATTTAAAACTGAAGCCAAACTTGTTGGACTGGAACCAGTCAGCACCTACTCTATCCGTGT ATCTGCGTTCACCAAAGTTGGAAATGGCAATCAATTTAGTAATGTAGTAAAATTCACAACCCAAGAAT CAGTTCCAGATGTCGTGCAGAATATGCAGTGCATGGCAACTAGCTGGCAGTCAGTTTTAGTGAAATGG GATCCACCCAAAAAGGCAAATGGAATAATAACGCAGTATATGGTAACAGTTGAAAGGAATTCTACAAA AGTTTCTCCCCAAGATCACATGTACACTTTCATAAAGCTTCTTGCCAATACCTCATATGTCTTTAAAG TAAGAGCTTCAACCTCAGCTGGTGAAGGTGATGAAAGCACATGCCATGTCAGCACACTACCTGAAACA GTTCCCAGTGTTCCCACAAATATTGCTTTTTCTGATGTTCAGTCAACTAGTGCAACATTGACATGGAT AAGACCTGACACTATCCTTGGCTACTTTCAAAATTACAAAATTACCACTCAACTTCGTGCTCAAAAAT GCAAAGAATGGGAATCCGAAGAATGTGTTGAATATCAAAAAATTCAATACCTCTATGAAGCTCACTTA ACTGAAGAGACAGTATATGGATTAAAGAAATTTAGATGGTATAGATTCCAAGTGGCTGCCAGCACCAA TGCTGGCTATGGCAATGCTTCAAACTGGATTTCTACAAAAACTCTGCCTGGCCCTCCAGATGGTCCTC CTGAAAATGTTCATGTAGTAGCAACATCACCTTTTAGCATCAGCATAAGCTGGAGTGAACCTGCTGTC ATTACTGGACCAACATGTTATCTGATTGATGTCAAATCGGTAGATAATGATGAATTTAATATATCCTT CATCAAGTCAAATGAAGAAAATAAAACCATAGAAATTAAAGATTTAGAAATATTCACAAGGTATTCTG TAGTGATCACTGCATTTACTGGGAACATTAGTGCTGCATATGTAGAAGGGAAGTCAAGTGCTGAAATG ATTGTTACTACTTTAGAATCAGCCCCAAAGGACCCACCTAACAACATGACATTTCAGAAGATACCAGA TGAAGTTACAAAATTTCAATTAACGTCCCTTCCTCCTTCTCAACCTAATGGAAATATCCAAGTATATC AAGCTCTGGTTTACCGAGAAGATGATCCTACTGCTGTCCAGATTCACAACCTCAGTATTATACAGAAA ACCAACACATTCGTCATTGCAATGCTAGAAGGACTAAAAGGTGGACATACATACAATATCAGTGTTTA CGCAGTCAATAGTGCTGGTGCAGGTCCAAAGGTTCCGATGAGAATAACCATGGATATCAAAGCTCCAG CACGACCAAAAACCAAACCAACCCCTATTTATGATGCCACAGGAAAACTGCTTGTGACTTCAACAACA ATTACAATCAGAATGCCAATATGTTACTACAGTGATGATCATGGACCAATAAAAAATGTACAAGTGCT TGTGACAGAAACAGGAGCTCAGCATGATGGAAATGTAACAAAGTGGTATGATGCATATTTTAATAAAG CAAGGCCATATTTTACAAATGAAGGCTTTCCTAACCCTCCATGTACAGAAGGAAAGACAAAGTTTAGT GGCAATGAAGAAATCTACATCATAGGTGCTGATAATGCATGCATGATTCCTGGCAATGAAGACAAAAT TTGCAATGGACCACTGAAACCAAAAAAGCAATACTTATTTAAATTTAGAGCTACAAATATTATGGGAC AATTTACTGACTCTGATTATTCTGACCCTGTTAAGACTTTAGGCGAAGGACTTTCAGAAAGAACCCTA GAGATCATTCTTTCCGTCACTTTGTGTATCCTTTCAATAATTCTCCTTGGAACAGCTATTTTTGCATT TGCAAGAATTCGACAGAAGCAGAAAGAAGGTGGCACATACTCTCCTCAGGATGCAGAAATTATTGACA CTAAATTGAAGCTGGATCAGCTCATCACAGTGGCAGACCTGGAACTGAAGGACGAGAGATTAACGCGG TTACTTAGTTATAGAAAATCCATCAAGCCAATAAGCAAGAAATCCTTCCTGCAACATGTTGAAGAGCT TTGCACAAACAACAACCTAAAGTTTCAAGAAGAATTTTCGGAATTACCAAAATTTCTTCAGGATCTTT CTTCAACTGATGCTGATCTGCCTTGGAATAGAGCAAAAAACCGCTTCCCAAACATAAAACCATATAAT AATAACAGAGTAAAGCTGATAGCTGACGCTAGTGTTCCAGGTTCGGATTATATTAATGCCAGCTATAT TTCTGGTTATTTATGTCCAAATGAATTTATTGCTACTCAAGGTCCACTACCAGGAACAGTTGGAGATT TTTGGAGAATGGTGTGGGAAACCAGAGCAAAAACATTAGTAATGCTAACACAGTGTTTTGAAAAAGGA CGGATCAGATGCCATCAGTATTGGCCAGAGGACAACAAGCCAGTTACTGTCTTTGGAGATATAGTGAT TACAAAGCTAATGGAGGATGTTCAAATAGATTGGACTATCAGGGATCTGAAAATTGAAAGGCATGGGG ATTGCATGACTGTTCGACAGTGTAACTTTACTGCCTGGCCAGAGCATGGGGTTCCTGAGAACAGCGCC CCTCTAATTCACTTTGTGAAGTTGGTTCGAGCAAGCAGGGCACATGACACCACACCTATGATTGTTCA CTGTAGTGCTGGAGTTGGAAGAACTGGAGTTTTTATTGCTCTGGACCATTTAACACAACATATAAATG
ACCATGATTTTGTGGATATATATGGACTAGTAGCTGAACTGAGAAGTGAAAGAATGTGCATGGTGCAG AATCTGGCACAGTATATCTTTTTACACCAGTGCATTCTGGATCTCTTATCAAATAAGGGAAGTAATCA GCCCATCTGTTTTGTTAACTATTCAGCACTTCAGAAGATGGACTCTTTGGACGCCATGGAAGGTGATG TTGAGCTTGAATGGGAAGAAACCACTATGTAA
NOV15b, CG50718-06 SEQ ID NO: 168 2299 aa MW at 257243.9kD Protein Sequence
MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTKPGPPVFLAGERVG SAGILLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVAAENS AGIGVFSDPFLFQTAESAPGKWNLTVEAYNASAVKLIWYLPRQPNGKITSFKISVKHARSGIWKDV SIRVEDILTGKLPECNENSESFLWSTASPSPTLGRVTPPSRTTHSSSTLTQNEISSVWKEPISFWTH LRPYTTYLFEVSAVTTEAGYIDSTIVRTPESVPEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSYRV ELYGPSGRILDNSTKDLKFAFTNLTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEV ESTQVRITWKKPRQPNGIINQYRVKVLVPETGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEG SAEMSSDLHSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIRRLVPFTEHMI SVSAFTIMGEGPPTVLSVRTRQQVPSSIKIINYKNISSSSILLY DPPEYPNGKITHYTIYAMELDTN RAFQITTIDNSFLITGLKKYTKYKMRVAASTHDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTAD EIRLKWSPPEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVSS LLSVRTSETVPDSAPENITYKNISSGEIELSFLPPSSPNGIIKKYTIYLKRSNGNEERTINTTSLTQN IKVLKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGI ILYYTVYVWNRSSLKTINVTETSLELSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGAPSDPP KDVYYANLSSSSIILFWTPPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTI FSYYTFWLTASTSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYYV SLILQQTPRHVRPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPII NTFKNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFAAARTR KGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLK SPSPLPGGIVKVYSFKIHEHETDTIYYKN ISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESVPDWQNMQCMATSWQSVLVKW DPPKKANGIITQYMVTVERNSTKVSPQDHMYTFIKLLANTSYVFKVRASTSAGEGDESTCHVSTLPET VPSVPTNIAFSDVQSTSATLTWIRPDTILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHL TEETVYGLKKFRWYRFQVAASTNAGYGNASNWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAV ITGPTCYLIDVKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEM IVTTLESAPKDPPNNMTFQKIPDEVTKFQLTSLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQK TNTFVIAMLEGLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDATGKLLVTSTT ITIRMPICYYSDDHGPIKNVQVLVTETGAQHDGNVTKWYDAYFNKARPYFTNEGFPNPPCTEGKTKFS GNEEIYIIGADNACMIPGNEDKICNGPLKPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERTL EIILSVTLCILSIILLGTAIFAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLTR LLSYRKSIKPISKKSFLQHVEELCTNNNLKFQEEFSELPKFLQDLSSTDADLP NRAKNRFPNIKPYN NNRVKLIADASVPGSDYINASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKG RIRCHQYWPEDNKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPENSA PLIHFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSERMCMVQ NLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGDVELE EETTM
NOVl 5c, 258979883 SEQ ID NO: 169 2220 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AGATCTCCTGAAGGACCACCACAAAACTGCGTAACAGGCAACATCACAGGAAAGTCCTTTTCAATTTT ATGGGACCCACCAACTATAGTAACAGGGAAATTTAGTTATAGAGTTGAATTATATGGACCATCAGGTC GCATTTTGGATAACAGCACAAAAGACCTCAAGTTTGCATTCACTAACCTAACACCATTTACAATGTAT GATGTCTATATTGCGGCTGAAACCAGTGCAGGGACTGGGCCCAAGTCAAATATTTCAGTATTCACTCC ACCAGATGTTCCAGGGGCAGTGTTTGATTTACAACTTGCAGAGGTAGAATCCACGCAAGTAAGAATTA CTTGGAAGAAACCACGACAACCAAATGGAATTATTAACCAATACCGAGTGAAAGTGCTAGTTCCAGAG ACAGGAATAATTTTGGAAAATACTTTGCTCACTGGAAATAATGAGTATATAAATGACCCCATGGCTCC AGAAATTGTGAACATAGTAGAGCCAATGGTAGGATTATATGAGGGTTCAGCAGAGATGTCGTCTGACC TTCACTCACTTGCTACATTTATATATAACAGCCATCCAGATAAAAACTTTCCTGCAAGGAATAGAGCT GAAGACCAGACTTCACCAGTTGTAACTACAAGGAATCAGTATATTACTGACATTGCAGCTGAACAGCT GTCTTATGTTATCAGGAGACTTGTACCTTTCACTGAGCACATGATTAGTGTATCTGCTTTCACCATCA TGGGAGAAGGACCACCAACAGTTCTCAGTGTTAGGACACGTCAGCAAGTGCCAAGCTCCATTAAAATT ATAAACTATAAAAATATTAGTTCTTCATCTATTTTGTTATATTGGGATCCTCCAGAATATCCCAATGG AAAAATAACTCACTATACGATTTATGCAATGGAATTGGATACAAACAGAGCATTCCAGATAACTACCA TAGATAACAGCTTTCTCATAACAGGGTTAAAGAAATACACAAAATACAAAATGAGAGTGGCAGCCTCA ACCCACGATGGAGAAAGTTCTTTGTCTGAAGAAAATGACATCTTTGTGAGAACTTCAGAAGATGAACC GGAATCATCACCTCAAGATGTCGAAGTAATTGATGTTACCGCAGATGAAATAAGGTTGAAGTGGTCAC CACCCGAAAAGCCCAATGGGATCATTATTGCTTATGAAGTGCTATATAAAAATATAGATACTTTATAT ATGAAGAACACATCAACAACAGACATAATATTAAGGAACTTAAGACCTCACACCCTCTATAACATTTC TGTAAGGTCTTACACCAGATTTGGTCATGGCAATCAGGTATCTTCTTTACTCTCTGTAAGGACTTCGG AGACTGTGCCTGATAGTGCACCAGAAAATATCACTTACAAAAATATTTCTTCTGGAGAGATTGAGCTA TCATTCCTTCCCCCAAGTAGTCCCAATGGAATCATAAAAAAATATACAATTTATCTCAAGAGAAGTAA TGGAAATGAGGAAAGAACTATAAATACAACCTCTTTAACCCAAAACATTAAAGTACTGAAGAAATATA CCCAATATATCATTGAGGTGTCTGCTAGTACACTGAAAGGTGAAGGAGTTCGGAGTGCTCCCATAAGT ATACTGACGGAGGAAGATGCTCCTGATTCTCCCCCTCAAGACTTCTCTGTAAAACAGTTGTCTGGTGT CACGGTGAAGTTGTCATGGCAACCACCCCTGGAGCCAAATGGAATTATCCTTTATTACACAGTTTATG TCTGGAATAGATCATCATTAAAAACTATTAATGTCACTGAAACATCATTGGAGTTATCAGATTTGGAT TATAATGTTGAATACAGTGCTTATGTAACAGCTAGCACCAGATTTGGTGATGGGAAAACAAGAAGCAA TATCATTAGCTTTCAAACACCAGAGGGAGCACCAAGCGATCCTCCCAAAGATGTTTATTATGCAAACC TCAGTTCTTCATCAATAATTCTTTTCTGGACACCTCCTTCAAAACCTAATGGGATTATACAATATTAC TCTGTTTATTACAGAAATACTTCAGGTACTTTTATGCAGAATTTTACACTCCATGAAGTAACCAATGA CTTTGACAATATGACTGTATCCACAATTATAGATAAACTGACAATATTCAGCTACTATACATTTTGGT TAACAGCAAGTACTTCAGTTGGAAATGGGAATAAAAGCCTCGAG
NOVl 5c, 258979883 SEQ ID NO: 170 740 aa MW at 82862.3kD Protein Sequence
RSPEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSYRVELYGPSGRILDNSTKDLKFAFTNLTPFTMY DVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVESTQVRITWKKPRQPNGIINQYRVKVLVPE TGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLATFIYNSHPDKNFPARNRA EDQTSPWTTRNQYITDIAAEQLSYVIRRLVPFTEHMISVSAFTI GEGPPTVLSVRTRQQVPSSIKI INYKNISSSSILLYWDPPEYPNGKITHYTIYAMELDTNRAFQITTIDNSFLITGLKKYTKYKMRVAAS THDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLK SPPEKPNGIIIAYEVLYKNIDTLY MKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVSSLLSVRTSETVPDSAPENITYKNISSGEIEL SFLPPSSPNGIIKKYTIYLKRSNGNEERTINTTSLTQNIKVLKKYTQYIIEVSASTLKGEGVRSAPIS ILTEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGIILYYTVYV NRSSLKTINVTETSLELSDLD YNVEYSAYVTASTRFGDGKTRSNIISFQTPEGAPSDPPKDVYYANLSSSSIILFWTPPSKPNGIIQYY SVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTASTSVGNGNKSLE
NOV15d, CG50718-01 SEQ ID NO: 171 6994 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAA at 6874
TGATTCTACTGGCTGAAAAATGTAATAAAGATGGATTTTCTTATCATTTTTCTTTTACTTTTTATTGG GACTTCAGAGACACAGGTAGATGTTTCCAATGTCGTTCCTGGTACTAGGTACGATATAACCATCTCTT CAATTTCTACAACATACACCTCACCTGTTACTAGAATAGGGGCTTCTAATGAACCAGGGCCTCCAGTC TTCCTAGCCGGGGAAAGAGTCGGATCTGCTGGGATTCTTCTGTCTTGGAATACACCACCTAATCCAAA TGGAAGGATTATATCTTACATTGTCAAATATAAGGAAGTTTGTCCGTGGATGCAAACAGTATATACAC AAGTCAGATCAAAGCCAGACAGTCTGGAAGTTCTTCTTACTAATCTTAATCCTGGAACAACATATGAA ATTAAGGTAGCTGCTGAAAACAGTGCTGGCATTGGAGTGTTTAGTGATCCATTTCTCTTCCAAACTGC AGAAAGTGCTCCAGGAAAAGTGGTGGATTTCACAGGTGAGGCTGTCCCGTTCAGCAGTAAGCTGATGT GGTATACCTCGGCAACCAAAAAAAAAATTACCAGCTTCAAGATTAGTGTCAAGCATAACAGAAGTGGG ATAGTAGTGAAAGAAGTGTCAATCAGAGTGGAGTGCATTTTAAGTGCTTCCCTTCCTTTGCACTGCAA CGAGAATAGTGAATCTTTTTTATGGAGTACAGCCAGCCCTTCTCCAACCCTTGGTAGAGTTACACCTC CATCGCGTACCACACATTCATCAAGCACGTTGACACAGAATGAGATCAGCTCTGTGAAAGAGCCTATC AGTTTTGTAGTGACACACTTGAGACCTTATACAACATATCTTTTTGAAGTTTCAGCTGCTACAACTGA AGCAGGTTATATTGATAGTACGATTGTCAGAACACCAGAATCAGTGCCTGAAGGACCACCACAAAACT GCGTAACAGGCAACATCACAGGAAAGTCCTTTTCAATTTTATGGGACCCACCAACTATAGTAACAGGG AAATTTAGTTATAGAGTTGAATTATATGGACCATCAGCAGGTCGCATTTTGGATAACAGCACAAAAGA CCTCAAGTTTGCATTCACTAACCTAACACCATTTACAATGTATGATGTCTATATTGCGGCTGAAACCA GTGCAGGGACTGGGCCCAAGTCAAATATTTCAGTATTCACTCCACCAGATGTTCCAGGGGCAGTGTTT GATTTACAACTTGCAGAGGTAGAATCCACGCAAGTAAGAATTACTTGGAAGAAACCACGACAACCAAA TGGAATTATTAACCAATACCGAGTGAAAGTGCTAGTTCCAGAGACAGGAATAATTTTGGAAAATACTT TGCTCACTGGAAATAATGAGATAAATGACCCCATGGCTCCAGAAATTGTGAACATAGTACAGCCAATG GTAGGATTATATGAGGGTTCAGCAGAGATGTCGTCTGACCTTCACTCACTTGCTACATTTATATATAA CAGCCATCCAGATAAAAACTTTCCTGCAAGGAATAGAGCTGAAGACCAGACTTCACCAGTTGTAACTA CAAGGAATCAGTATATTACTGACATTGCAGCTGAACAGCTGACTTATGTTCTTATCAGATTAAGGAGA TTTTGGGCTGAGACAATGGGGTTTTCTAGATATACAATCATGTCATCTGCAAGCAGGGACAATTTGAC TTCCCCAGGCCCTTTGTCAGCCCAAAATTTCAGAGTTACACATGTTACCATAACAGAAGTATTTTTAC ACTGGGATCCTCCAGATCCTGTATTTTTTCATCATTACCTTATCACTATTTTGGATGTTGAAAACCAA TCCAAGAGTATTATTTTAAGGACATTAAACAGTTTGTCTCTTGTCCTTATAGGGTTAAAGAAATACAC AAAATACAAAATGAGAGTGGCAGCCTCAACCCACGTTGGAGAAAGTTCTTTGTCTGAAGAAAATGACA TCTTTGTGAGAACTTCAGAAGATGAACCGGAATCATCACCTCAAGATGTCGAAGTAATTGATGTTACC GCAGATGAAATAAGGTTGAAGTGGTCACCACCCGAAAAGCCCAATGGGATCATTATTGCTTATGAAGT GCTATATAAAAATATAGATACTTTATATATGAAGAACACATCAACAACAGACATAATATTAAGGAACT TAAGACCTCACACCCTCTATAACATTTCTGTAAGGTCTTACACCAGATTTGGTCATGGCAATCAGGTA TCTTCTTTACTCTCTGTAAGGACTTCGGAGTCAGTGCCTGATAGTGCACCAGAAAATATCACTTACAA AAATATTTCTTCTGGAGAGATTGAGCTATCATTCCTTCCCCCAAGTAGTCCCAATGGAATCATACAAA AATATACAATTTATCTCAAGAGAAGTAATGGAAATGAGGAAAGAACTATAAATACAACCTCTTTAACC CAAAACATTAAAGGTCTGAAGAAATATACCCAATATATCATTGAGGTGTCTGCTAGTACACTCAAAGG TGAAGGAGTTCGGAGTGCTCCCATAAGTATACTGACGGAGGAAGATGCTCCTGATTCTCCCCCTCAAG ACTTCTCTGTAAAACAGTTGTCTGGTGTCACGGTGAAGTTGTCATGGCAACCACCCCTGGAGCCAAAT GGAATTATCCTTTATTACACAGTTTATGTCTGGAGATCATCATTAAAAACTATTAATGTCACTGAAAC ATCATTGGAGTTATCAGATTTGGATTATAATGTTGAATACAGTGCTTATGTAACAGCTAGCACCAGAT TTGGTGATGGGAAAACAAGAAGCAATATCATTAGCTTTCAAACACCAGAGGGACCAAGCGATCCTCCC AAAGATGTTTATTATGCAAACCTCAGTTCTTCATCAATAATTCTTTTCTGGACACCTCCTTCAAAACC TAATGGGATTATACAATATTACTCTGTTTATTACAGAAATACTTCAGGTACTTTTATGCAGAATTTTA CACTCCATGAAGTAACCAATGACTTTGACAATATGACTGTATCCACAATTATAGATAAACTGACAATA TTCAGCTACTATACATTTTGGTTAACAGCAAGTACTTCAGTTGGAAATGGGAATAAAAGCAGTGACAT CATTGAAGTATACACAGATCAAGACGTACCTGAAGGGTTTGTTGGAAACCTGACTTACGAATCCATTT CGTCAACTGCAATAAATGTAAGCTGGGTCCCACCGGCTCAACCAAACGGTCTAGTCTTCTACTATGTT TCACTGATCTTACAGCAGACTCCTCGCCATGTGAGACCACCTCTTGTTACATATGAGAGAAGCATATA
TTTTGATAATCTGGAAAAATACACTGATTATATATTAAAAATTACTCCATCAACAGAAAAGGGATTCT CTGATACCTATACTGCCCAGCTATACATCAAGACTGAAGAAGATATCCCAGAAACTTCACCAATAATC AACACTTTTAAAAACCTTTCCTCTACCTCAGTTCTCTTATCATGGGATCCCCCAGTAAAGCCAAATGG TGCAATAATAAGTTATGATTTAACTTTACAAGGACCAAATGAAAATTATTCTTTCATTACTTCTGATA ATTACATAATATTGGAAGAGCTTTCACCATTTACATTATATAGCTTTTTTGCTGCCGCAAGAACTAGA AAAGGACTTGGTCCTTCCAGTATTCTTTTCTTTTACACAGATGAGTCAGTGCCGTTAGCACCTCCACA AAATTTGACTTTAATCAACTGTACTTCAGACTTTGTATGGCTGAAATGGAGCCCAAGTCCTCTTCCAG GTGGTATTGTTAAAGTATATAGTTTTAAAATTCATGAACATGAAACTGACACTATATATTATAAGAAT ATATCAGGATTTAAAACTGAAGCCAAACTTGTTGGACTGGAACCAGTCAGCACCTACTCTATCCGTGT ATCTGCGTTCACCAAAGTTGGAAATGGCAATCAATTTAGTAATGTAGTAAAATTCACAACCCAAGAAT CAGTTCCAGATGTCGTGCAGAATATGCAGTGCATGGCAACTAGCTGGCAGTCAGTTTTAGTGAAATGG GATCCACCCAAAAAGGCAAATGGAATAATAACGCAGTATATGGTAACAGTTGAAAGGAATTCTACAAA AGTTTCTCCCCAAGATCACATGTACACTTTCATAAAGCTTCTTGCCAATACCTCATATGTCTTTAAAG TAAGAGCTTCAACCTCAGCTGGTGAAGGTGATGAAAGCACATGCCATGTCAGCACACTACCTGAAACA GTTCCCAGTGTTCCCACAAATATTGCTTTTTCTGATGTTCAGTCAACTAGTGCAACATTGACATGGAT AAGACCTGACACTATCCTTGGCTACTTTCAAAATTACAAAATTACCACTCAACTTCGTGCTCAAAAAT GCAAAGAATGGGAATCCGAAGAATGTGTTGAATATCAAAAAATTCAATACCTCTATGAAGCTCACTTA ACTGAAGAGACAGTATATGGATTAAAGAAATTTAGATGGTATAGATTCCAAGTGGCTGCCAGCACCAA TGCTGGCTATGGCAATGCTTCAAACTGGATTTCTACAAAAACTCTGCCTGGCCCTCCAGATGGTCCTC CTGAAAATGTTCATGTAGTAGCAACATCACCTTTTAGCATCAGCATAAGCTGGAGTGAACCTGCTGTC ATTACTGGACCAACATGTTATCTGATTGATGTCAAATCGGTAGATAATGATGAATTTAATATATCCTT CATCAAGTCAAATGAAGAAAATAAAACCATAGAAATTAAAGATTTAGAAATATTCACAAGGTATTCTG TAGTGATCACTGCATTTACTGGGAACATTAGTGCTGCATATGTAGAAGGGAAGTCAAGTGCTGAAATG ATTGTTACTACTTTAGAATCAGCCCCAAAGGACCCACCTAACAACATGACATTTCAGAAGATACCAGA TGAAGTTACAAAATTTCAATTAACGTTCCTTCCTCCTTCTCAACCTAATGGAAATATCCAAGTATATC AAGCTCTGGTTTACCGAGAAGATGATCCTACTGCTGTCCAGATTCACAACCTCAGTATTATACAGAAA ACCAACACATTCGTCATTGCAATGCTAGAAGGACTAAAAGGTGGACATACATACAATATCAGTGTTTA CGCAGTCAATAGTGCTGGTGCAGGTCCAAAGGTTCCGATGAGAATAACCATGGATATCAAAGCTCCAG CACGACCAAAAACCAAACCAACCCCTATTTATGATGCCACAGGAAAACTGCTTGTGACTTCAACAACA ATTACAATCAGAATGCCAATATGTTACTACAGTGATGATCATGGACCAATAAAAAATGTACAAGTGCT TGTGACAGAAACAGGAGCTCAGCATGATGGAAATGTAACAAAGTGGTATGATGCATATTTTAATAAAG CAAGGCCATATTTTACAAATGAAGGCTTTCCTAACCCTCCATGTACAGAAGGAAAGACAAAGTTTAGT GGCAATGAAGAAATCTACATCATAGGTGCTGATAATGCATGCATGATTCCTGGCAATGAAGACAAAAT TTGCAATGGACCACTGAAACCAAAAAAGCAATACTTATTTAAATTTAGAGCTACAAATATTATGGGAC AATTTACTGACTCTGATTATTCTGACCCTGTTAAGACTTTAGGCGAAGGACTTTCAGAAAGAACCGTA GAGATCATTCTTTCCGTCACTTTGTGTATCCTTTCAATAATTCTCCTTGGAACAGCTATTTTTGCATT TGCAAGAATTCGACAGAAGCAGAAAGAAGGTGGCACATACTCTCCTCAGGATGCAGAAATTATTGACA CTAAATTGAAGCTGGATCAGCTCATCACAGTGGCAGACCTGGAACTGAAGGACGAGAGATTAACGCGG CCAATAAGCAAGAAATCCTTCCTGCAACATGTTGAAGAGCTTTGCACAAACAACAACCTAAAGTTTCA AGAAGAATTTTCGGAATTACCAAAATTTCTTCAGGATCTTTCTTCAACTGATGCTGATCTGCCTTGGA ATAGAGCAAAAAACCGCTTCCCAAACATAAAACCATATAATAATAACAGAGTAAAGCTGATAGCTGAC GCTAGTGTTCCAGGTTCGGATTATATTAATGCCAGCTATATTTCTGGTTATTTATGTCCAAATGAATT TATTGCTACTCAAGGTCCACTACCAGGAACAGTTGGAGATTTTTGGAGAATGGTGTGGGAAACCAGAG CAAAAACATTAGTAATGCTAACACAGTGTTTTGAAAAAGGACGGATCAGATGCCATCAGTATTGGCCA GAGGACAACAAGCCAGTTACTGTCTTTGGAGATATAGTGATTACAAAGCTAATGGAGGATGTTCAAAT AGATTGGACTATCAGGGATCTGAAAATTGAAAGGCATGGGGATTGCATGACTGTTCGACAGTGTAACT TTACTGCCTGGCCAGAGCATGGGGTTCCTGAGAACAGCGCCCCTCTAATTCACTTTGTGAAGTTGGTT CGAGCAAGCAGGGCACATGACACCACACCTATGATTGTTCACTGCAGTGCTGGAGTTGGAAGAACTGG AGTTTTTATTGCTCTGGACCATTTAACACAACATATAAATGACCATGATTTTGTGGATATATATGGAC
TAGTAGCTGAACTGAGAAGTGAAAGAATGTGCATGGTGCAGAATCTGGCACAGTATATCTTTTTACAC CAGTGCATTCTGGATCTCTTATCAAATAAGGGAAGTAATCAGCCCATCTGTTTTGTTAACTATTCAGC ACTTCAGAAGATGGACTCTTTGGACGCCATGGAAGGTGGTGATGTTGAGCTTGAATGGGAAGAAACCA CTATGTAAATATTCAGACCAAAGGATACAATTGGAAGAGATTTTTAAATCCCAGGGGCCAAAGTTACC
CCCTCATTCTTCCGAATTGAAATGTGCAACCTTAAAGAAATATCTATGCTTCTCTCAC
NOVl 5d, CG50718-01 SEQ ID NO: 172 2281 aa MW at 255030.3kD Protein Sequence
MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIGASNEPGPPVFLAGERVGSA GILLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVAAENSAG IGVFSDPFLFQTAESAPGKWDFTGEAVPFSSKLM YTSATKKKITSFKISVKHNRSGIWKEVSIRV ECILSASLPLHCNENSESFL STASPSPTLGRVTPPSRTTHSSSTLTQNEISSVKEPISFWTHLRPY TTYLFEVSAATTEAGYIDSTIVRTPESVPEGPPQNCVTGNITGKSFSIL DPPTIVTGKFSYRVELYG PSAGRILDNSTKDLKFAFTNLTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVEST QVRITWKKPRQPNGIINQYRVKVLVPETGIILENTLLTGNNEINDPMAPEIVNIVQPMVGLYEGSAEM SSDLHSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLTYVLIRLRRF AETMGFSR YTIMSSASRDNLTSPGPLSAQNFRVTHVTITEVFLHWDPPDPVFFHHYLITILDVENQSKSIILRTLN SLSLVLIGLKKYTKYKMRVAASTHVGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLK SP PEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVSSLLSVRTSE SVPDSAPENITYKNISSGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTINTTSLTQNIKGLKKYT QY11EVSASTLKGEGVRSAPISILTEEDAPDSPPQDFSVKQLSGVTVKLS QPPLEPNGIILYYTVYV RSSLKTINVTETSLELSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGPSDPPKDVYYANLSS SSIILFWTPPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTF LTA STSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVS VPPAQPNGLVFYYVSLILQQTPRH VRPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDIPETSPIINTFKNLSSTS VLLS DPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFAAARTRKGLGPSSILF FYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVKVYSFKIHEHETDTIYYKNISGFKTEAKL VGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESVPDWQNMQCMATSWQSVLVKWDPPKKANGII TQYMv VERNSTKVSPQDHMYTFIKLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAF SDVQSTSATLTWIRPDTILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKK FR YRFQVAASTNAGYGNASNWISTKTLPGPPDGPPENVHWATSPFSISIS SEPAVITGPTCYLID VKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEMIVTTLESAPK DPPNNMTFQKIPDEVTKFQLTFLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQKTNTFVIAMLE GLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDATGKLLVTSTTITIRMPICYY SDDHGPIKNVQVLVTETGAQHDGNVTKWYDAYFNKARPYFTNEGFPNPPCTEGKTKFSGNEEIYIIGA DNACMIPGNEDKICNGPLKPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERTVEIILSVTLCI LSIILLGTAIFAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLTRPISKKSFLQH VEELCTNNNLKFQEEFSELPKFLQDLSSTDADLP NRAKNRFPNIKPYNNNRVKLIADASVPGSDYIN ASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKGRIRCHQYWPEDNKPVTVFG DIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPENSAPLIHFVKLVRASRAHDTTP MIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSERMCMVQNLAQYIFLHQCILDLLSNK GSNQPICFVNYSALQKMDSLDAMEGGDVELEWEETTM
NOVl 5e, CG50718-03 SEQ ID NO: 173 2739 bp DNA Sequence ORF Start: at 7 ORF Stop: at 2734
AGATCTCAGGTAGATGTTTCCAATGTCGTTCCTGGTACTAGGTACGATATAACCATCTCTTCAATTTC
TACAACATACACCTCACCTGTTACTAGAATAGTGACAACAAATGTAACAAAACCAGGGCCTCCAGTCT TCCTAGCCGGGGAAAGAGTCGGATCTGCTGGGATTCTTCTGTCTTGGAATACACCACCTAATCCAAAT GGAAGGATTATATCTTACATTGTCAAATATAAGGAAGTTTGTCCGTGGATGCAAACAGTATATACACA AGTCAGATCAAAGCCAGACAGTCTGGAAGTTCTTCTTACTAATCTTAATCCTGGAACAACATATGAAA TTAAGGTTGCTGCTGAAAACAGTGCTGGCATTGGAGTGTTTAGTGATCCATTTCTCTTCCAAACTGCA GAAAGTGCTCCAGGAAAAGTGGTGAATCTCACAGTTGAGGCCTACAACGCTTCAGCAGTTAAGCTGAT TTGGTATTTACCTCGGCAACCAAATGGCAAAATTACCAGCTTCAAGATTAGTGTCAAGCATGCCAGAA GTGGGATAGTAGTGAAAGATGTCTCAATCAGAGTAGAGGACATTTTGACTGGGAAATTGCCAGAATGC AATGAGAATAGTGAATCTTTTTTATGGAGTACAGCCAGCCCTTCTCCAACCCTTGGTAGAGTTACACC TCCATCGCGTACCACACATTCATCAAGCACGTTGACACAGAATGAGATCAGCTCTGTGTGGAAAGAGC CTATCAGTTTTGTAGTGACACACTTGAGACCTTATACAACATATCTTTTTGAAGTTTCAGCTGTTACA ACTGAAGCAGGTTATATTGATAGTACGATTGTCAGAACACCAGAATCAGTGCCTGAAGGACCACCACA AAACTGCGTAACAGGCAACATCACAGGAAAGTCCTTTTCAATTTTATGGGACCCACCAACTATAGTAA CAGGGAAATTTAGTTATAGAGTTGAATTATATGGACCATCAGGTCGCATTTTGGATAACAGCACAAAA GACCTCAAGTTTGCATTCACTAACCTAACACCATTTACAATGTATGATGTCTATATTGCGGCTGAAAC CAGTGCAGGGACTGGGCCCAAGTCAAATATTTCAGTATTCACTCCACCAGATGTTCCAGGGGCAGTGT TTGATTTACAACTTGCAGAGGTAGAATCCACGCAAGTAAGAATTACTTGGAAGAAACCACGACAACCA AATGGAATTATTAACCAATACCGAGTGAAAGTGCTAGTTCCAGAGACAGGAATAATTTTGGAAAATAC TTTGCTCACTGGAAATAATGAGTATATAAATGACCCCATGGCTCCAGAAATTGTGAACATAGTAGAGC CAATGGTAGGATTATATGAGGGTTCAGCAGAGATGTCGTCTGACCTTCACTCACTTGCTACATTTATA TATAACAGCCATCCAGATAAAAACTTTCCTGCAAGGAATAGAGCTGAAGACCAGACTTCACCAGTTGT AACTACAAGGAATCAGTATATTACTGACATTGCAGCTGAACAGCTGTCTTATGTTATCAGGAGACTTG TACCTTTCACTGAGCACATGATTAGTGTATCTGCTTTCACCATCATGGGAGAAGGACCACCAACAGTT CTCAGTGTTAGGACACGTCAGCAAGTGCCAAGCTCCATTAAAATTATAAACTATAAAAATATTAGTTC TTCATCTATTTTGTTATATTGGGATCCTCCAGAATATCCCAATGGAAAAATAACTCACTATACGATTT ATGCAATGGAATTGGATACAAACAGAGCATTCCAGATAACTACCATAGATAACAGCTTTCTCATAACA GGGTTAAAGAAATACACAAAATACAAAATGAGAGTGGCAGCCTCAACCCACGATGGAGAAAGTTCTTT GTCTGAAGAAAATGACATCTTTGTGAGAACTTCAGAAGATGAACCGGAATCATCACCTCAAGATGTCG AAGTAATTGATGTTACCGCAGATGAAATAAGGTTGAAGTGGTCACCACCCGAAAAGCCCAATGGGATC ATTATTGCTTATGAAGTGCTATATAAAAATATAGATACTTTATATATGAAGAACACATCAACAACAGA CATAATATTAAGGAACTTAAGACCTCACACCCTCTATAACATTTCTGTAAGGTCTTACACCAGATTTG GTCATGGCAATCAGGTATCTTCTTTACTCTCTGTAAGGACTTCGGAGACTGTGCCTGATAGTGCACCA GAAAATATCACTTACAAAAATATTTCTTCTGGAGAGATTGAGCTATCATTCCTTCCCCCAAGTAGTCC CAATGGAATCATACAAAAATATACAATTTATCTCAAGAGAAGTAATGGAAATGAGGAAAGAACTATAA ATACAACCTCTTTAACCCAAAACATTAAAGGACTGAAGAAATATACCCAATATATCATTGAGGTGTCT GCTAGTACACTCAAAGGTGAAGGAGTTCGGAGTGCTCCCATAAGTATACTGACGGAGGAAGATGCTCC TGATTCTCCCCCTCAAGACTTCTCTGTAAAACAGTTGTCTGGTGTCACGGTGAAGTTGTCATGGCAAC CACCCCTGGAGCCAAATGGAATTATCCTTTATTACACAGTTTATGTCTGGAATAGATCATCATTAAAA ACTATTAATGTCACTGAAACATCATTGGAGTTATCAGATTTGGATTATAATGTTGAATACAGTGCTTA TGTAACAGCTAGCCTCGAG
NOVl 5e, CG50718-03 SEQ ID NO: 174 909 aa MW at l00812.8kD Protein Sequence
QVDVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTKPGPPVFLAGERVGSAGILLS NTPPNPNGR IISYIVKYKEVCP MQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVAAENSAGIGVFSDPFLFQTAES APGKVVNLTVEAYNASAVKLIWYLPRQPNGKITSFKISVKHARSGIWKDVSIRVEDILTGKLPECNE NSESFLWSTASPSPTLGRVTPPSRTTHSSSTLTQNEISSVWKEPISFWTHLRPYTTYLFEVSAVTTE AGYIDSTIVRTPESVPEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSYRVELYGPSGRILDNSTKDL KFAFTNLTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVESTQVRIT KKPRQPNG IINQYRVKVLVPETGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLATFIYN SHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIRRLVPFTEHMISVSAFTIMGEGPPTVLS VRTRQQVPSSIKIINYKNISSSSILLYWDPPEYPNGKITHYTIYAMELDTNRAFQITTIDNSFLITGL KKYTKYKMRVAASTHDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLK SPPEKPNGIII AYEVLYKNIDTLYMKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVSSLLSVRTSETVPDSAPEN ITYKNISSGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTINTTSLTQNIKGLKKYTQYIIEVSAS TLKGEGVRSAPISILTEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWNRSSLKTI NVTETSLELSDLDYNVEYSAYVTAS
NOV15f, CG50718-04 SEQ ID NO: 175 2565 bp DNA Sequence ORF Start: at 7 ORF Stop: at 2560
AGATCTCCTGAAGGGTTTGTTGGAAACCTGACTTACGAATCCATTTCGTCAACTGCAATAAATGTAAGl
CTGGGTCCCACCGGCTCAACCAAACGGTCTAGTCTTCTACTATGTTTCACTGATCTTACAGCAGACTC CTCGCCATGTGAGACCACCTCTTGTTACATATGAGAGAAGCATATATTTTGATAATCTGGAAAAATAC ACTGATTATATATTAAAAATTACTCCATCAACAGAAAAGGGATTCTCTGATACCTATACTGCCCAGCT ATACATCAAGACTGAAGAAGATGTCCCAGAAACTTCACCAATAATCAACACTTTTAAAAACCTTTCCT CTACCTCAGTTCTCTTATCATGGGATCCCCCAGTAAAGCCAAATGGTGCAATAATAAGTTATGATTTA ACTTTACAAGGACCAAATGAAAATTATTCTTTCATTACTTCTGATAATTACATAATATTGGAAGAGCT TTCACCATTTACATTATATAGCTTTTTTGCTGCCGCAAGAACTAGAAAAGGACTTGGTCCTTCCAGTA TTCTTTTCTTTTACACAGATGAGTCAGTGCCGTTAGCACCTCCACAAAATTTGACTTTAATCAACTGT ACTTCAGACTTTGTATGGCTGAAATGGAGCCCAAGTCCTCTTCCAGGTGGTATTGTTAAAGTATATAG TTTTAAAATTCATGAACATGAAACTGACACTATATATTATAAGAATATATCAGGATTTAAAACTGAAG CCAAACTTGTTGGACTGGAACCAGTCAGCACCTACTCTATCCGTGTATCTGCGTTCACCAAAGTTGGA AATGGCAATCAATTTAGTAATGTAGTAAAATTCACAACCCAAGAATCAGTTCCAGATGTCGTGCAGAA TATGCAGTGCATGGCAACTAGCTGGCAGTCAGTTTTAGTGAAATGGGATCCACCCAAAAAGGCAAATG GAATAATAACGCAGTATATGGTAACAGTTGAAAGGAATTCTACAAAAGTTTCTCCCCAAGATCACATG TACACTTTCATAAAGCTTCTTGCCAATACCTCATATGTCTTTAAAGTAAGAGCTTCAACCTCAGCTGG TGAAGGTGATGAAAGCACATGCCATGTCAGCACACTACCTGAAACAGTTCCCAGTGTTCCCACAAATA TTGCTTTTTCTGATGTTCAGTCAACTAGTGCAACATTGACATGGATAAGACCTGACACTATCCTTGGC TACTTTCAAAATTACAAAATTACCACTCAACTTCGTGCTCAAAAATGCAAAGAATGGGAATCCGAAGA ATGTGTTGAATATCAAAAAATTCAATACCTCTATGAAGCTCACTTAACTGAAGAGACAGTATATGGAT TAAAGAAATTTAGATGGTATAGATTCCAAGTGGCTGCCAGCACCAATGCTGGCTATGGCAATGCTTCA AACTGGATTTCTACAAAAACTCTGCCTGGCCCTCCAGATGGTCCTCCTGAAAATGTTCATGTAGTAGC AACATCACCTTTTAGCATCAGCATAAGCTGGAGTGAACCTGCTGTCATTACTGGACCAACATGTTATC TGATTGATGTCAAATCGGTAGATAATGATGAATTTAATATATCCTTCATCAAGTCAAATGAAGAAAAT AAAACCATAGAAATTAAAGATTTAGAAATATTCACAAGGTATTCTGTAGTGATCACTGCATTTACTGG GAACATTAGTGCTGCATATGTAGAAGGGAAGTCAAGTGCTGAAATGATTGTTACTACTTTAGAATCAG CCCCAAAGGACCCACCTAACAACATGACATTTCAGAAGATACCAGATGAAGTTACAAAATTTCAATTA ACGTCCCTTCCTCCTTCTCAACCTAATGGAAATATCCAAGTATATCAAGCTCTGGTTTACCGAGAAGA TGATCCTACTGCTGTCCAGATTCACAACCTCAGTATTATACAGAAAACCAACACATTCGTCATTGCAA TGCTAGAAGGACTAAAAGGTGGACATACATACAATATCAGTGTTTACGCAGTCAATAGTGCTGGTGCA GGTCCAAAGGTTCCGATGAGAATAACCATGGATATCAAAGCTCCAGCACGACCAAAAACCAAACCAAC CCCTATTTATGATGCCACAGGAAAACTGCTTGTGACTTCAACAACAATTACAATCAGAATGCCAATAT GTTACTACAGTGATGATCATGGACCAATAAAAAATGTACAAGTGCTTGTGACAGAAACAGGAGCTCAG CATGATGGAAATGTAACAAAGTGGTATGATGCATATTTTAATAAAGCAAGGCCATATTTTACAAATGA AGGCTTTCCTAACCCTCCATGTACAGAAGGAAAGACAAAGTTTAGTGGCAATGAAGAAATCTACATCA TAGGTGCTGATAATGCATGCATGATTCCTGGCAATGAAGACAAAATTTGCAATGGACCACTGAAACCA AAAAAGCAATACTTATTTAAATTTAGAGCTACAAATATTATGGGACAATTTACTGACTCTGATTATTC TGACCCTGTTAAGACTTTAGGCGAAGGACTTTCAGAAAGAACCCTCGAG
NOVl 5f, CG50718-04 SEQ ID NO: 176 851 aa MW at 95001.6kD Protein Sequence
PEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYYVSLILQQTPRHVRPPLVTYERSIYFDNLEKYTD YILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPIINTFKNLSSTSVLLS DPPVKPNGAIISYDLTL QGPNENYSFITSDNYIILEELSPFTLYSFFAAARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTS DFVWLK SPSPLPGGIVKVYSFKIHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNG NQFSNVVKFTTQESVPDVVQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYT FIKLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPDTILGYF QNYKITTQLRAQKCKE ESEECVEYQKIQYLYEAHLTEETVYGLKKFR YRFQVAASTNAGYGNASNW ISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYLIDVKSVDNDEFNISFIKSNEENKT IEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEMIVTTLESAPKDPPNNMTFQKIPDEVTKFQLTS LPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQKTNTFVIAMLEGLKGGHTYNISVYAVNSAGAGP KVPMRITMDIKAPARPKTKPTPIYDATGKLLVTSTTITIRMPICYYSDDHGPIKNVQVLVTETGAQHD GNVTKYDAYFNKARPYFTNEGFPNPPCTEGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPLKPKK QYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERT
NOVl 5g, CG50718-05 SEQ ID NO: 177 6903 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 6901
ATGGATTTTCTTATCATTTTTCTTTTACTTTTTATTGGGACTTCAGAGACACAGGTAGATGTTTCCAA TGTCGTTCCTGGTACTAGGTACGATATAACCATCTCTTCAATTTCTACAACATACACCTCACCTGTTA CTAGAATAGTGACAACAAATGTAACAGAACCAGGGCCTCCAGTCTTCCTAGCCGGGGAAAGAGTCGGA TCTGCTGGGATTCTTCTGTCTTGGAATACACCACCTAATCCAAATGGAAGGATTATATCTTACATTGT CAAATATAAGGAAGTTTGTCCGTGGATGCAAACAGTATATACACAAGTCAGATCAAAGCCAGACAGTC TGGAAGTTCTTCTTACTAATCTTAATCCTGGAACAACATATGAAATTAAGGTAGCTGCTGAAAACAGT GCTGGCATTGGAGTGTTTAGTGATCCATTTCTCTTCCAAACTGCAGAAAGTCCAGCTCCAGGAAAAGT GGTGAATCTCACAGTTGAGGCCTACAACGCTTCAGCAGTTAAGCTGATTTGGTATTTACCTCGGCAAC CAAATGGCAAAATTACCAGCTTCAAGATTAGTGTCAAGCATGCCAGAAGTGGGATAGTAGTGAAAGAT GTCTCAATCAGAGTAGAGGACATTTTGACTGGGAAATTGCCAGAATGCAATGTAGAGAATAGTGAATC TTTTTTATGGAGTACAGCCAGCCCTTCTCCAACCCTTGGTAGAGTTACACCTCCATCGCGTACCACAC ATTCATCAAGCACGTTGACACAGAATGAGATCAGCTCTGTGTGGAAAGAGCCTATCAGTTTTGTAGTG ACACACTTGAGACCTTATACAACATATCTTTTTGAAGTTTCAGCTGCTACAACTGAAGCAGGTTATAT TGATAGTACGATTGTCAGAACACCAGAATCAGTGCCTGAAGGACCACCACAAAACTGCGTAACAGGCA ACATCACAGGAAAGTCCTTTTCAATTTTATGGGACCCACCAACTATAGTAACAGGGAAATTTAGTTAT AGAGTTGAATTATATGGACCATCAGGTCGCATTTTGGATAACAGCACAAAAGACCTCAAGTTTGCATT CACTAACCTAACACCATTTACAATGTATGATGTCTATATTGCGGCTGAAACCAGTGCAGGGACTGGGC CCAAGTCAAATATTTCAGTATTCACTCCACCAGATGTTCCAGGGGCAGTGTTTGATTTACAACTTGCA GAGGTAGAATCCACGCAAGTAAGAATTACTTGGAAGAAACCACGACAACCAAATGGAATTATTAACCA ATACCGAGTGAAAGTGCTAGTTCCAGAGACAGGAATAATTTTGGAAAATACTTTGCTCACTGGAAATA ATGAGATAAATGACCCCATGGCTCCAGAAATTGTGAACATAGTAGAGCCAATGGTAGGATTATATGAG GGTTCAGCAGAGATGTCGTCTGACCTTCACTCACTTGCTACATTTATATATAACAGCCATCCAGATAA AAACTTTCCTGCAAGGAATAGAGCTGAAGACCAGACTTCACCAGTTGTAACTACAAGGAATCAGTATA TTACTGACATTGCAGCTGAACAGCTGTCTTATGTTATCAGGAGACTTGTACCTTTCACTGAGCACATG ATTAGTGTATCTGCTTTCACCATCATGGGAGAAGGACCACCAACAGTTCTCAGTGTTAGGACACGTCA GCAAGTGCCAAGCTCCATTAAAATTATAAACTATAAAAATATTAGTTCTTCATCTATTTTGTTATATT GGGATCCTCCAGAATATCCCAATGGAAAAATAACTCACTATACGATTTATGCAATGGAATTGGATACA AACAGAGCATTCCAGATAACTACCATAGATAACAGCTTTCTCATAACAGGTATAGGGTTAAAGAAATA CACAAAATACAAAATGAGAGTGGCAGCCTCAACCCACGTTGGAGAAAGTTCTTTGTCTGAAGAAAATG ACATCTTTGTGAGAACTTCAGAAGATGAACCGGAATCATCACCTCAAGATGTCGAAGTAATTGATGTT ACCGCAGATGAAATAAGGTTGAAGTGGTCACCACCCGAAAAGCCCAATGGGATCATTATTGCTTATGA AGTGCTATATAAAAATATAGATACTTTATATATGAAGAACACATCAACAACAGACATAATATTAAGGA ACTTAAGACCTCACACCCTCTATAACATTTCTGTAAGGTCTTACACCAGATTTGGTCATGGCAATCAG GTATCTTCTTTACTCTCTGTAAGGACTTCGGAGACTGTGCCTGATAGTGCACCAGAAAATATCACTTA CAAAAATATTTCTTCTGGAGAGATTGAGCTATCATTCCTTCCCCCAAGTAGTCCCAATGGAATCATAC AAAAATATACAATTTATCTCAAGAGAAGTAATGGAAATGAGGAAAGAACTATAAATACAACCTCTTTA ACCCAAAACATTCTGAAGAAATATACCCAATATATCATTGAGGTGTCTGCTAGTACACTCAAAGGTGA AGGAGTTCGGAGTGCTCCCATAAGTATACTGACGGAGGAAGATGCTCCTGATTCTCCCCCTCAAGACT TCTCTGTAAAACAGTTGTCTGGTGTCACGGTGAAGTTGTCATGGCAACCACCCCTGGAGCCAAATGGA ATTATCCTTTATTACACAGTTTATGTCTGGAGGAATAGATCATCATTAAAAACTATTAATGTCACTGA AACATCATTGGAGTTATCAGATTTGGATTATAATGTTGAATACAGTGCTTATGTAACAGCTAGCACCA GATTTGGTGATGGGAAAACAAGAAGCAATATCATTAGCTTTCAAACACCAGAGGGACCAAGCGATCCT CCCAAAGATGTTTATTATGCAAACCTCAGTTCTTCATCAATAATTCTTTTCTGGACACCTCCTTCAAA ACCTAATGGGATTATACAATATTACTCTGTTTATTACAGAAATACTTCAGGTACTTTTATGCAGAATT TTACACTCCATGAAGTAACCAATGACTTTGACAATATGACTGTATCCACAATTATAGATAAACTGACA ATATTCAGCTACTATACATTTTGGTTAACAGCAAGTACTTCAGTTGGAAATGGGAATAAAAGCAGTGA CATCATTGAAGTATACACAGATCAAGACGTCCCTGAAGGGTTTGTTGGAAACCTGACTTACGAATCCA TTTCGTCAACTGCAATAAATGTAAGCTGGGTCCCACCGGCTCAACCAAACGGTCTAGTCTTCTACTAT GTTTCACTGATCTTACAGCAGACTCCTCGCCATGTGAGACCACCTCTTGTTACATATGAGAGAAGCAT
ATATTTTGATAATCTGGAAAAATACACTGATTATATATTAAAAATTACTCCATCAACAGAAAAGGGAT TCTCTGATACCTATACTGCCCAGCTATACATCAAGACTGAAGAAGATGTCCCAGAAACTTCACCAATA ATCAACACTTTTAAAAACCTTTCCTCTACCTCAGTTCTCTTATCATGGGATCCCCCAGTAAAGCCAAA TGGTGCAATAATAAGTTATGATTTAACTTTACAAGGACCAAATGAAAATTATTCTTTCATTACTTCTG ATAATTACATAATATTGGAAGAGCTTTCACCATTTACATTATATAGCTTTTTTGCTGCCGCAAGAACT AGAAAAGGACTTGGTCCTTCCAGTATTCTTTTCTTTTACACAGATGAGTCAGTGCCGTTAGCACCTCC ACAAAATTTGACTTTAATCAACTGTACTTCAGACTTTGTATGGCTGAAATGGAGCCCAAGTCCTCTTC CAGGTGGTATTGTTAAAGTATATAGTTTTAAAATTCATGAACATGAAACTGACACTATATATTATAAG AATATATCAGGATTTAAAACTGAAGCCAAACTTGTTGGACTGGAACCAGTCAGCACCTACTCTATCCG TGTATCTGCGTTCACCAAAGTTGGAAATGGCAATCAATTTAGTAATGTAGTAAAATTCACAACCCAAG AATCAGTTCCAGATGTCGTGCAGAATATGCAGTGCATGGCAACTAGCTGGCAGTCAGTTTTAGTGAAA TGGGATCCACCCAAAAAGGCAAATGGAATAATAACGCAGTATATGGTAACAGTTGAAAGGAATTCTAC AAAAGTTTCTCCCCAAGATCACATGTACACTTTCATAAAGCTTCTTGCCAATACCTCATATGTCTTTA AAGTAAGAGCTTCAACCTCAGCTGGTGAAGGTGATGAAAGCACATGCCATGTCAGCACACTACCTGAA ACAGTTCCCAGTGTTCCCACAAATATTGCTTTTTCTGATGTTCAGTCAACTAGTGCAACATTGACATG GATAAGACCTGACACTATCCTTGGCTACTTTCAAAATTACAAAATTACCACTCAACTTCGTGCTCAAA AATGCAAAGAATGGGAATCCGAAGAATGTGTTGAATATCAAAAAATTCAATACCTCTATGAAGCTCAC TTAACTGAAGAGACAGTATATGGATTAAAGAAATTTAGATGGTATAGATTCCAAGTGGCTGCCAGCAC CAATGCTGGCTATGGCAATGCTTCAAACTGGATTTCTACAAAAACTCTGCCTGGCCCTCCAGATGGTC CTCCTGAAAATGTTCATGTAGTAGCAACATCACCTTTTAGCATCAGCATAAGCTGGAGTGAACCTGCT GTCATTACTGGACCAACATGTTATCTGATTGATGTCAAATCGGTAGATAATGATGAATTTAATATATC CTTCATCAAGTCAAATGAAGAAAATAAAACCATAGAAATTAAAGATTTAGAAATATTCACAAGGTATT CTGTAGTGATCACTGCATTTACTGGGAACATTAGTGCTGCATATGTAGAAGGGAAGTCAAGTGCTGAA ATGATTGTTACTACTTTAGAATCAGCCCCAAAGGACCCACCTAACAACATGACATTTCAGAAGATACC AGATGAAGTTACAAAATTTCAATTAACGTCCCTTCCTCCTTCTCAACCTAATGGAAATATCCAAGTAT ATCAAGCTCTGGTTTACCGAGAAGATGATCCTACTGCTGTCCAGATTCACAACCTCAGTATTATACAG AAAACCAACACATTCGTCATTGCAATGCTAGAAGGACTAAAAGGTGGACATACATACAATATCAGTGT TTACGCAGTCAATAGTGCTGGTGCAGGTCCAAAGGTTCCGATGAGAATAACCATGGATATCAAAGCTC CAGCACGACCAAAAACCAAACCAACCCCTATTTATGATGCCACAGGAAAACTGCTTGTGACTTCAACA ACAATTACAATCAGAATGCCAATATGTTACTACAGTGATGATCATGGACCAATAAAAAATGTACAAGT GCTTGTGACAGAAACAGGAGCTCAGCATGATGGAAATGTAACAAAGTGGTATGATGCATATTTTAATA AAGCAAGGCCATATTTTACAAATGAAGGCTTTCCTAACCCTCCATGTACAGAAGGAAAGACAAAGTTT AGTGGCAATGAAGAAATCTACATCATAGGTGCTGATAATGCATGCATGATTCCTGGCAATGAAGACAA AATTTGCAATGGACCACTGAAACCAAAAAAGCAATACTTATTTAAATTTAGAGCTACAAATATTATGG GACAATTTACTGACTCTGATTATTCTGACCCTGTTAAGACTTTAGGCGAAGGACTTTCAGAAAGAACC CTAGAGATCATTCTTTCCGTCACTTTGTGTATCCTTTCAATAATTCTCCTTGGAACAGCTATTTTTGC ATTTGCAAGAATTCGACAGAAGCAGAAAGAAGGTGGCACATACTCTCCTCAGGATGCAGAAATTATTG ACACTAAATTGAAGCTGGATCAGCTCATCACAGTGGCAGACCTGGAACTGAAGGACGAGAGATTAACG CGGTTACTTAGTTATAGAAAATCCATCAAGCCAATAAGCAAGAAATCCTTCCTGCAACATGTTGAAGA GCTTTGCACAAACAACAACCTAAAGTTTCAAGAAGAATTTTCGGAATTACCAAAATTTCTTCAGGATC TTTCTTCAACTGATGCTGATCTGCCTTGGAATAGAGCAAAAAACCGCTTCCCAAACATAAAACCATAT AATAATAACAGAGTAAAGCTGATAGCTGACGCTAGTGTTCCAGGTTCGGATTATATTAATGCCAGCTA TATTTCTGGTTATTTATGTCCAAATGAATTTATTGCTACTCAAGGTCCACTACCAGGAACAGTTGGAG ATTTTTGGAGAATGGTGTGGGAAACCAGAGCAAAAACATTAGTAATGCTAACACAGTGTTTTGAAAAA GGACGGATCAGATGCCATCAGTATTGGCCAGAGGACAACAAGCCAGTTACTGTCTTTGGAGATATAGT GATTACAAAGCTAATGGAGGATGTTCAAATAGATTGGACTATCAGGGATCTGAAAATTGAAAGGCATG GGGATTGCATGACTGTTCGACAGTGTAACTTTACTGCCTGGCCAGAGCATGGGGTTCCTGAGAACAGC GCCCCTCTAATTCACTTTGTGAAGTTGGTTCGAGCAAGCAGGGCACATGACACCACACCTATGATTGT TCACTGTAGTGCTGGAGTTGGAAGAACTGGAGTTTTTATTGCTCTGGACCATTTAACACAACATATAA
ATGACCATGATTTTGTGGATATATATGGACTAGTAGCTGAACTGAGAAGTGAAAGAATGTGCATGGTG CAGAATCTGGCACAGTATATCTTTTTACACCAGTGCATTCTGGATCTCTTATCAAATAAGGGAAGTAA TCAGCCCATCTGTTTTGTTAACTATTCAGCACTTCAGAAGATGGACTCTTTGGACGCCATGGAAGGTG ATGTTGAGCTTGAATGGGAAGAAACCACTATGTAA
NOVl 5g, CG50718-05 SEQ ID NO: 178 2300 aa MW at 257261.9kD Protein Sequence
MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTEPGPPVFLAGERVG SAGILLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVAAENS AGIGVFSDPFLFQTAESPAPGKVVNLTVEAYNASAVKLIWYLPRQPNGKITSFKISVKHARSGIVVKD VSIRVEDILTGKLPECNVENSESFL STASPSPTLGRVTPPSRTTHSSSTLTQNEISSV KEPISFW THLRPYTTYLFEVSAATTEAGYIDSTIVRTPESVPEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSY RVELYGPSGRILDNSTKDLKFAFTNLTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLA EVESTQVRITWKKPRQPNGIINQYRVKVLVPETGIILENTLLTGNNEINDPMAPEIVNIVEPMVGLYE GSAEMSSDLHSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIRRLVPFTEHM ISVSAFTIMGEGPPTVLSVRTRQQVPSSIKIINYKNISSSSILLY DPPEYPNGKITHYTIYAMELDT NRAFQITTIDNSFLITGIGLKKYTKYKMRVAASTHVGESSLSEENDIFVRTSEDEPESSPQDVEVIDV TADEIRLK SPPEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQ VSSLLSVRTSETVPDSAPENITYKNISSGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTINTTSL TQNILKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQDFSVKQLSGVTVKLS QPPLEPNG IILYYTVYVWRNRSSLKTINVTETSLELSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGPSDP PKDVYYANLSSSSIILF TPPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLT IFSYYTF LTASTSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYY VSLILQQTPRHVRPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPI INTFKNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFAAART RKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVKVYSFKIHEHETDTIYYK NISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESVPDWQNMQCMATS QSVLVK DPPKKANGIITQYMVTVERNSTKVSPQDHMYTFIKLLANTSYVFKVRASTSAGEGDESTCHVSTLPE TVPSVPTNIAFSDVQSTSATLT IRPDTILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAH LTEETVYGLKKFRWYRFQVAASTNAGYGNASNWISTKTLPGPPDGPPENVHWATSPFSISIS SEPA VITGPTCYLIDVKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAE MIVTTLESAPKDPPNNMTFQKIPDEVTKFQLTSLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQ KTNTFVIAMLEGLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDATGKLLVTST TITIRMPICYYSDDHGPIKNVQVLVTETGAQHDGNVTKWYDAYFNKARPYFTNEGFPNPPCTEGKTKF SGNEEIYIIGADNACMIPGNEDKICNGPLKPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERT LEIILSVTLCILSIILLGTAIFAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLT RLLSYRKSIKPISKKSFLQHVEELCTNNNLKFQEEFSELPKFLQDLSSTDADLP NRAKNRFPNIKPY NNNRVKLIADASVPGSDYINASYISGYLCPNEFIATQGPLPGTVGDFWRMV ETRAKTLVMLTQCFEK GRIRCHQYWPEDNKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPENS APLIHFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSERMCMV QNLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGDVELE EETTM
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 15B.
Table 15B. Comparison of the NOV15 protein sequences.
NOV15a MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIGASNEPGPPVFL
NOV15b
NOV15C
NOV15d MDFLIIFLLLFIGTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIGASNEPGPPVFL
NOV15e
NOV15f N0V15g
NOV15a AGERVGSAGILLS NTPPNPNGRIISYIVKYKEVCP MQTVYTQVRSKPDSLEVLLTNLN
NOVl5b
NOV15C
NOV15d AGERVGSAGILLSWNTPPNPNGRIISYIVKYKEVCP MQTVYTQVRSKPDSLEVLLTNLN
NOV15e
NOVl5f
NOV15g
NOV15a PGTTYEIKVAAENSAGIGVFSDPFLFQTAESAPGKVVDFTGEAVPFSSKLM YTSATKKK
NOVl5b
NOV15C
NOV15d PGTTYEIKVAAENSAGIGVFSDPFLFQTAESAPGKVVDFTGEAVPFSSKLMWYTSATKKK
NOV15e
NOV15f
NOV15g
NOV15a ITSFKISVKHNRSGIWKEVSIRVECILSASLPLHCNENSESFLWSTASPSPTLGRVTPP
NOV15b
NOV15c
NOV15d ITSFKISVKHNRSGIWKEVSIRVECILSASLPLHCNENSESFL STASPSPTLGRVTPP
NOV15e
NOV15f
NOV15g
NOV15a SRTTHSSSTLTQNEISSVKEPISFWTHLRPYTTYLFEVSAATTEAGYIDSTIVRTPESV
NOV15b
NOV15c
NOV15d SRTTHSSSTLTQNEISSVKEPISFWTHLRPYTTYLFEVSAATTEAGYIDSTIVRTPESV
NOV15e
NOV15f
NOV15g
NOV15a PEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSYRVELYGPSAGRILDNSTKDLKFAFTN
NOV15b
NOVl5c
NOV15d PEGPPQNCVTGNITGKSFSILWDPPTIVTGKFSYRVELYGPSAGRILDNSTKDLKFAFTN
NOV15e --
NOV15f
NOVl5g
NOV15a LTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVESTQVRIT KKPRQP
NOVl5b
NOV15C
NOVl5d LTPFTMYDVYIAAETSAGTGPKSNISVFTPPDVPGAVFDLQLAEVESTQVRITWKKPRQP
NOV15e
NOVl5f
NOVl5g
NOV15a NGIINQYRVKVLVPETGIILENTLLTGNNEINDPMAPEIVNIVQPMVGLYEGSAEMSSDL
NOV15b
NOV15C
NOV15d NGIINQYRVKVLVPETGIILENTLLTGNNEINDPMAPEIVNIVQPMVGLYEGSAEMSSDL N0V15e
N0V15f
NOVl5g
NOV15a HSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLTYVLIRLRRF AETM
NOV15b
NOV15C
NOV15d HSLATFIYNSHPDKNFPARNRAEDQTSPWTTRNQYITDIAAEQLTYVLIRLRRF AETM
NOV15e
NOV15f
NOV15g
NOV15a GFSRYTIMSSASRDNLTSPGPLSAQNFRVTHVTITEVFLH DPPDPVFFHHYLITILDVE
NOV15b
NOV15C
NOV15d GFSRYTIMSSASRDNLTSPGPLSAQNFRVTHVTITEVFLHWDPPDPVFFHHYLITILDVE
NOV15e
NOV15f
NOV15g
NOV15a NQSKSIILRTLNSLSLVLIGLKKYTKYKMRVAASTHVGESSLSEENDIFVRTSEDEPESS
NOVl5b
NOV15C
NOV15d NQSKSIILRTLNSLSLVLIGLKKYTKYKMRVAASTHVGESSLSEENDIFVRTSEDEPESS
NOV15e
NOV15f
NOV15g
NOV15a PQDVEVIDVTADEIRLK SPPEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHT
NOVl5b
NOV15C
NOV15d PQDVEVIDVTADEIRLK SPPEKPNGIIIAYEVLYKNIDTLYMKNTSTTDIILRNLRPHT
NOV15e
NOV15f
NOV15g
NOV15a LYNISVRSYTRFGHGNQVSSLLSVRTSESVPDSAPENITYKNISSGEIELSFLPPSSPNG
NOV15b
NOV15C
NOV15d LYNISVRSYTRFGHGNQVSSLLSVRTSESVPDSAPENITYKNISSGEIELSFLPPSSPNG
NOV15e
NOV15f
NOVl5g
NOV15a IIQKYTIYLKRSNGNEERTINTTSLTQNIKGLKKYTQYIIEVSASTLKGEGVRSAPISIL
NOV15b
NOV15C
NOV15d IIQKYTIYLKRSNGNEERTINTTSLTQNIKGLKKYTQYIIEVSASTLKGEGVRSAPISIL
NOVl5e
NOV15f
NOV15g
NOV15a TEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWRSSLKTINVTETSLE
NOV15b MDFLIIFLLLFI NOV15C
NOV15d TEEDAPDSPPQDFSVKQLSGVTVKLSWQPPLEPNGI ILYYTVYVWRSSLKTINVTETSLE
NOV15e
NOV15f
NOV15g MDFLIIFLLLFI
NOV15a LSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGPSDPPKDVYYANLSSSSIILF T
NOV15b GTSETQVυVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTKPGPPVFLAGERVGSAGI
NOVl 5c
NOV15d LSDLDYNVEYSAYVTASTRFGDGKTRSNIISFQTPEGPSDPPKDVYYANLSSSSIILF T
NOV15e QVDVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTKPGPPVFLAGERVGSAGI
NOVl5f
NOV15g GTSETQVDVSNWPGTRYDITISSISTTYTSPVTRIVTTNVTEPGPPVFLAGERVGSAGI
NOVl5a PPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTA NOVl5b LLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVA NOVl5c NOV15d PPSKPNGIIQYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTA NOVl5e LLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVA NOVl5f NOV15g LLSWNTPPNPNGRIISYIVKYKEVCPWMQTVYTQVRSKPDSLEVLLTNLNPGTTYEIKVA
NOVl5a STSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNG NOVl5b AENSAGIGVFSDPFLFQTAES-APGKWNLTVEAYNASAVKLIWYLPRQPNGKITSFKIS NOVl5c NOVl5d STSVGNGNKSSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNG NOVl5e AENSAGIGVFSDPFLFQTAES-APGKWNLTVEAYNASAVKLIWYLPRQPNGKITSFKIS NOVl5f PEGFVGNLTYESISSTAINVSWVPPAQPNG NOV15g AENSAGIGVFSDPFLFQTAESPAPGKWNLTVEAYNASAVKLIWYLPRQPNGKITSFKIS
NOVl5a LVFYY VSLILQQTPRHVRPPLVTYERS NOVl5b VKHARSGIWKDVSIRVEDILTGKLPECNE-NSESFLWSTASPSPTLGRVTPPSRTTHSS NOVl5c NOVl5d LVFYY VSLILQQTPRHVRPPLVTYERS NOVl5e VKHARSGIWKDVSIRVEDILTGKLPECNE-NSESFLWSTASPSPTLGRVTPPSRTTHSS NOVl5f LVFYY VSLILQQTPRHVRPPLVTYERS NOV15g VKHARSGIWKDVSIRVEDILTGKLPECNVENSESFLWSTASPSPTLGRVTPPSRTTHSS
NOVl5a IYFDN LEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDIPETSPI NOVl5b STLTQNEISSVWKEPISFWTHLRPYTTYLFEVSAVTTEAGYIDSTIVRTPESVPEGPPQ NOVl5c RSPEGPPQ NOVl5d IYFDN LEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDIPETSPI NOVl5e STLTQNEISSVWKEPISFWTHLRPYTTYLFEVSAVTTEAGYIDSTIVRTPESVPEGPPQ NOVl5f IYFDN LEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPI NOV15g STLTQNEISSVWKEPISFWTHLRPYTTYLFEVSAATTEAGYIDSTIVRTPESVPEGPPQ
NOV15a INTFKNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPN-ENYSFITSDNYIILEELSPFTL NOVl5b NCVTGNITGKSFSILWDPPTIVT-GKFSYRVELYGPSGRILDNSTKDLKFAFTNLTPFTM NOVl5c NCVTGNITGKSFSILWDPPTIVT-GKFSYRVELYGPSGRILDNSTKDLKFAFTNLTPFTM NOV15d INTFKNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPN-ENYSFITSDNYIILEELSPFTL NOVl5e NCVTGNITGKSFSILWDPPTIVT-GKFSYRVELYGPSGRILDNSTKDLKFAFTNLTPFTM NOVl5f INTFKNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPN-ENYSFITSDNYIILEELSPFTL NOV15g NCVTGNITGKSFSILWDPPTIVT-GKFSYRVELYGPSGRILDNSTKDLKFAFTNLTPFTM NOV15a YSFFAAARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVK
NOV15b YDVYIAAETSAGTGPKSNISVFTPPDVPGA-VFDLQLAEVESTQVRITWKKPRQPNGIIN
NOV15C YDVYIAAETSAGTGPKSNISVFTPPDVPGA-VFDLQLAEVESTQVRITWKKPRQPNGIIN
NOV15d YSFFAAARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVK
NOV15e YDVYIAAETSAGTGPKSNISVFTPPDVPGA-VFDLQLAEVESTQVRITWKKPRQPNGIIN
NOV15f YSFFAAARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVK
NOV15g YDVYIAAETSAGTGPKSNISVFTPPDVPGA-VFDLQLAEVESTQVRITWKKPRQPNGIIN
NOVl5a VYSFKIHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFT
NOV15b QYRVKVLVPETGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLA
NOV15C QYRVKVLVPETGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLA
NOV15d VYSFKIHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFT
NOV15e QYRVKVLVPETGIILENTLLTGNNEYINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLA
NOV15f VYSFKIHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFT
NOV15g QYRVKVLVPETGIILENTLLTGNN-EINDPMAPEIVNIVEPMVGLYEGSAEMSSDLHSLA
NOV15a TQESVPDWQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYTFI
NOV15b TFIYNSHPDK NFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIR
NOV15C TFIYNSHPDK NFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIR
NOV15d TQESVPDWQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYTFI
NOV15e TFIYNSHPDK NFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIR
NOV15f TQESVPDWQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYTFI
NOV15g TFIYNSHPDK NFPARNRAEDQTSPWTTRNQYITDIAAEQLSYVIR
NOV15a KLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPD
NOV15b RLVPFTEHMISVSAFTIMGEG-PPTVLSVRTRQQVPSSIKIINYKNISSSSILLYWDPPE
NOV15C RLVPFTEHMISVSAFTIMGEG-PPTVLSVRTRQQVPSSIKIINYKNISSSSILLYWDPPE
NOV15d KLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPD
NOV15e RLVPFTEHMISVSAFTIMGEG-PPTVLSVRTRQQVPSSIKIINYKNISSSSILLYWDPPE
NOV15f KLLANTSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPD
NOV15g RLVPFTEHMISVSAFTIMGEG-PPTVLSVRTRQQVPSSIKIINYKNISSSSILLYWDPPE
NOV15a TILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKKFRWYRFQV
NOV15b YPNGKITHYTIY AMELDTNRAFQITTIDNSFLIT--GLKKYTKYKMRV
NOV15C YPNGKITHYTIY AMELDTNRAFQITTIDNSFLIT- -GLKKYTKYKMRV
NOV15d TILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKKFRWYRFQV
NOV15e YPNGKITHYTIY AMELDTNRAFQITTIDNSFLIT- -GLKKYTKYKMRV
NOV15f TILGYFQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKKFRWYRFQV
NOV15g YPNGKITHYTIY AMELDTNRAFQITTIDNSFLITGIGLKKYTKYKMRV
NOV15a AASTNAGYGNAS- -NWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYL
NOVl5b AASTHDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLKWSPPEKPNG I
NOV15C AASTHDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLKWSPPEKPNG I
NOV15d AASTNAGYGNAS- -NWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYL
NOV15e AASTHDGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLKWSPPEKPNG 1
NOV15f AASTNAGYGNAS- -NWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYL
NOV15g AASTHVGESSLSEENDIFVRTSEDEPESSPQDVEVIDVTADEIRLKWSPPEKPNG 1
NOV15a IDVKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEM
NOV15b IIAYEVLYKNIDTLYMK-NTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVS SLL
NOV15C IIAYEVLYKNIDTLYMK-NTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVS SLL
NOV15d IDVKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEM
NOVl5e 11AYEVLYKNIDTLYMK-NTSTTD11LRNLRPHTLYNISVRSYTRFGHGNQVS SLL
NOV15f IDVKSVDNDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEM NOV15g IIAYEVLYKNIDTLYMK-NTSTTDIILRNLRPHTLYNISVRSYTRFGHGNQVS SLL
NOV15a IVTTLESAPKDPPNNMTFQKIPDEVTKFQLTFLPPSQPNGNIQVYQALVYREDDPTAVQI
NOV15b SVRTSETVPDSAPENITYKNIS- -SGEIELSFLPPSSPNGIIKKYTIYLKRSNGNEERTI
NOV15C SVRTSETVPDSAPENITYKNIS--SGEIELSFLPPSSPNGIIKKYTIYLKRSNGNEERTI
NOVlδd IVTTLESAPKDPPNNMTFQKIPDEVTKFQLTFLPPSQPNGNIQVYQALVYREDDPTAVQI
NOV15e SVRTSETVPDSAPENITYKNIS- -SGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTI
NOV15f IVTTLESAPKDPPNNMTFQKIPDEVTKFQLTSLPPSQPNGNIQVYQALVYREDDPTAVQI
NOV15g SVRTSETVPDSAPENITYKNIS- -SGEIELSFLPPSSPNGIIQKYTIYLKRSNGNEERTI
NOV15a HNLSIIQKTNTFVIAMLEGLKGGHTYNISVYAVNSAG-AGPKVPMRITMDIKAP-ARPKT
NOV15b NTTSLTQNIK VLKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQD
NOV15C NTTSLTQNIK VLKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQD
NOV15d HNLSIIQKTNTFVIAMLEGLKGGHTYNISVYAVNSAG-AGPKVPMRITMDIKAP-ARPKT
NOV15e NTTSLTQNIK GLKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQD
NOV15f HNLSIIQKTNTFVIAMLEGLKGGHTYNISVYAVNSAG-AGPKVPMRITMDIKAP-ARPKT
NOV15g NTTSLTQNI LKKYTQYIIEVSASTLKGEGVRSAPISILTEEDAPDSPPQD
NOV15a KPTPIYDATGKLLVTSTTITIRMPICYYSDDHGP- -IKNVQVLVTETGAQH-DGNVTKWY
NOV15b FSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWN-RSSLKTINVTETSLELSDLDYNVEY
NOV15C FSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWN-RSSLKTINVTETSLELSDLDYNVEY
NOV15d KPTPIYDATGKLLVTSTTITIRMPICYYSDDHGP- -IKNVQVLVTETGAQH-DGNVTKWY
NOV15e FSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWN-RSSLKTINVTETSLELSDLDYNVEY
NOV15f KPTPIYDATGKLLVTSTTITIRMPICYYSDDHGP-- IKNVQVLVTETGAQH-DGNVTKWY
NOV15g FSVKQLSGVTVKLSWQPPLEPNGIILYYTVYVWRNRSSLKTINVTETSLELSDLDYNVEY
NOVlδa DAYFNKARPYFTNEGFPNPP- -CT-EGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPL
NOV15b SAYVTASTRFGDGKTRSNIISFQTPEGAPSDPPKDVYYANLSSSSIILFWTPPSKPNGII
NOV15C SAYVTASTRFGDGKTRSNIISFQTPEGAPSDPPKDVYYANLSSSSIILFWTPPSKPNGII
NOV15d DAYFNKARPYFTNEGFPNPP- -CT-EGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPL
NOV15e SAYVTAS
NOV15f DAYFNKARPYFTNEGFPNPP- -CT-EGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPL
NOV15g SAYVTASTRFGDGKTRSNIISFQTPEGP-SDPPKDVYYANLSSSSIILFWTPPSKPNGII
NOVl5a KPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERTVEIILSVTLCILSIILLGTAI NOVl5b QYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTASTSVGNGNK NOVl5c QYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTASTSVGNGNK NOV15d KPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERTVEIILSVTLCILSIILLGTAI NOVl5e NOVl5f KPKKQYLFKFRATNIMGQFTDSDYSDPVKTLGEGLSERT NOV15g QYYSVYYRNTSGTFMQNFTLHEVTNDFDNMTVSTIIDKLTIFSYYTFWLTASTSVGNGNK
NOV15a FAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLTRPISKKSFLQHVE
NOV15b SSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYYVSLILQQTPRHV
NOV15C SLE
NOV15d FAFARIRQKQKEGGTYSPQDAEIIDTKLKLDQLITVADLELKDERLTRPISKKSFLQHVE
NOVl5e
NOV15f
NOV15g SSDIIEVYTDQDVPEGFVGNLTYESISSTAINVSWVPPAQPNGLVFYYVSLILQQTPRHV
NOVl5a ELCTNNNLKFQEEFSELPKFLQDLSSTDADLPWNRAKNRFPNIKPYNNNRVKLIADASVP NOVl5b RPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPIINTF NOVl5c NOV15d ELCTNNNLKFQEEFSELPKFLQDLSSTDADLPWNRAKNRFPNIKPYNNNRVKLIADASVP N0V15e
NOV15f
NOV15g RPPLVTYERSIYFDNLEKYTDYILKITPSTEKGFSDTYTAQLYIKTEEDVPETSPIINTF
NOV15a GSDYINASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKGRIRCH
NOV15b KNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFA
NOV15C
NOV15d GSDYINASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKGRIRCH
NOV15e
NOV15f
NOV15g KNLSSTSVLLSWDPPVKPNGAIISYDLTLQGPNENYSFITSDNYIILEELSPFTLYSFFA
NOV15a QYWPEDNKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPE
NOV15b AARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVKVYSFK
NOVl5c
NOV15d QYWPEDNKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPE
NOVl5e
NOV15f
NOV15g AARTRKGLGPSSILFFYTDESVPLAPPQNLTLINCTSDFVWLKWSPSPLPGGIVKVYSFK
NOVl5a NSAPLIHFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVA
NOV15b IHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESV
NOVl5c
NOV15d NSAPLIHFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVA
NOV15e
NOV15f
NOV15g IHEHETDTIYYKNISGFKTEAKLVGLEPVSTYSIRVSAFTKVGNGNQFSNWKFTTQESV
NOV15a ELRSERMCMVQNLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGGDVEL
NOV15b PDWQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYTFIKLLAN
NOV15C
NOV15d ELRSERMCMVQNLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGGDVEL
NOV15e
NOV15f
NOV15g PDVVQNMQCMATSWQSVLVKWDPPKKANGIITQYMVTVERNSTKVSPQDHMYTFIKLLAN
NOVl5a EWEETTM
NOV15b TSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPDTILGY
NOV15C
NOV15d EWEETTM
NOV15e
NOV15f
NOV15g TSYVFKVRASTSAGEGDESTCHVSTLPETVPSVPTNIAFSDVQSTSATLTWIRPDTILGY
NOVl5a
NOV15b FQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKKFRWYRFQVAASTN
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g FQNYKITTQLRAQKCKEWESEECVEYQKIQYLYEAHLTEETVYGLKKFRWYRFQVAASTN
NOV15a
NOV15b AGYGNASNWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYLIDVKSVD NOV15C
NOV15d
NOV15e
NOV15f
NOV15g AGYGNASNWISTKTLPGPPDGPPENVHWATSPFSISISWSEPAVITGPTCYLIDVKSVD
NOVl5a
NOV15b NDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEMIVTTLES
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g NDEFNISFIKSNEENKTIEIKDLEIFTRYSWITAFTGNISAAYVEGKSSAEMIVTTLES
NOV15a
NOV15b APKDPPNNMTFQKIPDEVTKFQLTSLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQ
NOVl5c
NOV15d
NOVl5e
NOV15f
NOV15g APKDPPNNMTFQKIPDEVTKFQLTSLPPSQPNGNIQVYQALVYREDDPTAVQIHNLSIIQ
NOV15a
NOV15b KTNTFVIAMLEGLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDAT
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g KTNTFVIAMLEGLKGGHTYNISVYAVNSAGAGPKVPMRITMDIKAPARPKTKPTPIYDAT
NOV15a
NOV15b GKLLVTSTTITIRMPICYYSDDHGPIKNVQVLVTETGAQHDGNVTKWYDAYFNKARPYFT
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g GKLLVTSTTITIRMPICYYSDDHGPIKNVQVLVTETGAQHDGNVTKWYDAYFNKARPYFT
NOV15a
NOV15b NEGFPNPPCTEGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPLKPKKQYLFKFRATNI
NOV15c
NOV15d
NOV15e
NOVl5f
NOV15g NEGFPNPPCTEGKTKFSGNEEIYIIGADNACMIPGNEDKICNGPLKPKKQYLFKFRATNI
NOVl5a
NOV15b MGQFTDSDYSDPVKTLGEGLSERTLEIILSVTLCILSIILLGTAIFAFARIRQKQKEGGT
NOV15C
NOVl5d
NOV15e
NOVl5f
NOV15g MGQFTDSDYSDPVKTLGEGLSERTLEIILSVTLCILSIILLGTAIFAFARIRQKQKEGGT N0V15a
N0V15b YSPQDAEIIDTKLKLDQLITVADLELKDERLTRLLSYRKSIKPISKKSFLQHVEELCTNN
NOV15C
NOV15d
NOV15e
NOVl5f
NOV15g YSPQDAEIIDTKLKLDQLITVADLELKDERLTRLLSYRKSIKPISKKSFLQHVEELCTNN
NOV15a
NOV15b NLKFQEEFSELPKFLQDLSSTDADLPWNRAKNRFPNIKPYNNNRVKLIADASVPGSDYIN
NOVl5c
NOV15d
NOV15e
NOVl5f
NOV15g NLKFQEEFSELPKFLQDLSSTDADLPWNRAKNRFPNIKPYNNNRVKLIADASVPGSDYIN
NOV15a
NOV15b ASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKGRIRCHQYWPED
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g ASYISGYLCPNEFIATQGPLPGTVGDFWRMVWETRAKTLVMLTQCFEKGRIRCHQYWPED
NOV15a
NOV15b NKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPENSAPLI
NOV15C
NOVl5d
NOV15e
NOV15f
NOV15g NKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDCMTVRQCNFTAWPEHGVPENSAPLI
NOVl5a
NOV15b HFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSER
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g HFVKLVRASRAHDTTPMIVHCSAGVGRTGVFIALDHLTQHINDHDFVDIYGLVAELRSER
NOV15a
NOV15b MCMVQNLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGDVELEWEETTM
NOV15C
NOV15d
NOV15e
NOV15f
NOV15g MCMVQNLAQYIFLHQCILDLLSNKGSNQPICFVNYSALQKMDSLDAMEGDVELEWEETTM
NOVl5a (SEQ ID NO 166)
NOVl5b (SEQ ID NO 168)
NOVl5c (SEQ ID NO 170)
NOV15d (SEQ ID NO 172)
NOVl5e (SEQ ID NO 174)
NOVl5f (SEQ ID NO 176) N0V15g (SEQ ID NO : 178 )
Further analysis ofthe NOVl5a protein yielded the following properties shown in Table 15C.
Table 15C. Protein Sequence Properties NOV15a
SignalP analysis: Cleavage site between residues 18 and 19
PSORT π analysis:
PSG: a new signal peptide prediction method
N-region: length 2; pos. chg 0; neg.chg 1 H-region: length 13; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 2.26 possible cleavage site: between 17 and 18
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 3 INTEGRAL Likelihood = -2.55 Transmembrane 3 - 19 INTEGRAL Likelihood = -1.12 Transmembrane 605 - 621 INTEGRAL Likelihood =-10.46 Transmembrane 1894 -1910 PERIPHERAL Likelihood = 1.59 (at 2178) ALOM score: -10.46 (number of TMSs : 3)
MTOP: Prediction of membrane topology (Hartmann et al .. Center position for calculation: 10 Charge difference: -1.0 C(-1.0) - N( 0.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.60 Hyd Moment(95): 6.71 G content: 1 D/E content: 2 S/T content: 2 Score: -7.20
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: KKPR (4) at 415 pat4: KPKK (4) at 1855 pat7: PLKPKKQ (4) at 1853 bipartite: none content of basic residues: 8.8% NLS Score: 0.37 KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
56.5 % endoplasmic reticulum 26.1 % mitochondrial 17.4 % nuclear
>> prediction for CG50718 - 02 is end (k=23 )
A search ofthe NOVl 5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D.
Figure imgf000299_0001
In a BLAST search of public sequence databases, the NOVl 5a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E.
Figure imgf000300_0001
PFam analysis indicates that the NOVl 5a protein contains the domains shown in the Table 15F.
Figure imgf000301_0001
Example 16.
The NOVl 6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.
Table 16A. NOV16 Sequence Analysis
NOVlόa, CG50934-03 SEQ ID NO: 179 964 bp DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
GGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόa, CG50934-03 SEQ ID NO: 180 196 aa MW at 21256.7kD Protein Sequence
MSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRT WEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGGQEQDHLGGM RDDPECRC RPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGRRR
NOV16b, CG50934-01 SEQ ID NO: 181 1171 bp DNA Sequence ORF Start: at 187 ORF Stop: TGA at 805
ATGCTGTGGCTACTGCTCCTGACCCTCCCCTGCCTGATGGGCTCTGTGCCCAGGAACCCAGGCGAGTC
CGCCCCACCCAATGCCCCTGCTGCCCAGGACCCCCTCCTTGCCCTGCCCCGGGCTCAGAGTGCCAGCC
CTGGGGTGGGTGGGGACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCG
TCCGTCCCCCTCATGAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCG GCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGA GGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGC CTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCT CATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCG GCTGGGGTGTCATTGGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCG GAATGTCGGTGCAGGCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGG CCACAGGCCAGGTGGCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACA CTCCAGGCGTGGGCAGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGA
GCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGG
CTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGG
CCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCG
GCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTC
CCGCCGTTCCCCAGACGCTAGCTGGGGTGCAGTGGGGTCTGCATGATCCAGGAGGGCCCGTCTTCCTT
GTGGACACGCCTGCT
NOV16b, CG50934-01 SEQ ID NO: 182 206 aa MW at 22191.8kD Protein Sequence
ALGRPSSVPLMSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRH PQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG GVIGRGGQEQDHLGG MWRDDPECRCRPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGR RR
NOVlόc, CG50934-02 SEQ ID NO: 183 843 bp DNA Sequence ORF Start: ATG at 26 ORF Stop: TAG at 836
GAGGTGGAGGTTGCAGTAAGCCAAGATGGCGCCACTGCACTCTAGCCTGTTTCTGCTGAGCGGGACCA
TGAGCCCAAAAGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGTCAGC CTGAGGTTCTACAGCATGAAGAAGGGTCTGTGGGAGCCCATCTGTGGGGGCTCCCTCATCCACCCAGA GTGGGTGCTGACCGCCGCCCACTGCGTCGAGCTTGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGG TGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAG TACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCC GCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCT GCTGGGTGACCGGCTGGGGTGTCATTTGGGGACACGTTTTCCTGCTCCCGCCACCCCACCTCAGGGCA GCGGAAGGTCCAATCATGAGGACCCGAGCTTGCGAGAGGATGTATCACAAAGGCCCCACTGCCCACGT CACCATCATCAAGGCTGCCATGCCGTGTGCAGGGGCTGAGCGCCATCTCTCCCCACAGGGCGACAACG GGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTC TGCGGCCTTCGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGT CCCGCCGTTCCCCAGACGCTAGCTGGG
NOVlόc, CG50934-02 SEQ ID NO: 184 270 aa MW at 29993.6kD Protein Sequence
MAPLHSSLFLLSGTMSPKVGITGGCDVSARRHPWQVSLRFYSMKKGLWEPICGGSLIHPE VLTAAHC VELEELEACAFRVQVGQLRLYEDDQRTKVVEIVRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPV SLPSASLDVPSGKTCWVTG GVIWGHVFLLPPPHLRAAEGPIMRTRACERMYHKGPTAHVTIIIAAMP CAGAERHLSPQGDNGGPLLCRRNCTWVQVEWSWGKLCGLRYPGMYTRVTSYVSWIRQYVPPFPRR
NOVlόd, SNP13381559 of SEQ ID NO: 185 964 bp CG50934-03, DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
SNP Pos: 338 SNP Change: T to C
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGCCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
GGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόd, SNPl 3381559 of SEQ ID NO: 186! 196 aa MW at 21228.6kD CG50934-03, Protein Sequence SNP Pos: 91 SNP Change: Val to Ala
MSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPASLPSASRDVPSGKTCWVTGWGVIGRGGQEQDHLGGMWRDDPECRC RPGLQTRPG LPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGRRR
NOVlόe, SNP13381558 of SEQ ID NO: 187 964 bp CG50934-03, DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
SNP Pos: 359 SNP Change: G to T
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
GGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόe, SNP13381558 of SEQ ID NO: 188 196 aa MW at 21213.7kD CG50934-03, Protein Sequence SNP Pos: 98 SNP Change: Arg to Leu
MSPARGVS ASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGGQEQDHLGGMWRDDPECRC RPGLQTRPG LPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGRRR
NOVlόf, SNPl 3376399 of SEQ ID NO: 189 964 bp CG50934-03, DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
SNP Pos: 641 SNP Change: G to A
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTATGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
GGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόf, SNPl 3376399 of SEQ ID NO: 190 196 aa MW at 21316.7kD CG50934-03, Protein Sequence SNP Pos: 192 SNP Change: Cys to Tyr
MSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGGQEQDHLGGM RDDPECRC RPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSAYGRRR
NOVlόg, SNPl 3378301 of SEQ ID NO: 191 964 bp CG50934-03, DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
SNP Pos: 868 SNP Change: G to A
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
GGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTACGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόg, SNPl 3378301 of SEQ ID NO: 192 196 aa MW at 21256.7kD CG50934-03, Protein Sequence SNP Change: no change
MSPARGVS ASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGGQEQDHLGGMWRDDPECRC RPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGRRR
NOVlόh, SNP13378300 of SEQ ID NO: 193 964 bp CG50934-03, DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
SNP Pos: 907 SNP Change: C to T
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
AACCAGACCTGTCGCCGCCGCATTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGA
CATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCA
IGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTAT
CCCGGCATGTACACCCGCGTGATGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAG
ACGCTAGCTGGG
NOVlόh, SNPl 3378300 of SEQ ID NO: 194 196 aa MW at 21256.7kD CG50934-03, Protein Sequence SNP Change: no change
MSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGGQEQDHLGGMWRDDPECRC RPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGRRR
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 16B.
Table 16B. Comparison of the NOVl 6 protein sequences.
NOVl6a MSPARGVS WWASLGAATSRP GGTPGR--
NOV16b ALGRPSSVPLMSPARGVS WWASLGAATSRP GGTPGR--
N0V16C MAPLHSSLFLLSGTMSPKVGITGGCDVSARRHPWQVSLRFYSMKKGLWEPICGGSLIHPE
NOV16a EELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIAL
NOV16b EELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIAL
NOV16C WVLTAAHCVELEELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIAL
NOVlδa LKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIG RGGQEQDHLGGMWR
NOVlδb LKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIG RGGQEQDHLGGMWR
NOVl6c LKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIWGHVFLLPPPHLRAAEGPIMR NOVl6a D-DPECRCRPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPG
NOVl6b D-DPECRCRPGLQTRPGWLPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPG
NOV16C TRACERMYHKGPTAHVTIIKAAMPCAGAERHLSPQGDNGGPLLCRRN- -CTWVQVEWSW
NOV16a PSACGRRR
NOV16b PSACGRRR
NOV16C GKLCGLRYPGMYTRVTSYVSWIRQYVPPFPRR
NOV16a (SEQ ID NO 180) NOVl6b (SEQ ID NO 182) NOV16C (SEQ ID NO 184)
Further analysis ofthe NOVlόa protein yielded the following properties shown in Table 16C.
Table 16C. Protein Sequence Properties NOVlόa
SignalP analysis: Cleavage site between residues 19 and 20
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 5; pos . chg 1; neg.chg 0 H-region: length 13; peak value 6.79 PSG score: 2.39
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.86 possible cleavage site: between 18 and 19
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 4.88 (at 73) ALOM score: 4.88 (number of TMSs : 0)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 6 Charge difference: -3.0 C(-1.0) - N( 2.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment (75): 7.01 Hyd Moment (95): 6.08 G content: 5 D/E content: 1 S/T content: 6 Score: -2.71
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 29 SRP|GG
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 12.2%
NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: SPAR none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
55.6 %: extracellular, including cell wall 33.3 %: mitochondrial 11 . 1 % : cytoplasmic >> prediction for CG50934 - 03 is exc (k=9)
A search ofthe NOVlόa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D.
Figure imgf000308_0001
In a BLAST search of public sequence databases, the NOVlόa protein was found to have homology to the proteins shown in the BLASTP data in Table 16E.
Figure imgf000309_0001
PFam analysis indicates that the NOVlόa protein contains the domains shown in the Table 16F.
Figure imgf000309_0002
Example 17.
The NOV 17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A. Table 17A. NOV17 Sequence Analysis
NOVl 7a, CG51213-04 SEQ ID NO: 195 2804 bp DNA Sequence ORF Start: ATG at 71 ORF Stop: TAG at 2636
TGGCCAGCCAGGCCTGAAGCGATCGGTCAGCCGAGAGCGCTACGTGGAGACCCTGGTGGTGGCTGACA
AGATGATGGTGGCCTATCACGGGCGCCGGGATGTGGAGCAGTATGTCCTGGCCATCATGAACATTCAG GTTGCCAAACTTTTCCAGGACTCGAGTCTGGGAAGCACCGTTAACATCCTCGTAACTCGCCTCATCCT GCTCACGGAGGACCAGCCCACTCTGGAGATCACCCACCATGCCGGGAAGTCCCTGGACAGCTTCTGTA AGTGGCAGAAATCCATCGTGAACCACAGCGGCCATGGCAATGCCATTCCAGAGAACGGTGTGGCTAAC CATGACACAGCAGTGCTCATCACACGCTATGACATCTGCATCTACAAGAACAAACCCTGCGGCACACT AGGCCTGGCCCCGGTGGGCGGAATGTGTGAGCGCGAGAGAAGCTGCAGCGTCAATGAGGACATTGGCC TGGCCACAGCGTTCACCATTGCCCACGAGATCGGGCACACATTCGGCATGAACCATGACGGCGTGGGA AACAGCTGTGGGGCCCGTGGTCAGGACCCAGCCAAGCTCATGGCTGCCCACATTACCATGAAGACCAA CCCATTCGTGTGGTCATCCTGCAGCCGTGACTACATCACCAGCTTTCTAGACTCGGGCCTGGGGCTCT GCCTGAACAACCGGCCCCCCAGACAGGACTTTGTGTACCCGACAGTGGCACCGGGCCAAGCCTACGAT GCAGATGAGCAATGCCGCTTTCAGCATGGAGTCAAATCGCGTCAGTGTAAATACGGGGAGGTCTGCAG CGAGCTGTGGTGTCTGAGCAAGAGCAACCGGTGCATCACCAACAGCATCCCGGCCGCCGAGGGCACGC TGTGCCAGACGCACACCATCGACAAGGGGTGGTGCTACAAACGGGTCTGTGTCCCCTTTGGGTCGCGC CCAGAGGGTGTGGACGGAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGCAGCCGGACCTGTGGCGG CGGCGTGTCCTCTTCTAGCCGTCACTGCGACAGCCCCAGGCCAACCATCGGGGGCAAGTACTGTCTGA GTGAGAGAAGGCGGCACCGCTCCTGCAACACGGATGACTGTCCCCCTGGCTCCCAGGACTTCAGAGAA GTGCAGTGTTCTGAATTTGACAGCATCCCTTTCCGTGGGAAATTCTACAAGTGGAAAACGTACCGGGG AGGGGGCGTGAAGGCCTGCTCGCTCACGAGCCTAGCGGAAGGCTTCAACTTCTACACGGAGAGGGCGG CAGCCGTGGTGGACGGGACACCCTGCCGTCCAGACACGGTGGACATTTGCGTCAGTGGCGAATGCAAG CACGTGGGCTGCGACCGAGTCCTGGGCTCCGACCTGCGGGAGGACAAGTGCCGAGTGTGTGGCGGTGA CGGCAGTGCCTGCGAGACCATCGAGGGCGTCTTCAGCCCAGCCTCACCTGGGGCCGGGTACGAGGATG TCGTCTGGATTCCCAAAGGCTCCGTCCACATCTTCATCCAGGATCTGAACCTCTCTCTCAGTCACTTG GCCCTGAAGGGAGACCAGGAGTCCCTGCTGCTGGAGGGGCTGCCTGGGACCCCCCAGCCCCACCGTCT GCCTCTAGCTGGGACCACCTTTCAACTGCGACAGGGGCCAGACCAGGTCCAGAGCCTCGAAGCCCTGG GACCGATTAATGCATCTCTCATCGTCATGGTGCTGGCCCGGACCGAGCTGCCTGCCCTCCGCTACCGC TTCAATGCCCCCATCGCCCGTGACTCGCTGCCCCCCTACTCCTGGCACTATGCGCCCTGGACCAAGTG CTCGGCCCAGTGTGCAGGCGGTAGCCAGGTGCAGGCGGTGGAGTGCCGCAACCAGCTGGACAGCTCCG CGGTCGCCCCCCACTACTGCAGTGCCCACAGCAAGCTGCCCAAAAGGCAGCGCGCCTGCAACACGGAG CCTTGCCCTCCAGACTGGGTTGTAGGGAACTGGTCGCTCTGCAGCCGCAGCTGCGATGCAGGCGTGCG CAGTCGCTCGGTCGTGTGCCAGCGCCGCGTCTCTGCCGCGGAGGAGAAGGCGCTGGACGACAGCGCAT GCCCGCAGCCGCGCCCACCTGTACTGGAGGCCTGCCACGGCCCCACTTGCCCTCCGGAGTGGGCGGCC CTCGACTGGTCTGAGTGCACCCCCAGCTGCGGGCCGGGCCTCCGCCACCGCGTGGTCCTTTGCAAGAG CGCAGACCACCGCGCCACGCTGCCCCCGGCGCACTGCTCACCCGCCGCCAAGCCACCGGCCACCATGC GCTGCAACTTGCGCCGCTGCCCCCCGGCCCGCTGGGTGGCTGGCGAGTGGGGTGAGTGCTCTGCACAG TGCGGCGTCGGGCAGCGGCAGCGCTCGGTGCGCTGCACCAGCCACACGGGCCAGGCGTCGCACGAGTG CACGGAGGCCCTGCGGCCGCCCACCACGCAGCAGTGTGAGGCCAAGTGCGACAGCCCAACCCCCGGGG ACGGCCCTGAAGAGTGCAAGGATGTGAACAAGGTCGCCTACTGCCCCCTGGTGCTCAAATTTCAGTTC TGCAGCCGAGCCTACTTCCGCCAGATGTGCTGCAAAACCTGCCAGGGCCACTAGGGGGCGCGCGGCAC
CCGGAGCCACAGCTGGCGGGGTCTCCGCCGCCAGCCCTGCAGCGGGCCGGCCAAAGGGGGCCCCGGGG
GGGCGGGAACTGGGAGGGAAGGGTGAGACGGAGCCGGAAGTTATTTATTGGGAACCCCTGCAGGGCCC
TGGCTGGGGGGATGGA
NOV17a, CG51213-04 SEQ ID NO: 196 855 aa MW at 93285.7kD Protein Sequence
MMVAYHGRRDVEQYVLAIMNIQVAKLFQDSSLGSTVNILVTRLILLTEDQPTLEITHHAGKSLDSFCK WQKSIVNHSGHGNAIPENGVANHDTAVLITRYDICIYKNKPCGTLGLAPVGGMCERERSCSVNEDIGL ATAFTIAHEIGHTFGMNHDGVGNSCGARGQDPAKLMAAHITMKTNPFVWSSCSRDYITSFLDSGLGLC LNNRPPRQDFVYPTVAPGQAYDADEQCRFQHGVKSRQCKYGEVCSELWCLSKSNRCITNSIPAAEGTL CQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSRTCGGGVSSSSRHCDSPRPTIGGKYCLS ERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPFRGKFYKWKTYRGGGVKACSLTSLAEGFNFYTERAA AWDGTPCRPDTVDICVSGECKHVGCDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDV VWIPKGSVHIFIQDLNLSLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALG
Figure imgf000311_0001
AAGCTGCCCAAAAGGCAGCGCGCCTGCAACACGGAGCCTTGCCCTCCAGACTGGGTTGTAGGGAACTG GTCGCTCTGCAGCCGCAGCTGCGATGCAGGCGTGCGCAGCCGCTCGGTCGTGTGCCAGCGCCGCGTCT CTGCCGCGGAGGAGAAGGCGCTGGACGACAGCGCATGCCCGCAGCCGCGCCCACCTGTACTGGAGGCC TGCCACGGCCCCACTTGCCCTCCGGAGTGGGCGGCCCTCGACTGGTCTGAGTGCACCCCCAGCTGCGG GCCGGGCCTCCGCCACCGCGTGGTCCTTTGCAAGAGCGCAGACCACCGCGCCACGCTGCCCCCGGCGC ACTGCTCACCCGCCGCCAAGCCACCGGCCACCATGCGCTGCAACTTGCGCCGCTGCCCCCCGGCCCGC TGGGTGGCTGGCGAGTGGGGTGAGTGCTCTGCACAGTGCGGCGTCGGGCAGCGGCAGCGCTCGGTGCG CTGCACCAGCCACACGGGCCAGGCGTCGCACGAGTGCACGGAGGCCCTGCGGCCGCCCACCACGCAGC AGTGTGAGGCCAAGTGCCTCGAGGGC
NOV17c, 306345264 SEQ ID NO: 200 235 aa MW at 25395.4kD Protein Sequence
TGSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAVAPHYCSAHSKLPKRQRACNTEPCPPDWWGNW SLCSRSCDAGVRSRSWCQRRVSAAEEKALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCG PGLRHRWLCKSADHRATLPPAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSV CTSHTGQASHECTEALRP PTTQQCEAKCLEG
NOV17d, CG51213-02 SEQ ID NO: 201 3199 bp DNA Sequence ORF Start: at 1297 ORF Stop: at 3199
TAAAGGGTTCAGCCTGGTGCCTGGTCCAGAGATAGTGGTGGTCATTGTTACCCCATAATGGCATTGGTi
GCAAGTCCTTTCTTATCTATCCTGTCACGTGCCTCATAGCCATTTATATAGGCAAGACAGGCATTAGG!
CTGCCCATCTTGTAGATGAGTAAACTGAGGCCCAGAGAGGGGAAATATATTGCAAGTTGGTAGCAGAA:
TTGAGGTCTCTGCACAACTCAAATATGCCACAGTGCCTCCTTGTGGAGAGGAGGACAAAAGCAGAGCT!
GAAATCATTATCTTGAAGAGGTGTCAGAAGTGGGATTGCGACAGGACTGATGTGATATTTTTAGATAT!
GGCCAAGAGGACACAGTCTGAGTTTTTAGCTGAGAAATGTCCTCTATAAGGCAGAAGGCAGAGATTCT
AGAGGACCTTTGAGGGAGAATGTATTTGAGAACAACTCTTCCAGCTTCTTACATATGTACAGGTATCT!
CTCAGGGGCTGACCTAGGAAGGGTCCTTTCCTGTGGCCATTGATCGATCCAGTCCCACATCTGGAAAG!
CTTACAAGAATTGGGTTCAAAGCGGGGATTACACTTGATAATTACAGAAGGACCACCTACTTCTTAGAj
GGAAAGACGCTGGGAGGTTGCTTAGGATGTGGGCCAAGAGGGTCAGAGAGGACCACCTACTTTTTAGA
GGAAAGACGCTGGGAGGTTGCTTAGGATGTGGGCCAAGAGGGTCAGAGATTTTGCTTCACCTGAACTC
ACTGGGGCTTCTCCAGGGATATTAACCTGGACTTTAAGAGTCAGAGTGAGTCCCTGGGACTAGTTCAG
CCCATCCAGGATTCAGACGGGAAGAAGGTGGGGCTGATTTTTCACCTGGAGAAAGAGAGGCATGTCCC
ACACAGACCTAACTCGGCATTGTCCCCTCCCAAACTCCCACCCCTCCACATAGCTTAAAAGTGTTGGG
GGCTTCTCCAGTTTAGATGGGGGAACAAAGAGAACCAACAGCTGGAAAAAACTAGAGATGAGGCCGTT
GGCCTAGTCATCATCCAGGCCGATTTCTCAGAACCACCACTTTCTCTTCGGCTACTTTGCCCATCCCA
TAAAAGAACCCCAAATCCTTCCTGTTCATTCCTCAGCAGTTCCCACGTTTCCTTCCAGAAACTCAGAA
GGCACCAGGAACTGAATTGCAAAGTTCGTTAGAGCACAGACTCTGAATTAAAGAGCTGGGTTAAACTC
CAGGCTATTCCCTTAGTAGCTGTGTGACCTTACCTGTCTGAAGCTTGGTTTTCTCCCAGTAAGATGGG
GTAGTACTGCCTAAAGAGGTATATGGCATGTATAAAGTGCTCCATAAATGGAGCTTATTGGGAGAGTA
TAAGTCACAGGCCATGCCCCGCAAGGGGATGCACGAAGACCCACCGCGAGCCAGGAAGGGAGCACCGG GCTCTCTGCTCTGGGACCGGCAGTGAGCCGGACATCTGGGTCCTCCCAAGCCGGGCGGGCTGCCCCAG GGAGGAAGGGAGGGGGGCGAGCCTGAGCGGGCACCTCGGCCCGCAGGAGGTCTGCAGCGAGCTGTGGT GTCTGAGCAAGAGCAACCGGTGCATCACCAACAGCATCCCGGCCGCCGAGGGCACGCTGTGCCAGACG CACACCATCGACAAGGGGTGGTGCTACAAACGGGTCTGTGTCCCCTTTGGGTCGCGCCCAGAGGGTGT GGACGGAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGCAGCCGGACCTGTGGCGGCGGCGTGTCCT CTTCTAGCCGTCACTGCGACAGCCCCAGGCCAACCATCGGGGGCAAGTACTGTCTGGGTGAGAGAAGG CGGCACCGCTCCTGCAACACGGATGACTGTCCCCCTGGCTCCCAGGACTTCAGAGAAGTGCAGTGTTC TGAATTTGACAGCATCCCTTTCCGTGGGAAATTCTACAAGTGGAAAACGTACCGGGGAGGGGGCGTGA AGGCCTGCTCGCTCACGTGCCTAGCGGAAGGCTTCAACTTCTACACGGAGAGGGCGGCAGCCGTGGTG GACGGGACACCCTGCCGTCCAGACACGGTGGACATTTGCGTCAGTGGCGAATGCAAGCACGTGGGCTG CGACCGAGTCCTGGGCTCCGACCTGCGGGAGGACAAGTGCCGAGTGTGTGGCGGTGACGGCAGTGCCT GCGAGACCATCGAGGGCGTCTTCAGCCCAGCCTCACCTGGGGCCGGGTACGAGGATGTCGTCTGGATT CCCAAAGGCTCCGTCCACATCTTCATCCAGGATCTGAACCTCTCTCTCAGTCACTTGGCCCTGAAGGG AGACCAGGAGTCCCTGCTGCTGGAGGGGCTGCCCGGGACCCCCCAGCCCCACCGTCTGCCTCTAGCTG GGACCACCTTTCAACTGCGACAGGGGCCAGACCAGGTCCAGAGCCTCGAAGCCCTGGGACCGATTAAT GCATCTCTCATCGTCATGGTGCTGGCCCGGACCGAGCTGCCTGCCCTCCGCTACCGCTTCAATGCCCC CATCGCCCGTGACTCGCTGCCCCCCTACTCCTGGCACTATGCGCCCTGGACCAAGTGCTCGGCCCAGT GTGCAGGCGGTAGCCAGGTGCAGGCGGTGGAGTGCCGCAACCAGCTGGACAGCTCCGCGGTCGCCCCC CACTACTGCAGTGCCCACAGCAAGCTGCCCAAAAGGCAGCGCGCCTGCAACACGGAGCCTTGCCCTCC AGACTGGGTTGTAGGGAACTGGTCGCTCTGCAGCCGCAGCTGCGATGCAGGCGTGCGCAGCCGCTCGG TCGTGTGCCAGCGCCGCGTCTCTGCCGCGGAGGAGAAGGCGCTGGACGACAGCGCATGCCCGCAGCCG CGCCCACCTGTACTGGAGGCCTGCCACGGCCCCACTTGCCCTCCGGAGTGGGCGGCCCTCGACTGGTC TGAGTGCACCCCCAGCTGCGGGCCGGGCCTCCGCCACCGCGTGGTCCTTTGCAAGAGCGCAGACCACC GCGCCACGCTGCCCCCGGCGCACTGCTCACCCGCCGCCAAGCCACCGGCCACCATGCGCTGCAACTTG CGCCGCTGCCCCCCGGCCCGCTGGGTGGCTGGCGAGTGGGGTGAGTGCTCTGCACAGTGCGGCGTCGG GCAGCGGCAGCGCTCGGTGCGCTGCACCAGCCACACGGGCCAGGCGTCGCACGAGTGCACGGAGGCCC TGC
NOV17d, CG51213-02 SEQ ID NO: 202 634 aa MW at 68853. lkD Protein Sequence
YCLKRYMACIKCSINGAYWESISHRPCPARGCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPRE EGRGASLSGHLGPQEVCSELWCLSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVD GAWGPWTPWGDCSRTCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSE FDSIPFRGKFYKWKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVGCD RVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNLSLSHLALKGD QESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVMVLARTELPALRYRFNAPI ARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAVAPHYCSAHSKLPKRQRACNTEPCPPD WWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEKALDDSACPQPRPPVLEACHGPTCPPEWAALDWSE CTPSCGPGLRHRWLCKSADHRATLPPAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQ RQRSVRCTSHTGQASHECTEAL
NOVl 7e, CG51213-03 SEQ ID NO: 203 3700 bp
DNA Sequence lORF Start: at 1798 JORF Stop: at 3700
CTGACATTCCACCCTTGACACCCCCCAACATCCTAACTTAGCTGGTAACTGCAGCACCCTCTAAGGAA!
TTCCTAAAGAATTCTGAAGCTACTCCTCAACATCTGCTGTGACCCAGGTATCCTAACAATGATCATGG!
TGTCTGACATTTACTGAGCTCTCACTATGGGCTAAGCATGTGCTGTGTGTCACCATCTAAACTCCTGAi
CAATCCTGCTAGCCCCCACGTTACAGAGGAAGGGACTGAGCCATAGCATAGGGAGGATGACTTGTCCA!
AGGCCACAGTTTGAGACCATGACAGAGCTGGGATTTAAATCCAGGTCTCTCATGACTCTCTAAATTTTj
ACAAAGGGGCAGGGGAGGGGAGGAGCTGTCAAAATATCAAGCTTGGGCTGGCACTGGCTATATGTTGA
ATTGAGCCTTCCTTTTAGTTTTTGAAGGAACATCTTTCAGGCCATCTTGGCAAAGGGGGATTTATTTA
CTAAATGTGAACTGGTTAATATATGTAAAGGGTTCAGCCTGGTGCCTGGTCCAGAGATAGTGGTGGTC
ATTGTTACCCCATAATGGCATTGGTGCAAGTCCTTTCTTATCTATCCTGTCACGTGCCTCATAGCCAT
TTATATAGGCAAGACAGGCATTAGGCTGCCCATCTTGTAGATGAGTAAACTGAGGCCCAGAGAGGGGA
AATATATTGCAAGTTGGTAGCAGAATTGAGGTCTCTGCACAACTCAAATATGCCACAGTGCCTCCTTG
TGGAGAGGAGGACAAAAGCAGAGCTGAAATCATTATCTTGAAGAGGTGTCAGAAGTGGGATTGCGACAi
GGACTGATGTGATATTTTTAGATATGGCCAAGAGGACACAGTCTGAGTTTTTAGCTGAGAAATGTCCT
CTATAAGGCAGAAGGCAGAGATTCTAGAGGACCTTTGAGGGAGAATGTATTTGAGAACAACTCTTCCA
GCTTCTTACATATGTACAGGTATCTCTCAGGGGCTGACCTAGGAAGGGTCCTTTCCTGTGGCCATTGA
TCGATCCAGTCCCACATCTGGAAAGCTTACAAGAATTGGGTTCAAAGCGGGGATTACACTTGATAATT lACAGAAGGACCACCTACTTCTTAGAGGAAAGACGCTGGGAGGTTGCTTAGGATGTGGGCCAAGAGGGT
CAGAGAGGACCACCTACTTTTTAGAGGAAAGACGCTGGGAGGTTGCTTAGGATGTGGGCCAAGAGGGT
CAGAGATTTTGCTTCACCTGAACTCACTGGGGCTTCTCCAGGGATATTAACCTGGACTTTAAGAGTCA
GAGTGAGTCCCTGGGACTAGTTCAGCCCATCCAGGATTCAGACGGGAAGAAGGTGGGGCTGATTTTTC
ACCTGGAGAAAGAGAGGCATGTCCCACACAGACCTAACTCGGCATTGTCCCCTCCCAAACTCCCACCC:
CTCCACATAGCTTAAAAGTGTTGGGGGCTTCTCCAGTTTAGATGGGGGAACAAAGAGAACCAACAGCT!
GGAAAAAACTAGAGATGAGGCCGTTGGCCTAGTCATCATCCAGGCCGATTTCTCAGAACCACCACTTTj
CTCTTCGGCTACTTTGCCCATCCCATAAAAGAACCCCAAATCCTTCCTGTTCATTCCTCAGCAGTTCC
CACGTTTCCTTCCAGAAACTCAGAAGGCACCAGGAACTGAATTGCAAAGTTCGTTAGAGCACAGACTC iTGAATTAAAGAGCTGGGTTAAACTCCAGGCTATTCCCTTAGTAGCTGTGTGACCTTACCTGTCTGAAG
CTTGGTTTTCTCCCAGTAAGATGGGGTAGTACTGCCTAAAGAGGTATATGGCATGTATAAAGTGCTCC
ATAAATGGAGCTTATTGGGAGAGTATAAGTCACAGGCCATGCCCCGCAAGGGGATGCACGAAGACCCA CCGCGAGCCAGGAAGGGAGCACGGGGCTCTCTGCTCTGGGACCGGCAGTGAGCCGGACATCTGGGTCC TCCCAAGCCGGGCGGGCTGCCCCAGGGAGGAAGGGAGGGGGGCGAGCCTGAGCGGGCACCTCGGCCCG CAGGAGGTCTGCAGCGAGCTGTGGTGTCTGAGCAAGAGCAACCGGTGCATCACCAACAGCATCCCGGC CGCCGAGGGCACGCTGTGCCAGACGCACACCATCGACAAGGGGTGGTGCTACAAACGGGTCTGTGTCC CCTTTGGGTCGCGCCCAGAGGGTGTGGACGGAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGCAGC CGGACCTGTGGCGGCGGCGTGTCCTCTTCTAGCCGTCACTGCGACAGCCCCAGGCCAACCATCGGGGG CAAGTACTGTCTGGGTGAGAGAAGGCGGCACCGCTCCTGCAACACGGATGACTGTCCCCCTGGCTCCC
Figure imgf000314_0001
CATCGACAAGGGGTGGTGCTACAAACGGGTCTGTGTCCCCTTTGGGTCGCGCCCAGAGGGTGTGGACG GAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGCAGCCGGACCTGTGGCGGCGGCGTGTCCTCTTCT AGTCGTCACTGCGACAGCCCCAGGCCAACCATCGGGGGCAAGTACTGTCTGGGTGAGAGAAGGCGGCA CCGCTCCTGCAACACGGATGACTGTCCCCCTGGCTCCCAGGACTTCAGAGAAGTGCAGTGTTCTGAAT TTGACAGCATCCCTTTCCGTGGGAAATTCTACAAGTGGAAAACGTACCGGGGAGGGGGCGTGAAGGCC TGCTCGCTCACGAGCCTAGCGGAAGGCTTCAACTTCTACACGGAGAGGGCGGCAGCCGTGGTGGACGG GACACCCTGCCGTCCAGACACGGTGGACATTTGCGTCAGTGGCGAATGCAAGCACGTGGGCTGCGACC GAGTCCTGGGCTCCGACCTGCGGGAGGACAAGTGCCGAGTGTGTGGCGGTGACGGCAGTGCCTGCGAG ACCATCGAGGGCGTCTTCAGCCCAGCCTCACCTGGGGCCGGGTACGAGGATGTCGTCTGGATTCCCAA AGGCTCCGTCCACATCTTCATCCAGGATCTGAACCTCTCTCTCAGTCACTTGGCCCTGAAGGGAGACC AGGAGTCCCTGCTGCTGGAGGGGCTGCCTGGGACCCCCCAGCCCCACCGTCTGCCTCTAGCTGGGACC ACCTTTCAACTGCGACAGGGGCCAGACCAGGTCCAGAGCCTCGAAGCCCTGGGACCGATTAATGCATC TCTCATCGTCATGGTGCTGGCCCGGACCGAGCTGCCTGCCCTCCGCTACCGCTTCAATGCCCCCATCG CCCGTGACTCGCTGCCCCCCTACTCCTGGCACTATGCGCCCTGGACCAAGTGCTCGGCCCAGTGTGCA GGCGGTAGCCAGGTGCAGGCGGTGGAGTGCCGCAACCAGCTGGACAGCTCCGCGGTCGCCCCCCACTA CTGCAGTGCCCACAGCAAGCTGCCCAAAAGGCAGCGCGCCTGCAACACGGAGCCTTGCCCTCCAGACT GGGTTGTAGGGAACTGGTCGCTCTGCAGCCGCAGCTGCGATGCAGGCGTGCGCAGTCGCTCGGTCGTG TGCCAGCGCCGCGTCTCTGCCGCGGAGGAGAAGGCGCTGGACGACAGCGCATGCCCGCAGCCGCGCCC ACCTGTACTGGAGGCCTGCCACGGCCCCACTTGCCCTCCGGAGTGGGCGGCCCTCGACTGGTCTGAGT GCACCCCCAGCTGCGGGCCGGGCCTCCGCCACCGCGTGGTCCTTTGCAAGAGCGCAGACCACCGCGCC ACGCTGCCCCCGGCGCACTGCTCACCCGCCGCCAAGCCACCGGCCACCATGCGCTGCAACTTGCGCCG CTGCCCCCCGGCCCGCTGGGTGGCTGGCGAGTGGGGTGAGTGCTCTGCACAGTGCGGCGTCGGGCAGC GGCAGCGCTCGGTGCGCTGCACCAGCCACACGGGCCAGGCGTCGCACGAGTGCACGGAGGCCCTGCGG CCGCCCACCACGCAGCAGTGTGAGGCCAAGTGCGACAGCCCAACCCCCGGGGACGGCCCTGAAGAGTG CAAGGATGTGAACAAGGTCGCCTACTGCCCCCTGGTGCTCAAATTTCAGTTCTGCAGCCGAGCCTACT TCCGCCAGATGTGCTGCAAAACCTGCCAGGGCCACTAGGGGGCGCGCGGCACCCGGAGCCACAGCTGG
CGGGGTCTCCGCCGCCAGCCCTGCAGCGGGCCGGCCAAAGGGGGCCCCGGGGGGGCGGGAACTGGGAG
GGAAGGGTGAGACGGAGCCGGAAGTTATTTATTGGGAACCCCTGCAGGGCCCTGGCTGGGGGGATGGA
NOVl 7f, CG51213-05 SEQ ID NO: 206 1077 aa MW at l l8071.4kD Protein Sequence
RSQDEFLSSLESYEIAFPTRVDHNGALLAFSPPPPRRQRRGTGATAESRLFYKVASPSTHFLLNLTRS SRLLAGHVSVEYWTREGLAWQRAARPHCLYAGHLQGQASSSHVAISTCGGLHGLIVADEEEYLIEPLH GGPKGSRSPEESGPHWYKRSSLRHPHLDTACGVRDEKPWKGRPWWLRTLKPPPARPLGNETERGQPG LKRSVSRERYVETLVVADKMMVAYHGRRDVEQYVLAIMNIVAKLFQDSSLGSTVNILVTRLILLTEDQ PTLEITHHAGKSLDSFCKWQKSIVNHSGHGNAIPENGVANHDTAVLITRYDICIYKNKPCGTLGLAPV GGMCERERSCSVNEDIGLPQAFTIAHEIGHTFGMNHDGVGNSCGARGQDPAKLMAAHITMKTNPFVWS SCNRDYITSFLDSGLGLCLNNRPPRQDFVYPTVAPGQAYDADEQCRFQHGVKSRQCKYGEVCSELWCL SKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSRTCGGGVSSS SRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPFRGKFYKWKTYRGGGVKA CSLTSLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVGCDRVLGSDLREDKCRVCGGDGSACE TIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNLSLSHLALKGDQESLLLEGLPGTPQPHRLPLAGT TFQLRQGPDQVQSLEALGPINASLIVMVLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCA GGSQVQAVECRNQLDSSAVAPHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSW CQRRVSAAEEKALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRA TLPPAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHECTEALR PPTTQQCEAKCDSPTPGDGPEECKDVNKVAYCPLVLKFQFCSRAYFRQMCCKTCQGH
NOVl 7g, CG51213-06 SEQ ID NO: 207 978 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TCCATAAATGGAGCTTATTGGGAGAGTATAAGTCACAGGCCATGCCCCGCAAGGGGATGCACGAAGAC CCACCGCGAGCCAGGAAGGGAGCACCGGGCTCTCTGCTCTGGGACCGGCAGTGAGCCGGACATCTGGG TCCTCCCAAGCCGGGCGGGCTGCCCCAGGGAGGAAGGGAGGGGGGCGAGCCTGAGCGGGCACCTCGGC CCGCAGGAGGTCTGCAGCGAGCTGTGGTGTCTGAGCAAGAGCAACCGGTGCATCACCAACAGCATCCC GGCCGCCGAGGGCACGCTGTGCCAGACGCACACCATCGACAAGGGGTGGTGCTACAAACGGGTCTGTG TCCCCTTTGGGTCGCGCCCAGAGGGTGTGGACGGAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGC AGCCGGACCTGTGGCGGCGGCGTGTCCTCTTCTAGCCGTCACTGCGACAGCCCCAGGCCAACCATCGG GGGCAAGTACTGTCTGGGTGAGAGAAGGCGGCACCGCTCCTGCAACACGGATGACTGTCCCCCTGGCT CCCAGGACTTCAGAGAAGTGCAGTGTTCTGAATTTGACAGCATCCCTTTCCGTGGGAAATTCTACAAG TGGAAAACGTACCGGGGAGGGGGCGTGAAGGCCTGCTCGCTCACGTGCCTAGCGGAAGGCTTCAACTT CTACACGGAGAGGGCGGCAGCCGTGGTGGACGGGACACCCTGCCGTCCAGACACGGTGGACATTTGCG TCAGTGGCGAATGCAAGCACGTGGGCTGCGACCGAGTCCTGGGCTCCGACCTGCGGGAGGACAAGTGC CGAGTGTGTGGCGGTGACGGCAGTGCCTGCGAGACCATCGAGGGCGTCTTCAGCCCAGCCTCACCTGG GGCCGGGTACGAGGATGTCGTCTGGATTCCCAAAGGCTCCGTCCACATCTTCATCCAGGATCTGAACC TCTCTCTCAGTCACTTGGCCCTGAAG
NOV17g, CG51213-06 SEQ ID NO: 208 326 aa MW at 35330.2kD Protein Sequence
SINGAYWESISHRPCPARGCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLG PQEVCSELWCLSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDC SRTCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPFRGKFYK WKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVGCDRVLGSDLREDKC RVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNLSLSHLALK
NOVl 7h, CG51213-07 SEQ ID NO: 209 1866 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TCCATAAATGGAGCTTATTGGGAGAGTATAAGTCACAGGCCATGCCCCGCAAGGGGATGCACGAAGAC CCACCGCGAGCCAGGAAGGGAGCACCGGGCTCTCTGCTCTGGGACCGGCAGTGAGCCGGACATCTGGG TCCTCCCAAGCCGGGCGGGCTGCCCCAGGGAGGAAGGGAGGGGGGCGAGCCTGAGCGGGCACCTCGGC CCGCAGGAGGTCTGCAGCGAGCTGTGGTGTCTGAGCAAGAGCAACCGGTGCATCACCAACAGCATCCC GGCCGCCGAGGGCACGCTGTGCCAGACGCACACCATCGACAAGGGGTGGTGCTACAAACGGGTCTGTG TCCCCTTTGGGTCGCGCCCAGAGGGTGTGGACGGAGCCTGGGGGCCGTGGACTCCATGGGGCGACTGC AGCCGGACCTGTGGCGGCGGCGTGTCCTCTTCTAGCCGTCACTGCGACAGCCCCAGGCCAACCATCGG GGGCAAGTACTGTCTGGGTGAGAGAAGGCGGCACCGCTCCTGCAACACGGATGACTGTCCCCCTGGCT CCCAGGACTTCAGAGAAGTGCAGTGTTCTGAATTTGACAGCATCCCTTTCCGTGGGAAATTCTACAAG TGGAAAACGTACCGGGGAGGGGGCGTGAAGGCCTGCTCGCTCACGTGCCTAGCGGAAGGCTTCAACTT CTACACGGAGAGGGCGGCAGCCGTGGTGGACGGGACACCCTGCCGTCCAGACACGGTGGACATTTGCG TCAGTGGCGAATGCAAGCACGTGGGCTGCGACCGAGTCCTGGGCTCCGACCTGCGGGAGGACAAGTGC CGAGTGTGTGGCGGTGACGGCAGTGCCTGCGAGACCATCGAGGGCGTCTTCAGCCCAGCCTCACCTGG GGCCGGGTACGAGGATGTCGTCTGGATTCCCAAAGGCTCCGTCCACATCTTCATCCAGGATCTGAACC TCTCTCTCAGTCACTTGGCCCTGAAGGGAGACCAGGAGTCCCTGCTGCTGGAGGGGCTGCCCGGGACC CCCCAGCCCCACCGTCTGCCTCTAGCTGGGACCACCTTTCAACTGCGACAGGGGCCAGACCAGGTCCA GAGCCTCGAAGCCCTGGGACCGATTAATGCATCTCTCATCGTCATGGTGCTGGCCCGGACCGAGCTGC CTGCCCTCCGCTACCGCTTCAATGCCCCCATCGCCCGTGACTCGCTGCCCCCCTACTCCTGGCACTAT GCGCCCTGGACCAAGTGCTCGGCCCAGTGTGCAGGCGGTAGCCAGGTGCAGGCGGTGGAGTGCCGCAA CCAGCTGGACAGCTCCGCGGTCGCCCCCCACTACTGCAGTGCCCACAGCAAGCTGCCCAAAAGGCAGC GCGCCTGCAACACGGAGCCTTGCCCTCCAGACTGGGTTGTAGGGAACTGGTCGCTCTGCAGCCGCAGC TGCGATGCAGGCGTGCGCAGCCGCTCGGTCGTGTGCCAGCGCCGCGTCTCTGCCGCGGAGGAGAAGGC GCTGGACGACAGCGCATGCCCGCAGCCGCGCCCACCTGTACTGGAGGCCTGCCACGGCCCCACTTGCC CTCCGGAGTGGGCGGCCCTCGACTGGTCTGAGTGCACCCCCAGCTGCGGGCCGGGCCTCCGCCACCGC GTGGTCCTTTGCAAGAGCGCAGACCACCGCGCCACGCTGCCCCCGGCGCACTGCTCACCCGCCGCCAA GCCACCGGCCACCATGCGCTGCAACTTGCGCCGCTGCCCCCCGGCCCGCTGGGTGGCTGGCGAGTGGG GTGAGTGCTCTGCACAGTGCGGCGTCGGGCAGCGGCAGCGCTCGGTGCGCTGCACCAGCCACACGGGC CAGGCGTCGCACGAGTGCACGGAGGCCCTG
NOV17h, CG51213-07 SEQ ID NO: 210 622 aa MW at 67376.2kD Protein Sequence
SINGAYWESISHRPCPARGCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLG PQEVCSELWCLSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDC SRTCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPFRGKFYK WKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVGCDRVLGSDLREDKC RVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNLSLSHLALKGDQESLLLEGLPGT PQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVMVLARTELPALRYRFNAPIARDSLPPYSWHY APWTKCSAQCAGGSQVQAVECRNQLDSSAVAPHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRS CDAGVRSRSWCQRRVSAAEEKALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHR WLCKSADHRATLPPAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTG QASHECTEAL A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 17B.
Table 17B. Comparison of the NOV17 protein sequences.
NOV17a
NOVl7b
NOV17C
NOV17d
NOVl7e
NOVl7f RSQDEFLSSLESYEIAFPTRVDHNGALLAFSPPPPRRQRRGTGATAESRLFYKVASPSTH
NOV17g
NOV17h
NOV17a
NOV17b
NOV17C
NOVl7d
NOV17e
NOV17f FLLNLTRSSRLLAGHVSVEYWTREGLAWQRAARPHCLYAGHLQGQASSSHVAISTCGGLH
NOV17g
NOV17h
NOV17a
NOVl7b
NOVl7c
NOV17d
NOV17e
NOV17f GLIVADEEEYLIEPLHGGPKGSRSPEESGPHWYKRSSLRHPHLDTACGVRDEKPWKGRP
N0V17g
N0V17h
N0V17a MMVAYHGRRDVEQYVLAI
NOV17b
NOV17C
NOVl7d
NOVl7e
NOVl7f WWLRTLKPPPARPLGNETERGQPGLKRSVSRERYVETLWADKMMVAYHGRRDVEQYVLA
NOVl7g
NOV17h
NOV17a MNIQVAKLFQDSSLGSTVNILVTRLILLTEDQPTLEITHHAGKSLDSFCKWQKSIVNHSG
NOVl7b
NOV17C
NOV17d
NOV17e
NOV17f IMNIVAKLFQDSSLGSTVNILVTRLILLTEDQPTLEITHHAGKSLDSFCKWQKSIVNHSG
NOVl7g
NOVl7h
NOV17a HGNAIPENGVANHDTAVLITRYDICIYKNKPCGTLGLAPVGGMCERERSCSVNEDIGLAT
NOVl7b
NOV17C NOV17d
NOV17e
NOV17f HGNAIPENGVANHDTAVLITRYDICIYKNKPCGTLGLAPVGGMCERERSCSVNEDIGLPQ
NOV17g
NOV17h
NOVl7a AFTIAHEIGHTFGMNHDGVGNSCGARGQDPAKLMAAHITMKTNPFVWSSCSRDYITSFLD
NOV17b
NOVl7c
NOV17d
NOVl7e
NOV17f AFTIAHEIGHTFGMNHDGVGNSCGARGQDPAKLMAAHITMKTNPFVWSSCNRDYITSFLD
NOV17g
NOVl7h
NOV17a SGLGLCLNNRPPRQDFVYPTVAPGQAYDADEQCRFQHGVKSRQCKYGEVCSELWCLSKSN
NOV17b
NOVl7c
N0V17d YCLKRYMACIKCSINGAYWESISHRPCPAR
NOV17e YCLKRYMACIKCSINGAYWESISHRPCPAR
NOVl7f SGLGLCLNNRPPRQDFVYPTVAPGQAYDADEQCRFQHGVKSRQCKYGEVCSELWCLSKSN
NOV17g SINGAYWESISHRPCPAR
N0V17h SINGAYWESISHRPCPAR
NOV17a RCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSRTCGGG
NOV17b MGVQRD AGSPHSLCPSCPSSWVWG
NOVl7c
NOV17d GCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLGPQEVCSELWC
NOV17e GCTKTHREPGREHGALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLGPQEVCSELWC
NOV17f RCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSRTCGGG
NOV17g GCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLGPQEVCSELWC
NOV17h GCTKTHREPGREHRALCSGTGSEPDIWVLPSRAGCPREEGRGASLSGHLGPQEVCSELWC
NOVl7a VS- -S--SS ■-RHCD- NOVl7b LS- -L--LA --SLPQ- NOVl7c N0V17d LSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSR NOVl7e LSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSR NOVl7f VS S--SS RHCD NOV17g LSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSR NOV17h LSKSNRCITNSIPAAEGTLCQTHTIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSR
NOV17a S-PR- -P TIGGKYCLSERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF NOVl7b G-AS- -K EFRGGLARG VTGPCPPG NOVl7c NOV17d TCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF NOV17e TCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF NOVl7f S-PR- -P TIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF NOV17g TCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF NOV17h TCGGGVSSSSRHCDSPRPTIGGKYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPF
NOVl7a RGKFYKWKTYRGGGVKACSLTSLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG NOVl7b GVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG NOVl7c N0V17d RGKFYKWKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG N0V17e RGKFYKWKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG NOVl7f RGKFYKWKTYRGGGVKACSLTSLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG NOV17g RGKFYKWKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG NOV17h RGKFYKWKTYRGGGVKACSLTCLAEGFNFYTERAAAWDGTPCRPDTVDICVSGECKHVG
NOVl7a CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOVl7b CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOVl7c NOV17d CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOVl7e CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOVl7f CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOV17g CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL NOV17h CDRVLGSDLREDKCRVCGGDGSACETIEGVFSPASPGAGYEDWWIPKGSVHIFIQDLNL
NOV17a SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOV17b SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOVl7c
NOV17d SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOVl7e SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOVl7f SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOVl7g SLSHLALK
NOV17h SLSHLALKGDQESLLLEGLPGTPQPHRLPLAGTTFQLRQGPDQVQSLEALGPINASLIVM
NOV17a VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOVl7b VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOVl7c TGSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOVl7d VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOV17e VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOV17f VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOVl7g
NOV17h VLARTELPALRYRFNAPIARDSLPPYSWHYAPWTKCSAQCAGGSQVQAVECRNQLDSSAV
NOVl7a APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOVl7b APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOVl7c APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOV17d APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOV17e APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOVl7f APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOV17g
NOV17h APHYCSAHSKLPKRQRACNTEPCPPDWWGNWSLCSRSCDAGVRSRSWCQRRVSAAEEK
NOVl7a ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOVl7b ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOV17C ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOVl7d ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOV17e ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOVl7f ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOVl7g
NOV17h ALDDSACPQPRPPVLEACHGPTCPPEWAALDWSECTPSCGPGLRHRWLCKSADHRATLP
NOVl7a PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOV17b PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOV17C PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC NOV17d PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOVl7e PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOV17f PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOV17g
NOVl7h PAHCSPAAKPPATMRCNLRRCPPARWVAGEWGECSAQCGVGQRQRSVRCTSHTGQASHEC
NOV17a TEALRPPTTQQCEAKCDSPTPGDGPEECKDVNKVAYCPLVLKFQFCSRAYFRQMCCKTCQ
NOVl7b TEALRPPTTQQCEAKCDSPTPGDGPEECKDVNKVAYCPLVLKFQFCSRAYFRQMCCKTCQ
NOV17C TEALRPPTTQQCEAKCLEG
NOV17d TEAL
NOVl7e TEAL
NOV17f TEALRPPTTQQCEAKCDSPTPGDGPEECKDVNKVAYCPLVLKFQFCSRAYFRQMCCKTCQ
NOV17g
NOV17h TEAL
NOVl7a GH
NOVl7b GH
NOVl7c --
NOV17d --
NOVl7e --
NOVl7f GH
NOV17g --
NOV17h --
NOVl7a (SEQ ID NO 196)
NOVl7b (SEQ ID NO 198)
NOV17C (SEQ ID NO 200)
NOV17d (SEQ ID NO 202)
NOVl7e (SEQ ID NO 204)
NOVl7f (SEQ ID NO 206)
NOV17g (SEQ ID NO 208)
NOV17h (SEQ ID NO 210)
Further analysis of the NOV 17a protein yielded the following properties shown in Table 17C.
Table 17C. Protein Sequence Properties NOV17a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 10 ; pos . chg 2 ; neg . chg 1 H-region : length 1 ; peak value -0 . 15 PSG score : -4 . 55
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1 ) : - 8 . 03 possible cleavage site : between 33 and 34
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1
Number of TMS(s) for threshold 0.5: 0
PERIPHERAL Likelihood = 1.38 (at 31)
ALOM score: -1.70 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment (75): 5.01 Hyd Moment(95): 5.34 G content: 1 D/E content: 2 S/T content: 0 Score: -5.94
Gavel : prediction of cleavage sites for mitochondrial preseq R-2 motif at 18 GRR|DV
NUCDISC: discrimination of nuclear localization signals pat4: RRRH (3) 'at 342 pat4: RRHR (3) at 343 pat7: PKRQRAC (5) at 625 bipartite: none content of basic residues: 10.6% NLS Score: 0.33
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: found KLPK at 623
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LGSTVNILVTRLILLTEDQPTL at 32 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
95.7 %: nuclear 4.3 %: cytoplasmic
>> prediction for CG51213-04 is nuc (k=23)
A search ofthe NOVl 7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.
Figure imgf000323_0001
In a BLAST search of public sequence databases, the NOV 17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.
Figure imgf000324_0001
PFam analysis indicates that the NOV 17a protein contains the domains shown in the Table 17F.
Figure imgf000325_0001
Example 18.
The NOVl 8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A.
Table 18A. NOV18 Sequence Analysis
NOVl 8a, CG51448-05 SEQ ID NO: 211 1762 bp DNA Sequence ORF Start: ATG at 197 ORF Stop: TGA at 1760
TTTGAGTTAGACAAGCAGCAGCACACGCCTCCCTACCTCATGGCGACAGAAAATGGAGCAGTTGAGCT
GGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGGTCCCACAGGTGAAAGACCCCTGGCTGCAG
GGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGGATCCACCCACCCTGAAGAAAGATGCCAAA
GCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAACCCTCAACTAGCAGCCCTGCCCCAGCAGA CTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTGAGCAGGGAGCCTCAGGCAGCCAGGATCCT GGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAAGCAGCAGCCAGGAGGGGCTCACCTGCCTT TCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTCTGAGAAGCTGCTGGCCAAGAAGCCCCCAA GCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGACCCACAGCCCCACGGATCCCAGGCCAGCC AAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAGAAGGAAGTGGGAGAGAAAACCCCAGGCCA GGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGGGATTGAGTTCCAGGCTGTTCCCTCAGAGA AATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGGAGGAGGACTGCTTCCAGATTTTGGATGAT TGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTGGAGCTGAGGACCGGGAATGTCAGCAGTGA ATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGTGGCAAGTTTGGGGCAGTCTGTACCTGCATGGAGA AAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAGGAAATGGTG TTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGCAATCTGATCCAGCTGTATGCAGCCATCGA GACTCCGCATGAGATCGTCCTGTTCATGGAGTACATCGAGGGCGGAGAGCTCTTCGAGAGGATTGTGG ATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTGTCAGGCAGATCTGTGACGGGATCCTC TTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGTCAACACCAC CGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGAAGCTGAAGG TGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGGTGAATTATGACCAAATCTCCGATAAGACA GACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCTGGGAGATGA TGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTGGTACTTTGATGAAGAGACCTTTGAGGCCG TATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGGATGAACGCT GCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAGAAAGCCAAACGCTGTAACCGACGCCT TAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCGCTGGAAGAAAAACTTCATTGCTGTCA GCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCACTGATGGCTCTGGGGGTCTGA
NOVl 8a, CG51448-05 SEQ ID NO: 212 521 aa MW at 7751.9kD Protein Sequence
MPKPLPQRKGMVPWPNPQLAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQAAARRGS PAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKT PGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNV SSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYA AIETPHEIVLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NTTGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLLSGLSPFL GDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHPWLNNLAEKAKRCN RRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV18b, CG51448-01 SEQ ID NO: 213 1788 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOV 18b, CG51448-01 SEQ ID NO: 214 595 aa MW at 64501.9kD Protein Sequence
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOVlδc, 274051198 SEQ ID NO: 215 787 bp DNA Sequence ORF Start: at 2 jORF Stop: end of sequence
CACCAAGCTTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAAGTTTGGGGCAGTCTGTACCTGCATGG AGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAGGAAATG GTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGCAATCTGATCCAGCTGTATGCAGCCAT CGAGACTCCGCATGAGATCGTCCTGTTCATGGAGTACATCGAGGGCGGAGAGCTCTTCGAGAGGATTG TGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTGTCAGGCAGATCTGTGACGGGATC CTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGTCAACAC CACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGAAGCTGA AGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGGTGAATTATGACCAAATCTCCGATAAG ACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCTGGGAGA TGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTGGTACTTTGATGAAGAGACCTTTGAGG CCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGGATGAAC GCTGCCCAGTGTCTCGCCCATCCCTGGCTCGTCGACGGC
NOVlδc, 274051198 SEQ ID NO: 216 262 aa MW at 29771.1kD Protein Sequence
TKLMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAI ETPHEIVLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCVNT TGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYMLLSGLSPFLGD DDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHPWLVDG
NOV18d, 274051170 SEQ ID NO: 217 1813 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCAAGCTTCCCACCATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAG ACAAGGCACCTAAAGGTCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGAC CCAAAGAAAGCTCCGGATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGA TGGTACCCTGGCCCAACCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGC CCGCGGAGGGCAGTGCTGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTC AAGAAGCCCAAGGCTGAGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAA GGCAGCAGAGGGCCAAGCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTG CCATCATCTCCAGTTCTGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTT GAAGGGGTGCCCATGACCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACAT CCTGGCAGAGAGCCAGAAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAG GGGACACCTCGAGGGGGATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTC TGTCTCACAGCCAGGGAGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTT CCCTCACCGCATGGTGGAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGG CGCTCGGAGGTGGCAAGTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCA GCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAA CCAGCTGAACCACCGCAATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGT TCATGGAGTACATCGAGGGCGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAG GTGGACACCATGGTGTTTGTCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTT GCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTG ACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTC CTGTCACCTGAGGTGGTGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGAT CACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACG TTCTATCTGGCAACTGGTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTT GTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTG GCTCAACAACCTGGCGGAGAAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGA AATACCTCATGAAGAGGCGCTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAG ATCAGCAGCTCGGGGGCACTGATGGCTCTGGGGGTCGTCGACGGC
NOV18d, 274051170 SEQ ID NO: 218 604 aa MW at 65496. lkD Protein Sequence
TKLPTMATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGD GTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKK AAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNI LAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPF PHRMVELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMN QLNHRNLIQLYAAIETPHEIVLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVL HLDLKPENILCVNTTGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVI TYMLLSGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHPW LNNIJAEKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGVVDG
NOVl 8e, CG51448-02 SEQ ID NO: 219 2010 bp DNA Sequence ORF Start: ATG at 40 ORF Stop: TGA at 1828
TTTGAGTTAGACAAGCAGCAGCACACGCCTCCCTACCTCATGGCGACAGAAAATGGAGCAGTTGAGCT
GGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGGTCCCACAGGTGAAAGACCCCTGGCTGCAG GGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGGATCCACCCACCCTGAAGAAAGATGCCAAA GCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAACCCTCAACTAGCAGCCAAGGCCCCAAAGG AGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGCTGGGCCCCCGGCAGCCCTGCCCCAGCAGA CTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTGAGCAGGGAGCCTCAGGCAGCCAGGATCCT GGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAAGCAGCAGCCAGGAGGGGCTCACCTGCCTT TCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTCTGAGAAGCTGCTGGCCAAGAAGCCCCCAA GCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGACCCACAGCCCCACGGATCCCAGGCCAGCC AAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAGAAGGAAGTGGGAGAGAAAACCCCAGGCCA GGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGGGATTGAGTTCCAGGCTGTTCCCTCAGAGA AATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGGAGGAGGACTGCTTCCAGATTTTGGATGAT TGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTGGAGCTGAGGACCGGGAATGTCAGCAGTGA ATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGTGGCAAGTTTGGGGCAGTCTGTACCTGCATGGAGA AAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAGGAAATGGTG TTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGCAATCTGATCCAGCTGTATGCAGCCATCGA GACTCCGCATGAGATCGTCCTGTTCATGGAGTACATCGAGGGCGGAGAGCTCTTCGAGAGGATTGTGG ATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTGTCAGGCAGATCTGTGACGGGATCCTC TTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGTCAACACCAC CGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGAAGCTGAAGG TGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGCGGTGAATTATGACCAAATCTCCGATAAGACA GACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCTGGGAGATGA TGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTGGTACTTTGATGAAGAGACCTTTGAGGCCG TATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGGATGAACGCT GCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAGAAAGCCAAACGCTGTAACCGACGCCT TAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCGCTGGAAGAAAAACTTCATTGCTGTCA GCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCACTGATGGCTCTGGGGGTCTGAGCCCTG
GGCGCAGCTGAAGCCTGGACGCAGCCACACAGTGGCCGGGGCTGAAGCCACACAGCCCAGAAGGCCAG
AAAAGGCAGCCAGATCCCCAGGGCAGCCTCGTTAGGACAAGGCTGTGCCAGGCTGGGAGGCTCGGGGC
TCCCCACGCCCCCATGCAGTGACCGCTTCCCCGATGTG
NOV18e,CG51448-02 SEQ ID NO: 220 596 aa MW at 64656.lkD Protein Sequence
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLK PENILCVNTTGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEAVNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHP LNNLA EKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOVl8f,CG51448-03 SEQ ID NO: 221 1839 bp DNA Sequence ORF Start: ATG at 49 ORF Stop: TGA at 1837
CTAGAAAGACTTGAGTTAGACAAGCAGCAGCACACGCCTCCCTACCTCATGGCGACAGAAAATGGAGC
AGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGGTCCCACAGGTGAAAGACCCC TGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGGATCCACCCACCCTGAAGAAA GATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAACCCTCAACTAGCAGCCAAGG CCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGCTGGGCCCCCGGCAGCCCTGC CCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTGAGCAGGGAGCCTCAGGCAGC CAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAAGCAGCAGCCAGGAGGGGCTC ACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTCTGAGAAGCTGCTGGCCAAGA AGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGACCCACAGCCCCACGGATCCC AGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAGAAGGAAGTGGGAGAGAAAAC CCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGGGATTGAGTTCCAGGCTGTTC CCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGGAGGAGGACTGCTTCCAGATT TTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTGGAGCTGAGGACCGGGAATGT CAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGTGGCAAGTTTGGGGCAGTCTGTACCT GCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAG GAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGCAATCTGATCCAGCTGTATGC AGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGTACATCGAGGGCGGAGAGCTCTTCGAGA GGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTGTCAGGCAGATCTGTGAC GGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGT CAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGA AGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGCGGTGAATTATGACCAAATCTCC GATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCT GGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTGGTACTTTGATGAAGAGACCT TTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGG ATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAGAAAGCCAAACGCTGTAA CCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCGCTGGAAGAAAAACTTCA TTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCACTGATGGCTCTGGGGGTC TGA
NOVl 8f, CG51448-03 SEQ ID NO: 222 596 aa MW at 64656. lkD Protein Sequence
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASEL FEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLK PENILCVNTTGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEAVNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHPWLNNLA EKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV 18g, CG51448-04 SEQ ID NO: 223 2558 bp DNA Sequence ORF Start: ATG at 164 ORF Stop: TGA at 1949
CTTTGCTCCAGGTACCTCTCTCCCCTCAGTTAGCAGGCCTCGGCTTCCTGTCTCACTGCAGCCAGACG
AGAGGGGAAATTGGACAGCCTGACACACTCCACTCTTGTTTCTGCAGCTAGAAAGACTTGAGTTAGAC
AAGCAGCAGCACACGCCTCCCTACCTCATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAA
CCCATCAACAGACAAGGCACCTAAAGGTCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTG GCCCCCCAGACCCAAAGAAAGCTCCGGATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCA GAGAAAGGGGATGGTACCCTGGCCCAACCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAG GGGCGGGGGGCCCGCGGAGGGCAGTGCTGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTG AGACCAGCGTCAAGAAGCCCAAGGCTGAGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGG GTGGGCAAGAAGGCAGCAGAGGGCCAAGCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCC CAGCTGTCCCGCCATCATCTCCAGTTCTGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAG AGCTCACCTTTGAAGGGGTGCCCATGACCCACAGCCCCACGGATCCCAGGTCGGCCAAGGCAGAAGAA GGAAAGAACATCCTGGCAGAGAGCCAGAAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGC TAAGATGCAAGGGGACACCTCGAGGGGGATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGG GGCAGGCCCTCTGTCTCACAGCCAGGGAGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCT CCGGCCCCCTTCCCTCACCGCATGGTGGAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAA CTCCAAGGAGGCGCTCGGAGGGGGCAAGTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCC TCAAGCTGGCAGCCAAGGTCATCAAGAAACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATT GAGGTCATGAACCAGCTGAACCACCGCAATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGA GATCGTCCTGTTCATGGAGATCGAGGGCGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATC TGACCGAGGTGGACACCATGGTGTTTGTCAGGCAGATCTGTGACGGGATCCTCTTGATGCACAAGATG AGGGTTTTGCACCTGGACCTCAAGCCAGAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAA GATCATTGACTTTGGCCTGGCACGGAGGTATAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCC CAGAGTTCCTGTCACCTGAGGTGGTGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATG GGGGTGATCACCTACATGCTGCTGAGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCT AAACAACGTTCTATCTGGCAACTGGTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCA AAGACTTTGTCTCCAACCTCATCGTCAAGGACCAGAGGGCCCGGATGAACGCTGCCCAGTGTCTCGCC CATCCCTGGCTCAACAACCTGGCGGAGAAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTT GCTTAAGAAATACCTCATGAAGAGGCGCTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCT TCAAGAAGATCAGCAGCTCGGGGGCACTGATGGCTCTGGGGGTCTGAGCCCTGGGCGCAGCTGAAGCC
TGGACGCAGCCACACAGTGGCCGGGGCTGAAGCCACACAGCCCAGAAGGCCAGAAAAGGCAGCCAGAT
CCCCAGGGCAGCCTCGTTAGGACAAGGCTGTGCCAGGCTGGGAGGCTCGGGGCTCCCCACGCCCCCAT
GCAGTGACCGCTTCCCCGATGTGAGCCGCCTCGGAGTGTGGCCTGGATCCATCCTGCTAGCACCTCCq
CAGACAGGGCTCCAGCCTGTCGGCCACACCCCAGACTCCAGGCCCCCGTTGAAGCCGCTCCCGGTTCC
CTCCCCAGCTCCTCGTCTTTGAACTGCCGCCGCCGTGGTGACCCCTGCTTTGCCCCACTGGGAGAGTC!
CTTAGCCTGGGCCTCCTCCTAGCTGGAGTGCCATGGCTGGGGGGTCTCAGCATGTAGGGCTTCTGTGG
TTGTGGATGGGAGGCTCCTGGTGGGGCAGAAAGGCTGCAACGCTGATTCCTAAGGCCCAGCTGCCAGG
GAAGACAGAGCAGGCTTTGTGAGAGAGGACCTCCATGCCCCCGCCACCTCCCCACTCCAGCAGATAAG
GCCGAGCCCACACCATCTGGCCCAGGCTGGCCCCCACCACCT
NOVl 8g, CG51448-04 SEQ ID NO: 224 595 aa MW at 64476.9kD Protein Sequence
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRSAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILLMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYNPNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYMLLS GLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV18h, SNPl 3375535 of SEQ ID NO: 225 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 102 SNP Change: A to G
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAGGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVlδh, SNPl 3375535 of SEQ ID NO: 226 595 aa MW at 64501.9kD CG51448-01, Protein Sequence SNP Pos: 34 SNP Change: Lys to Lys
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYMLL SGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRR KKNFIAVSAANRFKKISSSGALMALGV
NOV18i, SNP13375536 of SEQ ID NO: 227 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786 SNP Pos: 287 SNP Change: C to T
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGTCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOV18i, SNP13375536 of SEQ ID NO: 228 595 aa MW at 64530.0kD CG51448-01, Protein Sequence SNP Pos: 96 SNP Change: Ala to Val
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAVLPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV18J, SNPl 3375537 of SEQ ID NO: 229 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 350 SNP Change: C to T
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGTCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOV18J, SNPl 3375537 of SEQ ID NO: 230| 595 aa MW at 64530.0kD CG51448-01, Protein Sequence SNP Pos: 117 SNP Change: Ala to Val
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGVSGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOVl 8k, SNPl 3375538 of SEQ ID NO: 231 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786 SNP Pos: 1249 SNP Change: A to T
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCTCCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVl 8k, SNPl 3375538 of SEQ ID NO: 232 595 aa MW at 64487.9kD CG51448-01, Protein Sequence SNP Pos: 417 SNP Change: Thr to Ser
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTSGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOVl 81, SNPl 3375539 of SEQ ID NO: 233 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 1358 SNP Change: T to C
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGCGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVl 81, SNPl 3375539 of SEQ ID NO: 234 595 aa MW at 64473.8kD CG51448-01, Protein Sequence SNP Pos: 453 SNP Change: Val to Ala
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEAVNYDQISDKTDM SMGVITYMLL SGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHP LNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV18m, SNP13375540 of SEQ ID NO: 235 178δ bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 1391 SNP Change: A to G
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGGCATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVl 8m, SNPl 3375540 of SEQ ID NO: 236 595 aa MW at 64443.9kD CG51448-01, Protein Sequence SNP Pos: 464 SNP Change: Asp to Gly
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTGMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV NOV18n, SNPl 3375541 of SEQ ID NO: 237 1788 bp CG51448-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 1511 SNP Change: A to G
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGGGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVlδn, SNP 13375541 of SEQ ID NO: 23δ 595 aa MW at 64429.δkD CG5144δ-01, Protein Sequence SNP Pos: 504 SNP Change: Glu to Gly
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEGTFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOVlδo, SNPl 3375542 of SEQ ID NO: 239 17δ bp CG5144δ-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 1675 SNP Change: C to T
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGTTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGTCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOVl 80, SNPl 3375542 of SEQ ID NO: 240 595 aa MW at 64535.9kD CG51448-01, Protein Sequence SNP Pos: 559 SNP Change: Leu to Phe
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKIAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILFKKYLMKRRWKKNFIAVSAANRFKKISSSGALMALGV
NOV18p, SNPl 3375543 of SEQ ID NO: 241 1788 bp CG5144δ-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1786
SNP Pos: 1724 SNP Change: T to G
ATGGCGACAGAAAATGGAGCAGTTGAGCTGGGAATTCAGAACCCATCAACAGACAAGGCACCTAAAGG TCCCACAGGTGAAAGACCCCTGGCTGCAGGGAAAGACCCTGGCCCCCCAGACCCAAAGAAAGCTCCGG ATCCACCCACCCTGAAGAAAGATGCCAAAGCCCCTGCCTCAGAGAAAGGGGATGGTACCCTGGCCCAA CCCTCAACTAGCAGCCAAGGCCCCAAAGGAGAGGGTGACAGGGGCGGGGGGCCCGCGGAGGGCAGTGC TGGGCCCCCGGCAGCCCTGCCCCAGCAGACTGCGACACCTGAGACCAGCGTCAAGAAGCCCAAGGCTG AGCAGGGAGCCTCAGGCAGCCAGGATCCTGGAAAGCCCAGGGTGGGCAAGAAGGCAGCAGAGGGCCAA GCAGCAGCCAGGAGGGGCTCACCTGCCTTTCTGCATAGCCCCAGCTGTCCTGCCATCATCTCCAGTTC TGAGAAGCTGCTGGCCAAGAAGCCCCCAAGCGAGGCATCAGAGCTCACCTTTGAAGGGGTGCCCATGA CCCACAGCCCCACGGATCCCAGGCCAGCCAAGGCAGAAGAAGGAAAGAACATCCTGGCAGAGAGCCAG AAGGAAGTGGGAGAGAAAACCCCAGGCCAGGCTGGCCAGGCTAAGATGCAAGGGGACACCTCGAGGGG GATTGAGTTCCAGGCTGTTCCCTCAGAGAAATCCGAGGTGGGGCAGGCCCTCTGTCTCACAGCCAGGG AGGAGGACTGCTTCCAGATTTTGGATGATTGCCCGCCACCTCCGGCCCCCTTCCCTCACCGCATGGTG GAGCTGAGGACCGGGAATGTCAGCAGTGAATTCAGTATGAACTCCAAGGAGGCGCTCGGAGGGGGCAA GTTTGGGGCAGTCTGTACCTGCATGGAGAAAGCCACAGGCCTCAAGCTGGCAGCCAAGGTCATCAAGA AACAGACTCCCAAAGACAAGGAAATGGTGTTGCTGGAGATTGAGGTCATGAACCAGCTGAACCACCGC AATCTGATCCAGCTGTATGCAGCCATCGAGACTCCGCATGAGATCGTCCTGTTCATGGAGATCGAGGG CGGAGAGCTCTTCGAGAGGATTGTGGATGAGGACTACCATCTGACCGAGGTGGACACCATGGTGTTTG TCAGGCAGATCTGTGACGGGATCCTCTTCATGCACAAGATGAGGGTTTTGCACCTGGACCTCAAGCCA GAGAACATCCTGTGTGTCAACACCACCGGGCATTTGGTGAAGATCATTGACTTTGGCCTGGCACGGAG GTACCACAACCCCAACGAGAAGCTGAAGGTGAACTTTGGGACCCCAGAGTTCCTGTCACCTGAGGTGG TGAATTATGACCAAATCTCCGATAAGACAGACATGTGGAGTATGGGGGTGATCACCTACATGCTGCTG AGCGGCCTCTCCCCCTTCCTGGGAGATGATGACACAGAGACCCTAAACAACGTTCTATCTGGCAACTG GTACTTTGATGAAGAGACCTTTGAGGCCGTATCAGACGAGGCCAAAGACTTTGTCTCCAACCTCATCG TCAAGGACCAGGCCCGGATGAACGCTGCCCAGTGTCTCGCCCATCCCTGGCTCAACAACCTGGCGGAG AAAGCCAAACGCTGTAACCGACGCCTTAAGTCCCAGATCTTGCTTAAGAAATACCTCATGAAGAGGCG CTGGAAGAAAAACTTCATTGCTGGCAGCGCTGCCAACCGCTTCAAGAAGATCAGCAGCTCGGGGGCAC TGATGGCTCTGGGGGTCTGA
NOV18p, SNPl 3375543 of SEQ ID NO: 242 595 aa MW at 64459.8kD CG51448-01, Protein Sequence SNP Pos: 575 SNP Change: Val to Gly
MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAKAPASEKGDGTLAQ PSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQGASGSQDPGKPRVGKKAAEGQ AAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELTFEGVPMTHSPTDPRPAKAEEGKNILAESQ KEVGEKTPGQAGQAKMQGDTSRGIEFQAVPSEKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMV ELRTGNVSSEFSMNSKEALGGGKFGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHR NLIQLYAAIETPHEIVLFMEIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKP ENILCVNTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYMLL SGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQARMNAAQCLAHPWLNNLAE KAKRCNRRLKSQILLKKYLMKRRWKKNFIAGSAANRFKKISSSGALMALGV
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 18B.
Table 18B. Comparison of the NOV18 protein sequences.
NOVl8a
N0V18b MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAK
N0V18C
NOVl8d TKLPTMATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAK
N0V18e MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAK
N0V18f MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAK
NOVlβg MATENGAVELGIQNPSTDKAPKGPTGERPLAAGKDPGPPDPKKAPDPPTLKKDAK
N0V18a MPKPLPQRKG-MVPWPNPQLAALPQQTATPETSVKKPKAEQ
NOVl8b APASEKGDGTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQ
NOVl8C
NOVlβd APASEKGDGTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQ
NOVlβe APASEKGDGTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQ
NOVl8f APASEKGDGTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQ
N0V18g APASEKGDGTLAQPSTSSQGPKGEGDRGGGPAEGSAGPPAALPQQTATPETSVKKPKAEQ
NOVl8a GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT NOVl8b GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT NOVl8c NOVl8d GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT NOVl8e GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT NOVl8f GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT NOVlβg GASGSQDPGKPRVGKKAAEGQAAARRGSPAFLHSPSCPAIISSSEKLLAKKPPSEASELT
NOVl8a FEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS NOVl8b FEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS NOVl8c NOV18d FEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS NOVl8e FEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS NOVl8f FEGVPMTHSPTDPRPAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS NOV18g FEGVPMTHSPTDPRSAKAEEGKNILAESQKEVGEKTPGQAGQAKMQGDTSRGIEFQAVPS
NOVl8a EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK NOV18b EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK NOV18C TKLMNSKEALGGGK NOVlθd EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK NOVlθe EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK NOVl8f EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK NOV18g EKSEVGQALCLTAREEDCFQILDDCPPPPAPFPHRMVELRTGNVSSEFSMNSKEALGGGK
NOVl8a FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVl8b FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVl8c FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVl8d FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVl8e FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVl8f FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI NOVlθg FGAVCTCMEKATGLKLAAKVIKKQTPKDKEMVLLEIEVMNQLNHRNLIQLYAAIETPHEI
NOVl8a VLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVl8b VLFMEIE-GGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVl8c VLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVl8 VLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVlδe VLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVl8f VLFMEYIEGGELFERIVDEDYHLTEVDTMVFVRQICDGILFMHKMRVLHLDLKPENILCV NOVlβg VLFMEIE-GGELFERIVDEDYHLTEVDTMVFVRQICDGILLMHKMRVLHLDLKPENILCV
NOVl8a NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYM NOVl8b NTTGHLVKIIDFGLARRYHNPNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYM NOVl8c NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYM NOVl8d NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEWNYDQISDKTDMWSMGVITYM NOVl8e NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEAVNYDQISDKTDMWSMGVITYM NOVl8f NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEAVNYDQISDKTDMWSMGVITYM NOVl8g NTTGHLVKIIDFGLARRYN-PNEKLKVNFGTPEFLSPEWNYDQISDKTDM SMGVITYM
NOVl8a LLSGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC NOVl8b LLSGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQ-ARMNAAQC NOVl8c LLSGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC NOVl8d LLSGLSPFLGDDDTETLNNVLSGNWYFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC NOVlβe LLSGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC NOVl8f LLSGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC NOV18g LLSGLSPFLGDDDTETLNNVLSGN YFDEETFEAVSDEAKDFVSNLIVKDQRARMNAAQC
NOVl8a LAHPWLNNLAEKAKRCNRRLKSQILLKKYLMKRR KKNFIAVSAANRFKKISSSGALMAL NOVl8b LAHPWLNNLAEKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMAL NOVl8c LAHPWLVDG NOVl8d LAHPWLNNLAEKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMAL NOVl8e LAHP LNNLAEKAKRCNRRLKSQILLKKYLMKRR KKNFIAVSAANRFKKISSSGALMAL NOVl8f LAHP LNNLAEKAKRCNRRLKSQILLKKYLMKRRWKKNFIAVSAANRFKKISSSGALMAL NOVl8g LAHPWLNNLAEKAKRCNRRLKSQILLKKYLMKRR KKNFIAVSAANRFKKISSSGALMAL
NOVl8a GV-- NOVl8b GV-- NOVl8c NOV18d GWDG NOVl8e GV NOVl8f GV NOV18g GV
NOV18a (SEQ ID NO: 212) NOVl8b (SEQ ID NO 214)
NOVl8c (SEQ ID NO 216)
NOVl8d (SEQ ID NO 218)
NOVlβe (SEQ ID NO 220)
NOVl8f (SEQ ID NO 222)
NOVlβg (SEQ ID NO 224)
Further analysis ofthe NOVl8a protein yielded the following properties shown in Table 18C.
Table 18C. Protein Sequence Properties NOVl8a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos. chg 3; neg.chg 0 H-region: length 20; peak value 1.84 PSG score: -2.56
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -10.69 possible cleavage site: between 29 and 30
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 1.48 (at 393) ALOM score: 1.48 (number of TMSs : 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 14.68 Hyd Moment(95): 9.57 G content: 1 D/E content: 1 S/T content: 2 Score: -2.37
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 18 QRK|GM
NUCDISC: discrimination of nuclear localization signals pat4: KKPK (4) at 34 pat7: none bipartite: RRLKSQILLKKYLMKRR at 477 content of basic residues: 12.9% NLS Score: 0.27
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: found RIVDEDYHL at 295
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
69.6 %: nuclear
17.4 %: mitochondrial
13.0 %: cytoplasmic
>> prediction for CG51448-05 is nuc (k=23)
A search ofthe NOVlδa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1 δD.
Figure imgf000341_0001
In a BLAST search of public sequence databases, the NOVlδa protein was found to have homology to the proteins shown in the BLASTP data in Table lδE.
Figure imgf000342_0001
PFam analysis inidcates that the NOV 18a protein contains the domains shown in the Table 18F.
Figure imgf000342_0002
Example 19.
The NOV 19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A. Table 19A. NOV19 Sequence Analysis
NOVl 9a, CG51752-02 SEQ ID NO: 243 1042 bp DNA Sequence ORF Start: ATG at 207 ORF Stop: TGA at 1008
AGAGTGCTCTAAACCCAGCTCGGCCTTTGCTGTATTAGACAGAAGCACCTCATTCATATCCCTGGGGC
CCCTGATGGTGCAGTGGTCTGGCTGTGGTCTGCACACCAGCTATTCTGTTTTGTTTTGTTTTGTTTTT
TCCTACCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGAGCT
ACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCCTTCCACTT GCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAAC TAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACA TGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATC TGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAA TGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGG AGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTAT GATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCA GGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGG TGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGG AGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAG ATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACTGATAATAAAATA GAGGCTATTCTTTCAACCGAAA
NOVl 9a, CG51752-02 SEQ ID NO: 244 267 aa MW at 29498.9kD Protein Sequence
MGFRFLGTANSATFETSLPLPLAPL FSATSPEELSWLGTNDLTSPSMEIKEVAS11LHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWREC VAGWGQTNAADKNSVKTDLMKVPMVIMDWEE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEK YQVGIIS GKSCGEKNTPGIYTSLV NYNL IEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
NOVl 9b, CG51752-03 SEQ ID NO: 245 δδδ bp DNA Sequence ORF Start: ATG at 79 ORF Stop: TGA at δδO
TTGTTTTTTCCTACCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTC
CTAGAGCTACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCC
TTCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAAC GACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAG AGCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGG TGCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGC CAGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGA CTGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATG AGAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAG TGGTACCAGGTGGGCATCATAACCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACAC CTCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAG AGAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGC AGCCCCAGATCCTGGCTCCCGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACTGATT ATAA
NOVl 9b, CG51752-03 SEQ ID NO: 246 267 aa MW at 2946δ.δkD Protein Sequence
MGFRFLGTANSATFETSLPLPLAPL FSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPAT RECWVAGWGQTNAADKNSVKTDLMKAPMVIMD EE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIITWGKSCGEKNTPGIYTSLV NYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRS LPLCPLSHVLFRAILY
NOV19c, 175069δ25 SEQ ID NO: 247 816 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCGCTTTTGAGACTTCCCTTCCCCT TCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACG ACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGA GCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGT GCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCC AGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGAC TGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGA GAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT GGTACCAGGTGGGCATCATAAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACC TCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGA GAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCA GCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19c, 175069825 SEQ ID NO: 248 272 aa MW at 29928.3kD Protein Sequence
GSTMGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKR ANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWREC VAGWGQTNAADKNSVKTDLMKAPMVIMD WEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIIS GKSCGEKNTPGIYT SLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRS LLLCPLSHVLFRAILYLE
NOV19d, 175069δ42 SEQ ID NO: 249 δlό bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCGCTTTTGAGACTTCCCTTCCCCT TCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACG ACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGA GCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGT GCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCC AGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGAC TGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGCGTGCCGGATACAAGAATGA GAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT GGTACCAGGTGGGCATCATAAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACC TCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGA GAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCA GCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19d, 175069δ42 SEQ ID NO: 250 272 aa MW at 299δl.3kD Protein Sequence
GSTMGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKR ANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWREC VAG GQTNAADKNSVKTDLMKAPMVIMD WEECSKMFPKLTKNMLRAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIIS GKSCGEKNTPGIYT SLVNYNL IEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOV19e, 25δ076315 SEQ ID NO: 251 729 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCAT GGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACA TTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACG CAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAA AAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGA TGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAG GGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCAT CAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGGTGAACTACAACC TCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGGAGGACTTCTGTC AAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCT GCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19e, 25δ076315 SEQ ID NO: 252 243 aa MW at 26δ02.7kD Protein Sequence
GSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPT QPGPAT REC VAG GQTNAADKNSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACK GDSGGPLVCTPEPGEKWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSV KQKPMGSPVSGVPEPGSPRS LLLCPLSHVLFRAILYLE
NOV19f, 25δ076366 SEQ ID NO: 253 729 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCAT GGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACA TTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACG CAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAA AAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGA TGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAG GGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCAT CAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGGTGAACTACAACC TCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGGAGGACTTCTGTC AAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCT GCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19f, 25δ076366 SEQ ID NO: 254 243 aa MW at 26830.8kD Protein Sequence
GSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPT QPGPAT RECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACK GDSGGPLVCTPEPGEKWYQVGIISWGKSCGEKNTPGIYTSLVNYNL IEKVTQLEGRPFNAEKRRTSV KQKPMGSPVSGVPEPGSPRS LLLCPLSHVLFRAILYLE
NOV19g, CG51752-04 SEQ ID NO: 255 δ52 bp DNA Sequence ORF Start: ATG at 46 ORF Stop: TGA at δ47
CTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGAGCTACATGGGATTTAGGTTTCTGGGCAC
AGCCAATTCTGCCACTTTTGAGGCTTCCCTTCCCCTTCCACTTGCCCCTCTCTGGTTCTCTGCCCCCA GTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCATGGAAATAAAGGAG GTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACATTGCCTTGCTGCT GCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACGCAGCCCGGCCCTG CCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACTCTGTGAAA ACGGATCTGATGAAAGCGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGATGTTTCCAAAACT TACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAGGGTGACAGTGGGG GGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCATCAGCTGGGGAAAG AGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGGTGAATTACAACCTCTGGATCGAGAA AGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGGAGGACTTCTGTCAAACAGAAACCTA TGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCTGCTCTGTCCCCTG TCCCATGTGTTGTTCAGAGCTATTTTGTACTGATAA
NOVl 9g, CG51752-04 SEQ ID NO: 256 267 aa MW at 29436.8kD Protein Sequence
MGFRFLGTANSATFEASLPLPLAPLWFSAPSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAG GQTNAADKNSVKTDLMKAPMVIMDWEE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEK YQVGIISWGKSCGEKNTPGIYTSLV NYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
NOV19h, 191887409 SEQ ID NO: 257 816 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCCT TCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACG ACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGA GCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGT GCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCC AGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGAC TGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGA GAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT GGTACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACC TCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGA GAAAAGGAGGACCTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCA GCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19h, 191887409 SEQ ID NO: 258 272 aa MW at 29986.4kD Protein Sequence
GSTMGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKR ANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAG GQTNAADKNSVKTDLMKVPMVIMD WEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEK YQVGIIS GKSCGEKNTPGIYT SLVNYNL IEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRS LLLCPLSHVLFRAILYLE
NOV19i, CG51752-01 SEQ ID NO: 259 1078 bp DNA Sequence ORF Start: ATG at 243 ORF Stop: TGA at 1044
TTGATCCGTGCCAAGTGGCTTTTTGTGGGCTCTGTAGAGTGCTCTAAACCCAGCTCGGCCTTTGCTGT
ATTAGACAGAAGCACCTCATTCATATCCCTGGGGCCCCTGATGGTGCAGTGGTCTGGCTGTGGTCTGCj
ACACCAGCTATTCTGTTTTGTTTTGTTTTGTTTTTTTCCTACCTTTTTCCAATCCTCACACCTTCTGA
TCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGAGCTACATGGGATTTAGGTTTCTGGGCACAGCCAAT
TCTGCCACTTTTGAGACTTCCCTTCCCCTTCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGA AGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCA GCATCATTCTTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCT TCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATG GCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATC TGATGAAAGTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAA AATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCT GGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTG GAGATAAGAACACCCCAGGGATATACACCTCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACC CAGCTAGGAGGCAGGCCCTTCAATGCAGAGAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTC CCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATG TGTTGTTCAGAGCTATTTTGTACTGATAATAAAATAGAGGCTATTCTTTCAACCGAAA
NOV 19i, CG51752-01 SEQ ID NO: 260 267 aa MW at 29412.8kD Protein Sequence
MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWREC VAGWGQTNAADKNSVKTDLMKVPMVIMD EE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEK YQVGIISWGKSCGDKNTPGIYTSLV NYNL IEKVTQLGGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
NOV19J, CG51752-05 SEQ ID NO: 261 816 bp DNA Sequence ORF Start: ATG at 10 ORF Stop: at 811
GGATCCACCATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCGCTTTTGAGACTTCCCTTCCCCT
TCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACG ACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGA GCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGT GCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCC AGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGAC TGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGA GAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT GGTACCAGGTGGGCATCATAAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACC TCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGA GAAAAGGAGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCA GCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOVl 9j, CG51752-05 SEQ ID NO: 262 267 aa MW at 29440.8kD Protein Sequence
MGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADKNSVKTDLMKAPMVIMD EE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIIS GKSCGEKNTPGIYTSLV NYNL IEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY NOVl 9k, CG51752-06 SEQ ID NO: 263 729 bp DNA Sequence ORF Start: at 7 ORF Stop: at 724
GGATCCGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAACTAGCCCATCCAT
GGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACATGGACAATGACA TTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATCTGCCTCCCCACG CAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAATGCTGCTGACAA AAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGGAGTGTTCAAAGA TGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTATGATGCCTGCAAG GGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCAGGTGGGCATCAT CAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGGTGAACTACAACC TCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGGAGGACCTCTGTC AAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAGATCCTGGCTCCT GCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOV19k, CG51752-06 SEQ ID NO: 264 239 aa MW at 26444.4kD Protein Sequence
ATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQP GPATWREC VAG GQTNAADKNSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGD SGGPLVCTPEPGEK YQVGI IS GKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQ KPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
NOV 191, CG51752-07 SEQ ID NO: 265 816 bp DNA Sequence ORF Start: ATG at 10 ORF Stop: at 811
GGATCCACCATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCCT
TCCACTTGCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACG ACTTAACTAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGA GCCAACATGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGT GCCCATCTGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCC AGACCAATGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGAC TGGGAGGAGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGA GAGCTATGATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGT GGTACCAGGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACC TCGTTGGTGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGA GAAAAGGAGGACCTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCA GCCCCAGATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACCTCGAG
NOVl 91, CG51752-07 SEQ ID NO: 266 267 aa MW at 29498.9kD Protein Sequence
MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPAT RECWVAGWGQTNAADKNSVKTDLMKVPMVIMDWEE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIISWGKSCGEKNTPGIYTSLV NYNL IEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRS LLLCPLSHVLFRAILY
NOVl 9m, SNP133745δ4 of SEQ ID NO: 267 1042 bp CG51752-02, DNA Sequence ORF Start: ATG at 207 ORF Stop: TGA at 100δ
SNP Pos: 243 SNP Change: A to G
AGAGTGCTCTAAACCCAGCTCGGCCTTTGCTGTATTAGACAGAAGCACCTCATTCATATCCCTGGGGC
CCCTGATGGTGCAGTGGTCTGGCTGTGGTCTGCACACCAGCTATTCTGTTTTGTTTTGTTTTGTTTTT
TCCTACCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGAGCT
ACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCGCTTTTGAGACTTCCCTTCCCCTTCCACTT GCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAAC TAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACA TGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATC TGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAA TGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGTGCCAATGGTCATCATGGACTGGGAGG AGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTAT GATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCA GGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGG TGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGG AGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAG ATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACTGATAATAAAATA GAGGCTATTCTTTCAACCGAAA
NOV19m, SNP133745δ4 of SEQ ID NO: 26δ 267 aa MW at 29468.8kD CG51752-02, Protein Sequence SNP Pos: 13 SNP Change: Thr to Ala
MGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWREC VAG GQTNAADKNSVKTDLMKVPMVIMD EE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIIS GKSCGEKNTPGIYTSLV NYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
NOV19n, SNP 13374585 of SEQ ID NO: 269 1042 bp CG51752-02, DNA Sequence ORF Start: ATG at 207 ORF Stop: TGA at 100δ
SNP Pos: 5δ6 SNP Change: T to C
AGAGTGCTCTAAACCCAGCTCGGCCTTTGCTGTATTAGACAGAAGCACCTCATTCATATCCCTGGGGC
CCCTGATGGTGCAGTGGTCTGGCTGTGGTCTGCACACCAGCTATTCTGTTTTGTTTTGTTTTGTTTTT
TCCTACCTTTTTCCAATCCTCACACCTTCTGATCAACAGCCCCAGTAGGGTTTAAAGGTCCTAGAGCT
ACATGGGATTTAGGTTTCTGGGCACAGCCAATTCTGCCACTTTTGAGACTTCCCTTCCCCTTCCACTT GCCCCTCTCTGGTTCTCTGCCACCAGTCCAGAAGAACTGAGTGTCGTGCTGGGGACCAACGACTTAAC TAGCCCATCCATGGAAATAAAGGAGGTCGCCAGCATCATTCTTCACAAAGACTTTAAGAGAGCCAACA TGGACAATGACATTGCCTTGCTGCTGCTGGCTTCGCCCATCAAGCTCGATGACCTGAAGGTGCCCATC TGCCTCCCCACGCAGCCCGGCCCTGCCACATGGCGCGAATGCTGGGTGGCAGGTTGGGGCCAGACCAA TGCTGCTGACAAAAACTCTGTGAAAACGGATCTGATGAAAGCGCCAATGGTCATCATGGACTGGGAGG AGTGTTCAAAGATGTTTCCAAAACTTACCAAAAATATGCTGTGTGCCGGATACAAGAATGAGAGCTAT GATGCCTGCAAGGGTGACAGTGGGGGGCCTCTGGTCTGCACCCCAGAGCCTGGTGAGAAGTGGTACCA GGTGGGCATCATCAGCTGGGGAAAGAGCTGTGGAGAGAAGAACACCCCAGGGATATACACCTCGTTGG TGAACTACAACCTCTGGATCGAGAAAGTGACCCAGCTAGAGGGCAGGCCCTTCAATGCAGAGAAAAGG AGGACTTCTGTCAAACAGAAACCTATGGGCTCCCCAGTCTCGGGAGTCCCAGAGCCAGGCAGCCCCAG ATCCTGGCTCCTGCTCTGTCCCCTGTCCCATGTGTTGTTCAGAGCTATTTTGTACTGATAATAAAATA GAGGCTATTCTTTCAACCGAAA
NOV19n, SNP133745δ5 of SEQ ID NO: 270 267 aa MW at 29470.δkD CG51752-02, Protein Sequence SNP Pos: 127 SNP Change: Val to Ala
MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASIILHKDFKRANM DNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWAGWGQTNAADKNSVKTDLMKAPMVIMDV.EE CSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGEKWYQVGIISWGKSCGEKNTPGIYTSLV NYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGSPVSGVPEPGSPRSWLLLCPLSHVLFRAILY
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 19B.
Table 19B. Comparison of the NOV19 protein sequences.
NOV19a MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19b MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19C GSTMGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19d GSTMGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19e GSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19f GSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19g MGFRFLGTANSATFEASLPLPLAPLWFSAPSPEELSWLGTNDLTSPSMEIKEVASI
NOV19h GSTMGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI NOV19i MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19j MGFRFLGTANSAAFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOV19k ATSPEELSWLGTNDLTSPSMEIKEVASI
NOV191 MGFRFLGTANSATFETSLPLPLAPLWFSATSPEELSWLGTNDLTSPSMEIKEVASI
NOVl9a ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19b ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19c ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19d ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19e ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19f ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19g ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19h ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19i ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19J ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19k ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOVl91 ILHKDFKRANMDNDIALLLLASPIKLDDLKVPICLPTQPGPATWRECWVAGWGQTNAADK
NOV19a NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19b NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19C NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19d NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLRAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19e NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19f NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl9g NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl9h NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOV19i NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl9j NSVKTDLMKAPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl9k NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl91 NSVKTDLMKVPMVIMDWEECSKMFPKLTKNMLCAGYKNESYDACKGDSGGPLVCTPEPGE
NOVl9a KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOVl9b KWYQVGIITWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19c KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19d KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19e KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOVl9f KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19g KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19h KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19i KWYQVGIISWGKSCGDKNTPGIYTSLVNYNLWIEKVTQLGGRPFNAEKRRTSVKQKPMGS
NOVl9j KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOVl9k KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV191 KWYQVGIISWGKSCGEKNTPGIYTSLVNYNLWIEKVTQLEGRPFNAEKRRTSVKQKPMGS
NOV19a PVSGVPEPGSPRSWLLLCPLSHVLFRAILY- -
NOV19b PVSGVPEPGSPRSWLPLCPLSHVLFRAILY- -
NOV19C PVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOV19d PVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOV19e PVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOVl9f PVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOV19g PVSGVPEPGSPRSWLLLCPLSHVLFRAILY- -
NOV19h PVSGVPEPGSPRSWLLLCPLSHVLFRAILYLE
NOV19i PVSGVPEPGSPRSWLLLCPLSHVLFRAILY--
NOV19j PVSGVPEPGSPRSWLLLCPLSHVLFRAILY-- NOVl9k PVSGVPEPGSPRSWLLLCPLSHVLFRAILY- -
NOVl91 PVSGVPEPGSPRSWLLLCPLSHVLFRAILY- -
NOVl9a (SEQ ID NO 244)
NOVl9b (SEQ ID NO 246)
NOVl9c (SEQ ID NO 248)
NOV19d (SEQ ID NO 250)
NOV19e (SEQ ID NO 252)
NOVl9f (SEQ ID NO 254)
NOV19g (SEQ ID NO 256)
NOV19h (SEQ ID NO 258)
NOVl9i (SEQ ID NO 260)
NOVl9j (SEQ ID NO 262)
NOVl9k (SEQ ID NO 264)
NOVl91 (SEQ ID NO 266)
Further analysis ofthe NOVl 9a protein yielded the following properties shown in Table 19C.
Table 19C. Protein Sequence Properties NOV19a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 4; pos. chg 1; neg.chg 0 H-region: length 10; peak value 4.03 PSG score: -0.38
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.06 possible cleavage site: between 32 and 33
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 2.38 (at 72) ALOM score: 0.05 (number of TMSs : 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 8.51 Hyd Moment(95): 7.65 G content: 2 D/E content : 2 S/T content : 8 Score: -4.16
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 14 FRFlLG NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 10.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: GFRF none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs:
Bacterial regulatory proteins, gntR family signature (PS00043) *** found ***
VASIILHKDFKRANMDNDIALL at 54
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Figure imgf000352_0001
A search ofthe NOV 19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19D.
Figure imgf000352_0002
In a BLAST search of public sequence databases, the NOV 19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19E.
Figure imgf000353_0001
PFam analysis indicates that the NOV 19a protein contains the domains shown in the Table 19F.
Table 19F. Domain Analysis of NOV19a
Identities/
Pfam Domain NOVl 9a Match Region Similarities Expect Value for the Matched Region trypsin 5..210 75/267 (28%) 8.6e-34 153/267 (57%)
Example 20. The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A. Table 20A. NOV20 Sequence Analysis
NOV20a, CG51914-02 SEQ ID NO: 271 [3261 bp DNA Sequence ORF Start: ATG at 92 ORF Stop: TGA at 3146
AGCGGGGCTCTGGGGTCTGGGGGCATTGCTCAGCGGTGCTAGGCTGGCGCGGCTTGAGCCGCCGCCGG
ACTGACAGCTCGGTCTGCGGACCATGGAGACCTGCGCCGGTCCACACCCGCTGCGCCTCTTCCTCTGC
CGGATGCAGCTCTGTCTCGCGCTGCTTTTGGGACCCTGGCGGCCTGGGACCGCCGAGGAAGTTATCCT CCTGGATTCCAAAGCCTCCCAGGCCGAGCTGGGCTGGACTGCACTGCCAAGTAATGGGTGGGAGGAGA TCAGCGGCGTGGATGAACACGACCGTCCCATCCGCACGTACCAAGTGTGCAATGTGCTGGAGCCCAAC CAGGACAACTGGCTGCAGACTGGCTGGATAAGCCGTGGCCGCGGGCAGCGCATCTTCGTGGAACTGCA GTTCACACTCCGTGACTGCAGCAGCATCCCTGGCGCCGCGGGTACCTGCAAGGAGACCTTCAACGTCT ACTACCTGGAAACTGAGGCCGACCTGGGCCGTGGGCGTCCCCGCCTAGGCGGCAGCCGGCCCCGCAAA ATCGACACGATCGCGGCGGACGAGAGCTTCACGCAGGGCGACCTGGGTGAGCGCAAGATGAAGCTGAA CACAGAGGTGCGCGAGATCGGACCGCTCAGCCGGCGGGGTTTCCACCTGGCCTTTCAGGACGTGGGCG CATGCGTGGCGCTTGTCTCGGTGCGCGTCTACTACAAGCAGTGCCGCGCCACCGTGCGGGGCCTGGCC ACGTTCCCAGCCACCGCAGCCGAGAGCGCCTTCTCCACACTGGTGGAAGTGGCCGGAACGTGCGTGGC GCACTCGGAAGGGGAGCCTGGCAGCCCCCCACGCATGCACTGCGGCGCCGACGGCGAGTGGCTGGTGC CTGTGGGCCGCTGCAGCTGCAGCGCGGGATTCCAGGAGCGTGGTGACTTCTGCGAATGTCCCCCAGGG TTTTACAAGGTGTCCCCGCGGCGGCCCCTCTGCTCACCGTGCCCAGAGCACAGCCGGGCCCTGGAAAA CGCCTCCACCTTCTGCGTGTGCCAGGACAGCTATGCGCGCTCACCCACCGACCCGCCCTCGGCTTCCT GCACCCGTCCGCCGTCGGCGCCGCGGGACCTGCAGTACAGCCTGAGCCGCTCGCCGCTGGTGCTGCGA CTGCGCTGGCTGCCGCCGGCCGACTCGGGAGGCCGCTCGGACGTCACCTACTCGCTGCTGTGCCTGCG CTGCGGCCGCGAGGGCCCGGCGGGCGCCTGCGAGCCGTGCGGGCCGCGCGTGGCCTTCCTACCGCGCC AGGCAGGGCTGCGGGAGCGAGCCGCCACGCTGCTGCACCTGCGGCCCGGGGCGCGCTACACCGTGCGC GTGGCCGTGCTCAACGGCGTCTCGTCAGCGCCCTGGGAGGAGGATGAGATCCGCAGGGACCGAGTGGA ACCCCAGAGCGTGTCCCTGTCGTGGCGGGAGCCCATCCCTGCCGGAGCCCCTGGGGCCAATGACACGG AGTACGAGATCCGATACTACGAGAAGGGTCAGAGTGAGCAGACTTACTCCATGGTGAAGACGGGGGCG CCCACAGTCACCGTCACCAACCTGAAGCCGGCTACCCGCTACGTCTTTCAGATCCGGGCCGCTTCCCC GGGGCCATCCTGGGAGGCCCAGAGTTTTAACCCCAGCATTGAAGTACAGACCCTGGGGGAGGCTGCCT CAGGGTCCAGGGACCAGAGCCCCGCCATTGTCGTCACCGTAGTGACCATCTCGGCCCTCCTCGTCCTG GGCTCCGTGATGAGTGTGCTGGCCATTTGGAGGAGGCCCTGCAGCTATGGCAAAGGAGGAGGGGATGC CCATGATGAAGAGGAGCTGTATTTCCACTTCAAAGTCCCAACACGTCGCACATTCCTGGACCCCCAGA GCTGTGGGGACCTGCTGCAGGCTGTGCATCTGTTCGCCAAGGAACTGGATGCGAAAAGCGTCACGCTG GAGAGGAGCCTTGGAGGAGGCAAGCTGGGCGCCCAGGAAGCCTTGTCCCCATCTGGAAGCCTCACCCA CTCTATAGGCCCCGCCCCTACTCTGTCCACACCTCTATCCGGGCGGTTTGGGGAGCTGTGCTGTGGCT GCTTGCAGCTCCCCGGTCGCCAGGAGCTGCTCGTAGCCGTGCATATGCTGAGGGACAGCGCCTCCGAC TCACAGAGGCTCGGCTTCCTGGCCGAGGCCCTCACGCTGGGCCAGTTTGACCATAGCCACATCGTGCG GCTGGAGGGCGTTGTTACCCGAGGTAGGGGAAGCACCTTGATGATTGTCACCGAGTACATGAGCCATG GGGCCCTGGACGGCTTCCTCAGGCGGCACGAGGGGCAGCTGGTGGCTGGGCAACTGATGGGGTTGCTG CCTGGGCTGGCATCAGCCATGAAGTATCTGTCAGAGATGGGCTACGTTCACCGGGGCCTGGCAGCTCG CCATGTGCTGGTCAGCAGCGACCTTGTCTGCAAGATCTCTGGCTTCGGGCGGGGCCCCCGGGACCGAT CAGAGGCTGTCTACACCACTGGCCGGAGCCCAGCGCTATGGGCCGCTCCCGAGACACTTCAGTTTGGC CACTTCAGCTCTGCCAGTGACGTGTGGAGCTTCGGCATCATCATGTGGGAGGTGATGGCCTTTGGGGA GCGGCCTTACTGGGACATGTCTGGCCAAGACGTGATCAAGGCTGTGGAGGATGGCTTCCGGCTGCCAC CCCCCAGGAACTGTCCTAACCTTCTGCACCGACTAATGCTCGACTGCTGGCAGAAGGACCCAGGTGAG CGGCCCAGGTTCTCCCAGATCCACAGCATCCTGAGCAAGATGGTGCAGGACCCAGAGCCCCCCAAGTG TGCCCTGACTACCTGTCCCAGGCCTCCCACCCCACTAGCGGACCGTGCCTTCTCCACCTTCCCCTCCT TTGGCTCTGTGGGCGCGTGGCTGGAGGCCCTGGACCTGTGCCGCTACAAGGACAGCTTCGCGGCTGCT GGCTATGGGAGCCTGGAGGCCGTGGCCGAGATGACTGCCCAGGACCTGGTGAGCCTAGGCATCTCTTT GGCTGAACATCGAGAGGCCCTCCTCAGCGGGATCAGCGCCCTGCAGGCACGAGTGCTCCAGCTGCAGG GCCAGGGGGTGCAGGTGTGAGTGGACCCCATTCTTCCAAGGCAGGACTCCGGTGGGGGTCCAGTCCCC
CAGCCCTGCCCAAGGACCGTGGCAAGCTGCGCTCCAGCAGTGTGGGAGGGAGCGCTCTCTTCCTC
NO V20a, CG51914-02 SEQ ID NO: 272 lOlδ aa MW at l l0δ51.δkD Protein Sequence
METCAGPHPLRLFLCRMQLCLALLLGP RPGTAEEVILLDSKASQAELGWTALPSNG EEISGVDEHD RPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAGTCKETFNVYYLETEAD LGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRRGFHLAFQDVGACVALVSV RVYYKQCRATVRGLATFPATAAESAFSTLVEVAGTCVAHSEGEPGSPPRMHCGADGEWLVPVGRCSCS AGFQERGDFCECPPGFYKVSPRRPLCSPCPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAP RDLQYSLSRSPLVLRLR LPPADSGGRSDVTYSLLCLRCGREGPAGACEPCGPRVAFLPRQAGLRERA ATLLHLRPGARYTVRVAVLNGVSSAPWEEDEIRRDRVEPQSVSLSWREPIPAGAPGANDTEYEIRYYE KGQSEQTYSMVKTGAPTVTVTNLKPATRYVFQIRAASPGPSWEAQSFNPSIEVQTLGEAASGSRDQSP AIVVTVVTISALLVLGSVMSVLAI RRPCSYGKGGGDAHDEEELYFHFKVPTRRTFLDPQSCGDLLQA VHLFAKELDAKSVTLERSLGGGKLGAQEALSPSGSLTHSIGPAPTLSTPLSGRFGELCCGCLQLPGRQ ELLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRGRGSTLMIVTEYMSHGALDGFLR RHEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTTG RSPAL AAPETLQFGHFSSASDV SFGIIMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPNL LHRLMLDCWQKDPGERPRFSQIHSILSKMVQDPEPPKCALTTCPRPPTPLADRAFSTFPSFGSVGA L EALDLCRYKDSFAAAGYGSLEAVAEMTAQDLVSLGISLAEHREALLSGISALQARVLQLQGQGVQV
NOV20b, CG51914-01 SEQ ID NO: 273 3003 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 3001
ATGGTATTGACAACTGCTATACCAGCCTGGCTTCTTAGCTGTTCCCTCCCACTCTCATCCTGGGCCCA CCATGCGACACCGCCCCTCCGTCTAGTAGTTATCCTCCTGGATTCCAAAGCCTCCCAGGCCGAGCTGG GCTGGACTGCACTGCCAAGTAATGGGTGGGAGGAGATCAGCGGCGTGGATGAACACGACCGTCCCATC CGCACGTACCAAGTGTGCAATGTGCTGGAGCCCAACCAGGACAACTGGCTGCAGACTGGCTGGATAAG CCGTGGCCGCGGGCAGCGCATCTTCGTGGAACTGCAGTTCACACTCCGTGACTGCAGCAGCATCCCTG GCGCCGCGGGTACCTGCAAGGAGACCTTCAACGTCTACTACCTGGAAACTGAGGCCGACCTGGGCCGT GGGCGTCCCCGCCTAGGCGGCAGCCGGCCCCGCAAAATCGACACGATCGCGGCGGACGAGAGCTTCAC GCAGGGCGACCTGGGTGAGCGCAAGATGAAGCTGAACACAGAGGTGCGCGAGATCGGACCGCTCAGCC GGCGGGGTTTCCACCTGGCCTTTCAGGACGTGGGCGCATGCGTGGCGCTTGTCTCGGTGCGCGTCTAC TACAAGCAGTGCCGCGCCACCGTGCGGGGCCTGGCCACGTTCCCAGCCACCGCAGCCGAGAGCGCCTT CTCCACACTGGTGGAAGTGGCCGGAACGTGCGTGGCGCACTCGGAAGGGGAGCCTGGCAGCCCCCCAC GCATGCACTGCGGCGCCGACGGCGAGTGGCTGGTGCCTGTGGGCCGCTGCAGCTGCAGCGCGGGATTC CAGGAGCGTGGTGACTTCTGCGAATGTCCCCCAGGGTTTTACAAGGTGTCCCCGCGGCGGCCCCTCTG CTCACCGTGCCCAGAGCACAGCCGGGCCCTGGAAAACGCCTCCACCTTCTGCGTGTGCCAGGACAGCT ATGCGCGCTCACCCACCGACCCGCCCTCGGCTTCCTGCACCCGTCCGCCGTCGGCGCCGCGGGACCTG CAGTACAGCCTGAGCCGCTCGCCGCTGGTGCTGCGACTGCGCTGGCTGCCGCCGGCCGACTCGGGAGG CCGCTCGGACGTCACCTACTCGCTGCTGTGCCTGCGCTGCGGCCGCGAGGGCCCGGCGGGCGCCTGCG AGCCGTGCGGGCCGCGCGTGGCCTTCCTACCGCGCCAGGCAGGGCTGCGGGAGCGAGCCGCCACGCTG CTGCACCTGCGGCCCGGCGCGCGCTACACCGTGCGCGTGGCCGCGCTCAACGGCGTCTCGGGCCCGGC GGCCGCCGCGGGAACCACCTACGCGCAGGTCACCGTCTCCACCGGGCCCTCAGCGCCCTGGGAGGAGG ATGAGATCCGCAGGGACCGAGTGGAACCCCAGAGCGTGTCCCTGTCGTGGCGGGAGCCCATCCCTGCC GGAGCCCCTGGGGCCAATGACACGGAGTACGAGATCCGATACTACGAGAAGCAGAGTGAGCAGACTTA CTCCATGGTGAAGACAGGGGCGCCCACAGTCACCGTCACCAACCTGAAGCCGGCTACCCGCTACGTCT TTCAGATCCGGGCCGCTTCCCCGGGGCCATCCTGGGAGGCCCAGAGTTTTAACCCCAGCATTGAAGTA CAGACCCTGGGGGAGGCTGCCTCAGGGTCCAGGGACCAGAGCCCCGCCATTGTCGTCACCGTAGTGAC CATCTCGGCCCTCCTCGTCCTGGGCTCCGTGATGAGTGTGCTGGCCATTTGGAGGAGGAGGCCCTGCA GCTATGGCAAAGGAGGAGGGGATGCCCATGATGAAGAGGAGCTGTATTTCCACTGTAAAGTCCCAACA CGTCGCACATTCCTGGACCCCCAGAGCTGTGGGGACCTGCTGCAGGCTGTGCATCTGTTCGCCAAGGA ACTGGATGCGAAAAGCGTCACGCTGGAGAGGAGCCTTGGAGGAGGCAAGTTTGGGGAGCTGTGCTGTG GCTGCTTGCAGCTCCCCGGTCGCCAGGAGCTGCTCGTAGCCGTGCACATGCTGAGGGACAGCGCCTCC GACTCACAGAGGCTCGGCTTCCTGGCCGAGGCCCTCACGCTGGGCCAGTTTGACCATAGCCACATCGT GCGGCTGGAGGGCGTTGTTACCCGAGGTAGGACCTTGATGATTGTCACCGAGTACATGAGCCATGGGG CCCTGGACGGCTTCCTCAGGCACGAGGGGCAGCTGGTGGCTGGGCAACTGATGGGGTTGCTGCCTGGG CTGGCATCAGCCATGAAGTATCTGTCAGAGATGGGCTACGTTCACCGGGGCCTGGCAGCTCGCCATGT GCTGGTCAGCAGCGACCTTGTCTGCAAGATCTCTGGCTTCGGGCGGGGCCCCCGGGACCGATCAGAGG CTGTCTACACCACTGGCCGGAGCCCAGCGCTATGGGCCGCTCCCGAGACACTTCAGTTTGGCCACTTC AGCTCTGCCAGTGACGTGTGGAGCTTCGGCATCATCATGTGGGAGGTGATGGCCTTTGGGGAGCGGCC TTACTGGGACATGTCTGGCCAAGACGTGAAGGCTGTGGAGGATGGCTTCCGGCTGCCACCCCCCAGGA ACTGTCCTAACCTTCTGCACCGACTAATGCTCGACTGCTGGCAGAAGGACCCAGGTGAGCGGCCCAGG TTCTCCCAGATCCACAGCATCCTGAGCAAGATGGTGCAGGACCCAGAGCCCCCCAAGTGTGCCCTGAC TACCTGTCCCAGGCCTCCCACTCCACTAGCCGACCGTGCCTTCTCCACCTTCCCCTCCTTTGGCTCTG TGGGCGCGTGGCTGGAGGCCCTGGACCTGTGCCGCTACAAGGACAGCTTCGCGGCTGCTGGCTATGGG AGCCTGGAGGCCGTGGCCGAGATGACTGCCCAGGACCTGGTGAGCCTAGGCATCTCTTTGGCTGAACA TCGAGAGGCCCTCCTCAGCGGGATCAGCGCCCTGCAGGCACGAGTGCTCCAGCTGCAGGGCCAGGGGG TGCAGGTGTGA
NOV20b, CG51914-01 SEQ ID NO: 274 1000 aa MW at 10δ840.5kD Protein Sequence
MVLTTAIPAWLLSCSLPLSSWAHHATPPLRLWILLDSKASQAELG TALPSNG EEISGVDEHDRPI RTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAGTCKETFNVYYLETEADLGR GRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRRGFHLAFQDVGACVALVSVRVY YKQCRATVRGLATFPATAAESAFSTLVEVAGTCVAHSEGEPGSPPRMHCGADGE LVPVGRCSCSAGF QERGDFCECPPGFYKVSPRRPLCSPCPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDL QYSLSRSPLVLRLRWLPPADSGGRSDVTYSLLCLRCGREGPAGACEPCGPRVAFLPRQAGLRERAATL LHLRPGARYTVRVAALNGVSGPAAAAGTTYAQVTVSTGPSAPWEEDEIRRDRVEPQSVSLSWREPIPA GAPGANDTEYEIRYYEKQSEQTYSMVKTGAPTVTVTNLKPATRYVFQIRAASPGPSWEAQSFNPSIEV QTLGEAASGSRDQSPAIWTWTISALLVLGSVMSVLAIWRRRPCSYGKGGGDAHDEEELYFHCKVPT RRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGKFGELCCGCLQLPGRQELLVAVHMLRDSAS DSQRLGFLAEALTLGQFDHSHIVRLEGWTRGRTLMIVTEYMSHGALDGFLRHEGQLVAGQLMGLLPG LASAMKYLSEMGYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTTGRSPALWAAPETLQFGHF SSASDVWSFGIIMWEVMAFGERPYWDMSGQDVKAVEDGFRLPPPRNCPNLLHRLMLDCWQKDPGERPR FSQIHSILSKMVQDPEPPKCALTTCPRPPTPLADRAFSTFPSFGSVGAWLEALDLCRYKDSFAAAGYG SLEAVAEMTAQDLVSLGISLAEHREALLSGISALQARVLQLQGQGVQV
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 20B.
Table 20B. Comparison of the NOV20 protein sequences.
NOV20a METCAGPHPLRLFLCRMQLCLALLLGPWRPGTAEEVILLDSKASQAELGWTALPSNGWEE
NOV20b -MVLTTAIPAWLLSC--SLPLSSWAHHATPPLRLWILLDSKASQAELGWTALPSNGWEE
NOV20a ISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAG
NOV20b ISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAG
NOV20a TCKETFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREI
NOV20b TCKETFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREI
NOV20a GPLSRRGFHLAFQDVGACVALVSV VYYKQCRATVRGLATFPATAAESAFSTLVEVAGTC
NOV20b GPLSRRGFHLAFQDVGACVALVSVRVYYKQCRATVRGLATFPATAAESAFSTLVEVAGTC
NOV20a VAHSEGEPGSPPRMHCGADGEWLVPVGRCSCSAGFQERGDFCECPPGFYKVSPRRPLCSP
NOV20b VAHSEGEPGSPPRMHCGADGEWLVPVGRCSCSAGFQERGDFCECPPGFYKVSPRRPLCSP
NOV20a CPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYSLSRSPLVLRLRWLP
NOV20b CPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYSLSRSPLVLRLRWLP
NOV20a PADSGGRSDVTYSLLCLRCGREGPAGACEPCGPRVAFLPRQAGLRERAATLLHLRPGARY
NOV20b PADSGGRSDVTYSLLCLRCGREGPAGACEPCGPRVAFLPRQAGLRERAATLLHLRPGARY
NOV20a TVRVAVLNGVS SAPWEEDEIRRDRVEPQSVSLSWREPIPAG
NOV20b TVRVAALNGVSGPAAAAGTTYAQVTVSTGPSAPWEEDEIRRDRVEPQSVSLSWREPIPAG
NOV20a APGANDTEYEIRYYEKGQSEQTYSMVKTGAPTVTVTNLKPATRYVFQIRAASPGPSWEAQ
NOV20b APGANDTEYEIRYYEK-QSEQTYSMVKTGAPTVTVTNLKPATRYVFQIRAASPGPSWEAQ
NOV20a SFNPSIEVQTLGEAASGSRDQSPAIWTWTISALLVLGSVMSVLAIWRR-PCSYGKGGG NOV20b SFNPSIEVQTLGEAASGSRDQSPAIWTWTISALLVLGSVMSVLAIWRRRPCSYGKGGG NOV2Oa DAHDEEELYFHFKVPTRRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGKLGAQE
NOV2Ob DAHDEEELYFHCKVPTRRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGG
NOV20a ALSPSGSLTHSIGPAPTLSTPLSGRFGELCCGCLQLPGRQELLVAVHMLRDSASDSQRLG
NOV2Ob KFGELCCGCLQLPGRQELLVAVHMLRDSASDSQRLG
NOV2Oa FLAEALTLGQFDHSHIVRLEGWTRGRGSTLMIVTEYMSHGALDGFLRRHEGQLVAGQLM
NOV20b FLAEALTLGQFDHSHIVRLEGWTRGR- -TLMIVTEYMSHGALDGFLR-HEGQLVAGQLM
NOV2Oa GLLPGLASAMKYLSEMGYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTTGRSPA
NOV2Ob GLLPGLASAMKYLSEMGYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTTGRSPA
NOV2Oa LWAAPETLQFGHFSSASDVWSFGIIMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRN
NOV20b LWAAPETLQFGHFSSASDVWSFGIIMWEVMAFGERPYWDMSGQD-VKAVEDGFRLPPPRN
NOV2Oa CPNLLHRLMLDCWQKDPGERPRFSQIHSILSKMVQDPEPPKCALTTCPRPPTPLADRAFS
NOV2Ob CPNLLHRLMLDCWQKDPGERPRFSQIHSILSKMVQDPEPPKCALTTCPRPPTPLADRAFS
NOV2Oa TFPSFGSVGAWLEALDLCRYKDSFAAAGYGSLEAVAEMTAQDLVSLGISLAEHREALLSG
NOV2Ob TFPSFGSVGAWLEALDLCRYKDSFAAAGYGSLEAVAEMTAQDLVSLGISLAEHREALLSG
NOV20a ISALQARVLQLQGQGVQV NOV2Ob ISALQARVLQLQGQGVQV
NOV20a (SEQ ID NO: 272) NOV20b (SEQ ID NO: 274)
Further analysis of the NOV20a protein yielded the following properties shown in Table 20C.
Table 20C. Protein Sequence Properties NOV20a
SignalP analysis: Cleavage site between residues 34 and 35
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 1; neg . chg 1 H-region: length 4; peak value 0.56 PSG score: -3.84
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 0.06 possible cleavage site: between 33 and 34
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5: Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = -9.08 Transmembrane 546 - 562 PERIPHERAL Likelihood = 0.85 (at 754) ALOM score: -9.08 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 553 Charge difference: 3.5 C( 1.5) - N(-2.0) C > N: C-terminal side will be inside
>>> membrane topology: type lb (cytoplasmic tail 546 to 1018)
MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment (75): 5.96 Hyd Moment(95): 3.64 G content: 3 D/E content: 2 S/T content: 2 Score: -5.44
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 39 WRP|GT
NUCDISC: discrimination of nuclear localization signals pat4: RPRK (4) at 148 pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: found RLFLCRMQL at 11
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 556 LL at 609 LL at 682 LL at 762 LL at 884 LL at 997 checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LSGRFGELCCGCLQLPGRQELL at 662 LVSLGISLAEHREALLSGISAL at 983 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
39.1 % nuclear
21.7 % cytoplasmic 17.4 % mitochondrial
8.7 % vesicles of secretory system
4.3 % vacuolar
4.3 % peroxisomal
4.3 % endoplasmic reticulum
>> prediction for CG51914-02 is nuc (k=23)
A search ofthe NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20D.
Figure imgf000360_0001
In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20E.
Figure imgf000361_0001
PFam analysis indicates that the NOV20a protein contains the domains shown in the Table 20F.
Figure imgf000361_0002
Example 21.
The NOV21 clone was analyzed, and the nucleotide and encoded poljφeptide sequences are shown in Table 21 A.
Table 21A. NOV21 Sequence Analysis
NOV21 a, CG51965-01 SEQ ID NO: 275 90δ7 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 90δ5
ATGGCGCCGCCGCCGCCGCCCGTGCTGCCCGTGCTGCTGCTCCTGGCCGCCGCCGCCGCCCTGCCGGC GATGGGGCTGCGAGCGGCCGCCTGGGAGCCGCGCGTACCCGGCGGGACCCGCGCCTTCGCCCTCCGGC CCGGCTGTACCTACGCGGTGGGCGCCGCTTGCACGCCCCGGGCGCCGCGGGAGCTGCTGGACGTGGGC CGCGATGGGCGGCTGGCAGGACGTCGGCGCGTCTCGGGCGCGGGGCGCCCGCTGCCGCTGCAAGTCCG CTTGGTGGCCCGCAGTGCCCCGACGGCGCTGAGCCGCCGCCTGCGGGCGCGCACGCACCTTCCCGGCT GCGGAGCCCGTGCCCGGCTCTGCGGAACCGGTGCCCGGCTCTGCGGGGCGCTCTGCTTCCCCGTCCCC GGCGGCTGCGCGGCCGCGCAGCATTCGGCGCTCGCAGCTCCGACCACCTTACCCGCCTGCCGCTGCCC GCCGCGCCCCAGGCCCCGCTGTCCCGGCCGTCCCATCTGCCTGCCGCCGGGCGGCTCGGTCCGCCTGC GTCTGCTGTGCGCCCTGCGGCGCGCGGCTGGCGCCGTCCGGGTGGGACTGGCGCTGGAGGCCGCCACC GCGGGGACGCCCTCCGCGTCGCCATCCCCATCGCCGCCCCTGCCGCCGAACTTGCCCGAAGCCCGGGC GGGGCCGGCGCGACGGGCCCGGCGGGGCACGAGCGGCAGAGGGAGCCTGAAGTTTCCGATGCCCAACT ACCAGGTGGCGTTGTTTGAGAACGAACCGGCGGGCACCCTCATCCTCCAGCTGCACGCGCACTACACC ATCGAGGGCGAGGAGGAGCGCGTGAGCTATTACATGGAGGGGCTGTTCGACGAGCGCTCCCGGGGCTA CTTCCGAATCGACTCTGCCACGGGCGCCGTGAGCACGGACAGCGTACTGGACCGCGAGACCAAGGAGA CGCACGTCCTCAGGGTGAAAGCCGTGGACTACAGTACGCCGCCGCGCTCGGCCACCACCTACATCACT GTCTTGGTCAAAGACACCAACGACCACAGCCCGGTCTTCGAGCAGTCGGAGTACCGCGAGCGCGTGCG GGAGAACCTGGAGGTGGGCTACGAGGTGCTGACCATCCGCGCCAGCGACCGCGACTCGCCCATCAACG CCAACTTGCGTTACCGCGTGTTGGGGGGCGCGTGGGACGTCTTCCAGCTCAACGAGAGCTCTGGCGTG GTGAGCACACGGGCGGTGCTGGACCGGGAGGAGGCGGCCGAGTACCAGCTCCTGGTGGAGGCCAACGA CCAGGGGCGCAATCCGGGCCCGCTCAGTGCCACGGCCACCGTGTACATCGAGGTGGAGGACGAGAACG ACAACTACCCCCAGTTCAGCGAGCAGAACTACGTGGTCCAGGTGCCCGAGGACGTGGGGCTCAACACG GCTGTGCTGCGAGTGCAGGCCACGGACCGGGACCAGGGCCAGAACGCGGCCATTCACTACAGCATCCT CAGCGGGAACGTGGCCGGCCAGTTCTACCTGCACTCGCTGAGCGGGATCCTGGATGTGATCAACCCCT TGGATTTCGAGGATGTCCAGAAATACTCGCTGAGCATTAAGGCCCAGGATGGGGGCCGGCCCCCGCTC ATCAATTCTTCAGGGGTGGTGTCTGTGCAGGTGCTGGATGTCAACGACAACGAGCCTATCTTTGTGAG CAGCCCCTTCCAGGCCACGGTGCTGGAGAATGTGCCCCTGGGCTACCCCGTGGTGCACATTCAGGCGG TGGACGCGGACTCTGGAGAGAACGCCCGGCTGCACTATCGCCTGGTGGACACGGCCTCCACCTTTCTG GGGGGCGGCAGCGCTGGGCCTAAGAATCCTGCCCCCACCCCTGACTTCCCCTTCCAGATCCACAACAG CTCCGGTTGGATCACAGTGTGTGCCGAGCTGGACCGCGAGGAGGTGGAGCACTACAGCTTCGGGGTGG AGGCGGTGGACCACGGCTCGCCCCCCATGAGCTCCTCCACCAGCGTGTCCATCACGGTGCTGGACGTG AATGACAACGACCCGGTGTTCACGCAGCCCACCTACGAGCTTCGTCTGAATGAGGATGCGGCCGTGGG GAGCAGCGTGCTGACCCTGCAGGCCCGCGACCGTGACGCCAACAGTGTGATTACCTACCAGCTCACAG GCGGCAACACCCGGAACCGCTTTGCACTCAGCAGCCAGAGAGGGGGCGGCCTCATCACCCTGGCGCTA CCTCTGGACTACAAGCAGGAGCAGCAGTACGTGCTGGCGGTGACAGCATCCGACGGCACACGGTCGCA CACTGCGCATGTCCTAATCAACGTCACTGATGCCAACACCCACAGGCCTGTCTTTCAGAGCTCCCATT ACACAGTGAGTGTCAGTGAGGACAGGCCTGTGGGCACCTCCATTGCTACCCTCAGTGCCAACGATGAG GACACAGGAGAGAATGCCCGCATCACCTACGTGATTCAGGACCCCGTGCCGCAGTTCCGCATTGACCC CGACAGTGGCACCATGTACACCATGATGGAGCTGGACTATGAGAACCAGGTCGCCTACACGCTGACCA TCATGGCCCAGGACAACGGCATCCCGCAGAAATCAGACACCACCACCCTAGAGATCCTCATCCTCGAT GCCAATGACAATGCACCCCAGTTCCTGTGGGATTTCTACCAGGGTTCCATCTTTGAGGATGCTCCACC CTCGACCAGCATCCTCCAGGTCTCTGCCACGGACCGGGACTCAGGTCCCAATGGGCGTCTGCTGTACA CCTTCCAGGGTGGGGACGACGGCGATGGGGACTTCTACATCGAGCCCACGTCCGGTGTGATTCGCACC CAGCGCCGGCTGGACCGGGAGAATGTGGCCGTGTACAACCTTTGGGCTCTGGCTGTGGATCGGGGCAG TCCCACTCCCCTTAGCGCCTCGGTAGAAATCCAGGTGACCATCTTGGACATTAATGACAATGCCCCCA TGTTTGAGAAGGACGAACTGGAGCTGTTTGTTGAGGAGAACAACCCAGTGGGGTCGGTGGTGGCAAAG ATTCGTGCTAACGACCCTGATGAAGGCCCTAATGCCCAGATCATGTATCAGATTGTGGAAGGGGACAT GCGGCATTTCTTCCAGCTGGACCTGCTCAACGGGGACCTGCGTGCCATGGTGGAGCTGGACTTTGAGG TCCGGCGGGAGTATGTGCTGGTGGTGCAGGCCACGTCGGCTCCGCTGGTGAGCCGAGCCACGGTGCAC ATCCTTCTCGTGGACCAGAATGACAACCCGCCTGTGCTGCCCGACTTCCAGATCCTCTTCAACAACTA
35δ TGTCACCAACAAGTCCAACAGTTTCCCCACCGGCGTGATCGGCTGCATCCCGGCCCATGACCCCGACG TGTCAGACAGCCTCAACTACACCTTCGTGCAGGGCAACGAGCTGCGCCTGTTGCTGCTGGACCCCGCC ACGGGCGAACTGCAGCTCAGCCGCGACCTGGACAACAACCGGCCGCTGGAGGCGCTCATGGAGGTGTC TGTGTCTGCAGATGGCATCCACAGCGTCACGGCCTTCTGCACCCTGCGTGTCACCATCATCACGGACG ACATGCTGACCAACAGCATCACTGTCCGCCTGGAGAACATGTCCCAGGAGAAGTTCCTGTCCCCGCTG CTGGCCCTCTTCGTGGAGGGGGTGGCCGCCGTGCTGTCCACCACCAAGGACGACGTCTTCGTCTTCAA CGTCCAGAACGACACCGACGTCAGCTCCAACATCCTGAACGTGACCTTCTCGGCGCTGCTGCCTGGCG GCGTCCGCGGCCAGTTCTTCCCGTCGGAGGACCTGCAGGAGCAGATCTACCTGAATCGGACGCTGCTG ACCACCATCTCCACGCAGCGCGTGCTGCCCTTCGACGACAACATCTGCCTGCGCGAGCCCTGCGAGAA CTACATGAAGTGCGTGTCCGTTCTGCGATTCGACAGCTCCGCGCCCTTCCTCAGCTCCACCACCGTGC TCTTCCGGCCCATCCACCCCATCAACGGCCTGCGCTGCCGCTGCCCGCCCGGCTTCACCGGCGACTAC TGCGAGACGGAGATCGACCTCTGCTACTCCGACCCGTGCGGCGCCAACGGCCGCTGCCGCAGCCGCGA GGGCGGCTACACCTGCGAGTGCTTCGAGGACTTCACTGGAGAGCACTGTGAGGTGGATGCCCGCTCAG GCCGCTGTGCCAACGGGGTGTGCAAGAACGGGGGCACCTGCGTGAACCTGCTCATCGGCGGCTTCCAC TGCGTGTGTCCTCCTGGCGAGTATGAGAGGCCCTACTGTGAGGTGACCACCAGGAGCTTCCCGCCCCA GTCCTTCGTCACCTTCCGGGGCCTGAGACAGCGCTTCCACTTCACCATCTCCCTCACGTTTGCCACTC AGGAAAGGAACGGCTTGCTTCTCTACAACGGCCGCTTCAATGAGAAGCACGACTTCATCGCCCTGGAG ATCGTGGACGAGCAGGTGCAGCTCACCTTCTCTGCAGGTGCAGGCGAGACAACAACGACCGTGGCACC GAAGGTTCCCAGTGGTGTGAGTGACGGGCGGTGGCACTCTGTGCAGGTGCAGTACTACAACAAGGTAA GATGGGCCCCACCACTTCCCCCTGGCCCCCAGCCCAATATTGGCCACCTGGGCCTGCCCCATGGGCCG TCCGGGGAAAAGATGGCCGTGGTGACAGTGGATGATTGTGACACAACCATGGCTGTGCGCTTTGGAAA GGACATCGGGAACTACAGCTGCGCTGCCCAGGGCACTCAGACCGGCTCCAAGAAGTCCCTGGATCTGA CCGGCCCTCTACTCCTGGGGGGTGTCCCCAACCTGCCAGAAGACTTCCCAGTGCACAACCGGCAGTTC GTGGGCTGCATGCGGAACCTGTCAGTCGACGGCAAAAATGTGGACATGGCCGGATTCATCGCCAACAA TGGCACCCGGGAAGGCTGCGCTGCTCGGAGGAACTTCTGCGATGGGAGGCGGTGTCAGAATGGAGGCA CCTGTGTCAACAGGTGGAATATGTATCTGTGTGAGTGTCCACTCCGATTCGGCGGGAAGAACTGTGAG CAAGCCATGCCTCACCCCCAGCTCTTCAGCGGTGAGAGCGTCGTGTCCTGGAGTGACCTGAACATCAT CATCTCTGTGCCCTGGTACCTGGGGCTCATGTTCCGGACCCGGAAGGAGGACAGCGTTCTGATGGAGG CCACCAGTGGTGGGCCCACCAGCTTTCGCCTCCAGATCCTGAACAACTACCTCCAGTTTGAGGTGTCC CACGGCCCCTCCGATGTGGAGTCCGTGATGCTGTCCGGGTTGCGGGTGACCGACGGGGAGTGGCACCA CCTGCTGATCGAGCTGAAGAATGTTAAGGAGGACAGTGAGATGAAGCACCTGGTCACCATGACCTTGG ACTATGGGATGGACCAGAACAAGGCAGATATCGGGGGCATGCTTCCCGGGCTGACGGTAAGGAGCGTG GTGGTCGGAGGCGCCTCTGAAGACAAGGTCTCCGTGCGCCGTGGATTCCGAGGCTGCATGCAGGGAGT GAGGATGGGGGGGACGCCCACCAACGTCGCCACCCTGAACATGAACAACGCACTCAAGGTCAGGGTGA AGGACGGCTGTGATGTGGACGACCCCTGTACCTCGAGCCCCTGTCCCCCCAATAGCCGCTGCCACGAC GCCTGGGAGGACTACAGCTGCGTCTGTGACAAAGGGTACCTTGGAATAAACTGTGTGGATGCCTGTCA CCTGAACCCCTGCGAGAACATGGGGGCCTGCGTGCGCTCCCCCGGCTCCCCGCAGGGCTACGTGTGCG AGTGTGGGCCCAGTCACTACGGGCCGTACTGTGAGAACAAACTCGACCTTCCGTGCCCCAGAGGCTGG TGGGGGAACCCCGTCTGTGGACCCTGCCACTGTGCCGTCAGCAAAGGCTTTGATCCCGACTGTAATAA GACCAACGGCCAGTGCCAATGCAAGGAGAATTACTACAAGCTCCTAGCCCAGGACACCTGTCTGCCCT GCGACTGCTTCCCCCATGGCTCCCACAGCCGCACTTGCGACATGGCCACCGGGCAGTGTGCCTGCAAG CCCGGCGTCATCGGCCGCCAGTGCAACCGCTGCGACAACCCGTTTGCCGAGGTCACCACGCTCGGCTG TGAAGTGATCTACAATGGCTGTCCCAAAGCATTTGAGGCCGGCATCTGGTGGCCACAGACCAAGTTCG GGCAGCCGGCTGCGGTGCCATGCCCTAAGGGATCCGTTGGAAATGCGGTCCGACACTGCAGCGGGGAG AAGGGCTGGCTGCCCCCAGAGCTCTTTAACTGTACCACCATCTCCTTCGTGGACCTCAGGGCCATGAA TGAGAAGCTGAGCCGCAATGAGACGCAGGTGGACGGCGCCAGGGCCCTGCAGCTGGTGAGGGCGCTGC GCAGTGCTACACAGCACACGGGCACGCTCTTTGGCAATGACGTGCGCACGGCCTACCAGCTGCTGGGC CACGTCCTTCAGCACGAGAGCTGGCAGCAGGGCTTCGACCTGGCAGCCACGCAGGACGCCGACTTTCA CGAGGACGTCATCCACTCGGGCAGCGCCCTCCTGGCCCCAGCCACCAGGGCGGCGTGGGAGCAGATCC
AGCGGAGCGAGGGCGGCACGGCACAGCTGCTCCGGCGCCTCGAGGGCTACTTCAGCAACGTGGCACGC AACGTGCGGCGGACGTACCTGCGGCCCTTCGTCATCGTCACCGCCAACATGGTTCTTGCTGTCGACAT CTTTGACAAGTTCAACTTTACGGGAGCCAGGGTCCCGCGATTCGACACCATCCATGAAGAGTTCCCCA GGGAGCTGGAGTCCTCCGTCTCCTTCCCAGCCGACTTCTTCAGACCACCTGAAGAAAAAGAAGGCCCC CTGCTGAGGCCGGCTGGCCGGAGGACCACCCCGCAGACCACGCGCCCGGGGCCTGGCACCGAGAGGGA GGCCCCGATCAGCAGGCGGAGGCGACACCCTGATGACGCTGGCCAGTTCGCCGTCGCTCTGGTCATCA TTTACCGCACCCTGGGGCAGCTCCTGCCCGAGCGCTACGACCCCGACCGTCGCAGCCTCCGGTTGCCT CACCGGCCCATCATTAATACCCCGATGGTGAGCACGCTGGTGTACAGCGAGGGGGCTCCGCTCCCGAG ACCCCTGGAGAGGCCCGTCCTGGTGGAGTTCGCCCTGCTGGAGGTGGAGGAGCGAACCAAGCCTGTCT GCGTGTTCTGGAACCACTCCCTGGCCGTTGGTGGGACGGGAGGGTGGTCTGCCCGGGGCTGCGAGCTC CTGTCCAGGAACCGGACACATGTCGCCTGCCAGTGCAGCCACACAGCCAGCTTTGCGGTGCTCATGGA TATCTCCAGGCGTGAGAACGGGGAGGTCCTGCCTCTGAAGATTGTCACCTATGCCGCTGTGTCCTTGT CACTGGCAGCCCTGCTGGTGGCCTTCGTCCTCCTGAGCCTGGTCCGCATGCTGCGCTCCAACCTGCAC AGCATTCACAAGCACCTCGCCGTGGCGCTCTTCCTCTCTCAGCTGGTGTTCGTGATTGGGATCAACCA GACGGAAAACCCGTTTCTGTGCACAGTGGTTGCCATCCTCCTCCACTACATCTACATGAGCACCTTTG CCTGGACCCTCGTGGAGAGCCTGCATGTCTACCGCATGCTGACCGAGGTGCGCAACATCGACACGGGG CCCATGCGGTTCTACTACGTCGTGGGCTGGGGCATCCCGGCCATTGTCACAGGACTGGCGGTCGGCCT GGACCCCCAGGGCTACGGGAACCCCGACTTCTGCTGGCTGTCGCTTCAAGACACCCTGATTTGGAGCT TTGCGGGGCCCATCGGAGCTGTTATAATCATCAACACAGTCACTTCTGTCCTATCTGCAAAGGTTTCC TGCCAAAGAAAGCACCATTATTATGGGAAAAAAGGGATCGTCTCCCTGCTGAGGACCGCATTCCTCCT GCTGCTGCTCATCAGCGCCACCTGGCTGCTGGGGCTGCTGGCTGTGAACCGCGATGCACTGAGCTTTC ACTACCTCTTCGCCATCTTCAGCGGCTTACAGGGCCCCTTCGTCCTCCTTTTCCACTGCGTGCTCAAC CAGGAGGTCCGGAAGCACCTGAAGGGCGTGCTCGGCGGGAGGAAGCTGCACCTGGAGGACTCCGCCAC CACCAGGGCCACCCTGCTGACGCGCTCCCTCAACTGCAACACCACCTTCGGTGACGGGCCTGACATGC TGCGCACAGACTTGGGCGAGTCCACCGCCTCGCTGGACAGCATCGTCAGGGATGAAGGGATCCAGAAG CTCGGCGTGTCCTCTGGGCTGGTGAGGGGCAGCCACGGAGAGCCAGACGCGTCCCTCATGCCCAGGAG CTGCAAGGATCCCCCTGGCCACGATTCCGACTCAGATAGCGAGCTGTCCCTGGATGAGCAGAGCAGCT CTTACGCCTCCTCACACTCGTCAGACAGCGAGGACGATGGGGTGGGAGCTGAGGAAAAATGGGACCCG GCCAGGGGCGCCGTCCACAGCACCCCCAAAGGGGACGCTGTGGCCAACCACGTTCCGGCCGGCTGGCC CGACCAGAGCCTGGCTGAGAGTGACAGTGAGGACCCCAGCGGCAAGCCCCGCCTGAAGGTGGAGACCA AGGTCAGCGTGGAGCTGCACCGCGAGGAGCAGGGCAGTCACCGTGGAGAGTACCCCCCGGACCAGGAG AGCGGGGGCGCAGCCAGGCTTGCTAGCAGCCAGCCCCCAGAGCAGAGGAGCATCTTGAAAAATAAAGT CACCTACCCGCCGCCGCTGACGCTGACGGAGCAGACGCTGAAGGGCCGGCTCCGGGAGAAGCTGGCCG ACTGTGAGCAGAGCCCCACATCCTCGCGCACGTCTTCCCTGGGCTCTGGCGGCCCCGACTGCGCCATC ACAGTCAAGAGCCCTGGGAGGGAGCCGGGGCGTGACCACCTCAACGGGGTGGCCATGAATGTGCGCAC TGGGAGCGCCCAGGCCGATGGCTCCGACTCTGAGAAACCGTGA
NOV21a, CG51965-01 SEQ ID NO: 276 3028 aa MW at 330865.9kD Protein Sequence
MAPPPPPVLPVLLL AAAAA PAMG RAAAWEPRVPGGTRAFALRPGCTYAVGAACTPRAPRELLDVG RDGRLAGRRRVSGAGRP PLQVRLVARSAPTA SRRLRARTHLPGCGARARLCGTGAR CGALCFPVP GGCAAAQHSALAAPTT PACRCPPRPRPRCPGRPICLPPGGSVR RLLCALRRAAGAVRVGLALEAAT AGTPSASPSPSPPLPPNLPEARAGPARRARRGTSGRGSLKFPMPNYQVALFENEPAGT I QLHAHYT IEGEEERVSYYMEGLFDERSRGYFRIDSATGAVSTDSV DRETKETHV RVKAVDYSTPPRSATTYIT VLVKDTNDHSPVFEQSEYRERVREN EVGYEVLTIRASDRDSPINAN RYRVLGGAWDVFQLNESSGV VSTRAVLDREEAAEYQLLVEA DQGRNPGPLSATATVYIEVEDEND YPQFSEQNYWQVPEDVG NT AVLRVQATDRDQGQNAAIHYSILSG VAGQFYLHSLSGILDVINPLDFEDVQKYSLSIKAQDGGRPPL INSSGWSVQVLDV DNEPIFVSSPFQATV ENVP GYPWHIQAVDADSGENARLHYRLVDTASTF GGGSAGPKNPAPTPDFPFQIHNSSG ITVCAE DREEVEHYSFGVEAVDHGSPPMSSSTSVSITVLDV NDNDPVFTQPTYELRLNEDAAVGSSVLTLQARDRDANSVITYQ TGGNTRNRFALSSQRGGGLITLAL P DYKQEQQYVLAVTASDGTRSHTAHV INVTDANTHRPVFQSSHYTVSVSEDRPVGTSIATLSANDE DTGENARITYVIQDPVPQFRIDPDSGT YTM E DYENQVAYTLTIMAQDNGIPQKSDTTT EILILD ANDNAPQFLWDFYQGS1FEDAPPSTSI QVSATDRDSGPNGR LYTFQGGDDGDGDFYIEPTSGVIRT QRRLDRENVAVYNLWA AVDRGSPTP SASVEIQVTILDINDNAPMFEKDELELFVEENNPVGSWAK IRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGD RAMVELDFEVRREYVLWQATSAPLVSRATVH ILLVDQNDNPPVliPDFQILFNNYVTNKSNSFPTGVIGCIPAHDPDVSDS NYTFVQGNELR L DPA TGELQ SRDLDNNRPLEALMEVSVSADGIHSVTAFCTLRVTIITDDMLTNSITVR ENMSQEKFLSPL ALFVEGVAAVLSTTKDDVFVFNVQNDTDVSSNILNVTFSALLPGGVRGQFFPSEDIiQEQIYLNRT L TXISTQRVLPFDDNIC REPCENYMKCVSVLRFDSSAPFLSSTTVLFRPIHPINGLRCRCPPGFTGDY CETEIDLCYSDPCGANGRCRSREGGYTCECFEDFTGEHCEVDARSGRCANGVCKNGGTCVNLLIGGFH CVCPPGEYERPYCEVTTRSFPPQSFVTFRGLRQRFHFTISLTFATQERNGLLLYNGRFNEKHDFIALE IVDEQVQ TFSAGAGETTTTVAPKVPSGVSDGR HSVQVQYYNKVRWAPPLPPGPQPNIGHLG PHGP SGEKMAWTVDDCDTTMAVRFGKDIGNYSCAAQGTQTGSKKSLDLTGP LLGGVPNLPEDFPVHNRQF VGCMRNLSVDGKNVDMAGFIANNGTREGCAARRNFCDGRRCQNGGTCVNR NMYLCECP RFGGKNCE QAMPHPQLFSGESWS SDLNIIISVP YLGLMFRTRKEDSVLMEATSGGPTSFRLQILNNY QFEVS HGPSDVESVM SGLRVTDGE HHLLIE KNVKEDSEMKHLVTMTLDYGMDQNKADIGGMLPGLTVRSV WGGASEDKVSVRRGFRGCMQGVRMGGTPTNVATLNM NAL VRVKDGCDVDDPCTSSPCPPNSRCHD AWEDYSCVCDKGYLGINCVDACHLNPCENMGACVRSPGSPQGYVCECGPSHYGPYCENKLD PCPRGW GNPVCGPCHCAVSKGFDPDCNKTNGQCQCKENYYK IiAQDTC PCDCFPHGSHSRTCDMATGQCACK PGVIGRQCNRCDNPFAEVTT GCEVIYNGCPKAFEAGIW PQTKFGQPAAVPCPKGSVGNAVRHCSGE KG LPPELFNCTTISFVD RAMNEK SRNETQVDGARALQ VRALRSATQHTGT FGNDVRTAYQLLG HVLQHES QQGFDLAATQDADFHEDVIHSGSALIiAPATRAA EQIQRSEGGTAQ RRLEGYFSNVAR VRRTYLRPFVIVTANMVLAVDIFDKFNFTGARVPRFDTIHEEFPRELESSVSFPADFFRPPEEKEGP L RPAGRRTTPQTTRPGPGTEREAPISRRRRHPDDAGQFAVALVIIYRTLGQLLPERYDPDRRSLRLP HRPIINTPMVSTLVYSEGAPLPRPLERPVLVEFA LEVEERTKPVCVFWNHSIJAVGGTGGWSARGCEL SRNRTHVACQCSHTASFAV MDISRRENGEVLP KIVTYAAVSLSLAALLVAFV LSLVRMLRSNLH SIHKHIiAVALFLSQLVFVIGINQTENPFLCTWAILLHYIYMSTFAWTLVESLHVYRMLTEVRNIDTG PMRFYYWGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLIWSFAGPIGAVIIINTVTSVLSAKVS CQRKHHYYGKKGIVSL RTAF LLLLISAT L GLLAVNRDALSFHYLFAIFSGLQGPFVLLFHCVLN QEVRKHLKGVLGGRKLHLEDSATTRATL TRSLNCNTTFGDGPDMLRTDLGESTASLDSIVRDEGIQK GVSSGLVRGSHGEPDASLMPRSCKDPPGHDSDSDSELSLDEQSSSYASSHSSDSEDDGVGAEEK DP ARGAVHSTPKGDAVANHVPAG PDQS AESDSEDPSGKPRLKVETICVSVELHREEQGSHRGEYPPDQE SGGAAR ASSQPPEQRSILKNKVTYPPPLTLTEQTLKGRLREKLADCEQSPTSSRTSSLGSGGPDCAI TVKSPGREPGRDHLNGVAMNVRTGSAQADGSDSEKP
NOV21b, 25δ076370 SEQ ID NO: 277 1263 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CTCAAGCTTGAAGTGATCTACAATGGCTGTCCCAAAGCATTTGAGGCCGGCATCTGGTGGCCACAGAC CAAGTTCGGGCAGCCGGCTGCGGTGCCATGCCCTAAGGGATCCGTTGGAAATGCGGTCCGACACTGCA GCGGGGAGAAGGGCTGGCTGCCCCCAGAGCTCTTTAACTGTACCACCATCTCCTTCGTGGACCTCAGG GCCATGAATGAGAAGCTGAGCCGCAATGAGACGCAGGTGGACGGCGCCAGGGCCCTGCAGCTGGTGAG GGCGCTGCGCAGTGCTACACAGCACACGGGCACGCTCTTTGGCAATGACGTGCGCACGGCCTACCAGC TGCTGGGCCACGTCCTTCAGCACGAGAGCTGGCAGCAGGGCTTCGACCTGGCAGCCACGCAGGACGCC GACTTTCACGAGGACGTCATCCACTCGGGCAGCGCCCTCCTGGCCCCAGCCACCAGGGCGGCGTGGGA GCAGATCCAGCGGAGCGAGGGCGGCACGGCACAGCTGCTCCGGCGCCTCGAGGGCTACTTCAGCAACG TGGCACGCAACGTGCGGCGGACGTACCTGCGGCCCTTCGTCATCGTCACCGCCAACATGATTCTTGCT GTCGACATCTTTGACAAGTTCAACTTTACGGGAGCCAGGGTCCCGCGATTCGACACCATCCATGAAGA GTTCCCCAGGGAGCTGGAGTCCTCCGTCTCCTTCCCAGCCGACTTCTTCAGACCACCTGAAGAAAAAG AAGGCCCCCTGCTGAGGCCGGCTGGCCGGAGGACCACCCCGCAGACCACGCGCCCGGGGCCTGGCACC GAGAGGGAGGCCCCGATCAGCAGGCGGAGGCGACACCCTGATGACGCTGGCCAGTTCGCCGTCGCTCT GGTCATCATTTACCGCACCCTGGGGCAGCTCCTGCCCGAGCGCTACGACCCCGACCGTCGCAGCCTCC GGTTGCCTCACCGGCCCATCATTAATACCCCGATGGTGAGCACGCTGGTGTACAGCGAGGGGGCTCCG CTCCCGAGACCCCTGGAGAGGCCCGTCCTGGTGGAGTTCGCCCTGCTGGAGGTGGAGGAGCGAACCAA GCCTGTCTGCGTGTTCTGGAACCACTCCCTGGCCGTTGGTGGGACGGGAGGGTGGTCTGCCCGGGGCT GCGAGCTCCTGTCCAGGAACCGGACACATGTCGCCTGCCAGTGCAGCCACACAGCCAGCTTTGCGGTG CTCATGGATATCTCCAGGCGTGAGAACGGGGAGAAGCTT
NOV21b, 25δ076370 SEQ ID NO: 27δ 421 aa MW at 4717δ.lkD Protein Sequence
LKLEVIYNGCPKAFEAGIW PQTKFGQPAAVPCPKGSVGNAVRHCSGEKGW PPE FNCTTISFVD R AIWEKLSRNETQVDGARALQLVRALRSATQHTGT FGNDVRTAYQ LGHVLQHESWQQGFDLAATQDA DFHEDVIHSGSALIiAPATRAAWEQIQRSEGGTAQLLRRLEGYFSNVARNVRRTYLRPFVIVTANMILA VDIFDKFNFTGARVPRFDTIHEEFPRE ESSVSFPADFFRPPEEKEGPLLRPAGRRTTPQTTRPGPGT EREAPISRRRRHPDDAGQFAVALVIIYRT GQL PERYDPDRRSLR PHRPIINTPMVST VYSEGAP PRPLERPVLVEFALLEVEERTKPVCVF NHS AVGGTGGWSARGCE SRNRTHVACQCSHTASFAV LMDISRRENGEKL
NOV21c, 317619δ62 SEQ ID NO: 279 750 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CGCAAGCTTGTCCTGCCTCTGAAGATTGTCACCTATGCCGCTGTGTCCTTGTCACTGGCAGCCCTGCT GGTGGCCTTCGTCCTCCTGAGCCTGGTCCGCATGCTGCGCTCCAACCTGCACAGCATTCACAAGCACC TCGCCGTGGCGCTCTTCCTCTCTCAGCTGGTGTTCGTGATTGGGATCAACCAGACGGAAAACCCGTTT CTGTGCACAGTGGTTGCCATCCTCCTCCACTACATCTACATGAGCACCTTTGCCTGGACCCTCGTGGA GAGCCTGCATGTCTACCGCATGCTGACCGAGGTGCGCAACATCGACACGGGGCCCATGCGGTTCTACT ACGTCGTGGGCTGGGGCATCCCGGCCATTGTCACAGGACTGGCGGTCGGCCTGGACCCCCAGGGCTAC GGGAACCCCGACTTCTGCTGGCTGTCGCTTCAAGACACCCTGATTTGGAGCTTTGCGGGGCCCATCGG AGCTGTTATAATCATCAACACAGTCACTTCTGTCCTATCTGCAAAGGTTTCCTGCCAAAGAAAGCACC ATTATTATGGGAAAAAAGGGATCGTCTCCCTGCTGAGGACCGCATTCCTCCTGCTGCTGCTCATCAGC GCCACCTGGCTGCTGGGGCTGCTGGCTGTGAACCGCGACGCACTGAGCTTTCACTACCTCTTCGCCAT CTTCAGCGGCTTACAGGGCCCCTTCGTCCTCCTTTTCCACTGCGTGCTCAACCAGGAGGTCAAGCTTG CG
NO V21c, 317619862 SEQ ID NO: 280 250 aa MW at 27799.9kD Protein Sequence
RK VLPLKIVTYAAVS S AALLVAFVLLSLVRMLRSNLHSIHKHIiAVALF SQ VFVIGINQTENPF LCTWAI HYIYMSTFA T VESLHVYRMLTEVRNIDTGP RFYYWGWGIPAIVTG AVGLDPQGY GNPDFC SLQDT IWSFAGPIGAVII INTVTSV SAKVSCQRKHHYYGKKGIVSL RTAF LLLLIS AT G LAVNRDA SFHYLFAIFSGLQGPFVL FHCV NQEV A
NOV21d, 317460050 SEQ ID NO: 281 J2541_bp
DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTTACCAGGTGGCGTTGTTTGAGAACGAACCGGCGGGCACCCTCATCCTCCAGCTGCACGCGCA CCACACCATCGAGGGCGAGGAGGAGCGCGTGAGCTATTACATGGAGGGGCTGTTCGACGAGCGCTCCC GGGGCTACTTCCGAATCGACTCTGCCGCGGGCGCCGTGAGCACGGACAGCGTACTGGACCGCGAGACC AAGGAGACGCACGTCCTCAGGGTGAAAGCCGTGGACTACAGTACGCCGCCGCGCTCGGCCACCACCTA CATCACTGTCTTGGTCAAAGACACCAACGACCACAGCCCGGTCTTCGAGCAGTCGGAGTACCGCGAGC GCGTGCGGGAGAACCTGGAGGTGGGCTACGAGGTGCTGACCATCCGCGCCAGCGACCGCGACTCGCCC ATCAACGCCAACTTGCGTTACCGCGTGTTGGGGGGCGCGTGGGACGTCTTCCAGCTCAACGAGAGCTC TGGCGTGGTGAGTACACGGGCGGTGCTGGACCGGGAGGAGGCGGCCGAGTACCAGCTGCTGGTGGAGG CCAACGACCAGGGGCGCAATCCGGGCCCGCTCAGTGCCACGGCCACCGTGTACATCGAGGTGGAGGAC GAGAACGACAACTACCCCCAGTTCAGCGAGCAGAACTACGTGGTCCAGGTGCCCGAGGACGTGGGGCT CAACACGGCTGTGCTGCGAGTGCAGGCCACGGACCGGGACCAGGGCCAGAACGCGGCCATTCACTACA GCATCCTCAGCGGGAACGTGGCCGGCCAGTTCTACCTGCACTCGCTGAGCGGGATCCTGGATGTGATC AACCCCTTGGATTTCGAGGATGTCCAGAAATACTCGCTGAGCATTAAGGCCCAGGATGGGGGCCGGCC CCCGCTCATCAATTCTTCAGGGGTGGTGTCTGTGCAGGTGCTGGATGTCAACGACAACGAGCCTATCT TTGTGAGCAGCCCCTTCCAGGCCACGGTGCTGGAGAATGTGCCCCTGGGCTACCCCGTGGTGCACATT CAGGCGGTGGACGCGGACTCTGGAGAGAACGCCCGGCTGCACTATCGCCTGGTGGACACGGCCTCCAC CTTTCTGGGGGGCGGCAGCGCTGGGCCTAAGAATCCTGCCCCCACCCCTGACTTCCCCTTCCAGATCC GCAACAGCTCCGGTTGGATCACAGTGTGTGCCGAGCTGGACCGCGAGGAGGTGGAGCACTACAGCTTC GGGGTGGAGGCGGTGGACCACGGCTGGCCCCCCATGAGCTCCTCCACCAGCGTGTCCATCACGGTGCT GGACGTGAATGACAACGACCCGGTGTTCACGCAGCCCACCTACGAGCTTCGTCTGAATGAGGATGCGG CCGTGGGGAGCAGCGTGCTGACCCTGCAGGCCCGCGACCGTGACGCCAACAGTGTGATTACCTACCAG CTCACAGGCGGCAACACCCGGAACCGCTTTGCACTCAGCAGCCAGAGAGGGGGCGGCCTCATCACCCT GGCGCTACCTCTGGACTACAAGCAGGAGCAGCAGTACGTGCTGGCGGTGACAGCATCCGACGGCACAC GGTCGCACACTGCGCATGTCCTAATCAACGTCACTGATGCCAACACCCACAGGCCTGTCTTTCAGAGC TCCCATTACACAGTGAGTGTCAGTGAGGACAGGCCTGTGGGCACCTCCATTGCTACCCTCAGTGCCAA CGATGAGGACACAGGAGAGAATGCCCGCATCACCTACGTGATTCAGGACCCCGTGCCGCAGTTCCGCA TTGACCCCGACAGTGGCACCATGTACACCATGATGGAGCTGGACTATGAGAACCAGGTCGCCTACACG CTGACCATCATGGCCCAGGACAACGGCATCCCGCAGAAATCAGACACCACCACCCTAGAGATCCTCAT CCTCGATGCCAATGACAATGCACCCCAGTTCCTGTGGGATTTCTACCAGGGTTCCATCTTTGAGGATG CTCCACCCTCGACCAGCATCCTCCAGGTCTCTGCCACGGACCGGGACTCAGGTCCCAATGGGCGTCTG CTGTACACCTTCCAGGGTGGGGACGACGGCGATGGGGACTTCTACATCGAGCCCACGTCCGGTGTGAT TCGCACCCAGCGCCGGCTGGACCGGGAGAATGTGGCCGTGTACAACCTTTGGGCTCTGGCTGTGGATC GGGGCAGTCCCACTCCCCTTAGCGCCTCGGTAGAAATCCAGGTGACCATCTTGGACATTAATGACAAT GCCCCCATGTTTGAGAAGGACGAACTGGAGCTGTTTGTTGAGGAGAACAACCCAGTGGGGTCGGTGGT GGCAAAGATTCGTGCTAACGACCCTGATGAAGGCCCTAATGCCCAGATCATGTATCAGATTGTGGAAG GGGACATGCGGCATTTCTTCCAGCTGGACCTGCTCAACGGGGACCTGCGTGCCATGGTGGAGCTGGAC TTTGAGGTCCGGCGGGAGTATGTGCTGGTGGTGCAGGCCACGTCGGCTCCGCTGGTGAGCCGAGCCAC GGTGCACATCCTTCTCGTGCTCGAG
NOV2 Id, 317460050 SEQ ID NO: 2δ2 δ47 aa MW at 9361 1.5kD Protein Sequence
KLYQVALFENEPAGT ILQLHAHHTIEGEEERVSYYMEGLFDERSRGYFRIDSAAGAVSTDSV DRET KETHVLRVKAVDYSTPPRSATTYITVLVKDTNDHSPVFEQSEYRERVRENLEVGYEVLTIRASDRDSP INAN RYRVLGGAWDVFQLNE S SGWSTRAVLDREEAAEYQLLVEANDQGRNPGPLS ATATVY I EVED ENDNYPQFSEQNYWQVPEDVGLNTAVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGI DVI NP DFEDVQKYS SIKAQDGGRPPLINSSGWSVQVLDVNDNEPIFVSSPFQATVLENVPLGYPWHI QAVDADSGENAR HYRLVDTASTFLGGGSAGPKNPAPTPDFPFQIRNSSGWITVCAELDREEVEHYSF GVEAVDHGWPPMSSSTSVSITVLDVNDNDPVFTQPTYE RLNEDAAVGSSV T QARDRDANSVITYQ LTGGNTRNRFA SSQRGGG ITIiALPLDYKQEQQYV AVTASDGTRSHTAHVl,INVTDANTHRPVFQS SHYTVSVSEDRPVGTSIATLSANDEDTGENARITYVIQDPVPQFRIDPDSGT YTMMELDYENQVAYT LTIMAQDNGIPQKSDTTTLEI ILDANDNAPQFLWDFYQGSIFEDAPPSTSILQVSATDRDSGPNGRL YTFQGGDDGDGDFYIEPTSGVIRTQRRLDRENVAVYNL ALAVDRGSPTP SASVEIQVTILDINDN APMFEKDE E FVEENNPVGSWAKIRANDPDEGPNAQIMYQIVEGDMRHFFQ DLLNGDLRAMVE D FEVRREYV WQATSAPLVSRATVHILLVLE
NOV21e, SNP133δ24δ3 of SEQ ID NO: 283 90δ7 bp CG51965-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 9085
SNP Pos: 8435 SNP Change: G to C
ATGGCGCCGCCGCCGCCGCCCGTGCTGCCCGTGCTGCTGCTCCTGGCCGCCGCCGCCGCCCTGCCGGC GATGGGGCTGCGAGCGGCCGCCTGGGAGCCGCGCGTACCCGGCGGGACCCGCGCCTTCGCCCTCCGGC CCGGCTGTACCTACGCGGTGGGCGCCGCTTGCACGCCCCGGGCGCCGCGGGAGCTGCTGGACGTGGGC CGCGATGGGCGGCTGGCAGGACGTCGGCGCGTCTCGGGCGCGGGGCGCCCGCTGCCGCTGCAAGTCCG CTTGGTGGCCCGCAGTGCCCCGACGGCGCTGAGCCGCCGCCTGCGGGCGCGCACGCACCTTCCCGGCT GCGGAGCCCGTGCCCGGCTCTGCGGAACCGGTGCCCGGCTCTGCGGGGCGCTCTGCTTCCCCGTCCCC GGCGGCTGCGCGGCCGCGCAGCATTCGGCGCTCGCAGCTCCGACCACCTTACCCGCCTGCCGCTGCCC GCCGCGCCCCAGGCCCCGCTGTCCCGGCCGTCCCATCTGCCTGCCGCCGGGCGGCTCGGTCCGCCTGC GTCTGCTGTGCGCCCTGCGGCGCGCGGCTGGCGCCGTCCGGGTGGGACTGGCGCTGGAGGCCGCCACC GCGGGGACGCCCTCCGCGTCGCCATCCCCATCGCCGCCCCTGCCGCCGAACTTGCCCGAAGCCCGGGC GGGGCCGGCGCGACGGGCCCGGCGGGGCACGAGCGGCAGAGGGAGCCTGAAGTTTCCGATGCCCAACT ACCAGGTGGCGTTGTTTGAGAACGAACCGGCGGGCACCCTCATCCTCCAGCTGCACGCGCACTACACC ATCGAGGGCGAGGAGGAGCGCGTGAGCTATTACATGGAGGGGCTGTTCGACGAGCGCTCCCGGGGCTA CTTCCGAATCGACTCTGCCACGGGCGCCGTGAGCACGGACAGCGTACTGGACCGCGAGACCAAGGAGA CGCACGTCCTCAGGGTGAAAGCCGTGGACTACAGTACGCCGCCGCGCTCGGCCACCACCTACATCACT GTCTTGGTCAAAGACACCAACGACCACAGCCCGGTCTTCGAGCAGTCGGAGTACCGCGAGCGCGTGCG GGAGAACCTGGAGGTGGGCTACGAGGTGCTGACCATCCGCGCCAGCGACCGCGACTCGCCCATCAACG CCAACTTGCGTTACCGCGTGTTGGGGGGCGCGTGGGACGTCTTCCAGCTCAACGAGAGCTCTGGCGTG GTGAGCACACGGGCGGTGCTGGACCGGGAGGAGGCGGCCGAGTACCAGCTCCTGGTGGAGGCCAACGA CCAGGGGCGCAATCCGGGCCCGCTCAGTGCCACGGCCACCGTGTACATCGAGGTGGAGGACGAGAACG ACAACTACCCCCAGTTCAGCGAGCAGAACTACGTGGTCCAGGTGCCCGAGGACGTGGGGCTCAACACG GCTGTGCTGCGAGTGCAGGCCACGGACCGGGACCAGGGCCAGAACGCGGCCATTCACTACAGCATCCT CAGCGGGAACGTGGCCGGCCAGTTCTACCTGCACTCGCTGAGCGGGATCCTGGATGTGATCAACCCCT TGGATTTCGAGGATGTCCAGAAATACTCGCTGAGCATTAAGGCCCAGGATGGGGGCCGGCCCCCGCTC ATCAATTCTTCAGGGGTGGTGTCTGTGCAGGTGCTGGATGTCAACGACAACGAGCCTATCTTTGTGAG CAGCCCCTTCCAGGCCACGGTGCTGGAGAATGTGCCCCTGGGCTACCCCGTGGTGCACATTCAGGCGG TGGACGCGGACTCTGGAGAGAACGCCCGGCTGCACTATCGCCTGGTGGACACGGCCTCCACCTTTCTG GGGGGCGGCAGCGCTGGGCCTAAGAATCCTGCCCCCACCCCTGACTTCCCCTTCCAGATCCACAACAG CTCCGGTTGGATCACAGTGTGTGCCGAGCTGGACCGCGAGGAGGTGGAGCACTACAGCTTCGGGGTGG AGGCGGTGGACCACGGCTCGCCCCCCATGAGCTCCTCCACCAGCGTGTCCATCACGGTGCTGGACGTG AATGACAACGACCCGGTGTTCACGCAGCCCACCTACGAGCTTCGTCTGAATGAGGATGCGGCCGTGGG GAGCAGCGTGCTGACCCTGCAGGCCCGCGACCGTGACGCCAACAGTGTGATTACCTACCAGCTCACAG GCGGCAACACCCGGAACCGCTTTGCACTCAGCAGCCAGAGAGGGGGCGGCCTCATCACCCTGGCGCTA CCTCTGGACTACAAGCAGGAGCAGCAGTACGTGCTGGCGGTGACAGCATCCGACGGCACACGGTCGCA CACTGCGCATGTCCTAATCAACGTCACTGATGCCAACACCCACAGGCCTGTCTTTCAGAGCTCCCATT ACACAGTGAGTGTCAGTGAGGACAGGCCTGTGGGCACCTCCATTGCTACCCTCAGTGCCAACGATGAG GACACAGGAGAGAATGCCCGCATCACCTACGTGATTCAGGACCCCGTGCCGCAGTTCCGCATTGACCC CGACAGTGGCACCATGTACACCATGATGGAGCTGGACTATGAGAACCAGGTCGCCTACACGCTGACCA TCATGGCCCAGGACAACGGCATCCCGCAGAAATCAGACACCACCACCCTAGAGATCCTCATCCTCGAT GCCAATGACAATGCACCCCAGTTCCTGTGGGATTTCTACCAGGGTTCCATCTTTGAGGATGCTCCACC CTCGACCAGCATCCTCCAGGTCTCTGCCACGGACCGGGACTCAGGTCCCAATGGGCGTCTGCTGTACA CCTTCCAGGGTGGGGACGACGGCGATGGGGACTTCTACATCGAGCCCACGTCCGGTGTGATTCGCACC CAGCGCCGGCTGGACCGGGAGAATGTGGCCGTGTACAACCTTTGGGCTCTGGCTGTGGATCGGGGCAG TCCCACTCCCCTTAGCGCCTCGGTAGAAATCCAGGTGACCATCTTGGACATTAATGACAATGCCCCCA TGTTTGAGAAGGACGAACTGGAGCTGTTTGTTGAGGAGAACAACCCAGTGGGGTCGGTGGTGGCAAAG ATTCGTGCTAACGACCCTGATGAAGGCCCTAATGCCCAGATCATGTATCAGATTGTGGAAGGGGACAT GCGGCATTTCTTCCAGCTGGACCTGCTCAACGGGGACCTGCGTGCCATGGTGGAGCTGGACTTTGAGG TCCGGCGGGAGTATGTGCTGGTGGTGCAGGCCACGTCGGCTCCGCTGGTGAGCCGAGCCACGGTGCAC ATCCTTCTCGTGGACCAGAATGACAACCCGCCTGTGCTGCCCGACTTCCAGATCCTCTTCAACAACTA
TGTCACCAACAAGTCCAACAGTTTCCCCACCGGCGTGATCGGCTGCATCCCGGCCCATGACCCCGACG TGTCAGACAGCCTCAACTACACCTTCGTGCAGGGCAACGAGCTGCGCCTGTTGCTGCTGGACCCCGCC ACGGGCGAACTGCAGCTCAGCCGCGACCTGGACAACAACCGGCCGCTGGAGGCGCTCATGGAGGTGTC TGTGTCTGCAGATGGCATCCACAGCGTCACGGCCTTCTGCACCCTGCGTGTCACCATCATCACGGACG ACATGCTGACCAACAGCATCACTGTCCGCCTGGAGAACATGTCCCAGGAGAAGTTCCTGTCCCCGCTG CTGGCCCTCTTCGTGGAGGGGGTGGCCGCCGTGCTGTCCACCACCAAGGACGACGTCTTCGTCTTCAA CGTCCAGAACGACACCGACGTCAGCTCCAACATCCTGAACGTGACCTTCTCGGCGCTGCTGCCTGGCG GCGTCCGCGGCCAGTTCTTCCCGTCGGAGGACCTGCAGGAGCAGATCTACCTGAATCGGACGCTGCTG ACCACCATCTCCACGCAGCGCGTGCTGCCCTTCGACGACAACATCTGCCTGCGCGAGCCCTGCGAGAA CTACATGAAGTGCGTGTCCGTTCTGCGATTCGACAGCTCCGCGCCCTTCCTCAGCTCCACCACCGTGC TCTTCCGGCCCATCCACCCCATCAACGGCCTGCGCTGCCGCTGCCCGCCCGGCTTCACCGGCGACTAC TGCGAGACGGAGATCGACCTCTGCTACTCCGACCCGTGCGGCGCCAACGGCCGCTGCCGCAGCCGCGA GGGCGGCTACACCTGCGAGTGCTTCGAGGACTTCACTGGAGAGCACTGTGAGGTGGATGCCCGCTCAG GCCGCTGTGCCAACGGGGTGTGCAAGAACGGGGGCACCTGCGTGAACCTGCTCATCGGCGGCTTCCAC TGCGTGTGTCCTCCTGGCGAGTATGAGAGGCCCTACTGTGAGGTGACCACCAGGAGCTTCCCGCCCCA GTCCTTCGTCACCTTCCGGGGCCTGAGACAGCGCTTCCACTTCACCATCTCCCTCACGTTTGCCACTC AGGAAAGGAACGGCTTGCTTCTCTACAACGGCCGCTTCAATGAGAAGCACGACTTCATCGCCCTGGAG ATCGTGGACGAGCAGGTGCAGCTCACCTTCTCTGCAGGTGCAGGCGAGACAACAACGACCGTGGCACC GAAGGTTCCCAGTGGTGTGAGTGACGGGCGGTGGCACTCTGTGCAGGTGCAGTACTACAACAAGGTAA GATGGGCCCCACCACTTCCCCCTGGCCCCCAGCCCAATATTGGCCACCTGGGCCTGCCCCATGGGCCG TCCGGGGAAAAGATGGCCGTGGTGACAGTGGATGATTGTGACACAACCATGGCTGTGCGCTTTGGAAA GGACATCGGGAACTACAGCTGCGCTGCCCAGGGCACTCAGACCGGCTCCAAGAAGTCCCTGGATCTGA CCGGCCCTCTACTCCTGGGGGGTGTCCCCAACCTGCCAGAAGACTTCCCAGTGCACAACCGGCAGTTC GTGGGCTGCATGCGGAACCTGTCAGTCGACGGCAAAAATGTGGACATGGCCGGATTCATCGCCAACAA TGGCACCCGGGAAGGCTGCGCTGCTCGGAGGAACTTCTGCGATGGGAGGCGGTGTCAGAATGGAGGCA CCTGTGTCAACAGGTGGAATATGTATCTGTGTGAGTGTCCACTCCGATTCGGCGGGAAGAACTGTGAG CAAGCCATGCCTCACCCCCAGCTCTTCAGCGGTGAGAGCGTCGTGTCCTGGAGTGACCTGAACATCAT CATCTCTGTGCCCTGGTACCTGGGGCTCATGTTCCGGACCCGGAAGGAGGACAGCGTTCTGATGGAGG CCACCAGTGGTGGGCCCACCAGCTTTCGCCTCCAGATCCTGAACAACTACCTCCAGTTTGAGGTGTCC CACGGCCCCTCCGATGTGGAGTCCGTGATGCTGTCCGGGTTGCGGGTGACCGACGGGGAGTGGCACCA CCTGCTGATCGAGCTGAAGAATGTTAAGGAGGACAGTGAGATGAAGCACCTGGTCACCATGACCTTGG ACTATGGGATGGACCAGAACAAGGCAGATATCGGGGGCATGCTTCCCGGGCTGACGGTAAGGAGCGTG GTGGTCGGAGGCGCCTCTGAAGACAAGGTCTCCGTGCGCCGTGGATTCCGAGGCTGCATGCAGGGAGT GAGGATGGGGGGGACGCCCACCAACGTCGCCACCCTGAACATGAACAACGCACTCAAGGTCAGGGTGA AGGACGGCTGTGATGTGGACGACCCCTGTACCTCGAGCCCCTGTCCCCCCAATAGCCGCTGCCACGAC GCCTGGGAGGACTACAGCTGCGTCTGTGACAAAGGGTACCTTGGAATAAACTGTGTGGATGCCTGTCA CCTGAACCCCTGCGAGAACATGGGGGCCTGCGTGCGCTCCCCCGGCTCCCCGCAGGGCTACGTGTGCG AGTGTGGGCCCAGTCACTACGGGCCGTACTGTGAGAACAAACTCGACCTTCCGTGCCCCAGAGGCTGG TGGGGGAACCCCGTCTGTGGACCCTGCCACTGTGCCGTCAGCAAAGGCTTTGATCCCGACTGTAATAA GACCAACGGCCAGTGCCAATGCAAGGAGAATTACTACAAGCTCCTAGCCCAGGACACCTGTCTGCCCT GCGACTGCTTCCCCCATGGCTCCCACAGCCGCACTTGCGACATGGCCACCGGGCAGTGTGCCTGCAAG CCCGGCGTCATCGGCCGCCAGTGCAACCGCTGCGACAACCCGTTTGCCGAGGTCACCACGCTCGGCTG TGAAGTGATCTACAATGGCTGTCCCAAAGCATTTGAGGCCGGCATCTGGTGGCCACAGACCAAGTTCG GGCAGCCGGCTGCGGTGCCATGCCCTAAGGGATCCGTTGGAAATGCGGTCCGACACTGCAGCGGGGAG AAGGGCTGGCTGCCCCCAGAGCTCTTTAACTGTACCACCATCTCCTTCGTGGACCTCAGGGCCATGAA TGAGAAGCTGAGCCGCAATGAGACGCAGGTGGACGGCGCCAGGGCCCTGCAGCTGGTGAGGGCGCTGC GCAGTGCTACACAGCACACGGGCACGCTCTTTGGCAATGACGTGCGCACGGCCTACCAGCTGCTGGGC CACGTCCTTCAGCACGAGAGCTGGCAGCAGGGCTTCGACCTGGCAGCCACGCAGGACGCCGACTTTCA CGAGGACGTCATCCACTCGGGCAGCGCCCTCCTGGCCCCAGCCACCAGGGCGGCGTGGGAGCAGATCC
AGCGGAGCGAGGGCGGCACGGCACAGCTGCTCCGGCGCCTCGAGGGCTACTTCAGCAACGTGGCACGC AACGTGCGGCGGACGTACCTGCGGCCCTTCGTCATCGTCACCGCCAACATGGTTCTTGCTGTCGACAT CTTTGACAAGTTCAACTTTACGGGAGCCAGGGTCCCGCGATTCGACACCATCCATGAAGAGTTCCCCA GGGAGCTGGAGTCCTCCGTCTCCTTCCCAGCCGACTTCTTCAGACCACCTGAAGAAAAAGAAGGCCCC CTGCTGAGGCCGGCTGGCCGGAGGACCACCCCGCAGACCACGCGCCCGGGGCCTGGCACCGAGAGGGA GGCCCCGATCAGCAGGCGGAGGCGACACCCTGATGACGCTGGCCAGTTCGCCGTCGCTCTGGTCATCA TTTACCGCACCCTGGGGCAGCTCCTGCCCGAGCGCTACGACCCCGACCGTCGCAGCCTCCGGTTGCCT CACCGGCCCATCATTAATACCCCGATGGTGAGCACGCTGGTGTACAGCGAGGGGGCTCCGCTCCCGAG ACCCCTGGAGAGGCCCGTCCTGGTGGAGTTCGCCCTGCTGGAGGTGGAGGAGCGAACCAAGCCTGTCT GCGTGTTCTGGAACCACTCCCTGGCCGTTGGTGGGACGGGAGGGTGGTCTGCCCGGGGCTGCGAGCTC CTGTCCAGGAACCGGACACATGTCGCCTGCCAGTGCAGCCACACAGCCAGCTTTGCGGTGCTCATGGA TATCTCCAGGCGTGAGAACGGGGAGGTCCTGCCTCTGAAGATTGTCACCTATGCCGCTGTGTCCTTGT CACTGGCAGCCCTGCTGGTGGCCTTCGTCCTCCTGAGCCTGGTCCGCATGCTGCGCTCCAACCTGCAC AGCATTCACAAGCACCTCGCCGTGGCGCTCTTCCTCTCTCAGCTGGTGTTCGTGATTGGGATCAACCA GACGGAAAACCCGTTTCTGTGCACAGTGGTTGCCATCCTCCTCCACTACATCTACATGAGCACCTTTG CCTGGACCCTCGTGGAGAGCCTGCATGTCTACCGCATGCTGACCGAGGTGCGCAACATCGACACGGGG CCCATGCGGTTCTACTACGTCGTGGGCTGGGGCATCCCGGCCATTGTCACAGGACTGGCGGTCGGCCT GGACCCCCAGGGCTACGGGAACCCCGACTTCTGCTGGCTGTCGCTTCAAGACACCCTGATTTGGAGCT TTGCGGGGCCCATCGGAGCTGTTATAATCATCAACACAGTCACTTCTGTCCTATCTGCAAAGGTTTCC TGCCAAAGAAAGCACCATTATTATGGGAAAAAAGGGATCGTCTCCCTGCTGAGGACCGCATTCCTCCT GCTGCTGCTCATCAGCGCCACCTGGCTGCTGGGGCTGCTGGCTGTGAACCGCGATGCACTGAGCTTTC ACTACCTCTTCGCCATCTTCAGCGGCTTACAGGGCCCCTTCGTCCTCCTTTTCCACTGCGTGCTCAAC CAGGAGGTCCGGAAGCACCTGAAGGGCGTGCTCGGCGGGAGGAAGCTGCACCTGGAGGACTCCGCCAC CACCAGGGCCACCCTGCTGACGCGCTCCCTCAACTGCAACACCACCTTCGGTGACGGGCCTGACATGC TGCGCACAGACTTGGGCGAGTCCACCGCCTCGCTGGACAGCATCGTCAGGGATGAAGGGATCCAGAAG CTCGGCGTGTCCTCTGGGCTGGTGAGGGGCAGCCACGGAGAGCCAGACGCGTCCCTCATGCCCAGGAG CTCCAAGGATCCCCCTGGCCACGATTCCGACTCAGATAGCGAGCTGTCCCTGGATGAGCAGAGCAGCT CTTACGCCTCCTCACACTCGTCAGACAGCGAGGACGATGGGGTGGGAGCTGAGGAAAAATGGGACCCG GCCAGGGGCGCCGTCCACAGCACCCCCAAAGGGGACGCTGTGGCCAACCACGTTCCGGCCGGCTGGCC CGACCAGAGCCTGGCTGAGAGTGACAGTGAGGACCCCAGCGGCAAGCCCCGCCTGAAGGTGGAGACCA AGGTCAGCGTGGAGCTGCACCGCGAGGAGCAGGGCAGTCACCGTGGAGAGTACCCCCCGGACCAGGAG AGCGGGGGCGCAGCCAGGCTTGCTAGCAGCCAGCCCCCAGAGCAGAGGAGCATCTTGAAAAATAAAGT CACCTACCCGCCGCCGCTGACGCTGACGGAGCAGACGCTGAAGGGCCGGCTCCGGGAGAAGCTGGCCG ACTGTGAGCAGAGCCCCACATCCTCGCGCACGTCTTCCCTGGGCTCTGGCGGCCCCGACTGCGCCATC ACAGTCAAGAGCCCTGGGAGGGAGCCGGGGCGTGACCACCTCAACGGGGTGGCCATGAATGTGCGCAC TGGGAGCGCCCAGGCCGATGGCTCCGACTCTGAGAAACCGTGA
[NOV21e, SNP13382483 of SEQ ID NO: 284 302δ aa MW at 330849.8kD CG51965-01, Protein Sequence SNP Pos: 2812 SNP Change: Cys to Ser APPPPPVLPV LL AAAAA PAMGLRAAA EPRVPGGTRAFALRPGCTYAVGAACTPRAPRELLDVG RDGRLAGRRRVSGAGRPLP QVRLVARSAPTA SRRLRARTHLPGCGARAR CGTGARLCGALCFPVP GGCAAAQHSALAAPTTLPACRCPPRPRPRCPGRPICLPPGGSVRLRLLCA RRAAGAVRVGLALEAAT AGTPSASPSPSPP PPNLPEARAGPARRARRGTSGRGSLKFPMPNYQVA FENEPAGTLILQLHAHYT IEGEEERVSYYMEGLFDERSRGYFRIDSATGAVSTDSV DRETKETHVLRVKAVDYSTPPRSATTYIT VLVKDTNDHSPVFEQSEYRERVREN EVGYEVLTIRASDRDSPINANLRYRVLGGAWDVFQ NESSGV VSTRAVLDREEAAEYQL VEANDQGRNPGPLSATATVYIEVEDENDNYPQFSEQNYWQVPEDVG NT AVLRVQATDRDQGQNAAIHYSILSGNVAGQFY HS SGI DVINPLDFEDVQKYSLSIKAQDGGRPP INSSGWSVQVLDVNDNEPIFVSSPFQATVIiENVPLGYPWHIQAVDADSGENARLHYR VDTASTF GGGSAGPKNPAPTPDFPFQIHNSSG ITVCAELDREEVEHYSFGVEAVDHGSPPMSSSTSVSITVLDV NDNDPVFTQPTYELRLNEDAAVGSSVLT QARDRDANSVITYQLTGGNTRNRFALSSQRGGGLITLAL P D KQEQQYV AV ASDGTRSHTAHVLIrVTDANTHRPVFQSSHYTVSVSEDRPVGTSIAT SANDE DTGENARITYVIQDPVPQFRIDPDSGTMYTMMELDYENQVAYT TIMAQDNGIPQKSDTTTLEILILD ANDNAPQFLWDFYQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGDFYIEPTSGVIRT QRRLDRENVAVYN WAAVDRGSPTPLSASVEIQVTILDINDNAPMFEKDELELFVEENNPVGSWAK IRANDPDEGPNAQIMYQIVEGDMRHFFQ D LNGDLRAMVELDFEVRREYVLWQATSAPLVSRATVH I LVDQNDNPPVLPDFQILFNNYVTNKSNSFPTGVIGCIPAHDPDVSDS NYTFVQGNELR L LDPA TGE QLSRDLDNNRP EALMEVSVSADGIHSVTAFCTLRVTIITDDM TNSITVRLENMSQEKF SP ALFVEGVAAVLSTTKDDVFVFNVQNDTDVSSNI NVTFSA PGGVRGQFFPSEDLQEQIYLNRT TTISTQRV PFDDNICLREPCENYMKCVSV RFDSSAPF SSTTVLFRPIHPINGLRCRCPPGFTGDY CETEIDLCYSDPCGANGRCRSREGGYTCECFEDFTGEHCEVDARSGRCA GVCKNGGTCVNLLIGGFH CVCPPGEYERPYCEVTTRSFPPQSFVTFRG RQRFHFTISLTFATQERNG LYNGRFNEKHDFIALE IVDEQVQLTFSAGAGETTTTVAPKVPSGVSDGRWHSVQVQYYNKVR APPLPPGPQPNIGHLGLPHGP SGEKMAWTVDDCDTTMAVRFGKDIGNYSCAAQGTQTGSKKSLDLTGP L GGVPNLPEDFPVHNRQF VGCMRN SVDGKNVDMAGFIANNGTREGCAARRNFCDGRRCQNGGTCVNR N YLCECPLRFGGKNCE QAMPHPQ FSGESWS SD NIIISVP Y G MFRTRKEDSVLMEATSGGPTSFR QI NNYLQFEVS HGPSDVESVMLSGLRVTDGE HHLLIE KNVKEDSEMKHLVTMT DYGMDQNKADIGGMLPGLTVRSV VVGGASEDKVSVRRGFRGCMQGVRMGGTPTNVATLNMNNA KVRVKDGCDVDDPCTSSPCPPNSRCHD AWEDYSCVCDKGY GINCVDACHLNPCENMGACVRSPGSPQGYVCECGPSHYGPYCENKLDLPCPRGW WGNPVCGPCHCAVSKGFDPDCNKT GQCQCIENYYK1.LAQDTCLPCDCFPHGSHSRTCDMATGQCACK PGVIGRQCNRCDNPFAEVTT GCEVIYNGCPKAFEAGIWWPQTKFGQPAAVPCPKGSVGNAVRHCSGE KGW PPELFNCTTISFVDLRAMNEϊOiSRNETQVDGARA QLVRALRSATQHTGTLFGNDVRTAYQL G HV QHES QQGFDLAATQDADFHEDVIHSGSALLAPATRAAWEQIQRSEGGTAQLLRRLEGYFSNVAR NVRRTY RPFVIVTANMVLAVDIFDKFNFTGARVPRFDTIHEEFPRELESSVSFPADFFRPPEEKEGP LLRPAGRRTTPQTTRPGPGTEREAPISRRRRHPDDAGQFAVA VIIYRT GQ LPERYDPDRRSLR P HRPIINTPMVST VYSEGAP PRPLERPV1,VEFALLEVEERTKPVCVFWNHS AVGGTGGWSARGCE LSRNRTHVACQCSHTASFAVLMDISRRENGEVLP KIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLH SIHKHLAVALFLSQ VFVIGINQTENPF CTWAI HYIYMSTFAWTVESLHVYRMLTEVRNIDTG PMRFYYWGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDT IWSFAGPIGAVIIINTVTSVLSAKVS CQRKHHYYGKKGIVSLLRTAFLLLL ISAT LG AVNRDA SFHY FAIFSGLQGPFV LFHCVLN QEVRKHLKGV GGRK HLEDSATTRAT LTRSLNCNTTFGDGPDM RTD GESTASLDSIVRDEGIQK LGVSSGLVRGSHGEPDASLMPRSSKDPPGHDSDSDSELSLDEQSSSYASSHSSDSEDDGVGAEEKWDP ARGAVHSTPKGDAVANHVPAGWPDQSLAESDSEDPSGKPRLKVETKVSVE HREEQGSHRGEYPPDQE SGGAARLASSQPPEQRSILKNKVTYPPPLT TEQT KGRLREKLADCEQSPTSSRTSS GSGGPDCAI TVKSPGREPGRDHLNGVAMNVRTGSAQADGSDSEKP
NOV21f, SNP13382484 of SEQ ID NO: 285 90δ7 bp CG51965-01, DNA Sequence 1ORF Start: ATG at 1 ORF Stop: TGA at 9085 SNP Pos: 8592 SNP Change: C to A
ATGGCGCCGCCGCCGCCGCCCGTGCTGCCCGTGCTGCTGCTCCTGGCCGCCGCCGCCGCCCTGCCGGC GATGGGGCTGCGAGCGGCCGCCTGGGAGCCGCGCGTACCCGGCGGGACCCGCGCCTTCGCCCTCCGGC CCGGCTGTACCTACGCGGTGGGCGCCGCTTGCACGCCCCGGGCGCCGCGGGAGCTGCTGGACGTGGGC CGCGATGGGCGGCTGGCAGGACGTCGGCGCGTCTCGGGCGCGGGGCGCCCGCTGCCGCTGCAAGTCCG CTTGGTGGCCCGCAGTGCCCCGACGGCGCTGAGCCGCCGCCTGCGGGCGCGCACGCACCTTCCCGGCT GCGGAGCCCGTGCCCGGCTCTGCGGAACCGGTGCCCGGCTCTGCGGGGCGCTCTGCTTCCCCGTCCCC GGCGGCTGCGCGGCCGCGCAGCATTCGGCGCTCGCAGCTCCGACCACCTTACCCGCCTGCCGCTGCCC GCCGCGCCCCAGGCCCCGCTGTCCCGGCCGTCCCATCTGCCTGCCGCCGGGCGGCTCGGTCCGCCTGC GTCTGCTGTGCGCCCTGCGGCGCGCGGCTGGCGCCGTCCGGGTGGGACTGGCGCTGGAGGCCGCCACC GCGGGGACGCCCTCCGCGTCGCCATCCCCATCGCCGCCCCTGCCGCCGAACTTGCCCGAAGCCCGGGC GGGGCCGGCGCGACGGGCCCGGCGGGGCACGAGCGGCAGAGGGAGCCTGAAGTTTCCGATGCCCAACT ACCAGGTGGCGTTGTTTGAGAACGAACCGGCGGGCACCCTCATCCTCCAGCTGCACGCGCACTACACC ATCGAGGGCGAGGAGGAGCGCGTGAGCTATTACATGGAGGGGCTGTTCGACGAGCGCTCCCGGGGCTA CTTCCGAATCGACTCTGCCACGGGCGCCGTGAGCACGGACAGCGTACTGGACCGCGAGACCAAGGAGA CGCACGTCCTCAGGGTGAAAGCCGTGGACTACAGTACGCCGCCGCGCTCGGCCACCACCTACATCACT GTCTTGGTCAAAGACACCAACGACCACAGCCCGGTCTTCGAGCAGTCGGAGTACCGCGAGCGCGTGCG GGAGAACCTGGAGGTGGGCTACGAGGTGCTGACCATCCGCGCCAGCGACCGCGACTCGCCCATCAACG CCAACTTGCGTTACCGCGTGTTGGGGGGCGCGTGGGACGTCTTCCAGCTCAACGAGAGCTCTGGCGTG GTGAGCACACGGGCGGTGCTGGACCGGGAGGAGGCGGCCGAGTACCAGCTCCTGGTGGAGGCCAACGA CCAGGGGCGCAATCCGGGCCCGCTCAGTGCCACGGCCACCGTGTACATCGAGGTGGAGGACGAGAACG ACAACTACCCCCAGTTCAGCGAGCAGAACTACGTGGTCCAGGTGCCCGAGGACGTGGGGCTCAACACG GCTGTGCTGCGAGTGCAGGCCACGGACCGGGACCAGGGCCAGAACGCGGCCATTCACTACAGCATCCT CAGCGGGAACGTGGCCGGCCAGTTCTACCTGCACTCGCTGAGCGGGATCCTGGATGTGATCAACCCCT TGGATTTCGAGGATGTCCAGAAATACTCGCTGAGCATTAAGGCCCAGGATGGGGGCCGGCCCCCGCTC ATCAATTCTTCAGGGGTGGTGTCTGTGCAGGTGCTGGATGTCAACGACAACGAGCCTATCTTTGTGAG CAGCCCCTTCCAGGCCACGGTGCTGGAGAATGTGCCCCTGGGCTACCCCGTGGTGCACATTCAGGCGG TGGACGCGGACTCTGGAGAGAACGCCCGGCTGCACTATCGCCTGGTGGACACGGCCTCCACCTTTCTG GGGGGCGGCAGCGCTGGGCCTAAGAATCCTGCCCCCACCCCTGACTTCCCCTTCCAGATCCACAACAG CTCCGGTTGGATCACAGTGTGTGCCGAGCTGGACCGCGAGGAGGTGGAGCACTACAGCTTCGGGGTGG AGGCGGTGGACCACGGCTCGCCCCCCATGAGCTCCTCCACCAGCGTGTCCATCACGGTGCTGGACGTG AATGACAACGACCCGGTGTTCACGCAGCCCACCTACGAGCTTCGTCTGAATGAGGATGCGGCCGTGGG GAGCAGCGTGCTGACCCTGCAGGCCCGCGACCGTGACGCCAACAGTGTGATTACCTACCAGCTCACAG GCGGCAACACCCGGAACCGCTTTGCACTCAGCAGCCAGAGAGGGGGCGGCCTCATCACCCTGGCGCTA CCTCTGGACTACAAGCAGGAGCAGCAGTACGTGCTGGCGGTGACAGCATCCGACGGCACACGGTCGCA CACTGCGCATGTCCTAATCAACGTCACTGATGCCAACACCCACAGGCCTGTCTTTCAGAGCTCCCATT ACACAGTGAGTGTCAGTGAGGACAGGCCTGTGGGCACCTCCATTGCTACCCTCAGTGCCAACGATGAG GACACAGGAGAGAATGCCCGCATCACCTACGTGATTCAGGACCCCGTGCCGCAGTTCCGCATTGACCC CGACAGTGGCACCATGTACACCATGATGGAGCTGGACTATGAGAACCAGGTCGCCTACACGCTGACCA TCATGGCCCAGGACAACGGCATCCCGCAGAAATCAGACACCACCACCCTAGAGATCCTCATCCTCGAT GCCAATGACAATGCACCCCAGTTCCTGTGGGATTTCTACCAGGGTTCCATCTTTGAGGATGCTCCACC CTCGACCAGCATCCTCCAGGTCTCTGCCACGGACCGGGACTCAGGTCCCAATGGGCGTCTGCTGTACA CCTTCCAGGGTGGGGACGACGGCGATGGGGACTTCTACATCGAGCCCACGTCCGGTGTGATTCGCACC CAGCGCCGGCTGGACCGGGAGAATGTGGCCGTGTACAACCTTTGGGCTCTGGCTGTGGATCGGGGCAG TCCCACTCCCCTTAGCGCCTCGGTAGAAATCCAGGTGACCATCTTGGACATTAATGACAATGCCCCCA TGTTTGAGAAGGACGAACTGGAGCTGTTTGTTGAGGAGAACAACCCAGTGGGGTCGGTGGTGGCAAAG ATTCGTGCTAACGACCCTGATGAAGGCCCTAATGCCCAGATCATGTATCAGATTGTGGAAGGGGACAT GCGGCATTTCTTCCAGCTGGACCTGCTCAACGGGGACCTGCGTGCCATGGTGGAGCTGGACTTTGAGG TCCGGCGGGAGTATGTGCTGGTGGTGCAGGCCACGTCGGCTCCGCTGGTGAGCCGAGCCACGGTGCAC ATCCTTCTCGTGGACCAGAATGACAACCCGCCTGTGCTGCCCGACTTCCAGATCCTCTTCAACAACTA
TGTCACCAACAAGTCCAACAGTTTCCCCACCGGCGTGATCGGCTGCATCCCGGCCCATGACCCCGACG TGTCAGACAGCCTCAACTACACCTTCGTGCAGGGCAACGAGCTGCGCCTGTTGCTGCTGGACCCCGCC ACGGGCGAACTGCAGCTCAGCCGCGACCTGGACAACAACCGGCCGCTGGAGGCGCTCATGGAGGTGTC TGTGTCTGCAGATGGCATCCACAGCGTCACGGCCTTCTGCACCCTGCGTGTCACCATCATCACGGACG ACATGCTGACCAACAGCATCACTGTCCGCCTGGAGAACATGTCCCAGGAGAAGTTCCTGTCCCCGCTG CTGGCCCTCTTCGTGGAGGGGGTGGCCGCCGTGCTGTCCACCACCAAGGACGACGTCTTCGTCTTCAA CGTCCAGAACGACACCGACGTCAGCTCCAACATCCTGAACGTGACCTTCTCGGCGCTGCTGCCTGGCG GCGTCCGCGGCCAGTTCTTCCCGTCGGAGGACCTGCAGGAGCAGATCTACCTGAATCGGACGCTGCTG ACCACCATCTCCACGCAGCGCGTGCTGCCCTTCGACGACAACATCTGCCTGCGCGAGCCCTGCGAGAA CTACATGAAGTGCGTGTCCGTTCTGCGATTCGACAGCTCCGCGCCCTTCCTCAGCTCCACCACCGTGC TCTTCCGGCCCATCCACCCCATCAACGGCCTGCGCTGCCGCTGCCCGCCCGGCTTCACCGGCGACTAC TGCGAGACGGAGATCGACCTCTGCTACTCCGACCCGTGCGGCGCCAACGGCCGCTGCCGCAGCCGCGA GGGCGGCTACACCTGCGAGTGCTTCGAGGACTTCACTGGAGAGCACTGTGAGGTGGATGCCCGCTCAG GCCGCTGTGCCAACGGGGTGTGCAAGAACGGGGGCACCTGCGTGAACCTGCTCATCGGCGGCTTCCAC TGCGTGTGTCCTCCTGGCGAGTATGAGAGGCCCTACTGTGAGGTGACCACCAGGAGCTTCCCGCCCCA GTCCTTCGTCACCTTCCGGGGCCTGAGACAGCGCTTCCACTTCACCATCTCCCTCACGTTTGCCACTC AGGAAAGGAACGGCTTGCTTCTCTACAACGGCCGCTTCAATGAGAAGCACGACTTCATCGCCCTGGAG ATCGTGGACGAGCAGGTGCAGCTCACCTTCTCTGCAGGTGCAGGCGAGACAACAACGACCGTGGCACC GAAGGTTCCCAGTGGTGTGAGTGACGGGCGGTGGCACTCTGTGCAGGTGCAGTACTACAACAAGGTAA GATGGGCCCCACCACTTCCCCCTGGCCCCCAGCCCAATATTGGCCACCTGGGCCTGCCCCATGGGCCG TCCGGGGAAAAGATGGCCGTGGTGACAGTGGATGATTGTGACACAACCATGGCTGTGCGCTTTGGAAA GGACATCGGGAACTACAGCTGCGCTGCCCAGGGCACTCAGACCGGCTCCAAGAAGTCCCTGGATCTGA CCGGCCCTCTACTCCTGGGGGGTGTCCCCAACCTGCCAGAAGACTTCCCAGTGCACAACCGGCAGTTC GTGGGCTGCATGCGGAACCTGTCAGTCGACGGCAAAAATGTGGACATGGCCGGATTCATCGCCAACAA TGGCACCCGGGAAGGCTGCGCTGCTCGGAGGAACTTCTGCGATGGGAGGCGGTGTCAGAATGGAGGCA CCTGTGTCAACAGGTGGAATATGTATCTGTGTGAGTGTCCACTCCGATTCGGCGGGAAGAACTGTGAG CAAGCCATGCCTCACCCCCAGCTCTTCAGCGGTGAGAGCGTCGTGTCCTGGAGTGACCTGAACATCAT CATCTCTGTGCCCTGGTACCTGGGGCTCATGTTCCGGACCCGGAAGGAGGACAGCGTTCTGATGGAGG CCACCAGTGGTGGGCCCACCAGCTTTCGCCTCCAGATCCTGAACAACTACCTCCAGTTTGAGGTGTCC CACGGCCCCTCCGATGTGGAGTCCGTGATGCTGTCCGGGTTGCGGGTGACCGACGGGGAGTGGCACCA CCTGCTGATCGAGCTGAAGAATGTTAAGGAGGACAGTGAGATGAAGCACCTGGTCACCATGACCTTGG ACTATGGGATGGACCAGAACAAGGCAGATATCGGGGGCATGCTTCCCGGGCTGACGGTAAGGAGCGTG GTGGTCGGAGGCGCCTCTGAAGACAAGGTCTCCGTGCGCCGTGGATTCCGAGGCTGCATGCAGGGAGT GAGGATGGGGGGGACGCCCACCAACGTCGCCACCCTGAACATGAACAACGCACTCAAGGTCAGGGTGA AGGACGGCTGTGATGTGGACGACCCCTGTACCTCGAGCCCCTGTCCCCCCAATAGCCGCTGCCACGAC GCCTGGGAGGACTACAGCTGCGTCTGTGACAAAGGGTACCTTGGAATAAACTGTGTGGATGCCTGTCA CCTGAACCCCTGCGAGAACATGGGGGCCTGCGTGCGCTCCCCCGGCTCCCCGCAGGGCTACGTGTGCG AGTGTGGGCCCAGTCACTACGGGCCGTACTGTGAGAACAAACTCGACCTTCCGTGCCCCAGAGGCTGG TGGGGGAACCCCGTCTGTGGACCCTGCCACTGTGCCGTCAGCAAAGGCTTTGATCCCGACTGTAATAA GACCAACGGCCAGTGCCAATGCAAGGAGAATTACTACAAGCTCCTAGCCCAGGACACCTGTCTGCCCT GCGACTGCTTCCCCCATGGCTCCCACAGCCGCACTTGCGACATGGCCACCGGGCAGTGTGCCTGCAAG CCCGGCGTCATCGGCCGCCAGTGCAACCGCTGCGACAACCCGTTTGCCGAGGTCACCACGCTCGGCTG TGAAGTGATCTACAATGGCTGTCCCAAAGCATTTGAGGCCGGCATCTGGTGGCCACAGACCAAGTTCG GGCAGCCGGCTGCGGTGCCATGCCCTAAGGGATCCGTTGGAAATGCGGTCCGACACTGCAGCGGGGAG AAGGGCTGGCTGCCCCCAGAGCTCTTTAACTGTACCACCATCTCCTTCGTGGACCTCAGGGCCATGAA TGAGAAGCTGAGCCGCAATGAGACGCAGGTGGACGGCGCCAGGGCCCTGCAGCTGGTGAGGGCGCTGC GCAGTGCTACACAGCACACGGGCACGCTCTTTGGCAATGACGTGCGCACGGCCTACCAGCTGCTGGGC CACGTCCTTCAGCACGAGAGCTGGCAGCAGGGCTTCGACCTGGCAGCCACGCAGGACGCCGACTTTCA CGAGGACGTCATCCACTCGGGCAGCGCCCTCCTGGCCCCAGCCACCAGGGCGGCGTGGGAGCAGATCC
AGCGGAGCGAGGGCGGCACGGCACAGCTGCTCCGGCGCCTCGAGGGCTACTTCAGCAACGTGGCACGC AACGTGCGGCGGACGTACCTGCGGCCCTTCGTCATCGTCACCGCCAACATGGTTCTTGCTGTCGACAT CTTTGACAAGTTCAACTTTACGGGAGCCAGGGTCCCGCGATTCGACACCATCCATGAAGAGTTCCCCA GGGAGCTGGAGTCCTCCGTCTCCTTCCCAGCCGACTTCTTCAGACCACCTGAAGAAAAAGAAGGCCCC CTGCTGAGGCCGGCTGGCCGGAGGACCACCCCGCAGACCACGCGCCCGGGGCCTGGCACCGAGAGGGA GGCCCCGATCAGCAGGCGGAGGCGACACCCTGATGACGCTGGCCAGTTCGCCGTCGCTCTGGTCATCA TTTACCGCACCCTGGGGCAGCTCCTGCCCGAGCGCTACGACCCCGACCGTCGCAGCCTCCGGTTGCCT CACCGGCCCATCATTAATACCCCGATGGTGAGCACGCTGGTGTACAGCGAGGGGGCTCCGCTCCCGAG ACCCCTGGAGAGGCCCGTCCTGGTGGAGTTCGCCCTGCTGGAGGTGGAGGAGCGAACCAAGCCTGTCT GCGTGTTCTGGAACCACTCCCTGGCCGTTGGTGGGACGGGAGGGTGGTCTGCCCGGGGCTGCGAGCTC CTGTCCAGGAACCGGACACATGTCGCCTGCCAGTGCAGCCACACAGCCAGCTTTGCGGTGCTCATGGA TATCTCCAGGCGTGAGAACGGGGAGGTCCTGCCTCTGAAGATTGTCACCTATGCCGCTGTGTCCTTGT CACTGGCAGCCCTGCTGGTGGCCTTCGTCCTCCTGAGCCTGGTCCGCATGCTGCGCTCCAACCTGCAC AGCATTCACAAGCACCTCGCCGTGGCGCTCTTCCTCTCTCAGCTGGTGTTCGTGATTGGGATCAACCA GACGGAAAACCCGTTTCTGTGCACAGTGGTTGCCATCCTCCTCCACTACATCTACATGAGCACCTTTG CCTGGACCCTCGTGGAGAGCCTGCATGTCTACCGCATGCTGACCGAGGTGCGCAACATCGACACGGGG CCCATGCGGTTCTACTACGTCGTGGGCTGGGGCATCCCGGCCATTGTCACAGGACTGGCGGTCGGCCT GGACCCCCAGGGCTACGGGAACCCCGACTTCTGCTGGCTGTCGCTTCAAGACACCCTGATTTGGAGCT TTGCGGGGCCCATCGGAGCTGTTATAATCATCAACACAGTCACTTCTGTCCTATCTGCAAAGGTTTCC TGCCAAAGAAAGCACCATTATTATGGGAAAAAAGGGATCGTCTCCCTGCTGAGGACCGCATTCCTCCT GCTGCTGCTCATCAGCGCCACCTGGCTGCTGGGGCTGCTGGCTGTGAACCGCGATGCACTGAGCTTTC ACTACCTCTTCGCCATCTTCAGCGGCTTACAGGGCCCCTTCGTCCTCCTTTTCCACTGCGTGCTCAAC CAGGAGGTCCGGAAGCACCTGAAGGGCGTGCTCGGCGGGAGGAAGCTGCACCTGGAGGACTCCGCCAC CACCAGGGCCACCCTGCTGACGCGCTCCCTCAACTGCAACACCACCTTCGGTGACGGGCCTGACATGC TGCGCACAGACTTGGGCGAGTCCACCGCCTCGCTGGACAGCATCGTCAGGGATGAAGGGATCCAGAAG CTCGGCGTGTCCTCTGGGCTGGTGAGGGGCAGCCACGGAGAGCCAGACGCGTCCCTCATGCCCAGGAG CTGCAAGGATCCCCCTGGCCACGATTCCGACTCAGATAGCGAGCTGTCCCTGGATGAGCAGAGCAGCT CTTACGCCTCCTCACACTCGTCAGACAGCGAGGACGATGGGGTGGGAGCTGAGGAAAAATGGGACCCG GCCAGGGGCGCCGTCCACAGCACACCCAAAGGGGACGCTGTGGCCAACCACGTTCCGGCCGGCTGGCC CGACCAGAGCCTGGCTGAGAGTGACAGTGAGGACCCCAGCGGCAAGCCCCGCCTGAAGGTGGAGACCA AGGTCAGCGTGGAGCTGCACCGCGAGGAGCAGGGCAGTCACCGTGGAGAGTACCCCCCGGACCAGGAG AGCGGGGGCGCAGCCAGGCTTGCTAGCAGCCAGCCCCCAGAGCAGAGGAGCATCTTGAAAAATAAAGT CACCTACCCGCCGCCGCTGACGCTGACGGAGCAGACGCTGAAGGGCCGGCTCCGGGAGAAGCTGGCCG ACTGTGAGCAGAGCCCCACATCCTCGCGCACGTCTTCCCTGGGCTCTGGCGGCCCCGACTGCGCCATC ACAGTCAAGAGCCCTGGGAGGGAGCCGGGGCGTGACCACCTCAACGGGGTGGCCATGAATGTGCGCAC TGGGAGCGCCCAGGCCGATGGCTCCGACTCTGAGAAACCGTGA
NOV21f, SNP133824δ4 of SEQ ID NO: 286| 3028 aa MW at 330δ65.9kD CG51965-01, Protein Sequence SNP Pos: 2864 SNP Change: Thr to Thr
MAPPPPPVLPVliLL AAAAALPAMGLRAAAWEPRVPGGTRAFA RPGCTYAVGAACTPRAPRE LDVG RDGRLAGRRRVSGAGRPLPLQ VARSAPTALSRRLRARTH PGCGARARLCGTGARLCGALCFPVP GGCAAAQHSALAAPTTLPACRCPPRPRPRCPGRPICLPPGGSVRLRLLCA RRAAGAVRVGLALEAAT AGTPSASPSPSPPLPPNLPEARAGPARRARRGTSGRGS KFPMPNYQVALFENEPAGT ILQLHAHYT IEGEEERVSYYMEGLFDERSRGYFRIDSATGAVSTDSV DRETKETHV RVKAVDYSTPPRSATTYIT V VKDTNDHSPVFEQSEYRERVRENLEVGYEV TIRASDRDSPINA LRYRVLGGAWDVFQLNESSGV VSTRAVLDREEAAEYQLLVEANDQGRNPGPLSATATVYIEVEDENDNYPQFSEQNYWQVPEDVG NT AV RVQATDRDQGQNAAIHYSILSG VAGQFYLHSLSGI DVINP DFEDVQKYSLSIKAQDGGRPP INSSGWSVQVLDVNDNEPIFVSSPFQATVLENVPLGYPWHIQAVDADSGENARLHYRLVDTASTF GGGSAGPKNPAPTPDFPFQIHNSSG ITVCAELDREEVEHYSFGVEAVDHGSPPMSSSTSVSITV DV NDNDPVFTQPTYELRLNEDAAVGSSVLTLQARDRDANSVITYQLTGGNTRNRFALSSQRGGGLITLA P DYKQEQQYVLAVTASDGTRSHTAHV INVTDANTHRPVFQSSHYTVSVSEDRPVGTSIATLSANDE DTGENARITYVIQDPVPQFRIDPDSGTMYTMME DYENQVAYTLTIMAQDNGIPQKSDTTTLEILI D ANDNAPQFL DFYQGSIFEDAPPSTSILQVSATDRDSGPNGR YTFQGGDDGDGDFYIEPTSGVIRT
36δ QRRLDRENVAVY L ALAVDRGSPTPLSASVEIQVTI DINDNAPMFEKDELELFVEENNPVGSWAK IRANDPDEGPNAQI YQIVEGDMRHFFQLD LNGDLRAMVE DFEVRREYVLWQATSAP VSRATVH ILLVDQNDNPPVLPDFQI FNNYVTNKSNSFPTGVIGCIPAHDPDVSDSLNYTFVQGNE R L LDPA TGELQLSRDLDN RP EA MEVSVSADGIHSVTAFCT RV IITDDM TNSITVRLENMSQEKFLSP A FVEGVAAVLSTTKDDVFVFNVQNDTDVSSNILNVTFSAL PGGVRGQFFPSED QEQIY NRT L TTISTQRVLPFDDNICLREPCENYMKCVSVLRFDSSAPF SSTTVLFRPIHPING RCRCPPGFTGDY CETEID CYSDPCGANGRCRSREGGYTCECFEDFTGEHCEVDARSGRCANGVCKNGGTCVN LIGGFH CVCPPGEYERPYCEVTTRSFPPQSFVTFRG RQRFHFTISLTFATQERNG LLYNGRFNEKHDFIALE IVDEQVQ TFSAGAGETTTTVAPKVPSGVSDGR HSVQVQYYNKVRWAPP PPGPQPNIGHLGLPHGP SGEKMAVVTVDDCDTTMAVRFGKDIGNYSCAAQGTQTGSKKSLDLTGP GGVPNLPEDFPVHNRQF VG(_MRNLSVDGKNVDMAGFIANNGTREGCAARRNFCDGRRCQNGGTCVNRWNMYLCECPLRFGGKNCE QAMPHPQLFSGESWS SD NIIISVPWY GLMFRTRIEDSVLMEATSGGPTSFRLQILNNYLQFEVS HGPSDVESVM SG RV DGEWHHL IELKNVKEDSEMKHLVTMTLDYGMDQNKADIGGMLPGLTVRSV VVGGASED^VSVRRGFRGCMQGVR GGTP NVATL ^1NNA KVRVKDGCDVDDPCTSSPCPPNSRCHD A EDYSCVCDKGYLGINCΓVDACHLNPCENMGACVRSPGSPQGYVCECGPSHYGPYCENKLD PCPRGW WGNPVCGPCHCAVSKGFDPDCNKTNGQCQCKENYYKL AQDTCLPCDCFPHGSHSRTCDMATGQCACK PGVIGRQCNRCDNPFAEVTT GCEVIYNGCPIAFEAGI WPQTKFGQPAAVPCPKGSVGNAVRHCSGE KGWLPPELFNCTTISFVDLRAMNEKLSRNETQVDGARALQ VRALRSATQHTGTLFGNDVRTAYQL G HVLQHES QQGFDLAATQDADFHEDVIHSGSA LAPATRAAWEQIQRSEGGTAQ LRRLEGYFSNVAR NVRRTYLRPFVIVTANMVLAVDIFDKFNFTGARVPRFDTIHEEFPRELESSVSFPADFFRPPEEKEGP LRPAGRRTTPQTTRPGPGTEREAPISRRRRHPDDAGQFAVAVIIYRTLGQL PERYDPDRRSLR P HRPIINTPMVSTLVYSEGAP PRPLERP'V VEFA EVEERTKPVCVFWNHSLAVGGTGGWSARGCE SRNRTHVACQCSHTASFAVLMDISRRENGEVLPLKIVTYAAVSLSLAAL VAFVL S VRMLRSNLH SIHKHLAVA FLSQ VFVIGINQTENPFLCTWAILLHYIYMSTFA TLVES HVYRMLTEVRNIDTG PMRFYYWG GIPAIVTGLAVG DPQGYGNPDFCW SLQDT IWSFAGPIGAVIIINTVTSVLSAKVS CQRKHHYYGKKGIVSLLRTAFLL LISATW LGLLAV RDA SFHY FAIFSGLQGPFVL FHCVLN QEVRKHLKGVLGGRKLH EDSATTRAT TRS NCNTTFGDGPDMLRTDLGESTASLDSIVRDEGIQK GVSSG VRGSHGEPDAS PRSCKDPPGHDSDSDSELSLDEQSSSYASSHSSDSEDDGVGAEEK DP ARGAVHSTPKGDAVANHVPAGWPDQSLAESDSEDPSGKPRLICVETKVSVELHREEQGSHRGEYPPDQE SGGAARIΛSSQPPEQRSILKNKVTYPPP TLTEQTLKGRLREKLADCEQSPTSSRTSS GSGGPDCAI TVKSPGREPGRDHLNGVAMNVRTGSAQADGSDSEKP
NOV21g, SNP133824δ5 of SEQ ID NO: 2δ7 90δ7 bp CG51965-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 90δ5
SNP Pos: δ752 SNP Change: G to C
ATGGCGCCGCCGCCGCCGCCCGTGCTGCCCGTGCTGCTGCTCCTGGCCGCCGCCGCCGCCCTGCCGGC GATGGGGCTGCGAGCGGCCGCCTGGGAGCCGCGCGTACCCGGCGGGACCCGCGCCTTCGCCCTCCGGC CCGGCTGTACCTACGCGGTGGGCGCCGCTTGCACGCCCCGGGCGCCGCGGGAGCTGCTGGACGTGGGC CGCGATGGGCGGCTGGCAGGACGTCGGCGCGTCTCGGGCGCGGGGCGCCCGCTGCCGCTGCAAGTCCG CTTGGTGGCCCGCAGTGCCCCGACGGCGCTGAGCCGCCGCCTGCGGGCGCGCACGCACCTTCCCGGCT GCGGAGCCCGTGCCCGGCTCTGCGGAACCGGTGCCCGGCTCTGCGGGGCGCTCTGCTTCCCCGTCCCC GGCGGCTGCGCGGCCGCGCAGCATTCGGCGCTCGCAGCTCCGACCACCTTACCCGCCTGCCGCTGCCC GCCGCGCCCCAGGCCCCGCTGTCCCGGCCGTCCCATCTGCCTGCCGCCGGGCGGCTCGGTCCGCCTGC GTCTGCTGTGCGCCCTGCGGCGCGCGGCTGGCGCCGTCCGGGTGGGACTGGCGCTGGAGGCCGCCACC GCGGGGACGCCCTCCGCGTCGCCATCCCCATCGCCGCCCCTGCCGCCGAACTTGCCCGAAGCCCGGGC GGGGCCGGCGCGACGGGCCCGGCGGGGCACGAGCGGCAGAGGGAGCCTGAAGTTTCCGATGCCCAACT ACCAGGTGGCGTTGTTTGAGAACGAACCGGCGGGCACCCTCATCCTCCAGCTGCACGCGCACTACACC ATCGAGGGCGAGGAGGAGCGCGTGAGCTATTACATGGAGGGGCTGTTCGACGAGCGCTCCCGGGGCTA CTTCCGAATCGACTCTGCCACGGGCGCCGTGAGCACGGACAGCGTACTGGACCGCGAGACCAAGGAGA CGCACGTCCTCAGGGTGAAAGCCGTGGACTACAGTACGCCGCCGCGCTCGGCCACCACCTACATCACT GTCTTGGTCAAAGACACCAACGACCACAGCCCGGTCTTCGAGCAGTCGGAGTACCGCGAGCGCGTGCG GGAGAACCTGGAGGTGGGCTACGAGGTGCTGACCATCCGCGCCAGCGACCGCGACTCGCCCATCAACG CCAACTTGCGTTACCGCGTGTTGGGGGGCGCGTGGGACGTCTTCCAGCTCAACGAGAGCTCTGGCGTG GTGAGCACACGGGCGGTGCTGGACCGGGAGGAGGCGGCCGAGTACCAGCTCCTGGTGGAGGCCAACGA CCAGGGGCGCAATCCGGGCCCGCTCAGTGCCACGGCCACCGTGTACATCGAGGTGGAGGACGAGAACG ACAACTACCCCCAGTTCAGCGAGCAGAACTACGTGGTCCAGGTGCCCGAGGACGTGGGGCTCAACACG GCTGTGCTGCGAGTGCAGGCCACGGACCGGGACCAGGGCCAGAACGCGGCCATTCACTACAGCATCCT CAGCGGGAACGTGGCCGGCCAGTTCTACCTGCACTCGCTGAGCGGGATCCTGGATGTGATCAACCCCT TGGATTTCGAGGATGTCCAGAAATACTCGCTGAGCATTAAGGCCCAGGATGGGGGCCGGCCCCCGCTC ATCAATTCTTCAGGGGTGGTGTCTGTGCAGGTGCTGGATGTCAACGACAACGAGCCTATCTTTGTGAG CAGCCCCTTCCAGGCCACGGTGCTGGAGAATGTGCCCCTGGGCTACCCCGTGGTGCACATTCAGGCGG TGGACGCGGACTCTGGAGAGAACGCCCGGCTGCACTATCGCCTGGTGGACACGGCCTCCACCTTTCTG GGGGGCGGCAGCGCTGGGCCTAAGAATCCTGCCCCCACCCCTGACTTCCCCTTCCAGATCCACAACAG CTCCGGTTGGATCACAGTGTGTGCCGAGCTGGACCGCGAGGAGGTGGAGCACTACAGCTTCGGGGTGG AGGCGGTGGACCACGGCTCGCCCCCCATGAGCTCCTCCACCAGCGTGTCCATCACGGTGCTGGACGTG AATGACAACGACCCGGTGTTCACGCAGCCCACCTACGAGCTTCGTCTGAATGAGGATGCGGCCGTGGG GAGCAGCGTGCTGACCCTGCAGGCCCGCGACCGTGACGCCAACAGTGTGATTACCTACCAGCTCACAG GCGGCAACACCCGGAACCGCTTTGCACTCAGCAGCCAGAGAGGGGGCGGCCTCATCACCCTGGCGCTA CCTCTGGACTACAAGCAGGAGCAGCAGTACGTGCTGGCGGTGACAGCATCCGACGGCACACGGTCGCA CACTGCGCATGTCCTAATCAACGTCACTGATGCCAACACCCACAGGCCTGTCTTTCAGAGCTCCCATT ACACAGTGAGTGTCAGTGAGGACAGGCCTGTGGGCACCTCCATTGCTACCCTCAGTGCCAACGATGAG GACACAGGAGAGAATGCCCGCATCACCTACGTGATTCAGGACCCCGTGCCGCAGTTCCGCATTGACCC CGACAGTGGCACCATGTACACCATGATGGAGCTGGACTATGAGAACCAGGTCGCCTACACGCTGACCA TCATGGCCCAGGACAACGGCATCCCGCAGAAATCAGACACCACCACCCTAGAGATCCTCATCCTCGAT GCCAATGACAATGCACCCCAGTTCCTGTGGGATTTCTACCAGGGTTCCATCTTTGAGGATGCTCCACC CTCGACCAGCATCCTCCAGGTCTCTGCCACGGACCGGGACTCAGGTCCCAATGGGCGTCTGCTGTACA CCTTCCAGGGTGGGGACGACGGCGATGGGGACTTCTACATCGAGCCCACGTCCGGTGTGATTCGCACC CAGCGCCGGCTGGACCGGGAGAATGTGGCCGTGTACAACCTTTGGGCTCTGGCTGTGGATCGGGGCAG TCCCACTCCCCTTAGCGCCTCGGTAGAAATCCAGGTGACCATCTTGGACATTAATGACAATGCCCCCA TGTTTGAGAAGGACGAACTGGAGCTGTTTGTTGAGGAGAACAACCCAGTGGGGTCGGTGGTGGCAAAG ATTCGTGCTAACGACCCTGATGAAGGCCCTAATGCCCAGATCATGTATCAGATTGTGGAAGGGGACAT GCGGCATTTCTTCCAGCTGGACCTGCTCAACGGGGACCTGCGTGCCATGGTGGAGCTGGACTTTGAGG TCCGGCGGGAGTATGTGCTGGTGGTGCAGGCCACGTCGGCTCCGCTGGTGAGCCGAGCCACGGTGCAC ATCCTTCTCGTGGACCAGAATGACAACCCGCCTGTGCTGCCCGACTTCCAGATCCTCTTCAACAACTA
TGTCACCAACAAGTCCAACAGTTTCCCCACCGGCGTGATCGGCTGCATCCCGGCCCATGACCCCGACG TGTCAGACAGCCTCAACTACACCTTCGTGCAGGGCAACGAGCTGCGCCTGTTGCTGCTGGACCCCGCC ACGGGCGAACTGCAGCTCAGCCGCGACCTGGACAACAACCGGCCGCTGGAGGCGCTCATGGAGGTGTC TGTGTCTGCAGATGGCATCCACAGCGTCACGGCCTTCTGCACCCTGCGTGTCACCATCATCACGGACG ACATGCTGACCAACAGCATCACTGTCCGCCTGGAGAACATGTCCCAGGAGAAGTTCCTGTCCCCGCTG CTGGCCCTCTTCGTGGAGGGGGTGGCCGCCGTGCTGTCCACCACCAAGGACGACGTCTTCGTCTTCAA CGTCCAGAACGACACCGACGTCAGCTCCAACATCCTGAACGTGACCTTCTCGGCGCTGCTGCCTGGCG GCGTCCGCGGCCAGTTCTTCCCGTCGGAGGACCTGCAGGAGCAGATCTACCTGAATCGGACGCTGCTG ACCACCATCTCCACGCAGCGCGTGCTGCCCTTCGACGACAACATCTGCCTGCGCGAGCCCTGCGAGAA CTACATGAAGTGCGTGTCCGTTCTGCGATTCGACAGCTCCGCGCCCTTCCTCAGCTCCACCACCGTGC TCTTCCGGCCCATCCACCCCATCAACGGCCTGCGCTGCCGCTGCCCGCCCGGCTTCACCGGCGACTAC TGCGAGACGGAGATCGACCTCTGCTACTCCGACCCGTGCGGCGCCAACGGCCGCTGCCGCAGCCGCGA GGGCGGCTACACCTGCGAGTGCTTCGAGGACTTCACTGGAGAGCACTGTGAGGTGGATGCCCGCTCAG GCCGCTGTGCCAACGGGGTGTGCAAGAACGGGGGCACCTGCGTGAACCTGCTCATCGGCGGCTTCCAC TGCGTGTGTCCTCCTGGCGAGTATGAGAGGCCCTACTGTGAGGTGACCACCAGGAGCTTCCCGCCCCA GTCCTTCGTCACCTTCCGGGGCCTGAGACAGCGCTTCCACTTCACCATCTCCCTCACGTTTGCCACTC AGGAAAGGAACGGCTTGCTTCTCTACAACGGCCGCTTCAATGAGAAGCACGACTTCATCGCCCTGGAG ATCGTGGACGAGCAGGTGCAGCTCACCTTCTCTGCAGGTGCAGGCGAGACAACAACGACCGTGGCACC GAAGGTTCCCAGTGGTGTGAGTGACGGGCGGTGGCACTCTGTGCAGGTGCAGTACTACAACAAGGTAA GATGGGCCCCACCACTTCCCCCTGGCCCCCAGCCCAATATTGGCCACCTGGGCCTGCCCCATGGGCCG TCCGGGGAAAAGATGGCCGTGGTGACAGTGGATGATTGTGACACAACCATGGCTGTGCGCTTTGGAAA GGACATCGGGAACTACAGCTGCGCTGCCCAGGGCACTCAGACCGGCTCCAAGAAGTCCCTGGATCTGA CCGGCCCTCTACTCCTGGGGGGTGTCCCCAACCTGCCAGAAGACTTCCCAGTGCACAACCGGCAGTTC GTGGGCTGCATGCGGAACCTGTCAGTCGACGGCAAAAATGTGGACATGGCCGGATTCATCGCCAACAA TGGCACCCGGGAAGGCTGCGCTGCTCGGAGGAACTTCTGCGATGGGAGGCGGTGTCAGAATGGAGGCA CCTGTGTCAACAGGTGGAATATGTATCTGTGTGAGTGTCCACTCCGATTCGGCGGGAAGAACTGTGAG CAAGCCATGCCTCACCCCCAGCTCTTCAGCGGTGAGAGCGTCGTGTCCTGGAGTGACCTGAACATCAT CATCTCTGTGCCCTGGTACCTGGGGCTCATGTTCCGGACCCGGAAGGAGGACAGCGTTCTGATGGAGG CCACCAGTGGTGGGCCCACCAGCTTTCGCCTCCAGATCCTGAACAACTACCTCCAGTTTGAGGTGTCC CACGGCCCCTCCGATGTGGAGTCCGTGATGCTGTCCGGGTTGCGGGTGACCGACGGGGAGTGGCACCA CCTGCTGATCGAGCTGAAGAATGTTAAGGAGGACAGTGAGATGAAGCACCTGGTCACCATGACCTTGG ACTATGGGATGGACCAGAACAAGGCAGATATCGGGGGCATGCTTCCCGGGCTGACGGTAAGGAGCGTG GTGGTCGGAGGCGCCTCTGAAGACAAGGTCTCCGTGCGCCGTGGATTCCGAGGCTGCATGCAGGGAGT GAGGATGGGGGGGACGCCCACCAACGTCGCCACCCTGAACATGAACAACGCACTCAAGGTCAGGGTGA AGGACGGCTGTGATGTGGACGACCCCTGTACCTCGAGCCCCTGTCCCCCCAATAGCCGCTGCCACGAC GCCTGGGAGGACTACAGCTGCGTCTGTGACAAAGGGTACCTTGGAATAAACTGTGTGGATGCCTGTCA CCTGAACCCCTGCGAGAACATGGGGGCCTGCGTGCGCTCCCCCGGCTCCCCGCAGGGCTACGTGTGCG AGTGTGGGCCCAGTCACTACGGGCCGTACTGTGAGAACAAACTCGACCTTCCGTGCCCCAGAGGCTGG TGGGGGAACCCCGTCTGTGGACCCTGCCACTGTGCCGTCAGCAAAGGCTTTGATCCCGACTGTAATAA GACCAACGGCCAGTGCCAATGCAAGGAGAATTACTACAAGCTCCTAGCCCAGGACACCTGTCTGCCCT GCGACTGCTTCCCCCATGGCTCCCACAGCCGCACTTGCGACATGGCCACCGGGCAGTGTGCCTGCAAG CCCGGCGTCATCGGCCGCCAGTGCAACCGCTGCGACAACCCGTTTGCCGAGGTCACCACGCTCGGCTG TGAAGTGATCTACAATGGCTGTCCCAAAGCATTTGAGGCCGGCATCTGGTGGCCACAGACCAAGTTCG GGCAGCCGGCTGCGGTGCCATGCCCTAAGGGATCCGTTGGAAATGCGGTCCGACACTGCAGCGGGGAG AAGGGCTGGCTGCCCCCAGAGCTCTTTAACTGTACCACCATCTCCTTCGTGGACCTCAGGGCCATGAA TGAGAAGCTGAGCCGCAATGAGACGCAGGTGGACGGCGCCAGGGCCCTGCAGCTGGTGAGGGCGCTGC GCAGTGCTACACAGCACACGGGCACGCTCTTTGGCAATGACGTGCGCACGGCCTACCAGCTGCTGGGC CACGTCCTTCAGCACGAGAGCTGGCAGCAGGGCTTCGACCTGGCAGCCACGCAGGACGCCGACTTTCA CGAGGACGTCATCCACTCGGGCAGCGCCCTCCTGGCCCCAGCCACCAGGGCGGCGTGGGAGCAGATCC
AGCGGAGCGAGGGCGGCACGGCACAGCTGCTCCGGCGCCTCGAGGGCTACTTCAGCAACGTGGCACGC AACGTGCGGCGGACGTACCTGCGGCCCTTCGTCATCGTCACCGCCAACATGGTTCTTGCTGTCGACAT CTTTGACAAGTTCAACTTTACGGGAGCCAGGGTCCCGCGATTCGACACCATCCATGAAGAGTTCCCCA GGGAGCTGGAGTCCTCCGTCTCCTTCCCAGCCGACTTCTTCAGACCACCTGAAGAAAAAGAAGGCCCC CTGCTGAGGCCGGCTGGCCGGAGGACCACCCCGCAGACCACGCGCCCGGGGCCTGGCACCGAGAGGGA GGCCCCGATCAGCAGGCGGAGGCGACACCCTGATGACGCTGGCCAGTTCGCCGTCGCTCTGGTCATCA TTTACCGCACCCTGGGGCAGCTCCTGCCCGAGCGCTACGACCCCGACCGTCGCAGCCTCCGGTTGCCT CACCGGCCCATCATTAATACCCCGATGGTGAGCACGCTGGTGTACAGCGAGGGGGCTCCGCTCCCGAG ACCCCTGGAGAGGCCCGTCCTGGTGGAGTTCGCCCTGCTGGAGGTGGAGGAGCGAACCAAGCCTGTCT GCGTGTTCTGGAACCACTCCCTGGCCGTTGGTGGGACGGGAGGGTGGTCTGCCCGGGGCTGCGAGCTC CTGTCCAGGAACCGGACACATGTCGCCTGCCAGTGCAGCCACACAGCCAGCTTTGCGGTGCTCATGGA TATCTCCAGGCGTGAGAACGGGGAGGTCCTGCCTCTGAAGATTGTCACCTATGCCGCTGTGTCCTTGT CACTGGCAGCCCTGCTGGTGGCCTTCGTCCTCCTGAGCCTGGTCCGCATGCTGCGCTCCAACCTGCAC AGCATTCACAAGCACCTCGCCGTGGCGCTCTTCCTCTCTCAGCTGGTGTTCGTGATTGGGATCAACCA GACGGAAAACCCGTTTCTGTGCACAGTGGTTGCCATCCTCCTCCACTACATCTACATGAGCACCTTTG CCTGGACCCTCGTGGAGAGCCTGCATGTCTACCGCATGCTGACCGAGGTGCGCAACATCGACACGGGG CCCATGCGGTTCTACTACGTCGTGGGCTGGGGCATCCCGGCCATTGTCACAGGACTGGCGGTCGGCCT GGACCCCCAGGGCTACGGGAACCCCGACTTCTGCTGGCTGTCGCTTCAAGACACCCTGATTTGGAGCT TTGCGGGGCCCATCGGAGCTGTTATAATCATCAACACAGTCACTTCTGTCCTATCTGCAAAGGTTTCC TGCCAAAGAAAGCACCATTATTATGGGAAAAAAGGGATCGTCTCCCTGCTGAGGACCGCATTCCTCCT GCTGCTGCTCATCAGCGCCACCTGGCTGCTGGGGCTGCTGGCTGTGAACCGCGATGCACTGAGCTTTC ACTACCTCTTCGCCATCTTCAGCGGCTTACAGGGCCCCTTCGTCCTCCTTTTCCACTGCGTGCTCAAC CAGGAGGTCCGGAAGCACCTGAAGGGCGTGCTCGGCGGGAGGAAGCTGCACCTGGAGGACTCCGCCAC CACCAGGGCCACCCTGCTGACGCGCTCCCTCAACTGCAACACCACCTTCGGTGACGGGCCTGACATGC TGCGCACAGACTTGGGCGAGTCCACCGCCTCGCTGGACAGCATCGTCAGGGATGAAGGGATCCAGAAG CTCGGCGTGTCCTCTGGGCTGGTGAGGGGCAGCCACGGAGAGCCAGACGCGTCCCTCATGCCCAGGAG CTGCAAGGATCCCCCTGGCCACGATTCCGACTCAGATAGCGAGCTGTCCCTGGATGAGCAGAGCAGCT CTTACGCCTCCTCACACTCGTCAGACAGCGAGGACGATGGGGTGGGAGCTGAGGAAAAATGGGACCCG GCCAGGGGCGCCGTCCACAGCACCCCCAAAGGGGACGCTGTGGCCAACCACGTTCCGGCCGGCTGGCC CGACCAGAGCCTGGCTGAGAGTGACAGTGAGGACCCCAGCGGCAAGCCCCGCCTGAAGGTGGAGACCA AGGTCAGCGTGGAGCTGCACCGCGAGGAGCAGGGCAGTCACCGTGGACAGTACCCCCCGGACCAGGAG AGCGGGGGCGCAGCCAGGCTTGCTAGCAGCCAGCCCCCAGAGCAGAGGAGCATCTTGAAAAATAAAGT CACCTACCCGCCGCCGCTGACGCTGACGGAGCAGACGCTGAAGGGCCGGCTCCGGGAGAAGCTGGCCG ACTGTGAGCAGAGCCCCACATCCTCGCGCACGTCTTCCCTGGGCTCTGGCGGCCCCGACTGCGCCATC ACAGTCAAGAGCCCTGGGAGGGAGCCGGGGCGTGACCACCTCAACGGGGTGGCCATGAATGTGCGCAC TGGGAGCGCCCAGGCCGATGGCTCCGACTCTGAGAAACCGTGA
NOV21g, SNP13382485 of SEQ ID NO: 2δ 3028 aa MW at 330δ64.9kD
CG51965-01, Protein Sequence gjjP pos: 2918 SNP Change: Glu to Gin
MAPPPPPVLPVLLLLAAAAALPAMGLRAAAWEPRVPGGTRAFALRPGCTYAVGAACTPRAPRELLDVG RDGR AGRRRVSGAGRP PLQVRLVARSAPTA SRR RARTHLPGCGARARLCGTGAR CGALCFPVP GGCAAAQHSALAAPTTLPACRCPPRPRPRCPGRPIC PPGGSVR RL CALRRAAGAVRVGLALEAAT AGTPSASPSPSPPLPPNLPEARAGPARRARRGTSGRGSLKFPMPNYQVA FENEPAGTLI QLHAHYT IEGEEERVSYYMEGLFDERSRGYFRIDSATGAVSTDSVLDRETKETHVLRVKAVDYSTPPRSATTYIT VLVKDTNDHSPVFEQSEYRERVRENLEVGYEVLTIRASDRDSPINAN RYRVLGGA DVFQLNESSGV VSTRAV DREEAAEYQL VEANDQGRNPGP SATATVYIEVEDENDNYPQFSEQNYWQVPEDVGLNT AVLRVQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGI DVINPLDFEDVQKYSLSIKAQDGGRPP INSSGWSVQVLDVNDNEPIFVSSPFQATVLENVPLGYPWHIQAVDADSGENARLHYR VDTASTF GGGSAGPKNPAPTPDFPFQIHNSSGWITVCAELDREEVEHYSFGVEAVDHGSPPMSSSTSVSITVliDV NDNDPVFTQPTYELR NEDAAVGSSVLT QARDRDANSVITYQLTGGNTRNRFALSSQRGGG ITLA PL.DYKQEQQYVLAVTASDGTRSHTAHVLINVTDANTHRPVFQSSHYTVSVSEDRPVGTSIAT SANDE DTGENARITYVIQDPVPQFRIDPDSGTMYTMMELDYENQVAYTLTIMAQDNGIPQKSDTTTLEI ILD ANDNAPQFLWDFYQGSIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGDFYIEPTSGVIRT QRRLDRENVAVYNLWALAVDRGSPTP SASVEIQVTILDINDNAPMFEKDE ELFVEENNPVGSWAK IRANDPDEGPNAQIMYQIVEGDMRHFFQ D LNGD RAMVELDFEVRREYVLWQATSAP VSRATVH I LVDQNDNPPVLPDFQILFNNYVTNKSNSFPTGVIGCIPAHDPDVSDSIiNYTFVQGNELRL LLDPA TGELQ SRDLDNNRPLEALMEVSVSADGIHSVTAFCTLRVTIITDDM TNSITVRLENMSQEKFLSP LALFVEGVAAV STTKDDVFVFNVQNDTDVSSNILNVTFSALLPGGVRGQFFPSEDLQEQIY NRTLL TTISTQRV PFDDNIC REPCENYMKCVSV RFDSSAPFLSSTTVLFRPIHPINGLRCRCPPGFTGDY CETEIDLCYSDPCGANGRCRSREGGYTCECFEDFTGEHCEVDARSGRCANGVCKNGGTCVNLLIGGFH CVCPPGEYERPYCEVTTRSFPPQSFVTFRGLRQRFHFTISLTFATQERNG L YNGRFNEKHDFIALE IVDEQVQLTFSAGAGETTTTVAPKVPSGVSDGRWHSVQVQYYNKVRWAPP PPGPQPNIGH GLPHGP SGEKMAWTVDDCDTTMAVRFGKDIGNYSCAAQGTQTGSKKSLDLTGPLLLGGVPNLPEDFPVHNRQF VGCMRNLSVDGKNVDMAGFIANNGTREGCAARRNFCDGRRCQNGGTCVNR NMYLCECPLRFGGFOJCE QAMPHPQ FSGESVVS SDLNIIISVPWYLG MFRTRKEDSVLMEATSGGPTSFRLQILNNYLQFEVS HGPSDVESVMLSGLRVTDGEWHH IELKNVKEDSEMKH VTMTLDYGMDQNKADIGGMLPGLTVRSV WGGASED VSVRRGFRGCMQGVRMGGTPTNVATLNMNNALKVRVKDGCDVDDPCTSSPCPPNSRCHD AWEDYSCVCDKGYLGINCVDACH NPCENMGACVRSPGSPQGYVCECGPSHYGPYCENK D PCPRGW GNPVCGPCHCAVSKGFDPDCNKTNGQCQCKENYYKLLAQDTCLPCDCFPHGSHSRTCDMATGQCACK PGVIGRQCNRCDNPFAEOTT GCEVIYNGCPKAFEAGIWWPQTKFGQPAAVPCPKGSVGNAVRHCSGE KG LPPELFNCTTISFVD RAMNEK SRNETQVDGARA Q VRALRSATQHTGTLFGNDVRTAYQLLG HVLQHESWQQGFDLAATQDADFHEDVIHSGSALLAPATRAAWEQIQRSEGGTAQLLRR EGYFSNVAR NVRRTYLRPFVIVTANMV AVDIFDKFNFTGARVPRFDTIHEEFPRELESSVSFPADFFRPPEEKEGP L RPAGRRTTPQTTRPGPGTEREAPISRRRRHPDDAGQFAVA VIIYRTLGQLLPERYDPDRRSLRLP HRP11NTPMVST VYSEGAP PRP ERPVIJVEFALLEVEERTKPVCVFWNHSLAVGGTGGWSARGCEL LSR RTHVACQCSHTASFAVLMDISRRENGEV PLKIVTYAAVS SLAALLVAFVLLS VRMLRSNLH SIHKHLAVALF SQLVFVIGINQTENPFLCTWAILLHYIYMSTFA T VESLHVYRM TEVRNIDTG PMRFYYVVGWGIPAIVTGIAVG DPQGYGNPDFCW S QDT IWSFAGPIGAVIIINTVTSVLSAKVS CQRKHHYYGKKGIVS RTAFL LLLISATW G LAVNRDA SFHY FAIFSG QGPFVLLFHCVLN QEVRKHLKGV GGRKLHLEDSATTRAT LTRSLNCNTTFGDGPDMLRTD GESTASLDSIVRDEGIQK GVSSG VRGSHGEPDASLMPRSCKDPPGHDSDSDSE SLDEQSSSYASSHSSDSEDDGVGAEEKWDP ARGAVHSTPKGDAVANHVPAG PDQSLAESDSEDPSGKPRLKVETKVSVELHREEQGSHRGQYPPDQE SGGAARLASSQPPEQRSILKN VTYPPPLTLTEQTLKGR REKLADCEQSPTSSRTSSLGSGGPDCAI TVKSPGREPGRDH NGVAMNVRTGSAQADGSDSEKP
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 2 IB.
Table 21B. Comparison ofthe NOV21 protein sequences.
NOV2la MAPPPPPV PVL LLAAAAALPAMGLRAAAWEPRVPGGTRAFALRPGCTYAVGAACTPRA
NOV21b
NOV2lc
NOV21d
NOV2la PRE LDVGRDGRLAGRRRVSGAGRP P QVR VARSAPTALSRR RARTH PGCGARARL
NOV21b
NOV2lc
NOV2Id N0V2la CGTGARLCGALCFPVPGGCAAAQHSALAAPTTLPACRCPPRPRPRCPGRPICLPPGGSVR
N0V21b
N0V21C
N0V21d
N0V2la LR CALRRAAGAVRVG ALEAATAGTPSASPSPSPP PPNLPEARAGPARRARRGTSGR
N0V21b
NOV2lc
NOV21d
NOV21a GSLKFPMPNYQVALFENEPAGTLILQLHAHYTIEGEEERVSYYMEG FDERSRGYFRIDS
NOV2lb
NOV21C
NOV21d K YQVALFENEPAGTLILQLHAHHTIEGEEERVSYYMEG FDERSRGYFRIDS
NOV2la ATGAVSTDSV DRETKETHVLRVKAVDYSTPPRSATTYITV VKDTNDHSPVFEQSEYRE
NOV2lb LKLEVIYNGCPKAFEAGIWWPQTK
NOV2lc
NOV2Id AAGAVSTDSVLDRETKETHVLRVKAVDYSTPPRSATTYITV VKDTNDHSPVFEQSEYRE
N0V2la RVREN EVGYEV TIRASDRDSPINANLRYRVLGGAWDVFQLNESSGWSTRAVLDREEA
N0V2lb FGQPAAVPCPKGSVGNAVRHCSGEKGWLPPELFNCTTISFVDLRAMNEKLSRNETQVDGA
N0V21C - -RK-LVLPLKIVTYAAVS-LS-LAALLVAFVL SLVRMLRSNLHS-IHKHLAVALF- -
NOV2Id RVRENLEVGYEV TIRASDRDSPINAN RYRV GGAWDVFQLNESSGWSTRAVLDREEA
N0V2la AEYQ VEANDQGRNPGPLSATATVYIEVEDENDNYPQFSEQNYWQVPEDVGLNTAVLR
NOV2lb RALQ VRALRSATQHTGTLFGNDVRTAYQLLGHVLQHES QQGFDLAATQDADFHEDVIH
NOV2lc SQ VFVIGIN-QTENP-FLC WAILLHYIYMS TFAWT- -LVES LHVYR
NOV2Id AEYQLLVEANDQGRNPGPLSATATVYIEVEDENDNYPQFSEQNYWQVPEDVGLNTAVLR
NOV21a VQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGI DVINPLDFEDVQKYSLSIKAQDGG
NOV2lb SGSALLAPATRAAWEQIQRSEG-GTAQLLRRLEGYFSNVARNVRRTY RPFVIVTANMIL
NOV2lc MLTEVRN IDTG- -PMRFYYWGWGIPAIVT G LAVG DPQGYG
NOV2Id VQATDRDQGQNAAIHYSILSGNVAGQFYLHSLSGI DVINPLDFEDVQ YSLSIKAQDGG
NOV21a RPPLINSSGWSVQVLDVNDNEPIFVSSPFQATVLENVPLGYPWHIQAVDADSGENARL
NOV2lb AVDIFDKFNFTGARVPRFDTIHEEFPRELESSVSFPADFFRPPEEKEGPLLRPAGRRTTP
NOV2lc NPDFC W SLQDT I SFAG-PIGAVIIINT VTSVLSAKVSCQRK
NOV21d RPP INSSGWSVQVLDVNDNEPIFVSSPFQATVLENVP GYPWHIQAVDADSGENAR
NOV2la HYR VDTASTF GGGSAGPKNPAPTPDFPFQIHNSSGWITVCAELDRE-EVEHYSFGVEA
NOV lb QTTRPGPGTEREAPISRRRRHPDDAGQFAVA VII RTLGQL PERYD-PDRRSLR PHR
NOV21C HH YYG- -KKGIVSLLRT-AFL LLLISAT GLLAVNRDALSFHYLFAIFS
NOV21d HYR VDTASTFLGGGSAGPKNPAPTPDFPFQIRNSSGWITVCAELDREEVE-HYSFGVEA
NOV2la VDHGSPPMSSSTSVSITVLDVNDNDPVFTQPTYELR NEDAAVGSSV TLQARDRDANSV
NOV2lb PIINTPMVST VYSEGAPLPRP ERPVLVEFAL EVEERTKPVCVFWNHSLAVGGTGGWS
NOV2lc G QG-P FV-LLFHCV-LNQEVK A
NOV2Id VDHG PPMSSSTSVSITVLDVNDNDPVFTQPTYELRLNEDAAVGSSV TLQARDRDANSV
NOV21a ITYQ TGGNTRNRFA SSQRGGGLIT ALPLDYKQEQQYV AVTASDGTRSHTAHV INV NOV21b ARGCELLSRNRTHVACQCSHTASFAVLMDISRRENGEKL NOV21C NOV2Id ITYQLTGGNTRNRFALSSQRGGGLITLALPLDYKQEQQYVLAVTASDGTRSHTAHV INV
NOV21a TDANTHRPVFQSSHYTVSVSEDRPVGTSIAT SANDEDTGENARITYVIQDPVPQFRIDP
NOV2lb
NOV2lc
NOV21d TDANTHRPVFQSSHYTVSVSEDRPVGTSIAT SANDEDTGENARITYVIQDPVPQFRIDP
NOV21a DSGTMYTMMELDYENQVAYT TIMAQDNGIPQKSDTTT EI ILDANDNAPQFL DFYQG
NOV2 lb
NOV21C
NOV21d DSGTMYTMMELDYENQVAYTLTIMAQDNGIPQKSDTTT EILILDANDNAPQFL DFYQG
NOV21a SIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGDFYIEPTSGVIRTQRR DRE
NOV21b
NOV2lc
NOV21d SIFEDAPPSTSILQVSATDRDSGPNGRLLYTFQGGDDGDGDFYIEPTSGVIRTQRRLDRE
NOV2 la NVAVYNL ALAVDRGSPTPLSASVEIQVTILDINDNAPMFEKDE E FVEENNPVGSWA
NOV21b
NOV2lc
NOV2Id NVAVYN WALAVDRGSPTPLSASVEIQVTI DINDNAPMFEKDELE FVEENNPVGSWA
NOV2la KIRANDPDEGPNAQIMYQIVEGDMRHFFQLD LNGDLRAMVE DFEVRREYVLWQATSA
NOV2lb
NOV2 lc
NOV2Id KIRANDPDEGPNAQIMYQIVEGDMRHFFQLDLLNGDLRA VE DFEVRREYVLWQATSA
NOV2 la PLVSRATVHILLVDQNDNPPVLPDFQI FNNYVTNKSNSFPTGVIGCIPAHDPDVSDSLN
NOV2lb
NOV21C
NOV2Id P VSRATVHIL VLE
NOV2 la YTFVQGNELR LLDPATGELQLSRDLDNNRP EALMEVSVSADGIHSVTAFCTLRVTII
NOV2 lb
NOV2 lc
NOV21d
NOV2la TDDM TNSITVR EN SQEKFLSPLLA FVEGVAAV STTKDDVFVFNVQNDTDVSSNIL
NOV2 lb
NOV21c
NOV2Id
NOV2 la NVTFSAL PGGVRGQFFPSEDLQEQIYLNRT LTTISTQRVLPFDDNICLREPCENYMKC
NOV2 lb
NOV21C
NOV21d
NOV21a VSV RFDSSAPFLSSTTVLFRPIHPINGLRCRCPPGFTGDYCETEIDLCYSDPCGANGRC
NOV2lb
NOV2lc
NOV2 Id
NOV2la RSREGGYTCECFEDFTGEHCEVDARSGRCANGVCKNGGTCVNLLIGGFHCVCPPGEYERP
NOV21b NOV2 lc
NOV2Id
NOV2la YCEVTTRSFPPQSFVTFRGLRQRFHFTISLTFATQERNGL LYNGRFNEKHDFIALEIVD
NOV2 lb
NOV2lc
NOV21d
NOV21a EQVQ TFSAGAGETTTTVAPKVPSGVSDGRWHSVQVQYYNKVRWAPP PPGPQPNIGH G
NOV2lb
NOV2lc
NOV2 Id
NOV2la LPHGPSGEKMAWTVDDCDTTMAVRFGKDIGNYSCAAQGTQTGSKKSLDLTGPLL GGVP
NOV2lb
NOV2lc
NOV2Id
NOV2la NLPEDFPVHNRQFVGCMRNLSVDGKNVDMAGFIANNGTREGCAARRNFCDGRRCQNGGTC
NOV2 lb
NOV2lc
NOV21d
NOV21a VNRWNMYLCECPLRFGGKNCEQAMPHPQLFSGESWSWSDLNIIISVP Y GLMFRTRKE
NOV2lb
NOV2lc
NOV2Id
NOV2la DSV MEATSGGPTSFRLQI NNYLQFEVSHGPSDVESVM SG RVTDGEWHH IELKNV
NOV21b
NOV2lc
NOV2Id
NOV2la KEDSEMKHLVTMTLDYGMDQNKADIGGM PGLTVRSVVVGGASEDKVSVRRGFRGCMQGV
NOV2lb
NOV2lc
NOV21d
NOV2 la RMGGTPTNVATLNMNNALKVRVKDGCDVDDPCTSSPCPPNSRCHDAWEDYSCVCDKGYLG
NOV2lb
NOV2lc
NOV2Id
NOV2la INCVDACHLNPCENMGACVRSPGSPQGYVCECGPSHYGPYCENKLD PCPRGWWGNPVCG
NOV21b
NOV2lc
NOV2Id
NOV 1a PCHCAVSKGFDPDCNKTNGQCQCKENYYK LiAQDTCLPCDCFPHGSHSRTCDMATGQCAC
NOV21b
NOV2lc
NOV2Id
NOV21a KPGVIGRQCNRCDNPFAEVTT GCEVIYNGCPKAFEAGI WPQTKFGQPAAVPCPKGSVG NOV21b
NOV21c
NOV2Id
NOV2la NAVRHCSGEKGWLPPE FNCTTISFVD RAMNEKLSRNETQVDGARA QLVRALRSATQH
NOV21b
NOV21c
NOV21d
NOV21a TGTLFGNDVRTAYQLLGHVLQHESWQQGFDLAATQDADFHEDVIHSGSALLAPATRAAWE
NOV2lb
NOV2lc
NOV21d
NOV2la QIQRSEGGTAQLLRRLEGYFSNVARNVRRTYLRPFVIVTANMVLAVDIFDKFNFTGARVP
NOV2lb
NOV2lc
NOV21d
NOV21a RFDTIHEEFPRELESSVSFPADFFRPPEEKEGPLLRPAGRRTTPQTTRPGPGTEREAPIS
NOV21b
NOV2lc
NOV21d
NOV2la RRRRHPDDAGQFAVALVIIYRTLGQLLPERYDPDRRSLRLPHRPIINTPMVSTLVYSEGA
NOV2lb
NOV21C
NOV2Id
NOV2la PLPRPLERPVLVEFALLEVEERTKPVCVF NHSLAVGGTGGWSARGCELLSRNRTHVACQ
NOV21b
NOV2lc
NOV21d
NOV2la CSHTASFAVLMDISRRENGEVLPLKIVTYAAVSLSLAALLVAFVLLSLVRMLRSNLHSIH
NOV2lb
NOV21C
NOV21d
NOV21a KHLAVALFLSQLVFVIGINQTENPFLCTWAILLHYIYMSTFA TLVESLHVYRMLTEVR
NOV21b
NOV2lc
NOV2Id
NOV21a NIDTGPMRFYYWGWGIPAIVTGLAVGLDPQGYGNPDFCWLSLQDTLI SFAGP1GAVII
NOV21b
NOV21C
NOV2Id
NOV2la INTVTSVLSAKVSCQRKHHYYGKKGIVSLLRTAFLLLLLISATWLLGLLAVNRDALSFHY
NOV2lb
NOV2lc
NOV2Id NOV2la LFAIFSGLQGPFVLLFHCVLNQEVRKHLKGVLGGRKLHLEDSATTRATLLTRSLNCNTTF
NOV2lb
NOV21c
NOV21d
NOV2la GDGPDMLRTDLGESTASLDSIVRDEGIQKLGVSSGLVRGSHGEPDASLMPRSCKDPPGHD
NOV2lb
NOV2lc
NOV21d
NOV21a SDSDSELSLDEQSSSYASSHSSDSEDDGVGAEEKWDPARGAVHSTPKGDAVANHVPAG P
NOV2 lb
NOV2lc
NOV21d
NOV2la DQSLAESDSEDPSGKPRLKVETKVSVELHREEQGSHRGEYPPDQESGGAARLASSQPPEQ
NOV2lb
NOV2lc
NOV2Id
NOV21a RSILKNKVTYPPPLTLTEQTLKGRLREKLADCEQSPTSSRTSSLGSGGPDCAITVKSPGR
NOV21b
NOV2lc
NOV2Id
NOV21a EPGRDHLNGVAMNVRTGSAQADGSDSEKP
NOV2lb
NOV2lc
NOV21d
NOV21a (SEQ ID NO 276)
NOV21b (SEQ ID NO 278)
NOV21C (SEQ ID NO 280)
NOV21d (SEQ ID NO 282)
Further analysis ofthe NOV21a protein yielded the following properties shown in Table 21C.
Table 21C. Protein Sequence Properties NOV21a
SignalP analysis: Cleavage site between residues 21 and 22
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos. chg 0; neg.chg 0 H-region: length 26; peak value 9.94 PSG score: 5.54
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 3.49 possible cleavage site: between 20 and 21
>>> Seems to have a cleavable signal peptide (1 to 20) ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 21
Tentative number of TMS(s) for the threshold 0.5: 10
INTEGRAL Likelihood -4.99 Transmembrane 1220 -1236
INTEGRAL Likelihood -0.53 Transmembrane 2251 -2267
INTEGRAL Likelihood -0.06 Transmembrane 2351 -2367
INTEGRAL Likelihood -9.92 Transmembrane 2489 -2505
INTEGRAL Likelihood -5.95 Transmembrane 2521 -2537
INTEGRAL Likelihood -1.54 Transmembrane 2544 -2560
INTEGRAL Likelihood -2.81 Transmembrane 2591 -2607
INTEGRAL Likelihood -1.59 Transmembrane 2631 -2647
INTEGRAL Likelihood -8.92 Transmembrane 2674 -2690
INTEGRAL Likelihood -1.17 Transmembrane 2703 -2719
PERIPHERAL Likelihood 2.81 (at 1076)
ALOM score: -9.92 (number of TMSs: 10)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 10 Charge difference: 1.0 C( 2.0) - N( 1.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 1.33 Hyd Moment(95): 2.60 G content: 1 D/E content : 1 S/T content : 0 Score: -5.63
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 69 PRA|PR
NUCDISC: discrimination of nuclear localization signals pat4: RRRR (5) at 2340 pat4 : RRRH (3) at 2341 pat7: PARRARR (4) at 229 pat7: PISRRRR (5) at 2337 bipartite: none content of basic residues: 9.1% NLS Score: 0.80
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: DSEK
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
37δ RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum
11.1 %: vacuolar
11.1 %: mitochondrial
11.1 %: cytoplasmic
>> prediction for CG51965-01 is end (k=9)
A search ofthe NOV2 la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2 ID.
Figure imgf000384_0001
In a BLAST search of public sequence databases, the NOV21 a protein was found to have homology to the proteins shown in the BLASTP data in Table 2 IE.
Figure imgf000385_0001
PFam analysis indicates that the NOV21a protein contains the domains shown in the Table 21F.
Figure imgf000386_0001
Figure imgf000387_0001
Example 22.
The NOV22 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 22A.
Figure imgf000387_0002
3δ3 TAGCCTGTGAAGAAACCTTACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATT GTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAG CCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTG AGCCAATCCTGCCAGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGAT CCCAATCAAAGTGCCAAGTGGTAG
NOV22a, CG519δ3-05 SEQ ID NO: 290 755 aa MW at δ5δόδ.5kD Protein Sequence
MLPGCIFLMILLIPQVlv-EKFILGVEGQQLTOPKKLPLIQKRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYS KGEAFTRHPQIMEHCYYKGNILNEK SVASISTCDGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTEL FTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRIWGM FVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS FWQEKILKTRKDFDHWLLSGK LYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIA RMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTSITILVWLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIAD PNQSAKW
NOV22b, CG51983-01 SEQ ID NO: 291 2431 bp DNA Sequence ORF Start: ATG at 51 ORF Stop: TAG at 2385
GAACTCCTTTTCTCAAGCACTTCTGCTCTCCTCTACCAGAATCACTCAGAATGCTTCCCGGGTGTATA
TTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCTTGGAGTAGAGGGTCAACAACT GGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGATACTGGACACACCCATGATGATGACATAA AAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGAAAAACCTTAGTCCTTCATCTTCTA AGATCCAGGAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTACTCCATGAAAGGAGAAGCGTT CACCAGGCATCCTCAGATCATGGATCATTGTTTTTACCAAGGATCCATAGTACACGAATATGATTCAG CTGCCAGTATCAGTACGTGTAATGGTCTAAGGGGATTCTTCAGAATAAACGACCAAAGATACCTCATT GAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATATAACCTGAGGGTGCCGTATGG TGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTCCAGGGGATAATGAATCTGAAG AAGACTCCAAAATAAAACAGGGCATCCATGATGAAAAGTATGTTGAATTGTTCATTGTTGCTGATGAT ACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCGAATTTGGGGAATGGTCAATTT TGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTGGCATTGAAATATGGACACATG AAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGTTTTTCATTTTGGCAAGAAAAG ATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGGGAAGTGGCTCTACTCACATGT GCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCACCAGTATCATTAAGGATCTTT TACCTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGGCATAACCTTGGGATGCAGCAT GACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAGTGATGGAAGCATTCCTGCACT GAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGGATTATAAGCCAACATGCATGC TCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGAAACAAGAAGTTGGATGAGGGT GAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTGATGCACACACATGTGTACT GAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAGATAAAAAAAGCAGGGTCCA TATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGGCCACTCGCCTGCCTGTCCT AAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGGCTACTGTTTCATGGGGAAATG TCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAATAGAGAGTCATGATATCTGCT ACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAGGAAAACAGATTTCTTCCCTGT GAGGAGAAGGATGTCAGATGTGGAAAGATCTACTGCACTGGAGGGGAGCTTTCCTCTCTCCTTGGAGA AGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCAAATGCAAAACTATTTTTTTAT ACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGTGGAGAGGGAATGGTATGCAAC AATGGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACCAATTGCCCCTCTCAGTGCAATGAAAA TCCTGTAGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGGCACCTGTAGCCTGTGAAGAAA CCTTACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATTGTCGGTATCGGAGTT CTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAGCCCACCTACAGAAAC CCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTGAGCCAATCCTGCCAG AAATTCATTTCCTAAATCAGAGAACTCCAGAATCCTTGGAAAGCCTGCCCACTAGTTTTTCAAGTCCC CACTACATCACACTGAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGATCCCAATCAAAGTGCCAA GTGGTAGGTTACCCTGACAGATAGTACCTCCCTTTTTTATTTTTCAAATGC NOV22b, CG51983-01 SEQ ID NO: 292 778 aa MW at 8δ471.2kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDIKTYEEELLYEIKLNRKT LVLHLLRSRREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDSAASISTCNGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKQGIHDEKYVEL FIVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRF SF QEKILKTRKDFDHWLLSGK LYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGH NLGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGN KKLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTG HSPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKE NRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCG EGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTSITILVWLVLV IVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNQRTPESLESLP TSFSSPHYITLKPASKDSRGIADPNQSAK
NOV22c, CG519δ3-02 SEQ ID NO: 293 2583 bp DNA Sequence ORF Start: ATG at 85 ORF Stop: TGA at 2347
GATCCCTGCAGTGGAAGTGAGGAGGAAGAAAGGTGAACTCCTTTTCTCAAGCACTTCTGCTCTCCTCT
ACCAGAATCACTCAGAATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAG
AAAAGTTCATCCTTGGAGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAG CGAGATACTGGACACACCCATGATGATGACATACTGAAAACGTATGAAGAAGAATTGTTGTATGAAAT AAAACTAAATAGAAAAACCTTAGTCCTTCATCTTCTAAGATCCAGGGAGTTCCTAGGCTCAAATTACA GTGAAACATTCTACTCCATGAAAGGAGGAGCGTTCACCAGGCATCCTCAGATCATGGATCATTGTTTT TACCAAGGATCCATAGTACACGAATATGATTCAGCTGCCAGTATCAGTACGTGTAATGGTCTAAGGGG ATTCTTCAGAATAAACGACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATT TGGTGTTCAAATATAACCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACC AGAAAAACTGTTCCAGGGGATAATGAATCTGAAGAAGACTCCAAAATAAAAGGCATCCATGATGAAAA GTATGTTGAATTGTTCATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAAC TAAGGAACCGAATTTGGGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTG ACGTTGGTTGGCATTGAAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTAC CTTATTGCGTTTTTCATTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTAT TACTCAGTGGGAAGTGGCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCC TATTATTCCACCAGTATCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACA TCAACTGGGGCATAACCTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCG TGATGGACAGTGATGGAAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAG TACTTGAAGGATTATAAGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCA ATTTTGTGGAAACAAGAAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTA ATCCTTGCTGTGATGCACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGT GAATCTTGTCAGATAAAAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGA GATGTGCACTGGCCACTCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGA ACTCAGAAGGCTACTGTTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGAT GATGATGCAATAGAGAGTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTG CAAAAACAAGGAAAACAGATTTCTTCCCTGTGAGGAGAAAGATGTCAGATGTGGAAAGATCTACTGCA CTGGAGGGGAGCTTTCCTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAAT GCTACTGTCAAATGCAAAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGG AACAAAATGTGGAGAGGGAATGGTGTGCAACAATGGTGAATGTCTAAACATGGAAAAGGTCTATATCT CAACCAATTGCCCCTCTCAGTGCAATGAAAATCCTGTGGATGGCCACGGACTCCAGTGCCACTGTGAG GAAGGACAGGCACCTGTAGCCTGTGAAGAAACCTTACATGTTACCAATATCACCATCTTGGTTGTTGT GCTTGTCCTGGTTATTGTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGT TGAAGCAAGTTCAGAGCCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAG CAGCAGATAAGGACTGAGCCAATCCTGCCAGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTC AAGAGGAATCGCAGATCCCAATCAAAGTGCCAAGTGAGCTTGAAGTTGGATATCCAAAATGGCCGTGC AAGCTTAGGCTGGGGATTCTGGATGCAACGTCTTTACAACCTTACCTAGATATCTGCTACTCACATTT TTGGTAGTGTTTCAAACGTTCTTTATCCAGACAGACAATGTTTAAGAGAAACAACTTATTTCTGTTAA TATTTACCGGTAGAATTCACACCCTCTATCATAAACATATGCTGCAGAAAAAAAAAAAAAAAAAAAA NOV22c, CG51983-02 SEQ ID NO: 294 754 aa MW at 855δ2.1kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGGAFTRHPQIMDHCFYQGSIVHEYDSAASISTCNGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS F QEKILKTRKDFDHWLLSGKWLYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDDAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTNITILVWLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIAD PNQSAK
NOV22d, CG51983-03 SEQ ID NO: 295 2274 bp DNA Sequence ORF Start: ATG at 4 ORF Stop: TAG at 2272
AGAATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCT
TGGAGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGATACTGGAC ACACCCATGATGATGACATAAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGAAAA ACCTTAGTCCTTCATCTTCTAAGATCCAGGAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTA CTCCATGAAAGGAGAAGCGTTCACCAGGCATCCTCAGATCATGGATCATTGTTTTTACCAAGGATCCA TAGTACACGAATATGATTCAGCTGCCAGTATCAGTACGTGTAATGGTCTAAGGGGATTCTTCAGAATA AACGACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATA TAACCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTC CAGGGGATAATGAATCTGAAGAAGACTCCAAAATAAAACAGGGCATCCATGATGAAAAGTATGTTGAA TTGTTCATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCG AATTTGGGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTG GCATTGAAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGT TTTTCATTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGG GAAGTGGCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCA CCAGTATCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGG CATAACCTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAG TGATGGAAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGG ATTATAAGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGA AACAAGAAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTG TGATGCACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTC AGATAAAAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACT GGCCACTCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGG CTACTGTTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAA TAGAGAGTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAG GAAAACAGATTTCTTCCCTGTGAGGAGAAGGATGTCAGATGTGGAAAGATCTACTGCACTGGAGGGGA GCTTTCCTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCA AATGCAAAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGT GGAGAGGGAATGGTATGCAACAATGGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACCAATTG CCCCTCTCAGTGCAATGAAAATCCTGTAGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGG CACCTGTAGCCTGTGAAGAAACCTTACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTG GTTATTGTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGT TCAGAGCCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAA GGACTGAGCCAATCCTGCCAGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTCAAGAGGAATC GCAGATCCCAATCAAAGTGCCAAGTGGTAG
NOV22d, CG51983-03 SEQ ID NO: 296 756 aa MW at 85998.5kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDIKTYEEELLYEIKLNRKT LVLHLLRSRREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDSAASISTCNGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKQGIHDEKYVEL FIVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRF SFWQEKILKTRKDFDHWLLSGK LYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGH NLGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGN KKLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTG HSPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKE NRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCG EGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTSITILVWLVLV IVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIA DPNQSAKW
NOV22e, CG51983-04 SEQ ID NO: 297 2283 bp DNA Sequence ORF Start: ATG at 12 ORF Stop: TGA at 2274
AATCACTCAGAATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAG
TTCATCCTTGGAGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGA TACTGGACACACCCATGATGATGACATACTGAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAAC TAAATAGAAAAACCTTAGTCCTTCATCTTCTAAGATCCAGGGAGTTCCTAGGCTCAAATTACAGTGAA ACATTCTACTCCATGAAAGGAGGAGCGTTCACCAGGCATCCTCAGATCATGGATCATTGTTTTTACCA AGGATCCATAGTACACGAATATGATTCAGCTGCCAGTATCAGTACGTGTAATGGTCTAAGGGGATTCT TCAGAATAAACGACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTG TTCAAATATAACCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAA AACTGTTCCAGGGGATAATGAATCTGAAGAAGACTCCAAAATAAAAGGCATCCATGATGAAAAGTATG TTGAATTGTTCATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGG AACCGAATTTGGGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTT GGTTGGCATTGAAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTAT TGCGTTTTTCATTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTC AGTGGGAAGTGGCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTA TTCCACCAGTATCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACATCAAC TGGGGCATAACCTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATG GACAGTGATGGAAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTT GAAGGATTATAAGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTT GTGGAAACAAGAAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCT TGCTGTGATGCACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATC TTGTCAGATAAAAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGT GCACTGGCCACTCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCA GAAGGCTACTGTTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGA TGCAATAGAGAGTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAA ACAAGGAAAACAGATTTCTTCCCTGTGAGGAGAAAGATGTCAGATGTGGAAAGATCTACTGCACTGGA GGGGAGCTTTCCTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTAC TGTCAAATGCAAAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAA AATGTGGAGAGGGAATGGTGTGCAACAATGGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACC AATTGCCCCTCTCAGTGCAATGAAAATCCTGTGGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGG ACAGGCACCTGTAGCCTGTGAAGAAACCTTACATGTTACCAATATCACCATCTTGGTTGTTGTGCTTG TCCTGGTTATTGTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAG CAAGTTCAGAGCCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCA GATAAGGACTGAGCCAATCCTGCCGGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTCAAGAG GAATCGCAGATCCCAATCAAAGTGCCAAGTGAGCTTGAA
NOV22e, CG51983-04 SEQ ID NO: 298 754 aa MW at δ55δ2.1kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGGAFTRHPQIMDHCFYQGSIVHEYDSAASISTCNGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS F QEKILKTRKDFDHWLLSGKWLYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDDAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE
3δ7 GMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTNITILVWLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIAD PNQSAK
NOV22f, CG51983-06 SEQ ID NO: 299 2464 bp DNA Sequence ORF Start: ATG at 4 ORF Stop: TGA at 2248
AGAATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCT
TGGAGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGATACTGGAC ACACCCATGATGATGACATACTGAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGA AAAACCTTAGTCCTTCATCTTCTAAGATCCAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTA CTCCATGAAAGGAGAAGCGTTCACCAGGCATCCTCAGATCATGGATCATTGTTTTTACCAAGGATCCA TAGTACACGAATATGATTCAGCTGCCAGTATCAGTACGTGTAATGGTCTAAGGGGATTCTTCAGAATA AACGACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATA TAACCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTC CAGGGGATAATGAATCTGAAGAAGACTCCAAAATAAAAGGCATCCATGATGAAAAGTATGTTGAATTG TTCATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCGAAT TTGGGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTGGCA TTGAAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGTTTT TCATTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGGGAA GTGGCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCACCA GTATCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGGCAT AACCTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAGTGA TGGAAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGGATT ATAAGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGAAAC AAGAAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTGA TGCACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAGA TAAAAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGGC CACTCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGGCTA CTGTTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAATAG AGAGTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAGGAA AACAGATTTCTTCCCTGTGAGGAGAAAGATGTCAGATGTGGAAAGACCTACTGCACTGGAGGGGAGCT TTCCTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCAAAT GCAAAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGTGGA GAGGGAATGGTGGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGGCACCTGTAGCCTGTGA AGAAACCTTACATGTTACCAATATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATTGTCGGTATCG GAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAGCCCACCTACA GAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTGAGCCAATCCT GCCAGAAATTCATTTCCTAAATAGAACTCCAGAATCCTTGGAAAGCCTGCCCACTAGTTTTTCAAGTC CCCACTACATCACACTGAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGATCCCAATCAAAGTGCC AAGTGAGCTTGAAGTTGGATATCCAAAATGGCCGTGCAAGCTTAGGCTGGGGATTCTGGATGCAACGT
CTTTACAACCTTACCTAGATATCTGCTACTCACATTTTTGGTAGTGTTTCAAACGTTCTTTATCCAGA
CAGACAATGTTTAAGAGAAACAACTTATTTCTGTTAATATTTACCGGTAGAATTCACACCCTCTATCA iTAAACATATGCTGCAG
NOV22f, CG51983-06 SEQ ID NO: 300 748 aa MW at δ5014.4kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDSAASISTCNGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS FWQEKILKTRKDFDHWLLSGKWLYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKTYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVDGHGLQCHCEEGQAPVACEETLHVTNITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTE TLGVENKGYFGDEQQIRTEPILPEIHFLNRTPESLESLPTSFSSPHYITLKPASKDSRGIADPNQSAK
3δδ NOV22g, SNP133765δ5 of SEQ ID NO: 301 226δ bp CG519δ3-05, DNA Sequence ORF Start: ATG at 1 ORF Stop: TAG at 2266
SNP Pos: 119 SNP Change: A to G
ATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCTTGG AGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAGGCGAGATACTGGACACA CCCATGATGATGACATACTGAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGAAAA ACCTTAGTCCTTCATCTTCTAAGATCCAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTACTC CATGAAAGGAGAAGCGTTCACCAGGCATCCTCAGATCATGGAACACTGTTACTATAAAGGAAACATCC TAAATGAAAAGAATTCTGTTGCCAGCATCAGTACTTGTGACGGGTTGAGGGGATTCTTCAGAATAAAC GACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATATAA CCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTCCAG GGGATAATGAATCTGAAGAAGACTCCAAAATAAAAGGCATCCATGATGAAAAGTATGTTGAATTGTTC ATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCGAATTTG GGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTGGCATTG AAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGTTTTTCA TTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGGGAAGTG GCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCACCAGTA TCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGGCATAAC CTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAGTGATGG AAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGGATTATA AGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGAAACAAG AAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTGATGC ACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAGATAA AAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGGCCAC TCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGGCTACTG TTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAATAGAGA GTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAGGAAAAC AGATTTCTTCCCTGTGAGGAGAAGGATGTCAGATGTGGAAAGATCTACTGCACTGGAGGGGAGCTTTC CTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCAAATGCA AAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGTGGAGAG GGAATGGTATGCAACAATGGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACCAATTGCCCCTC TCAGTGCAATGAAAATCCTGTAGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGGCACCTG TAGCCTGTGAAGAAACCTTACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATT GTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAG CCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTG AGCCAATCCTGCCAGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGAT CCCAATCAAAGTGCCAAGTGGTAG
NOV22g, SNPl 33765δ5 of S SEQ ID NO: 302 755 aa MW at 85896.5kD
CG519δ3-05, Protein Sequence gsjsjp pos: _ Q SNP Change: Lys to Arg
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQRRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMEHCYYKGNILNEKNSVASISTCDGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS FWQEKILKTRKDFDHWLLSGKWLYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTSITILVWLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIAD PNQSAKW
3δ9 NOV22h, SNP133765δό of SEQ ID NO: 303 226δ bp CG519δ3-05, DNA Sequence ORF Start: ATG at 1 ORF Stop: TAG at 2266
SNP Pos: 125 SNP Change: A to G
ATGCTTCCCGGGTGTATATTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCTTGG AGTAGAGGGTCAACAACTGGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGGTACTGGACACA CCCATGATGATGACATACTGAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGAAAA ACCTTAGTCCTTCATCTTCTAAGATCCAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTACTC CATGAAAGGAGAAGCGTTCACCAGGCATCCTCAGATCATGGAACACTGTTACTATAAAGGAAACATCC TAAATGAAAAGAATTCTGTTGCCAGCATCAGTACTTGTGACGGGTTGAGGGGATTCTTCAGAATAAAC GACCAAAGATACCTCATTGAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATATAA CCTGAGGGTGCCGTATGGTGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTCCAG GGGATAATGAATCTGAAGAAGACTCCAAAATAAAAGGCATCCATGATGAAAAGTATGTTGAATTGTTC ATTGTTGCTGATGATACTGTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCGAATTTG GGGAATGGTCAATTTTGTCAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTGGCATTG AAATATGGACACATGAAGATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGTTTTTCA TTTTGGCAAGAAAAGATCCTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGGGAAGTG GCTCTACTCACATGTGCAAGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCACCAGTA TCATTAAGGATCTTTTACCTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGGCATAAC CTTGGGATGCAGCATGACGAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAGTGATGG AAGCATTCCTGCACTGAAATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGGATTATA AGCCAACATGCATGCTCAACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGAAACAAG AAGTTGGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTGATGC ACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAGATAA AAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGGCCAC TCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGGCTACTG TTTCATGGGGAAATGTCCAACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAATAGAGA GTCATGATATCTGCTACAAGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAGGAAAAC AGATTTCTTCCCTGTGAGGAGAAGGATGTCAGATGTGGAAAGATCTACTGCACTGGAGGGGAGCTTTC CTCTCTCCTTGGAGAAGACAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCAAATGCA AAACTATTTTTTTATACCATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGTGGAGAG GGAATGGTATGCAACAATGGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACCAATTGCCCCTC TCAGTGCAATGAAAATCCTGTAGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGGCACCTG TAGCCTGTGAAGAAACCTTACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATT GTCGGTATCGGAGTTCTTATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAG CCCACCTACAGAAACCCTGGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTG AGCCAATCCTGCCAGAAATTCATTTCCTAAATAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGAT CCCAATCAAAGTGCCAAGTGGTAG
NOV22h, SNP133765δό of SEQ ID NO: 304; 755 aa MW at δ5δl0.5kD CG519δ3-05, Protein Sequence SNP Pos: 42 SNP Change: Asp to Gly
MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRGTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMEHCYYKGNILNEKNSVASISTCDGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRI GMVNFVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS F QEKILKTRKDFDHWLLSGK LYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVACEETLHVTSITILVWLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNKPASKDSRGIAD PNQSAKW
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 22B. Table 22B. Comparison ofthe NOV22 protein sequences.
NOV22a MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL NOV22b MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDIK-TYEEELL NOV22C MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL NOV22d MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDIK-TYEEELL NOV22e MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL NOV22f MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL
NOV22a YEIKLNRKTLVLHLLRSR-EFLGSNYSETFYSMKGEAFTRHPQIMEHCYYKGNILNEKNS NOV22b YEIKLNRKTLVLHLLRSRREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDS NOV22c YEIKLNRKTLVLHLLRSR-EFLGSNYSETFYSMKGGAFTRHPQIMDHCFYQGSIVHEYDS NOV22d YEIKLNRKTLVLHLLRSRREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDS NOV22e YEIKLNRKTLVLHLLRSR-EFLGSNYSETFYSMKGGAFTRHPQIMDHCFYQGSIVHEYDS NOV22f YEIKLNRKTLVLHLLRSR-EFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDS
NOV22a VASISTCDGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVP GANYSCTELNFTRKT NOV22b AASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKT NOV22C AASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKT NOV22d AASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKT NOV22e AASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKT NOV22f AASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKT
NOV22a VPGDNESEEDSKIKG- IHDEKYVELFIVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYK NOV22b VPGDNESEEDSKIKQGIHDEKYVELFIVADDTVYRRNGHPHNKLRNRI GMVNFVNMIYK NOV22C VPGDNESEEDSKIKG-IHDEKYVELFIVADDTVYRRNGHPHNKLRNRI GMVNFVNMIYK NOV22d VPGDNESEEDSKIKQGIHDEKYVELFIVADDTVYRRNGHPHNKLRNRI GMVNFVNMIYK NOV22e VPGDNESEEDSKIKG- IHDEKYVELFIVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYK NOV22f VPGDNESEEDSKIKG- IHDEKYVELFIVADDTVYRRNGHPHNKLRNRI GMVNFVNMIYK
NOV22a TLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGKWLYS NOV22b TLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGKWLYS NOV22C TLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGK LYS NOV22d TLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGKWLYS NOV22e TLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGK LYS NOV22f TLNIHVTLVGIEI THEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHWLLSGKWLYS
NOV22a HVQGISYPGGMCLPYYSTSI IKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV NOV22b HVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV NOV22C HVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV NOV22d HVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV NOV22e HVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV NOV22f HVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCV
NOV22a MDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC NOV22b MDSDGSI ALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC NOV22c MDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC NOV22d MDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC NOV22e MDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC NOV22f MDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDC
NOV22a GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP NOV2 b GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP NOV22C GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP
NOV22d GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP
NOV22e GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP
NOV22f GPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSP
NOV22a ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGY NOV22b ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGY NOV22C ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDDAIESHDICYKMNTKGNKFGY NOV22d ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGY NOV22e ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDDAIESHDICYKMNTKGNKFGY NOV22f ACPKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGY
NOV22a CKNKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS NOV22b CKNKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS NOV22C CKNKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS NOV22d CKNKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS NOV22e CKNKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS NOV22f CKNKENRFLPCEEKDVRCGKTYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDS
NOV22a TDIGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPV NOV22b TDIGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPV N0V22C TDIGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPV N0V22d TDIGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPV NOV22e TDIGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPV NOV22f TDIGLVASGTKCGEGMVD GHGLQCHCEEGQAPV
NOV22a ACEETLHVTSITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG NOV22b ACEETLHVTSITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG NOV22C ACEETLHVTNITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG NOV22d ACEETLHVTSITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG NOV22e ACEETLHVTNITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG NOV22f ACEETLHVTNITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFG
NOV22a DEQQIRTEPILPEIHFLN KPASKDSRGIADPNQSAKW N0V22b DEQQIRTEPILPEIHFLNQRTPESLESLPTSFSSPHYITLKPASKDSRGIADPNQSAKW NOV22C DEQQIRTEPILPEIHFLN KPASKDSRGIADPNQSAK- NOV22d DEQQIRTEPILPEIHFLN KPASKDSRGIADPNQSAKW NOV22e DEQQIRTEPILPEIHFLN KPASKDSRGIADPNQSAK- NOV22f DEQQIRTEPILPEIHFLN-RTPESLESLPTSFSSPHYITLKPASKDSRGIADPNQSAK-
NOV22a (SEQ ID NO 290) NOV22b (SEQ ID NO 292) NOV22c (SEQ ID NO 294) NOV22d (SEQ ID NO 296) NOV22e (SEQ ID NO 298) NOV22f (SEQ ID NO 300)
Further analysis ofthe NOV22a protein yielded the following properties shown in Table 22C. Table 22C. Protein Sequence Properties NOV22a
SignalP analysis: Cleavage site between residues 19 and 20
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos. chg 0; neg.chg 0 H-region: length 16; peak value 12.97 PSG score: 8.57
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.58 possible cleavage site: between 18 and 19
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 2 INTEGRAL Likelihood = -2.18 Transmembrane 1 - 17 INTEGRAL Likelihood =-18.52 Transmembrane 671 - 687 PERIPHERAL Likelihood = 4.35 (at 235) ALOM score: -18.52 (number of TMSs: 2)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 8 Charge difference: 0.0 C( 1.0) - N{ 1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.80 Hyd Moment(95): 1.48 G content: 1 D/E content : 1 S/T content : 0 Score: -6.33
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: RPKK (4) at 31 pat7: none bipartite: none content of basic residues: 11.5% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: QSAK
SKL: peroxisomal targeting signal in the C-terminus: none PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs:
Bacterial regulatory proteins, gntR family signature (PS00043) *** found ***
EEELLYEIKLNRKTLVLHLLRS at 56
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
34.8 %: nuclear
30.4 %: endoplasmic reticulum
21.7 %: mitochondrial
4.3 %: vesicles of secretory system
4.3 %: cytoplasmic
4.3 %: peroxisomal
>> prediction for CG51983-05 is nuc (k=23)
A search ofthe NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22D.
Figure imgf000399_0001
In a BLAST search of public sequence databases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22E.
Figure imgf000400_0001
PFam analysis indicates that the NOV22a protein contains the domains shown in the Table 22F.
Figure imgf000401_0001
Example 23.
The NOV23 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 23A.
Table 23A. NOV23 Sequence Analysis
NOV23a, CG53390-02 SEQ ID NO: 305 994 bp DNA Sequence ORF Start: ATG at 27 ORF Stop: TGA at 969
TGCAGCTAAAGTGCATTGTGTAAAACATGGGGGATGTGAATCAGTCGGTGGCCTCAGACTTCATTCTG
GTGGGCCTCTTCAGTCACTCAGGATCACGCCAGCTCCTCTTCTCCCTGGTGGCTGTCATGTTTGTCAT AGGCCTTCTGGGCAACACCGTTCTTCTCTTCTTGATCCGTGTGGACTCCCGGCTCCATACACCCATGT ACTTCCTGCTCAGCCAGCTCTCCCTGTTTGACATTGGCTGTCCCATGGTCACCATCCCCAAGATGGCA TCAGACTTTCTGCGGGGAGAAGGTGCCACCTCCTATGGAGGTGGTGCAGCTCAAATATTCTTCCTCAC ACTGATGGGTGTGGCTGAGGGCGTCCTGTTGGTCCTCATGTCTTATGACCGTTATGTTGCTGTGTGCC AGCCCCTGCAGTATCCTGTACTTATGAGACGCCAGGTATGTCTGCTGATGATGGGCTCCTCCTGGGTG GTAGGTGTGCTCAACGCCTCCATCCAGACCTCCATCACCCTGCATTTTCCCTACTGTGCCTCCCGTAT TGTGGATCACTTCTTCTGTGAGGTGCCAGCCCTACTGAAGCTCTCCTGTGCAGATACCTGTGCCTACG AGATGGCGCTGTCCACCTCAGGGGTGCTGATCCTAATGCTCCCTCTTTCCCTCATCGCCACCTCCTAC GGCCACGTGTTGCAGGCTGTTCTAAGCATGCGCTCAGAGGAGGCCAGACACAAGGCTGTCACCACCTG CTCCTCGCACATCACGGTAGTGGGGCTCTTTTATGGTGCCGCCGTGTTCATGTACATGGTGCCTTGCG CCTACCACAGTCCACAGCAGGATAACGTGGTTTCCCTCTTCTATAGCCTTGTCACCCCTACACTCAAC CCCCTTATCTACAGTCTGAGGAATCCGGAGGTGTGGATGGCTTTGGTCAAAGTGCTTAGCAGAGCTGG ACTCAGGCAAATGTGCTGACTACATAGAAACTGCTGGTGAGA
NOV23a, CG53390-02 SEQ ID NO: 306 314 aa MW at 34443.4kD Protein Sequence
MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMYFLLSQLSL FDIGCPMVTIPKMASDFLRGEGATSYGGGAAQIFFLTLMGVAEGVLLVLMSYDRYVAVCQPLQYPVLM RRQVCLLM GSS WGVLNASIQTSITLHFPYCASRIVDHFFCEVPALLKLSCADTCAYEMALSTSGV LILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTTCSSHITWGLFYGAAVF YMVPCAYHSPQQDN WSLFYSLVTPTLNPLIYSLRNPEVWMALVKVLSRAGLRQMC
NOV23b, CG53390-01 SEQ ID NO: 307 994 bp DNA Sequence ORF Start: ATG at 27 ORF Stop: TGA at 969
TGCAGCTAAAGTGCATTGTGTAAAACATGGGGGATGTGAATCAGTCGGTGGCCTCAGACTTCATTCTG GTGGGCCTCTTCAGTCACTCAGGATCACGCCAGCTCCTCTTCTCCCTGGTGGCTGTCATGTTTGTCAT AGGCCTTCTGGGCAACACCGTTCTTCTCTTCTTGATCCGTGTGGACTCCCGGCTCCATACACCCATGT ACTTCCTGCTCAGCCAGCTCTCCCTGTTTGACATTGGCTGTCCCATGGTCACCATCCCCAAGATGGCA TCAGACTTTCTGCGGGGAGAAGGTGCCACCTCCTATGGAGGTGGTGCAGCTCAAATATTCTTCCTCAC ACTGATGGGTGTGGCTGAGGGCGTCCTGTTGGTCCTCATGTCTTATGACCGTTATGTTGCTGTGTGCC AGCCCCTGCAGTATCCTGTACTTATGAGACGCCAGGTATGTCTGCTGATGATGGGCTCCTCCTGGGTG GTAGGTGTGCTCAACGCCTCCATCCAGACCTCCATCACCCTGCATTTTCCCTACTGTGCCTCCCGTAT TGTGGATCACTTCTTCTGTGAGGTGCCAGCCCTACTGAAGCTCTCCTGTGCAGATACCTGTGCCTACG AGATGGCGCTGTCCACCTCAGGGGTGCTGATCCTAATGCTCCCTCTTTCCCTCATCGCCACCTCCTAC GGCCACGTGTTGCAGGCTGTTCTAAGCATGCGCTCAGAGGAGGCCAGACACAAGGCTGTCACCACCTG CTCCTCGCACATCACGGTAGTGGGGCTCTTTTATGGTGCCGCCGTGTTCATGTACATGGTGCCTTGCG CCTACCACAGTCCACAGCAGGATAACGTGGTTTCCCTCTTCTATAGCCTTGTCACCCCTACACTCAAC CCCCTTATCTACAGTCTGAGGAATCCGGAGGTGTGGATGGCTTTGGTCAAAGTGCTTAGCAGAGCTGG ACTCAGGCAAATGTGCTGACTACATAGAAACTGCTGGTGAGA
NOV23b, CG53390-01 SEQ ID NO: 308 314 aa MW at 34443.4kD Protein Sequence
MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMYFLLSQLSL FDIGCPMVTIPKMASDFLRGEGATSYGGGAAQIFFLTLMGVAEGVLLVLMSYDRYVAVCQPLQYPVLM RRQVCLLMMGSSWVVGVLNASIQTSITLHFPYCASRIVDHFFCEVPALLKLSCADTCAYEMALSTSGV LILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTTCSSHITWGLFYGAAVFMYMVPCAYHSPQQDN WSLFYSLVTPTLNPLIYSLRNPEVWMALVKVLSRAGLRQMC
NOV23c, CG53390-03 SEQ ID NO: 309 977 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TGA at 958
TGCATTGTGTAAAACATGGGGGATGTGAATCAGTCGGTGGCCTCAGACTTCATTCTGGTGGGCCTCTT
CAGTCACTCAGGATCACGCCAGCTCCTCTTCTCCCTGGTGGCTGTCATGTTTGTCATAGGCCTTCTGG GCAACACCGTTCTTCTCTTCTTGATCCGTGTGGACTCCCGGCTCCATACACCCATGTACTTCCTGCTC AGCCAGCTCTCCCTGTTTGACATTGGCTGTCCCATGGTCACCATCCCCAAGATGGCATCAGACTTTCT GCGGGGAGAAGGTGCCACCTCCTATGGAGGTGGTGCAGCTCAAATATTCTTCCTCACACTGATGGGTG TGGCTGAGGGCGTCCTGTTGGTCCTCATGTCTTATGACCGTTATGTTGCTGTGTGCCAGCCCCTGCAG TATCCTGTACTTATGAGACGCCAGGTATGTCTGCTGATGATGGGCTCCTCCTGGGTGGTAGGTGTGCT CAACGCCTCCATCCAGACCTCCATCACCCTGCATTTTCCCTACTGTGCCTCCCGTATTGTGGATCACT TCTTCTGTGAGGTGCCAGCCCTACTGAAGCTCTCCTGTGCAGATACCTGTGCCTACGAGATGGCGCTG TCCACCTCAGGGGTGCTGATCCTAATGCTCCCTCTTTCCCTCATCGCCACCTCCTACGGCCACGTGTT GCAGGCTGTTCTAAGCATGCGCTCAGAGGAGGCCAGACACAAGGCTGTCACCACCTGCTCCTCGCACA TCACGGTAGTGGGGCTCTTTTATGGTGCCGCCGTGTTCATGTACATGGTGCCTTGCGCCTACCACAGT CCACAGCAGGATAACGTGGTTTCCCTCTTCTATAGCCTTGTCACCCCTACACTCAACCCCCTTATCTA CAGTCTGAGGAATCCGGAGGTGTGGATGGCTTTGGTCAAAGTGCTTAGCAGAGCTGGACTCAGGCAAA TGTGCTGACTACATAGAAACTGCTG
NOV23c, CG53390-03 SEQ ID NO: 310 314 aa MW at 34443.4kD Protein Sequence
MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMYFLLSQLSL FDIGCPMVTI PKMASDFLRGEGATSYGGGAAQI FFLTLMGVAEGVLLVLMSYDRYVAVCQPLQYPVLM RRQVCLLM GSS WGVLNASIQTSITLHFPYCASRIVDHFFCEVPALLKLSCADTCAYEMALSTSGV LILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTTCSSHITWGLFYGAAVFMYMVPCAYHSPQQDN WSLFYSLVTPTLNPLIYSLRNPEV MALVKVLSRAGLRQMC A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 23B.
Table 23B. Comparison of the NOV23 protein sequences.
NOV23a MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMY NOV23b MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMY NOV23C MGDVNQSVASDFILVGLFSHSGSRQLLFSLVAVMFVIGLLGNTVLLFLIRVDSRLHTPMY NOV23a FLLSQLSLFDIGCPMVTIPKMASDFLRGEGATSYGGGAAQIFFLTLMGVAEGVLLVLMSY NOV23b FLLSQLSLFDIGCPMVTIPKMASDFLRGEGATSYGGGAAQIFFLTLMGVAEGVLLVLMSY NOV23C FLLSQLSLFDIGCPMVTIPK ASDFLRGEGATSYGGGAAQIFFLTLMGVAEGVLLVLMSY
NOV23a DRYVAVCQPLQYPVLMRRQVCLLMMGSS WGVLNASIQTSITLHFPYCASRIVDHFFCE NOV23b DRYVAVCQPLQYPVLMRRQVCLLMMGSS WGVLNASIQTSITLHFPYCASRIVDHFFCE NOV23C DRYVAVCQPLQYPVLMRRQVCLLMMGSS WGVLNASIQTSITLHFPYCASRIVDHFFCE
NOV23a VPALLKLSCADTCAYEMALSTSGVLILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTT NOV23b VPALLKLSCADTCAYEMALSTSGVLILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTT NOV23C VPALLKLSCADTCAYEMALSTSGVLILMLPLSLIATSYGHVLQAVLSMRSEEARHKAVTT
NOV23a CSSHITWGLFYGAAVFMY VPCAYHSPQQDNWSLFYSLVTPTLNPLIYSLRNPEVWMA NOV23b CSSHITWGLFYGAAVF YMVPCAYHSPQQDNWSLFYSLVTPTLNPLIYSLRNPEVWMA NOV23C CSSHITVVGLFYGAAVFMY VPCAYHSPQQDNVVSLFYSLVTPTLNPLIYSLRNPEVWMA
NOV23a LVKVLSRAGLRQMC NOV23b LVKVLSRAGLRQMC NOV23c LVKVLSRAGLRQMC
NOV23a (SEQ ID NO 306) NOV23b (SEQ ID NO 308) NOV23C (SEQ ID NO 310)
Further analysis ofthe NOV23a protein yielded the following properties shown in Table 23C.
Table 23C. Protein Sequence Properties NOV23a
SignalP analysis: Cleavage site between residues 42 and 43
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos . chg 0; neg.chg 2 H-region: length 12; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.30 possible cleavage site: between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5: 5
INTEGRAL Likelihood -8.60 Transmembrane 33 - 49 INTEGRAL Likelihood -7.17 Transmembrane 101 - 117 INTEGRAL Likelihood -1.38 Transmembrane 140 - 156 INTEGRAL Likelihood -4.09 Transmembrane 198 - 214 INTEGRAL Likelihood -3.77 Transmembrane 245 - 261 PERIPHERAL Likelihood 1.38 (at 62) ALOM score: -8.60 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 40 Charge difference: 1.0 C( 1.5) - N( 0.5) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Momen (75): 0.74 Hyd Moment (95): 7.13 G content: 1 D/E content: 2 S/T content: 2 Score: -7.54
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 5.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
55.6 %: endoplasmic reticulum
11.1 %: Golgi
11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG53390-02 is end (k=9)
A search ofthe NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23D.
Figure imgf000406_0001
In a BLAST search of public sequence databases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23E.
Figure imgf000407_0001
PFam analysis indicates that the NOV23a protein contains the domains shown in the Table 23F.
Figure imgf000407_0002
Example 24.
The NOV24 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 24A.
Table 24A. NOV24 Sequence Analysis
NOV24a, CG53482-01 SEQ ID NO: 311 llOOδ bp DNA Sequence ORF Start: ATG at 27 JORF Stop: TAG at 999
AGCTGGAGATCTGGAACTTCCACAGCATGGAGCTCTGGAACTACCACAGCATGGAGCTCTGGAACTTC
ACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGGGTCTCCTGAACTGCTCTGTGC TACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTACTGCTCCTGGCTATCACCATGG AAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCTCTCATGGACCTCCTGTTCACA TCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAACACCATCTCCTTTGGAGGCTG TGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACCTCCTACTGGCCTTCATGGCCT ATGACAGGTATGTGGCCATTTGTCATCCTCTGACATACATGACCCTCATGAGCTCAAGAGCCTGCTGG CTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAATATATACCGTGTATACCATGCA CTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGATCCCACACTTGCTGAAGTTGG CCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGTGTGACCTTCCTGATTCCCTCT CTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCTCCATATGCCATCAAATGAGGG GAGGAAGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTGGGATGTTCTATGGAGCTGCCA CATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGACAACATCATCTCTGTTTTCTAC ACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAATAAGGAGGTCATGCGGGCCTT GAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCTAGGGAAGGA
NOV24a, CG534δ2-01 SEQ ID NO: 312 324 aa MW at 36344.δkD Protein Sequence
MELWNYHSMELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITMEARLHMPMY LLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLALTMGGAEDLLLAFMAYDRYVAICH PLTYMTLMSSRACWLMVATSWILASLSALIYTVYTMHYPFCRAQEIRHLLCEIPHLLKLACADTSRYE LMVYVMGVTFLIPSLAAILASYTQILLTVLHMPSNEGRKKALVTCSSHLTWGMFYGAATFMYVLPSS FHSTRQDNIISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24b, CG534δ2-02 SEQ ID NO: 313 1050 bp DNA Sequence ORF Start: ATG at 72 ORF Stop: TAG at 1020
AAACTAGAGTTCATCTTAGCAAAAATTCATGAAGTATCCATCTTGTTCTAGGTGATGAAAGAAACCAC
AGCATGGAGCTCTGGAACTTCACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGG GTCTCCTGAACTGCTCTGTGCTACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTAC TGCTCCTGGCTATCACCATGGAAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCT CTCATGGACCTCCTGTTCACATCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAA CACCATCTCCTTTGGAGGCTGTGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACC TCCTACTGGCCTTCATGGCCTATGACAGGTATGTGGCCATTTGTCATCCTCTGACATACATGACCCTC ATGAGCTCAAGAGCCTGCTGGCTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAAT ATATACCGTGTATACCATGCACTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGA TCCCACACTTGCTGAAGGTGGCCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGT GTGACCTTCCTGATTCCCTCTCTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCT CCATATGCCATCAAATGAGGGGAGGAAGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTG GGATGTTCTATGGAGCTGCCACATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGAC AACATCATCTCTGTTTTCTACACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAA TAAGGAGGTCATGCGGGCCTTGAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCT AGGGAAGGATCATGGCTAGCTTCCAGAATT
NOV24b, CG534δ2-02 SEQ ID NO: 314 316 aa MW at 35269.6kD Protein Sequence
MEL NFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITMEARLHMPMYLLLGQLSL MDLLFTSVVTPKALADFLRRENTISFGGCALQMFLALTMGGAEDLLLAFMAYDRYVAICHPLTYMTLM SSRACWLMVATSWILASLSALIYTVYTMHYPFCRAQEIRHLLCEIPHLLKVACADTSRYELMVYVMGV TFLIPSLAAILASYTQILLTVLHMPSNEGRKKALVTCSSHLTWGMFYGAATFMYVLPSSFHSTRQDN IISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24c, CG534δ2-03 SEQ ID NO: 315 1010 bp DNA Sequence ORF Start: at 4 ORF Stop: TAG at 1000
TAGCTGGAGATCTGGAACTTCCACAGCATGGAGCTCTGGAACTACCACAGCATGGAGCTCTGGAACTT CACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGGGTCTCCTGAACTGCTCTGTG CTACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTACTGCTCCTGGCTATCACCATG GAAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCTCTCATGGACCTCCTGTTCAC ATCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAACACCATCTCCTTTGGAGGCT GTGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACCTCCTACTGGCCTTCATGGCC TATGACAGGTATGTGGCCATTTGTCATCCTCTGACATACATGACCCTCATGAGCTCAAGAGCCTGCTG GCTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAATATATACCGTGTATACCATGC ACTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGATCCCACACTTGCTGAAGTTG GCCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGTGTGACCTTCCTGATTCCCTC TCTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCTCCATATGCCATCAAATGAGG GGAGGAAGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTGGGATGTTCTATGGAGCTGCC ACATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGACAACATCATCTCTGTTTTCTA CACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAATAAGGAGGTCATGCGGGCCT TGAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCTAGGGAAGGAA
NOV24c, CG534δ2-03 SEQ ID NO: 316 332 aa MW at 37371.9kD Protein Sequence
LEI NFHSMEL NYHSMELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITME ARLHMPMYLLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLALTMGGAEDLLLAFMAY DRYVAICHPLTYMTLMSSRACWLMVATSWILASLSALIYTVYTMHYPFCRAQEIRHLLCEIPHLLKLA CADTSRYELMVYVMGVTFLIPSLAAILASYTQILLTVLHMPSNEGRKKALVTCSSHLTVVGMFYGAAT FMYVLPSSFHSTRQDNIISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24d, SNP133737δ7 of SEQ ID NO: 317 lOO bp CG534δ2-01, DNA Sequence ORF Start: ATG at 27 ORF Stop: TAG at 999
SNP Pos: 430 SNP Change: G to A
AGCTGGAGATCTGGAACTTCCACAGCATGGAGCTCTGGAACTACCACAGCATGGAGCTCTGGAACTTC
ACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGGGTCTCCTGAACTGCTCTGTGC TACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTACTGCTCCTGGCTATCACCATGG AAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCTCTCATGGACCTCCTGTTCACA TCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAACACCATCTCCTTTGGAGGCTG TGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACCTCCTACTGGCCTTCATGGCCT ATGACAGGTATGTGGCCATTTATCATCCTCTGACATACATGACCCTCATGAGCTCAAGAGCCTGCTGG CTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAATATATACCGTGTATACCATGCA CTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGATCCCACACTTGCTGAAGTTGG CCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGTGTGACCTTCCTGATTCCCTCT CTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCTCCATATGCCATCAAATGAGGG GAGGAAGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTGGGATGTTCTATGGAGCTGCCA CATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGACAACATCATCTCTGTTTTCTAC ACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAATAAGGAGGTCATGCGGGCCTT GAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCTAGGGAAGGA
NOV24d, SNP133737δ7 of SEQ ID NO: 31δ 324 aa MW at 36404.δkD CG534δ2-01, Protein Sequence SNP Pos: 135 SNP Change: Cys to Tyr
MELWNYHSMELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITMEARLHMPMY LLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLALTMGGAEDLLLAFMAYDRYVAIYH PLTYMTLMS SRAC LMVATS WI LASLSALI YTVYTMHYP FCRAQE I RHLLCE I PHLLKLACADTSRYE LMVYVMGVTFLIPSLAAILASYTQILLTVLHMPSNEGRKKALVTCSSHLTVVGMFYGAATFMYVLPSS FHSTRQDNI ISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24e, SNP133737δ6 of SEQ ID NO: 319 lOOδ bp CG534δ2-01, DNA Sequence ORF Start: ATG at 27 ORF Stop: TAG at 999
SNP Pos: 442 SNP Change: C to A
AGCTGGAGATCTGGAACTTCCACAGCATGGAGCTCTGGAACTACCACAGCATGGAGCTCTGGAACTTC
ACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGGGTCTCCTGAACTGCTCTGTGC TACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTACTGCTCCTGGCTATCACCATGG AAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCTCTCATGGACCTCCTGTTCACA TCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAACACCATCTCCTTTGGAGGCTG TGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACCTCCTACTGGCCTTCATGGCCT ATGACAGGTATGTGGCCATTTGTCATCCTCTGAAATACATGACCCTCATGAGCTCAAGAGCCTGCTGG CTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAATATATACCGTGTATACCATGCA CTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGATCCCACACTTGCTGAAGTTGG CCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGTGTGACCTTCCTGATTCCCTCT CTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCTCCATATGCCATCAAATGAGGG GAGGAAGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTGGGATGTTCTATGGAGCTGCCA CATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGACAACATCATCTCTGTTTTCTAC ACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAATAAGGAGGTCATGCGGGCCTT GAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCTAGGGAAGGA
NOV24e, SNP133737δ6 of SEQ ID NO: 320 324 aa MW at 36371.9kD CG534δ2-01, Protein Sequence SNP Pos: 139 SNP Change: Thr to Lys
MELWNYHSMELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITMEARLHMPMY LLLGQLSLMDLLFTSWTPKALADFLRRENTI SFGGCALQMFLALTMGGAEDLLLAFMAYDRYVAI CH PLKYMTLMSSRACWLMVATSWILASLSALIYTVYTMHYPFCRAQEIRHLLCEIPHLLKLACADTSRYE LMVY MGVTFLIPSLAAII-ASYTQILLTVIJHMPSNEGRKKALVTCSSHLTVVGMFYGAATFMYVLPSS FHSTRQDNIISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24f, SNP133737δ5 of SEQ ID NO: 321 [1008 bp CG53482-01, DNA Sequence ORF Start: ATG at 27 ORF Stop: TAG at 999
SNP Pos: 754 [SNP Change: A to G
AGCTGGAGATCTGGAACTTCCACAGCATGGAGCTCTGGAACTACCACAGCATGGAGCTCTGGAACTTC
ACCTTGGGAAGTGGCTTCATTTTGGTGGGGATTCTGAATGACAGTGGGTCTCCTGAACTGCTCTGTGC TACAATTACAATCCTATACTTGTTGGCCCTGATCAGCAATGGCCTACTGCTCCTGGCTATCACCATGG AAGCCCGGCTCCACATGCCCATGTACCTCCTGCTTGGGCAGCTCTCTCTCATGGACCTCCTGTTCACA TCTGTTGTCACTCCCAAGGCCCTTGCGGACTTTCTGCGCAGAGAAAACACCATCTCCTTTGGAGGCTG TGCCCTTCAGATGTTCCTGGCACTGACAATGGGTGGTGCTGAGGACCTCCTACTGGCCTTCATGGCCT ATGACAGGTATGTGGCCATTTGTCATCCTCTGACATACATGACCCTCATGAGCTCAAGAGCCTGCTGG CTCATGGTGGCCACGTCCTGGATCCTGGCATCCCTAAGTGCCCTAATATATACCGTGTATACCATGCA CTATCCCTTCTGCAGGGCCCAGGAGATCAGGCATCTTCTCTGTGAGATCCCACACTTGCTGAAGTTGG CCTGTGCTGATACCTCCAGATATGAGCTCATGGTATATGTGATGGGTGTGACCTTCCTGATTCCCTCT CTTGCTGCTATACTGGCCTCCTATACACAAATTCTACTCACTGTGCTCCATATGCCATCAAATGAGGG GAGGAGGAAAGCCCTTGTCACCTGCTCTTCCCACCTGACTGTGGTTGGGATGTTCTATGGAGCTGCCA CATTCATGTATGTCTTGCCCAGTTCCTTCCACAGCACCAGACAAGACAACATCATCTCTGTTTTCTAC ACAATTGTCACTCCAGCCCTGAATCCACTCATCTACAGCCTGAGGAATAAGGAGGTCATGCGGGCCTT GAGGAGGGTCCTGGGAAAATACATGCTGCCAGCACACTCCACGCTCTAGGGAAGGA
NOV24f, SNP133737δ5 of SEQ ID NO: 322 324 aa MW at 36372.δkD CG534δ2-01, Protein Sequence SNP Pos: 243 SNP Change: Lys to Arg
MELWNYHSMELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGLLLLAITMEARLHMPMY LLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLALTMGGAEDLLLAFMAYDRYVAICH PLTYMTLMSSRACWLMVATSWILASLSALIYTVYTMHYPFCRAQEIRHLLCEIPHLLKLACADTSRYE LMVYVMGVTFLIPSLAAILASYTQILLTVLHMPSNEGRRKALVTCSSHLTVVGMFYGAATFMYVLPSS FHSTRQDNIISVFYTIVTPALNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 24B.
Table 24B. Comparison of the NOV24 protein sequences.
NOV24a MELWNYHSMEL NFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGL
NOV24b MELWNFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGL
NOV24C LEIWNFHSMELWNYHSMEL NFTLGSGFILVGILNDSGSPELLCATITILYLLALISNGL
NOV24a LLLAITMEARLHMPMYLLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLA
NOV24b LLLAITMEARLHMPMYLLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLA
NOV24C LLLAITMEARLHMPMYLLLGQLSLMDLLFTSWTPKALADFLRRENTISFGGCALQMFLA
NOV24a LTMGGAEDLLLAFMAYDRYVAICHPLTYMTLMSSRACWLMVATSWILASLSALIYTVYTM
NOV24b LTMGGAEDLLLAFMAYDRYVAICHPLTYMTLMSSRACWLMVATSWILASLSALIYTVYTM
NOV24C LTMGGAEDLLLAFMAYDRYVAICHPLTYMTLMSSRACWLMVATSWILASLSALIYTVYTM
NOV24a HYPFCRAQEIRHLLCEIPHLLKLACADTSRYELMVYVMGVTFLIPSLAAILASYTQILLT NOV24b HYPFCRAQEIRHLLCEIPHLLKVACADTSRYELMVYVMGVTFLIPSLAAILASYTQILLT
NOV24C HYPFCRAQEIRHLLCEIPHLLKLACADTSRYELMVYVMGVTFLIPSLAAILASYTQILLT
NOV24a VLHMPSNEGRKKALVTCSSHLTWGMFYGAATFMYVLPSSFHSTRQDNIISVFYTIVTPA
NOV24b VLHMPSNEGRKKALVTCSSHLTWGMFYGAATFMYVLPSSFHSTRQDNIISVFYTIVTPA
NOV24C VLHMPSNEGRKKALVTCSSHLTWGMFYGAATFMYVLPSSFHSTRQDNIISVFYTIVTPA
NOV24a LNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24b LNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24C LNPLIYSLRNKEVMRALRRVLGKYMLPAHSTL
NOV24a (SEQ ID NO 312) NOV24b (SEQ ID NO 314) NOV24C (SEQ ID NO 316)
Further analysis ofthe NOV24a protein yielded the following properties shown in Table 24C.
Table 24C. Protein Sequence Properties NOV24a
SignalP analysis: Cleavage site between residues 62 and 63
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region: length 10 ; pos . chg 0 ; neg . chg 2 H-region : length 17 ; peak value 0. 00 PSG score : -4 .40
GvH: von Heijne ' s method for signal seq. recognition GvH score (threshold : -2 . 1 ) : -3 .29 possible cleavage site : between 56 and 57
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation : Tentative number of TMS (s) for the threshold 0.5 :
INTEGRAL Likelihood = -7. .75 Transmembrane 41 - - 57
INTEGRAL Likelihood = -1. .65 Transmembrane 69 • - 85
INTEGRAL Likelihood = -2. .07 Transmembrane 150 - - 166
INTEGRAL Likelihood = -5. .10 Transmembrane 207 ■ - 223
INTEGRAL Likelihood = -0. .80 Transmembrane 253 - - 269
INTEGRAL Likelihood = -0. .80 Transmembrane 281 - 297
PERIPHERAL Likelihood = 0. .85 (at 109)
ALOM score: -7.75 (number of TMSs : 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 48 Charge difference: 2.5 C ( 0.5) - ( -2.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 4.76 Hyd Moment (95): 6.14 G content: 0 D/E content : 2 S/T content : 1 Score: -6.93
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 6.2% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
40δ Final Results (k = 9/23)
44.4 %: endoplasmic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG53482-01 is end (k=9)
A search ofthe NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24D.
Figure imgf000414_0001
In a BLAST search of public sequence databases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.
Figure imgf000415_0001
PFam analysis indicates that the NOV24a protein contains the domains shown in the Table 24F.
Figure imgf000415_0002
Example 25.
The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25 A.
Figure imgf000415_0003
TCTTTCCTGGACTTTTGCTACTCTTCCATCACAGCACCTAGGATGCTGGTTGACTTGCTCTCAGGCAA CCCTACCATTTCCTTTGGTGGATGCCTGACTCAACTCTTCTTCTTCCACTTCATTGGAGGCATCAAGA TCTTCCTGCTGACTGTCATGGCGTATGACCGCTACATTGCCATTTCCCAGCCCCTGCACTACACGCTC ATTATGAATCAGACTGTCTGTGCACTCCTTATGGCAGCCTCCTGGGTGGGGGGCTTCATCCACTCCAT AGTACAGATTGCATTGACTATCCAGCTGCCATTCTGTGGGCCTGACAAGCTGGACAACTTTTATTGTG ATGTGCCTCAGCTGATCAAATTGGCCTGCACAGATACCTTTGTCTTAGAGCTTTTAATGGTGTCTAAC AATGGCCTGGTGACCCTGATGTGTTTTCTGGTGCTTCTGGGATCGTACACAGCACTGCTAGTCATGCT CCGAAGCCACTCACGGGAGGGCCGCAGCAAGGCCCTGTCTACCTGTGCCTCTCACATTGCTGTGGTGA CCTTAATCTTTGTGCCTTGCATCTACGTCTATACAAGGCCTTTTCGGACATTCCCCATGGACAAGGCC GTCTCTGTGCTATACACAATTGTCACCCCCATGCTGAATCCTGCCATCTATACCCTGAGAAACAAGGA AGTGATCATGGCCATGAAGAAGCTGTGGAGGAGGAAAAAGGACCCTATTGGTCCCCTGGAGCACAGAC CCTTACATTAGCAGAGGCAGTGACCTGAGAATCTGAAAGATGCTACAGGGTATTAGCAGAGGCA
NOV25a, CG53530-03 SEQ ID NO: 324 31δ aa MW at 35770.3kD Protein Sequence
MNPANHSQVAGFVLLGLSQV ELRFVFFTVFSAVYF TWGNLLIWIVTSDPHLHTTMYFLLGNLSF LDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTV AYDRYIAISQPLHYTLIM NQTVCALLMAAS VGGFIHSIVQIALTIQLPFCGPDKLDNFYCDVPQLIKLACTDTFVLELLMVSNNG LVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTCASHIAWTLIFVPCIYVYTRPFRTFPMDKAVS VLYTIVTPMLNPAIYTLRNKEVIMAMKKLWRRKKDPIGPLEHRPLH
NOV25b, CG53530-01 SEQ ID NO: 325 1077 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAG at 9δ5
CAGGTTCATTGACAAGGTCATACCAACCAGATGAATCCAGCAAATCATTCCCAGGTGGCAGGATTTGT
TCTACTGGGGCTCTCTCAGGTTTGGGAGCTTCGGTTTGTTTTCTTCACTGTTTTCTCTGCTGTGTATT TTATGACTGTAGTGGGAAACCTTCTTATTGTGGTCATAGTGACCTCCGACCCACACCTGCACACAACC ATGTATTTTCTCTTGGGCAATCTTTCTTTCCTGGACTTTTGCTACTCTTCCATCACAGCACCTAGGAT GCTGGTTGACTTGCTCTCAGGCAACCCTACCATTTCCTTTGGTGGATGCCTGACTCAACTCTTCTTCT TCCACTTCATTGGAGGCATCAAGATCTTCCTGCTGACTGTCATGGCGTATGACCGCTACATTGCCATT TCCCAGCCCCTGCACTACACGCTCATTATGAATCAGACTGTCTGTGCACTCCTTATGGCAGCCTCCTG GGTGGGGGGCTTCATCCACTCCATAGTACAGATTGCATTGACTATCCAGCTGCCATTCTGTGGGCCTG ACAAGCTGGACAACTTTTATTGTGATGTGCCTCAGCTGATCAAATTGGCCTGCACAGATACCTTTGTC TTAGAGCTTTTAATGGTGTCTAACAATGGCCTGGTGACCCTGATGTGTTTTCTGGTGCTTCTGGGATC GTACACAGCACTGCTAGTCATGCTCCGAAGCCACTCACGGGAGGGCCGCAGCAAGGCCCTGTCTACCT GTGCCTCTCACATTGCTGTGGTGACCTTAATCTTTGTGCCTTGCATCTACGTCTATACAAGGCCTTTT CGGACATTCCCCATGGACAAGGCCGTCTCTGTGCTATACACAATTGTCACCCCCATGCTGAATCCTGC CATCTATACCCTGAGAAACAAGGAAGTGATCATGGCCATGAAGAAGCTGTGGAGGAGGAAAAAGGACC CTATTGGTCCCCTGGAGCACAGACCCTTACATTAGCAGAGGCAGTGACCTGAGAATCTGAAAGATGCT
ACAGGGTATTAGCAGAGGCAGTGACCTGAGAATCTGAAAGATGCTACAGGGTATTAG
NOV25b, CG53530-01 SEQ ID NO: 326 31δ aa MW at 35770.3kD
Protein Sequence
MNPANHSQVAGFVLLGLSQVWELRFVFFTVFSAVYFMTWGNLLIWIVTSDPHLHTTMYFLLGNLSF LDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTVMAYDRYIAISQPLHYTLIM NQTVCALLMAASWVGGFIHSIVQIALTIQLPFCGPDKLDNFYCDVPQLIKLACTDTFVLELLMVSNNG LVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTCASHIAWTLIFVPCIYVYTRPFRTFPMDKAVS VLYTIVTPMLNPAIYTLRNKEVIMAMKKLWRRKKDPIGPLEHRPLH
NOV25c, CG53530-02 SEQ ID NO: 327 1077 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAG at 9δ5
CAGGTTCATTGACAAGGTCATACCAACCAGATGAATCCAGCAAATCATTCCCAGGTGGCAGGATTTGT
TCTACTGGGGCTCTCTCAGGTTTGGGAGCTTCGGTTTGTTTTCTTCACTGTTTTCTCTGCTGTGTATT TTATGACTGTAGTGGGAAACCTTCTTATTGTGGTCATAGTGACCTCCGACCCACACCTGCACACAACC ATGTATTTTCTCTTGGGCAATCTTTCTTTCCTGGACTTTTGCTACTCTTCCATCACAGCACCTAGGAT GCTGGTTGACTTGCTCTCAGGCAACCCTACCATTTCCTTTGGTGGATGCCTGACTCAACTCTTCTTCT TCCACTTCATTGGAGGCATCAAGATCTTCCTGCTGACTGTCATGGCGTATGACCGCTACATTGCCATT TCCCAGCCCCTGCACTACACGCTCATTATGAATCAGACTGTCTGTGCACTCCTTATGGCAGCCTCCTG GGTGGGGGGCTTCATCCACTCCATAGTACAGATTGCATTGACTATCCAGCTGCCATTCTGTGGGCCTG ACAAGCTGGACAACTTTTATTGTGATGTGCCTCAGCTGATCAAATTGGCCTGCACAGATACCTTTGTC TTAGAGCTTTTAATGGTGTCTAACAATGGCCTGGTGACCCTGATGTGTTTTCTGGTGCTTCTGGGATC GTACACAGCACTGCTAGTCATGCTCCGAAGCCACTCACGGGAGGGCCGCAGCAAGGCCCTGTCTACCT GTGCCTCTCACATTGCTGTGGTGACCTTAATCTTTGTGCCTTGCATCTACGTCTATACAAGGCCTTTT CGGACATTCCCCATGGACAAGGCCGTCTCTGTGCTATACACAATTGTCACCCCCATGCTGAATCCTGC CATCTATACCCTGAGAAACAAGGAAGTGATCATGGCCATGAAGAAGCTGTGGAGGAGGAAAAAGGACC CTATTGGTCCCCTGGAGCACAGACCCTTACATTAGCAGAGGCAGTGACCTGAGAATCTGAAAGATGCT
ACAGGGTATTAGCAGAGGCAGTGACCTGAGAATCTGAAAGATGCTACAGGGTATTAG
NOV25c, CG53530-02 SEQ ID NO: 328 318 aa MW at 35770.3kD Protein Sequence
MNPANHSQVAGFVLLGLSQVWELRFVFFTVFSAVYFMTWGNLLIWIVTSDPHLHTTMYFLLGNLSF LDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTVMAYDRYIAISQPLHYTLIM NQTVCALLMAAS VGGFIHSIVQIALTIQLPFCGPDKLDNFYCDVPQLIKLACTDTFVLELLMVSNNG LVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTCASHIAWTLIFVPCIYVYTRPFRTFPMDKAVS VLYTIVTPMLNPAIYTLRNKEVIMAMKKLWRRKKDPIGPLEHRPLH
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 25B.
Table 25B. Comparison of the NOV25 protein sequences.
NOV25a MNPANHSQVAGFVLLGLSQVWELRFVFFTVFSAVYFMTWGNLLIWIVTSDPHLHTTMY
NOV25b MNPANHSQVAGFVLLGLSQVWELRFVFFTVFSAVYFMTWGNLLIWIVTSDPHLHTTMY
NOV25C MNPANHSQVAGFVLLGLSQV ELRFVFFTVFSAVYFMTVVGNLLIVVIVTSDPHLHTTMY
NOV25a FLLGNLSFLDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTVMAY
NOV25b FLLGNLSFLDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTVMAY
NOV25C FLLGNLSFLDFCYSSITAPRMLVDLLSGNPTISFGGCLTQLFFFHFIGGIKIFLLTVMAY
NOV25a DRYIAISQPLHYTLIMNQTVCALLMAAS VGGFIHSIVQIALTIQLPFCGPDKLDNFYCD
NOV25b DRYIAISQPLHYTLIMNQTVCALLMAAS VGGFIHSIVQIALTIQLPFCGPDKLDNFYCD
NOV25C DRYIAISQPLHYTLIMNQTVCALLMAAS VGGFIHSIVQIALTIQLPFCGPDKLDNFYCD
NOV25a VPQLIKLACTDTFVLELLMVSNNGLVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTC
NOV25b VPQLIKLACTDTFVLELLMVSNNGLVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTC
NOV25C VPQLIKLACTDTFVLELLMVSNNGLVTLMCFLVLLGSYTALLVMLRSHSREGRSKALSTC
NOV25a ASHIAWTLIFVPCIYVYTRPFRTFPMDKAVSVLYTIVTPMLNPAIYTLRNKEVIMAMKK
NOV25b ASHIAVVTLIFVPCIYVYTRPFRTFPMDKAVSVLYTIVTPMLNPAIYTLRNKEVIMAMKK
NOV25C ASHIAWTLIFVPCIYVYTRPFRTFPMDKAVSVLYTIVTPMLNPAIYTLRNKEVIMAMKK
NOV25a LWRRKKDPIGPLEHRPLH
NOV25b LWRRKKDPIGPLEHRPLH
NOV25C LWRRKKDPIGPLEHRPLH
NOV25a (SEQ ID NO 324) NOV 5b (SEQ ID NO 326) NOV25C (SEQ ID NO 328)
Further analysis ofthe NOV25a protein yielded the following properties shown in Table 25C. Table 25C. Protein Sequence Properties NOV25a
SignalP analysis: Cleavage site between residues 52 and 53
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos . chg 0; neg.chg 0 H-region: length 21; peak value 9.57 PSG score: 5.17
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.51 possible cleavage site: between 32 and 33
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -8. .23 Transmembrane 33 - - 49
INTEGRAL Likelihood = -4. .04 Transmembrane 101 - - 117
INTEGRAL Likelihood = -0. .90 Transmembrane 142 - - 158
INTEGRAL Likelihood = -0, .90 Transmembrane 184 - - 200
INTEGRAL Likelihood = -6. .37 Transmembrane 208 - - 224
INTEGRAL Likelihood = -4. .51 Transmembrane 241 - - 257
PERIPHERAL Likelihood = 0. .79 (at 12)
ALOM score : -8.23 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 40 Charge difference: 0.0 C( 0.0) - N( 0.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 1.55 Hyd Moment(95): 4.07 G content: 2 D/E content: 1 S/T content: 2 Score: -6.22
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 132 DRY|lA
NUCDISC: discrimination of nuclear localization signals pat4: RRKK (5) at 303 pat7: none bipartite: none content of basic residues: 6.9% NLS Score: -0.16
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 % endoplasmic reticulum 22.2 % mitochondrial
11.1 % nuclear
>> prediction for CG53530-03 is end (k=9)
A search ofthe NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25D.
Figure imgf000420_0001
In a BLAST search of public sequence databases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25E.
Figure imgf000421_0001
PFam analysis indicates that the NOV25a protein contains the domains shown in the Table 25F.
Figure imgf000421_0002
Example 26.
The NOV26 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 26A.
Table 26A. NOV26 Sequence Analysis
NOV26a, CG53563-03 SEQ ID NO: 329 102δ bp DNA Sequence ORF Start: ATG at 2δ ORF Stop: TAG at 961
AGGGAGAGAGACCAAGGGTGAGAAGAAATGTCCAACGCCAGCCTACTGACAGCGTTCATCCTCATGGG
CCTTCCCCATGCCCCAGCGCTGGACGCCCCCCTCTTTGGAGTCTTCCTGGTGGTTTACGTGCTCACTG TGCTGGGGAACCTCCTCATCCTGCTGGTGATCAGGGTGGATTCTCACCTCCACACCACCATGTACTAC TTCCTCACCAACCTGTCGTTCATTGACATGTGGTTCTCCACTGTCACGGTGCCCAAATTGCTGATGAC TTTGGTGTTCCCAAGTGGCAGGGCTATCTCCTTCCACAGCTGCATGGCTCAGCTCTATTTCTTTCACT TCCTAGGGGGCACCGAGTGTTTCCTCTACAGGGTCATGTCCTGTGATCGCTACCTGGCCATCAGTTAC CCGCTCAGGTACACCAGCATGATGACTGGGCGCTCGTGTACTCTTCTGGCCACCAGCACTTGGCTCAG TGGCTCTCTGCACTCTGCTGTCCAGGCCATATTGACTTTCCATTTGCCCTACTGTGGACCCAACTGGA TCCAGCACTATTTGTGTGATGCACCGCCCATCCTGAAACTGGCCTGTGCAGACACCTCAGCCATAGAG ACTGTCATTTTTGTGACTGTTGGAATAGTGGCCTCGGGCTGCTTTGTCCTGATAGTGCTGTCCTATGT GTCCATCGTCTGTTCCATCCTGCGGATCCGCACCTCAGAGGGGAAGCACAGAGCCTTTCAGACCTGTG CCTCCCACTGTATCGTGGTCCTTTGCTTCTTTGGCCCTGGTCTTTTCATTTACCTGAGGCCAGGCTCC AGGAAAGCTGTGGATGGAGTTGTGGCCGTTTTCTACACTGTGCTGACGCCCCTTCTCAACCCTGTTGT GTACACCCTGAGGAACAAGGAGGTGAAGAAAGCTCTGTTGAAGCTGAAAGACAAAGTAGCACATTCTC AGAGCAAATAGACACTAGGGAAGATTACATATCTTAGCTCTTGTGAATAGTGCTGTGAAAAACATACA GGGGCAGG
NOV26a, CG53563-03 SEQ ID NO: 330 311 aa MW at 3451δ.7kD Protein Sequence
MSNASLLTAFILMGLPHAPALDAPLFGVFLWYVLTVLGNLLILLVIRVDSHLHTTMYYFLTNLSFID MWFSTVTVPKLLMTLVFPSGRAISFHSCMAQLYFFHFLGGTECFLYRVMSCDRYLAISYPLRYTSMMT GRSCTLLATSTWLSGSLHSAVQAILTFHLPYCGPNWIQHYLCDAPPILKLACADTSAIETVIFVTVGI VASGCFVLIVLSYVSIVCSILRIRTSEGKHRAFQTCASHCIVVLCFFGPGLFIYLRPGSRKAVDGWA VFYTVLTPLLNPWYTLRNKEVKKALLKLKDKVAHSQSK
NOV26b, CG53563-01 SEQ ID NO: 331 103δ bp DNA Sequence ORF Start: ATG at 2δ ORF Stop: TAG at 961
AGGGAGAGAGACCAAGGGTGAGAAGAAATGTCCAACGCCAGCCTACTGACAGCGTTCATCCTCATGGG
CCTTCCCCATGCCCCAGCGCTGGACGCCCCCCTCTTTGGAGTCTTCCTGGTGGTTTACGTGCTCACTG TGCTGGGGAACCTCCTCATCCTGCTGGTGATCAGGGTGGATTCTCACCTCCACACCACCATGTACTAC TTCCTCACCAACCTGTCGTTCATTGACATGTGGTTCTCCACTGTCACGGTGCCCAAATTGCTGATGAC TTTGGTGTTCCCAAGTGGCAGGGCTATCTCCTTCCACAGCTGCATGGCTCAGCTCTATTTCTTTCACT TCCTAGGGGGCACCGAGTGTTTCCTCTACAGGGTCATGTCCTGTGATCGCTACCTGGCCATCAGTTAC CCGCTCAGGTACACCAGCATGATGACTGGGCGCTCGTGTACTCTTCTGGCCACCAGCACTTGGCTCAG TGGCTCTCTGCACTCTGCTGTCCAGGCCATATTGACTTTCCATTTGCCCTACTGTGGACCCAACTGGA TCCAGCACTATTTGTGTGATGCACCGCCCATCCTGAAACTGGCCTGTGCAGACACCTCAGCCATAGAG ACTGTCATTTTTGTGACTGTTGGAATAGTGGCCTCGGGCTGCTTTGTCCTGATAGTGCTGTCCTATGT GTCCATCGTCTGTTCCATCCTGCGGATCCGCACCTCAGAGGGGAAGCACAGAGCCTTTCAGACCTGTG CCTCCCACTGTATCGTGGTCCTTTGCTTCTTTGGCCCTGGTCTTTTCATTTACCTGAGGCCAGGCTCC AGGAAAGCTGTGGATGGAGTTGTGGCCGTTTTCTACACTGTGCTGACGCCCCTTCTCAACCCTGTTGT GTACACCCTGAGGAACAAGGAGGTGAAGAAAGCTCTGTTGAAGCTGAAAGACAAAGTAGCACATTCTC AGAGCAAATAGACACTAGGGAAGATTACATATCTTAGCTCTTGTGAATAGTGCTGTGAAAAACATACA
GGGGCAGGTATCTTTTGG
NOV26b, CG53563-01 SEQ ID NO: 332 311 aa MW at 3451δ.7kD Protein Sequence
MSNASLLTAFILMGLPHAPALDAPLFGVFLWYVLTVLGNLLILLVIRVDSHLHTTMYYFLTNLSFID MWFSTVTVPKLLMTLVFPSGRAISFHSCMAQLYFFHFLGGTECFLYRVMSCDRYLAISYPLRYTSM T GRSCTLLATSTWLSGSLHSAVQAILTFHLPYCGPN IQHYLCDAPPILKLACADTSAIETVIFVTVGI VASGCFVLIVLSYVSIVCSILRIRTSEGKHRAFQTCASHCIWLCFFGPGLFIYLRPGSRKAVDGWA VFYTVLTPLLNPWYTLRNKEVKKALLKLKDKVAHSQSK
NOV26c, CG53563-02 SEQ ID NO: 333 1040 bp DNA Sequence ORF Start: ATG at 36 ORF Stop: TAG at 969
TTTCTGTAAGAACAGAGCCCCATATATGAGAAGAAATGTCCAACGCCACCCTACTGACAGCGTTCATC
CTCACGGGCCTTCCCCATGCCCCAGGGCTGGACGCCCCCCTCTTTGGAATCTTCCTGGTGGTTTACGT GCTCACTGTGCTGGGGAACCTCCTCATCCTGCTGGTGATCAGGGTGGATTCTCACCTCCACACCCCCA TGTACTACTTCCTCACCAACCTGTCCTTCATTGACATGTGGTTCTCCACTGTCACGGTGCCCAAAATG CTGATGACCTTGGTGTCCCCAAGCGGCAGGACTATCTCCTTCCACAGCTGCGTGGCTCAGCTCTATTT TTTCCACTTCCTGGGGAGCACCGAGTGTTTCCTCTACACAGTCATGTCCTATGATCGCTACCTGGCCA TCAGTTACCCGCTCAGGTACACCAACATGATGACTGGGCGCTCGTGTGCCCTCCTGGCCACCGGCACT TGGCTCAGTGGCTCTCTGCACTCTGCTGTCCAGACCATATTGACTTTCCATTTGCCCTACTGTGGACC CAACCAGATCCAGCACTACTTCTGTGACGCACCGCCCATCCTGAAACTGGCCTGTGCAGACACCTCAG
41δ CCAACGAGATGGTCATCTTTGTGAATATTGGGCTAGTGGCCTCGGGCTGCTTTGTCCTGATAGTGCTG TCCTATGTGTCCATCGTCTGTTCCATCCTGCGGATCCGCACCTCAGAGGGGAGGCACAGAGCCTTTCA GACCTGTGCCTCCCACTGTATCGTGGTCCTTTGCTTCTTTGGCCCTGGTCTTTTCATTTACCTGAGGC CAGGCTCCAGGGACGCCTTGCATGGGGTTGTGGCCGTTTTCTACACCACGCTGACTCCTCTTTTCAAC CCTGTTGTGTACACCCTGAGAAACAAGGAGGTAAAGAAAGCTCTGTTGAAGCTGAAAAATGGGTCAGT ATTTGCTCAGGGTGAATAGTTAAGAAAGGCCATATATGGCTAACTTTTCTTTTTTTATTTGTAATTAA ATTAAACCTTCAACATAAGC
NOV26c, CG53563-02 SEQ ID NO: 334 311 aa MW at 34516.4kD Protein Sequence
MSNATLLTAFILTGLPHAPGLDAPLFGIFLWYVLTVLGNLLILLVIRVDSHLHTPMYYFLTNLSFID M FSTVTVPKMLMTLVSPSGRTISFHSCVAQLYFFHFLGSTECFLYTVMSYDRYLAISYPLRYTNMMT GRSCALLATGT LSGSLHSAVQTILTFHLPYCGPNQIQHYFCDAPPILKLACADTSANEMVIFVNIGL VASGCFVLIVLSYVSIVCSILRIRTSEGRHRAFQTCASHCIWLCFFGPGLFIYLRPGSRDALHGWA VFYTTLTPLFNPWYTLRNKEVKKALLKLKNGSVFAQGE
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 26B.
Table 26B. Comparison of the NOV26 protein sequences.
NOV26a MSNASLLTAFILMGLPHAPALDAPLFGVFLWYVLTVLGNLLILLVIRVDSHLHTTMYYF
NOV26b MSNASLLTAFILMGLPHAPALDAPLFGVFLWYVLTVLGNLLILLVIRVDSHLHTTMYYF
NOV26c MSNATLLTAFILTGLPHAPGLDAPLFGIFLWYVLTVLGNLLILLVIRVDSHLHTPMYYF
NOV26a LTNLSFIDMWFSTVTVPKLLMTLVFPSGRAISFHSCMAQLYFFHFLGGTECFLYRV SCD
NOV26b LTNLSFIDMWFSTVTVPKLLMTLVFPSGRAISFHSCMAQLYFFHFLGGTECFLYRV SCD
NOV26c LTNLSFIDM FSTVTVPKMLMTLVSPSGRTISFHSCVAQLYFFHFLGSTECFLYTVMSYD
NOV26a RYLAISYPLRYTSMMTGRSCTLLATSTWLSGSLHSAVQAILTFHLPYCGPN IQHYLCDA
NOV26b RYLAISYPLRYTSMMTGRSCTLLATST LSGSLHSAVQAILTFHLPYCGPN IQHYLCDA
NOV26c RYLAISYPLRYTNMMTGRSCALLATGTWLSGSLHSAVQTILTFHLPYCGPNQIQHYFCDA
NOV26a PPILKIiACADTSAIETVIFVTVGIVASGCFVLIVLSYVSIVCSILRIRTSEGKHRAFQTC
NOV26b PPILKLACADTSAIETVIFVTVGIVASGCFVLIVLSYVSIVCSILRIRTSEGKHRAFQTC
NOV26c PPILKLACADTSANEMVIFVNIGLVASGCFVLIVLSYVSIVCSILRIRTSEGRHRAFQTC
NOV26a ASHCIVVLCFFGPGLFIYLRPGSRKAVDGWAVFYTVLTPLLNPVVYTLRNKEVKKALLK
NOV26b ASHCIWLCFFGPGLFIYLRPGSRKAVDGWAVFYTVLTPLLNPWYTLRNKEVKKALLK
NOV26c ASHCIWLCFFGPGLFIYLRPGSRDALHGWAVFYTTLTPLFNPWYTLRNKEVKKALLK
NOV26a LKDKVAHSQSK
NOV26b LKDKVAHSQSK
NOV26c LKNGSVFAQGE
NOV26a (SEQ ID NO 330) NOV26b (SEQ ID NO 332) NOV26C (SEQ ID NO 334)
Further analysis ofthe NOV26a protein yielded the following properties shown in Table 26C. Table 26C. Protein Sequence Properties NOV26a
SignalP analysis: Cleavage site between residues 52 and 53
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos . chg 0; neg.chg 0 H-region: length 21; peak value 11.19 PSG score: 6.79
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.58 possible cleavage site: between 51 and 52
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 4 INTEGRAL Likelihood =-10.61 Transmembrane 31 - 47 INTEGRAL Likelihood =-10.08 Transmembrane 197 - 213 INTEGRAL Likelihood = -4.46 Transmembrane 243 - 259 INTEGRAL Likelihood = -2.60 Transmembrane 270 - 286 PERIPHERAL Likelihood = 0.85 (at 5) ALOM score: -10.61 (number of TMSs : 4)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 38 Charge difference: 1.5 C ( 1.0) - N ( -0.5) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 4.41 Hyd Moment(95): 3.21 G content: 1 D/E content: 1 S/T content: 3 Score: -5.14
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 99 GRA|lS
NUCDISC: discrimination of nuclear localization signals pat4 : none pa 7: none bipartite: none content of basic residues: 7.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
44.4 %: endoplasmic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG53563-03 is end (k=9)
A search ofthe NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26D.
Figure imgf000426_0001
In a BLAST search of public sequence databases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26E.
Figure imgf000427_0001
PFam analysis indicates that the NOV26a protein contains the domains shown in the Table 26F.
Figure imgf000427_0002
Example 27.
The NOV27 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 27A.
Figure imgf000428_0001
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 27B. Table 27B. Comparison of the NOV27 protein sequences.
NOV27a MSVIEANNISGPVSELSS ASPACCRETKILLFWFSLIYLLTLMGNTSIICAVWSSQKL
NOV27b MSVIEANNISGPVSEFILLGFPACCRETKILLFWFSLIYLLTLMGNTSIICAVWSSQKL
NOV27a HTPMYILLANFSFLEICCISSDVPMLANLISHIKSISYAGCLLQFFYFSMCAAEGYFLSV
NOV27b HTPMYILLANFSFLEICCISSDVPMLANLISHIKSISYAGCLLQFFYFSMCAAEGYFLSV
NOV27a MSFDRFLTICRPLHYPTVMTHHLCVRLVAFCRAGGFLSILMPAVLMSRVPFCGPNITDHF
NOV27b MSFDRFLTICRPLHYPTVMTHHLCVRLVAFCRAGGFLSILMPAVLMSRVPFCGPNITDHF
NOV27a FCNLGPLLALSCAPVPKTTLTCATVSSLIIFITFLYILGSHILVLRAVLWVPAGSGRNKA
NOV27b FCNLGPLLALSCAPVPKTTLTCATVSSLIIFITFLYILGSHILVLRAVLWVPAGSGRNKA
NOV27a FSTCASHFLWSFFYGSVMVMYVSPGSRSRPGTQKFVTLFYCTANPFFNPLTYSLWNKDM
NOV27b FSTCASHFLWSFFYGSVMVMYVSPGSRSRPGTQKFVTLFYCTATPFFNPLTYSLWNKDM
NOV27a TDALKKVLGVPSKEISWNTLK
NOV27b TDALKKVLGVPSKEIYWNTLK
NOV27a (SEQ ID NO: 336) NOV27b (SEQ ID NO: 338)
Further analysis ofthe NOV27a protein yielded the following properties shown in Table 27C.
Table 27C. Protein Sequence Properties NOV27a
SignalP analysis: Cleavage site between residues 47 and 4δ
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 5; pos. chg 0; neg.chg 1 H-region: length 9; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1) : -3.31 possible cleavage site: between 43 and 44
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 5 INTEGRAL Likelihood = -9.34 Transmembrane 30 - 46
INTEGRAL Likelihood = -1.28 Transmembrane 64 - 80
INTEGRAL Likelihood = -0.96 Transmembrane 156 - 172 INTEGRAL Likelihood = -7.54 Transmembrane 208 - 224 INTEGRAL Likelihood = -2.50 Transmembrane 248 - 264 PERIPHERAL Likelihood = 1.48 (at 180) ALOM score: -9.34 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 37 Charge difference: 1.5 C( 1.5) - N( 0.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 0.86 Hyd Moment (95): 3.03 G content: 1 D/E content: 2 S/T content: 3 Score: -7.70
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 6.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
44.4 %: endoplas ic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG53719-02 is end (k=9)
A search ofthe NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27D.
Figure imgf000432_0001
In a BLAST search of public sequence databases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27E.
Figure imgf000433_0001
PFam analysis indicates that the NOV27a protein contains the domains shown in the Table 27F.
Figure imgf000433_0002
Example 28.
The NOV2δ clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2δA.
Table 28A. NOV28 Sequence Analysis
NOV2δa, CG53746-04 SEQ ID NO: 339 1604 bp DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV2δa, CG53746-04 SEQ ID NO: 340 311 aa MW at 34309.4kD Protein Sequence
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISI IVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV28b, CG53746-01 SEQ ID NO: 341 984 bp
DNA Sequence JORF Start: ATG at 24 ORF Stop: TGA at 957
AGTTGGCACCATTCCCAATATAGATGGGGACTGGAAATGACACCACTGTGGTAGAGTTTACTCTTTTG
GGGTTATCTGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAATTTATGTTGTCAC CTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATACACCCATGTACA TTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCTGTCATGCTCATG AGCTTCCTAAGGAAAGAAACCTCTCTCCCTGTTGCTGGTTGTGTGGCCCAGCTCTGTTCTGTAGTGAC GTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGGCCATCTGCTCAC CCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATGTCCTACCTGGGT GGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGGGCCAAATAAAGT CAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATTTTACTTTTGAAA TAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCCATATCCTACATC TATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTTCTCCACCTGCAC CTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGATGCCCAAGTCCA GCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCCATGTTGAACCCC CTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAGAATAAAAATATT TTCTTGATGAAACTAGTTAGTTTGAAGAATCT
NOV28b, CG53746-01 SEQ ID NO: 342 311 aa MW at 34295.4kD Protein Sequence
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV2δc, CG53746-02 SEQ ID NO: 343 952 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: TGA at 940
ATATAGATGGGGACTGGAAATGACACCACTGTGGTAGAGTTTACTCTTTTGGGGTTATCCGAGGATAC
TACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAATTTATGTTGTCACCTTAATGGGTAATATCA GCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATACACCCATGTACATTTTCCTCTGCCATTTG GCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCTGTCATGCTCATGAGCTTCCTAAGGAAAGA AACCTCTCTCCCTGTTGCTGGTTGTGTGGCCCAGCTCTGTTCTGTGGTGACGTTTGGTACGGCCGAGT GCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGGCCATCTGCTCACCCCTGCTCTACTCTACC TGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATGTCCTACCTGGGTGGATGTGTGAATGCTTG GACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGGGCCAAATAAAGTCAATCACTTTTTCTGTG ACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATTTTACTTTTGAAATAATTCCAGCTATCTCT TCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCCATATCCTACATCTATATCCTCATCACCAT CCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTTCTCCACCTGCACCTCCCACCTCACTGCAG TCACTCTGTTTTATGGGACCATTACCTTCATTTATGTGATGCCCAAGTCCAGCTACTCAACTGACCAG AACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCCATGTTGAACCCCCTGATCTACAGCCTCAG GAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAGAATAAAAATATTTTCTTGATGAAACTAGT
NOV2δc, CG53746-02 SEQ ID NO: 344 311 aa MW at 34295.4kD Protein Sequence
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNA TFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWI PMLNPLI YSLRNKE IKGALKRELRI KI FS
NOV2δd, CG53746-03 SEQ ID NO: 345 964 bp DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 941
TATATAGATGGGGACTGGAAATGACACCACTGTGGTAGAGTTTACTCTTTTGGGGTTATCCGAGGATA
CTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAATTTATGTTGTCACCTTAATGGGTAATATC AGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATACACCCATGTACATTTTCCTCTGCCATTT GGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCTGTCATGCTCATGAGCTTCCTAAGGAAAG AAACCTCTCTCCCTGTTGCTGGTTGTGTGGCCCAGCTCTGTTCTGTGGTGACGTTTGGTACGGCCGAG TGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGGCCATCTGCTCACCCCTGCTCTACTCTAC CTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATGTCCTACCTGGGTGGATGTGTGAATGCTT GGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGGGCCAAATAAAGTCAATCACTTTTTCTGT GACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATTTTACTTTTGAAATAATTCCAGCTATCTC TTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCCATATCCTACATCTATATCCTCATCACCA TCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTTCTCCACCTGCACCTCCCACCTCACTGCA GTCACTCTGTTTTATGGGACCATTACCTTCATTTATGTGATGCCCAAGTCCAGCTACTCAACTGACCA GAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCCATGTTGAACCCCCTGATCTACAGCCTCA GGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAGAATAAAAATATTTTCTTGATGAAACTAG TTAGTTTGAAGA
NOV2δd, CG53746-03 SEQ ID NO: 346 311 aa MW at 34295.4kD Protein Sequence
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWI PMLNPLI YSLRNKE I KGALKRELRIKIFS
NOV2δe, SNPl 3373967 of SEQ ID NO: 347 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 466 SNP Change: T to C
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGCTTTAAAGTCT TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV2δe, SNPl 3373967 of SEQ ID NO: 348 311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Change: no change
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEI IPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV28f, SNPl 3373968 of SEQ ID NO: 349 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 648 ORF Stop: TGA at 1581
SNP Pos: 550 SNP Change: T to C
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA
AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA
TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGCTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV28f, SNP1337396δ of SEQ ID NO: 350 311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Change: no change
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWI PMLNPLI YSLRNKE I KGALKRELRI KI FS
NOV2δg, SNP133δ2432 of SEQ ID NO: 351 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 644 SNP Change: T to A
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA
AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA
TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATATAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV28g, SNP133δ2432 of SEQ ID NO: 352 311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Change: no change
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGI YWTLMGNI S 11 VLI RRSHHLHTPMYI FLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNA TFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SI IVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV28h, SNPl 3373969 of SEQ ID NO: 353 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 695 SNP Change: A to G
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA lAATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA
TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG jTCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGGTTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV28h, SNPl 3373969 of SEQ ID NO: 354 311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Pos: 16 SNP Change: Gly to Gly
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEI IPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV28i, SNP 13373970 of SEQ ID NO: 355 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 927 SNP Change: A to G
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA
AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA
TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTGTTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV28i, SNPl 3373970 of tø SE] Q ID NO: 356 311 aa MW at 34295.4kD
CG53746-04, Protein Sequence | |SSΪNP Pos: 94 SNP Change: He to Val
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCI ILVGMSYLGGCVNA TFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEI IPAISSG SI IVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV2δj, SNPl 3373971 of SEQ ID NO: 357 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ|θRF Stop: TGA at 1581
SNP Pos: 959 SNP Change: A to G
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA ;AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT jGCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA
TGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
ITCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTGGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV28J, SNPl 3373971 of SEQ ID NO: 35δ|311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Pos: 104 SNP Change: Val to Val
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEI IPAISSG SIIVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV2δk, SNPl 3373972 of SEQ ID NO: 359 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 105δ SNP Change: C to T iACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA
AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
'GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA jTGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
TCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT iTTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCTCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACACCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV2δk, SNPl 3373972 of SEQ ID NO: 360 311 aa MW at 34309.4kD CG53746-04, Protein Sequence SNP Pos: 137 jSNP Change: Ser to Ser
MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMG IS11VLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNA TFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SIIVATVCVIAISYIYILITILK HSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYTWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
NOV2δl, SNP133δ2433 of SEQ ID NO: 361 1604 bp CG53746-04, DNA Sequence ORF Start: ATG at 64δ ORF Stop: TGA at 1581
SNP Pos: 1482 SNP Change: A to G
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTTGGATATTTGGTGTACTTTTCCTCAATTGTGA
AATCTCTGGGTGGGGACCACAGCTCAGTGTTGAGTTACTGACCTCTTCTTGGTCCTGTGGATTAGCAT
GCAGCTAATCTGTTTGACCTCTGTTTGGAATTCGGAATTCTTAATGACTACACATCTTTGATACAATA
GATGATACCTCAAACATCCTTTTGAACAGCTGTTCTTTTCCATGAGTCTTGGTCTATTCTGACATTTA jTGTCTCCCTTCAATCACGTCTTTGGCCTTAGAAGATTGAGTTACTGGATTCTTTATATATTCTAGTGG
ITCATCTCTGAAATGTGCTCAGAGAGCACCTAAATTAACCATCCAATACGAGTTGAGTGTGTTAAGTTA
AAAAAAAAAAAAAGATTTTTCTGAGTATTCCTGACCTTACATCAGTGAACATTTATGTTTTAAAGTCT
TACATAAGATACTGTGTGTGAAAGCATTTTCTTCCCAAATTTACATGAGTGCCTAAATTGTTATACTT
TTTGGTTAAATAGATATTGGAAAAATAAGTGTGCAATTATAGCATTTAATCCCATTATAATATTCATT
TGTTTTTCTTTCAGTTGGCACCATTCCCAATTTAGATGGGGACTGGAAATGACACCACTGTGGTAGAG
TTTACTCTTTTGGGATTATCCGAGGATACTACAGTTTGTGCTATTTTATTTCTTGTGTTTCTAGGAAT TTATGTTGTCACCTTAATGGGTAATATCAGCATAATTGTATTGATCAGAAGAAGTCATCATCTTCATA CACCCATGTACATTTTCCTCTGCCATTTGGCCTTTGTAGACATTGGGTACTCCTCATCAGTCACACCT GTCATGCTCATGAGCTTCCTAAGGAAAGAAACCTCTCTCCCTATTGCTGGTTGTGTGGCCCAGCTCTG TTCTGTAGTGACGTTTGGTACGGCCGAGTGCTTCCTGCTGGCTGCCATGGCCTATGATCGCTATGTGG CCATCTGCTCACCCCTGCTCTACTCTACCTGCATGTCCCCTGGAGTCTGCATCATCTTAGTGGGCATG TCCTACCTGGGTGGATGTGTGAATGCTTGGACATTCATTGGCTGCTTATTAAGACTGTCCTTCTGTGG GCCAAATAAAGTCAATCACTTTTTCTGTGACTATTCACCACTTTTGAAGCTTGCTTGTTCCCATGATT TTACTTTTGAAATAATTCCAGCTATCTCTTCTGGATCTATCATTGTGGCCACTGTGTGTGTCATAGCC ATATCCTACATCTATATCCTCATCACCATCCTGAAGATGCACTCCACCAAGGGCCGCCACAAGGCCTT CTCCACCTGCACCTCCCACCTCACTGCAGTCACTCTGTTCTATGGGACCATTACCTTCATTTATGTGA TGCCCAAGTCCAGCTACTCAACTGACCAGAACAAGGTGGTGTCTGTGTTCTACGCCGTGGTGATTCCC ATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGATTAAGGGGGCTCTGAAGAGAGAGCTTAG AATAAAAATATTTTCTTGATGAAACTAGTTAGTTTGAAGA
NOV281, SNPl 3382433 of SEQ ID NO: 362 311 aa MW at 34279.4kD CG53746-04, Protein Sequence SNP Pos: 279 SNP Change: Thr to Ala
MGTGNDTTWE FTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMYIFLCHLAF VDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAYDRYVAICSPLLYSTCM SPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCDYSPLLKLACSHDFTFEIIPAISSG SI IVATVCVIAISYIYILITILKMHSTKGRHKAFSTCTSHLTAVTLFYGTITFIYVMPKSSYSTDQNK WSVFYAWIPMLNPLIYSLRNKEIKGALKRELRIKIFS
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 2δB.
Table 28B. Comparison of the NOV28 protein sequences.
NOV28a MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMY
NOV28b MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMY
NOV28c MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMY
NOV28d MGTGNDTTWEFTLLGLSEDTTVCAILFLVFLGIYWTLMGNISIIVLIRRSHHLHTPMY NOV28a IFLCHLAFVDIGYSSSVTPVMLMSFLRKETSLPIAGCVAQLCSWTFGTAECFLLAAMAY
NOV28b IFLCHLAFVDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAY
NOV28C IFLCHLAFVDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAY
NOV28d IFLCHLAFVDIGYSSSVTPVMLMSFLRKETSLPVAGCVAQLCSWTFGTAECFLLAAMAY
NOV28a DRYVAICSPLLYSTCMSPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCD
NOV28b DRYVAICSPLLYSTCMSPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCD
NOV28C DRYVAICSPLLYSTCMSPGVCIILVGMSYLGGCVNA TFIGCLLRLSFCGPNKVNHFFCD
NOV28d DRYVAICSPLLYSTCMSPGVCIILVGMSYLGGCVNAWTFIGCLLRLSFCGPNKVNHFFCD
NOV28a YSPLLKLACSHDFTFEIIPAISSGSIIVATVCVIAISYIYILITILKMHSTKGRHKAFST
NOV28b YSPLLKLACSHDFTFEIIPAISSGSIIVATVCVIAISYIYILITILKMHSTKGRHKAFST
NOV28C YSPLLKLACSHDFTFEIIPAISSGSIIVATVCVIAISYIYILITILKMHSTKGRHKAFST
NOV28d YSPLLKLACSHDFTFEIIPAISSGSIIVATVCVIAISYIYILITILKMHSTKGRHKAFST
NOV28a CTSHLTAVTLFYGTITFIYVMPKSSYSTDQNKWSVFYTWIPMLNPLIYSLRNKEIKGA
NOV28b CTSHLTAVTLFYGTITFIYVMPKSSYSTDQNKWSVFYTWIPMLNPLIYSLRNKEIKGA
NOV28C CTSHLTAVTLFYGTITFIYVMPKSSYSTDQNKWSVFYTWIPMLNPLIYSLRNKEIKGA
NOV28d CTSHLTAVTLFYGTITFIYVMPKSSYSTDQNKWSVFYTWIPMLNPLIYSLRNKEIKGA
NOV28a LKRELRIKIFS NOV28b LKRELRIKIFS NOV28c LKRELRIKIFS NOV28d LKRELRIKIFS
NOV28a (SEQ ID NO 340)
NOV28b (SEQ ID NO 342)
NOV28c (SEQ ID NO 344)
NOV28d (SEQ ID NO 346)
Further analysis ofthe NOV2δa protein yielded the following properties shown in Table 2δC.
Table 28C. Protein Sequence Properties NOV28a
SignalP analysis: Cleavage site between residues 42 and 43
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 11 ; pos . chg 0 ; neg . chg 2 H-region : length 7 ; peak value 0 . 00 PSG score : -4 . 40
GvH : von Heij ne ' s method for signal seq . recognition GvH score ( threshold : - 2 . 1 ) : -5 . 11 possible cleavage site : between 38 and 39
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation Init position for calculation : 1
Tentative number of TMS ( s) for the threshold 0 . 5 : INTEGRAL Likelihood = - 11 .46 Transmembrane 23 39 INTEGRAL Likelihood = -1.49 Transmembrane 101 - 117
INTEGRAL Likelihood = -2.23 Transmembrane 140 - 156
INTEGRAL Likelihood = -9.82 Transmembrane 206 - 222
INTEGRAL Likelihood = -0.85 Transmembrane 245 - 261
INTEGRAL Likelihood = -3.13 Transmembrane 273 - 289
PERIPHERAL Likelihood = 1.48 (at 61)
ALOM score: -11.46 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 30 Charge difference: 7.5 C( 3.5) - N (-4.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Momen (75): 5.92 Hyd Moment(95): 6.18 G content: 2 D/E content : 2 S/T content : 3 Score: -7.11
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 6.8% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: IKIF
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhard 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: mitochondrial
>> prediction for CG53746-04 is end (k=9)
A search ofthe NOV2δa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2δD.
Figure imgf000444_0001
In a BLAST search of public sequence databases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 2δE.
Figure imgf000445_0001
PFam analysis indicates that the NOV2δa protein contains the domains shown in the Table 2δF.
Figure imgf000445_0002
Example 29.
The NOV29 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 29A.
Table 29A. NOV29 Sequence Analysis
NOV29a, CG53767-02 SEQ ID NO: 363 137δ bp DNA Sequence ORF Start: ATG at 473 ORF Stop: TAA at 1331
TGAAATTGGAGAGTCATACAAAATCCAGAATGGAGAAAAGAGAGATAAACAGTGCTTTTGGGGTAAAA TCCAGGTATAGGTATTTGGGCCCACTCTATGTCATCTATACATATTATCATATTAGAATCATTCTTCT CTTCACTCAGGCTCCTGACCTTGACCTCTTTCCAGGTGCATTTAACTCCCTTTCCTCAGGTTCTCTAA GAGTTGCCTGACACTTGCCCAGGTCCCCTGAATAAAATACAGGTAAATCAGTGCATAAGAAGCTTTAT
ACAGTGATCTCAGACTTGTGACCAAGAGCCCCTCTGCACCATTGATAGACAGTGGCCGTGCCCACCAG
GAGGATGGGCAATCACACTGCAGTGAGCCTATTCCTTCTGTGGGGATTTTCCAGTTTTTCAGACCTGC
AGAGTCTACTTTTTGTGGTGATTCTCTTCTACATGTGACCATCCTAGCTGCAAACGTGTCCATAATGG
GGGCCATCAAGCTCAGCCACAACCTTCACACTCCTATGTACTTTTTCCTCTGTGGCCTGTCCTTTTCA GAAACTTGTACCACTGTGGTAGTAATCCCTCGCATGTTGGTGGACTTTCTATCAGAGAGCAAGACCAT TTCTCTTCCTGAGTGTGCCACACAGATGTTTTTCTTTCTGGGCTTTGCATCCAACAACTGTTTCATCA TGGCCGCTATGTCCTACGACCGCTACACGGCCATCCACAACCCACTGCAGTACCACACCCTTATGACA AGAAAGATCTGCTTGCAGATGATGATGGCTTCTTGGATGGTTGGGTTCCTGTTTTCTCTGTGCATCAT CGTCACTGTATTCAACTTGTCTCTTTGCGACTTGAACACTATCCAGCACTATTTCTGTGATATCTCAC CAGTGGTCTCCCTTGCTTGTAATTACACTTTCTATCATGAAATGGCTATTTTTGTGCTCTCTGCCTTT GTGTTGGTGGGCAGCTGTATTTTAATTATGATTTCCTATGTCTTCATTGTGTTCATAGTCATAAAGAT GCCCTCTGCAAAGGGGAGGTCTAAGGCCTTCTCAACTTGCTCCTCCCACCTCACTGTTGTGTCCATAC ACTATGGATTTGCTTGCTTTGTCTATTTGAGGCCCAAGAACAGCAACTCCTTCGATGAAGACATGCCG ACGGCCATGATATATACAATACTGATGCCTCTGCTTAACCCCATCGTGTACAGTCTGAGAAACAAAGA AATGCAGATAGCCCTAAGAAAAACACTAGGCAGTGTATTTGGGGTTTTCCCTCAGAAGACAAAAAAAG AGCCTGAACATTTAAAAAAATTACACAGCATTGATAAATAAAGGTGAGAAAAGCGAAAAAAAAAAAAA AAAAAAAAAAAAAAAGGG
NOV29a, CG53767-02 SEQ ID NO: 364 286 aa MW at 32538.4kD Protein Sequence
MGAIKLSHNLHTPMYFFLCGLSFSETCTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCF IMAAMSYDRYTAIHNPLQYHTLMTRKICLQMMMASWMVGFLFSLCI IVTVFNLSLCDLNTIQHYFCDI SPWSLACNYTFYHEMAIFVLSAFVLVGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSSHLTWS IHYGFACFVYLRPKNSNSFDEDMPTAMIYTILMPLLNPIVYSLRNKEMQIALRKTLGSVFGVFPQKTK KEPEHLKKLHSIDK
NOV29b, CG53767-01 SEQ ID NO: 365 102 bp DNA Sequence ORF Start: ATG at 23 ORF Stop: TAA at 1007
AGTGGCCGTGCCCACCAGGAGGATGGGCAATCACACTGCAGTGAGCCTATTCCTTCTGTGGGGATTTT
CCAGTTTTTCAGACCTGCAGAGTCTACTTTGTGGTGATTCTCTTCTACATGTGACCATCCTAGCTGCA AACGTGTCCATAATGGGGGCCATCAAGCTCAGCCACAACCTTCACACTCCTATGTACTTTTTCCTCTG TGGCCTGTCCTTTTCAGAAACTTGTACCACTGTGGTAGTAATCCCTCGCATGTTGGTGGACTTTCTAT CAGAGAGCAAGACCATTTCTCTTCCTGAGTGTGCCACACAGATGTTTTTCTTTCTGGGCTTTGCATCC AACAACTGTTTCATCATGGCCGCTATGTCCTACGACCGCTACACGGCCATCCACAACCCACTGCAGTA CCACACCCTTATGACAAGAAAGATCTGCTTGCAGATGATGATGGCTTCTTGGATGGTTGGGTTCCTGT TTTCTCTGTGCATCATCGTCACTGTATTCAACTTGTCTCTTTGCGACTTGAACACTATCCAGCACTAT TTCTGTGATATCTCACCAGTGGTCTCCCTTGCTTGTAATTACACTTTCTATCATGAAATGGCTATTTT TGTGCTCTCTGCCTTTGTGTTGGTGGGCAGCTGTATTTTAATTATGATTTCCTATGTCTTCATTGTGT TCATAGTCATAAAGATGCCCTCTGCAAAGGGGAGGTCTAAGGCCTTCTCAACTTGCTCCTCCCACCTC ACTGTTGTGTCCATACACTATGGATTTGCTTGCTTTGTCTATTTGAGGCCCAAGAACAGCAACTCCTT CGATGAAGACATGCTGACGGCCATGATATATACAATACTGATGCCTCTGCTTAACCCCATCGTGTACA GTCTGAGAAACAAAGAAATGCAGATAGCCCTAAGAAAAACACTAGGCAGTGTATTTGGGGTTTTCCCT CAGAAGACAAAAAAAGAGCCTGAACATTTAAAAAAATTACACAGCATTGATAAATAAAGGTGAGAAAA GTGGAGTA
NOV29b, CG53767-01 SEQ ID NO: 366 32 aa MW at 37015.5kD Protein Sequence
MGNHTAVSLFLLWGFSSFSDLQSLLCGDSLLHVTILAANVSIMGAIKLSHNLHTPMYFFLCGLSFSET CTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCFIMAAMSYDRYTAIHNPLQYHTLMTRK ICLQMMMAS MVGFLFSLCIIVTVFNLSLCDLNTIQHYFCDISPWSLACNYTFYHEMAIFVLSAFVL VGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSSHLTWSIHYGFACFVYLRPKNSNSFDEDMLTA M I YT I MPLLNP I VYSLRNKEMQI ALRKTLGS VFGVFPQKTKKE PEHLKKLHS I DK
NOV29c, SNP133δ2437 of SEQ ID NO: 367 137δ bp CG53767-02, DNA Sequence ORF Start: ATG at 473 ORF Stop: TAA at 1331
SNP Pos: 961 SNP Change: G to A
TGAAATTGGAGAGTCATACAAAATCCAGAATGGAGAAAAGAGAGATAAACAGTGCTTTTGGGGTAAAA TCCAGGTATAGGTATTTGGGCCCACTCTATGTCATCTATACATATTATCATATTAGAATCATTCTTCT
CTTCACTCAGGCTCCTGACCTTGACCTCTTTCCAGGTGCATTTAACTCCCTTTCCTCAGGTTCTCTAA
GAGTTGCCTGACACTTGCCCAGGTCCCCTGAATAAAATACAGGTAAATCAGTGCATAAGAAGCTTTAT
ACAGTGATCTCAGACTTGTGACCAAGAGCCCCTCTGCACCATTGATAGACAGTGGCCGTGCCCACCAG
GAGGATGGGCAATCACACTGCAGTGAGCCTATTCCTTCTGTGGGGATTTTCCAGTTTTTCAGACCTGC
AGAGTCTACTTTTTGTGGTGATTCTCTTCTACATGTGACCATCCTAGCTGCAAACGTGTCCATAATGG
GGGCCATCAAGCTCAGCCACAACCTTCACACTCCTATGTACTTTTTCCTCTGTGGCCTGTCCTTTTCA GAAACTTGTACCACTGTGGTAGTAATCCCTCGCATGTTGGTGGACTTTCTATCAGAGAGCAAGACCAT TTCTCTTCCTGAGTGTGCCACACAGATGTTTTTCTTTCTGGGCTTTGCATCCAACAACTGTTTCATCA TGGCCGCTATGTCCTACGACCGCTACACGGCCATCCACAACCCACTGCAGTACCACACCCTTATGACA AGAAAGATCTGCTTGCAGATGATGATGGCTTCTTGGATGGTTGGGTTCCTGTTTTCTCTGTGCATCAT CGTCACTGTATTCAACTTGTCTCTTTGCGACTTGAACACTATCCAGCACTATTTCTGTGATATCTCAC CAGTGGTCTCCCTTGCTTGTAATTACACTTTCTATCATGAAATGGCTATTTTTGTGCTCTCTGCCTTT GTGTTGGTAGGCAGCTGTATTTTAATTATGATTTCCTATGTCTTCATTGTGTTCATAGTCATAAAGAT GCCCTCTGCAAAGGGGAGGTCTAAGGCCTTCTCAACTTGCTCCTCCCACCTCACTGTTGTGTCCATAC ACTATGGATTTGCTTGCTTTGTCTATTTGAGGCCCAAGAACAGCAACTCCTTCGATGAAGACATGCCG ACGGCCATGATATATACAATACTGATGCCTCTGCTTAACCCCATCGTGTACAGTCTGAGAAACAAAGA AATGCAGATAGCCCTAAGAAAAACACTAGGCAGTGTATTTGGGGTTTTCCCTCAGAAGACAAAAAAAG AGCCTGAACATTTAAAAAAATTACACAGCATTGATAAATAAAGGTGAGAAAAGCGAAAAAAAAAAAAA AAAAAAAAAAAAAAAGGG
NOV29c, SNP133 2437 of SEQ ID NO: 36δ 2δό aa MW at 3253δ.4kD CG53767-02, Protein Sequence SNP Pos: 163 SNP Change: Val to Val
MGAIKLSHNLHTPMYFFLCGLSFSETCTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCF IMAAMSYDRYTAIHNPLQYHTLMTRKICLQMMMASWMVGFLFSLCIIVTVFNLSLCDLNTIQHYFCDI SPWSLACNYTFYHEMAIFVLSAFVLVGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSSHLTWS IHYGFACFVYLRPKNSNSFDEDMPTAMIYTILMPLLNPIVYSLRNKEMQIALRKTLGSVFGVFPQKTK KEPEHLKKLHSIDK
NOV29d, SNP133δ2436 of SEQ ID NO: 369 137δ bp CG53767-02, DNA Sequence ORF Start: ATG at 473 ORF Stop: TAA at 1331 SNP Pos: 1283 SNP Change: A to G jTGAAATTGGAGAGTCATACAAAATCCAGAATGGAGAAAAGAGAGATAAACAGTGCTTTTGGGGTAAAA
ITCCAGGTATAGGTATTTGGGCCCACTCTATGTCATCTATACATATTATCATATTAGAATCATTCTTCT
CTTCACTCAGGCTCCTGACCTTGACCTCTTTCCAGGTGCATTTAACTCCCTTTCCTCAGGTTCTCTAA
GAGTTGCCTGACACTTGCCCAGGTCCCCTGAATAAAATACAGGTAAATCAGTGCATAAGAAGCTTTAT
ACAGTGATCTCAGACTTGTGACCAAGAGCCCCTCTGCACCATTGATAGACAGTGGCCGTGCCCACCAG
GAGGATGGGCAATCACACTGCAGTGAGCCTATTCCTTCTGTGGGGATTTTCCAGTTTTTCAGACCTGC
AGAGTCTACTTTTTGTGGTGATTCTCTTCTACATGTGACCATCCTAGCTGCAAACGTGTCCATAATGG
GGGCCATCAAGCTCAGCCACAACCTTCACACTCCTATGTACTTTTTCCTCTGTGGCCTGTCCTTTTCA GAAACTTGTACCACTGTGGTAGTAATCCCTCGCATGTTGGTGGACTTTCTATCAGAGAGCAAGACCAT TTCTCTTCCTGAGTGTGCCACACAGATGTTTTTCTTTCTGGGCTTTGCATCCAACAACTGTTTCATCA TGGCCGCTATGTCCTACGACCGCTACACGGCCATCCACAACCCACTGCAGTACCACACCCTTATGACA AGAAAGATCTGCTTGCAGATGATGATGGCTTCTTGGATGGTTGGGTTCCTGTTTTCTCTGTGCATCAT CGTCACTGTATTCAACTTGTCTCTTTGCGACTTGAACACTATCCAGCACTATTTCTGTGATATCTCAC CAGTGGTCTCCCTTGCTTGTAATTACACTTTCTATCATGAAATGGCTATTTTTGTGCTCTCTGCCTTT GTGTTGGTGGGCAGCTGTATTTTAATTATGATTTCCTATGTCTTCATTGTGTTCATAGTCATAAAGAT GCCCTCTGCAAAGGGGAGGTCTAAGGCCTTCTCAACTTGCTCCTCCCACCTCACTGTTGTGTCCATAC ACTATGGATTTGCTTGCTTTGTCTATTTGAGGCCCAAGAACAGCAACTCCTTCGATGAAGACATGCCG ACGGCCATGATATATACAATACTGATGCCTCTGCTTAACCCCATCGTGTACAGTCTGAGAAACAAAGA AATGCAGATAGCCCTAAGAAAAACACTAGGCAGTGTATTTGGGGTTTTCCCTCAGAAGGCAAAAAAAG AGCCTGAACATTTAAAAAAATTACACAGCATTGATAAATAAAGGTGAGAAAAGCGAAAAAAAAAAAAA AAAAAAAAAAAAAAAGGG
NOV29d, SNP133δ2436 of SEQ ID NO: 370 2δ6 aa MW at 3250δ.4kD CG53767-02, Protein Sequence SNP Pos: 271 SNP Change: Thr to Ala
MGAIKLSHNLHTPMYFFLCGLSFSETCTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCF IMAAMSYDRYTAIHNPLQYHTLMTRKICLQMMMASWMVGFLFSLCIIVTVFNLSLCDLNTIQHYFCDI SPWSLACNYTFYHEMAIFVLSAFVLVGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSSHLTWS IHYGFACFVYLRPKNSNSFDEDMPTAMIYTILMPLLNPIVYSLRNKEMQIALRKTLGSVFGVFPQKAK KEPEHLKKLHSIDK
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 29B.
Table 29B. Comparison ofthe NOV29 protein sequences.
N0V29a MGAIKLSHNLHTPMYFFL
NOV29b MGNHTAVSLFLLWGFSSFSDLQSLLCGDSLLHVTILAANVSIMGAIKLSHNLHTPMYFFL
NOV29a CGLSFSETCTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCFIMAAMSYDRY
NOV29b CGLSFSETCTTVWIPRMLVDFLSESKTISLPECATQMFFFLGFASNNCFIMAAMSYDRY
NOV29a TAIHNPLQYHTLMTRKICLQMMMAS MVGFLFSLCIIVTVFNLSLCDLNTIQHYFCDISP
NOV29b TAIHNPLQYHTLMTRKICLQMMMASWMVGFLFSLCIIVTVFNLSLCDLNTIQHYFCDISP
NOV29a WSLACNYTFYHEMAIFVLSAFVLVGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSS
NOV29b WSLACNYTFYHEMAIFVLSAFVLVGSCILIMISYVFIVFIVIKMPSAKGRSKAFSTCSS
NOV29a HLTWSIHYGFACFVYLRPKNSNSFDEDMPTAMIYTILMPLLNPIVYSLRNKEMQIALRK
NOV29b HLTWSIHYGFACFVYLRPKNSNSFDEDMLTAMIYTILMPLLNPIVYSLRNKEMQIALRK
NOV29a TLGSVFGVFPQKTKKEPEHLKKLHSIDK
NOV29b TLGSVFGVFPQKTKKEPEHLKKLHSIDK
NOV29a (SEQ ID NO: 364)
NOV29b (SEQ ID NO: 366)
Further analysis ofthe NOV29a protein yielded the following properties shown in Table 29C.
Table 29C. Protein Sequence Properties NOV29a
SignalP analysis: Cleavage site between residues 25 and 26
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 5 ; pos . chg 1 ; neg . chg 0 H-region : length 19 ; peak value 10 . 63 PSG score : 6 .23
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1 ) : -2 .51 possible cleavage site : between 29 and 30
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation Init position for calculation : 1 Tentative number of TMS (s) for the threshold 0 .5 : INTEGRAL Likelihood = -0.43 Transmembrane 17 - 33
INTEGRAL Likelihood = -7.17 Transmembrane 105 - 121
INTEGRAL Likelihood = -1.33 Transmembrane 148 - 164
INTEGRAL Likelihood =-12.52 Transmembrane 165 - 181
PERIPHERAL Likelihood = 0.53 (at 231)
ALOM score: -12.52 (number of TMSs : 4)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 24 Charge difference: -0.5 C(-1.0) - N(-0.5) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 4.10 Hyd Moment(95): 4.80 G content: 2 D/E content : 1 S/T content : 4 Score: -5.17
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 45 PRM | V
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PQKTKKE (4) at 268 bipartite: RKTLGSVFGVFPQKTKK at 257 content of basic residues: 7.7% NLS Score: 0.36
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum 44.4 %: mitochondrial
>> prediction for CG53767-02 is end (k=9)
A search ofthe NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29D.
Figure imgf000451_0001
In a BLAST search of public sequence databases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29E.
Figure imgf000452_0001
PFam analysis indicates that the NOV29a protein contains the domains shown in the Table 29F.
Table 29F. Domain Analysis of NOV29a
Identities/
Pfam Domain NOV29a Match Region Similarities Expect Value for the Matched Region
7rm 1 3..245 47/278 (17%) 3.1e-19 169/278 (61%)
Example 30.
The NOV30 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 30A.
Figure imgf000452_0002
CTGAAGGACGGGAATCACACCGCTCTGACGGGGTTCATCCTATTGGGCTTAACAGATGATCCAATCCT TCGAGTCATCCTCTTCATGATCATCCTATGCATCTACCTGGTAACCATATCTGGTAATCTCAGCATAA TTATTCTTATCAGAATTTCTTCTCAGCTCCATCATCCTATGTATTTCTTTCTGAGCCACTTGGCTTTT GCTGACATGGCCTATTCATCTTCTGTCACACCCAACATGCTTGTAAACTTCCTGGTGGAGAGAAATAC AGTCTCCTACCTTGGATGTGCCATCCAGCTTGGTTCAGCGGCTTTCTTTGCAACAGTCGAATGCGTCT TTCTGGCTGCCATGGCCTATGACCGCTTTGTGGCAATTTGCAGTCCACTGCTTTATTCAACCAAAATG TCCACACAAGTCAGTGTCCAGCTACTCTTAGTAGTTTACATAGCTGGTTTTCTCATTGCTGTCTCCTA TACTACTTCCTTCTATTTTTTACTCTTCTGTGGACCAAATCAAGTCAATCATTTTTTCTGTGATTTCG CTCCCTTACTTGAACTCTCCTGTTCTGATATCAGTGTCTCCACAGTTGTTCTCTCATTTTCTTCTGGA TCCATCATTGTGGTCACTGTGTGTGTCATAGCCGTCTGCTACATCTATATCCTCATCACCATCCTGAA GATGCGCTCCACTGAGGGGCACCACAAGGCCTTCTCCACCTGCACTTCCCACCTCACTGTGGTTACCC TGTTCTATGGGACCATTACCTTCATTTATGTGATGCCCAATTTTAGCTACTCAACTGACCAGAACAAG GTGGTGTCTGTGTTGTACACAGTGGTGATTCCCATGTTGAACCCCTTGATCTACAGCCTCAGGAACAA GGAGATTAAGGGGGCTCTGAAGAGAGAGCTTGTTAGAAAAATACTTTCTCATGATGCTTGTTATTTTA GTAGAACTTCAAATAATGATATTACATAGAACCCTATCTCTTCTCTTGAGAA
NOV30a, CG53776-02 SEQ ID NO: 372 345 aa MW at 38430.9kD Protein Sequence
MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMI ILCIYLVTISGNLSIIILI RISSQLHHPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQLGSAAFFATVECVFLAA MAYDRFVAICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTTSFYFLLFCGPNQVNHFFCDFAPLL ELSCSDISVSTWLSFSSGSI IWTVCVIAVCYIYILITILKMRSTEGHHKAFSTCTSHLTWTLFYG TITFIYVMPNFSYSTDQNKWSVLYTWIPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTS NNDIT
NOV30b, CG53776-03 SEQ ID NO: 373 1050 bp DNA Sequence ORF Start: at 207 jORF Stop: end of sequence
TTCTCAAGAGAAGAGATAGGGTTCTATGTAATATCATTATTTGAAGTTCTACTAAAATAACAAGCATC
ATGAGAAAGTATTTTTCTAACAAGCTCTCTCTTCAGAGCCCCCTTAATCTCCTTGTTCCTGAGGCTGT
AGATCAGGGGGTTCAACATGGGAATCACCACTGTGTACAACACAGACACCACCTTGTTCTGGTCAGTT
GAGTAGCTAAAATTGGGCATCACATAAATGAAGGTAATGGTCCCATAGAACAGGGTAACCACAGTGAG GTGGGAAGTGCAGGTGGAGAAGGCCTTGTGGTGCCCCTCAGTGGAGCGCATCTTCAGGATGGTGATGA GGATATAGATGTAGCAGACGGCTATGACACACACAGTGACCACAATGATGGATCCAGAAGAAAATGAG AGAACAACTGTGGAGACACTGATATCAGAACAGGAGAGTTCAAGTAAGGGAGCGAAATCACAGAAAAA ATGATTGACTTGATTTGGTCCACAGAAGAGTAAAAATAGAAGGAAGTAGTATAGGAGACAGCAATGAG AAAACCAGCTATGTAAACTACTAAGAGTAGCTGGACACTGACTTGTGTGGACATTTTGGTTGAATAAA GCAGTGGACTGCAAATTGCCACAAAGCGGTCATAGGCCATGGCAGCCAGAAGGACGCATTCGACTGTT GCAAAGAAAGCCGCTGAACCAAGCTGGATGGCACATCCAAGGTAGGAGACTGTATTTCTCTCCACCAG GAAGTTTACAAGCATGTTGGGTGTGACAGAAGATGAATAGGCCATGTCAGCAAAAGCCAAGTGGCTCA GAAAGAAATACATAGGATGATGGAGCTGAGAAGAAATTCTGATAAGAATAATTATGCTGAGATTACCA GATAGGATGATCATGAAGAGGATGACTCGAAGGATTGGATCATCTGTTAAGCCCAATAGGATGAACCC CGTCAGAGCGGTGTGATTCCCGTCCTTCAGGGAATTCATGAGACGAAGTAGCTGCTGACTAAATGAAC CCTAATGAGAACAGCACATTAAAATGTTAA
NOV30b, CG53776-03 SEQ ID NO: 374 33δ aa MW at 37640.9kD Protein Sequence
MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMI ILCGNLSII ILIRISSQLH HPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQLGSAAFFATVECVFLAAMAYDRFV AICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTTSFYFLLFCGPNQVNHFFCDFAPLLELSCSDI SVSTWLSFSSGSI IWTVCVIAVCYIYILITILKMRSTEGHHKAFSTCTSHLTWTLFYGTITFIYV MPNFSYSTDQNKWSVLYTWIPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTSNNDIT
NOV30c, CG53776-01 SEQ ID NO: 375 1070 bp DNA Sequence ORF Start: ATG at 27 ORF Stop: TAG at 1041
GAAGCCATCAAATTTATAACATTTTAATGTGCTGTTCTCATTTGGGTTCATTTAGTCAGCAGCTACTT
CGTCTCATGAATTCCCTGAAGGACGGGAATCACACCGCTCTGACGGGGTTCATCCTATTGGGCTTAAC AGATGATCCAATCCTTCGAGTCATCCTCTTCATGATCATCCTATCTGGTAATCTCAGCATAATTATTC TTATCAGAATTTCTTCTCAGCTCCATCATCCTATGTATTTCTTTCTGAGCCACTTGGCTTTTGCTGAC: ATGGCCTATTCATCTTCTGTCACACCCAACATGCTTGTAAACTTCCTGGTGGAGAGAAATACAGTCTC CTACCTTGGATGTGCCATCCAGCTTGGTTCAGCGGCTTTCTTTGCAACAGTCGAATGCGTCCTTCTGG CTGCCATGGCCTATGACCGCTTTGTGGCAATTTGCAGTCCACTGCTTTATTCAACCAAAATGTCCACA CAAGTCAGTGTCCAGCTACTCTTAGTAGTTTACATAGCTGGTTTTCTCATTGCTGTCTCCTATACTAC TTCCTTCTATTTTTTACTCTTCTGTGGACCAAATCAAGTCAATCATTTTTTCTGTGATTTCGCTCCCT TACTTGAACTCTCCTGTTCTGATATCAGTGTCTCCACAGTTGTTCTCTCATTTTCTTCTGGATCCATC ATTGTGGTCACTGTGTGTGTCATAGCCGTCTGCTACATCTATATCCTCATCACCATCCTGAAGATGCG CTCCACTGAGGGGCACCACAAGGCCTTCTCCACCTGCACTTCCCACCTCACTGTGGTTACCCTGTTCT ATGGGACCATTACCTTCATTTATGTGATGCCCAATTTTAGCTACTCAACTGACCAGAACAAGGTGGTG TCTGTGTTGTACACAGTGGTGATTCCCATGTTGAACCCCCTGATCTACAGCCTCAGGAACAAGGAGAT TAAGGGGGCTCTGAAGAGAGAGCTTGTTAGAAAAATACTTTCTCATGATGCTTGTTATTTTAGTAGAA CTTCAAATAATGATATTACATAGAACCCTATCTCTTCTCTTGAGAATACT
NOV30c, CG53776-01 SEQ ID NO: 376 33δ aa MW at 37590.δkD Protein Sequence
MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMIILSGNLSIIILIRISSQLH HPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQLGSAAFFATVECVLLAAMAYDRFV AICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTTSFYFLLFCGPNQVNHFFCDFAPLLELSCSDI SVSTWLSFSSGSIIWTVCVIAVCYIYILITILKMRSTEGHHKAFSTCTSHLTWTLFYGTITFIYV MPNFSYSTDQNKWSVLYTWIPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTSNNDIT
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 30B.
Table 30B. Comparison ofthe NOV30 protein sequences.
NOV3 Oa MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMIILCIYLVTISG NOV3 Ob MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMIILC G NOV30C MCCSHLGSFSQQLLRLMNSLKDGNHTALTGFILLGLTDDPILRVILFMIILS G
NOV3 Oa NLSIIILIRISSQLHHPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQL NOV3 Ob NLSIIILIRISSQLHHPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQL NOV30C NLSIIILIRISSQLHHPMYFFLSHLAFADMAYSSSVTPNMLVNFLVERNTVSYLGCAIQL
NOV30a GSAAFFATVECVFLAAMAYDRFVAICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTT NOV3 Ob GSAAFFATVECVFLAAMAYDRFVAICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTT NOV30C GSAAFFATVECVLLAAMAYDRFVAICSPLLYSTKMSTQVSVQLLLWYIAGFLIAVSYTT
NOV3 Oa SFYFLLFCGPNQVNHFFCDFAPLLELSCSDISVSTWLSFSSGSIIWTVCVIAVCYIYI NOV3 Ob SFYFLLFCGPNQVNHFFCDFAPLLELSCSDISVSTWLSFSSGSIIWTVCVIAVCYIYI NOV30C SFYFLLFCGPNQVNHFFCDFAPLLELSCSDISVSTWLSFSSGSIIWTVCVIAVCYIYI
NOV3 Oa LITILKMRSTEGHHKAFSTCTSHLTWTLFYGTITFIYVMPNFSYSTDQNKWSVLYTW NOV3 Ob LITILKMRSTEGHHKAFSTCTSHLTWTLFYGTITFIYVMPNFSYSTDQNKWSVLYTW NOV30C LITILKMRSTEGHHKAFSTCTSHLTWTLFYGTITFIYVMPNFSYSTDQNKWSVLYTW
NOV30a IPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTSNNDIT NOV3 Ob IPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTSNNDIT NOV30C IPMLNPLIYSLRNKEIKGALKRELVRKILSHDACYFSRTSNNDIT
NOV30a (SEQ ID NO 372) NOV3 Ob (SEQ ID NO 374) NOV30c (SEQ ID NO 376) Further analysis ofthe NOV30a protein yielded the following properties shown in Table 30C.
Table 30C. Protein Sequence Properties NOV30a
SignalP analysis: Cleavage site between residues 61 and 62
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 0 ; pos . chg 0 ; neg . chg 0 H-region : length 14 ; peak value 5 . 07 PSG score : 0 .67
GvH : von Heijne ' s method for signal seq. recognition GvH score (threshold : -2 . 1) : -5 .40 possible cleavage site : between 57 and 58
>>> Seems to have no N- terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood =-10, .56 Transmembrane 41 - 57
INTEGRAL Likelihood = -2, .07 Transmembrane 122 - 138
INTEGRAL Likelihood = -7, .70 Transmembrane 159 - 175
INTEGRAL Likelihood =-12, .68 Transmembrane 225 - 241
INTEGRAL Likelihood = -2, .13 Transmembrane 264 - 280
INTEGRAL Likelihood = -3, .66 Transmembrane 292 - 308
PERIPHERAL Likelihood = 1, .91 (at 58)
ALOM score : -12.68 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 48 Charge difference: 3.0 C( 2.0) - N(-1.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 3.87 Hyd Moment(95): 1.84 G content: 1 D/E content: 1 S/T content: 4 Score: -4.16
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 25 LRL|MN
NUCDISC: discrimination of nuclear localization signals pat4 : none pa 7: none bipartite: none content of basic residues: 5.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
44.4 % endoplasmic reticulum 22.2 % vacuolar 11.1 % Golgi 11.1 % vesicles of secretory system 11.1 % mitochondrial
>> prediction for CG53776-02 is end (k=9) A search ofthe NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30D.
Figure imgf000457_0001
In a BLAST search of public sequence databases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30E.
Figure imgf000458_0001
PFam analysis indicates that the NOV30a protein contains the domains shown in the Table 30F.
Figure imgf000458_0002
Example 31.
The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 31 A.
Figure imgf000458_0003
AGGAATCTGAGCATGGAGCCCACCTTTGCCCTTTTAGGTTTCACAGATTACCCAAAGCTTCAGATTCC TCTCTTCCTTGTGTTTCTGCTCATGTATGTTATCACAGTGGTAGGAAACCTTGGGATGATCATAATAA TCAAGATTAACCCCAAATTTCACACTCCTATGTACTTTTTCCTTAGTCACCTCTCTTTTGTTGATTTT TGTTACTCTTCCATTGTCACTCCCAAGCTGCTTGAGAACTTGGTAATGGCAGATAAAAGCATCTTCTA CTTTAGCTGCATGATGCAGTACTTCCTGTCCTGCACTGCTGTGGTGACAGAGTCTTTCTTGCTGGCAG TGATGGCCTATGACCGCTTTGTGGCCATCTGCAATCCTCTGCTTTATACAGTGGCCATGTCACAGAGG CTCTGTGCCCTGCTGGTGGCTGGGTCATATCTCTGGGGCATGTTTGGCCCCTTGGTACTCCTTTGTTA TGCTCTCCGGTTAAACTTCTCTGGACCTAATGTAATCAACCACTTCTTTTGTGAGTATACTGCTCTCA TCTCTGTGTCTGGCTCTGATATACTCATCCCCCACCTGCTGCTTTTCAGCTTCGCCACCTTCAATGAG ATGTGTACACTACTGATCATCCTCACTTCCTATGTTTTCATTTTTGTGACTGTACTAAAAATCCGTTC TGTTAGTGGGCGCCACAAAGCCTTCTCCACCTGGGCCTCCCACCTGACTGCTATCACCATCTTCCATG GGACCATCCTTTTCCTTTACTGTGTACCCAACTCCAAAAACTCTCGGCAAACAGTCAAAGTGGCCTCT GTATTTTACACAGTTGTCAACCCCATGCTGAACCCTCCGATCTACAGCCTAAGGAATAAAGACGTGAA GGATGCTTTCTGGAAGTTAATACATACACAAGTTCCATTTCACTGAACCAGTCTCAAAAGTTGTTTTC AATCCAAATGAACAACCCANNNNNNNNNN
NOV31a, CG53803-02 SEQ ID NO: 378 314 aa MW at 35790.4kD Protein Sequence
MMMVLRNLSMEPTFALLGFTDYPKLQIPLFLVFLLMYVITWGNLGMIIIIKINPKFHTPMYFFLSHL SFVDFCYSSIVTPKLLENLVMADKSIFYFSCMMQYFLSCTAVVTESFLLAVMAYDRFVAICNPLLYTV AMSQRLCALLVAGSYL GMFGPLVLLCYALRLNFSGPNVINHFFCEYTALISVSGSDILIPHLLLFSF ATFNEMCTLLIILTSYVFIFVTVLKIRSVSGRHKAFST ASHLTAITIFHGTILFLYCVPNSKNSRQT VKVASVFYTVVNPMLNPPIYSLRNKDVKDAFWKLIHTQVPFH
NOV31b, CG53803-01 SEQ ID NO: 379 1039 bp DNA Sequence ORF Start: ATG at 54 lORF Stop: TGA at 996
ATATTTTGCTTTGGCAGGAACAATTCTCTTCAACCCTTCCATTAAAAGGAATTATGATGATGGTTTTA
AGGAATCTGAGCATGGAGCCCACCTTTGCCCTTTTAGGTTTCACAGATTACCCAAAGCTTCAGATTCC TCTCTTCCTTGTGTTTCTGCTCATGTATGTTATCACAGTGGTAGGAAACCTTGGGATGATCATAATAA TCAAGATTAACCCCAAATTTCACACTCCTATGTACTTTTTCCTTAGTCACCTCTCTTTTGTTGATTTT TGTTACTCTTCCATTGTCACTCCCAAGCTGCTTGAGAACTTGGTAATGGCAGATAAAAGCATCTTCTA CTTTAGCTGCATGATGCAGTACTTCCTGTCCTGCACTGCTGTGGTGACAGAGTCTTTCTTGCTGGCAG TGATGGCCTATGACCGCTTTGTGGCCATCTGCAATCCTCTGCTTTATACAGTGGCCATGTCACAGAGG CTCTGTGCCCTGCTGGTGGCTGGGTCATATCTCTGGGGCATGTTTGGCCCCTTGGTACTCCTTTGTTA TGCTCTCCGGTTAAACTTCTCTGGACCTAATGTAATCAACCACTTCTTTTGTGAGTATACTGCTCTCA TCTCTGTGTCTGGCTCTGATATACTCATCCCCCACCTGCTGCTTTTCAGCTTCGCCACCTTCAATGAG ATGTGTACACTACTGATCATCCTCACTTCCTATGTTTTCATTTTTGTGACTGTACTAAAAATCCGTTC TGTTAGTGGGCGCCACAAAGCCTTCTCCACCTGGGCCTCCCACCTGACTGCTATCACCATCTTCCATG GGACCATCCTTTTCCTTTACTGTGTACCCAACTCCAAAAACTCTCGGCAAACAGTCAAAGTGGCCTCT GTATTTTACACAGTTGTCAACCCCATGCTGAACCCTCCGATCTACAGCCTAAGGAATAAAGACGTGAA GGATGCTTTCTGGAAGTTAATACATACACAAGTTCCATTTCACTGAACCAGTCTCAAAAGTTGTTTTC AATCCAAATGAACAACCCA
NOV31b, CG53δ03-01 SEQ ID NO: 3δ0 314 aa MW at 35790.4kD Protein Sequence
MMMVLRNLSMEPTFALLGFTDYPKLQIPLFLVFLLMYVITWGNLGMIIIIKINPKFHTPMYFFLSHL SFVDFCYSSIVTPKLLENLVMADKSIFYFSCMMQYFLSCTAWTESFLLAV AYDRFVAICNPLLYTV AMSQRLCALLVAGSYLWGMFGPLVLLCYALRLNFSGPNVINHFFCEYTALISVSGSDILIPHLLLFSF ATFNEMCTLLIILTSYVFIFVTVLKIRSVSGRHKAFSTWASHLTAITIFHGTILFLYCVPNSKNSRQT VKVASVFYTWNPMLNPPIYSLRNKDVKDAFWKLIHTQVPFH
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 3 IB.
Table 31B. Comparison of the NOV31 protein sequences.
NOV3la MMMVLRNLSMEPTFALLGFTDYPKLQIPLFLVFLLMYVITWGNLGMIIIIKINPKFHTP NOV3lb MMMVLRNLSMEPTFALLGFTDYPKLQIPLFLVFLLMYVITWGNLGMIIIIKINPKFHTP NOV31a MYFFLSHLSFVDFCYSSIVTPKLLENLVMADKSIFYFSCMMQYFLSCTAWTESFLLAVM
NOV31b MYFFLSHLSFVDFCYSSIVTPKLLENLVMADKSIFYFSCMMQYFLSCTAWTESFLLAVM
NOV3la AYDRFVAICNPLLYTVAMSQRLCALLVAGSYLWGMFGPLVLLCYALRLNFSGPNVINHFF
NOV3lb AYDRFVAICNPLLYTVAMSQRLCALLVAGSYLWGMFGPLVLLCYALRLNFSGPNVINHFF
NOV31a CEYTALISVSGSDILIPHLLLFSFATFNEMCTLLIILTSYVFIFVTVLKIRSVSGRHKAF
NOV31b CEYTALISVSGSDILIPHLLLFSFATFNEMCTLLIILTSYVFIFVTVLKIRSVSGRHKAF
NOV3la STWASHLTAITIFHGTILFLYCVPNSKNSRQTVKVASVFYTWNPMLNPPIYSLRNKDVK
NOV31b STWASHLTAITIFHGTILFLYCVPNSKNSRQTVKVASVFYTWNPMLNPPIYSLRNKDVK
NOV31a DAFWKLIHTQVPFH
NOV31b DAFWKLIHTQVPFH
NOV31a (SEQ ID NO: 378)
NOV31b (SEQ ID NO: 380)
Further analysis of the NOV31 a protein yielded the following properties shown in Table 31C.
Table 31C. Protein Sequence Properties NOV31a
SignalP analysis: Cleavage site between residues 44 and 45
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos . chg 1; neg.chg 1 H-region: length 9; peak value 9.41 PSG score: 5.01
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.06 possible cleavage site: between 43 and 44
>>> Seems to have a cleavable signal peptide (1 to 43)
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 44
Tentative number of TMS(s) for the threshold 0. 5:
INTEGRAL Likelihood -2.23 Transmembrane 104 120
INTEGRAL Likelihood -0.64 Transmembrane 145 161
INTEGRAL Likelihood -0.80 Transmembrane 186 202
INTEGRAL Likelihood -8.39 Transmembrane 212 228
INTEGRAL Likelihood -2.71 Transmembrane 247 263
PERIPHERAL Likelihood 2.07 (at 63)
ALOM score: -8.39 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 21
Charge difference: 3.0 C ( 1.0) - N ( -2.0)
C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75) : 7.94 Hyd Moment (95): 8.95 G content: 1 D/E content: 2 S/T content: 3 Score: -5.12
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 16 LRN|LS
NUCDISC: discrimination of nuclear localization signals pat4 : none pa 7: none bipartite: none content of basic residues: 6.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LLVAGSYLWGMFGPLVLLCYAL at 145 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
44.4 % endoplasmic reticulum
22.2 % vacuolar
22.2 % mitochondrial
11.1 % Golgi
>> prediction for CG53803-02 is end (k=9)
A search ofthe NOV3 la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3 ID.
45δ
Figure imgf000463_0001
In a BLAST search of public sequence databases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 3 IE.
Figure imgf000464_0001
PFam analysis indicates that the NOV31a protein contains the domains shown in the Table 3 IF.
Figure imgf000464_0002
Example 32.
The NOV32 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 32A. Table 32A. NOV32 Sequence Analysis
NOV32a, CG539δ9-03 SEQ ID NO: 3δl 1092 bp DNA Sequence ORF Start: ATG at 30 ORF Stop: TAG at 1047
CCGGGACAGTCACCTCCAGCAGCATCCTGATGTTCTGGGGACACTGGTGCTGGGGGGTCAGTGGGGAA
GGGCTCCTGGGTCCTCATGACCCTCTCCCTTGGGTGAGCACAAAACACCATGGCACTTTGGGGTCTTG GAAACAGACTAAAGGGGATGTCAAGTCCTCATTCCTTGGAGCTGCTGACGAGTCCAGAATGGGTCATG TTTTCTTGCCCCGACCCCAGCACCTCAGGGCAGCGGAAGGTCCAGAGAGAGGTCGGGGACCGGGGCCG CTCCTTGCATCCTGGGCTTGTGTCTGTTGCCCCCTGGCTGGTGACTTGCACTCTCCTGGAGCTGGTTC TTGCAGCCGAGGCCGTCACGGGGCTGGGATGTCGCTGCTGCTTCTCTTCGTGGTGTTGACCATTTCTC AGACCTCCCCCCGCCCCTGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTG AGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAG CCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGC TCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACC GGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAA GGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGT TTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGAC AACGGGGGCCCCCTCCTGTGCGGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAA ATTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACTCGCGTGACGAGCTACGTGTCCTGGATCCGCC AGTACGTCCCGCCGTTCCCCAGACGCTAGCTGGGGTGCAGTGGGGTCTGCATGATCCAGGAGGGCCCG TCTT
NOV32a, CG539δ9-03 SEQ ID NO: 3δ2 339 aa MW at 37349.5kD Protein Sequence
MF GHWCWGVSGEGLLGPHDPLP VSTKHHGTLGSWKQTKGDVKSSFLGAADESRMGHVFLPRPQHLR AAEGPERGRGPGPLLASWACVCCPLAGDLHSPGAGSCSRGRHGAGMSLLLLFWLTISQTSPRPCREE LEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSA SLDVPSGKTC VTGWGVIGRGELLP PLSL EATVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDML CAGDGNHGS PGDNGGPLLCGRNCT VQVEWS GKFCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32b, CG539δ9-04 SEQ ID NO: 3δ3 δδl bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAG at δ32
GCTCTGGGAAGACCCTCGTCCGTCCCCCTCATGAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACT
GGGGGCTGCGACGTCCCGGCCAGGAGGCACCCCTGGTAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAG TGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCAC CCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCC GGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGA AGACCTGCTGGGCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCA CAGGCCAGGTGGCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTC CAGGCGTGGGCAGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCA ACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTC ATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCC CCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAATTCTGCGGCC TTCGCGGCTATCCCGGCATGTACACTCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCG CCGTTCCCCAGACGCTAGCTGGGGTGCAGTGGGGTCTGCATGATCCAGGAGGGCCCGTCTAAGCG
NOV32b, CG539δ9-04 SEQ ID NO: 3δ4 267 aa MW at 30126.0kD Protein Sequence
MSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQ GGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTC AWAPDASWMASCRCRDG PQARWLRAAGM YYLTALQAERPHSRRGQELLPWPLSLWEATVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLCAGD GNHGS PGDNGGPLLCRRNCTWVQVEWS GKFCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32c, 306076095 SEQ ID NO: 385 819 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CGCAAGCTTATGAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCC AGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGT TCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTG TCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCAT CCACCCGGTCTCGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGCCTGGGCTC CAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTGGCTCAGAGCA GCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGCAGGAACTACT GCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCT GTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGT GCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTG CACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGT ACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCGTCGAC GCG
NOV32c, 306076095 SEQ ID NO: 3δό 273 aa MW at 30808.8kD Protein Sequence
RKLMSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRFYEDDQRTKWEIVRHPQYNESL SAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTC AWAPDASWMASCRCRDGWPQAR LRA AGMYYLTALQAERPHSRRGQELLP PLSLWEATVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLC AGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRRVD A
NOV32d, CG53989-01 SEQ ID NO: 3δ7 δ5δ bp DNA Sequence ORF Start: ATG at 1 IORF Stop: TAG at δ56
ATGCTGTGGCTACTGCTCCTGACCCTCCCCTGCCTGATGGGCTCTGTGCCCAGGAACCCAGGCGAGGG CACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGG TCAGCCTGAGGTTCTACAGCATGAAGAAGGGTCTGTGGGAGCCCATCTGTGGGGGCTCCCTCATCCAC CCAGAGTGGGTGCTGACCGCCGCCCACTGCCTTTTGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCA GGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCC AGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTG CCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGAC CTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCAGCTTGTGGG AGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAAC CACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTC CTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGG TGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTG TCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCTAG
NOV32d, CG539δ9-01 SEQ ID NO: 3δδ 2δ5 aa MW at 31927.6kD Protein Sequence
MLWLLLLTLPCLMGSVPRNPGEGTGRELVGITGGCDVSARRHP QVSLRFYSMKKGLWEPICGGSLIH PEWVLTAAHCLLEELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLEAPV PLSELIHPVSLPSASLDVPSGKTCVTGWGVIGRGELLP PLSLWEATVKVRSNVLCNQTCRRRFPSN HTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWS GKLCGLRGYPGMYTRVTSYV SWIRQYVPPFPRR
NOV32e, CG539δ9-02 SEQ ID NO: 3δ9 660 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTT TAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCC GTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAG GCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCGGGACGTGCCCTC GGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCA GCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTT CCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAA CCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGG TGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACG AGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGC NOV32e, CG53989-02 SEQ ID NO: 390 220 aa iMW at 24527.8kD Protein Sequence
SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLE APVPLSELIHPVSLPSASRDVPSGKTCWVTG GVIGRGELLPWPLSL EATVKVRSNVLCNQTCRRRF PSNHTERFERLIKDDMLCAGDGNHGS PGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVT SYVS IRQYVPPFPRR
NOV32f, CG539δ9-05 SEQ ID NO: 391 2δ47 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAG at 2845
ATGGTCAGCAAGGGGGGAGTTGCTGCAGAGCCAGAGCCACACTATTGTGAGGACAGTGAAAGAGGCCC CAACACCCTCACAGGTCCGGGCAGCCTTCCTAGAGGAGGTGGCATTGAGGTGGGCATGGAGTTTCCGG GATGCAGCGGTGAAGGGTGCGTGAAGCCCCATGAGGAGGCGGCCCGGGAGGGGGCGGGCAGAGGCAAG AGGGCTGTGCCGGGACCCAAGCGACGGCAGCAGGGGTCAGCAGAGGGGCCTGCGGCGGGGTGGACGCT GGAGCAGGAGACCAGGGGAGATGTCTTAGAGGATAAAAATGAGCGGGCAGATGAAGAGATACTCAGGC TGGCACCAGGGAAAGGCAGGCTCCCAATAGACAGCAAACACCTGAAACCGGTGATCAGCAGCTTCCCG GTAAGATCTCAGGAGCTGGGCGAGGGGGCTGGAGCAGGCACACTAAGAGGCAAAATGGCAGAGTTTAA CTGGTCTATGGCCTTCAAGGGACCTGCGGCTGGTCATGAAGAGCGCCTCAACTCTGTGTCCAGCAGGG CCAAGAAGGGCATTGGCTGGGATGTCGCTGCTGCTTCTCTTCGTGGTGTTGACCATTTCTCAGACCTC CCCCCGCCCCTGCAGGTCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAG GCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCC TGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTC ATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGG CTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGG TCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGTTT GAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAA CGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAAC TCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAG CCATGCCCCTCAGCTCAGACCCCTGCTGTGGTCCGAAGATTTGTGCTCCCCCCAAATCCAGATGTTGA AGCCCTAACTCCCAGTGTGATGGGATCAGGAGCGCCGCTGCCCCCGGCCCCCGACCTGCAAGAGGCCG AGGTCCCCATCATGAGGACCCGAGCTTGCGAGAGGATGTATCACAAAGGCCCCACTGCCCACGGCCAG GTCACCATCATCAAGGCTGCCATGCCGTGTGCAGGGAGGAAGGGGCAGGGTTCCTGCCAGGCCGCTCT GAGGACGGAGGACCTCACCCCAACCACACCCAACACGGAGGTGTCTCCACGTGCAGACCCCAGGCTGA GCCAGCCGGAGGACATCTGGCCAGAGTGGGCTTGGCCAGTTGTGGTGGGCACCACCATGCTGCTGCTG CTGCTGTTCCTGGCTGTCTCCTCCCTGGGGAGCTGTAGCACTGGGAGTCCAGCTCCCGTCCCCGAGAA TGACCTGGTGGGCATTGTGGGGGGCCACAACACCCCAGGGGAAGTGGTCGTGGCAGTGGGTGCTGACC GCCGCTCACTGCATTTTCCGGAAGGACACCGACCCGTCCACCTACCGGATTCACACCAGGGATGTGTA TCTGTACGGGGGCCGGGGGCTGCTGAATGTCAGCCAGATCGTCGTCCACCCAACTACTCTGTCTTCTT CCTGGGGGCAGACATCGCCCTGCTGAAGCTGGCCACCAGTTCCCTGGAGTTCACTGACAGTGACAACT GCTGGAACACAGGCTGGGGCATGGTCGGCTTGTTGGATATGCTGCCGCCTCCTTACCGCCCGCAGCAG GTGAAGGTCCTCACACTGAGCAATGCAGACTGTGAGCGGCAGACCTACGATGCTTTTCCTGGTGCTGG AGACAGAAAGTTCATCCAGGATGACATGATCTGTGCCGGCCGCACGGGCCGCCGCACCTGGAAGGGTG ACTCAGGCGGCCCCCTGGTCTGCAAGAAGAAGGGTACCTGGCTCCAGGCGGGAGTAGTGAGCTGGGGA TTTTACAGTGATCGGCCCAGCATTGGCGTCTACACACGCCCAGAGACCAGCTGGCAGGGTGCCAACCA TGCAGACGCCCAGAGACCAGCTGGCAGGGTGCCAACCATGCAGAGGCCCAGAGACATGGGCCAGGGCC AGGAGTGGGTCTGCAGGCCCTTCACCCACGTCACCTGCTACCCGACGGCCATCCCCAGGCCCTTCACC CATGTCACCTGCTACCTGATGGCTGTCCCCAGCACCCTCACCCACGTCACCTGCTACCCGACGGCCGT CCCCAGGCCCTTCACCCATGTCACCTGCTACCTGATGGCTGTCCCCAGCACCCTCACCCACATCACCT GCTACATGATGGCCGTCCCCAGGCCCTTTACCCACATCACCTGCTACCCAATGGCTGTCCCCAGCACC CTTACCCACGTCACCTGCCACCCGACGGCCATCCCCAGGCCCTTCACCCACATCACCTGCTACACGAT GGCCATCCCCAGGCCTTCAACCACGCCACCTGCTACACGACGGCCATCCCCAGCACCCTCACCCACGT CACCTGCTACACGATGGCCGTCCCCAGGCCCATCACCCATGTCACCTGCTACACGATAG
NOV32f, CG53989-05 SEQ ID NO: 392 94δ aa MW at 102839.3kD Protein Sequence
MVSKGGVAAEPEPHYCEDSERGPNTLTGPGSLPRGGGIEVGMEFPGCSGEGCVKPHEEAAREGAGRGK RAVPGPKRRQQGSAEGPAAGWTLEQETRGDVLEDKNERADEEILRLAPGKGRLPIDSKHLKPVISSFP VRSQELGEGAGAGTLRGKMAEFN SMAFKGPAAGHEERLNSVSSRAKKGIGWDVAAASLRGVDHFSDL PPPLQVREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLEAPVPLSEL IHPVSLPSASLDVPSGKTC VTG GVIGRGELLP PLSL EATVKVRSNVLCNQTCRRRFPSNHTERF ERLIKDDMLCAGDGNHGS PGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQ PCPSAQTPAWRRFVLPPNPDVEALTPSVMGSGAPLPPAPDLQEAEVPIMRTRACERMYHKGPTAHGQ VTIIKAAMPCAGRKGQGSCQAALRTEDLTPTTPNTEVSPRADPRLSQPEDIWPE AWPVWGTTMLLL LLFLAVSSLGSCSTGSPAPVPENDLVGIVGGHNTPGEWVAVGADRRSLHFPEGHRPVHLPDSHQGCV SVRGPGAAECQPDRRPPNYSVFFLGADIALLKLATSSLEFTDSDNC NTGWGMVGLLDMLPPPYRPQQ VKVLTLSNADCERQTYDAFPGAGDRKFIQDDMICAGRTGRRT KGDSGGPLVCKKKGT LQAGWS G FYSDRPSIGVYTRPETSWQGANHADAQRPAGRVPTMQRPRDMGQGQE VCRPFTHVTCYPTAIPRPFT HVTCYLMAVPSTLTHVTCYPTAVPRPFTHVTCYLMAVPSTLTHITCYMMAVPRPFTHITCYPMAVPST LTHVTCHPTAIPRPFTHITCYTMAIPRPSTTPPATRRPSPAPSPTSPATR PSPGPSPMSPATR
NOV32g, CG53989-06 SEQ ID NO: 393 660 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTT TAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCC GTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAG GCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCGGGACGTGCCCTC GGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCA GCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTT CCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAA CCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGG TGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACG AGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGC
NOV32g, CG53989-06 SEQ ID NO: 394 220 aa MW at 24527.8kD Protein Sequence
SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLE APVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGELLP PLSLWEATVKVRSNVLCNQTCRRRF PSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVT SYVSWIRQYVPPFPRR
NOV32h, CG53989-07 SEQ ID NO: 395 672 bp DNA Sequence ORF Start: at 7 ORF Stop: at 667
AGATCTTCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTG
CGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGA TCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAG CTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGT GCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGC CCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGC CGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGA CGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGG TCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGC GTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCCTCGAG
NOV32h, CG53989-07 SEQ ID NO: 396 220 aa MW at 24484.8kD Protein Sequence
SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLE APVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSL EATVKVRSNVLCNQTCRRRF PSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWS GKLCGLRGYPGMYTRVT SYVSWIRQYVPPFPRR
NOV32i, CG539δ9-0δ SEQ ID NO: 397 1171 bp DNA Sequence ORF Start: at 187 ORF Stop: TGA at 805
ATGCTGTGGCTACTGCTCCTGACCCTCCCCTGCCTGATGGGCTCTGTGCCCAGGAACCCAGGCGAGTC CGCCCCACCCAATGCCCCTGCTGCCCAGGACCCCCTCCTTGCCCTGCCCCGGGCTCAGAGTGCCAGCC CTGGGGTGGGTGGGGACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCG TCCGTCCCCCTCATGAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCG GCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGA GGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGC CTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCT CATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCG GCTGGGGTGTCATTGGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCG GAATGTCGGTGCAGGCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGG CCACAGGCCAGGTGGCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACA CTCCAGGCGTGGGCAGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGA
GCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGG
CTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGG
CCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCG
GCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTC
CCGCCGTTCCCCAGACGCTAGCTGGGGTGCAGTGGGGTCTGCATGATCCAGGAGGGCCCGTCTTCCTT
GTGGACACGCCTGCT
NOV32i, CG53989-08 SEQ ID NO: 398 206 aa MW at 22191.8kD Protein Sequence
ALGRPSSVPLMSPARGVSWWASLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRH PQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG GVIGRGGQEQDHLGG MWRDDPECRCRPGLQTRPG LPAAAETDGHRPGGSEQQECTISRLCRRNVHTPGVGRNYCPGPSACGR RR
NOV32J, CG539δ9-09 SEQ ID NO: 399 δ43 bp DNA Sequence ORF Start: ATG at 26 ORF Stop: TAG at 836
GAGGTGGAGGTTGCAGTAAGCCAAGATGGCGCCACTGCACTCTAGCCTGTTTCTGCTGAGCGGGACCA
TGAGCCCAAAAGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGTCAGC CTGAGGTTCTACAGCATGAAGAAGGGTCTGTGGGAGCCCATCTGTGGGGGCTCCCTCATCCACCCAGA GTGGGTGCTGACCGCCGCCCACTGCGTCGAGCTTGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGG TGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAG TACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCC GCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGTGCCCTCGGGGAAGACCT GCTGGGTGACCGGCTGGGGTGTCATTTGGGGACACGTTTTCCTGCTCCCGCCACCCCACCTCAGGGCA GCGGAAGGTCCAATCATGAGGACCCGAGCTTGCGAGAGGATGTATCACAAAGGCCCCACTGCCCACGT CACCATCATCAAGGCTGCCATGCCGTGTGCAGGGGCTGAGCGCCATCTCTCCCCACAGGGCGACAACG GGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGGTGGAGGTGGTGAGCTGGGGCAAACTC TGCGGCCTTCGCTATCCCGGCATGTACACCCGCGTGACGAGCTACGTGTCCTGGATCCGCCAGTACGT CCCGCCGTTCCCCAGACGCTAGCTGGG
NOV32J, CG539δ9-09 SEQ ID NO: 400 270 aa MW at 29993.6kD Protein Sequence
MAPLHSSLFLLSGTMSPKVGITGGCDVSARRHPWQVSLRFYSMKKGLWEPICGGSLIHPEWVLTAAHC VELEELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPV SLPSASLDVPSGKTCWVTGWGVIWGHVFLLPPPHLRAAEGPIMRTRACERMYHKGPTAHVTIIKAAMP CAGAERHLSPQGDNGGPLLCRRNCTWVQVEWSWGKLCGLRYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32k, CG539δ9-10 SEQ ID NO: 401 964 bp DNA Sequence ORF Start: ATG at 67 ORF Stop: TGA at 655
GACCATCTGATTGCCGGTCTCTCCTGGTGCCCCTGAGCTCTGGGAAGACCCTCGTCCGTCCCCCTCAT
GAGCCCGGCACGGGGCGTGAGCTGGTGGGCATCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCC CTGGCAGGGAGGAGTTGGAGGCTTGCGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGAC GACCAGCGGACGAAGGTGGTTGAGATCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGG CGGTGCGGACATCGCCCTGCTGAAGCTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCT CGCTCCCGTCTGCCTCCCGGGACGTGCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATT GGACGTGGAGGTCAGGAGCAGGACCACTTGGGTGGGATGTGGAGAGATGACCCGGAATGTCGGTGCAG GCCTGGGCTCCAGACGCGTCCTGGATGGCTTCCTGCCGCTGCCGAGACGGATGGCCACAGGCCAGGTG GCTCAGAGCAGCAGGAATGTACTATCTCACGGCTCTGCAGGCGGAACGTCCACACTCCAGGCGTGGGC AGGAACTACTGCCCTGGCCCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGT
Figure imgf000470_0001
DDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPF PRR
NOV32n, CG53989-13 SEQ ID NO: 407 870 bp DNA Sequence ORF Start: ATG at 43 ORF Stop: TAA at δ6δ
ATCTGGCCAGAGTGGGCTTGGCCAGTTGTGGTGGGCACCACCATGCTGCTGCTGCTGCTGTTCCTGGC
TGTCTCCTCCCTGGGGAGCTGTAGCACTGGGAGTCCAGCTCCCGTCCCCGAGAATGACCTGGTGGGCA TTGTGGGGGGCCACAACACCCAGGGGAAGTGGTCGTGGCAGGTCAGCCTGAGGATCTATAGCTACCAC TGGGCCTCCTGGGTGCCCATCTGCGGGGGCTCCCTCATCCACCCCCAGTGGGTGCTGACCGCCGCTCA CTGCATTTTCCGGAAGGACACCGACCCGTCCACCTACCGGATTCACACCAGGGATGTGTATCTGTACG GGGGCCGGGGGCTGCTGAATGTCAGCCAGATCGTCGTCCACCCCAACTACTCTGTCTTCTTCCTGGGG GCAGACATCGCCCTGCTGAAGCTGGCCACCAGTGTGAGAACAACAAACACTCTCGCGGCAGTCGCCCT GCCGTCATTGTCCCTGGAGTTCACTGACAGTGACAACTGCTGGAACACAGGCTGGGGCATGGTCGGCT TGTTGGATATGCTGCCGCCTCCTTACCGCCCGCAGCAGGTGAAGGTCCTCACACTGAGCAATGCAGAC TGTGAGCGGCAGACCTACGATGCTTTTCCTGGTGCTGGAGACAGAAAGTTCATCCAGGATGACATGAT CTGTGCCGGCCGCACGGGCCGCCGCACCTGGAAGGGTGACTCAGGCGGCCCCCTGGTCTGCAAGAAGA AGGGTACCTGGCTCCAGGCGGGAGTAGTGAGCTGGGGATTTTACAGTGATCGGCCCAGCATTGGCGTC TACACGTGGGTCCAGACCTATGTGCCCTGGATCCTGCAGCAAATGCACCTCTAA
NOV32n, CG539δ9-13 SEQ ID NO: 40δ 275 aa MW at 30467.7kD
Protein Sequence
MLLLLLFLAVSSLGSCSTGSPAPVPENDLVGIVGGHNTQGKWSWQVSLRIYSYHWASWVPICGGSLIH PQWVLTAAHCIFRKDTDPSTYRIHTRDVYLYGGRGLLNVSQIWHPNYSVFFLGADIALLKLATSVRT TNTLAAVALPSLSLEFTDSDNCWNTGWGMVGLLDMLPPPYRPQQVKVLTLSNADCERQTYDAFPGAGD RKFIQDDMICAGRTGRRTWKGDSGGPLVCKKKGTWLQAGWSWGFYSDRPSIGVYTWVQTYVPWILQQ MHL
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 32B.
Table 32B. Comparison ofthe NOV32 protein sequences.
NOV32a
N0V32b
N0V32C
N0V32d
NOV32e
NOV32f MVSKGGVAAEPEPHYCEDSERGPNTLTGPGSLPRGGGIEVGMEFPGCSGEGCVKPHEEAA
NOV32g
NOV32h
NOV32i
NOV32j
NOV32k
NOV321
NOV32m
NOV32n
NOV32a MFWGH CWGVSGEGLLGPHDPLPWVSTKHHGTLGSWKQTKGDVKS
NOV32b
NOV32c
NOV32d MLWLLLLTLP
NOV32e
NOV32f REGAGRGKRAVPGPKRRQQGSAEGPAAGWTLEQETRGDVLEDKNERADEEILRLAPGKGR
NOV32g
NOV32h NOV32i NOV32J -MAPLH NOV32k NOV321 -MPLLPSR NOV32m - - -MGSQR NOV32n MLLL
NOV32a SFLGAADESRMGHVFLPRPQHLRAAEGPERGRGPGPLLASWACVCCPLAGDLHSPGAGSC NOV32b MSPARG VSWWA SLGAATS NOV32C RKLMSPARG VSWWA SLGAATS NOV32d CLMGSVPRNPG EGTGRELVGITGGCDVSARRHPWQVS LR- -FYSMKKGLW NOV32e SLGAATS NOV32f LPIDSKHLKPVISSFPVRSQELGEGAGAGTLRGKMAEFNWSMAFKGPAAGHEERLNSVSS NOV32g SLGAATS NOV32h SLGAATS NOV32i ALGRPS-SVPLMSPARG VSWWA SLGAATS NOV3 J SSLFLLS GTMSPKVGITGGCDVSARRHPWQVS LR- -FYSMKKGLW NOV3 MSPARG VSWWA SLGAATS NOV321 SL VPLSSGKTLVRPPHEPGTGRELVGITGGCDVSARRHPWQVS LR- -FYSMKKGLW NOV32m CQGG- -G PGTGRELVGITGGCDVSARRHPWQVS LR- -FYSMKKGLW NOV32n LLFLAVSSLGSCSTGSPAPVPENDLVGIVGGHNTQG-KWSWQVSLR IYSYHWASW
NOV32a SRGR-HGAGMSLLLLFWLTISQTSPRPC-REELEACAFRVQVGQLRLYEDDQRTKWEI NOV32b RPG G TPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV32c RPG G TPG REELEACAFRVQVGQLRFYEDDQRTKWEI NOV32d EPIC-GG SLIHPEWVLTAAHCL-LEELEACAFRVQVGQLRLYEDDQRTKWEI NOV32e RPG GTPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV32f RAKKGIGWDVAAASLRGVDHFSDLPPPLQVREELEACAFRVQVGQLRLYEDDQRTKWEI NOV32g RPG GTPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV3 h RPG GTPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV32i RPG G TPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV3 J EPIC-GG SLIHPEWVLTAAHCVELEELEACAFRVQVGQLRLYEDDQRTKWEI NOV32k RPG G TPG REELEACAFRVQVGQLRLYEDDQRTKWEI NOV321 EPIC-GG SLIHPEWVLTAAHCLGPEELEACAFRVQVGQLRLYEDDQRTKWEI NOV32m EPIC-GG SLIHPEWVLTAAHCLGREELEACAFRVQVGQLRLYEDDQRTKWEI NOV32n VPIC-GG SLIHPQWVLTAAHCIFRKDTDPSTYRIHTRDVYLYGGRGLLNVSQI
NOV32a VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32b VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWAWAPDASW NOV32C VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWAWAPDASW NOV32d VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32e VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTG W NOV32f VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32g VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTG W NOV32h VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32i VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32J VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32k VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTG W NOV321 VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTG W NOV32m VRHPQYNESLSAQGGADIALLKLEAPVPLSELIHPVSLPSASRPGLQTRPGWLPA A NOV32n WHPNYSVFF LGADIALLKLATSVRTTNTLAAVALPSLSLEFTDSDNCWNTG W
NOV32a GVIG- -R-G ELLPWP LSLWEATVKVRSNV NOV32b MASCRCRDGWPQARWLRAAGMYYLTALQAERPHSR-R-GQELLPWPLSLWEATVKVRSNV
46δ NOV32C MASCRCRDGWPQARWLRAAGMYYLTALQAERPHSR-R-GQELLPWPLSLWEATVKVRSNV
NOV32d GVIG R GELLPWP LSLWEATVKVRSNV
NOV32e GVIG- -R-G ELLPWP LSLWEATVKVRSNV
NOV32f GVIG RG ELLPWP LSLWEATVKVRSNV
NOV32g GVIG- -R-G ELLPWP LSLWEATVKVRSNV
NOV32h GVIG- -R-G ELLPWP LSLWEATVKVRSNV
NOV32i GVIG- -RGGQEQD HLGGMWR DDPECRCRPGLQTRPGWLPAAAETDGHRPGG
NOV32j GVIW G HVFLLPP PHLRAAEGPIMR- -
NOV32k GVIG- -RGGQEQD HLGGMWR DDPECRCRPGLQTRPGWLPAAAETDGHRPGG
NOV321 GVIG R GELLPWP LSLWEATVKVRSNV
NOV32m AETD G QELLPWP LSLWEATVKVRSNV
NOV32n GMVG L LDMLP PPYRPQQVKVLT- -
NOV32a LCNQTCRRRFPSNHTERFER- IKDDMLCAGDGNHGSWPGDNGGPLLCGRNCTWVQVEW
NOV32b LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32c LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32d LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32e LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32f LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32g LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32h LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32i SEQQECT ISR-LCRRNVHTPGVG-RNYCPG PSACGRRR
NOV32J --TRACERMYHKGPTAHVT--IIKAAMPCAGAERHLSPQGDNGGPLLCRRNCTWVQVEW
NOV32k SEQQECT ISR-LCRRNVHTPGVG-RNYCPG PSACGRRR
NOV321 LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDERHLSPQGDNGGPLLCRRNCTWVQVEW
NOV32m LCNQTCRRRFPSNHTERFER-LIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEW
NOV32n LSNADCERQTYDAFPGAGDRKFIQDDMICAGRTGRRTWKGDSGGPLVCKKKGTWLQAGW
NOV32a SWGKFCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32b SWGKFCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32C SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRRVDA
NOV32d SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32e SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32f SWGKLCGLRGYPGMYTRVTSYVSWIRQPCPSAQTPAWRRFVLPPNPDVEALTPSVMGSG
NOV32g SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32h SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32i
NOV32j SWGKLCGLR-YPGMYTRVTSYVSWIRQYVPPFPRR
NOV32k
NOV321 SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32m SWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR
NOV32n SWGFYSDRP-SIGVYTWVQTYVPWILQQMHL
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e
NOV32f APLPPAPDLQEAEVPIMRTRACERMYHKGPTAHGQVTIIKAAMPCAGRKGQGSCQAALRT
NOV32g
NOV32h
NOV32i
NOV32j
NOV32k NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32C
NOV32d
NOV32e
NOV32f EDLTPTTPNTEVSPRADPRLSQPEDIWPEWAWPVWGTTMLLLLLFLAVSSLGSCSTGSP
NOV32g
NOV32h
NOV32i
NOV32J
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e
NOV32f APVPENDLVGIVGGHNTPGEVWAVGADRRSLHFPEGHRPVHLPDSHQGCVSVRGPGAAE
NOV32g
NOV32h
NOV32i
NOV32J
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32C
NOV32d
NOV32e
NOV32f CQPDRRPPNYSVFFLGADIALLKLATSSLEFTDSDNCWNTGWGMVGLLDMLPPPYRPQQV
NOV32g
NOV32h
NOV32i
NOV32J
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e NOV32f KVLTLSNADCERQTYDAFPGAGDRKFIQDDMICAGRTGRRTWKGDSGGPLVCKKKGTWLQ
NOV32g
NOV32h
NOV32i
NOV32J
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e
NOV32f AGWSWGFYSDRPSIGVYTRPETSWQGANHADAQRPAGRVPTMQRPRDMGQGQEWVCRPF
NOV32g
NOV32h
NOV32i
NOV32j
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e
NOV32f THVTCYPTAIPRPFTHVTCYLMAVPSTLTHVTCYPTAVPRPFTHVTCYLMAVPSTLTHIT
NOV32g
NOV32h
NOV32i
NOV32j
NOV32k
NOV321
NOV32m
NOV32n
NOV32a
NOV32b
NOV32c
NOV32d
NOV32e
NOV32f CYMMAVPRPFTHITCYPMAVPSTLTHVTCHPTAIPRPFTHITCYTMAIPRPSTTPPATRR
NOV32g
NOV32h
NOV32i
NOV32J
NOV32k
NOV321
NOV32m
NOV32n NOV32a NOV32b NOV32C NOV32d NOV32e NOV32f PSPAPSPTSPATRWPSPGPSPMSPATR
NOV32g
NOV32h NOV32i NOV32J
NOV32k NOV321 NOV32m NOV32n
NOV32a (SEQ ID NO 382)
NOV32b (SEQ ID NO 384)
NOV32C (SEQ ID NO 386)
NOV32d (SEQ ID NO 388)
NOV32e (SEQ ID NO 390)
NOV32f (SEQ ID NO 392)
NOV32g (SEQ ID O 394)
NOV32h (SEQ ID NO 396)
NOV32i (SEQ ID NO 398)
NOV32J (SEQ ID NO 400)
NOV32k (SEQ ID NO 402)
NOV321 (SEQ ID NO 404)
NOV32m (SEQ ID NO 406)
NOV32n (SEQ ID NO 408)
Further analysis ofthe NOV32a protein yielded the following properties shown in Table 32C.
Table 32C. Protein Sequence Properties NOV32a
SignalP analysis: Cleavage site between residues 13 and 14
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos. chg 0; neg.chg 0 H-region: length 12; peak value 6.67 PSG score: 2.27
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.63 possible cleavage site: between 34 and 35
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -2.76 Transmembrane 110 - 126
PERIPHERAL Likelihood = 1.80 (at 81)
ALOM score: -2.76 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 117 Charge difference: -2.0 C( 0.0) - N ( 2.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 2 (cytoplasmic tail 1 to 110)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 4.93 Hyd Moment(95): 1.50 G content: 5 D/E content: 2 S/T content: 1 Score: -9.83
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.6% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 15 LL at 82 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
34 . 8 % cytoplasmic
30 . 4 % mitochondrial
13 . 0 % Golgi
8 . 7 % endoplasmic reticulum
4 , . 3 % extracellular, including cell wall
4 , . 3 % nuclear
4 , . 3 % vesicles of secretory system
>> prediction for CG53989-03 is cyt (k=23)
A search ofthe NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32D.
Figure imgf000479_0001
In a BLAST search of public sequence databases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32E.
Figure imgf000480_0001
PFam analysis indicates that the NOV32a protein contains the domains shown in the Table 32F.
Figure imgf000480_0002
Example 33.
The NOV33 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 33 A.
Table 33A. NOV33 Sequence Analysis
NOV33a, CG54203-02 TSEQ ID NO: 409 1028 bp DNA Sequence ORF Start: ATG at 1 g ORF Stop: TGA at 975
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33a, CG54203-02 SEQ ID NO: 410 319 aa MW at 35072.3kD Protein Sequence
MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MSKAAYMPMAASSWAIGGAASVVHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLR KDVKAAVRRLLRPKGFTQ
NOV33b, CG54203-01 SEQ ID NO: 411 1031 bp DNA Sequence ORF Start: ATG at 22 JORF Stop: TGA at 979
TGATGGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCT
GAGGCTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGA TCCTGCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTAC TTCTTCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGA CAGCTTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTG CCATGGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAAC CCCCTTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTAT TGGTGGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCA TCAACCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTG ATCAGCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGT CTTCATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCT CTGCCCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCT AAGGACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGT GACCCCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGAC TGCTGAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAG TAAGGAATCAC
NOV33b, CG54203-01 SEQ ID NO: 412 319 aa MW at 35171.4kD Protein Sequence
MEKANETSPVMGFVLLRLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MSKAAYMPMAASS AIGGAASWHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISI VISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLRNKDVKAAVRRLLRPKGFTQ
NOV33c, SNP133δ2442 of SEQ ID NO: 413 102δ bp CG54203-02, DNA Sequence ORF Start: ATG at lδ ORF Stop: TGA at 975 SNP Pos: 66 SNP Change: G to A
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGAGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33c, SNP133δ2442 of SEQ ID NO: 414 319 aa MW at 35171.4kD CG54203-02, Protein Sequence SNP Pos: 17 SNP Change: Gly to Arg
MEKANETSPVMGFVLLRLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MSKAAYMPMAASSWAIGGAASWHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGVVTPMLNPIIYSLRNKDVKAAVRRLLRPKGFTQ
NOV33d, SNP13373δδO of SEQ ID NO: 415 102δ bp CG54203-02, DNA Sequence ORF Start: ATG at lδ ORF Stop: TGA at 975
SNP Pos: 324 SNP Change: G to A
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGACACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33d, SNP13373δδO of SEQ ID NO: 416 319 aa MW at 35102.3kD CG54203-02, Protein Sequence SNP Pos: 103 SNP Change: Ala to Thr
MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMTLSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MSKAAYMPMAASS AIGGAASVVHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLRNKDVKAAVRRLLRPKGFTQ
NOV33e, SNPl 3373881 of SEQ ID NO: 417 1028 bp CG54203-02, DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 975
SNP Pos: 429 SNP Change: A to G
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGGGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33e, SNP133738δl of SEQ ID NO: 41 δ 319 aa MW at 35042.3kD CG54203-02, Protein Sequence SNP Pos: 138 SNP Change: Ser to Gly
MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MGKAAYMPMAASS AIGGAASVVHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNP11YSLRNKDVKAAVRRLLRPKGFTQ
NOV33f, SNP13382443 of SEQ ID NO: 419 1028 bp CG54203-02, DNA Sequence ORF Start: ATG at lδ ORF Stop: TGA at 975
SNP Pos: 444 SNP Change: A to G
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACGTGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33f, SNPl 3382443 of SEQ ID NO: 420 319 aa MW at 35040.2kD CG54203-02, Protein Sequence SNP Pos: 143 SNP Change: Met to Val
MEKA ETSPV GFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSIWLAFDRYVAICNPLRYSVI MSKAAYVPMAASS AIGGAASVVHTSLAIQLPFCGD VINHFTCEILAVLKLACADISI VISMEVTN VIFLGVPVLFISFSYWIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLR KDVKAAVRRLLRPKGFTQ
NOV33g, SNP13373844 of SEQ ID NO: 421 102δ bp CG54203-02, DNA Sequence ORF Start: ATG at lδ ORF Stop: TGA at 975
SNP Pos: 719 SNP Change: G to A
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGAAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACCGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33g, SNP13373δ44 of SEQ ID NO: 422 319 aa MW at 35072.3kD CG54203-02, Protein Sequence SNP Pos: 234 SNP Change: Gly to Gly
MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAIC PLRYSVI MSKAAYMPMAASS AIGGAASVVHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVISMEVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLRNKDVKAAVRRLLRPKGFTQ
NOV33h, SNPl 3373883 of SEQ ID NO: 423 102δ bp CG54203-02, DNA Sequence ORF Start: ATG at 18 ORF Stop: TGA at 975
SNP Pos: 75δ SNP Change: C to T
TGCAGAGGGGATATCACATGGAAAAAGCCAATGAGACCTCCCCTGTGATGGGGTTCGTTCTCCTGGGG
CTCTCTGCCCACCCAGAGCTGGAAAAGACATTCTTCGTGCTCATCCTGCTGATGTACCTCGTGATCCT GCTGGGCAATGGGGTCCTCATCCTGGTGACCATCCTTGACTCCCGCCTGCACACGCCCATGTACTTCT TCCTAGGGAACCTCTCCTTCCTGGACATCTGCTTCACTACCTCCTCAGTCCCACTGGTCCTGGACAGC TTTTTGACTCCCCAGGAAACCATCTCCTTCTCAGCCTGTGCTGTGCAGATGGCACTCTCCTTTGCCAT GGCAGGAACAGAGTGCTTGCTCCTGAGCATGATGGCATTTGATCGCTATGTGGCCATCTGCAACCCCC TTAGGTACTCCGTGATCATGAGCAAGGCTGCCTACATGCCCATGGCTGCCAGCTCCTGGGCTATTGGT GGTGCTGCTTCCGTGGTACACACATCCTTGGCAATTCAGCTGCCCTTCTGTGGAGACAATGTCATCAA CCACTTCACCTGTGAGATTCTGGCTGTTCTAAAGTTGGCCTGTGCTGACATTTCCATCAATGTGATCA GCATGGAGGTGACGAATGTGATCTTCCTAGGAGTCCCGGTTCTGTTCATCTCTTTCTCCTATGTCTTC ATCATCACCACCATCCTGAGGATCCCCTCAGCTGAGGGGAGGAAAAAGGTCTTCTCCACCTGCTCTGC CCACCTCACTGTGGTGATCGTCTTCTACGGGACCTTATTCTTCATGTATGGGAAGCCTAAGTCTAAGG ACTCCATGGGAGCAGACAAAGAGGATCTTTCAGACAAACTCATCCCCCTTTTCTATGGGGTGGTGACC CCGATGCTCAACCCCATCATCTATAGCCTGAGGAACAAGGATGTGAAGGCTGCTGTGAGGAGACTGCT GAGACCAAAAGGCTTCACTCAGTGATGGTGGAAGGGTCCTCTGTGATTGTCACCCACATGGAAGTAAG GAATCACA
NOV33h, SNP13373δδ3 of SEQ ID NO: 424 319 aa MW at 35072.3kD CG54203-02, Protein Sequence SNP Pos: 247 SNP Change: Thr to Thr
MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPMYFFLGNLS FLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMAFDRYVAICNPLRYSVI MSKAAYMPMAASSWAIGGAASVVHTSLAIQLPFCGDNVINHFTCEILAVLKLACADISINVIS EVTN VIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFSTCSAHLTWIVFYGTLFFMYGKPKSKDSMGAD KEDLSDKLIPLFYGWTPMLNPIIYSLRNKDVKAAVRRLLRPKGFTQ
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 33B.
Table 33B. Comparison ofthe NOV33 protein sequences.
NOV33a MEKANETSPVMGFVLLGLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPM
NOV33b MEKA ETSPVMGFVLLRLSAHPELEKTFFVLILLMYLVILLGNGVLILVTILDSRLHTPM
NOV33a YFFLGNLSFLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFA AGTECLLLSMMA
NOV33b YFFLGNLSFLDICFTTSSVPLVLDSFLTPQETISFSACAVQMALSFAMAGTECLLLSMMA
NOV33a FDRYVAICNPLRYSVIMSKAAYMP AASSWAIGGAASWHTSLAIQLPFCGDNVINHFTC NOV33b FDRYVAICNPLRYSVIMSKAAYMPMAASS AIGGAASWHTSLAIQLPFCGDNVINHFTC
NOV33a EILAVLKLACADISI VISMEVTNVIFLGVPVLFISFSYVFIITTILRIPSAEGRK VFS
NOV33b EILAVLKLACADISINVISMEVTNVIFLGVPVLFISFSYVFIITTILRIPSAEGRKKVFS
NOV33a TCSAHLTWIVFYGTLFFMYGKPKSKDSMGADKEDLSDKLIPLFYGWTPMLNPIIYSLR
NOV33b TCSAHLTWIVFYGTLFFMYGKPKSKDS GADKEDLSDKLIPLFYGWTPMLNPIIYSLR
NOV33a NKDVKAAVRRLLRPKGFTQ
NOV33b NKDVKAAVRRLLRPKGFTQ
NOV33a (SEQ ID NO: 410)
NOV33b (SEQ ID NO: 412)
Further analysis ofthe NOV33a protein yielded the following properties shown in Table 33C.
Table 33C. Protein Sequence Properties NOV33a
SignalP analysis: Cleavage site between residues 45 and 46
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 6; pos . chg 1; neg.chg 2 H-region: length 16; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.59 possible cleavage site: between 44 and 45
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0, 5: 7
INTEGRAL Likelihood -9.50 Transmembrane 31 - 47
INTEGRAL Likelihood -0.22 Transmembrane 67 - 83
INTEGRAL Likelihood -0.32 Transmembrane 93 - 109
INTEGRAL Likelihood -3.77 Transmembrane 182 - 198
INTEGRAL Likelihood -6.95 Transmembrane 206 - 222
INTEGRAL Likelihood -1.81 Transmembrane 242 - 258
INTEGRAL Likelihood -0.22 Transmembrane 280 - 296
PERIPHERAL Likelihood 2.38 (at 151)
ALOM score : -9.50 (number of TMSs : 7)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 38 Charge difference: 1.0 C( 0.5) - N(-0.5) C > N: C-terminal side will be inside
>>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 6.12 Hyd Moment (95): 11.03 G content: 0 D/E content : 2 S/T content : 0 Score: -6.47
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 7.2% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus : KGFT
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
11.1 %: mitochondrial
11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: Golgi
>> prediction for CG54203- 02 is end (k=9)
A search ofthe NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33D.
Figure imgf000487_0001
In a BLAST search of public sequence databases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33E.
Figure imgf000488_0001
PFam analysis indicates that the NOV33a protein contains the domains shown in the Table 33F.
Figure imgf000488_0002
Example 34.
The NOV34 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 34A. Table 34A. NOV34 Sequence Analysis
NOV34a, CG54212-02 SEQ ID NO: 425 1953 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: TGA at 947
ACTCTGCAGCATGGAGCCGCTCAACAGAACAGAGGTGTCCGAGTTCTTTCTGAAAGGATTTTCTGGCT
ACCCAGCCCTGGAGCATCTGCTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAAC ACAGCCATCATGGCGGTGAGCGTGCTAGATATCCACCTGCACACGCCTGTGTACTTCTTCCTGGGCAA CCTCTCTACCCTGGACATCTGCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCAT CCCGGAAGACCATCTCCTTTGCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACG GAGTGCCTGCTACTGGCCATCACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCG CGTGCTCATGAGCCACCGGCTCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGT CGGTGACTGAGATGGTCATCTCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACC TGCAAGATCCTGGCAGTGCTGAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGC GGGCTCCATCCTGCTGCTGCCTGTACCCCTGGCATTCATCTGCCTGTCCTACTTGCTCATCCTGGCCA CCATCCTGAGGGTGCCCTCGGCCGCCAGGTGCTGCAAAGCCTTCTCCACCTGCTTGGCACACCTGGCT GTAGTGCTGCTTTTCTACGGCACCATCATCTTCATGTACTTGAAGCCCAAGAGTAAGGAAGCCCACAT CTCTGATGAGGTCTTCACAGTCCTCTATGCCATGGTCACGACCATGCTGAACCCCACCATCTACAGCC TGAGGAACAAGGAGGTGAAGGAGGCCGCCAGGAAGGTGTGGGGCAGGAGTCGGGCCTCCAGGTGAGGG A
NOV34a, CG54212-02 SEQ ID NO: 426 312 aa MW at 34707.2kD Protein Sequence
MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVYFFLGNLST LDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYRVLM SHRLCVLLMGAAVLCLLKSVTEMVISMRLPFCGHHWSHFTCKILAVLKLACGNTSVSEDFLLAGSI LLLPVPLAFICLSYLLILATILRVPSAARCCKAFSTCLAHLAWLLFYGTIIFMYLKPKSKEAHISDE VFTVLYAMVTTMLNPTIYSLRNKEVKEAARKV GRSRASR
NOV34b, CG54212-01 SEQ ID NO: 427 1050 bp DNA Sequence ORF Start: ATG at 59 ORF Stop: TGA at 995
CCCTGTACCCTCTCTCCTTCCATCCCAGCTGTGGACCATCTCTTCAGAACTCTGCAGCATGGAGCCGC
TCAACAGAACAGAGGTGTCCGAGTTCTTTCTGAAAGGATTTTCTGGCTACCCAGCCCTGGAGCATCTG CTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAACACAGCCATCATGGCGGTGAG CGTGCTAGATATCCACCTGCACACGCCCGTGTACTTCTTCCTGGGCAACCTCTCTACCCTGGACATCT GCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCATCCCGGAAGACCATCTCCTTT GCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACGGAGTGCCTGCTACTGGCCAT CACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCACGTGCTCATGAGCCACCGGC TCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGTCGGTGACTGAGATGGTCATC TCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACCTGCAAGATCCTGGCAGTGCT GAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGCGGGCTCCATCCTGCTGCTGC CTGTACCCCTGGCATTCATCTGCCTGTCCTACTTGCTCATCCTGGCCACCATCCTGAGGGTGCCCTCG GCCGCCAGGTGCTGCAAAGCCTTCTCCACCTGCTTGGCACACCTGGCTGTAGTGCTGCTTTTCTACGG CACCATCATCTTCATGTACTTGAAGCCCAAGAGTAAGGAAGCCCACATCTCTGATGAGGTCTTCACAG TCCTCTATGCCATGGTCACGACCATGCTGAACCCCACCATCTACAGCCTGAGGAACAAGGAGGTGAAG GAGGCCGCCAGGAAGGTGTGGGGCAGGAGTCGGGCCTCCAGGTGAGGGAGGGCGGGGCTCTGTACAGA CGCAGGTCTCAGGTTAGTAGCTGAGGCCAT
NOV34b, CG54212-01 SEQ ID NO: 42δ 312 aa MW at 346δδ.2kD Protein Sequence
MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVYFFLGNLST LDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYHVLM SHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCKILAVLKLACGNTSVSEDFLLAGSI LLLPVPLAFICLSYLLILATILRVPSAARCCKAFSTCLAHLAWLLFYGTIIFMYLKPKSKEAHISDE VFTVLYAMVTTMLNPTIYSLRNKEVKEAARKVWGRSRASR
NOV34c, CG54212-03 SEQ ID NO: 429 917 bp DNA Sequence ORF Start: at 3 ORF Stop: TGA at 861
TGCTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAACACAGCCATCATGGCGGTG AGCGTGCTAGATATCCACCTGCACACGCCCGTGTACTTCTTCCTGGGCAACCTCTCTACCCTGGACAT CTGCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCATCCCGGAAGACCATCTCCT TTGCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACGGAGTGCCTGCTACTGGCC ATCACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCACGTGCTCATGAGCCACCG GCTCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGTCGGTGACTGAGATGGTCA TCTCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACCTGCAAGATCCTGGCAGTG CTGAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGCGGGCTCCATCCTGCTGCT GCCTGTACCCCTGGCATTCATCTGCCTGTCCTACTTGCTCATCCTGGCCACCATCCTGAGGGTGCCCT CGGCCGCCAGGTGCTGCAAAGCCTTCTCCACCTGCTTGGCACACCTGGCTGTAGTGCTGCTTTTCTAC GGCACCATCATCTTCATGTACTTGAAGCCCAAGAGTAAGGAAGCCCACATCTCTGATGAGGTCTTCAC AGTCCTCTATGCCATGGTCACGACCATGCTGAACCCCACCATCTACAGCCTGAGGAACAAGGAGGTGA AGGAGGCCGCCAGGAAGGTGTGGGGCAGGAGTCGGGCCTCCAGGTGAGGGAGGGCGGGGCTCTGTACA GACGCAGGTCTCAGGTTAGTAGCTGAGGCCATC
NOV34c, CG54212-03 SEQ ID NO: 430 286 aa MW at 31693.δkD Protein Sequence
LFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVYFFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISF AVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYHVLMSHRLCVLLMGAAWVLCLLKSVTEMVI SMRLPFCGHHWSHFTCKILAVLKLACGNTSVSEDFLLAGSILLLPVPLAFICLSYLLILATILRVPS AARCCKAFSTCLAHLAVVLLFYGTIIFMYLKPKSKEAHISDEVFTVLYAMVTTMLNPTIYSLRNKEVK EAARKVWGRSRASR
NOV34d, CG54212-04 SEQ ID NO: 431 1025 bp DNA Sequence ORF Start: ATG at 33 ORF Stop: TGA at 969
AGCTGTGGACCATCTCTTCAGAACTCTGCAGCATGGAGCCGCTCAACAGAACAGAGGTGTCCGAGTTC
TTTCTGAAAGGATTTTCTGGCTACCCAGCCCTGGAGCATCTGCTCTTCCCTCTGTGCTCAGCCATGTA CCTGGTGACCCTCCTGGGGAACACAGCCATCATGGCGGTGAGCGTGCTAGATATCCACCTGCACACGC CCGTGTACTTCTTCCTGGGCAACCTCTCTACCCTGGACATCTGCTACACGCCCACCTTTGTGCCTCTG ATGCTGGTCCACCTCCTGTCATCCCGGAAGACCATCTCCTTTGCTGTCTGTGCCATCCAGATGTGTCT GAGCCTGTCCACGGGCTCCACGGAGTGCCTGCTACTGGCCATCACGGCCTATGACCGCTACCTGGCCA TCTGCCAGCCACTCAGGTACCACGTGCTCATGAGCCACCGGCTCTGCGTGCTGCTGATGGGAGCTGCC TGGGTCCTCTGCCTCCTCAAGTCGGTGACTGAGATGGTCATCTCCATGAGGCTGCCCTTCTGTGGCCA CCACGTGGTCAGTCACTTCACCTGCAAGATCCTGGCAGTGCTGAAGCTGGCATGCGGCAACACGTCGG TCAGCGAAGACTTCCTGCTGGCGGGCTCCATCCTGCTGCTGCCTGTACCCCTGGCATTCATCTGCCTG TCCTACTTGCTCATCCTGGCCACCATCCTGAGGGTGCCCTCGGCCGCCAGGTGCTGCAAAGCCTTCTC CACCTGCTTGGCACACCTGGCTGTAGTGCTGCTTTTCTACGGCACCATCATCTTCATGTACTTGAAGC CCAAGAGTAAGGAAGCCCACATCTCTGATGAGGTCTTCACAGTCCTCTATGCCATGGTCACGACCATG CTGAACCCCACCATCTACAGCCTGAGGAACAAGGAGGTGAAGGAGGCCGCCAGGAAGGTGTGGGGCAG GAGTCGGGCCTCCAGGTGAGGGAGGGCGGGGCTCTGTACAGACGCAGGTCTCAGGTTAGTAGCTGAGG CCATC
NOV34d, CG54212-04 SEQ ID NO: 432 312 aa MW at 346δ8.2kD Protein Sequence
MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVYFFLGNLST LDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYHVLM SHRLCVLLMGAA VLCLLKSVTEMVISMRLPFCGHHVVSHFTCKILAVLKLACGNTSVSEDFLLAGSI LLLPVPLAFICLSYLLILATILRVPSAARCCKAFSTCLAHLAWLLFYGTIIFMYLKPKSKEAHISDE VFTVLYAMVTTMLNPTIYSLRNKEVKEAARKV GRSRASR
NOV34e, SNPl 3373981 of SEQ ID NO: 433 953 bp CG54212-02, DNA Sequence ORF Start: ATG at 11 ORF Stop: TGA at 947
SNP Pos: 184 SNP Change: T to C
ACTCTGCAGCATGGAGCCGCTCAACAGAACAGAGGTGTCCGAGTTCTTTCTGAAAGGATTTTCTGGCT
ACCCAGCCCTGGAGCATCTGCTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAAC ACAGCCATCATGGCGGTGAGCGTGCTAGATATCCACCTGCACACGCCCGTGTACTTCTTCCTGGGCAA CCTCTCTACCCTGGACATCTGCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCAT CCCGGAAGACCATCTCCTTTGCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACG GAGTGCCTGCTACTGGCCATCACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCG CGTGCTCATGAGCCACCGGCTCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGT CGGTGACTGAGATGGTCATCTCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACC TGCAAGATCCTGGCAGTGCTGAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGC GGGCTCCATCCTGCTGCTGCCTGTACCCCTGGCATTCATCTGCCTGTCCTACTTGCTCATCCTGGCCA CCATCCTGAGGGTGCCCTCGGCCGCCAGGTGCTGCAAAGCCTTCTCCACCTGCTTGGCACACCTGGCT GTAGTGCTGCTTTTCTACGGCACCATCATCTTCATGTACTTGAAGCCCAAGAGTAAGGAAGCCCACAT CTCTGATGAGGTCTTCACAGTCCTCTATGCCATGGTCACGACCATGCTGAACCCCACCATCTACAGCC TGAGGAACAAGGAGGTGAAGGAGGCCGCCAGGAAGGTGTGGGGCAGGAGTCGGGCCTCCAGGTGAGGG A
NOV34e, SNP133739δl of SEQ ID NO: 434 312 aa MW at 34707.2kD CG54212-02, Protein Sequence SNP Pos: 5δ SNP Change: Pro to Pro
MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVYFFLGNLST LDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYRVLM SHRLCVLLMGAA VLCLLKSVTEMVISMRLPFCGHHWSHFTCKILAVLKLACGNTSVSEDFLLAGSI LLLPVPLAFICLSYLLILATILRVPSAARCCKAFSTCLAHLAWLLFYGTIIFMYLKPKSKEAHISDE VFTVLYAMVTTMLNPTIYSLRNKEVKEAARKVWGRSRASR
NOV34f, SNP133739δ2 of SEQ ID NO: 435 953 bp CG54212-02, DNA Sequence ORF Start: ATG at 11 ORF Stop: TGA at 947
SNP Pos: lδδ SNP Change: T to C
ACTCTGCAGCATGGAGCCGCTCAACAGAACAGAGGTGTCCGAGTTCTTTCTGAAAGGATTTTCTGGCT
ACCCAGCCCTGGAGCATCTGCTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAAC ACAGCCATCATGGCGGTGAGCGTGCTAGATATCCACCTGCACACGCCTGTGCACTTCTTCCTGGGCAA CCTCTCTACCCTGGACATCTGCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCAT CCCGGAAGACCATCTCCTTTGCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACG GAGTGCCTGCTACTGGCCATCACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCG CGTGCTCATGAGCCACCGGCTCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGT CGGTGACTGAGATGGTCATCTCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACC TGCAAGATCCTGGCAGTGCTGAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGC GGGCTCCATCCTGCTGCTGCCTGTACCCCTGGCATTCATCTGCCTGTCCTACTTGCTCATCCTGGCCA CCATCCTGAGGGTGCCCTCGGCCGCCAGGTGCTGCAAAGCCTTCTCCACCTGCTTGGCACACCTGGCT GTAGTGCTGCTTTTCTACGGCACCATCATCTTCATGTACTTGAAGCCCAAGAGTAAGGAAGCCCACAT CTCTGATGAGGTCTTCACAGTCCTCTATGCCATGGTCACGACCATGCTGAACCCCACCATCTACAGCC TGAGGAACAAGGAGGTGAAGGAGGCCGCCAGGAAGGTGTGGGGCAGGAGTCGGGCCTCCAGGTGAGGG A
NOV34f, SNP133739δ2 of SEQ ID NO: 436 312 aa MW at 346δl.2kD CG54212-02, Protein Sequence SNP Pos: 60 SNP Change: Tyr to His
MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVHFFLGNLST LDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAYDRYLAICQPLRYRVLM SHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCKILAVLKLACGNTSVSEDFLLAGSI LLLPVPLAFICLSYLLILATILRVPSAARCCKAFSTCLAHLAWLLFYGTIIFMYLKPKSKEAHISDE VFTVLYAMVTTMLNPTIYSLRNKEVKEAARKWϊGRSRASR
NOV34g, SNPl 3373984 of SEQ ID NO: 437 953 bp CG54212-02, DNA Sequence ORF Start: ATG at 11 ORF Stop: TGA at 947
SNP Pos: 408 SNP Change: G to A
ACTCTGCAGCATGGAGCCGCTCAACAGAACAGAGGTGTCCGAGTTCTTTCTGAAAGGATTTTCTGGCT
ACCCAGCCCTGGAGCATCTGCTCTTCCCTCTGTGCTCAGCCATGTACCTGGTGACCCTCCTGGGGAAC ACAGCCATCATGGCGGTGAGCGTGCTAGATATCCACCTGCACACGCCTGTGTACTTCTTCCTGGGCAA CCTCTCTACCCTGGACATCTGCTACACGCCCACCTTTGTGCCTCTGATGCTGGTCCACCTCCTGTCAT CCCGGAAGACCATCTCCTTTGCTGTCTGTGCCATCCAGATGTGTCTGAGCCTGTCCACGGGCTCCACG GAGTGCCTGCTACTGGCCATCACGGCCTATGACCGCTACCTGGCCATCTGCCAGCCACTCAGGTACCA CGTGCTCATGAGCCACCGGCTCTGCGTGCTGCTGATGGGAGCTGCCTGGGTCCTCTGCCTCCTCAAGT CGGTGACTGAGATGGTCATCTCCATGAGGCTGCCCTTCTGTGGCCACCACGTGGTCAGTCACTTCACC TGCAAGATCCTGGCAGTGCTGAAGCTGGCATGCGGCAACACGTCGGTCAGCGAAGACTTCCTGCTGGC
Figure imgf000492_0001
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 34B.
Table 34B. Comparison of the NOV34 protein sequences.
NOV34a MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVY
NOV34b MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVY
NOV34C LFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVY
NOV34d MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMAVSVLDIHLHTPVY
NOV34a FFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAY
NOV34b FFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAY
NOV34C FFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAY
4δδ NOV34d FFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISFAVCAIQMCLSLSTGSTECLLLAITAY
NOV34a DRYLAICQPLRYRVLMSHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCK
NOV34b DRYLAICQPLRYHVLMSHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCK
NOV34C DRYLAICQPLRYHVLMSHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCK
NOV34d DRYLAICQPLRYHVLMSHRLCVLLMGAAWVLCLLKSVTEMVISMRLPFCGHHWSHFTCK
NOV34a ILAVLKLACGNTSVSEDFLLAGSILLLPVPLAFICLSYLLILATILRVPSAARCCKAFST
NOV34b ILAVLKLACGNTSVSEDFLLAGSILLLPVPLAFICLSYLLILATILRVPSAARCCKAFST
NOV3 C ILAVLKLACGNTSVSEDFLLAGSILLLPVPLAFICLSYLLILATILRVPSAARCCKAFST
NOV34d ILAVLKLACGNTSVSEDFLLAGSILLLPVPLAFICLSYLLILATILRVPSAARCCKAFST
NOV34a CLAHLAWLLFYGTIIFMYLKPKSKEAHISDEVFTVLYAMVTTMLNPTIYSLRNKEVKEA
NOV34b CLAHLAWLLFYGT11FMYLKPKSKEAHISDEVFTVLYAMVTTMLNPTIYSLRNKEVKEA
NOV34c CLAHLAWLLFYGT11FMYLKPKSKEAHISDEVFTVLYAMVTTMLNPTIYSLRNKEVKEA
NOV34d CIJAHLAVVLLFYGTIIFMYLKPKSKEAHISDEVFTVLYAMVTTMLNPTIYSLRNKEVKEA
NOV34a ARKV GRSRASR NOV34b ARKVWGRSRASR NOV34C ARKVWGRSRASR NOV34d ARKVWGRSRASR
NOV3 a (SEQ ID NO 426)
NOV34b (SEQ ID NO 428)
NOV34C (SEQ ID NO 430)
NOV34d (SEQ ID NO 432)
Further analysis ofthe NOV34a protein yielded the following properties shown in Table
34C.
Table 34C. Protein Sequence Properties NOV34a
SignalP analysis: Cleavage site between residues 4δ and 49
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 1; neg.chg 3 H-region: length 3; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -2.43 possible cleavage site: between 33 and 34
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 6 INTEGRAL Likelihood = -1.86 Transmembrane 35 - 51 INTEGRAL Likelihood = -0.11 Transmembrane 92 - 108 INTEGRAL Likelihood = -4.88 Transmembrane 141 - 157 INTEGRAL Likelihood = -0.27 Transmembrane 173 189
4δ9 INTEGRAL Likelihood = -7.80 Transmembrane 204 - 220 INTEGRAL Likelihood = -6.26 Transmembrane 241 - 257 PERIPHERAL Likelihood = 0.79 (at 71) ALOM score: -7.80 (number of T Ss: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 42 Charge difference: 0.5 C( 0.0) - N(-0.5) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 6.33 Hyd Moment(95): 9.16 G content: 0 D/E content: 2 S/T content: 1 Score: -5.44
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 8.3% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
11.1 %: Golgi
11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG54212-02 is end (k=9)
A search ofthe NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34D.
Figure imgf000496_0001
In a BLAST search of public sequence databases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34E.
Figure imgf000497_0001
PFam analysis indicates that the NOV34a protein contains the domains shown in the Table 34F.
Figure imgf000497_0002
Example 35.
The NOV35 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 35A. Table 35A. NOV35 Sequence Analysis
NOV35a, CG54236-01 SEQ ID NO: 441 1260 bp DNA Sequence ORF Start: ATG at 105 ORF Stop: TAA at 1143
TGCTCCCTGTTTCATTAAAACCTAGAGAGATGTAATCAGTAAGCAAGAAGGAAAAAGGGAAATTCACA
AAGTAACTTTTTGTGTCTGTTTCTTTTTAACCCAGCATGGAGAGAAAATTTATGTCCTTGCAACCATC
CATCTCCGTATCAGAAATGGAACCAAATGGCACCTTCAGCAATAACAACAGCAGGAACTGCACAATTG AAAACTTCAAGAGAGAATTTTTCCCAATTGTATATCTGATAATATTTTTCTGGGGAGTCTTGGGAAAT GGGTTGTCCATATATGTTTTCCTGCAGCCTTATAAGAAGTCCACATCTGTGAACGTTTTCATGCTAAA TCTGGCCATTTCAGATCTCCTGTTCATAAGCACGCTTCCCTTCAGGGCTGACTATTATCTTAGAGGCT CCAATTGGATATTTGGAGACCTGGCCTGCAGGATTATGTCTTATTCCTTGTATGTCAACATGTACAGC AGTATTTATTTCCTGACCGTGCTGAGTGTTGTGCGTTTCCTGGCAATGGTTCACCCCTTTCGGCTTCT GCATGTCACCAGCATCAGGAGTGCCTGGATCCTCTGTGGGATCATATGGATCCTTATCATGGCTTCCT CAATAATGCTCCTGGACAGTGGCTCTGAGCAGAACGGCAGTGTCACATCATGCTTAGAGCTGAATCTC TATAAAATTGCTAAGCTGCAGACCATGAACTATATTGCCTTGGTGGTGGGCTGCCTGCTGCCATTTTT CACACTCAGCATCTGTTATCTGCTGATCATTCGGGTTCTGTTAAAAGTGGAGGTCCCAGAATCGGGGC TGCGGGTTTCTCACAGGAAGGCACTGACCACCATCATCATCACCTTGATCATCTTCTTCTTGTGTTTC CTGCCCTATCACACACTGAGGACCGTCCACTTGACGACATGGAAAGTGGGTTTATGCAAAGACAGACT GCATAAAGCTTTGGTTATCACACTGGCCTTGGCAGCAGCCAATGCCTGCTTCAATCCTCTGCTCTATT ACTTTGCTGGGGAGAATTTTAAGGACAGACTAAAGTCTGCACTCAGAAAAGGCCATCCACAGAAGGCA AAGACAAAGTGTGTTTTCCCTGTTAGTGTGTGGTTGAGAAAGGAAACAAGAGTATAAGGAGCTCTTAG
ATGAGACCTGTTCTTGTATCCTTGTGTCCATCTTCATTCACTCATAGTCTCCAAATGACTTTGTATTT
ACATCACTCCCAACAAATGTTGATTCTTAATATTTA
NOV35a, CG54236-01 SEQ ID NO: 442 346 aa MW at 39634.7kD Protein Sequence
MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSIYVFLQPYK KSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYVNMYSSIYFLTVLSWR FLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQNGSVTSCLELNLYKIAKLQTMNYI ALWGCLLPFFTLSICYLLIIRVLLKVEVPESGLRVSHRKALTTIIITLIIFFLCFLPYHTLRTVHLT TWKVGLCKDRLHKALVITLALAAANACFNPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWL RKETRV
NOV35b, CG54236-02 SEQ ID NO: 443 1193 bp DNA Sequence ORF Start: ATG at 105 ORF Stop: TAA at 1143
TGCTCCCTGTTTCATTAAAACCTAGAGAGATGTAATCAGTAAGCAAGAAGGAAAAAGGGAAATTCACA
AAGTAACTTTTTGTGTCTGTTTCTTTTTAACCCAGCATGGAGAGAAAATTTATGTCCTTGCAACCATC
CATCTCCGTATCAGAAATGGAACCAAATGGCACCTTCAGCAATAACAACAGCAGGAACTGCACAATTG AAAACTTCAAGAGAGAATTTTTCCCAATTGTATATCTGATAATATTTTTCTGGGGAGTCTTGGGAAAT GGGTTGTCCATATATGTTTTCCTGCAGCCTTATAAGAAGTCCACATCTGTGAACGTTTTCATGCTAAA TCTGGCCATTTCAGATCTCCTGTTCATAAGCACGCTTCCCTTCAGGGCTGACTATTATCTTAGAGGCT CCAATTGGATATTTGGAGACCTGGCCTGCAGGATTATGTCTTATTCCTTGTATGTCAACATGTACAGC AGTATTTATTTCCTGACCGTGCTGAGTGTTGTGCGTTTCCTGGCAATGGTTCACCCCTTTCGGCTTCT GCATGTCACCAGCATCAGGAGTGCCTGGATCCTCTGTGGGATCATATGGATCCTTATCATGGCTTCCT CAATAATGCTCCTGGACAGTGGCTCTGAGCAGAACGGCAGTGTCACATCATGCTTAGAGCTGAATCTC TATAAAATTGCTAAGCTGCAGACCATGAACTATATTGCCTTGGTGGTGGGCTGCCTGCTGCCATTTTT CACACTCAGCATCTGTTATCTGCTGATCATTCGGGTTCTGTTAAAAGTGGAGGTCCCAGAATCGGGGC TGCGGGTTTCTCACAGGAAGGCACTGACCACCATCATCATCACCTTGATCATCTTCTTCTTGTGTTTC CTGCCCTATCACACACTGAGGACCGTCCACTTGACGACATGGAAAGTGGGTTTATGCAAAGACAGACT GCATAAAGCTTTGGTTATCACACTGGCCTTGGCAGCAGCCAATGCCTGCTTCAATCCTCTGCTCTATT ACTTTGCTGGGGAGAATTTTAAGGACAGACTAAAGTCTGCACTCAGAAAAGGCCATCCACAGAAGGCA AAGACAAAGTGTGTTTTCCCTGTTAGTGTGTGGTTGAGAAAGGAAACAAGAGTATAAGGAGCTCTTAG ATGAGACCTGTTCTTGTATCCTTGTGTCCATCTTCAT
NOV35b, CG54236-02 SEQ ID NO: 444 346 aa MW at 39634.7kD Protein Sequence !
MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSIYVFLQPYK KSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYVNMYSSIYFLTVLSWR FIJ^rVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQNGSVTSCLELNLYKIAKLQTMNYI ALWGCLLPFFTLS I CYLLI IRVLLKVEVPESGLRVSHRKALTTI I ITLI I FFLCFLPYHTLRTVHLT TWKVGLCKDRLHKALVITLALAAANACFNPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWL RKETRV
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 35B.
Table 35B. Comparison of the NOV35 protein sequences.
NOV35a MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSI
NOV35b MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSI
NOV35a YVFLQPYKKSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYV
NOV35b YVFLQPYKKSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYV
NOV35a NMYSSIYFLTVLSWRFLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQ
NOV35b NMYSSIYFLTVLSWRFLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQ
NOV35a NGSVTSCLELNLYKIAKLQTMNYIALWGCLLPFFTLSICYLLIIRVLLKVEVPESGLRV
NOV35b NGSVTSCLELNLYKIAKLQTMNYIALWGCLLPFFTLSICYLLIIRVLLKVEVPESGLRV
NOV35a SHRKALTTIIITLIIFFLCFLPYHTLRTVHLTTWKVGLCKDRLHKALVITLALAAANACF
NOV35b SHRKALTTIIITLIIFFLCFLPYHTLRTVHLTTWKVGLCKDRLHKALVITLALAAANACF
NOV35a NPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWLRKETRV
NOV35b NPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWLRKETRV
NOV35a (SEQ ID NO: 442)
NOV35b (SEQ ID NO: 444)
Further analysis ofthe NOV35a protein yielded the following properties shown in Table 35C.
Table 35C. Protein Sequence Properties NOV35a
SignalP analysis: Cleavage site between residues 60 and 61
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 4; pos. chg 2; neg.chg 1 H-region: length 11; peak value 5.18 PSG score: 0.78
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -0.37 possible cleavage site: between 55 and 56
>>> Seems to have a cleavable signal peptide (1 to 55)
ALOM: Klein et al's method for TM region allocation Init position for calculation: 56 Tentative number of TMS(s) for the threshold 0 .5: 6
INTEGRAL Likelihood = -2.81 Transmembrane 75 - 91
INTEGRAL Likelihood = -3.72 Transmembrane 125 - 141
INTEGRAL Likelihood = -8.86 Transmembrane 157 - 173
INTEGRAL Likelihood = -7.75 Transmembrane 204 - 220
INTEGRAL Likelihood =-11.36 Transmembrane 245 - 261
INTEGRAL Likelihood = -1.06 Transmembrane 287 - 303
PERIPHERAL Likelihood = 2.38 (at 222)
ALOM score : -11.36 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 27 Charge difference: 2.0 C( 1.0) - N(-1.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 11.72 Hyd Moment(95): 9.21 G content: 0 D/E content: 2 S/T content: 4 Score: -3.79
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 13 ERK|FM
NUCDISC: discrimination of nuclear localization signals pat : none pat7: none bipartite: none content of basic residues: 10.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: ERKF
KKXX-like motif in the C-terminus: KETR
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
66 .7 % endoplasmic reticulum
11. 1 % Golgi
11. 1 % vacuolar
11 . 1 % cytoplasmic
>> prediction for CG54236 - 01 is end (k=9)
A search ofthe NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35D.
Figure imgf000502_0001
In a BLAST search of public sequence databases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35E.
Figure imgf000503_0001
PFam analysis indicates that the NOV35a protein contains the domains shown in the Table 35F.
Figure imgf000503_0002
Example 36.
The NOV36 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 36A. Table 36A. NOV36 Sequence Analysis
NOV36a, CG54479-06 SEQ ID NO: 445 2066 bp DNA Sequence ORF Start: ATG at 22 ORF Stop: TAG at 2032
ACAGGTTTCACAACTTCCCGGATGGGGCTGTGGTGGGTCACAGTGCAGCCTCCAGCCAGAAGGATGGG
GTGGCTCCCACTCCTGCTGCTTCTGACTCAATGCTTAGGGGTCCCTGGGCAGCGCTCGCCATTGAATG ACTTCCAAGTGCTCCGGGGCACAGAGCTACAGCACCTGCTACATGCGGTGGTGCCCGGGCCTTGGCAG GAGGATGTGGCAGATGCTGAAGAGTGTGCTGGTCGCTGTGGGCCCTTAATGGACTGCCGGGCCTTCCA CTACAACGTGAGCAGCCATGGTTGCCAACTGCTGCCATGGACTCAACACTCGCCCCACACGAGGCTGC GGCGTTCTGGGCGCTGTGACCTCTTCCAGAAGAAAGACTACGTACGGACCTGCATCATGAACAATGGG GTTGGGTACCGGGGCACCATGGCCACGACCGTGGGTGGCCTGCCCTGCCAGGCTTGGAGCCACAAGTT CCCGAATGATCACAAGTACACGCCCACTCTCCGGAATGGCCTGGAAGAGAACTTCTGCCGTAACCCTG ATGGCGACCCCGGAGGTCCTTGGTGCTACACAACAGACCCTGCTGTGCGCTTCCAGAGCTGCGGCATC AAATCCTGCCGGGAGGCCGCGTGTGTCTGGTGCAATGGCGAGGAATACCGCGGCGCGGTAGACCGCAC GGAGTCAGGGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCGCACCAGCACCCCTTCGAGCCGGGCA AGTTCCTCGACCAAGGTCTGGACGACAACTATTGCCGGAATCCTGACGGCTCCGAGCGGCCATGGTGC TACACTACGGATCCGCAGATCGAGCGAGAGTTCTGTGACCTCCCCCGCTGCGGGTCCGAGGCACAGCC CCGCCAAGAGGCCACAACTGTCAGCTGCTTCCGCGGGAAGGGTGAGGGCTACCGGGGCACAGCCAATA CCACCACTGCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAATCCCTCATCAGCACCGATTTACGCCA GAAAAATACGCGTGCAAAGACCTTCGGGAGAACTTCTGCCGGAACCCCGACGGCTCAGAGGCGCCCTG GTGCTTCACACTGCGGCCCGGCATGCGCGCGGCCTTTTGCTACCAGATCCGGCGTTGTACAGACGACG TGCGGCCCCAGGACTGCTACCACGGCGCAGGGGAGCAGTACCGCGGCACGGTCAGCAAGACCCGCAAG GGTGTCCAGTGCCAGCGCTGGTCCGCTGAGACGCCGCACAAGCCGCAGTTCACGTTTACCTCCGAACC GCATGCACAACTGGAGGAGAACTTCTGCCGGAACCCAGATGGGGATAGCCATGGGCCCTGGTGCTACA CGATGGACCCAAGGACCCCATTCGACTACTGTGCCCTGCGACGCTGCGCTGATGACCAGCCGCCATCA ATCCTGGACCCCCCAGACCAGGTGCAGTTTGAGAAGTGTGGCAAGAGGGTGGATCGGCTGGATCAGCG GCGTTCCAAGCTGCGCGTGGTTGGGGGCCATCCGGGCAACTCACCCTGGACAGTCAGCTTGCGGAATC GGCAGGGCCAGCATTTCTGCGGGGGGTCTCTAGTGAAGGAGCAGTGGATACTGACTGCCCGGCAGTGC TTCTCCTCCTGCCATATGCCTCTCACGGGCTATGAGGTATGGTTGGGCACCCTGTTCCAGAACCCACA GCATGGAGAGCCAAGCCTACAGCGGGTCCCAGTAGCCAAGATGGTGTGTGGGCCCTCAGGCTCCCAGC TTGTCCTGCTCAAGCTGGAGAGATCTGTGACCCTGAACCAGCGTGTGGCCCTGATCTGCCTGCCCCCT GAATGGTATGTGGTGCCTCCAGGGACCAAGTGTGAGGGTGACTACGGGGGCCCACTTGCCTGCTTTAC CCACAACTGCTGGGTCCTGGAAGGAATTATAATCCCCAACCGAGTATGCGCAAGGTCCCGCTGGCCAG CTGTCTTCACGCGTGTCTCTGTGTTTGTGGACTGGATTCACAAGGTCATGAGACTGGGTTAGGCCCAG CCTTGATGCCATATGCCTTGGGGAGG
NOV36a, CG54479-06 SEQ ID NO: 446 670 aa MW at 76160.6kD Protein Sequence
MGLWWVTVQPPARRMGWLPLLLLLTQCLGVPGQRSPLNDFQVLRGTELQHLLHAWPGPWQEDVADAE ECAGRCGPLMDCRAFHYNVSSHGCQLLPWTQHSPHTRLRRSGRCDLFQKKDYVRTCIMNNGVGYRGTM ATTVGGLPCQAWSHKFPNDHKYTPTLRNGLEENFCRNPDGDPGGPWCYTTDPAVRFQSCGIKSCREAA CVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFEPGKFLDQGLDDNYCRNPDGSERPWCYTTDPQI EREFCDLPRCGSEAQPRQEATTVSCFRGKGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKD LRENFCRNPDGSEAPWCFTLRPGMRAAFCYQIRRCTDDVRPQDCYHGAGEQYRGTVSKTRKGVQCQRW SAETPHKPQFTFTSEPHAQLEENFCRNPDGDSHGPWCYTMDPRTPFDYCALRRCADDQPPSILDPPDQ VQFEKCGKRVDRLDQRRSKLRWGGHPGNSPWTVSLRNRQGQHFCGGSLVKEQWILTARQCFSSCHMP LTGYEVWLGTLFQNPQHGEPSLQRVPVAKMVCGPSGSQLVLLKLERSVTLNQRVALICLPPEWYWPP GTKCEGDYGGPLACFTHNCWVLEGIIIPNRVCARSRWPAVFTRVSVFVDWIHKVMRLG
NOV36b, CG54479-05 S SEEQ( ID NO: 447 1698 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1696
ATGACTTCTAGGTGCTCCGGGGCACAGAGCTACCTACAAGCGGTGGTGCCCGGGCCTTGGCAGGAGGA TGTGGCAGATGCTGAAGAGTGTGCTGGTCGCTGTGGGCCCTTAATGGACTGCGCGTTCCACTACAATG TGAGCAGCCATGGTTGCCAACTGCTGCCATGGACTCAACACTCACCCCACACGAGGCTGCGGCATTCT GGGCGCTGTGACCTCTTCCAGGAGAAAGACTACATACGGACCTGCATCATGAACAATGGGGTTGGGTA CCGGGGCACCATGGCCACGACCGTGGGTGGCCTGTCCTGCCAGGCTTGGAGCCACAAGTTCCCGAACG ATCACCAGTACATGCCCACGCTCCGGAATGGCCTGGAAGAGAACTTCTGCCGTAACCCTGATGGCGAC CCCGGAGGTCCTTGGTGCCACACAACAGACCCTGCCGTGCGCTTCCAGAGCTGCGGCATCAAATCCTG CCGGGTGGCCGCGTGTGTCTGGTGCAATGGCGAGGAATACCGCGGCGCGGTAGACCGCACCGAGTCAG GGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCGCACCAGCACCCCTTCGAGCCGGGCAAGTTCCTC GACCAAGGTCTGGACGACAACTATTGCCGGAATCCTGACGGCTCCGAGCGGCCATGGTGCTACACTAC GGATCCGCAGATCGAGCGAGAATTCTGTGACCTCCCCCGCTGCGGTTCCGAGGCACAGCCCCGCCAAG AGGCCACAAGTGTCAGCTGCTTCCGCGGGAAGGGTGAGGGCTACCGGGGCACAGCCAATACCACCACC GCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAATCCCGCATCAGCACCGATTTACGCCAGAAAAATA CGCGTGCAAGGACCTTCGGGAGAACTTCTGCCGGAACCCCGACGGCTCAGAGGCGCCCTGGTGCTTCA CACTGCGGCCCGGCATGCGCGTGGGCTTTTGCTACCAGATCCGGCGTTGTACAGACGACGTGCGGCCC CAGGACTGCTACCACGGCGCGGGGGAGCAGTACCGCGGCACGGTCAGCAAGACCCGCAAGGGTGTCCA GTGCCAGCGCGGGTCCGCTGAGACGCCGCACAAGCCGCAGTTCACGTTTACCTCCGAACCGCATGCAC AACTGGAGGAGAACTTCTGCCAGGACCCAGATGGGGATAGCCATGGGCCCTGGTGCTACACGATGGAC CCAAGGACCCCATTCGACTACTGTGCCCTGCGACGCTGCGCTGATGACCAGCCGCCATCAATCCTGGA CCCCCCCGACCAGGTGCAGTTTGAGAAGTGTGGCAAGAGGGTGGATCGGCTGGATCAGCGTTGTTCCA AGCTGCGCGTGGCTGGGGGCCATCCGGGCAACTCACCCTGGACAGTCAGCTTGCGGAATAGGCAGGGC CAGCATTTCTGCGGGGGGTCTCTAGTGAAGGAGCAGTGGATACTGACTGCCCGGCAGTGCTTCTCCTC CAGCCATATGCCTCTCACGGGCTATGAGGTATGGTTGGGCACCCTGTTCCAGAACCCACAACATGGAG AGCCAGGCCTACAGCGGGTCCCAGTAGCCAAGATGCTGTGTGGGCCCTCAGGCTCTCAGCTTGTCCTG CTCAAGCTGGAGAGGTCTGTGACCCTGAACCAGCGTGTGGCCCTGATCTGCCTGCCGCCTGAATGA
NOV36b, CG54479-05 SEQ ID NO: 44δ 565 aa MW at 63751.δkD
Protein Sequence
MTSRCSGAQSYLQAWPGPWQEDVADAEECAGRCGPLMDCAFHYNVSSHGCQLLPWTQHSPHTRLRHS GRCDLFQEKDYIRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHQYMPTLRNGLEENFCRNPDGD PGGPWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFEPGKFL DQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRGKGEGYRGTANTTT AGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTLRPGMRVGFCYQIRRCTDDVRP QDCYHGAGEQYRGTVSKTRKGVQCQRGSAETPHKPQFTFTSEPHAQLEENFCQDPDGDSHGPWCYTMD PRTPFDYCALRRCADDQPPSILDPPDQVQFEKCGKRVDRLDQRCSKLRVAGGHPGNSPWTVSLRNRQG QHFCGGSLVKEQWILTARQCFSSSHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQLVL LKLERSVTLNQRVALICLPPE
NOV36c, CG54479-01 SEQ ID NO: 449 2200 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TAG at 2157
TGCAGCCTCCAGCCAGAAGGATGGGGTGGCTCCCACTCCTGCTGCTTCTGACTCAATGCTTAGGGGTC
CCTGGGCAGCGCTCGCCATTGAATGACTTCGAGGTGCTCCGGGGCACAGAGCTACAGCGGCTGCTACA AGCGGTGGTGCCCGGGCCTTGGCAGGAGGATGTGGCAGATGCTGAAGAGTGTGCTGGTCGCTGTGGGC CCTTAATGGACTGCCGGGCGTTCCACTACAATGTGAGCAGCCATGGTTGCCAACTGCTGCCATGGACT CAACACTCACCCCACACGAGGCTGCGGCATTCTGGGCGCTGTGACCTCTTCCAGGAGAAAGACTACAT ACGGACCTGCATCATGAACAATGGGGTTGGGTACCGGGGCACCATGGCCACGACCGTGGGTGGCCTGT CCTGCCAGGCTTGGAGCCACAAGTTCCCGAACGATCACAGGTACATGCCCACGCTCCGGAATGGCCTG GAAGAGAACTTCTGCCGTAACCCTGATGGCGACCCCGGAGGTCCTTGGTGCCACACAACAGACCCTGC CGTGCGCTTCCAGAGCTGCGGCATCAAATCCTGCCGGTCTGCCGCGTGTGTCTGGTGCAATGGCGAGG AATACCGCGGCGCGGTAGACCGCACCGAGTCAGGGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCG CACCAGCACCCCTTCGAGCCGGGCAAGTACCCCGACCAAGGTCTGGACGACAACTATTGCCGGAATCC TGACGGCTCCGAGCGGCCATGGTGCTACACTACGGATCCGCAGATCGAGCGAGAATTCTGTGACCTCC CCCGCTGCGGTTCCGAGGCACAGCCCCGCCAAGAGGCCACAAGTGTCAGCTGCTTCCGCGGGAAGGGT GAGGGCTACCGGGGCACAGCCAATACCACCACCGCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAAT CCCGCATCAGCACCGATTTACGCCAGAAAAATACGCGTGCAAGGACCTTCGGGAGAACTTCTGCCGGA ACCCCGACGGCTCAGAGGCGCCCTGGTGCTTCACACTGCGGCCCGGCATGCGCGTGGGCTTTTGCTAC CAGATCCGGCGTTGTACAGACGACGTGCGGCCCCAGGGTTGCTACCACGGCGCGGGGGAGCAGTACCG CGGCACGGTCAGCAAGACCCGCAAGGGTGTCCAGTGCCAGCGCGCGTCCGCTGAGACGCCGCACAAGC CGCAGTTTACCTTTACCTCCGAACCGCATGCACAACTGGAGGAGAACTTCTGCCGCGACCCAGATGGG GATAGCTATGGGCCCTGGTGCTACACGATGGACCCAAGGACCCCATTCGACTACTGTGCCCTGCGACG CTGCGCTGATGACCAGCCGCCATCAATCCTGGACCCCCCCGACCAGGTGCAGTTTGAGAAGTGTGGCA AGAGGGTGGATCGGCTGGATCAGCGTTGTTCCAAGCTGCGCGTGGCTGGGGGCCATCCGGGCAACTCA CCCTGGACAGTCAGCTTGCGGAATAGGCAGGGCCAGCATTTCTGCGGGGGGTCTCTAGTGAAGGAGCA GTGGATACTGACTGCCCGGCAGTGCTTCTCCTCCAGCCATATGCCTCTCACGGGCTATGAGGTATGGT TGGGCACCCTGTTCCAGAACCCACAACATGGAGAGCCAGGCCTACAGCGGGTCCCAGTAGCCAAGATG CTGTGTGGGCCCTCAGGCTCTCAGCTTGTCCTGCTCAAGCTGGAGAGATCTGTGACCCTGAACCAGCG TGTGGCCCTGATCTGCCTGCCGCCTGAATGGTATGTGGTGCCTCCAGGGACCAAGTGTGAGATTGCAG GCCGGGGTGAGACCAAAGGTACGGGTAATGACACAGTCCTAAATGTGGCCTTGCTGAATGTCATCTCC AACCAGGAGTGTAACATCAAGCACCGAGGACATGTGCGGGAGAGCGAGATGTGCACTGAGGGACTGTT GGCCCCTGTGGGGGCCTGTGAGGGGGGTGACTACGGGGGCCCACTTGCCTGCTTTACCCACAACTGCT GGGTCCTGGAAGGAATTAGAATCCCCAACCGAGTATGCGCAAGGTCGCGCTGGCCAGCCGTCTTCACA CGTGTCTCTGTGTTTGTGGACTGGATTCACAAGGTCATGAGACTGGGTTAGGCCCAGCCTTGACGCCA TATGCTTTGGGGAGGACAAAACTT
NOV36c, CG54479-01 SEQ ID NO: 450 712 aa MW at δ0097.δkD Protein Sequence
MGWLPLLLLLTQCLGVPGQRSPLNDFEVLRGTELQRLLQAWPGPWQEDVADAEECAGRCGPLMDCRA FHYNVSSHGCQLLPWTQHSPHTRLRHSGRCDLFQEKDYIRTCIMNNGVGYRGTMATTVGGLSCQAWSH KFPNDHRYMPTLRNGLEENFCRNPDGDPGGPWCHTTDPAVRFQSCGIKSCRSAACVWCNGEEYRGAVD RTESGRECQRWDLQHPHQHPFEPGKYPDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEA QPRQEATSVSCFRGKGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEA PWCFTLRPGMRVGFCYQIRRCTDDVRPQGCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTFTS EPHAQLEENFCRDPDGDSYGPWCYTMDPRTPFDYCALRRCADDQPPSILDPPDQVQFEKCGKRVDRLD QRCSKLRVAGGHPGNSPWTVSLRNRQGQHFCGGSLVKEQWILTARQCFSSSHMPLTGYEVWLGTLFQN PQHGEPGLQRVPVAKMLCGPSGSQLVLLKLERSVTLNQRVALICLPPEWYWPPGTKCEIAGRGETKG TGNDTVLNVALLNVISNQECNIKHRGHVRESEMCTEGLLAPVGACEGGDYGGPLACFTHNCWVLEGIR IPNRVCARSRWPAVFTRVSVFVDWIHKVMRLG
NOV36d, CG54479-02 SEQ ID NO: 451 1710 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1705
ATGACTTCCAGGTGCTCCGGGGCACAGAGCTACCTGCTACATGCGGTGGTGCCTGGGCCTTGGCAGGA GGATGTGGCAGATGCTGAAGAGTGTGCTGGTCGCTGTGGGCCCTTAACGGACTGCTGGGCCTTCCACT ACAATGTGAGCAGCCATGGTTGCCAACTGCTGCCATGGACTCAACACTCGCCCCACTCAAGGCTGTGG CATTCTGGGCGCTGTGACCTCTTCCAGAAGAAAGACTACATACGGACCTGCATCATGAACAATGGGGT TGGGTACCGGGGCACCATGGCCACGACCGTGGGTGGCCTGTCCTGCCAGGCTTGGAGCCACAAGTTCC CGAATGATCACAAGTACATGCCCACGCTCCGGAATGGCCTGGAAGAGAACTTCTGCCATAACCCTGAT GGCGACCCCGGAGGTCCTTGGTGCCACACAACAGACCCTGCCGTGCGCTTCCAGAGCTGCGGCATCAA ATCCTGCCGGGTGGCCGCGTGTGTCTGGTGCAATGGCGAGGAATACCGCGGCGCGGTAGACCGCACCG AGTCAGGGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCGCACCAGCACCCCTTCGAGCCGGGCAAG TACCTCGACCAAGGTCTGGACGACAACTATTGCCGGAATCCTGACGGCTCCGAGCGGCCATGGTGCTA CACTACGGATCCGCAGATCGAGCGAGAATTCTGTGACCTCCCCCGCTGCGGTTCCGAGGCACAGCCCC GCCAAGAGGCCACAAGTGTCAGCTGCTTCCGCGGGAAGGGTGAGGGCTACCGGGGCACAGCCAATACC ACCACCGCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAATCCCGCATCAGCACCGATTTACGCCAGA AAAATACGCGTGCAAGGACCTTCGGGAGAACTTCTGCCGGAACCCCGACGGCTCAGAGGCGCCCTGGT GCTTCACACTGCGGCCCGGCATGCGCGTGGGCTTTTGCTACCAGATCCGGCGTTGTACAGACGACGTG CGGCCCCAGGACTGCTACCACGGCGCGGGGGAGCAGTACCGCGGCACGGTCAGCAAGACCCGCAAGGG TGTCCAGTGCCAGCGCGCGTCCGCTGAGACGCCGCACAAGCCGCAGTTCACGTTTACCTCCGAACCGC ATGCACAACTGGAGGAGAACTTCTGCCAGGACCCAGATGGGGATAGCCATGGGCCCTGGTGCTACACG ATGGACCCAAGGACCCCATTCGACTACTGTGCCCTGCGACGCTGCGCTGATGACCAGCCGCCATCAAT CCTGGACCCCCCCACAGACCAGGTGCAGTTTGAGAAGTGTGGCAAGAGGGTGGATCGGCTGGATCAGC GTCGTTCCAAGCTGCGCGTGGCTGGGGGCCATCCGGGCAACTCACCCTGGACAGTCAGCTTGGGGAAT CGGAGGCAGGGCCAGCATTTCTGCGGGGGGTCTCTAGTGAAGGAGCAGTGGATACTGACTGCCCGGCA GTGCTTCTCCTCCCATATGCCTCTCACGGGCTATGAGGTATGGTTGGGCACCCTGTTCCAGAACCCAC AACATGGAGAGCCAGGCCTACAGCGGGTCCCAGTAGCCAAGATGCTGTGTGGGCCCTCAGGCTCCCAG CTTGTCCTGCTCAAGCTGGAGAGATCTGTGACCCTGAACCAGCGTGTGGCCCTGATCTGCCTGCCGCC TGAATGATAT
NOV36d, CG54479-02 SEQ ID NO: 452 568 aa MW at 641δ0.3kD Protein Sequence
MTSRCSGAQSYLLHAWPGPWQEDVADAEECAGRCGPLTDCWAFHYNVSSHGCQLLPWTQHSPHSRLW HSGRCDLFQKKDYIRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHKYMPTLRNGLEENFCHNPD GDPGGPWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFEPGK YLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRGKGEGYRGTANT TTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTLRPGMRVGFCYQIRRCTDDV RPQDCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTFTSEPHAQLEENFCQDPDGDSHGPWCYT MDPRTPFDYCALRRCADDQPPSILDPPTDQVQFEKCGKRVDRLDQRRSKLRVAGGHPGNSPWTVSLGN RRQGQHFCGGSLVKEQWILTARQCFSSHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQ LVLLKLERSVTLNQRVALICLPPE
NOV36e, CG54479-03 SEQ ID NO: 453 1011 bp DNA Sequence ORF Start: at 7 ORF Stop: at 1006
AAGCTTTGCATCATGAACAATGGGGTTGGGTACCGGGGCACCATGGCCACGACCGTGGGTGGCCTGCC
CTGCCAGGCTTGGAGCCACAAGTTCCCAAATGATCACAAGTACACGCCCACTCTCCGGAATGGCCTGG AAGAGAACTTCTGCCGTAACCCTGATGGCGACCCCGGAGGTCCTTGGTGCTACACAACAGACCCTGCT GTGCGCTTCCAGAGCTGCGGCATCGAATCCTGCCGGGAGGCCGCGTGTGTCTGGTGCAATGGCGAGGA ATACCGCGGCGCGGTAGACCGCACGGAGTCAGGGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCGC ACCAGCACCCCTTCGAGCCGGGCAAGTTCCTCGACCAAGGTCTGGACGACAACTATTGCCGGAATCCT GACGGCTCCGAGCGGCCATGGTGCTACACTACGGATCCGCAGATCGAGCGAGAGTTCTGTGACCTCCC CCGCTGCGGGTCCGAGGCACAGCCCCGCCAAGAGGCCACAACTGTCAGCTGCTTCCGCGGGAAGGGTG AGGGCTACCGGGGCACAGCCAATACCACCACTGCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAATC CCTCATCAGCACCGATTTACGCCAGAAAAATACGCGTGCAAAGACCTTCGGGAGAACTTCTGCCGGAA CCCCGACGGCTCAGAGGCGCCCTGGTGCTTCACACTGCGGCCCGGCATGCGCGCGGCCTTTTGCTACC AGATCCGGCGTTGTACAGACGACGTGCGGCCCCAGGGGGAGCAGTACCGCGGCACGGTCAGCAAGACC CGCAAGGGTGTCCAGTGCCAGCGCTGGTCCGCTGAGACGCCGCACAAGCCGCAGTTCACGTTTACCTC CGAACCGCATGCACAACTGGAGGAGAACTTCTGCCGGAACCCAGATGGGGATAGCCATGGGCCCTGGT GCTACACGATGGACCCAAGGACCCCATTCGACTACTGTGCCCTGCGACGCTGCCTCGAG
NOV36e, CG54479-03 SEQ ID NO: 454 333 aa MW at 3δl29.9kD Protein Sequence
CIMNNGVGYRGTMATTVGGLPCQAWSHKFPNDHKYTPTLRNGLEENFCRNPDGDPGGPWCYTTDPAVR FQSCGIESCREAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFEPGKFLDQGLDDNYCRNPDG SERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATTVSCFRGKGEGYRGTANTTTAGVPCQRWDAQIPH QHRFTPEKYACKDLRENFCRNPDGSEAPWCFTLRPGMRAAFCYQIRRCTDDVRPQGEQYRGTVSKTRK GVQCQRWSAETPHKPQFTFTSEPHAQLEENFCRNPDGDSHGPWCYTMDPRTPFDYCALRRC
NOV36f, CG54479-04 SEQ ID NO: 455 lδδl bp DNA Sequence ORF Start: ATG at 76 ORF Stop: TGA at 1777
ACACATTACTGACATGTATGCCCACCTGACCTGCACCCACTCATGCCCACTCTGCAGGGCAGCGCTCG,
CCATTGAATGACTTCCAGGTGCTCCGGGGCACAGAGCTACCTGCTACATGCGGTGGTGCCTGGGCCTT
GGCAGGAGGATGTGGCAGATGCTGAAGAGTGTGCTGGTCGCTGTGGGCCCTTAACGGACTGCTGGGCC TTCCACTACAATGTGAGCAGCCATGGTTGCCAACTGCTGCCATGGACTCAACACTCGCCCCACTCAAG GCTGTGGCATTCTGGGCGCTGTGACCTCTTCCAGAAGAAAGACTACATACGGACCTGCATCATGAACA ATGGGGTTGGGTACCGGGGCACCATGGCCACGACCGTGGGTGGCCTGTCCTGCCAGGCTTGGAGCCAC AAGTTCCCGAATGATCACAAGTACATGCCCACGCTCCGGAATGGCCTGGAAGAGAACTTCTGCCATAA CCCTGATGGCGACCCCGGAGGTCCTTGGTGCCACACAACAGACCCTGCCGTGCGCTTCCAGAGCTGCG GCATCAAATCCTGCCGGGTGGCCGCGTGTGTCTGGTGCAATGGCGAGGAATACCGCGGCGCGGTAGAC CGCACCGAGTCAGGGCGCGAGTGCCAGCGCTGGGATCTTCAGCACCCGCACCAGCACCCCTTCGAGCC GGGCAGGTTCCTCGACCAAGGTCTGGACGACAACTATTGCCGGAATCCTGACGGCTCCGAGCGGCCAT GGTGCTACACTACGGATCCGCAGATCGAGCGAGAATTCTGTGACCTCCCCCGCTGCGGTTCCGAGGCA CAGCCCCGCCAAGAGGCCACAAGTGTCAGCTGCTTCCGCGGGAAGGGTGAGGGCTACCGGGGCACAGC CAATACCACCACCGCGGGCGTACCTTGCCAGCGTTGGGACGCGCAAATCCCGCATCAGCACCGATTTA CGCCAGAAAAATACGCGTGCAAGGACCTTCGGGAGAACTTCTGCCGGAACCTCGACGGCTCAGAGGCG CCCTGGTGCTTCACACTGCGGCCCGGCATGCGCGTGGGCTTTTGCTACCAGATCCGGCGTTGTACAGA CGACGTGCGGCCCCAGGACTGCTACCACGGCGCGGGGGAGCAGTACCGCGGCACGGTCAGCAAGACCC GCAAGGGTGTCCAGTGCCAGCGCGCGTCCGCTGAGACGCCGCACAAGCCGCAGTTCACGTTTACCTCC GAACCGCATGCACAACTGGAGGAGAACTTCTGCCAGACCCCAGATGGGGATAGCCATGGGCCCTGGTG CTACACGATGGACCCAAGGACCCCATTCGACTACTGTGCCCTGCGACGCTGCGCTGATGACCAGCCGC CATCAATCCTGGACCCCCCCGACCAGGTGCAGTTTGAGAAGTGTGGCAAGAGGGTGGATCGGCTGGAT CAGCGTCGTTCCAAGCTGCGCGTGGCTGGGGGCCATCCGGGCAACTCACCCTGGACAGTCAGCTTGGG GAATCGGCAGGGCCAGCATTTCTGCGGGGGGTCTCTAGTGAAGGAGCAGTGGATACTGACTGCCCGGC AGTGCTTCTCCTCCCAGCATATGCCTCTCACGGGCTATGAGGTATGGTTGGGCACCCTGTTCCAGAAC CCACAACATGGAGAGCCAGGCCTACAGCGGGTCCCAGTAGCCAAGATGCTGTGTGGGCCCTCAGGCTC CCAGCTTGTCCTGCTCAAGCTGGAGAGGTCTGTGACCCTGAACCAGCGTGTGGCCCTGATCTGCCTGC CGCCTGAATGATATGTGGTGCCTCCAGGGACCAAGTGTGAGATTGCAGGCCGGGGTGAGACCAAAGGT
IAAGAGCATAGTGCACAGGACTGCTGGTGGCCAGGAGGCCCAGCCC
NOV36f, CG54479-04 SEQ ID NO: 456 567 aa MW at 64065.2kD Protein Sequence
MTSRCSGAQSYLLHAWPGPWQEDVADAEECAGRCGPLTDCWAFHYNVSSHGCQLLPWTQHSPHSRLW HSGRCDLFQKKDYIRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHKYMPTLRNGLEENFCHNPD GDPGGPWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFEPGR FLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRGKGEGYRGTANT TTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNLDGSEAPWCFTLRPGMRVGFCYQIRRCTDDV RPQDCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTFTSEPHAQLEENFCQTPDGDSHGPWCYT MDPRTPFDYCALRRCADDQPPSILDPPDQVQFEKCGKRVDRLDQRRSKLRVAGGHPGNSPWTVSLGNR QGQHFCGGSLVKEQWILTARQCFSSQHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQL VLLKLERSVTLNQRVALICLPPE
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 36B.
Table 36B. Comparison of the NOV36 protein sequences.
NOV36a MGLWWVTVQPPARRMGWLPLLLLLTQCLGVPGQRSPLNDFQVLRGTELQHLLHAWPGPW NOV36b MTSRCSGAQSY LQAWPGPW NOV36C MGWLPLLLLLTQCLGVPGQRSPLNDFEVLRGTELQRLLQAWPGPW NOV36d MTSRCSGAQSYL LHAWPGPW NOV36e NOV36f -MTSRCSGAQSYL- -LHAWPGPW
NOV36a QEDVADAEECAGRCGPLMDCRAFHYNVSSHGCQLLPWTQHSPHTRLRRSGRCDLFQKKDY NOV36b QEDVADAEECAGRCGPLMDC-AFHYNVSSHGCQLLPWTQHSPHTRLRHSGRCDLFQEKDY NOV36C QEDVADAEECAGRCGPLMDCRAFHYNVSSHGCQLLPWTQHSPHTRLRHSGRCDLFQEKDY NOV36d QEDVADAEECAGRCGPLTDCWAFHYNVSSHGCQLLPWTQHSPHSRLWHSGRCDLFQKKDY NOV36e NOV36f QEDVADAEECAGRCGPLTDCWAFHYNVSSHGCQLLPWTQHSPHSRLWHSGRCDLFQKKDY
NOV36a VRTCIMNNGVGYRGTMATTVGGLPCQAWSHKFPNDHKYTPTLRNGLEENFCRNPDGDPGG
NOV36b IRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHQYMPTLRNGLEENFCRNPDGDPGG
NOV36C IRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHRYMPTLRNGLEENFCRNPDGDPGG
NOV36d IRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHKYMPTLRNGLEENFCHNPDGDPGG
NOV36e CIMNNGVGYRGTMATTVGGLPCQAWSHKFPNDHKYTPTLRNGLEENFCRNPDGDPGG
NOV36f IRTCIMNNGVGYRGTMATTVGGLSCQAWSHKFPNDHKYMPTLRNGLEENFCHNPDGDPGG
NOV36a PWCYTTDPAVRFQSCGIKSCREAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36b PWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36C PWCHTTDPAVRFQSCGIKSCRSAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36d PWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36e PWCYTTDPAVRFQSCGIESCREAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36f PWCHTTDPAVRFQSCGIKSCRVAACVWCNGEEYRGAVDRTESGRECQRWDLQHPHQHPFE
NOV36a PGKFLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATTVSCFRG
NOV36b PGKFLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRG
NOV36C PGKYPDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRG
NOV36d PGKYLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRG
NOV36e PGKFLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATTVSCFRG NOV36f PGRFLDQGLDDNYCRNPDGSERPWCYTTDPQIEREFCDLPRCGSEAQPRQEATSVSCFRG
NOV36a KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTL NOV36b KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTL NOV36c KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTL NOV36d KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTL NOV36e KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNPDGSEAPWCFTL NOV36f KGEGYRGTANTTTAGVPCQRWDAQIPHQHRFTPEKYACKDLRENFCRNLDGSEAPWCFTL
NOV36a RPGMRAAFCYQIRRCTDDVRPQDCYHGAGEQYRGTVSKTRKGVQCQRWSAETPHKPQFTF NOV36b RPGMRVGFCYQIRRCTDDVRPQDCYHGAGEQYRGTVSKTRKGVQCQRGSAETPHKPQFTF NOV36c RPGMRVGFCYQIRRCTDDVRPQGCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTF NOV36d RPGMRVGFCYQIRRCTDDVRPQDCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTF NOV36e RPGMRAAFCYQIRRCTDDVRPQ G-EQYRGTVSKTRKGVQCQRWSAETPHKPQFTF NOV36f RPGMRVGFCYQIRRCTDDVRPQDCYHGAGEQYRGTVSKTRKGVQCQRASAETPHKPQFTF
NOV36a TSEPHAQLEENFCRNPDGDSHGPWCYTMDPRTPFDYCALRRCADDQPPSILDPP-DQVQF NOV36 TSEPHAQLEENFCQDPDGDSHGPWCYTMDPRTPFDYCALRRCADDQPPSILDPP-DQVQF NOV36c TSEPHAQLEENFCRDPDGDSYGPWCYTMDPRTPFDYCALRRCADDQPPSILDPP-DQVQF NOV36d TSEPHAQLEENFCQDPDGDSHGPWCYTMDPRTPFDYCALRRCADDQPPSILDPPTDQVQF NOV36e TSEPHAQLEENFCRNPDGDSHGPWCYTMDPRTPFDYCALRRC NOV36f TSEPHAQLEENFCQTPDGDSHGPWCYTMDPRTPFDYCALRRCADDQPPSILDPP-DQVQF
NOV36a EKCGKRVDRLDQRRSKLRWGGHPGNSPWTVSLRNR-QGQHFCGGSLVKEQWILTARQCF NOV36b EKCGKRVDRLDQRCSKLRVAGGHPGNSPWTVSLRNR-QGQHFCGGSLVKEQWILTARQCF NOV36c EKCGKRVDRLDQRCSKLRVAGGHPGNSPWTVSLRNR-QGQHFCGGSLVKEQWILTARQCF NOV36d EKCGKRVDRLDQRRSKLRVAGGHPGNSPWTVSLGNRRQGQHFCGGSLVKEQWILTARQCF NOV36e NOV36f EKCGKRVDRLDQRRSKLRVAGGHPGNSPWTVSLGNR-QGQHFCGGSLVKEQWILTARQCF
NOV36a SSCHMPLTGYEVWLGTLFQNPQHGEPSLQRVPVAKMVCGPSGSQLVLLKLERSVTLNQRV NOV36b SSSHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQLVLLKLERSVTLNQRV NOV36c SSSHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQLVLLKLERSVTLNQRV NOV36d SS-HMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQLVLLKLERSVTLNQRV NOV36e NOV36f SSQHMPLTGYEVWLGTLFQNPQHGEPGLQRVPVAKMLCGPSGSQLVLLKLERSVTLNQRV
NOV36a ALICLPPEWYWPPGTKCEG NOV36b ALICLPPE NOV36c ALICLPPEWYWPPGTKCEIAGRGETKGTGNDTVLNVALLNVISNQECNIKHRGHVRESE NOV36d ALICLPPE NOV36e NOV36f ALICLPPE
NOV36a DYGGPLACFTHNCWVLEGIIIPNRVCARSRWPAVFTRVSVFVDW NOV36b NOV36c MCTEGLLAPVGACEGGDYGGPLACFTHNCWVLEGIRIPNRVCARSRWPAVFTRVSVFVDW NOV36d NOV36e NOV36f
NOV36a IHKVMRLG NOV36b NOV36c IHKVMRLG NOV36d
NOV36e
NOV36f
NOV36a (SEQ ID NO 446)
NOV36b (SEQ ID NO 448)
NOV36C (SEQ ID NO 450)
NOV36d (SEQ ID NO 452)
NOV36e (SEQ ID NO 454)
NOV36f (SEQ ID NO 456)
Further analysis ofthe NOV36a protein yielded the following properties shown in Table 36C.
Table 36C. Protein Sequence Properties NOV36a
SignalP analysis: Cleavage site between residues 30 and 31
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos. chg 0; neg.chg 0 H-region: length 12; peak value 9.09 PSG score: 4.69
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 6.16 possible cleavage site: between 29 and 30
>>> Seems to have a cleavable signal peptide (1 to 29)
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 30
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 3.07 (at 623) ALOM score: 3.07 (number of TMSs: 0)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 14 Charge difference: -3.0 C( 0.0) - N ( 3.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment(75): 1.11 Hyd Moment(95): 1.26 G content: 4 D/E content: 1 S/T content: 3 Score: -4.52
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 44 QRS I PL
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PHTRLRR (3) at 102 bipartite: none content of basic residues: 11.8% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
66.7 %: extracellular, including cell wall 22.2 %: mitochondrial 11.1 %: vacuolar
>> prediction for CG54479-06 is exc (k=9) A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36D.
Figure imgf000512_0001
In a BLAST search of public sequence databases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36E.
Figure imgf000513_0001
PFam analysis indicates that the NOV36a protein contains the domains shown in the Table 36F.
Figure imgf000514_0001
Example 37.
The NOV37 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 37A.
Figure imgf000514_0002
TTCCGTGTGAACTTGCCTGCAGAACCCAGTGTGCTTTGAAGCAATGTTGTGGGACACTACCACAAGCC CCTTCTGGAAAGGATGCAGAAAAGACCCCAGCAGTTAGCATTTCTTGTTTAGAACTTAGTAACAATCT AGAGAAGAAGCCCAGGAGGACTAAAGCTGAAAACATCCCTGCTGTTGTGATAGAGATTAAAAACATGC CAAACAAACAACCTGAATCATCTTTGTGAGTCTTGAAAAAGATGTGATATTTGACTTTTGCTTTAAAC TGC
NOV37a, CG54539-02 SEQ ID NO: 458 507 aa MW at 55325.3kD Protein Sequence
MGCWGRNRGRL CMIΛLTFMFMV EVVVSRVTSS AM SDSFHMLSDVLALVVALVAERFARRTHATQ KNTFGWIRAEVMGA VNAIFLTGLCFAIL EAIERFIEPHEMQQPLWLGVGVAG VNVLGLCLFHH HSGFSQDSGHGHSHGGHGYGHGLPKGPRVKSTRPGSSDINVAPGEQGPDQEETNTLVANTSNSNGLKL DPADPENPRSGDTVEVQVNGNLVREPDHMELEEDRAGQLNMRGVFLHVLGDALGSVIVWNALVFYFS WKGCSEGDFCVNPCFPDPCKAFVEIINSTHASVYEAGPCWVLY DPTLCWMVCI LYTTYPLLKESA LIL QTVPKQIDIRN IKELRNVEGVEEVHELHVWQ AGSRIIATAHIKCEDPTSYMEVAKTIKDVFH NHGIHATTIQPEFASVGSKSSWPCELACRTQCA KQCCGTLPQAPSGKDAEKTPAVSISCLELSNN EKKPRRTKAENIPAWIEIKNMPNKQPESSL
NOV37b, CG54539-01 SEQ ID NO: 459 1665 bp DNA Sequence ORF Start: ATG at 77 ORF Stop: TGA at 1598
CGACCCTCCGCGTCCCGCCAACGCCGCCGCTGCACCAGTCTCCGGGCCGGGCTCGGCGGGCCCCGCAG
CCGCAGCCATGGGGTGTTGGGGTCGGAACCGGGGCCGGCTGCTGTGCATGCTGGCGCTGACCTTCATG
TTCATGGTGCTGGAGGTGGTGGTGAGCCGGGTGACCTCGTCGCTGGCGATGCTCTCCGACTCCTTCCA CATGCTGTCGGACGTGCTGGCGCTGGTGGTGGCGCTGGTGGCCGAGCGCTTCGCCCGGCGGACCCACG CCACCCAGAAGAACACGTTCGGCTGGATCCGAGCCGAGGTAATGGGGGCTCTGGTGAACGCCATCTTC CTGACTGGCCTCTGTTTCGCCATCCTGCTGGAGGCCATCGAGCGCTTCATCGAGCCGCACGAGATGCA GCAGCCGCTGGTGGTCCTTGGGGTCGGCGTGGCCGGGCTGCTGGTCAACGTGCTGGGGCTCTGCCTCT TCCACCATCACAGCGGCTTCAGCCAGGACTCCGGCCACGGCCACTCGCACGGGGGTCACGGCCACGGC CACGGCCTCCCCAAGGGGCCTCGCGTTAAGAGCACCCGCCCCGGGAGCAGCGACATCAACGTGGCCCC GGGCGAGCAGGGTCCCGACCAGGAGGAGACCAACACCCTGGTGGCCAATACCAGCAACTCCAACGGGC TGAAATTGGACCCCGCGGACCCAGAAAACCCCAGAAGTGGTGATACAGTGGAAGTACAAGTGAATGGA AATCTTGTCAGAGAACCTGACCATATGGAACTGGAAGAAGATAGGGCTGGACAACTTAACATGCGTGG AGTTTTTCTGCATGTCCTTGGAGATGCCTTGGGTTCAGTGATTGTAGTAGTAAATGCCTTAGTCTTTT ACTTTTCTTGGAAAGGTTGTTCTGAAGGGGATTTTTGTGTGAATCCATGTTTCCCTGACCCCTGCAAA GCATTTGTAGAAATAATTAATAGTACTCATGCATCAGTTTATGAGGCTGGTCCTTGCTGGGTGCTATA TTTAGATCCAACTCTTTGTGTTGTAATGGTTTGTATACTTCTTTACACAACCTATCCATTACTTAAGG AATCTGCTCTTATTCTTCTACAAACTGTTCCTAAACAAATTGATATCAGAAATTTGATAAAAGAACTT CGAAATGTTGAAGGAGTTGAGGAAGTTCATGAATTACATGTTTGGCAACTTGCTGGAAGCAGAATCAT TGCCACTGCTCACATAAAATGTGAAGATCCAACATCATACATGGAGGTGGCTAAAACCATTAAAGACG TTTTTCATAATCACGGAATTCACGCTACTACCATTCAGCCTGAATTTGCTAGTGTAGGCTCTAAATCA AGTGTAGTTCCGTGTGAACTTGCCTGCAGAACCCAGTGTGCTTTGAAGCAATGTTGTGGGACACTACC ACAAGCCCCTTCTGGAAAGGATGCAGAAAAGACCCCAGCAGTTAGCATTTCTTGTTTAGAACTTAGTA ACAATCTAGAGAAGAAGCCCAGGAGGACTAAAGCTGAAAACATCCCTGCTGTTGTGATAGAGATTAAA AACATGCCAAACAAACAACCTGAATCATCTTTGTGAGTCTTGAAAAAGATGTGATATTTGACTTTTGC TTTAAACTGCAAGAGGAAAAAGACTCCACTGAA
NOV37b, CG54539-01 SEQ ID NO: 460 507 aa MW at 55299.3kD Protein Sequence
MGCWGRNRGR LCMLALTFMFMVLEVVVSRVTSSIiAMLSDSFHM SDVLALVVALVAERFARRTHATQ KNTFGWIRAEVMGALVNAIFLTGLCFAILLEAIERFIEPHEMQQPLWLGVGVAGLLVNVLG C FHH HSGFSQDSGHGHSHGGHGHGHGLPKGPRVKSTRPGSSDINVAPGEQGPDQEETNT VANTSNSNG KL DPADPENPRSGDTVEVQVNGN VREPDHMELEEDRAGQ NMRGVFLHV GDALGSVIVWNALVFYFS WKGCSEGDFCVNPCFPDPC AFVEIINSTHASVYEAGPC V YLDPTLCWMVCILLYTTYPLLKESA LIL QTVPKQIDIRN IKELRNVEGVEEVHE HVWQ AGSRIIATAHIKCEDPTSYMEVAKTIKDVFH NHGIHATTIQPEFASVGSKSSWPCELACRTQCALKQCCGTLPQAPSGKDAEKTPAVSISC ELSNN EKKPRRTKAENIPAWIEIKNMPNKQPESSL NOV37c, SNP1338243δ of SEQ ID NO: 461 1567 bp CG54539-02, DNA Sequence ORF Start: ATG at 2 ORF Stop: TGA at 1523 SNP Pos: 464 SNP Change: T to C
TATGGGGTGTTGGGGTCGGAACCGGGGCCGGCTGCTGTGCATGCTGGCGCTGACCTTCATGTTCATGG TGCTGGAGGTGGTGGTGAGCCGGGTGACCTCGTCGCTGGCGATGCTCTCCGACTCCTTCCACATGCTG TCGGACGTGCTGGCGCTGGTGGTGGCGCTGGTGGCCGAGCGCTTCGCCCGGCGGACCCACGCCACCCA GAAGAACACGTTCGGCTGGATCCGAGCCGAGGTAATGGGGGCTCTGGTGAACGCCATCTTCCTGACTG GCCTCTGTTTCGCCATCCTGCTGGAGGCCATCGAGCGCTTCATCGAGCCGCACGAGATGCAGCAGCCG CTGGTGGTCCTTGGGGTCGGCGTGGCCGGGCTGCTGGTCAACGTGCTGGGGCTCTGCCTCTTCCACCA TCACAGCGGCTTCAGCCAGGACTCCGGCCACGGCCACTCGCACGGGGGTCACGGCCACGGCCACGGCC TCCCCAAGGGGCCTCGCGTTAAGAGCACCCGCCCCGGGAGCAGCGACATCAACGTGGCCCCGGGCGAG CAGGGTCCCGACCAGGAGGAGACCAACACCCTGGTGGCCAATACCAGCAACTCCAACGGGCTGAAATT GGACCCCGCAGACCCAGAAAACCCCAGAAGTGGTGATACAGTGGAAGTACAAGTGAATGGAAATCTTG TCAGAGAACCTGACCATATGGAACTGGAAGAAGATAGGGCTGGACAACTTAACATGCGTGGAGTTTTT CTGCATGTCCTTGGAGATGCCTTGGGTTCAGTGATTGTAGTAGTAAATGCCTTAGTCTTTTACTTTTC TTGGAAAGGTTGTTCTGAAGGGGATTTTTGTGTGAATCCATGTTTCCCTGACCCCTGCAAAGCATTTG TAGAAATAATTAATAGTACTCATGCATCAGTTTATGAGGCTGGTCCTTGCTGGGTGCTATATTTAGAT CCAACTCTTTGTGTTGTAATGGTTTGTATACTTCTTTACACAACCTATCCATTACTTAAGGAATCTGC TCTTATTCTTCTACAAACTGTTCCTAAACAAATTGATATCAGAAATTTGATAAAAGAACTTCGAAATG TTGAAGGAGTTGAGGAAGTTCATGAATTACATGTTTGGCAACTTGCTGGAAGCAGAATCATTGCCACT GCTCACATAAAATGTGAAGATCCAACATCATACATGGAGGTGGCTAAAACCATTAAAGACGTTTTTCA TAATCACGGAATTCACGCTACTACCATTCAGCCTGAATTTGCTAGTGTAGGCTCTAAATCAAGTGTAG TTCCGTGTGAACTTGCCTGCAGAACCCAGTGTGCTTTGAAGCAATGTTGTGGGACACTACCACAAGCC CCTTCTGGAAAGGATGCAGAAAAGACCCCAGCAGTTAGCATTTCTTGTTTAGAACTTAGTAACAATCT AGAGAAGAAGCCCAGGAGGACTAAAGCTGAAAACATCCCTGCTGTTGTGATAGAGATTAAAAACATGC CAAACAAACAACCTGAATCATCTTTGTGAGTCTTGAAAAAGATGTGATATTTGACTTTTGCTTTAAAC TGC
NOV37c, SNP133δ243δ of SEQ ID NO: 462 507 aa MW at 55299.3kD CG54539-02, Protein Sequence SNP Pos: 155 SNP Change: Tyr to His
MGC GRNRGRLLCMLALTFMFMVLEVVVSRVTSSLAMLSDSFHMLSDVLALVVALVAERFARRTHATQ KNTFGWIRAEVMGALWAIFLTGLCFAILLEAIERFIEPHEMQQPLVVLGVGVAGLLVNVLGLCLFHH HSGFSQDSGHGHSHGGHGHGHGLPKGPRVKSTRPGSSDINVAPGEQGPDQEETNTLVANTSNSNGLKL DPADPENPRSGDTVEVQ GNLVREPDHMELEEDRAGQLNMRGVFLHVLGDALGSVIWVNALVFYFS KGCSEGDFCVNPCFPDPCKAFVEIINSTHASVYEAGPC VLYLDPTLCWMVCILLYTTYPLLKESA LILLQTVPKQIDIRNLIKELRNVEGVEEVHELHV QLAGSRIIATAHIKCEDPTSYMEVAKTIKDVFH NHGIHATTIQPEFASVGSKSSWPCELACRTQCALKQCCGTLPQAPSGKDAEKTPAVSISCLELSNNL EKKPRRTKAENIPAWIEIKNMPNKQPESSL
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 37B.
Table 37B. Comparison of the NOV37 protein sequences.
NOV37a MGCWGRNRGRLLCMIjALTFMFMVLEVVVSRVTSSLAMLSDSFHMLSDVLALVVALVAERF
NOV37b MGCWGRNRGRLLCMLALTFMFMVLEVWSRVTSSLAMLSDSFHMLSDVLALWALVAERF
NOV37a ARRTHATQKNTFGWIRAEVMGALVNAIFLTGLCFAILLEAIERFIEPHEMQQPLWLGVG
NOV37b ARRTHATQKNTFGWIRAEVMGALVNAIFLTGLCFAILLEAIERFIEPHEMQQPLWLGVG
NOV37a VAGLLVNVLGLCLFHHHSGFSQDSGHGHSHGGHGYGHGLPKGPRVKSTRPGSSDINVAPG
NOV37b VAGLLVNVLGLCLFHHHSGFSQDSGHGHSHGGHGHGHGLPKGPRVKSTRPGSSDINVAPG NOV37a EQGPDQEETNTLVANTSNSNGLKLDPADPENPRSGDTVEVQVNGNLVREPDHMELEEDRA
NOV37b EQGPDQEETNTLVANTSNSNGLKLDPADPENPRSGDTVEVQVNGNLVREPDHMELEEDRA
NOV37a GQLNMRGVFLHVLGDALGSVIVWNALVFYFS KGCSEGDFCVNPCFPDPCKAFVEIINS
NOV37b GQLNMRGVFLHVLGDALGSVI VNALVFYFSWKGCSEGDFCVNPCFPDPCKAFVEIINS
NOV37a THASVYEAGPCWVLYLDPTLCWMVCILLYTTYPLLKESALILLQTVPKQIDIRNLIKEL
NOV37b THASVYEAGPCWVLYLDPTLCWMVCILLYTTYPLLKESALILLQTVPKQIDIRNLIKEL
NOV37a RNVEGVEEVHELHVWQLAGSRIIATAHIKCEDPTSYMEVAKTIKDVFHNHGIHATTIQPE
NOV37b RNVEGVEEVHELHVWQLAGSRIIATAHIKCEDPTSYMEVAKTIKDVFHNHGIHATTIQPE
NOV37a FASVGSKSSWPCELACRTQCALKQCCGTLPQAPSGKDAEKTPAVSISCLELSNNLEKKP
NOV37b FASVGSKSSWPCELACRTQCALKQCCGTLPQAPSGKDAEKTPAVSISCLELSNNLEKKP
NOV37a RRTKAENIPAWIEIKNMPNKQPESSL
NOV37b RRTKAENIPAWIEIKNMPNKQPESSL
NOV37a (SEQ ID NO: 458) NOV37b (SEQ ID NO: 460)
Further analysis ofthe NOV37a protein yielded the following properties shown in Table
37C.
Table 37C. Protein Sequence Properties NOV37a
SignalP analysis: Cleavage site between residues 30 and 31
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 3; neg.chg 0 H-region: length 14; peak value 12.34 PSG score: 7.94
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -2.29 possible cleavage site: between 29 and 30
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5:
INTEGRAL Likelihood -8. .76 Transmembrane 12 28
INTEGRAL Likelihood -3, .66 Transmembrane 41 57
INTEGRAL Likelihood -7, .54 Transmembrane 82 98
INTEGRAL Likelihood -7. .43 Transmembrane 114 130
INTEGRAL Likelihood -5. .57 Transmembrane 248 264
INTEGRAL Likelihood -7. .01 Transmembrane 313 329
PERIPHERAL Likelihood 6. .21 (at 421)
ALOM score: -8.76 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 19
Charge difference: -4.0 C( 0.0) - N( 4.0)
N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment(75): 5.99 Hyd Moment(95): 2.66 G content: 3 D/E content: 1 S/T content: 1 Score: -3.81
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 40 SRV|TS
NUCDISC: discrimination of nuclear localization signals pat4: KKPR (4) at 478 pat4: KPRR (4) at 479 pat7: PRRTKAE (5) at 480 bipartite: none content of basic residues: 8.3% NLS Score: 0.46
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhard 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum 22.2 %: mitochondrial 11.1 %: nuclear
>> prediction for CG54539-02 is end (k=9)
A search ofthe NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37D.
Figure imgf000520_0001
In a BLAST search of public sequence databases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37E.
Figure imgf000521_0001
PFam analysis indicates that the NOV37a protein contains the domains shown in the Table 37F.
Figure imgf000521_0002
Example 38.
The NOV38 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3δA.
Table 38A. NOV38 Sequence Analysis
NOV38a, CG54683-05 SEQ ID NO: 463 1416 bp DNA Sequence ORF Start: ATG at 4 ORF Stop: TGA at 1402
GAGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATATTGAAACCAAATGTTTG
TGCTGCTTCTAACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAAACAAACCCAAGAAACTA GAATGAAGAAAGATGACAGTACCAAAGCGCGGCCTCAGAAATATGAGCAACTTCTCCATATAGAGGAC AACGATTTCGCAATGAGACCTGGATTTGGAGGGTCTCCAGTGCCAGTAGGTATAGATGTCCATGTTGA AAGCATTGACAGCATTTCAGAGACTAACATGGTAGACTTTACAATGACTTTTTATCTCAGGCATTACT GGAAAGACGAGAGGCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGACATTTGATCATAGATTGACC AGAAAGATCTGGGTGCCTGATATCTTTTTTGTCCACTCTAAAAGATCCTTCATCCATGATACAACTAT GGAGAATATCATGCTGCGCGTACACCCTGATGGAAACGTCCTCCTAAGTCTCAGGATAACGGTTTCGG CCATGTGCTTTATGGATTTCAGCAGGTTTCCTCTTGACACTCAAAATTGTTCTCTTGAACTGGAAAGC GCCTACAATGAGGATGACCTAATGCTATACTGGAAACACGGAAACAAGTCCTTAAATACTGAAGAACA TATGTCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATCTAGTGGATTAGCTTTCTATAGCAGCA CAGGTTGGTACAATAGGCTTTTCATCAACTTTGTGCTAAGGAGGCATGTTTTCTTCTTTGTGCTGCAA ACCTATTTCCCAGCCATATTGATGGTGATGCTTTCATGGGTTTCATTTTGGATTGACCGAAGAGCTGT TCCTGCAAGAGTTTCCCTGGGTGGAATCACCACAGTGCTGACCATGTCCACAATCATCACTGCTGTGA GCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTACCTGTGGGTCAGCTCCCTCTTT GTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACCACAGTGGAAGAGCGGAAACAATT CAAGAAGACAGGAAAGATTTCTAGGATGTACAATATTGATGCAGTTCAAGCTATGGCCTTTGATGGTT GTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCTCTCTCTAAACTCAGAAGACTTCATGAGA AGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGATAAAGAGAAGAAAATCCCTAGGAGGACA TGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGACACCTATTCTAGGATTNTATTCCCCATTG TGTATATCTTATTTAATTTGTTTTACTGGGGTGTATATGTATGAAGGGGAATTTCA
NOV38a, CG546δ3-05 SEQ ID NO: 464 466 aa MW at 53919.5kD Protein Sequence
MVLAFQLVSFTYIWII KPNVCAASNIKMTHQRCSSSMKQTQETR KKDDSTKARPQKYEQLLHIEDN DFAMRPGFGGSPVPVGIDVHVESIDSISETNMVDFTMTFYLRHYWKDERLSFPSTANKSMTFDHRLTR KIWVPDIFFVHSKRSFIHDTT ENIMLRVHPDGNVLLSLRITVSAMCFMDFSRFPLDTQNCSLELESA YNEDDLMLY KHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQT YFPAILMVMLSWVSF IDRRAVPARVSLGGITTVLTMSTIITAVSASMPQVSYLKAVDVYL VSSLFV FLSVIEYAAVNYLTTVEERKQFKKTGKISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFMRR KSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRIXFPIVYILFNLFY GVYV
NOV3δb, CG54683-01 |SEQ ID NO: 465 lδ75 bp
DNA Sequence ORF Start: ATG at 10 ORF Stop: TGA at 1411
TTGGAAGAGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATATTGAAACCAAA
TGTTTGTGCTGCTTCTAACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAAACAAACCTGGA TGCAAGAAACTAGAATGAAGAAAGATGACAGTACCAAAGCGCGGCCTCAGAAATATGAGCAACTTCTC CATATAGAGGACAACGATTTCGCAATGAGACCTGGATTTGGAGGTTCTCCAGTGCCAGTAGGTATAGA TGTCCATGTTGAAAGCATTGACAGCATTTCAGAGACTAACATGGACTTTACAATGACTTTTTATCTCA GGCATTACTGGAAAGACGAGAGGCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGACATTTGATCAT AGACACTTGCGGTATTCGTTATTCATCAGAAGGCTGTATCTGTTATACTGCCAGAGGTCTTTCTTCTC ACCCTCATCCATACTTCCCTCATCTCCAGACATCCATGCACCTGGTACATCTAAAAGCAGTTTGTCTG ATAGCCTTGTATGTATATCTGAAAAAAACTTGCCAGGACACAGTAAAAACACACCTCTTGCAATGTCA GATGTAGCCTACAATGAGGATGACCTAATGCTATACTGGAAACACGGAAACAAGTCCTTAAATACTGA AGAACATATGTCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATCTAGTGGATTAGCTTTCTATA GCAGCACAGGTACAGCATTTTACATGGGTGATTCATCAGCATTTATTGGACATCTACTGTTTTTGATC TGGAGTTCCAGGAAAAGACCAGGTTTAGAGATGTTGGGTTTGGGAATTCTCAGAATCTGGGTAATAAC TAGAGCCATGGATAAGAAAATGGAAATGGGAATCACCACAGTGCTGACCATGTCCACAATCATCACTG CTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTACCTGTGGGTCAGCTCC CTCTTTGTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACCACAGTGGAAGAGCGGAA ACAATTCAAAAAAAGTTTTTCAAAGATTTCTAGGATGTACAATATTGATGCAGTTCAAGCTATGGCCT TTGATGGTTGTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCTCTCTCTAAACTCAGAAGAC TTCATGAGAAGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGATAAAGAGAAGAAAATCCCT AGGAGGACATGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGACACCTATTCTAGGATTTTAT TCCCCATTGTGTATATCTTTTTTAATTTGTTTTACTGGGGTGTATATGTATGAAGGGGAATTTCAAAT GTATACAACTTTAAAGCCAGATGATGTTTAAAAACAAAACTCTTGAATATGAGTTGGATAGTCCTAGA TGGAACTGGGAAAGAGCAAGTCACCTCTCCTGCCCTAATGAAAATTTGAAAGCTGTCTGATTTACATC TAAGAAAGAGTTTAGGTCCTAGAAAAGTTTGACTCCATAAATAAGAGTCATAGGCATGTGTATTATGG GAAAAACAGTTTTCCATTGGGAAGGGCTTTATAACTACTTCATCTGAACCCTCCTTCTTTCTTAATGA AATGTTCTTTATTTAACTAGGGAAGAAAGCTGGACTATAACAATAATTCAAAGATATTTTGTTTCTTA GTGCCAGCCAAGTGCCTGGTTATCTACCAGAGCTCAACCGTCCTAGGCAAGAACATCCACATAGAGGT GGTATCATCCACACTCACACAGCTGAGAATCCTATGAAG NOV38b, CG546δ3-01 SEQ ID NO: 466 467 aa MW at 53522.9kD Protein Sequence
MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTWMQETRMKKDDSTKARPQKYEQLLHIE DNDFAMRPGFGGSPVPVGIDVHVESIDSISETNMDFTMTFYLRHYWKDERLSFPSTANKSMTFDHRHL RYSLFIRRLYLLYCQRSFFSPSSILPSSPDIHAPGTSKSSLSDSLVCISEKNLPGHSKNTPLAMSDVA YNEDDLMLYWKHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGTAFYMGDSSAFIGHLLFLIWSS RKRPGLEMLGLGILRIWVITRAMDKKMEMGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFV FLSVIEYAAVNYLTTVEERKQFKKSFSKISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFMR RKSICSPSTDSSRIKRRKSLGGHVGRIILEN HVIDTYSRILFPIVYIFFNLFYWGVYV
NOV3δc, CG546δ3-02 SEQ ID NO: 467 1444 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TGA at 1425
GTTTTTTTGTTTTGGAAGAGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATA
TTGAAACCAAATGTTTGTGCTGCTTCTAACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAA ACAAACCTGCAAACAAGAAACTAGAATGAAGAAAGATGACAGTACCAAAGCGCGGCCTCAGAAATATG AGCAACTTCTCCATATAGAGGACAACGATTTCGCAATGAGACCTGGATTTGGAGGGTCTCCAGTGCCA GTAGGTATAGATGCCCATGTTGAAAGCATTGACAGCATTTCAGAGACTAACATGGACTTTACAATGAC TTTTTATCTCAGGCATTACTGGAAAGACGAGAGGCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGA CATTTGATCATAGATTGACCAGAAAGATCTGGGTGCCTGATATCTTTTTTGTCCACTCTAAAAGATCC TTCATCCATGATACAACTATGGAGAATATCATGCTGCGCGTACACCCTGATGGAAACGTCCTCCTAAG TCTCAGGATAACGGTTTCGGCCATGTGCTTTATGGATTTCAGCAGGTTTCCTCTTGACGACACTCAAA ATTGTTCTCTTGAACTGGAAAGCTGTGCCTACAATGAGGATGACCTAATGCTATACTGGAAACACGGA AACAAGTCCTTAAATACTGAAGAACATATGTCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATC TAGTGGATTAGCTTTCTATAGCAGCACAGGTTGGTACAATAGGCTTTTCATCAACTTTGTGCTAAGGA GGCATGTTTTCTTCTTTGTGCTGCAAACCTATTTCCCAGCCATATTGATGGTGATGCTTTCATGGGTT TCATTTTGGATTGACCGAAGAGCTGTTCCTGCAAGAGTTTCCCTGGGTATCACCACAGTGCTGACCAT GTCCACAATCATCACTGCTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGT ACCTGTGGGTCAGCTCCCTCTTTGTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACC ACAGTGGAAGAGCGGAAACAATTCAAGAAGACAGGAAAGGTATCTAGGATGTACAATATTGATGCAGT TCAAGCTATGGCCTTTGATGGTTGTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCTCTCTC TAAACTCAGAAGACTTCATGAGAAGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGATAAAG AGAAGAAAATCCCTAGGAGGACATGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGACACCTA TTCTAGGATTTTATTCCCCATTGTGTATATTTTATTTAATTTGTTTTACTGGGGTGTATATGTATGAA GGGGAATTTCAAATGT
NOV3δc, CG546δ3-02 SEQ ID NO: 468 468 aa MW at 54283.9kD Protein Sequence
MVLAFQLVSFT IWIILKPNVCAASNIKMTHQRCSSSMKQTCKQETRMKKDDSTKARPQKYEQLLHIE DNDFAMRPGFGGSPVPVGIDAHVESIDSISETNMDFTMTFYLRHYWKDERLSFPSTANKSMTFDHRLT RKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGNVLLSLRITVSAMCFMDFSRFPLDDTQNCSLELE SCAYNEDDLMLYWKHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFV LQTYFPAILMVMLSWVSFWIDRRAVPARVSLGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSL FVFLSVIEYAAVNYLTTVEERKQFKKTGKVSRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFM RRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYILFNLFYWGVYV
NOV38d, CG54683-03 SEQ ID NO: 469 1438 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TGA at 1419
GTTTTTTTGTTTTGGAAGAGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATA
TTGAAACCAAATGTTTGTGCTGCTTCTAACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAA ACAAACCTGCAAACAAGAAACTAGAATGAAGAAAGATGACAGTACCAAAGCGCGGCCTCAGAAATATG AGCAACTTCTCCATATAGAGGACAACGATTTCGCAATGAGACCTGGATTTGGAGGGTCTCCAGTGCCA GTAGGTATAGATGTCCATGTTGAAAGCATTGACAGCATTTCAGAGACTAACATGGACTTTACAATGAC TTTTTATCTCAGGCATTACTGGAAAGACGAGAGGCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGA CATTTGATCATAGATTGACCAGAAAGATCTGGGTGCCTGATATCTTTTTTGTCCACTCTAAAAGATCC TTCATCCATGATACAACTATGGAGAATATCATGCTGCGCGTACACCCTGATGGAAACGTCCTCCTAAG TCTCAGGATAACGGTTTCGGCCATGTGCTTTATGGATTTCAGCAGGTTTCCTCTGACTCAAAATTGTT CTCTTGAACTGGAAAGCTGTGCCTACAATGAGGATGACCTAATGCTATACTGGAAACACGGAAACAAG TCCTTAAATACTGAAGAACATATGTCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATCTAGTGG ATTAGCTTTCTATAGCAGCACAGGTTGGTACAATAGGCTTTTCATCAACTTTGTGCTAAGGAGGCATG TTTTCTTCTTTGTGCTGCAAACCTATTTCCCAGCCATATTGATGGTGATGCTTTCATGGGTTTCATTT TGGATTGACCGAAGAGCTGTTCCTGCAAGAGTTTCCCTGGGTATCACCACAGTGCTGACCATGTCCAC AATCATCACTGCTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTACCTGT GGGTCAGCTCCCTCTTTGTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACCACAGTG GAAGAGCGGAAACAATTCAAGAAGACAGGAAAGGTATCTAGGATGTACAATATTGATGCAGTTCAAGC TATGGCCTTTGATGGTTGTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCTCTCTCTAAACT CAGAAGACTTCATGAGAAGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGATAAAGAGAAGA AAATCCCTAGGAGGACATGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGACACCTATTCTAG GATTTTATTCCCCATTGTGTATATTTTATTTAATTTGTTTTACTGGGGTGTATATGTATGAAGGGGAA TTTCAAATGT
NOV38d, CG54683-03 SEQ ID NO: 470 466 aa MW at 54081. δkD Protein Sequence
MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTCKQETRMKKDDSTKARPQKYEQLLHIE DNDFAMRPGFGGSPVPVGIDVHVESIDSISETNMDFTMTFYLRHYWKDERLSFPSTANKSMTFDHRLT RKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGNVLLSLRITVSAMCFMDFSRFPLTQNCSLELESC AYNEDDLMLYWKHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQ TYFPAILJ^rVMLSWVSFWIDRRAVPARVSLGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFV FLSVIEYAAVNYLTTVEERKQFKKTGKVSRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFMRR KSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYILFNLFYWGVYV
NOV38e, CG546δ3-04 SEQ ID NO: 471 1799 bp
DNA Sequence ORF Start: ATG at 71 ORF Stop: TGA at 1445
AAGAAGAAACTGTGATCACAGTATTGGTTGCGTTCACCTGCATCCTTTCTGTTTTTTTGTTTTGGAAG
AGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATATTGGTTTGTGCTGCTTCT AACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAAACAAACCGTAAGATGCTCAATGAAGAA AGATGACAGTACCAAAGCGCGGCCTCAGAAATATGAGCAACTTCTCCATATAGAGGACAACGATTTCG CAATGAGACCTGGATTTGGAGGTTCTCCAGTGCCAGTAGGTATAGATGTCCATGTTGAAAGCATTGAC AGCATTTCAGAGACTAACATGGACTTTACAATGACTTTTTATCTCAGGCATTACTGGAAAGACGAGAG GCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGACATTTGATCATAGAAAGAGTATCCCCCGCCCTG AACACTTGCGGTATTCGTTATTCATCAGAAGGCTGTATCTGTTATACTGCCAGAGGTCTTTCTTCTCA CCCTCATCCATACTTCCCTCATCTCCAGACATCCATGCACCTGGTACATCTAAAAGCAGTTTGTCTGA TAGCCTTGTATGTATATCTGAAAAAAACTTGCCAGGACACAGTAAAAACACACCTCTTGCAATGGCCT ACAATGAGGATGACCTAATGCTATACTGGAAACACGGAAACAAGTCCTTAAATACTGAAGAACATATG TCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATCTAGTGGATTAGCTTTCTATAGCAGCACAGG TACAGCATTTTACATGGGTGATTCATCAGCATTTATTGGACATCTACTGTTTTTAAATAGACATTTAC ATTTCTTCATCATAAATTTTGAAATTACTCAAATATTGATGATTGGAATCACCACAGTGCTGACCATG TCCACAATCATCACTGCTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTA CCTGTGGGTCAGCTCCCTCTTTGTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACCA CAGTGGAAGAGCGGAAACAATTCAAGAAGACAGGAAAGGTACAGATTTCTAGGATGTACAATATTGAT GCAGTTCAAGCTATGGCCTTTGATGGTTGTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCT CTCTCTAAACTCAGAAGACTTCATGAGAAGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGA TAAAGAGAAGAAAATCCCTAGGAGGACATGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGAC ACCTATTCTAGGATTTTATTCCCCATTGTGTATATCCCATTGTGTATATCTTTATTTAATTTGTTTTA CTGGGGTGTATATGTATGAAGGGGAATTTCAAATGTATACAACTTTAAAGCCAGATGATGTTTAAAAA
CAAAACTCTTGAATATGAGTTGGAATTGAAGACTTCAGTGCATCTAGTGGATTAGCTTTCTATAGCAG
CACAGGTACAGCATTTTACATGGGTGATTCATCAGCATTTATTGGACATCTACTGTTTTACTTTTGGT
CTTTGATGATGGTGATGTACAGATGGGTTGGAATCACCACAGTGCTGACCATGTCCACAATCATCACT
GCTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTACCTGTGGGTCAGCTC
CCTCTTTGTGTTCCTGTCAGTCATTGAGTAT
NOV38e, CG54683-04 SEQ ID NO: 472 458 aa MW at 52330.5kD Protein Sequence
MVLAFQLVSFTYIWIILVCAASNIKMTHQRCSSSMKQTVRCSMKKDDSTKARPQKYEQLLHIEDNDFA MRPGFGGSPVPVGIDVHVESIDSISETNMDFTMTFYLRHYWKDERLSFPSTANKSMTFDHRKSIPRPE HLRYSLFIRRLYLLYCQRSFFSPSSILPSSPDIHAPGTSKSSLSDSLVCISEKNLPGHSKNTPLAMAY NEDDLMLYWKHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGTAFYMGDSSAFIGHLLFLNRHLH FFIINFEITQILMIGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEYAAVNYLTT VEERKQFKKTGKVQISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFMRRKSICSPSTDSSRI KRRKSLGGHVGRIILEN HVIDTYSRILFPIVYIPLCISLFNLFYWGVYV
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 3δB.
Table 38B. Comparison of the NOV38 protein sequences.
NOV38a MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQT- -QETRMKKDDSTKARPQK
NOV38b MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTWMQETRMKKDDSTKARPQK
NOV38C MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTCKQETRMKKDDSTKARPQK
NOV38d MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTCKQETRMKKDDSTKARPQK
NOV38e MVLAFQLVSFTYIWIIL VCAASNIKMTHQRCSSSMKQTVRCS- -MKKDDSTKARPQK
NOV38a YEQLLHIEDNDFAMRPGFGGSPVPVGIDVHVESIDSISETNMVDFTMTFYLRHYWKDERL
NOV38b YEQLLHIEDNDFAMRPGFGGSPVPVGIDVHVESIDSISETN-MDFTMTFYLRHYWKDERL
NOV38C YEQLLHIEDNDFAMRPGFGGSPVPVGIDAHVESIDSISETN-MDFTMTFYLRHYWKDERL
NOV38d YEQLLHIEDNDFAMRPGFGGSPVPVGIDVHVESIDSISETN-MDFTMTFYLRHYWKDERL
NOV38e YEQLLHIEDNDFAMRPGFGGSPVPVGIDVHVESIDSISETN-MDFTMTFYLRHYWKDERL
NOV38a SFPSTANKSMTFDHR LTRKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGN
NOV38b SFPSTANKSMTFDHR HLRYSLFIRRLYLLYCQRSFFSPSSILPSSPDIHAPG-
NOV38C SFPSTANKSMTFDHR LTRKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGN
NOV38d SFPSTANKSMTFDHR LTRKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGN
NOV38e SFPSTANKSMTFDHRKSIPRPEHLRYSLFIRRLYLLYCQRSFFSPSSILPSSPDIHAPG-
NOV38a VLLSLRITVSAMCFMDFSRFPLD-TQNCSLELES-AYNEDDLMLYWKHGNKSLNTEEHMS
NOV38b - -TSKSSLSDSLVCISEKNLPG-HSKNTPLAMSDVAYNEDDLMLYWKHGNKSLNTEEHMS
NOV38C VLLSLRITVSAMCFMDFSRFPLDDTQNCSLELESCAYNEDDLMLYWKHGNKSLNTEEHMS
NOV38d VLLSLRITVSAMCFMDFSRFPL--TQNCSLELESCAYNEDDLMLYWKHGNKSLNTEEHMS
NOV38e - -TSKSSLSDSLVCISEKNLPG-HSKNTPLAM AYNEDDLMLYWKHGNKSLNTEEHMS
NOV38a LSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQT-YFPAILMVMLSWVSF
NOV38b LSQFFIEDFSASSGLAFYSSTGTAFYMGDSSAFIGHLLFLIWSSRKRPGLEMLGLGILRI
NOV38C LSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQT-YFPAILMVMLSWVSF
NOV38d LSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQT-YFPAILMVMLSWVSF
NOV38e LSQFFIEDFSASSGLAFYSSTGTAFYMGDSSAFIGHLLFLN R HLHF
NOV38a WIDRRAVPARVSLGGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEY
NOV38b WVITRAMDKKMEMG-ITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEY
NOV38C WIDRRAVPARVSLG-ITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEY
NOV38d WIDRRAVPARVSLG-ITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEY
NOV38e FIINFEITQILMIG-ITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEY
NOV38a AAVNYLTTVEERKQFKKT- -GKISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDF
NOV38b AAVNYLTTVEERKQFKKS-FSKISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDF
NOV38C AAVNYLTTVEERKQFKKT- -GKVSRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDF
NOV38d AAVNYLTTVEERKQFKKT- -GKVSRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDF
NOV38e AAVNYLTTVEERKQFKKTGKVQISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDF
NOV38a MRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRIXFPIVYI LFNLF
NOV38b MRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYI FFNLF
NOV38C MRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYI LFNLF
NOV38d MRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYI LFNLF NOV38e MRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVΎIPLCISLFNLF
NOV38a Y GVYV
NOV38b YWGVYV
NOV38C YWGVYV
NOV38d YWGVYV
NOV38e YWGVYV
NOV38a (SEQ ID NO 464)
NOV38b (SEQ ID NO 466)
NOV38C (SEQ ID NO 468)
NOV38d (SEQ ID NO 470)
NOV38e (SEQ ID NO 472)
Further analysis of the NOV3δa protein yielded the following properties shown in Table 3δC.
Table 38C. Protein Sequence Properties NOV38a
SignalP analysis: Cleavage site between residues 25 and 26
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 0 ; pos . chg 0 ; neg . chg 0 H-region : length 17 ; peak value 9 .53 PSG score : 5 . 12
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1 ) : -7. 09 possible cleavage site : between 24 and 25
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation Init position for calculation : 1 Tentative number of TMS ( s) for the threshold 0 . 5: 5
INTEGRAL Likelihood -4.51 Transmembrane 1 - 17
INTEGRAL Likelihood -0.43 Transmembrane 171 - 187
INTEGRAL Likelihood -3.98 Transmembrane 265 - 281
INTEGRAL Likelihood -0.64 Transmembrane 300 - 316
INTEGRAL Likelihood -3.98 Transmembrane 329 - 345
INTEGRAL Likelihood -0.85 Transmembrane 448 - 464
PERIPHERAL Likelihood 7.48 (at 229)
ALOM score : -4.51 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 8 Charge difference: 1.5 C ( 2.5) - N( 1.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 2.39 Hyd Moment (95): 3.90 G content: 0 D/E content: 1 S/T content: 8 Score: -2.44
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 43 QRC|SS
NUCDISC: discrimination of nuclear localization signals pat4: KRRK (5) at 422 pat7: none bipartite: RRKSICSPSTDSSRIKR at 407 bipartite: RKSICSPSTDSSRIKRR at 408 content of basic residues: 10.3% NLS Score: 0.99
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
11.1 %: vacuolar
11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG54683-05 is end (k=9)
A search ofthe NOV3δa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3 D.
Figure imgf000528_0001
In a BLAST search of public sequence databases, the NOV3δa protein was found to have homology to the proteins shown in the BLASTP data in Table 3δE.
Figure imgf000529_0001
PFam analysis indicates that the NOV38a protein contains the domains shown in the Table 3δF.
Figure imgf000529_0002
Example 39.
The NOV39 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 39A.
Table 39A. NOV39 Sequence Analysis
NOV39a, CG54692-06 SEQ ID NO: 473 1125 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1111
ATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTTGCCCTGGGACCCGAGACCAGCAG CGGGACCCCAAGCCCGAGAGGGATACTCGGTTCGACCCCGAGCGGCGCCGTCCTGCCGGGCCGAGGGC CGCCCTTCTCTGTCTTCACGGTCCTGGTGGTGACGCTGCTAGTGCTGCTGATCGCTGCCACTTTCCTG TGGAACCTGCTGGTTCCGGTCACCATCCCGCGGGTCCGTGCCTTCCACCGCGTGCCGCATAACTTGGT GGCCTCGACGGCCGTCTCGGACGAACTAGTGGCAGCGCTGGCGATGCCACCGAGCCTGGCGAGTGAGC TGTCGACCGGGCGACGTCGGCTGCTGGGCCGGAGCCTGTGCCACGTGTGGATCTCCTTCGACGCCCTG TGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCATCGCCCTGGGCCGCGACGGGGCCATCACACGGCA CCTGCAGCACACGCTGCGCACCCGCAGCCGCGCCTCGTTGCTCATGATCGCGCTCGCCCGGGTGCCGT CGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGGCCGGGGCGAGGTGTGCGACGCTCGGCTCCAGCGC TGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCTTCTCCACCCGCGGCGCCTTCCACCTGCCGCTTGG CGTGGTGCCGTTTGTCTACCGGAAGATCTACGAGGCGGCCAAGTTTCGTTTCGGCCGCCGCCGGAGAG CTGTGCTGCCGTTGCCGGCCACCATGCAGGTGAAGGAAGCACCTGATGAGGCTGAAGTGGTGTTCACG GCACATTGCAAAGCAACGGTGTCCTTCCAGGTGAGCGGGGACTCCTGGCGGGAGCAGAAGGAGAGGCG AGCAGCCATGATGGTGGGAATTCTGATTGGCGTGTTTGTGCTGTGCTGGATCCCCTTCTTCCTGACGG AACTCATCAGCCCACTCTGTGCCTGCAGCCTGCCCCCCATCTGGAAAAGCATATTTCTGTGGCTTGGC TACTCCAATTCTTTCTTCAACCCCCTGATTTACACAGCTTTTAACAAGAACTACAACAATGCCTTCAA GAGCCTCTTTACTAAGCAGAGATGAACACAGGGGTTA
NOV39a, CG54692-06 SEQ ID NO: 474 370 aa MW at 40243.7kD Protein Sequence
MEAASLSVATAGVALALGPETSSGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLWTLLVLLIAATFL
WNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLGRSLCHWISFDAL
CCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQR CQVSREPSYAAFSTRGAFHLPLGWPFVYRKIYEAAKFRFGRRRRAVLPLPATMQVKEAPDEAEWFT AHCKATVSFQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPI KSIFLWLG YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR
NOV39b, CG54692-01 SEQ ID NO: 475 1150bp DNA Sequence ORF Start: ATG at 24 ORF Stop: TGA at 1134
CTGGAGCTGCGATCCCAAGCGCCATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTT
GCCCTGGGACCCGAGACCAGCAGCGGGACCCCAAGCCCGAGAGGGATACTCGGTTCGACCCCGAGCGG CGCCGTCCTGCCGGGCCGAGGGCCGCCCTTCTCTGTCTTCACGGTCCTGGTGGTGACGCTGCTAGTGC TGCTGATCGCTGCCACTTTCCTGTGGAACCTGCTGGTTCCGGTCACCATCCCGCGGGTCCGTGCCTTC CACCGCGTGCCGCATAACTTGGTGGCCTCGACGGCCGTCTCGGACGAACTAGTGGCAGCGCTGGCGAT GCCACCGAGCCTGGCGAGTGAGCTGTCGACCGGGCGACGTCGGCTGCTGGGCCGGAGCCTGTGCCACG TGTGGATCTCCTTCGACGCCCTGTGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCATCGCCCTGGGC CGCGACGGGGCCATCACACGGCACCTGCAGCACACGCTGCGCACCCGCAGCCGCGCCTCGTTGCTCAT GATCGCGCTCGCCCGGGTGCCGTCGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGGCCGGGGCGAGG TGTGCGACGCTCGGCTCCAGCGCTGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCTTCTCCACCCGC GGCGCCTTCCACCTGCCGCTTGGCGTGGTGCCGTTTGTCTACCGGAAGATCTACGAGGCGGCCAAGTT TCGTTTCGGCCGCCGCCGGAGAGCTGTGCTGCCGTTGCCGGCCACCTCCAAGGTAAAGGAAGCACCTG ATGAGGCTGAAGTGGTGTTCACGGCACATTGCAAAGCAACGGTGTCCTTCCAGGTGAGCGGGGACTCC TGGCGGGAGCAGAAGGAGAGGCGAGCAGCCATGATGGTGGGAATTCTGATTGGCGTGTTTGTGCTGTG CTGGATCCCCTTCTTCCTGACGGAACTCATCAGCCCACTCTGTGCCTGCAGCCTGCCCCCCATCTGGA AAGCATATTTCTGTGGCTTGGCTACTCCAATTCTTTCTTCAACCCCCTGATTTACACAGCTTTTAAC AAGAACTACAACAATGCCTTCAAGAGCCTCTTTACTAAGCAGAGATGAACACAGGGGTTAGA NOV39b, CG54692-01 SEQ ID NO: 476 370 aa MWat40199.7kD Protein Sequence
MEAASLSVATAGVALALGPETSSGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLWTLLVLLIAATFL WNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLGRSLCHV ISFDAL CCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQR CQVSREPSYAAFSTRGAFHLPLGWPFVYRKIYEAAKFRFGRRRRAVLPLPATSKVKEAPDEAEWFT AHCKATVSFQVSGDSWREQKERRAAMMVGILIGVFVLC IPFFLTELISPLCACSLPPIWKSIFL LG YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR
NOV39c, CG54692-02 SEQ ID NO: 477 1150bp DNA Sequence ORF Start: ATG at 24 ORF Stop: TGA at 1134
CTGGAGCTGCGATCCCAAGCGCCATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTT
GCCCTGGGACCCGAGACCAGCAGCGGGACCCCAAGCCCGAGAGGGATACTCGGTTCGACCCCGAGCGG CGCCGTCCTGCCGGGCCGAGGGCCGCCCTTCTCTGTCTTCACGGTCCTGGTGGTGACGCTGCTAGTGC TGCTGATCGCTGCCACTTTCCTGTGGAACCTGCTGGTTCCGGTCACCATCCCGCGGGTCCGTGCCTTC CACCGCGTGCCGCATAACTTGGTGGCCTCGACGGCCGTCTCGGACGAACTAGTGGCAGCGCTGGCGAT GCCACCGAGCCTGGCGAGTGAGCTGTCGACCGGGCGACGTCGGCTGCTGGGCCGGAGCCTGTGCCACG TGTGGATCTCCTTCGACGCCCTGTGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCATCGCCCTGGGC CGCGACGGGGCCATCACACGGCACCTGCAGCACACGCTGCGCACCCGCAGCCGCGCCTCGTTGCTCAT GATCGCGCTCGCCCGGGTGCCGTCGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGGCCGGGGCGAGG TGTGCGACGCTCGGCTCCAGCGCTGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCTTCTCCACCCGC GGCGCCTTCCACCTGCCGCTTGGCGTGGCGCCGTTTGTCTACCGGAAGATCTACGAGGCGGCCAAGTT TCGTTTCGGCCGCCGCCGGAGAGCTGTGCTGCCGTTGCCGGCCACCATGCAAGTAAAGGAAGCACCTG ATGAGGCTGAAGTGGTGTTCACGGCACATTGCAAAGCAACGGTGTCCTTCCAGGTGAGCGGGGACTCC TGGCGGGAGCAGAAGGAGAGGCGAGCAGCCATGATGGTGGGAATTCTGATTGGCGTGTTTGTGCTGTG CTGGATCCCCTTCTTCCTGACGGAACTCATCAGCCCACTCTGTGCCTGCAGCCTGCCCCCCATCTGGA AAAGCATATTTCTGTGGCTTGGCTACTCCAATTCTTTCTTCAACCCCCTGATTTACACAGCTTTTAAC AAGAACTACAACAATGCCTTCAAGAGCCTCTTTACTAAGCAGAGATGAACACAGGGGTTAGA
NOV39c, CG54692-02 SEQ ID NO: 47δ 370 aa MWat40215.7kD Protein Sequence
MEAASLSVATAGVALALGPETSSGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLWTLLVLLIAATFL WNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLGRSLCHVWISFDAL CCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQR CQVSREPSYAAFSTRGAFHLPLGVAPFVYRKIYEAAKFRFGRRRRAVLPLPATMQVKEAPDEAEWFT AHCKATVSFQVSGDSWREQKERRAAMMVGILIGVFVLC IPFFLTELISPLCACSLPPIWKSIFL LG YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR
NOV39d, CG54692-03 SEQ ID NO: 479 1127bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1117
ATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTTGCCCTGGGACCCGAGACCAGCAG CGGGACCCCAAGCCCGAGAGGGATACTCGGTTCGACCCCGAGCGGCGCCGTCCTGCCGGGCCGAGGGC CGCCCTTCTCTGTCTTCACGGTCCTGGTGGTGACGCTGCTAGTGCTGCTGATCGCCGCCACTTTCCTG TGGAACCTGCTGGTTCCGGTCACCATCCCGCGGGTCCGTGCCTTCCACCGCGTGCCGCATAACTTGGT GGCCTCGACGGCCGTCTCGGACGAACTAGTGGCAGCGCTGGCGATGCCACCGAGCCTGGCGAGTGAGC TGTCGACCGGGCGACGTCGGCTGCTGGGCCGGAGCCTGTGCCACGTGTGGATCTCCTTCCACGGCCCA CGGCTGTGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCATCGCCCTGGGCCGCGACGGGGCCATCAC ACGGCACCTGCAGCACACGCTGCGCACCCGCAGCCGCGCCTCGTTGCTCATGATCGCGCTCACCCGGG TGCCGTCGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGGCCGGGGCGAGGTGTGCGACGCTCGGCTC CAGCGCTGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCTTCTCCACCCGCGGCGCCTTCCACCTGCC GCTTGGCGTGGTGCCGTTTGTCTACCGGAAGATCTACGAGGCGGCCAAGTTTCGTTTCGGCCGCCGCC GGAGAGCTGTGCTGCCGTTGCCGGCCACCATGCAGGTGAAGGAAGCACCTGATGAGGCTGAAGTGGTG TTCACGGCACATTGCAAAGCAACGGTGTCCTTCCAGGTGAGCGGGGACTCCTGGCGGGAGCAGAAGGA GAGGCGAGCAGCCATGATGGTGGGAATTCTGATTGGCGTGTTTGTGCTGTGCTGGATCCCCTTCTTCC TGACGGAACTCATCAGCCCACTCTGTGCCTGCAGCCTGCCCCCCATCTGGAAAAGCATATTTCTGTGG CTTGGCTACTCCAATTCTTTCTTCAACCCCCTGATTTACACAGCTTTTAACAAGAACTACAACAATGC CTTCAAGAGCCTCTTTACTAAGCAGAGATGAACACAGGG NOV39d, CG54692-03 SEQ ID NO: 480 372 aa MWat40535.1kD Protein Sequence
MEAASLSVATAGVALALGPETSSGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLWTLLVLLIAATFL WNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLGRSLCHVWISFHGP RLCCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALTRVPSALIALAPLLFGRGEVCDARL QRCQVSREPSYAAFSTRGAFHLPLGWPFVΎRKIYEAAKFRFGRRRRAVLPLPATMQVKEAPDEAEW FTAHCKATVSFQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPI KSIFLW LGYSNSFFNPLIYTAFNKNYNNAFKSLFTKQR
NOV39e, CG54692-04 SEQ ID NO: 481 1155bp DNA Sequence ORE Start: ATG at 5 ORF Stop: TGA at 1145
CGCCATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTTGCCCCCGAGACCAGCAGCC
CGGCGTTGCCCTTGCCCTGGGACCCGAGACCAGCAGCAGGACCCGGGACCCCAAGCCCGAGAGGGATA CTCGGTTCGACCCCGAGCGGCGCCGTCCTGCCGGGCCGAGGGCCGCCCTTCTCTGTCTTCACGGTCCT GGTGGTGACGCTGCTAGTGCTGCTGATCGCTGCCACTTTCCTGTGGAACCTGCTGGTTCCGGTCACCA TCCCGCGGGTCCGTGCCTTCCACCGCGTGCCGCATAACTTGGTGGCCTCGACGGCCGTCTCGGACGAA CTAGTGGCAGCGCTGGCGATGCCACCGAGCCTGGCGAGTGAGCTGTCGACCGGGCGACGTCGGCTGCT GGGCCGCCACGTGTGGATCTCCTTCGACGCCCTGTGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCA TCGCCCTGGGCCGCGACGGGGCCATCACACGGCACCTGCAGCACACGCTGCGCACCCGCAGCCGCGCC TCGTTGCTCATGATCGCGCTCGCCCGGGTGCCGTCGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGG CCGGGGCGAGGTGTGCGACGCTCGGCTCCAGCGCTGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCT TCTCCACCCGCGGCGCCTTCCACCTGCCGCTTGGCGTGGTGCCGTTTGTCTACCGGAAGATCTACGAG GCGGCCAAGTTTCGTTTCGGCCGCCGCCGGAGAGCTGTGCTGCCGTTGCCGGCCACCATGCAGGTGAA GGAAGCACCTGATGAGGCTGAAGTGGTGTTCACGGCACATTGCAAAGCAACGGTGTCCTTCCAGGTGA GCGGGGACTCCTGGCGGGAGCAGAAGGAGAGGCGAGCAGCCATGATGGTGGGAATTCTGATTGGCGTG TTTGTGCTGTGCTGGATCCCCTTCTTCCTGACGGAACTCATCAGCCCACTCTGTGCCTGCAGCCTGCC CCCCATCTGGAAAAGCATATTTCTGTGGCTTGGCTACTCCAATTCTTTCTTCAACCCCCTGATTTACA CAGCTTTTAACAAGAACTACAACAATGCCTTCAAGAGCCTCTTTACTAAGCAGAGATGAACACAGGG
NOV39e, CG54692-04 SEQ ID NO: 482 380 aa MW at 41306.9kD Protein Sequence
MEAASLSVATAGVALAPETSSPALPLPWDPRPAAGPGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLV VTLLVLLIAATFL NLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLG RHV ISFDALCCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALARVPSALIALAPLLFGR GEVCDARLQRCQVSREPSYAAFSTRGAFHLPLGWPFVYRKIYEAAKFRFGRRRRAVLPLPATMQVKE APDEAEWFTAHCKATVSFQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPP IWKSIFLWLGYSNSFFNPLIYTAFNKNYN AFKSLFTKQR
NOV39f, CG54692-05 SEQ ID NO: 483 1152bp DNA Sequence ORF Start: ATG at 5 ORF Stop: TGA at 1142
CGCCATGGAGGCCGCTAGCCTTTCAGTGGCCACCGCCGGCGTTGCCCTTGCCCTGGGACCCGAGACCA
GCAGCGGACCCGGGACCCCAAGCCCGAGAGGGATACTCGGTTCGACCCCGAGCGGCGCCGTCCTGCCG GGCCGAGGGCCGCCCTTCTCTGTCTTCACGGTCCTGGTGGTGACGCTGCTAGTGCTGCTGATCGCTGC CACTTTCCTGTGGAACCTGCTGGTTCCGGTCACCATCCCGCGGGTCCGTGCCTTCCACCGCGTGCCGC ATAACTTGGTGGCCTCGACGGCCGTCTCGGACGAACTAGTGGCAGCGCTGGCGATGCCACCGAGCCTG GCGAGTGAGCTGTCGACCGGGCGACGTCGGCTGCTGGGCCGGAGCCTGTGCCACGTGTGGATCTCCTT CGACGCCGGAGCCTGTCTGTGCTGCCCCGCCGGCCTCGGGAACGTGGCGGCCATCGCCCTGGGCCGCG ACGGGGCCATCACACGGCACCTGCAGCACACGCTGCGCACCCGCAGCCGCGCCTCGTTGCTCATGATC GCGCTCGCCCGGGTGCCGTCGGCGCTCATCGCCCTCGCGCCGCTGCTCTTTGGCCGGGGCGAGGTGTG CGACGCTCGGCTCCAGCGCTGCCAGGTGAGCCGGGAACCCTCCTATGCCGCCTTCTCCACCCGCGGCG CCTTCCACCTGCCGCTTGGCGTGGTGCCGTTTGTCTACCGGAAGATCTACGAGGCGGCCAAGTTTCGT TTCGGCCGCCGCCGGAGAGCTGTGCTGCCGTTGCCGGCCACCATGCAGGTGAGGTCCAAGGTAAAGGA AGCACCTGATGAGGCTGAAGTGGTGTTCACGGCACATTGCAAAGCAACGGTGTCCTTCCAGGTGAGCG GGGACTCCTGGCGGGAGCAGAAGGAGAGGCGAGCAGCCATGATGGTGGGAATTCTGATTGGCGTGTTT GTGCTGTGCTGGATCCCCTTCTTCCTGACGGAACTCATCAGCCCACTCTGTGCCTGCAGCCTGCCCCC CATCTGGAAAAGCATATTTCTGTGGCTTGGCTACTCCAATTCTTTCTTCAACCCCCTGATTTACACAG CTTTTAACAAGAACTACAACAATGCCTTCAAGAGCCTCTTTACTAAGCAGAGATGAACACAGGG NOV39f, CG54692-05 SEQ ID NO: 484 379 aa MW at 41099.7kD Protein Sequence
MEAASLSVATAGVALALGPETSSGPGTPSPRGILGSTPSGAVLPGRGPPFSVFTVLWTLLVLLIAAT FLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMPPSLASELSTGRRRLLGRSLCHVWISFD AGACLCCPAGLGNVAAIALGRDGAITRHLQHTLRTRSRASLLMIALARVPSALIALAPLLFGRGEVCD ARLQRCQVSREPSYAAFSTRGAFHLPLGWPFVYRKIYEAAKFRFGRRRRAVLPLPATMQVRSKVKEA PDEAEWFTAHCKATVSFQVSGDS REQKERRAAMMVGILIGVFVLC IPFFLTELISPLCACSLPPI WKS I FLWLGYSNS FFNPLI YTAFNKNYNNAFKSLFTKQR
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 39B.
Table 39B. Comparison of the NOV39 protein sequences.
NOV39a MEAASLSVATAGVALA LGPETSSG- -TPSPRGILGSTPSGAVLPGRGPP NOV39b MEAASLSVATAGVALA LGPETSSG- -TPSPRGILGSTPSGAVLPGRGPP NOV39c MEAASLSVATAGVALA LGPETSSG- -TPSPRGILGSTPSGAVLPGRGPP NOV39d MEAASLSVATAGVALA LGPETSSG- -TPSPRGILGSTPSGAVLPGRGPP NOV39e MEAASLSVATAGVALAPETSSPALPLPWDPRPAAGPGTPSPRGILGSTPSGAVLPGRGPP NOV39f MEAASLSVATAGVALA LGPETSSGPGTPSPRGILGSTPSGAVLPGRGPP
NOV39a FSVFTVLWTLLVLLIAATFLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39b FSVFTVLWTLLVLLIAATFL NLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39c FSVFTVLWTLLVLLIAATFLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39d FSVFTVLWTLLVLLIAATFLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39e FSVFTVLWTLLVLLIAATFLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39f FSVFTVLWTLLVLLIAATFLWNLLVPVTIPRVRAFHRVPHNLVASTAVSDELVAALAMP
NOV39a PSLASELSTGRRRLLGRSLCHVWISFDA LCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39b PSLASELSTGRRRLLGRSLCHVWISFDA LCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39c PSLASELSTGRRRLLGRSLCHVWISFDA LCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39d PSLASELSTGRRRLLGRSLCHVWISFHG-PRLCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39e PSLASELSTGRRRLLGR HVWISFDA LCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39f PSLASELSTGRRRLLGRSLCHVWISFDAGACLCCPAGLGNVAAIALGRDGAITRHLQHTL
NOV39a RTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39b RTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39c RTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39d RTRSRASLLMIALTRVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39e RTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39f RTRSRASLLMIALARVPSALIALAPLLFGRGEVCDARLQRCQVSREPSYAAFSTRGAFHL
NOV39a PLGWPFVYRKIYEAAKFRFGRRRRAVLPLPAT MQVKEAPDEAEWFTAHCKATVS
NOV39b PLGWPFVYRKIYEAAKFRFGRRRRAVLPLPAT SKVKEAPDEAEWFTAHCKATVS
NOV39c PLGVAPFVYRKIYEAAKFRFGRRRRAVLPLPAT MQVKEAPDEAEWFTAHCKATVS
NOV39d PLGWPFVYRKIYEAAKFRFGRRRRAVLPLPAT MQVKEAPDEAEWFTAHCKATVS
NOV39e PLGWPFVYRKIYEAAKFRFGRRRRAVLPLPAT MQVKEAPDEAEWFTAHCKATVS
NOV39f PLGWPFVYRKIYEAAKFRFGRRRRAVLPLPATMQVRSKVKEAPDEAEWFTAHCKATVS
NOV39a FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG
NOV39b FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG
NOV39C FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG
NOV39d FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG N0V39e FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG N0V39f FQVSGDSWREQKERRAAMMVGILIGVFVLCWIPFFLTELISPLCACSLPPIWKSIFLWLG
N0V39a YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR NOV39b YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR NOV39c YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR NOV39d YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR NOV39e YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR NOV39f YSNSFFNPLIYTAFNKNYNNAFKSLFTKQR
NOV39a (SEQ ID NO 474) NOV39b (SEQ ID NO 476) NOV39c (SEQ ID NO 478) NOV39d (SEQ ID NO 480) NOV 9e (SEQ ID NO 482) NOV39f (SEQ ID NO 484)
Further analysis of the NOV39a protein yielded the following properties shown in Table 39C.
Table 39C. Protein Sequence Properties NOV39a
SignalP analysis: Cleavage site between residues 25 and 26
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 2 ; pos . chg 0 ; neg . chg 1 H-region : length 17 ; peak value 0 . 00 PSG score : -4 .40
GvH : von Heijne ' s method for signal seq . recognition GvH score ( threshold : -2 . 1) : -4 .24 possible cleavage site : between 23 and 24
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0 5:
INTEGRAL Likelihood = 0, 32 Transmembrane 1 17
INTEGRAL Likelihood =-12. 10 Transmembrane 48 64
INTEGRAL Likelihood = -0, 48 Transmembrane 135 151
INTEGRAL Likelihood = -4. 94 Transmembrane 172 188
INTEGRAL Likelihood = -9. 66 Transmembrane 300 316
PERIPHERAL Likelihood = 0. 69 (at 90)
ALOM score: -12.10 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 8 Charge difference: 0.0 C( 0.0) - N( 0.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.56 Hyd Moment(95): 5.35 G content: 2 D/E content: 2 S/T content: 3 Score: -7.53
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 95 HRV|PH
NUCDISC: discrimination of nuclear localization signals pat4: RRRR (5) at 246 pat7: none bipartite: RKIYEAAKFRFGRRRRA at 234 content of basic residues: 10.5% NLS Score: 0.50
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: FTKQ
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) -.
66.7 %: endoplasmic reticulum 22.2 %: mitochondrial 11.1 %: nuclear
>> prediction for CG54692-06 is end (k=9)
A search ofthe NOV39a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 39D.
Figure imgf000536_0001
In a BLAST search of public sequence databases, the NOV39a protein was found to have homology to the proteins shown in the BLASTP data in Table 39E.
Figure imgf000537_0001
PFam analysis indicates that the NOV39a protein contains the domains shown in the Table 39F.
Table 39F. Domain Analysis of NOV39a
Identities/
Pfam Domain NOV39a Match Region Similarities Expect Value for the Matched Region
7tm 1 69..351 75/314 (24%) 1.2e-43 197/314 (63%)
TRA 1801479vl Example 40.
The NOV40 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 40A.
Table 40A. NOV40 Sequence Analysis
NOV40a, CG55069-01 SEQ ID NO: 485 8657 bp DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at 8326
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG
CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA
TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA
IAGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC lAGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG
CACTGTATTTAACTAACTTTA
NOV40a, CG55069-01 SEQ ID NO: 486 2725 aa MW at 303959.6kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGVVTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTVVNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40b, CG55069-04 SEQ ID NO: 487 783 bp DNA Sequence ORF Start: at 7 ORF Stop: at 778
AAGCTTTGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGG
ATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCA AGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATT GACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAACTCAGGATACAAAGG AGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGG AATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAG TGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCC AGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTC GCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCAC GGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGAGGG TTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGTGTGCC AGCCTGGATGGAGAGGAGCAGGCTGTGACGTCGAC
NOV40b, CG55069-04 SEQ ID NO: 48δ 257 aa MW at 26δ66.7kD Protein Sequence
CPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDP QCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCS GHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGT CKDGKCECSQGWNGEHCTIEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCD
NOV40c, 24δ993047 SEQ ID NO: 489 2448 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGTACCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATAC CATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAA ATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATC TTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGA TGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGC TCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGG CAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCT GGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGG TGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGA TTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAA GGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTG ACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAAAGGA GAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGA ATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGT GCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCA GACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCG CTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACG GGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGAGGGT TGTCCTGGTCTGTCCAACAGCAATGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGTGTGCCA GCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATG AAGGAGATGGACTCATTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCC TATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGC TGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAG AAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCA CTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGG AATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCA CTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGAAGAAA
Figure imgf000542_0001
53δ TCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATAT AATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGA CCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTG GCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAA AACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCGTCGACCCAGCAGCCTCCAGTCGTGAGTA GCG
NOV40d, 26280248δ SEQ ID NO: 492 δ3δ aa MW at 91545.9kD Protein Sequence
GTNWQLQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGI FWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGR QARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPG FLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKG ESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGP DCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAH YLDKIVKDKIGYKEGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDC MDPDCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSL ASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWI PWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPG TDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAY NQKVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGE NQFISQQPPWSSVDPAASSRE
NOV40e, 24δ993606 SEQ ID NO: 493 2536 bp DNA Sequence ORF Start: at 1 ORF Stop: at 2536
GGTACCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATAC CATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAA ATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATC TTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGA TGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGC TCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGG CAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCT GGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGG TGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGA TTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAA GGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTG ACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAAAGGA GAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGA ATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGT GCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCA GACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCG CTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACG GGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCAC TATTTGGATAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGA CCAAAATGGCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGA CTCTTTGCACAGATAGTAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCGATTGCTGC CTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCA AAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGAT CTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGC CAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATA TGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTT TGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTAT GTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGATTCGT GAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGACAGTC CCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACTCTCC TACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTATTCC ATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTTCCTG CCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTATGGT CTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGGAAAA GAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGATAAAC ATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTCCCAG CAGCCTCCAGTCGTGAGTAGCGTCGACGCTACACACGACTGGAGGCTGCTGGTCATTTTCAGCTCTGC AGTAGCTGCCAGTTGGTACC
NOV40e, 24δ993606 SEQ ID NO: 494 845 aa MW at 92534.0kD Protein Sequence
GTNWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGI FWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGR QARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPG FLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKG ESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGP DCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAH YLDKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCC LQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRG QVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFY VMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLS YLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYG LSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQ QPPWSSVDATHDWRLLVIFSSAVAASWY
NOV40f, 314411758 SEQ ID NO: 495 2500 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCAAGCTTAACTGGCAGCTACAGCAGACTGAAAATGACGCATTTGAGAATGGAAAAGTGAATTCTG ATACCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAA GAAAATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGG GATCTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGA AGGATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTG GAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGG GCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGC ATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCT GTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCC AGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACT CCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGT ATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAACTCAGGATACAA AGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACG GGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGAC CAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGG CCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGT GCCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAG CACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGC TCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGCAACA GCAATGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGCGTGCCAGCCTGGATGGAGAGGAGCA GGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGA CTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGG ATCCTCAGGGCATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGAT CGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAG CCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCT CGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCA AATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTG GATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCA GCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTC AGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCC AGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCA CCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGA CTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGC ATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTT TGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATG GGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGG GGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCCTCGAGGGC
NOV40f, 31441 1758 SEQ ID NO: 496 δ33 aa MW at 91 1 16.5kD Protein Sequence
TKLNWQLQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPG IFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAG RQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFP GFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYK GESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTG PDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIA HYLDKIVKDKIGYKEGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLID CMDPDCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKS LASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVW IPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIP GTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDA YNQKVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNG ENQFISQQPPWSSLEG
NO V40g, 319067006 SEQ ID NO: 497 730 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCTCGCGAACAGAACCTTCTTACGAACTTGTGAAGAGTCAGCAGTGGGATGATATACCGCCCATCT TCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGCCTTCCTGTCGCTGGGGAAGATGGCCGAGGTG CAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCTGGCTGTGGTTCGCCACGGTCAAGTCGCTGAT CGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGCGTGCAGACCAACGTGCTCAACATCGCCAACG AGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGCCTTCTACCTGGAGAACCTGCACTTCACCATC GAGGGCAAGGACACGCACTACTTCATCAAGACCACCACGCCCGAGAGCGACCTGGGCACGCTGCGGTT GACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAACGTGACGGTGTCGCAGTCCACCACGGTGGTGA ACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCAGTTCGGCGCGCTGGCGCTGCACGTGCGCTAC GGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGGAGCAGGCGCAGCAGCGCGTGCGCGACGGCAA GGTGCAGGGCTACGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCA ACAACATCCAGTTCCTGCGGCAGAGCGAGATCGGCAGGAGGGTCGACGGC
NO V40g, 319067006 SEQ ID NO: 49δ 243 aa MW at 27175.5kD Protein Sequence
TSRTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKSLI GKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTLRL TSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQAQQRVRDGK VQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRRVDG
NOV40h, 3195060δ6 SEQ ID NO: 499 117δ bp DNA Sequence ORF Start: at 7δ ORF Stop: end of sequence
CACCTCGCGACCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACACAG
AAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAGAA
GGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTACA GTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGAAG GATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGAGCAACCTGCAAGCAATCAAGGCCAGTC TACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCATCACTTCTC TCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTGCCCGCCGAG CTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGTACCACTGGA AAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAACCCCAGGAT ACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACCCTATCAAGA AGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTGTGCCGTAGG GGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCCTCAACTGGC AGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATGCCAACAAAC ACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAACACCATAGA TTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCTGGAGATCAC AGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCATTGATTGGA GTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGCTCCTGGATGGCAG CAGGCTGATTGCCCTCGAGGGC
NOV40h, 319506086 SEQ ID NO: 500 367 aa MW at 40968.5kD Protein Sequence
SMDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLV HREADEFTRQEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQT TPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAF KFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPTNTVS LPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYG RKGLPPSHTQYDFVELLDGSRLIALEG
NOV40i, CG55069-03 SEQ ID NO: 501 58473 bp DNA Sequence ORF Start: ATG at 258 ORF Stop: TAA at 8142 iTTGACAGAAAAAGGCAGTAAACGGGGAATCTCTTTTTTTGAATAAAGAAGAAGAAGAAATAAAGTACC
TGTCATCTTGACAAGTGGCGGAGCGGAGGAGTCAAGGATTATAAATGATCACAGCCAGGTCCAGCTCG
CCCCGTGATTGGGCTCTCCCGCGATCTGCACCGGGGGAAGCGCATGAGAGGCCAATGAGACTTGAACC
CTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACACAGAAGGAATGAAGTATGGATGTGAAAGAA
CGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAGAAGGAACGGCGCTACACAAATTCCTCCGC AGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTACAGTTCCAGCGAGACATTGAAAGCTTTTG ATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGAAGGATTTGGTTCACAGAGAAGCAGACGAG TTCACTAGACAAGAGCAACCTGCAAGCAATCAAGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCA TAAGCAGCACTCTGCACAGCATCATCCATCCATCACTTCTCTCAACAGAAACTCCCTGACCAATAGAA GGAACCAGAGTCCGGCCCCGCCGGCTGCTTTGCCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAG CTGCAGGACAGCTGGGTCCTTGGCAGTAATGTACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGG AACAGGTACAACGCCACTGTTCAGTACTGCAACCCCAGGATACACAATGGCATCTGGCTCTGTTTATT CACCACCTACTCGGCCACTACCTAGAAACACCCTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCA AAGTACTGTAGCTGGAAATGCACTGCACTGTGTGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCT GTCTTATTTTATAGCAATGCATCTCTTTGGCCTCAACTGGCAGCTACAGCAGACTGAAAATGACACAT TTGAGAATGGAAAAGTGAATTCTGATACCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAAT GGAAAATTAGGTGGATTTACGCAAGAAAATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAG AGCAATTCAAGAGATTCCTCCCGGGATCTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTC TTAAATTCAATATCTCTCTTCAGAAGGATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCT TCCCATACTCAGTATGACTTCGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAG CCTGCTTGAGACGGAGAGAGCCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCC AGTACTTGGATTCTGGAATCTGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCT TTTAATACCATTGTTATAGAGTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGT TTCTGGAACTTGCCATTGTTTTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGT TATGTAGTGGCAACGGGCAGTACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAG TGTGATGTGCCGACTACCCAGTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTC TTGTGCTTGCAACTCAGGATACAAAGGAAAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTT CTAATCATGGTGTGTGTATCCACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAA ATACTGAAGACCATGTGTCCAGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTG CACGTGTGACCCTAACTGGACTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCAC ACGGCGTTTGCATGGGGGGGACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGA GCCTGCCACCCCCGCTGTGCCGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTG GAATGGAGAGCACTGCACTATCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAG AGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTG TGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGA CAATGAAGGGGATGGACTCATTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATC AGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAG CAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACC TGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAA CTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAG GACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATT CCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGG AGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTG TCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGT ACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAG GGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCAT CTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATAC TTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAG TTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGC
TATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAA CGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCA TCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAG TTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGT GCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATA GCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGAC ACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGA AGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGG CCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTT GATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTT GACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCA CTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATC ACTGAAAATCGTCAAGTTCGCATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATA TCCTGTGGGGAAGCACGCGGTGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTG GGGTCCTGTACATTACTGAAACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGA GAAATCTCCTTAGTGGCCGGAATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTA CCAGAGTGGAGATGGCTACGCCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAG ATGGTACACTGTATATTGCAGATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTA CTTAACTCTATGAACTTCTATGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAA TGGTACTCACCAATATACTGTAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATG ACAATGATATTACTGCTGTGACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGC ATGCCAGTTCGAGTGGTGTCTCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTT GAAAGGCATGACTGCTCAAGGACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAG CCACTAAAAGTGATGAAACTGGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAAT GTTACGTTTCCAACTGGAGTGGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACAT TGAGTCATCTAGCCGAGAAGAAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACA CCATGGTTCAAGATCAGTTAAGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTAC GCCAGTGGCCTGGACTCACACTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGT TGCCAAAAGAAACATGACTTTGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAG AGCAAGCCCAAGGGAAAGTCAATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCA GTTGACTTTGATCGAACAACAAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGAT CGCCTACGACACGTCTGGGCACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCA CCTATTCATCCACAGGTCAAATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGAC GGACAGGGGAGGATCGTGTCTCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAA GTCCATGGTTCTTCTGCTTCATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGT CTGCCATCACCATGCCCAGTGTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGC AACATATACAACCCCCCGGAAAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCT ACAAACAGCTTTCTTGGGTACAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAG AAATTTTATATGATAGCACAAGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTA AACCTCCAGAGTGATGGTTTTATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCA GATTTTCCGCTTTAGTGAAGATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTC GAGTGACCAGCATGCAGGGTGTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGAC ATTTCTGGCAAAGTTGAGCAGTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTC TACAGCTGTAATGACCTATACGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGA TATTCAGGTCGCTCATGTACTGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAG ATTAAAATAGGGCCCTTTGCCAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCA AACAGTTTACCTCAATGAAAAGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTAC TGAACCCAAGTAACAGTGCGCGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTG GGTGATGTTCAATATCGGTTGGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATA
TAGCTCCAAGGGGCTTCTAACTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATG
ACGGCCTGGGAAGGCGTGTTTCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGAC
TTAACTTATCCCACTAGGATTACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTA
TGATCTCCAAGGACATCTTTTTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATA
ACACAGGGACACCACTGGCTGTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCA
TATGGGGAAATCTATTTTGACTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTA
TGACCCACTCACCAAATTAATCCACTTTGGAGAAA _GAGATTATGACATTTTGGCAGGACGGTGGACAA CACCTGACATAGAAATCTGGAAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGG AATAACAACCCTGCAAGCAAAATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGT GACATTTGGTTTCCATCTGCACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAAC CTTCTTACGAACTTGTGAAGAGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAA GTGGCGCGGCAGGCCAAGGCCTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCG GGCCGGCGGCGCGCAGTCCTGGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGC TGGCCGTCAGCCAGGGCCGCGTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTG GCGGCCGTGCTCAACAACGCCTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCA CTACTTCATCAAGACCACCACGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGG CGCTGGAGAACGGCATCAACGTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGG TTCGCGGACGTGGAGATGCAGTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGA GGAGAAGGCGCGCATCCTGGAGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGC AGCGCGTGCGCGACGGCGAGGAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGC GCCGGCAAGGTGCAGGGCTACGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGA CAGCGCCAACAACATCCAGTTCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCC
GCCGAGCCGCTCACGCCCTGCCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAA
GAGCCTTCCTCCCGGGGGAATGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGC
TTTTTTCCGAATGACCTTAAAGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACT
CAGTCGGACTGAACGTAGCCAGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTG
GGCCGTCTGTTCCTTCTAGGCACTGTATTTAACTAACTTTA
NOV40i, CG55069-03 SEQ ID NO: 502 2628 aa MW at 293503.3kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTT PESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFK FKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPTNTVSL PSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGR KGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKN AEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSG WKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGKSCEEADCIDPGCSNHGVCIHGECHCSPGWG GSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGP ACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYKEGCPGLCNSNGRCTLDQN GGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSL QSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGY TITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVRP NPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFN LMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCPSCNGQ ADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSSNPAHRYYLATDPVTGD LYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNG LIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNN WLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQ VTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVS KNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIR RDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFDYDSE GRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQLRNSYQIGYDGS LRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNLVEWRFRKEQAQGKVNVFGRKLRVNG RNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLWLPSSKLMAVNVTYSSTGQIASIQRGTTSE KVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRS IGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAG VLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDL YQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGR VTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLTPLRYDLRD RITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDGLGRRVSSKTSLGQHLQ FFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGDEFYIASDNTGTPLAVFSSNGLMLKQ IQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGERDYDILAGRWTTPDIEIWKRIGKDPAPFN LYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIF GVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANE DCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWN GRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWTEGEK RQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
NOV40J, 219937039 SEQ ID NO: 503 1854 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGAT CCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTAC GGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTG ACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCA GTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAAT CATATCAACTCTTCTGGGTTCTAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGC ACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTAT GTCCTGGATAATGTCGAC
NOV40J, 219937039 SEQ ID NO: 504 618 aa MW at 6δ016.2kD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSSNPAHRYYLATD PVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMA VDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIY VLDNVD
NO V40k, 219937046 SEQ ID NO: 505 Ilδ54 bp DNA Sequence ORF Start: at 1 [ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGTTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAGTGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGCGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGAT CCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTAC GGGGGCAAAAGACTCGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTG ACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCA GTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAAT CATATCAACTCTTCTGGGTTCTAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGC ACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTAT GTCCTGGATAATGTCGAC
NOV40k, 219937046 SEQ ID NO: 506 61 δ aa MW at 67935.1kD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVASGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHALDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSSNPAHRYYLATD PVTGDLYVSDTNTRRIYRPKSLTGAKDSTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMA VDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIY VLDNVD
NOV401, 2199375δ3 SEQ ID NO: 507 lδ34 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
TAAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAG CCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCC GATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACAT CATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCC TTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTC ATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTA CCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCT CTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAAT GTCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAG TGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTG AAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTG AAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTC TATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGT GGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAA GTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCT GTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACAT TAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTC ATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCC CAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATG GCAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTC TTAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTA CGTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTA AAAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGAT GGAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAAT CTACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGTT CTAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTG GAATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV401, 219937583 SEQ ID NO: 50δ 611 aa MW at 67062.2kD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLY VSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLI YFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV40m, 219937000 SEQ ID NO: 509 1833 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTAC GTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAA AAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATG GAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATC TACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGTTC TAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGG AATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV40m, 219937000 SEQ ID NO: 510 611 aa MW at 67062.2kD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLY VSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLI YFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD NO V40n, 219937005 SEQ ID NO: 511 1833 bp DNA Sequence ORF Start: at 1 [ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGCTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACGGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTAC GTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAA AAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATG GAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATC TACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGTTC TAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGG AATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV40n, 219937005 SEQ ID NO: 512 611 aa MW at 67062.2kD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSAGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVRNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLY VSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLI YFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV40o, 219937013 SEQ ID NO: 513 1833 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTAC GTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAA AAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATG GAGGGAAGGCCGCGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATC TACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTC TAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGG AATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV40o, 219937013 SEQ ID NO: 514 61 1 aa MW at 67034. lkD Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWI PWNVFYVMDTLVMKKEENDI PSCDLS GFVRPNPI IVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLY VSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAAEATLMSPKGMAVDKNGLI YFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV40p, 219937063 SEQ ID NO: 515 1833 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGTCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGCACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTAC GTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAA AAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATG GAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATC TACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGTTC TAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGG AATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV40p, 219937063 SEQ ID NO: 516 611 aa MW at 67026. lkD
Protein Sequence
KLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQSYCRGLPDPQDI ISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHY PEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLS GFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQS IIPFNLMKVHLMVAVVGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAVVSVGYEYESCLDLTL WEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCP SCNGQADGNKLLAPVALACGIDGSLHVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLY VSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLI YFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV40q, CG55069-09 SEQ ID NO: 517 2536 bp DNA Sequence ORF Start: at 7 ORF Stop: at 2470
GGTACCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATAC
CATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAA ATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATC TTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGA TGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGC TCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGG CAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCT GGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGG TGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGA TTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAA GGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTG ACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAAAGGA GAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGA ATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGT GCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCA GACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCG CTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACG GGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCAC TATTTGGATAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGA CCAAAATGGCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGA CTCTTTGCACAGATAGTAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCGATTGCTGC CTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCA AAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGAT CTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGC CAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATA TGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTT TGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTAT GTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGATTCGT GAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGACAGTC CCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACTCTCC TACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTATTCC ATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTTCCTG CCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTATGGT CTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGGAAAA GAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGATAAAC ATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTCCCAG CAGCCTCCAGTCGTGAGTAGCGTCGACGCTACACACGACTGGAGGCTGCTGGTCATTTTCAGCTCTGC AGTAGCTGCCAGTTGGTACC
NOV40q, CG55069-09 SEQ ID NO: 51 δ 821 aa MW at 898δ6.1kD Protein Sequence
NWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFW RSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQ SSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQV LTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVM DTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYL SSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLS EAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQP PWSS
NOV40r, 309327410 SEQ ID NO: 519 2482 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCTCGCGAAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTG ATACCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAA GAAAATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGG GATCTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGA AGGATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTG GAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGG GCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGC ATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCT GTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCC AGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACT CCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGT ATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAA AGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACG GGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGAC CAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGG CCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGT GTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAG CACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGC TCACTATTTGGATAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCC TGGACCAAAATGGCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATG GAGACTCTTTGCACAGATAGTAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCGATTG CTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTA GCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATA GGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAG AGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAG AATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTA ACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTT TTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGAT TCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGAC AGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACT CTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTA TTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTT CCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTA TGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGG AAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGAT AAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTC CCAGCAGCCTCCAGTCGTGAGTAGCCTCGAGGGC
NOV40r, 309327410 SEQ ID NO: 520 827 aa MW at 90529.δkD Protein Sequence
TSRNWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPG IFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAG RQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFP GFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYK GESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTG PDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIA HYLDKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDC CLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIR GQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVF YVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKL SYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVY GLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFIS QQPPWSSLEG
NOV40s, CG55069-02 SEQ ID NO: 521 8645 bp DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at 8314
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGCTCCT GGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGGCAGG CGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCTGGCT TTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGGTGGA ATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGATTTC TGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAAGGGC CGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTGACCC ACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGATACAAAGGAGAAA GTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGAATGT CACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGTGCTC CGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCAGACT GCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCGCTGT GAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACGGGAC CTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCACTATT TGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGA AGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGA CGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCATTGACTGCATGG ATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAG GACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAG TTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCAT CTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTC CATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGG GGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCAT GGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATTCCCAGCTGTGAT CTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTC TCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAG ATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACC CAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCA
AAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATC AGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTG ACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTG GACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACC AGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCC TGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGAT CGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTGGAAATGTAACAA GTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGATACTACCTTGCA ACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTC ACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTC CGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGA ATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAA TGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCA GCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCC ATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCGCATTGCTGCTGG ACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGGTGCAGACAACAC TGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAAACTGATGAGAAG AAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGGAATACCTTCAGA GTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACGCCAAGGATGCCA AACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCAGATCTAGGGAAT ATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTATGAAGTTGCGTC TCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTGTAAGTTTAGTCA CTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTGACAGACAGCAAT GGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTCTCCTGATAACCA AGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAGGACTGGAATTAG TTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACTGGATGGACAACG TTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGTGGTCACAAACCT GCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAGAAGATGTCAGCA TCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTAAGAAACAGCTAC CAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACACTACCAAACAGA GCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTTTGCCTGGCGAGA ACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTCAATGTCTTTGGC CGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAACAAAGACAGAAAA GATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGCACCCGACTCTCT GGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAAATTGCCAGCATC CAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTCTCGGGTCTTTGC TGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTCATAGCCAGCGGC AGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGTGTGGCTCGCCAC ACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGAAAGCAACGCCTC CATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTACAAGTCGGAGGG TCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACAAGAGTCAGTTTT ACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTTTATTTGCACCAT TAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAGATGGGATGGTAA ATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGTGTGATCAATGAA ACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCAGTTTGGAAAGTT TGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATACGAAGCACTTTG ATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTACTGGATTACAATT CAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGCCAACACCACCAA ATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAAAGATAATGTGGC
GGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCGCGTCTGACACCC CTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTTGGATGAAGATGG TTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAACTCGAGTTTACA GTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTTTCTAGCAAAACC AGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGATTACTCATGTCTA CAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTTTTGCCATGGAAA TCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCTGTGTTCAGTAGC AATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGACTCTAATATTGA CTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAATCCACTTTGGAG AAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGGAAAAGAATTGGG AAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAAAATCCATGACGT GAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGCACAATGCTATTC CTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAGAGTCAGCAGTGG GATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGCCTTCCTGTCGCT GGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCTGGCTGTGGTTCG CCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGCGTGCAGACCAAC GTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGCCTTCTACCTGGA GAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCACGCCCGAGAGCG ACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAACGTGACGGTGTCG CAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCAGTTCGGCGCGCT GGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGGAGCAGGCGCGGC AGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAGGAGGGCGCGCGC CTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTACGACGGGTACTA CGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGTTCCTGCGGCAGA GCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTGCCCACATTGTCC
TGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAATGAGACTGCTGT
TACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAAAGGTGATCGGCT
TTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCCAGAGGAAAAAAA
AATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGGCACTGTATTTAA
CTAACTTTA
NOV40s, CG55069-02 SEQ ID NO: 522 2721 aa MW at 303489.1kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVS LHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFLGPDC SRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGESCEEA DCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEI CSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIV KDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCC LQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRG QVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFY VMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLS YLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYG LSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQ QPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLEL RNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEA RCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHIS QVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTLESAT AIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAKLSAP SSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVTGDYL YNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTY HGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSITSNL SSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNL VEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLWLPSS KLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQYIFE YDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRVLFKY RRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVNARFD YSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGR IKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYD LNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSG WTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGD EFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGERDYD ILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIPGFPV PKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKS LIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTL RLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALA RAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGR NOV40t, CG55069-05 SEQ ID NO: 523 δlO bp DNA Sequence ORF Start: at 7 ORF Stop: at δ05
AAGCTTTGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGG
ATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCA AGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATT GACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAAAGG AGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGG AATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAG TGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCC AGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTC GCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCAC GGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCA CTATTTGGATAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGG ACCAAAATGGCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTCGAC
NOV40t, CG55069-05 SEQ ID NO: 524 266 aa MW at 27935.0kD Protein Sequence
CPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDP QCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCS GHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGT CKDGKCECSQGWNGEHCTIAHYLDKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCD
NOV40u, CG55069-06 SEQ ID NO: 525 δ204 bp DNA Sequence ORF Start: ATG at 4 ORF Stop: TAA at δ 179
AGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAGAAGGAACGGCG CTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTACAGTTCCAGCG AGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGAAGGATTTGGTT CACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTAGGAGTTTGTGA ACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGGTTACTCTATCA GTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCATGAGACTTTGG GGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCCCTCACCCTGAC AGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCAAGGCCAGTCTA CCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCATCACTTCTCTC AACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTGCCCGCCGAGCT GCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGTACCACTGGAAA GCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAACCCCAGGATAC ACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACCCTATCAAGAAG TGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTGTGCCGTAGGGG TCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCCTCAACTGGCAG CTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATGCCAACAAACAC TGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAACACCATAGATT CCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCTGGAGATCACAG CTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCATTGATTGGAGT ATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTTCGTGGAGCTCC TGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGGCAG GCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCTGGC TTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGGTGG AATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGATTT CTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAAGGG CCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTGACC CACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGATACAAAGGAGAA AGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGAATG TCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGTGCT CCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCAGAC TGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCGCTG TGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACGGGA CCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCACTAT TTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGG AAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTG ACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCATTGACTGCATG GATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCA GGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCA GTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCA TCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTT CCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTG GGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCA TGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATTCCCAGCTGTGA TCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTT CTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACA GATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGAC CCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCC AAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAAT CAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCT
GACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCT GGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAAC CAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTC CTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGA TCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTGGAAATGTAACA AGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGATACTACCTTGC AACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGT CACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTT CCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGG AATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAA ATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACC AGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTC CATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCGCATTGCTGCTG GACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGGTGCAGACAACA CTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAAACTGATGAGAA GAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGGAATACCTTCAG AGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACGCCAAGGATGCC AAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCAGATCTAGGGAA TATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTATGAAGTTGCGT CTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTGTAAGTTTAGTC ACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTGACAGACAGCAA TGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTCTCCTGATAACC AAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAGGACTGGAATTA GTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACTGGATGGACAAC GTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGTGGTCACAAACC TGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAGAAGATGTCAGC ATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTAAGAAACAGCTA CCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACACTACCAAACAG AGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTTTGCCTGGCGAG AACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTCAATGTCTTTGG CCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAACAAAGACAGAAA AGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGCACCCGACTCTC TGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAAATTGCCAGCAT CCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTCTCGGGTCTTTG CTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTCATAGCCAGCGG CAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGTGTGGCTCGCCA CACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGAAAGCAACGCCT CCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTACAAGTCGGAGG GTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACAAGAGTCAGTTT TACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTTTATTTGCACCA TTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAGATGGGATGGTA AATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGTGTGATCAATGA AACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCAGTTTGGAAAGT TTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATACGAAGCACTTT GATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTACTGGATTACAAT TCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGCCAACACCACCA AATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAAAGATAATGTGG CGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCGCGTCTGACACC CCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTTGGATGAAGATG
GTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAACTCGAGTTTAC AGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTTTCTAGCAAAAC CAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGATTACTCATGTCT ACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTTTTGCCATGGAA ATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCTGTGTTCAGTAG CAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGACTCTAATATTG ACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAATCCACTTTGGA GAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGGAAAAGAATTGG GAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAAAATCCATGACG TGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGCACAATGCTATT CCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAGAGTCAGCAGTG GGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGCCTTCCTGTCGC TGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCTGGCTGTGGTTC GCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGCGTGCAGACCAA CGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGCCTTCTACCTGG AGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCACGCCCGAGAGC GACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAACGTGACGGTGTC GCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCAGTTCGGCGCGC TGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGGAGCAGGCGCGG CAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAGGAGGGCGCGCG CCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTACGACGGGTACT ACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGTTCCTGCGGCAG AGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGC
NOV40u, CG55069-06 SEQ ID NO: 526 2725 aa MW at 303959.6kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIPSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40v, CG55069-07 SEQ ID NO: 527 1833 bp DNA Sequence ORF Start: at 7 ORF Stop: at l82δ
AAGCTTGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGC
CATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCG ATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATC ATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCT TATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCA TCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTAC CCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTC TCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATG TCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGT GGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGA AGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGA AACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCT ATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTG GTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAG TCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTG TGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATT AGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCA TCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCC AGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGG CAGTCTGTACGTAGGCGATTTCAACTATGTGCGGCGGATATTCCCTTCTGGAAATGTAACAAGTGTCT TAGAACTAAGCAGCAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTAC GTTTCTGACACAAACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAA AAATGCAGAAGTCGTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATG GAGGGAAGGCCGTGGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATC TACTTTGTTGATGGAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGTTC TAACGATTTGACTTCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGG AATGGCCCACTGACCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATGTCGAC
NOV40v, CG55069-07 SEQ ID NO: 52δ 607 aa MW at 66606.6kD Protein Sequence
DQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIIS QSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPE YGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGF VRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSII PFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWE KRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCPSC NGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELSSNPAHRYYLATDPVTGDLYVS DTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLIYF VDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDN
55δ NOV40w, CG55069-0δ SEQ ID NO: 529 δ4δ7 bp DNA Sequence ORF Start: ATG at 299 ORF Stop: TAA at 8138
ACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTCCCATTTGACAGAAAAAGGCAGTAAACGGGGA
ATCTCTTTTTTTGAATAAAGAAGAAGAAGAAATAAAGTACCTGTCATCTTGACAAGTGGCGGAGCGGA
GGAGTCAAGGATTATAAATGATCACAGCCAGGTCCAGCTCGCCCCGTGATTGGGCTCTCCCGCGATCT
GCACCGGGGGAAGCGCATGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGAC,
TGATGTGCACACAGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAG
AGCAGACGAGAGAAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCAC ACAGAAGTCCTACAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACG GCAACAGAGTGAAGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGAGCAACCTGCAAGC AATCAAGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCC ATCCATCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTG CTTTGCCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGT AATGTACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTAC TGCAACCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAA ACACCCTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCA CTGTGTGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTT TGGCCTCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATA CCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAA AATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGAT CTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGG ATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAG CTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCG GCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATC TGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTG GTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGG ATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCA AGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATT GACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAACTCAGGATACAAAGG AGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGG AATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAG TGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCC AGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTC GCTGTGAAGAAGGCTGGACGGGCCCAACCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCAC GGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCATGGCTGGAATGGAGAGCACTGCACTATCGAGGG TTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGTGTGCC AGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAAT GAAGGAGATGGACTCATTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCC CTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAG CTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGA GAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCC ACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACG GAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTC ACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAA AGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCAT CACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTC CACGAGGAAACTACAATTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTA TAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTA TGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTC ATATGGGATAAAACAGATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGG ATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATG
AATTGGATGCGTCCAACATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGT ATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCAT GGGCAATGGGCGAAGGCGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTAC TGGCCCCAGTGGCGCTAGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGG CGGATATTCCCTTCTGGAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAG CAACCCAGCTCATAGATACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAA ACACCCGCAGAATTTATCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTC GTCGCAGGGACAGGGGAGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGT GGAAGCCACACTCATGAGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATG GAACCATGATTAGGAAAGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACT TCAGCCAGACCTTTAACTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGA CCTAGCCATTAACCCTATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTG AAAATCGTCAAGTTCGCATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCT GTGGGGAAGCACGCGGTGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGT CCTGTACATTACTGAAACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAA TCTCCTTAGTGGCCGGAATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAG AGTGGAGATGGCTACGCCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGG TACACTGTATATTGCAGATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTA ACTCTATGAACTTCTATGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGT ACTCACCAATATACTGTAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAA TGATATTACTGCTGTGACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGC CAGTTCGAGTGGTGTCTCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAA GGCATGACTGCTCAAGGACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCAC TAAAAGTGATGAAACTGGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTA CGTTTCCAACTGGAGTGGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAG TCATCTAGCCGAGAAGAAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCAT GGTTCAAGATCAGTTAAGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCA GTGGCCTGGACTCACACTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCC AAAAGAAACATGACTTTGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCA AGCCCAAGGGAAAGTCAATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTG ACTTTGATCGAACAACAAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCC TACGACACGTCTGGGCACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTA TTCATCCACAGGTCAAATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGAC AGGGGAGGATCGTGTCTCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCC ATGGTTCTTCTGCTTCATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGC CATCACCATGCCCAGTGTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACA TATACAACCCCCCGGAAAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAA ACAGCTTTCTTGGGTACAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAAT TTTATATGATAGCACAAGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACC TCCAGAGTGATGGTTTTATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATT TTCCGCTTTAGTGAAGATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGT GACCAGCATGCAGGGTGTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTT CTGGCAAAGTTGAGCAGTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACA GCTGTAATGACCTATACGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATT CAGGTCGCTCATGTACTGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTA AAATAGGGCCCTTTGCCAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACA GTTTACCTCAATGAAAAGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAA CCCAAGTAACAGTGCGCGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTG ATGTTCAATATCGGTTGGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGC
TCCAAGGGGCTTCTAACTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGG CCTGGGAAGGCGTGTTTCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAA CTTATCCCACTAGGATTACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGAT CTCCAAGGACATCTTTTTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACAC AGGGACACCACTGGCTGTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATG GGGAAATCTATTTTGACTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGAC CCACTCACCAAATTAATCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACC TGACATAGAAATCTGGAAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATA ACAACCCTGCAAGCAAAATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACA TTTGGTTTCCATCTGCACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTC TTACGAACTTGTGAAGAGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGG CGCGGCAGGCCAAGGCCTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCC GGCGGCGCGCAGTCCTGGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGC CGTCAGCCAGGGCCGCGTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGG CCGTGCTCAACAACGCCTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTAC TTCATCAAGACCACCACGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCT GGAGAACGGCATCAACGTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCG CGGACGTGGAGATGCAGTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAG AAGGCGCGCATCCTGGAGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCG CGTGCGCGACGGCGAGGAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCG GCAAGGTGCAGGGCTACGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGC GCCAACAACATCCAGTTCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCG
AGCCGCTCACGCCCTGCCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGC
CTTCCTCCCGGGGGAATGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTT
TTCCGAATGACCTTAAAGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGT
CGGACTGAACGTAGCCAGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCC
GTCTGTTCCTTCTAGGCACTGTATTTAACTAACTTTAAAAAAAAAAAAAAAAAAG
NOV40w, CG55069-08 SEQ ID NO: 530 12613 aa MW at 291899.4kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTT PESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFK FKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPTNTVSL PSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGR KGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKN AEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSG WKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWG GSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGP TCNQRACHPRCAEHGTCKDGKCECSHGWNGEHCTIEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGC DVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRI SFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANG GASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRS SPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLF QKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGG WTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACG IDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPK SLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQ NGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAA GRPMHCQVPGVEYPVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPS ECDCKNDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVA SPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDN QVIWLTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTN LHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQT EPHVLAGTANPTVAKRNMTLPGENGQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTE KIYDDHRKFLLRIAYDTSGHPTLWLPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVF ADGKTWSYTYLEKSMVLLLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNA SIITDYNEEGLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICT IRYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGK FGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTT KYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDED GFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHV YNHSSSEITSLYYDLQGHLFAMEISSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNI DFQLVIGFHGGLYDPLTKLIHFGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHD VKDYITDVNSWLVTFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLS LGKMAEVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYL ENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGA LALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGY YVLSVEQYPELADSANNIQFLRQSEIGRR
NOV40x, CG55069-10 SEQ ID NO: 531 2519 bp DNA Sequence ORF Start: at 7 ORF Stop: at 24δδ
GGTACCAACTGGCAGCTACAGCAGACTGAAAATGACGCATTTGAGAATGGAAAAGTGAATTCTGATAC
CATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAA ATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATC TTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGA TGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGC TCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGG CAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGCATCT GGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGG TGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGA TTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAA GGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTG ACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAACTCAGGATACAAAGGA GAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGA ATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGT GCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCA GACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGCCG CTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACG GGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCAC TATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAA TGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGCGTGCCAGCCTGGATGGAGAGGAGCAGGCT GTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGACTGC ATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCC TCAGGGCATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAA TCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTT GCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTT TTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATG GTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATT CCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTG TGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGAT CTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGA ACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCAT GACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCT TCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATAT AATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGA CCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTG GCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAA AACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCGTCGACCCAGCAGCCTCCAGTCGTGAGTA GCG
NOV40x, CG55069-10 SEQ ID NO: 532 δ27 aa MW at 90474.δkD Protein Sequence
NWQLQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFW RSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSS
NOV40y, CG55069-11 SEQ ID NO: 533 24δ2 bp DNA Sequence ORF Start: at 11 ORF Stop: at 2474
CACCTCGCGAAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTG
ATACCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAA GAAAATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGG GATCTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGA AGGATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTG GAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGG GCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGC ATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCT GTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCC AGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACT CCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGT ATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAA AGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACG GGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGAC CAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGG CCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGT GTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAG CACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGC TCACTATTTGGATAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCC TGGACCAAAATGGCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATG GAGACTCTTTGCACAGATAGTAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCGATTG CTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTA GCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATA GGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAG AGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAG AATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTA ACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTT TTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGAT TCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGAC AGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACT CTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTA TTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTT CCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTA TGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGG AAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGAT AAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTC CCAGCAGCCTCCAGTCGTGAGTAGCCTCGAGGGC
NOV40y, CG55069-l l SEQ ID NO: 534 821 aa MW at 89δδ6.1kD Protein Sequence
NWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFW RSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQ SSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQV LTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVM DTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYL SSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLS EAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQP PWSS
NOV40z, CG55069-12 SEQ ID NO: 535 2500 bp DNA Sequence ORF Start: at 11 ORF Stop: at 2492
CACCAAGCTTAACTGGCAGCTACAGCAGACTGAAAATGACGCATTTGAGAATGGAAAAGTGAATTCTG
ATACCATGCCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAA GAAAATAACACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGG GATCTTCTGGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGA AGGATGCATTGATTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTG GAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGG GCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATCTGGC ATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCT GTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCC AGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACT CCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGT ATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAACTCAGGATACAA AGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACG GGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGAC CAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGG CCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGT GCCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAG CACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGC TCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGCAACA GCAATGGAAGATGTACCCTGGACCAAAATGGCTGGCATTGTGCGTGCCAGCCTGGATGGAGAGGAGCA GGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGAGATGGACTCATTGA CTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGG ATCCTCAGGGCATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGAT CGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAG CCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCT CGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCA AATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTGTGTG GATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCA GCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTC AGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAATTCC AGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCA CCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGA CTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAGATGC ATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTT TGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATG GGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAAACGG GGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCCTCGAGGGC
NOV40z, CG55069-12 SEQ ID NO: 536 δ27 aa MW at 90474.δkD Protein Sequence
NWQLQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFW RSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSS
NOV40aa, CG55069-13 SEQ ID NO: 537 2541 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 2530
CACCGCGGCCGCACCATGCTGCCCGGTTTGGCACTGCTCCTGCTGGCCGCCTGGACGGCTCGGGCGAA
CTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATGCCAA CAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAACACC ATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCTGGAG ATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCATTGA TTGGAGTATATGGCCGGAAAGGCTTACCGCCTTCCCATACTCAGTATGACTTCGTGGAGCTCCTGGAT GGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAGCCGGGCGGCAGGCGAG ATCCGTCAGCCTTCATGAGGCCGGCTCTATCCAGTACTTGGATTCTGGAATCTGGCATCTGGCTTTTT ATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGAGTCTGTGGTGGAATGT CCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTTTTCCAGGATTTCTGGG TCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAGTACTCCAAGGGCCGCT GCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCAGTGTATTGACCCACAG TGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAACTCAGGATACAAAGGAGAAAGTTG TGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATCCACGGGGAATGTCACT GCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCCAGACCAGTGCTCCGGC CACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGACTGGCCCAGACTGCTC AAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGGACGTGTCGCTGTGAAG AAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGCCGAGCACGGGACCTGC AAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTATCGCTCACTATTTGGA TAAGATAGTTAAAGAGGGTTGTCCTGGTCTGTGCAACAGCAATGGAAGATGTACCCTGGACCAAAATG GCTGGCATTGTGTGTGCCAGCCTGGATGGAGAGGAGCAGGCTGTGACGTAGCCATGGAGACTCTTTGC ACAGATAGTAAGGACAATGAAGGAGATGGACTCATTGACTGCATGGATCCCGATTGCTGCCTACAGAG TTCCTGCCAGAATCAGCCCTATTGTCGGGGACTGCCGGATCCTCAGGACATCATTAGCCAAAGCCTTC AATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTATGATCGAATCAGTTTCCTTATAGGATCTGATAGC ACCCATGTTATACCTGGAGAAAGTCCTTTCAATAAGAGCCTTGCATCTGTCATCAGAGGCCAAGTACT GACTGCTGATGGAACTCCACTTATTGGAGTAAATGTCTCGTTTTTCCATTACCCAGAATATGGATATA CTATTACCCGCCAGGACGGAATGTTTGACTTGGTGGCAAATGGTGGGGCCTCTCTAACTTTGGTATTT GAACGATCCCCATTCCTCACTCAGTATCATACTGTGTGGATTCCATGGAATGTCTTTTATGTGATGGA TACCCTAGTCATGAAGAAAGAAGAGAATGACATTCCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAA ATCCCATCATTGTGTCATCACCTTTATCCACCTTTTTCAGATCTTCTCCTGAAGACAGTCCCATCATT CCCGAAACACAGGTACTCCACGAGGAAACTACAATTCCAGGAACAGATTTGAAACTCTCCTACTTGAG TTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAGATCACCATGACCCAGTCTATTATTCCATTTAATT TAATGAAGGTTCATCTTATGGTAGCTGTAGTAGGAAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCA AACTTGGCCTATACTTTCATATGGGATAAAACAGATGCATATAATCAGAAAGTCTATGGTCTATCTGA AGCTGTTGTGTCAGTTGGATATGAGTATGAGTCGTGTTTGGACCTGACTCTGTGGGAAAAGAGGACTG CCATTCTGCAGGGCTATGAATTGGATGCGTCCAACATGGGTGGCTGGACATTAGATAAACATCACGTG CTGGATGTACAGAACGGTATACTGTACAAGGGAAACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCC AGTCGTGAGTAGCTAGGTCGACGGC
NOV40aa, CG55069-13 SEQ ID NO: 53δ 838 aa MW at 91589. lkD Protein Sequence
MLPGLALLLLAAWTARANWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGE LDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLI AREQRSLLETERAGRQARSVSLHEAGSIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCH GNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRG ICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYL QESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKC ECSQGWNGEHCTIAHYLDKIVKEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKD NEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIP GESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPF LTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQV LHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYT FIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQN GILYKGNGENQFISQQPPWSS
NOV40ab, CG55069-14 SEQ ID NO: 539 1755 bp DNA Sequence ORF Start: ATG at 890 ORF Stop: TAA at 1532
GAGAAAGGAGATTAAAAATAACCTCTGGATATTCCTCTCATGTGATCTTTATTCTGGATGAAGCATTA GGACAGCTAATAGCCGTGTGTCACTGTGTGATTTCTTCCCTAAGACTAAGGACCCATCATTTTAGTGC AACCTTCTTCATTTAAATGGAGAGTTGTAATTGCCAATGCTCACAGCTACTCCTGCTCCGGCAATTTG CTGCCAGAAGTGTGTTTTCCTTTTTAAAAGGCAGTAAATTCAAGATGTTGTGGTGGATGTAGATTTTT GCTGCAAGGAAATAACAGCTGGTGATGGAATTTCATTCTTTTGACTTCTAGATTGCCTGTGAAGAGCT GCTTCCTCGGAAGAGCACCCTAAGGCTGGGTGGCCACTATCCTTTGCCTTGGCAGAGCCAGCCAGAAG GCCTAGGCACAACCCGCTGTGTTTGCTGACAGCCAACCTACCCTGGAGTTCCGGAGCGGCTTCCTAGG AAGACTGGGGAGCGGTAGAAAAATGGCTCTGCTGAGATGAGCTCTTAATTAATGCACTGAGAGCCTGC AAGTCCCACCTCTCAACAGGAATGATTGACGTCCAAGGATACATAAATTACACTAACTGAGCTCTGCC TCTATATAAGCTTTCCACATCCAACTCATCAGAGAAGCTAGGCTTGTACCATAACCAATACCCCTGCT TGGCAACTCTAATGAGCAAACTGCCGCAAAATTGAGAGAGAACACACCTTTTTGATTTCCTGCTCTTC TAAGACACAGTGATTTAGAATTTCTGTTCAAGCAAGAGAACTAAAGACTTCTTTAAAGAAGAGAAGAG AGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACACAGAAGGAAT GAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAGAAGGAACGG
CGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACACAACTCCTACAGTTCCAG CGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGAAGGATTTGG TTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTAGGAGTTTGT GAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGGTTACTCTAT CAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCATGAGACTTT GGGGCAGGGGGTTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCCCTCACCCTG ACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGGAGGGTCAAGCAGTTGGTTCGGTTTTCA TTGGAATTTTTATGTGAGTAAAGCTTCCTGTTTGCTGCGCTTGCCTAGGATTTTCTTATCCCACAACT ACAATGTGAACAAAGAGATGAGAGAGAAATTATGCTAATGCATTTTGGTGGATCAAATGAGTGTTTCA
TGAGACAACTCAAATTTTTGTTAGCTATATGGTGTTGGAATATAATTTCAAAGACAACTAAGCCCTAA
AATAGGAGATTTATTTAAAACATAACTTTTCCTTGAATGAAAGGATGTTTTTGTTCTTTCTCTGACAA
ATATGATTTGAGAATAAAAGACCTGCCCGGGCAGCCGCTCGAGCCCTATAGTGAG
NOV40ab, CG55069-14 SEQ ID NO: 540 214 aa MW at 24449.8kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTHNSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGFKSGRSSCLSSRSNSALTLTDTEHENKSDSENGGSSSWFGFHWNFYVSKASCLLRLPRIFLSHNYN VNKEMREKLC
NOV40ac, CG55069-15 SEQ ID NO: 541 768 bp DNA Sequence ORF Start: ATG at 65 ORF Stop: TAA at 707
AGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACACAGAAGGAATGAAGTATGG
ATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAGAAGGAACGGCGCTACACA AATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTACAGTTCCAGCGAGACATT GAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGAAGGATTTGGTTCACAGAG AAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTAGGAGTTTGTGAACCAGCA ACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGGTTACTCTATCAGTGCAGG GTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCATGAGACTTTGGGGCAGGG GGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCCCTCACCCTGACAGATACG GAGCACGAAAACAAGTCCGACAGTGAGAATGGAGGGTCAAGCAGTTGGTTCGGTTTTCATTGGAATTT TTATGTGGGTAAAGCTTCCTGTTTGCTGCGCTTGCCTAGGATTTTCTTATCCCACAACTACAATGTGA ACAAAGAGATGAGAGAGAAATTATGCTAATGCATTTTGGTGGATCAATGCTAATGCATTTTGGTGGAT CAATGCTAATGCATTTTGGT
NOV40ac, CG55069-15 SEQ ID NO: 542 214 aa MW at 24376.8kD Protein Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENGGSSSWFGFHWNFYVGKASCLLRLPRIFLSHNYN VNKEMREKLC
NOV40ad, SNP13374479 of SEQ ID NO: 543 δ657 bp CG55069-01, DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at δ326
SNP Pos: 465 SNP Change: C to T
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTTCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA AGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC AGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG CACTGTATTTAACTAACTTTA
56δ NOV40ad, SNPl 3374479 of SEQ ID NO: 544 2725 aa MW at 303959.6kD CG55069-01, Protein Sequence SNP Pos: 105 SNP Change: Leu to Leu
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40ae, SNP133δ2453 of SEQ ID NO: 545 8657 bp CG55069-01, DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at 8326
SNP Pos: 973 SNP Change: T to C
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCACCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA AGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC AGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG CACTGTATTTAACTAACTTTA
NOV40ae, SNPl 3382453 of SSBEQ ID NO: 546 2725 aa MW at 303969.7kD
CG55069-01, Protein Sequence SgN^ pos: 275 SNP Change: Ser to Pro
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MAPGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTVVNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40af, SNP13382454 of SEQ ID NO: 547 δ657 bp CG55069-01, DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at δ326
SNP Pos: 1953 SNP Change: C to T
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCTTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA AGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC AGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG CACTGTATTTAACTAACTTTA
NOV40af, SNP133δ2454 of SEQ ID NO: 54δ 2725 aa MW at 303959.6kD CG55069-01, Protein Sequence SNP Pos: 601 SNP Change: Ser to Ser
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40ag, SNP133δ2455 of SEQ ID NO: 549 δ657 bp CG55069-01, DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at δ326 SNP Pos: 2559 SNP Change: C to T
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGTAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTCAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA AGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC AGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG CACTGTATTTAACTAACTTTA
NOV40ag, SNP133δ2455 of SEQ ID NO: 550: 2725 aa MW at 303959.6kD CG55069-01, Protein Sequence SNP Pos: δ03 SNP Change: Ser to Ser
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS EIGRR
NOV40ah, SNP1337δ354 of SEQ ID NO: 551 δ657 bp CG55069-01, DNA Sequence ORF Start: ATG at 151 ORF Stop: TAA at δ326
SNP Pos: 7770 SNP Change: C to T
TTTGGCCTCGGGCCAGAATTCGGCACGAGGGGTCTGGAGCTTGGAGGAGAAGTCTGAACTAAGGATAA
ACTAAAGAGAGGCCAATGAGACTTGAACCCTGAGCCTAAGTTGTCACCAGCAGGACTGATGTGCACAC
AGAAGGAATGAAGTATGGATGTGAAAGAACGCAGGCCTTACTGCTCCCTGACCAAGAGCAGACGAGAG
AAGGAACGGCGCTACACAAATTCCTCCGCAGACAATGAGGAGTGCCGGGTACCCACACAGAAGTCCTA CAGTTCCAGCGAGACATTGAAAGCTTTTGATCATGATTCCTCGCGGCTGCTTTACGGCAACAGAGTGA AGGATTTGGTTCACAGAGAAGCAGACGAGTTCACTAGACAAGGACAGAATTTTACCCTAAGGCAGTTA GGAGTTTGTGAACCAGCAACTCGAAGAGGACTGGCATTTTGTGCGGAAATGGGGCTCCCTCACAGAGG TTACTCTATCAGTGCAGGGTCAGATGCTGATACTGAAAATGAAGCAGTGATGTCCCCAGAGCATGCCA TGAGACTTTGGGGCAGGGGGGTCAAATCAGGCCGCAGCTCCTGCCTGTCAAGTCGGTCCAACTCAGCC
57δ CTCACCCTGACAGATACGGAGCACGAAAACAAGTCCGACAGTGAGAATGAGCAACCTGCAAGCAATCA AGGCCAGTCTACCCTGCAGCCCTTGCCGCCTTCCCATAAGCAGCACTCTGCACAGCATCATCCATCCA TCACTTCTCTCAACAGAAACTCCCTGACCAATAGAAGGAACCAGAGTCCGGCCCCGCCGGCTGCTTTG CCCGCCGAGCTGCAAACCACACCCGAGTCCGTCCAGCTGCAGGACAGCTGGGTCCTTGGCAGTAATGT ACCACTGGAAAGCAGGCATTTCCTATTCAAAACAGGAACAGGTACAACGCCACTGTTCAGTACTGCAA CCCCAGGATACACAATGGCATCTGGCTCTGTTTATTCACCACCTACTCGGCCACTACCTAGAAACACC CTATCAAGAAGTGCTTTTAAATTCAAGAAGTCTTCAAAGTACTGTAGCTGGAAATGCACTGCACTGTG TGCCGTAGGGGTCTCGGTGCTCCTGGCAATACTCCTGTCTTATTTTATAGCAATGCATCTCTTTGGCC TCAACTGGCAGCTACAGCAGACTGAAAATGACACATTTGAGAATGGAAAAGTGAATTCTGATACCATG CCAACAAACACTGTGTCATTACCTTCTGGAGACAATGGAAAATTAGGTGGATTTACGCAAGAAAATAA CACCATAGATTCCGGAGAACTTGATATTGGCCGAAGAGCAATTCAAGAGATTCCTCCCGGGATCTTCT GGAGATCACAGCTCTTCATTGATCAGCCACAGTTTCTTAAATTCAATATCTCTCTTCAGAAGGATGCA TTGATTGGAGTATATGGCCGGAAGAAGTTACCGCCTTCCCATACTCAGTCCTCCCCCCAGTATGACTT CGTGGAGCTCCTGGATGGCAGCAGGCTGATTGCCAGAGAGCAGCGGAGCCTGCTTGAGACGGAGAGAG CCGGGCGGCAGGCGAGATCCGTCAGCCTTCATGAGGCCGGCTTTATCCAGTACTTGGATTCTGGAATC TGGCATCTGGCTTTTTATAATGATGGGAAAAATGCAGAGCAGGTGTCTTTTAATACCATTGTTATAGA GTCTGTGGTGGAATGTCCCCGAAATTGCCATGGAAATGGAGAATGCGTTTCTGGAACTTGCCATTGTT TTCCAGGATTTCTGGGTCCGGATTGTTCAAGAGCCGCCTGTCCAGTGTTATGTAGTGGCAACGGGCAG TACTCCAAGGGCCGCTGCCTGTGTTTCAGCGGCTGGAAGGGCACCGAGTGTGATGTGCCGACTACCCA GTGTATTGACCCACAGTGTGGGGGTCGTGGGATTTGTATCATGGGCTCCTGTGCTTGCAGCTCAGGAT ACAAAGGAGAAAGTTGTGAAGAAGCTGACTGTATAGACCCTGGGTGTTCTAATCATGGTGTGTGTATC CACGGGGAATGTCACTGCAGTCCAGGATGGGGAGGTAGCAATTGTGAAATACTGAAGACCATGTGTCC AGACCAGTGCTCCGGCCACGGAACGTATCTTCAAGAAAGTGGCTCCTGCACGTGTGACCCTAACTGGA CTGGCCCAGACTGCTCAAACGAAATATGTTCTGTGGACTGTGGCTCACACGGCGTTTGCATGGGGGGG ACGTGTCGCTGTGAAGAAGGCTGGACGGGCCCAGCCTGTAATCAGAGAGCCTGCCACCCCCGCTGTGC CGAGCACGGGACCTGCAAGGATGGCAAGTGTGAATGCAGCCAGGGCTGGAATGGAGAGCACTGCACTA TCGCTCACTATTTGGATAAGATAGTTAAAGACAAGATAGGATATAAAGAGGGTTGTCCTGGTCTGTGC AACAGCAATGGAAGATGTACCCTGGACCAAAATGGCGGACATTGTGTGTGCCAGCCTGGATGGAGAGG AGCAGGCTGTGACGTAGCCATGGAGACTCTTTGCACAGATAGCAAGGACAATGAAGGGGATGGACTCA TTGACTGCATGGATCCCGATTGCTGCCTACAGAGTTCCTGCCAGAATCAGCCCTATTGTCGGGGACTG CCGGATCCTCAGGACATCATTAGCCAAAGCCTTCAATCGCCTTCTCAGCAAGCTGCCAAATCCTTTTA TGATCGAATCAGTTTCCTTATAGGATCTGATAGCACCCATGTTATACCTGGAGAAAGTCCTTTCAATA AGAGCCTTGCATCTGTCATCAGAGGCCAAGTACTGACTGCTGATGGAACTCCACTTATTGGAGTAAAT GTCTCGTTTTTCCATTACCCAGAATATGGATATACTATTACCCGCCAGGACGGAATGTTTGACTTGGT GGCAAATGGTGGGGCCTCTCTAACTTTGGTATTTGAACGATCCCCATTCCTCACTCAGTATCATACTG TGTGGATTCCATGGAATGTCTTTTATGTGATGGATACCCTAGTCATGGAGAAAGAAGAGAATGACATT CCCAGCTGTGATCTGAGTGGATTCGTGAGGCCAAATCCCATCATTGTGTCATCACCTTTATCCACCTT TTTCAGATCTTCTCCTGAAGACAGTCCCATCATTCCCGAAACACAGGTACTCCACGAGGAAACTACAA TTCCAGGAACAGATTTGAAACTCTCCTACTTGAGTTCCAGAGCTGCAGGGTATAAGTCAGTTCTCAAG ATCACCATGACCCAGTCTATTATTCCATTTAATTTAATGAAGGTTCATCTTATGGTAGCTGTAGTAGG
AAGACTCTTCCAAAAGTGGTTTCCTGCCTCACCAAACTTGGCCTATACTTTCATATGGGATAAAACAG ATGCATATAATCAGAAAGTCTATGGTCTATCTGAAGCTGTTGTGTCAGTTGGATATGAGTATGAGTCG TGTTTGGACCTGACTCTGTGGGAAAAGAGGACTGCCATTCTGCAGGGCTATGAATTGGATGCGTCCAA CATGGGTGGCTGGACATTAGATAAACATCACGTGCTGGATGTACAGAACGGTATACTGTACAAGGGAA ACGGGGAAAACCAGTTCATCTCCCAGCAGCCTCCAGTCGTGAGTAGCATCATGGGCAATGGGCGAAGG CGCAGCATTTCCTGCCCCAGTTGCAATGGTCAAGCTGATGGTAACAAGTTACTGGCCCCAGTGGCGCT AGCTTGTGGGATCGATGGCAGTCTGTACGTAGGCGATTTCAACTACGTGCGGCGGATATTCCCTTCTG GAAATGTAACAAGTGTCTTAGAACTAAGAAATAAAGATTTTAGACATAGCAGCAACCCAGCTCATAGA TACTACCTTGCAACGGATCCAGTCACGGGAGATCTGTACGTTTCTGACACAAACACCCGCAGAATTTA TCGCCCAAAGTCACTTACGGGGGCAAAAGACTTGACTAAAAATGCAGAAGTCGTCGCAGGGACAGGGG AGCAATGCCTTCCGTTTGACGAGGCGAGATGTGGGGATGGAGGGAAGGCCGTGGAAGCCACACTCATG AGTCCCAAAGGAATGGCAGTTGATAAGAATGGATTAATCTACTTTGTTGATGGAACCATGATTAGGAA AGTTGACCAAAATGGAATCATATCAACTCTTCTGGGCTCTAACGATTTGACTTCAGCCAGACCTTTAA CTTGTGACACCAGCATGCACATCAGCCAGGTACGTCTGGAATGGCCCACTGACCTAGCCATTAACCCT ATGGATAACTCCATTTATGTCCTGGATAATAATGTAGTTTTACAGATCACTGAAAATCGTCAAGTTCG CATTGCTGCTGGACGGCCCATGCACTGTCAGGTTCCCGGAGTGGAATATCCTGTGGGGAAGCACGCGG TGCAGACAACACTGGAATCAGCCACTGCCATTGCTGTGTCCTACAGTGGGGTCCTGTACATTACTGAA ACTGATGAGAAGAAAATTAACCGGATAAGGCAGGTCACAACAGATGGAGAAATCTCCTTAGTGGCCGG AATACCTTCAGAGTGTGACTGCAAAAATGATGCCAACTGTGACTGTTACCAGAGTGGAGATGGCTACG CCAAGGATGCCAAACTCAGTGCCCCATCCTCCCTGGCTGCTTCTCCAGATGGTACACTGTATATTGCA GATCTAGGGAATATCCGGATCCGGGCTGTGTCAAAGAATAAGCCTTTACTTAACTCTATGAACTTCTA TGAAGTTGCGTCTCCAACTGATCAAGAACTCTACATCTTTGACATCAATGGTACTCACCAATATACTG TAAGTTTAGTCACTGGTGATTACCTTTACAATTTTAGCTACAGCAATGACAATGATATTACTGCTGTG ACAGACAGCAATGGCAACACCCTTAGAATTAGACGGGACCCAAATCGCATGCCAGTTCGAGTGGTGTC TCCTGATAACCAAGTGATATGGTTGACAATAGGAACAAATGGATGTTTGAAAGGCATGACTGCTCAAG GACTGGAATTAGTTTTGTTTACTTACCATGGCAATAGTGGCCTTTTAGCCACTAAAAGTGATGAAACT GGATGGACAACGTTTTTTGACTATGACAGTGAAGGTCGTCTGACAAATGTTACGTTTCCAACTGGAGT GGTCACAAACCTGCATGGGGACATGGACAAGGCTATCACAGTGGACATTGAGTCATCTAGCCGAGAAG AAGATGTCAGCATCACTTCAAATCTGTCCTCGATCGATTCTTTCTACACCATGGTTCAAGATCAGTTA AGAAACAGCTACCAGATTGGTTATGACGGCTCCCTCAGAATTATCTACGCCAGTGGCCTGGACTCACA CTACCAAACAGAGCCGCACGTTCTGGCTGGCACCGCTAATCCGACGGTTGCCAAAAGAAACATGACTT TGCCTGGCGAGAACGGTCAAAACTTGGTGGAATGGAGATTCCGAAAAGAGCAAGCCCAAGGGAAAGTC AATGTCTTTGGCCGCAAGCTCAGGGTTAATGGCAGAAACCTCCTTTCAGTTGACTTTGATCGAACAAC AAAGACAGAAAAGATCTATGACGACCACCGTAAATTTCTACTGAGGATCGCCTACGACACGTCTGGGC ACCCGACTCTCTGGCTGCCAAGCAGCAAGCTGATGGCCGTCAATGTCACCTATTCATCCACAGGTCAA ATTGCCAGCATCCAGCGAGGCACCACTAGCGAGAAAGTAGATTATGACGGACAGGGGAGGATCGTGTC TCGGGTCTTTGCTGATGGTAAAACATGGAGTTACACATATTTAGAAAAGTCCATGGTTCTTCTGCTTC ATAGCCAGCGGCAGTACATCTTCGAATACGATATGTGGGACCGCCTGTCTGCCATCACCATGCCCAGT GTGGCTCGCCACACCATGCAGACCATCCGATCCATTGGCTACTACCGCAACATATACAACCCCCCGGA AAGCAACGCCTCCATCATCACGGACTACAACGAGGAAGGGCTGCTTCTACAAACAGCTTTCTTGGGTA CAAGTCGGAGGGTCTTATTCAAATACAGAAGGCAGACTAGGCTCTCAGAAATTTTATATGATAGCACA AGAGTCAGTTTTACCTATGATGAAACAGCAGGAGTCCTAAAGACAGTAAACCTCCAGAGTGATGGTTT TATTTGCACCATTAGATACAGGCAAATTGGTCCCCTGATTGACAGGCAGATTTTCCGCTTTAGTGAAG ATGGGATGGTAAATGCAAGATTTGACTATAGCTATGACAACAGCTTTCGAGTGACCAGCATGCAGGGT GTGATCAATGAAACGCCACTGCCTATTGATCTGTATCAGTTTGATGACATTTCTGGCAAAGTTGAGCA GTTTGGAAAGTTTGGAGTTATATATTATGATATTAACCAGATCATTTCTACAGCTGTAATGACCTATA CGAAGCACTTTGATGCTCATGGCCGTATCAAGGAGATTCAATATGAGATATTCAGGTCGCTCATGTAC TGGATTACAATTCAGTATGATAACATGGGTCGGGTAACCAAGAGAGAGATTAAAATAGGGCCCTTTGC CAACACCACCAAATATGCTTATGAATATGATGTTGATGGACAGCTCCAAACAGTTTACCTCAATGAAA
AGATAATGTGGCGGTACAACTACGATCTGAATGGAAACCTCCATTTACTGAACCCAAGTAACAGTGCG CGTCTGACACCCCTTCGCTATGACCTGCGAGACAGAATCACTCGACTGGGTGATGTTCAATATCGGTT GGATGAAGATGGTTTCCTACGTCAAAGGGGCACGGAAATCTTTGAATATAGCTCCAAGGGGCTTCTAA CTCGAGTTTACAGTAAAGGCAGTGGCTGGACAGTGATCTACCGTTATGACGGCCTGGGAAGGCGTGTT TCTAGCAAAACCAGTCTAGGACAGCACCTGCAGTTTTTTTATGCTGACTTAACTTATCCCACTAGGAT TACTCATGTCTACAACCATTCGAGTTCAGAAATTACCTCCCTGTATTATGATCTCCAAGGACATCTTT TTGCCATGGAAATCAGCAGTGGGGATGAATTCTATATTGCATCGGATAACACAGGGACACCACTGGCT GTGTTCAGTAGCAATGGGCTTATGCTGAAACAGATTCAGTACACTGCATATGGGGAAATCTATTTTGA CTCTAATATTGACTTTCAACTGGTAATTGGATTTCATGGTGGCCTGTATGACCCACTCACCAAATTAA TCCACTTTGGAGAAAGAGATTATGACATTTTGGCAGGACGGTGGACAACACCTGACATAGAAATCTGG AAAAGAATTGGGAAGGACCCAGCTCCTTTTAACTTGTACATGTTTAGGAATAACAACCCTGCAAGCAA AATCCATGACGTGAAAGATTACATCACAGATGTTAACAGCTGGCTGGTGACATTTGGTTTCCATCTGC ACAATGCTATTCCTGGATTCCCTGTTCCCAAATTTGATTTAACAGAACCTTCTTACGAACTTGTGAAG AGTCAGCAGTGGGATGATATACCGCCCATCTTCGGAGTCCAGCAGCAAGTGGCGCGGCAGGCCAAGGC CTTCCTGTCGCTGGGGAAGATGGCCGAGGTGCAGGTGAGCCGGCGCCGGGCCGGCGGCGCGCAGTCCT GGCTGTGGTTCGCCACGGTCAAGTCGCTGATCGGCAAGGGCGTCATGCTGGCCGTCAGCCAGGGCCGC GTGCAGACCAACGTGCTTAACATCGCCAACGAGGACTGCATCAAGGTGGCGGCCGTGCTCAACAACGC CTTCTACCTGGAGAACCTGCACTTCACCATCGAGGGCAAGGACACGCACTACTTCATCAAGACCACCA CGCCCGAGAGCGACCTGGGCACGCTGCGGTTGACCAGCGGCCGCAAGGCGCTGGAGAACGGCATCAAC GTGACGGTGTCGCAGTCCACCACGGTGGTGAACGGCAGGACGCGCAGGTTCGCGGACGTGGAGATGCA GTTCGGCGCGCTGGCGCTGCACGTGCGCTACGGCATGACCCTGGACGAGGAGAAGGCGCGCATCCTGG AGCAGGCGCGGCAGCGCGCGCTCGCCCGGGCCTGGGCGCGCGAGCAGCAGCGCGTGCGCGACGGCGAG GAGGGCGCGCGCCTCTGGACGGAGGGCGAGAAGCGGCAGCTGCTGAGCGCCGGCAAGGTGCAGGGCTA CGACGGGTACTACGTACTCTCGGTGGAGCAGTACCCCGAGCTGGCCGACAGCGCCAACAACATCCAGT TCCTGCGGCAGAGCGAGATCGGCAGGAGGTAACGCCCGGGCCGCGCCCGCCGAGCCGCTCACGCCCTG CCCACATTGTCCTGTGGCACAACCCGAGTGGGACTCTCCAACGCCCAAGAGCCTTCCTCCCGGGGGAA TGAGACTGCTGTTACGACCCACACCCACACCGCGAAAACAAGGACCGCTTTTTTCCGAATGACCTTAA AGGTGATCGGCTTTAACGAATATGTTTACATATGCATAGCGCTGCACTCAGTCGGACTGAACGTAGCC AGAGGAAAAAAAAATCATCAAGGACAAAGGCCTCGACCTGTTGCGCTGGGCCGTCTGTTCCTTCTAGG
5δ0 CACTGTATTTAACTAACTTTA
NOV40ah, SNP1337δ354 of SEQ ID NO: 552 2725 aa MW at 303959.6kD
CG55069-01, Protein Sequence JsNP Pos: 2540 SNP Change: Leu to Leu
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDLVH READEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWG RGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLN RNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYT MASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQL QQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQL FIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETERAGRQA RSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFL GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGES CEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYL DKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMD PDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLAS VIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTD LKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQ KVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQ FISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTS VLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLP FDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTS MHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTL ESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAK LSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTΉQYTVSLVT GDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELV LFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGEN GQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLW LPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQ YIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVN ARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFD AHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWR YNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYS KGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEI SSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGE RDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIP GFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFA TVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESD LGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQ RALARAWAREQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS
EIGRR
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 40B.
Table 40B. Comparison of the NOV40 protein sequences.
NOV4Oa
NOV4Ob
NOV4Oc
NOV4Od
NOV4Oe
NOV4Of N0V4 Og
NOV4 Oh
N0V4 Oi
N0V4Oj
N0V4Ok
NOV401
N0V4Om
N0V4 On
NOV4Oo
NOV4Op
NOV4Oq
NOV4Or
NOV4 Os
NOV4 Ot
NOV4 Ou
NOV4 Ov
NOV40W MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYG
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4Oac
NOV40a
NOV4Ob
NOV4 Oc
NOV4Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV4 Oh
NOV4 Oi
NOV4 Oj
NOV4Ok
NOV401
NOV40m
NOV40n
NOV4 Oo
N0V4 Op
N0V4Oq
N0V4 Or
N0V4 Os
N0V4Ot
N0V4Ou
NOV40v
N0V4 Ow NRVKDLVHREADEFTRQEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRN
N0V4Ox
N0V4Oy
N0V4Oz
N0V4 Oaa
N0V4Oab
N0V4Oac N0V4 Oa
N0V4Ob
N0V4Oc
NOV4Od
NOV4Oe
NOV4 Of '
NOV4 Og
NOV4 Oh
NOV4Oi
NOV4Oj
NOV4 Ok
NOV401
N0V4 Om
N0V4 On
N0V4 Oo
N0V4 Op
N0V4 Oq
N0V4 Or
N0V4 Os
N0V4 Ot
NOV4 Ou
NOV4Ov
NOV4 Ow QSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTM
NOV4 Ox
NOV4 Oy
NOV40Z
NOV4Oaa
NOV4 Oab
NOV40ac
NOV4 Oa
NOV4 Ob
NOV4 Oc
NOV4 Od
NOV4 Oe
N0V4 Of
N0V4 Og
N0V4Oh
NOV40i
N0V40j
N0V4 Ok
NOV401
N0V4 Om
N0V4 On
N0V4 Oo
N0V4 Op
NOV4 Oq
NOV4 Or
NOV4 Os
NOV4Ot
NOV4Ou
NOV4Ov
NOV4 Ow ASGSVYSPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHL
NOV4 Ox NOV4Oy
NOV4 Oz
NOV4 Oaa
NOV4Oab
NOV40ac
NOV4 Oa
NOV4Ob
NOV4Oc
NOV4Od
NOV4 Oe
NOV4Of
NOV4Og
NOV4 Oh
NOV4 Oi
NOV40J
NOV40k
NOV401
N0V4 Om
N0V4 On
N0V4Oo
NOV40p
NOV4Oq
N0V4 Or
N0V4Os
N0V4Ot
N0V4 Ou
N0V4Ov
NOV40W FGLNWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRR
NOV4Ox
N0V4 Oy
N0V4 Oz
N0V4 Oaa
N0V4 Oab
N0V4Oac
N0V4Oa
NOV40b
N0V4 Oc
N0V4 Od
N0V4 Oe
N0V4 Of
N0V4 Og
N0V4 Oh
NOV40i
N0V4 Oj
N0V4 Ok
N0V401
N0V4 Om
N0V4 On
N0V4 Oo
N0V4 Op
N0V4Oq
N0V4Or N0V4 Os
N0V4 Ot
N0V4 Ou
N0V4 Ov
N0V40W AIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHTQYDFVELLDGSR
NOV4Ox
NOV4Oy
NOV40z
NOV4 Oaa
NOV4 Oab
NOV40ac
NOV40a
NOV4Ob
NOV4 Oc
NOV4Od
NOV4Oe
NOV4 Of
NOV4Og
NOV4Oh
NOV40i
NOV4Oj
NOV40k
NOV401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV40q
NOV4 Or
NOV4 Os
NOV4 Ot
N0V4Ou
NOV4Ov
NOV40w IAREQRSLLETERAGRQARSVSLHEAGFIQYLDSGI HLAFYNDGKNAEQVSFNTIVIE
NOV4Ox
NOV40y
NOV4Oz
NOV4Oaa
NOV4Oab
N0V4Oac
N0V4Oa
NOV4 Ob
NOV4Oc
NOV4Od
NOV4 Oe
NOV4Of
NOV4Og
NOV4 Oh
NOV4 Oi
NOV40j
NOV4 Ok
NOV401 NOV4Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV4 Oq
NOV4 Or
NOV4Os
NOV40t
NOV4Ou
NOV4 Ov
NOV4 Ow SWECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGT
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4Oaa
NOV4Oab
NOV4 Oac
NOV4 Oa
NOV4Ob
NOV4 Oc
NOV4 Od
NOV40e
NOV4Of
NOV4Og
NOV4Oh
NOV4Oi
NOV4Oj
NOV4Ok
NOV401
NOV4Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV4Oq
NOV4Or
NOV4 Os
NOV4 Ot
NOV4 Ou
NOV4Ov
NOV40W ECDVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCS
NOV4Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4 Oac
NOV4Oa
NOV4Ob
NOV4 Oc
N0V4 Od
NOV40e
NOV4 Of NOV4Og
NOV4Oh
NOV4Oi
NOV4 Oj
NOV4 Ok
NOV401
NOV4Om
NOV4On
NOV4Oo
NOV4 Op
NOV4 Oq
NOV4Or
NOV40S
NOV4Ot
NOV40u
NOV4Ov
NOV40W PGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMG
NOV4Ox
NOV4Oy
NOV4Oz
NOV4 Oaa
NOV4 Oab
NOV4 Oac
NOV4Oa
NOV4 Ob
NOV4Oc
NOV4Od
NOV4Oe
NOV4Of
NOV4 Og
NOV4 Oh
NOV4 Oi
NOV4 Oj
NOV4Ok
NOV401
NOV4Om
NOV4On
NOV4 Oo
NOV4Op
NOV4Oq
NOV4Or
NOV4Os
NOV4Ot
NOV4Ou
NOV4Ov
NOV40w GTCRCEEGWTGPTCNQRACHPRCAEHGTCKDGKCECSHGWNGEHCTIEGCPGLCNSNGRC
NOV4 Ox
NOV4Oy
NOV4 Oz
NOV4Oaa
NOV4 Oab
NOV40ac N0V4Oa
N0V4Ob
NOV4 Oc
NOV40d
NOV4Oe
NOV4 Of
NOV4Og
NOV4Oh
NOV40i
NOV4 Ok
NOV401
N0V4 Om
N0V4 On
N0V4 Oo
N0V4Op
NOV40q
NOV4 Or
NOV4Os
NOV4 Ot
NOV4 Ou
NOV4 Ov
NOV40W TLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCR
NOV4Ox
NOV4 Oy
NOV4Oz
NOV4Oaa
N0V4 Oab
N0V4Oac
NOV40a
NOV4 Ob
N0V4Oc
NOV4 Od
N0V4 Oe
N0V4 Of
N0V4 Og
NOV4Oh
NOV4 Oi
N0V4Oj
NOV4Ok
NOV401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4Op
NOV4Oq
NOV4 Or
NOV4 Os
NOV4 Ot
NOV4 Ou
NOV4 Ov
NOV40w GLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESPFNKSLASVIRGQVLT
NOV4Ox NOV4Oy
NOV4 Oz
NOV4Oaa
NOV4 Oab
NOV40ac
NOV4 Oa
NOV40b
NOV4 Oc
NOV4Od
NOV4Oe
NOV4Of
NOV4 Og
NOV4 Oh
NOV40i
NOV4 Oj
NOV4Ok
NOV401
NOV4Om
NOV40n
NOV4Oo
NOV4Op
NOV40q
NOV40r
NOV40S
NOV4Ot
NOV4 Ou
NOV40V
NOV4 Ow ADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFERSPFLTQYHTVWIPW
NOV4Ox
NOV4Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV4Oac
NOV4Oa
NOV4Ob
NOV40c
NOV4 Od
NOV4Oe
NOV4Of
NOV4 Og
N0V4Oh
NOV4Oi
NOV4Oj
NOV4Ok
NOV401
N0V4 Om
N0V4On
N0V4 Oo
N0V4 Op
N0V4Oq
N0V4Or NOV4Os
N0V4Ot
N0V4Ou
NOV40v
NOV40w NVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHE
NOV40x
NOV4 Oy
NOV4 Oz
NOV40aa
NOV4 Oab
NOV4Oac
NOV4 Oa
NOV4Ob
NOV4 Oc
NOV40d
NOV4 Oe
NOV4 Of
NOV4 Og
NOV4 Oh
NOV4 Oi
NOV4 Oj
NOV4 Ok
N0V401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV4Oq
NOV4 Or
NOV4 Os
NOV4 Ot
NOV40U
NOV4 Ov
NOV4 Ow ETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMVAWGRLFQKWFPASP
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4Oac
NOV4 Oa
NOV4 Ob
NOV4Oc
NOV40d
NOV4 Oe
N0V4Of
NOV4Og
NOV40h
NOV4 Oi
N0V4Oj
N0V4Ok
NOV401 N0V4Om
NOV4On
NOV4Oo
NOV4 Op
NOV4 Oq
NOV4 Or
NOV4Os
NOV4Ot
NOV40U
NOV4 Ov
NOV4 Ow NLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRTAILQGYELDASNMGG
NOV4 Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV40ab
NOV4Oac
NOV4Oa
NOV4Ob '
NOV4 Oc
NOV4 Od
NOV4Oe
NOV40f
NOV4 Og
NOV4 Oh
NOV4Oi
NOV40J
NOV4Ok
NOV401
NOV4 Om
NOV4On
NOV4Oo
NOV4 Op
NOV4 Oq
NOV40r
NOV4Os
NOV40t
NOV4Ou
NOV4Ov
NOV4 Ow WTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSISCPSCNGQADGNKLL
NOV4 Ox ^
NOV4Oy
NOV4Oz
NOV4 Oaa
NOV40ab
NOV4Oac
NOV4 Oa
NOV4 Ob
NOV4Oc
NOV4 Od
NOV4 Oe
NOV40f N0V4Og
N0V4Oh
N0V4Oi
NOV4Oj
NOV4Ok
NOV401
NOV40m
NOV40n
NOV40O
NOV4Op
NOV40q
NOV4Or
NOV4Os
NOV4Ot
NOV4Ou
NOV4Ov
NOV4Ow APVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSSNPAHRYYLATDPVTG
NOV4Ox
NOV40y
NOV4Oz
NOV4 Oaa
NOV40ab
NOV4Oac
NOV40a
NOV40b
NOV4Oc
NOV40d
N0V4Oe
N0V4Of
N0V4Og
NOV40h
NOV40i
N0V4Oj
NOV40k
NOV401
N0V4Om
N0V4On
N0V4Oo
N0V4Op
N0V4Oq
N0V4Or
N0V4Os
N0V4Ot
N0V4Ou
N0V4Ov
N0V4Ow DLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEARCGDGGKAVEATLMSP
N0V4Ox
N0V4 Oy
N0V4Oz
NOV40aa
N0V4Oab
N0V4Oac NOV4 Oa
NOV4Ob
NOV4 Oc
NOV40d
NOV4Oe
NOV4 Of
NOV4Og
NOV4 Oh
NOV4 Oi
NOV4Oj
NOV40k
NOV401
NOV4Om
NOV4 On
NOV4Oo
NOV40p
NOV40q
NOV4Or
NOV4 Os
NOV4 Ot
NOV4Ou
NOV4Ov
NOV40W KGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTCDTSMHISQVRLEWPT
NOV4Ox
NOV4Oy
NOV4Oz
NOV40aa
NOV4 Oab
NOV4Oac
NOV4Oa
NOV4 Ob
NOV40C
NOV40d
NOV4 Oe
NOV4 Of
NOV4 Og
NOV4Oh
NOV4Oi
NOV4Oj
NOV4Ok
NOV401
NOV4Om
NOV4 On
NOV4Oo
NOV4Op
NOV4Oq
NOV4Or
NOV4 Os
NOV4Ot
NOV4Ou
NOV4Ov
NOV4Ow DLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEYPVGKHAVQTTLESAT
NOV4Ox NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4 Oac
N0V4Oa
NOV4 Ob
NOV4 Oc
NOV4 Od
NOV4 Oe
NOV4 Of
NOV4Og
NOV4 Oh
NOV4 Oi
NOV4Oj
NOV40k
N0V401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4Op
NOV4 Oq
NOV4 Or
NOV4 Os
NOV4 Ot
NOV4 Ou
NOV4 Ov
NOV40W AIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCKNDANCDCYQSGDGYA
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4 Oac
NOV4Oa
N0V4Ob
NOV4 Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV4 Oh
NOV4 Oi
NOV4 Oj
NOV4 Ok
NOV401
NOV4 Om
NOV40n
NOV4Oo
NOV40p
NOV4 Oq
NOV40r N0V4 Os
N0V4 Ot
N0V4Ou
N0V4 Ov
NOV4 Ow KDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFYEVASPTDQELYIFDI
NOV4Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV40ac
NOV4 Oa
N0V4 Ob
N0V4 Oc
N0V4 Od
N0V4Oe
N0V4Of
N0V4Og
NOV4Oh
N0V4 Oi
N0V40j
N0V4 Ok
N0V401 ;
N0V4Om
N0V4On
N0V4 Oo
N0V4 Op
N0V4 Oq
N0V4 Or
N0V4Os
N0V4 Ot
N0V4 Ou
N0V4 Ov
N0V4 Ow NGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPNRMPVRWSPDNQVIW
NOV40x
N0V4Oy
NOV40z
N0V4Oaa
N0V4Oab
N0V4Oac
NOV40a
N0V4Ob
N0V4Oc
N0V4Od
NOV4 Oe
N0V4 Of
N0V4 Og
N0V4 Oh
N0V4 Oi
NOV40J
N0V4Ok
N0V401 NOV4 Om
NOV4 On
NOV4Oo
NOV4 Op
NOV4Oq
NOV4Or
NOV4Os
NOV40t
NOV4 Ou
NOV4Ov
NOV40w LTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFDYDSEGRLTNVTFPTG
NOV4Ox
NOV4 Oy
NOV40z
NOV40aa
N0V4 Oab
N0V4Oac
NOV40a
NOV40b
NOV4Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV4Oh
NOV4Oi
NOV4 Oj
NOV4 Ok
NOV401
N0V4Om
NOV4On
NOV4Oo
NOV4 Op
NOV4Oq
NOV4Or
NOV4Os
NOV4 Ot
NOV4Ou MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFD
NOV4 Ov
NOV4Ow WTNLHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRI
NOV4Ox
NOV4Oy
NOV4 Oz
NOV4Oaa
NOV4Oab
NOV4Oac
NOV4 Oa
NOV4Ob
NOV4Oc
NOV4 Od
NOV4Oe
NOV4Of NOV40g
N0V4Oh
N0V4Oi
N0V4Oj
NOV40k
NOV401
NOV4Om
NOV4On
NOV4Oo
NOV4 Op
NOV4Oq
NOV4Or
NOV4Os
NOV4Ot
NOV40u HDSSRLLYGNRVKDLVHREADEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYS
NOV4Ov
NOV4Ow IYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNLVEWRFRKEQAQGKVNVFGRK
NOV4Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4 Oab
NOV4Oac
NOV4Oa
NOV4Ob
NOV4Oc
NOV4Od
NOV40e
NOV4Of
NOV4Og
NOV4 Oh
NOV4Oi
N0V4Oj
NOV4Ok
NOV401
N0V4Om
N0V4 On
N0V4Oo
N0V4Op
NOV40q
N0V4Or
N0V40S
NOV4 Ot
N0V4 Ou ISAGSDADTENEAVMSPEHAMRLWGRGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENE
N0V4Ov
N0V4Ow LRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLWLPSSKLMAVNVTYSST
N0V4Ox
N0V4Oy
N0V4Oz
N0V4 Oaa
N0V4 Oab
N0V4Oac NOV4Oa
NOV4Ob
NOV4Oc
NOV4 Od
NOV4Oe
NOV4Of
NOV40g
NOV40h
NOV4Oi
NOV4Oj
NOV4 Ok
NOV401
NOV4Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV40q
NOV4 Or
NOV4 Os
NOV4 Ot
NOV4 Ou QPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTTPE
NOV4Ov
NOV4 Ow GQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVLLLHSQRQYIFEYDMW
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4 Oac
N0V4 Oa MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQK
N0V4 Ob
N0V4 Oc
N0V4 Od
NOV4 Oe
NOV4Of
N0V4 Og
NOV4 Oh
N0V4 Oi '
NOV40j
N0V4 Ok
N0V401
N0V4 Om
N0V4 On
NOV4 Oo
NOV4 Op
N0V4 Oq
N0V4Or
NOV4 Os
NOV4 Ot
N0V4 Ou SVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTL
N0V4Ov
NOV40W DRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEEGLLLQTAFLGTSRRV
NOV4 Ox N0V4Oy
N0V4 Oz
N0V4Oaa
N0V4 Oab
NOV4 Oac
NOV40a SYSSSETLKAFDHDSSRLLYGNRVKDLVHREADEFTRQGQNFTLRQLGVCEPATRRGLAF
NOV40b
NOV4 Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV40g
NOV4 Oh
NOV4Oi MDVKER
NOV4 Oj
NOV4 Ok
NOV401
NOV4Om
NOV40n
NOV4Oo
NOV4Op
NOV4Oq
NOV4 Or
N0V4 Os
NOV4 Ot
NOV4 Ou SRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENG
NOV4 Ov
NOV40W LFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTIRYRQIGPLIDRQIFR
NOV4Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4Oac
NOV4Oa CAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWGRGVKSGRSSCLSSRSNSALTLTD
NOV4Ob
NOV4Oc
NOV4Od
NOV4Oe
NOV4Of
NOV4Og
NOV4Oh
NOV40i RPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYGNRVKDL
N0V40j
NOV4 Ok
NOV401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4Op
NOV4Oq
N0V4Or NOV4Os
NOV4Ot
NOV40u KVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFID
NOV4Ov
NOV4Ow FSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISGKVEQFGKFGVIYYDI
NOV4Ox
N0V4Oy
NOV4 Oz
NOV4Oaa
NOV4Oab
NOV4 Oac
NOV40a TEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPP
NOV4Ob
NOV4Oc
NOV4Od
N0V4Oe
N0V4 Of
NOV4 Og
NOV4 Oh
N0V4 Oi VHREADEFTRQEQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPP
NOV40j
N0V4 Ok
N0V401
N0V4 Om
N0V4On
N0V4Oo
N0V4 Op
N0V4Oq
N0V4Or
NOV40S
N0V4 Ot
N0V4 Ou QPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLIAREQRSLLETER
N0V4Ov
NOV4 Ow NQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGRVTKREIKIGPFANTT
N0V4Ox
NOV4 Oy
N0V4Oz
N0V4 Oaa
NOV4 Oab
NOV4Oac
NOV4 Oa AALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVY
NOV4Ob
NOV4Oc
NOV40d
N0V4Oe
N0V4 Of
NOV4 Og
NOV4 Oh
N0V4Oi AALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVY
NOV4Oj
N0V4Ok
N0V401 NOV4Om
NOV4 On
NOV4 Oo
NOV4Op
NOV4 Oq
NOV40r
NOV4 Os
NOV4 Ot
NOV4Ou AGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESWECPRNCHGNGE
NOV4Ov
NOV40W KYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLTPLRYDLRDRITRLGD
NOV4Ox
NOV4Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV40ac
NOV4 Oa SPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQ
NOV40b
NOV4Oc GTNWQ
NOV4 Od GTNWQ
NOV4 Oe GTNWQ
NOV4 Of TKLNWQ
NOV4Og
NOV4 Oh
NOV4 Oi SPPTRPLPRNTLSRSAFKFKKSSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQ
NOV40j
NOV4 Ok
NOV401
NOV4Om
NOV4 On
NOV4Oo
NOV4Op
NOV40q NWQ
NOV4 Or TSRNWQ
NOV4 Os
NOV4 Ot
NOV40U CVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQC
NOV4 Ov
NOV40w VQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDGLGRRVSSKTSLGQHL
NOV4 Ox NWQ
NOV4Oy NWQ
NOV4Oz NWQ
NOV4Oaa MLPGLALLLLAAWTARANWQ
NOV40ab
NOV4 Oac
NOV4 Oa LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Ob
NOV4Oc LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Od LQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Oe LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Of LQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP N0V4 Og
N0V4 Oh
N0V4 Oi LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
N0V40j
N0V4 Ok
NOV401
NOV40m
N0V4On
N0V4 Oo
N0V4 Op
NOV4 Oq LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Or LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 OS
NOV4 Ot
NOV40U GGRGICIMGSCACSSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTM
NOV40V
NOV40W QFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGDEFYIASDNTGTPLAVF
NOV4 Ox LQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Oy LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Oz LQQTENDAFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV40aa LQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIP
NOV4 Oab
NOV4 Oac
NOV40a PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKKLPPSHTQSSPQYDFVELLDGSRLI
NOV4Ob
NOV40C PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Od PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV40e PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Of PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Og
NOV4 Oh
NOV40i PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Oj
NOV4 Ok
NOV401
NOV4Om
NOV40n
NOV4Oo
NOV4 Op
NOV4 Oq PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Or PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Os
NOV4 Ot
NOV4 Ou CPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHG VCMGGTCRCEEGWT
NOV4 Ov
NOV40W SSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIHFGERDYDILAGRWTT
NOV40X PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV40y PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV40Z PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV40aa PGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGLPPSHT QYDFVELLDGSRLI
NOV4 Oab
NOV4 Oac N0V4 Oa AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40b
N0V4Oc AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
N0V4 Od AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
N0V4Oe AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV4Of AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40g
NOV40h
NOV4Oi AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40J
NOV40k
NOV401
NOV40m
NOV40n
NOV40O
NOV 0p
NOV4Oq AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV4Or AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40s
NOV40t
NOV4Ou GPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYKEGCPGLCN
NOV40v
NOV4Ow PDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLVTFGFHLHNAIPGFPV
NOV 0X AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40y AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV4Oz AREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV 0aa AREQRSLLETERAGRQARSVSLHEAGSIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESV
NOV40ab
NOV40ac
NOV40a VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4Ob - -CPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV40c VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4 Od VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV40e VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV40f VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4Og - -TSRTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLG KMAEVQVSRRRAGGA
NOV4Oh SMDVKERRPYCSLTKSRREKERRYTNSSADNEEC
NOV40i VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV40j KLDQNG GHCVCQPGWRGAGC
N0V4Ok KLDQNG GHCVCQPGWRGAGC
NOV401 KLDQNG GHCVCQPGWRGAGC
N0V4 Om KLDQNG GHCVCQPGWRGAGC
N0V4 On KLDQNG GHCVCQPGWRGAGC
N0V4Oo KLDQNG GHCVCQPGWRGAGC
NOV4Op KLDQNG GHCVCQPGWRGAGC
NOV4Oq VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4Or VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
N0V4OS MDVKERRPYCSLTKSRREKERRYTNSSADNEEC
NOV40t --CPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4Ou SNGRCTLDQNG GHCVCQPGWRGAGC
NOV4Ov DQNG GHCVCQPGWRGAGC
N0V4 Ow PKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLG KMAEVQVSRRRAGGA
N0V4Ox VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC NOV40y VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC NOV40z VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC NOV40aa VECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTEC
NOV4 Oab MDVKERRPYCSLTKSRREKERRYTNSSADNEEC
NOV4Oac MDVKERRPYCSLTKSRREKERRYTNSSADNEEC
NOV40a DVPTTQCIDPQCGGRGICIMGSCACSSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40b DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40C DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40d DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40e DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40f DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
N0V4Og QSWLWFATVKSLIGKGVMLAVSQG-RVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIE
N0V4Oh RVPTQKSYSSSE TLKAFDHDSSRLLYGNRVKDLVHREADEFTRQ
NOV40i DVPTTQCIDPQCGGRGICIMGSCACNSGYKGKSCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40j DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4Ok DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV401 DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4Om DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4On DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4Oo DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4 Op DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QSYCRGL
NOV40q DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40r DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV4OS RVPTQKSYSSSE TLKAFDHDSSRLLYGNRVKDLVHREADEFTRQ
NOV40t DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV4Ou DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4Ov DVAMETLCTDSK DNEGDGLIDCMDPDCCLQSSCQN-QPYCRGL
NOV4Ow QSWLWFATVKSLIGKGVMLAVSQG-RVQTNVLNIANEDCIKVAAVLNNAFYLENLHFTIE
NOV40x DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40y DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40Z DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV40aa DVPTTQCIDPQCGGRGICIMGSCACNSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPG
NOV4Oab RVPTHNSYSSSE TLKAFDHDSSRLLYGNRVKDLVHREADEFTRQ
NOV4Oac RVPTQKSYSSSE TLKAFDHDSSRLLYGNRVKDLVHREADEFTRQ
NOV40a WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV4Ob WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV40C WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV4Od WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV40e WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV40f WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV4Og -GKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFG
NOV40h EQPASNQGQSTLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTTP
NOV40i WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV40J PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40k PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV401 PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40m PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40n PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40O PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40p PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ
NOV40q WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT
NOV40r WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV40S GQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWGR NOV40t WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV4 Ou PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ NOV4 Ov PDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGES PFNKSLASVIRGQ NOV40W -GKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTRRFADVEMQFG NOV40X WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV40y WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV40Z WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV40aa WGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGT NOV40ab GQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWGR NOV40ac GQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADTENEAVMSPEHAMRLWGR
NOV4 Oa CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV40b CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTI NOV40c CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTI NOV40d CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV40e CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV40f CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV4Og ALALHVRYGMTLDEEKARILEQA QQRVRDG NOV4 Oh ESVQLQDSWVLG-SNVPLESRHFLFKTGTGTTP NOV40i CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV40J VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV40k VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV401 VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV4 Om VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV4 On VLTADGTPLIGVNVSFFHYPEYGYTITRQ N0V40O VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV40p VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV40q CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV40r CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV40S GVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQSTLQPLPPSHKQHSAQHH NOV40t CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV40U VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV4 Ov VLTADGTPLIGVNVSFFHYPEYGYTITRQ NOV4Ow ALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWTEGEKRQL NOV4 Ox CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV40y CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV40Z CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVKDKIGYK NOV40aa CRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGEHCTIAHYLDKIVK NOV4 Oab GFKSGRSSCLSSRSNSALTLTDTEHENKSDSEN NOV40ac GVKSGRSSCLSSRSNSALTLTDTEHENKSDSEN
NOV40a NOV40b NOV40C NOV40d NOV40e NOV40f NOV4 Og NOV4 Oh NOV40i NOV40J NOV40k NOV401 NOV40m NOV40n NOV40o NOV4Op NOV4 Oq NOV40r NOV40s PSITSLNRNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWVLGSNVPLESRHFLFKTG NOV40t NOV4 Ou NOV4 Ov NOV4 Ow NOV4 Ox NOV4Oy NOV40z NOV4Oaa NOV40ab NOV40ac
NOV40a --EGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV4 Ob - -EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCD NOV40C --EGCPGLSNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV4 Od - -EGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40e - -EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40f - -EGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV4 Og KVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRRVDG NOV4 Oh LFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFKFKKS-SKYCSWKCTALCAVG NOV40i --EGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40J DGMFDLVANGGASLTLVFERSP NOV40k DGMFDLVASGGASLTLVFERSP NOV401 DGMFDLVANGGASLTLVFERSP NOV4 Om DGMFDLVANGGASLTLVFERSP NOV4 On DGMFDLVANGGASLTLVFERSP NOV4Oo DGMFDLVANGGASLTLVFERSP NOV40p DGMFDLVANGGASLTLVFERSP NOV40q --EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV4Or --EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40S TGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFKFKKS-SKYCSWKCTALCAVG NOV40t - -EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCD NOV40u DGMFDLVANGGASLTLVFERSP NOV4 Ov DGMFDLVANGGASLTLVFERSP N0V4 Ow - -LSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR NOV40x - -EGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP N0V4 Oy --EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40z --EGCPGLCNSNGRCTLDQNGWHCACQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV40aa --EGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETLCTDSKDNEGDGLIDCMDP NOV4 Oab GGSSSWFGFHWNFYVSKASCLLRLPRIFLSHNYNVNKEMREKLC NOV4 Oac GGSSSWFGFHWNFYVGKASCLLRLPRIFLSHNYNVNKEMREKLC
NOV40a DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP NOV4 Ob NOV40C DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP NOV40d DCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP NOV4 Oe DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP NOV40f DCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP NOV4Og
NOV4Oh VSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGF
NOV40i DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV4 Oj
NOV40k
NOV401
NOV4Om
NOV4 On
NOV4Oo
NOV4Op
NOV40q DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV40r DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV40s VSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPTNTVSLPSGDNGKLGGF
NOV4Ot
NOV40U
NOV4Ov
NOV4Ow
NOV40x DCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV40y DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV40Z DCCLQSSCQNQPYCRGLPDPQGIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV40aa DCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRISFLIGSDSTHVIPGESP
NOV4Oab
NOV40ac
NOV4Oa FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Ob
NOV4Oc FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4 Od FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Oe FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV40f FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV40g
NOV40h TQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGL
NOV4Oi FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4 Oj
NOV4Ok
NOV401
NOV40m
NOV4On
NOV4Oo
NOV4Op
NOV4Oq FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Or FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV40s TQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNISLQKDALIGVYGRKGL
NOV4Ot
NOV4Ou
NOV4Ov
NOV4Ow
NOV4Ox FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Oy FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Oz FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Oaa FNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDGMFDLVANGGASLTLVFE
NOV4Oab
NOV4Oac NOV40a RSPFLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
N0V4Ob
NOV40C RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
N0V4 Od RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40e RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40f RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV4Og
NOV4Oh PPSHTQYDFVELLDGSRLIALEG
NOV40i RSPFLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40j FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40k FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV401 FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40m FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40n FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40o FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40p FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV4 Oq RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40r RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40S PPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVSLHEAGFIQYLDSGIWHLAFY
NOV4Ot
NOV4 Ou FLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40V FLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV4Ow
NOV40X RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV4 Oy RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40Z RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV40aa RSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFVRPNPIIVSSPLSTFFRSS
NOV4Oab
NOV4Oac
NOV4 Oa PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSI IPFNLMKVHLMV
NOV4 Ob
NOV40C PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40d PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40e PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40f PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV4 Og
NOV40h
NOV40i PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40J PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40k PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV401 PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40m PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40n PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40o PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40p PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40q PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40r PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV4OS NDGKNAEQVSFNTIVIESWECPRNCHGNGECVSGTCHCFPGFLGPDCSRAACPVLCSGN
NOV4 Ot
NOV40U PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMIVHLMV
NOV40V PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV4Ow
NOV40x PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV NOV40y PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40Z PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40aa PEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKITMTQSIIPFNLMKVHLMV
NOV40ab
NOV4Oac
NOV4Oa AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV40b
NOV4Oc AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Od AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Oe AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Of AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Og
NOV4Oh
NOV40i AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV40j AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Ok AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV401 AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Om AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4On AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSAGYEYESCLDLTLWEKRT
NOV4Oo AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Op AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4 Oq AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Or AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV40S GQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCACSSGYKGESCEEADCID
NOV4 Ot
NOV4 Ou AWGRLFQKWFPASPNLAYTFI WDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4 Ov AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4 Ow
NOV4Ox AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Oy AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Oz AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Oaa AWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSVGYEYESCLDLTLWEKRT
NOV4Oab
NOV40ac
NOV4Oa AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40b
NOV4Oc AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSVD
NOV40d AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSVDPAASSRE-
NOV40e AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSVDATHDWRLL
NOV4 Of AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSLEG
NOV40g
NOV4Oh
NOV40i AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40J AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV4Ok AILQGYELDASNMGGWTLDKHHALDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV401 AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40m AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV4 On AILQGYELDASNMGGWTLDKHHVLDVRNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40o AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40p AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV4Oq AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSS
NOV4Or AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSLEG NOV40S PGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQESGSCTCDPNWTGPDC
NOV4 Ot
NOV40u AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV4Ov AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSSIMGNGRRRSI
NOV40w
NOV4Ox AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPP SS
NOV4 Oy AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSS
NOV40z AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSS
NOV4Oaa AILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQQPPWSS
NOV4 Oab
NOV4Oac
NOV4Oa SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSS
NOV4 Ob
NOV40C
NOV4Od
NOV4Oe VIFSSAVAASWY
NOV4Of
NOV40g
NOV4 Oh
NOV40i SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSS
NOV40j SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSS
NOV40k SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSS
NOV401 SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELS S
NOV40m SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELS S
NOV4On SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELS S
NOV4 Oo SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELS S
NOV4Op SCPSCNGQADGNKLLAPVALACGIDGSLHVGDFNYVRRIFPSGNVTSVLELS S
NOV40q
NOV40r
NOV40s SNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHGTCKDGKCECSQGWNGE
NOV4Ot
NOV40u SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELRNKDFRHSS
NOV4Ov SCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSGNVTSVLELS S
NOV40w
NOV40x
NOV4Oy
NOV4Oz
NOV40aa
NOV4 Oab
NOV4Oac
NOV4 Oa NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV40b
NOV4 Oc
NOV4Od
NOV4Oe
NOV4 Of
NOV4Og
NOV4Oh
NOV40i NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV40j NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4Ok NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDSTKNAEWAGTGEQCLPFDEAR
NOV401 NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR NOV4Om NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4 On NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4Oo NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4Op NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4Oq
NOV4Or
NOV40s HCTIAHYLDKIVKDKIGYKEGCPGLCNSNGRCTLDQNGGHCVCQPGWRGAGCDVAMETLC
NOV4 Ot
NOV4Ou NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4 Ov NPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEWAGTGEQCLPFDEAR
NOV4Ow
NOV4 Ox
NOV4Oy
NOV4 Oz
NOV40aa
NOV4 Oab
NOV4Oac
NOV4Oa CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4 Ob
NOV4Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV4Oh
NOV40i CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV40j CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
N0V4Ok CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV401 CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4 Om CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4 On CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
N0V40O CGDGGKAAEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4 Op CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4Oq
NOV4 Or
NOV40S TDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDRI
NOV4 Ot
NOV4 Ou CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4Ov CGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGSNDLTSARPLTC
NOV4 Ow
NOV4Ox
NOV4 Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV4 Oac
NOV4 Oa DTSMHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEY
NOV4Ob
NOV4 Oc
NOV4Od
NOV4 Oe
NOV40f N0V4 Og
NOV4 Oh
NOV4 Oi DTSMHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEY
NOV40j DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4 Ok DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV401 DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4 Om DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4 On DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4 Oo DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4Op DTSMHISQVRLEWPTDLAINPMDNSIYVLDNVD
NOV4 Oq
NOV40r
NOV40s SFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQDG
NOV4 Ot
NOV4 Ou DTSMHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQVRIAAGRPMHCQVPGVEY
NOV4Ov DTSMHISQVRLEWPTDLAINPMDNSIYVLDN
NOV4 Ow
NOV4Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4 Oab
NOV4 Oac
NOV40a PVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCK
NOV4 Ob
NOV4 Oc
NOV4 Od
NOV4 Oe
NOV4Of
NOV4 Og
NOV4 Oh
NOV40i PVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCK
NOV4 Oj
NOV4 Ok
NOV401
NOV4 Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV4 Oq
NOV4 Or
NOV40S MFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMEKEENDIPSCDLSGFVR
NOV4 Ot
NOV40u PVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISLVAGIPSECDCK
NOV4 Ov
NOV4 Ow
NOV4 Ox
N0V4 Oy
N0V4Oz
N0V4 Oaa
N0V4Oab
N0V4 Oac N0V4 Oa NDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFY
N0V4 Ob
N0V4Oc
NOV40d
N0V4Oe
N0V4Of
N0V4Og
N0V4 Oh
NOV40i NDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFY
N0V4Oj
N0V4 Ok
N0V401
N0V4Om
N0V4 On
N0V4Oo
N0V4Op
N0V4 Oq
NOV40r
NOV40S PNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKIT
N0V4Ot
NOV4 Ou NDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSKNKPLLNSMNFY
NOV4Ov
NOV4Ow
NOV4 Ox
NOV4 Oy
N0V4Oz
NOV4Oaa
N0V4Oab
NOV4 Oac
NOV4Oa EVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPN
N0V4 Ob
NOV4 Oc
NOV4Od
N0V4Oe
NOV4 Of
N0V4 Og
NOV4 Oh
N0V40i EVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPN
NOV40j
NOV4Ok
NOV401
NOV4Om
NOV4On
NOV4 Oo
NOV40p
NOV4Oq
NOV4Or
NOV4 Os MTQSIIPFNLMKVHLMVAWGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAWSV
NOV40t
NOV40U EVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSNGNTLRIRRDPN
N0V4Ov
NOV4 Ow
NOV4Ox NOV4Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV40ac
NOV4Oa RMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFD
NOV40b
NOV40C
NOV4Od
NOV40e
NOV40f
NOV40g
NOV4Oh
NOV40i RMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFD
NOV40k
NOV401
NOV4 Om
NOV4On
NOV4Oo
NOV4Op
NOV4Oq
NOV4Or
NOV40S GYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFISQ
NOV4Ot
NOV4 Ou RMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTYHGNSGLLATKSDETGWTTFFD
NOV4Ov
NOV4Ow
NOV4Ox
NOV4 Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV4 Oac
NOV4 Oa YDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQ
N0V4Ob
N0V4Oc
NOV4 Od
N0V4Oe
NOV4 Of
N0V4Og
NOV4Oh
N0V4 Oi YDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQ
N0V4Ok
N0V401
N0V4Om
NOV4On
N0V4Oo
N0V4Op
N0V4 Oq
NOV40r NOV4 Os QPPWSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPSG
NOV40t
NOV4Ou YDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSITSNLSSIDSFYTMVQDQ
NOV40V
NOV4Ow
NOV4 Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4Oac
N0V4Oa LRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNLVEWRF
NOV40b
NOV4Oc
NOV4Od
N0V4Oe
N0V4Of
NOV40g
NOV40h
NOV40i LRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNLVEWRF
NOV40j
NOV4Ok
NOV401
N0V4Om
N0V4On
N0V4Oo
NOV4Op
NOV4Oq
NOV4Or
NOV4Os NVTSVLELRNKDFRHSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNA
NOV4Ot
NOV4Ou LRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPGENGQNLVEWRF
NOV40V
NOV40W
NOV4Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4Oac
NOV4Oa RKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKI DDHRKFLLRIAYDTSGHPTLWL
NOV4Ob
NOV4Oc
N0V4Od
NOV4Oe
NOV4Of
NOV4Og
NOV4Oh
N0V40i RKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLWL
NOV40J
NOV4Ok
NOV401 N0V4 Om
NOV4 On
NOV4 Oo
NOV4 Op
NOV4 Oq
NOV4 Or
NOV40 s EWAGTGEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGI I
NOV4 Ot
NOV4Ou RKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIAYDTSGHPTLWL
NOV4Ov
NOV4Ow
NOV4Ox
NOV4 Oy
NOV4 Oz
NOV4Oaa
NOV40ab
NOV4Oac
NOV4 Oa PSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVL
N0V4Ob
N0V4 Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV4 Oh
NOV4 Oi PSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVL
NOV40j
NOV4 Ok
NOV401
N0V4Om
N0V4 On
N0V4Oo
N0V4Op
NOV4 Oq
NOV4Or
NOV4 Os STLLGSNDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNNWLQITENRQV
NOV4Ot
NOV4 Ou PSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTWSYTYLEKSMVL
NOV4Ov
NOV4Ow
NOV4 Ox
NOV4Oy
NOV4Oz
NOV4 Oaa
NOV40ab
NOV4 Oac
N0V4Oa LLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEE
N0V4 Ob
N0V4 Oc '
N0V4Od
N0V4 Oe
N0V4Of N0V4Og
N0V4Oh
NOV40i LLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEE
N0V40j
N0V4 Ok
NOV401
N0V4Om
NOV4On
NOV4 Oo
NOV4Op
NOV40q
NOV4 Or
NOV40s RIAAGRPMHCQVPGVEYPVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTT
NOV4Ot
NOV40U LLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPESNASIITDYNEE
NOV4 Ov
NOV4 Ow
NOV4 Ox
NOV4 Oy
NOV4Oz
NOV4 Oaa
NOV4 Oab
NOV4Oac
NOV40a GLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTI
N0V4 Ob
NOV4 Oc
N0V4Od
NOV4Oe
NOV40f
NOV4 Og
NOV4 Oh
NOV40i GLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTI
NOV40J
NOV4Ok
NOV401
NOV40m
NOV4 On
NOV4Oo
NOV40p
NOV4Oq
NOV4Or
NOV4Os DGEISLVAGIPSECDCKNDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIR
NOV4 Ot
NOV40U GLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTVNLQSDGFICTI
NOV4Ov
NOV4Ow
NOV4Ox
NOV4 Oy
NOV4Oz
NOV4 Oaa
NOV4Oab
NOV4Oac NOV40a RYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISG
N0V4Ob
NOV4 Oc
NOV4 Od
NOV4 Oe
NOV4Of
NOV40g
NOV40h
NOV40i RYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISG
NOV4Oj
NOV4 Ok
NOV401
NOV40m
NOV4On
NOV40O
NOV4Op
NOV4Oq
NOV4Or
NOV4Os IRAVSKNKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDIT
NOV4Ot
NOV40U RYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLPIDLYQFDDISG
NOV4Ov
NOV4Ow
NOV40X
NOV4Oy
NOV40z
NOV4Oaa
NOV4Oab
NOV4Oac
NOV40a KVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGR
NOV4Ob
NOV4Oc
NOV4Od
NOV4Oe
NOV4Of
NOV4Og
NOV40h
NOV40i KVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGR
NOV4 Oj
NOV4Ok
NOV401
NOV40m
NOV40n
NOV40O
NOV4Op
N0V4Oq
N0V4Or
N0V40s AVTDSNGNTLRIRRDPNRMPVRWSPDNQVIWLTIGTNGCLKGMTAQGLELVLFTYHGNS
N0V4 Ot
NOV40U KVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMYWITIQYDNMGR
NOV Ov
NOV4Ow
N0V4Ox N0V4Oy
NOV4 Oz
N0V4Oaa
N0V4 Oab
N0V4 Oac
N0V4 Oa VTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLT
NOV4 Ob
NOV4Oc
NOV4 Od
NOV4Oe
NOV4 Of
NOV4 Og
NOV40h
NOV4 Oi VTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLT
NOV4Oj
NOV40k
NOV401
NOV4Om
NOV4On
NOV4Oo
NOV40p
NOV4 Oq
NOV4Or
NOV4 Os GLLATKSDETGWTTFFDYDSEGRLTNVTFPTGWTNLHGDMDKAITVDIESSSREEDVSI
NOV4Ot
NOV4 Ou VTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLHLLNPSNSARLT
NOV40V
NOV4Ow
NOV40X
NOV40y
NOV40z
NOV40aa
NOV4Oab
NOV4 Oac
NOV40a PLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDG
NOV40b
NOV4Oc
NOV4Od
NOV4Oe
NOV40f
NOV40g
NOV4Oh
NOV40i PLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDG
NOV4Oj
NOV40k
NOV401
NOV4Om
NOV4On
NOV4Oo
NOV40p
NOV40q
NOV40r NOV40S TSNLSSIDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKR
NOV4 Ot
NOV4Ou PLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKGSGWTVIYRYDG
NOV4Ov
NOV4 Ow
NOV4Ox
NOV40y
NOV4 Oz
NOV4 Oaa
NOV4Oab
NOV4 Oac
NOV40a LGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGDE
NOV40b
NOV40C
NOV40d
NOV40e
NOV4 Of
NOV40g
NOV4Oh
NOV40i LGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGDE
NOV40J
NOV4Ok
NOV401
NOV40m
N0V4 On
N0V4Oo
NOV40p
NOV4Oq
NOV4Or
NOV40S NMTLPGENGQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRK
NOV4 Ot
NOV4 Ou LGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGHLFAMEISSGDE
NOV4Ov
NOV40w
NOV4Ox
NOV40y
NOV4 Oz
NOV40aa
NOV4Oab
NOV40ac
NOV40a FYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIH
N0V4 Ob
N0V4 Oc
N0V4 Od
N0V4 Oe
NOV40f
N0V4 Og
N0V4Oh
NOV40i FYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIH
NOV40j
N0V4 Ok
N0V401 N0V4Om
N0V4On
N0V4Oo
N0V4Op
NOV40q
NOV4Or
NOV4Os FLLRIAYDTSGHPTLWLPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVF
NOV4Ot
NOV40u FYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHGGLYDPLTKLIH
NOV4Ov
NOV40W
NOV4 Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV40ab
NOV40ac
NOV4Oa FGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLV
NOV4Ob
NOV40C
NOV4 Od
NOV4Oe
NOV40f
NOV4Og
NOV4Oh
NOV40i FGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLV
NOV4Oj
NOV4Ok
NOV401
N0V4 Om
N0V4On
NOV40o
N0V4 Op
NOV40q
NOV40r
N0V4 Os ADGKTWSYTYLEKSMVLLLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNI
NOV40t
NOV40U FGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVKDYITDVNSWLV
NOV Ov
N0V4Ow
N0V4Ox
NOV40y
N0V4 Oz
NOV40aa
N0V4Oab
N0V4 Oac
NOV40a TFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMA
N0V4Ob
N0V4Oc
NOV40d
NOV4 Oe
N0V4Of N0V4 Og
N0V4 Oh
NOV40i TFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMA
NOV4 Oj
NOV4 Ok
NOV401
NOV4 Om
NOV4On
NOV4Oo
NOV4 Op
NOV4 Oq
NOV4 Or
NOV40S YNPPESNASIITDYNEEGLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETA
NOV4Ot
NOV40U TFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQAKAFLSLGKMA
NOV4 Ov
NOV4 Ow
NOV4Ox
NOV4Oy
N0V4 Oz
NOV4 Oaa
NOV4 Oab
NOV4Oac
N0V4Oa EVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNA
N0V4Ob
N0V4Oc
N0V4Od
N0V4Oe
NOV40f
N0V4 Og
N0V4 Oh
NOV40i EVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNA
NOV40J
NOV40k
NOV401
N0V4 Om
NOV40n
N0V4Oo
NOV40p
NOV4 Oq
NOV40r
NOV40s GVLKTVNLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVI
NOV4Ot
N0V4 Ou EVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANEDCIKVAAVLNNA
NOV40v
N0V4Ow
N0V4Ox
N0V4Oy
N0V4Oz
NOV40aa
NOV40ab
NOV40ac N0V4Oa FYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTR
N0V4Ob
N0V4Oc
NOV4Od
NOV4 Oe
NOV4 Of
NOV4Og
NOV4 Oh
NOV40i FYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTR
NOV4Oj
NOV4Ok
NOV401
NOV4Om
NOV4On
NOV4 Oo
NOV4Op
NOV4 Oq
NOV4Or
NOV4 Os NETPLPIDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEI
NOV4 Ot
NOV4Ou FYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVSQSTTWNGRTR
NOV4 Ov
NOV4Ow
NOV4 Ox
NOV40y
NOV40Z
NOV4Oaa
NOV4 Oab
NOV4Oac
NOV4Oa RFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWT
NOV4Ob
NOV4Oc
NOV4Od
NOV40e
NOV40f
NOV4 Og
NOV4 Oh
NOV4 Oi RFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWT
NOV4Oj
NOV4 Ok
NOV401
NOV4 Om
NOV4On
NOV4 Oo
NOV4Op
NOV40q
NOV40r
NOV4 Os FRSLMYWITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYD
NOV40t
NOV4 Ou RFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRVRDGEEGARLWT
NOV4 Ov
NOV4Ow
NOV4Ox N0V4Oy
N0V4Oz
NOV4Oaa
NOV4Oab
NOV4 Oac
NOV4Oa EGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
NOV4 Ob
NOV40C
NOV4Od
NOV4 Oe
NOV4 Of
NOV40g
NOV4 Oh
NOV4 Oi EGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
NOV4Oj
NOV40k
NOV401
N0V4Om
N0V4 On
N0V4Oo
NOV40p
NOV4 Oq
NOV4 Or
NOV40S LNGNLHLLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLT
NOV4 Ot
N0V4 Ou EGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
N0V4Ov
N0V4 Ow
N0V4 Ox
N0V4 Oy
N0V4 Oz
N0V4Oaa
N0V4 Oab
N0V4 Oac
NOV40a
N0V4 Ob
N0V4Oc
N0V4Od
N0V4 Oe
N0V4 Of
N0V4Og
N0V4Oh
N0V4Oi
N0V4 Oj
N0V4 Ok
N0V401
N0V4Om
N0V4 On
N0V4Oo
N0V4 Op
N0V4 Oq
NOV40r N0V4OS RVYSKGSGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLY
NOV4 Ot
NOV4 Ou
NOV4 Ov
NOV40W
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4 Oaa
NOV4Oab
NOV40ac
NOV4 Oa
NOV4 Ob
NOV4 Oc
NOV4 Od
NOV4 Oe
NOV4 Of
NOV4 Og
NOV40h
NOV4 Oi
N0V4 Oj
N0V4Ok
NOV401
NOV4Orn
NOV4On
NOV4Oo
NOV4Op
N0V4 Oq
NOV4Ox
NOV40S YDLQGHLFAMEISSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQL
NOV40t
N0V4 On
N0V4Ov
NOV40-W
N0V4Ox
N0V4Oy
NOV40Z
NOV40aa
N0V4Oab
N0V4Oac
N0V4Oa
N0V4Ob
N0V4Oc
N0V4Od
NOV40e
N0V4Of
N0V4Og
N0V40
N0V4Oi
N0V4Oj
N0V4Ok
N0V401 NOV40m
NOV4On
NOV4 Oo
NOV4Op
NOV40q
NOV4Or
NOV40S VIGFHGGLYDPLTKLIHFGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPAS
NOV4 Ot
NOV4Ou
NOV4Ov
NOV4Ow
NOV40x
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4 Oac
NOV4Oa
NOV4 Ob
NOV4Oc
NOV4 Od
NOV4 Oe
NOV4Of
NOV4 Og
NOV4Oh
NOV4 Oi
NOV40j
NOV4Ok
NOV401
N0V4 Om
NOV40n
N0V4 Oo
NOV4Op
NOV4 Oq
NOV4Or
NOV40S KIHDVKDYITDVNSWLVTFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQ
NOV4 Ot
NOV4Ou
NOV4 Ov
NOV4 Ow
N0V4 Ox
N0V4 Oy
N0V4Oz
N0V4 Oaa
N0V4 Oab
N0V4Oac
N0V4Oa
N0V4 Ob
N0V4 Oc
N0V4Od
N0V4 Oe
NOV40f N0V4Og
NOV4Oh
NOV4 Oi
NOV4Oj
NOV40k
NOV401
NOV4Om
NOV4On
NOV4Oo
NOV4Op
NOV4Oq
NOV4Or
N0V4 OS QQVARQAKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVL
NOV4Ot
NOV4 Ou
NOV4Ov
NOV4Ow
NOV4 Ox
NOV4 Oy
NOV4Oz
NOV40aa
NOV4Oab
NOV4 Oac
NOV4Oa
NOV4Ob
NOV4Oc
NOV4Od
NOV4Oe
NOV4 Of
NOV4Og
NOV4Oh
NOV4Oi
NOV40J
NOV4Ok
NOV401
NOV4Om
NOV4 On
NOV4Oo
NOV4 Op
NOV4Oq
NOV4Or
N0V4OS NIANEDCIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENG
N0V4Ot
NOV40u
N0V4Ov
N0V4Ow
N0V4 Ox
NOV4Oy
NOV4Oz
NOV4Oaa
NOV4Oab
NOV4 Oac NOV40a
NOV4Ob
NOV4Oc
N0V4 Od
NOV4Oe
NOV4Of
NOV4 Og
NOV4 Oh
NOV40i
NOV40j
N0V4Ok
NOV401
N0V4Om
NOV4 On
NOV4 Oo
N0V4Op
NOV4 Oq
NOV40r
NOV40s INVTVSQSTTVVNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWA
NOV4Ot
NOV4Ou
NOV4 Ov
NOV40W
NOV4 Ox
NOV4 Oy
NOV4 Oz
NOV4Oaa
NOV4 Oab
NOV4 Oac
NOV4 Oa
NOV4 Ob
NOV4Oc
NOV4Od
NOV4 Oe
NOV4Of
NOV4Og
NOV4 Oh
NOV40i
NOV4 Oj
NOV4Ok
NOV401
N0V4Om
NOV4On
NOV40O
NOV4 Op
NOV4Oq
NOV4Or
NOV40s REQQRVRDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQS
NOV4Ot
NOV40U
NOV4Ov
NOV40W
NOV4 Ox N0V4 Oy
NOV40Z
NOV4 Oaa NOV40ab
NOV4 Oac
NOV40a NOV4 Ob NOV40C NOV40d NOV40e NOV40f NOV40g
NOV4 Oh NOV40i NOV40J
NOV40k NOV401 NOV40m NOV4 On N0V40O NOV4 Op
NOV40q
NOV40r
NOV40S EIGRR
NOV40t
NOV4 Ou
NOV40v
NOV4 Ow
NOV4Ox
NOV40y
NOV40z
NOV40aa
NOV40ab
NOV40ac
NOV40a (SEQ ID O 486)
NOV4 Ob (SEQ ID NO 488)
NOV40C (SEQ ID O 490)
NOV4 Od (SEQ ID NO 492)
NOV40e (SEQ ID NO 494)
NOV40f (SEQ ID O 496)
NOV4Og (SEQ ID NO 498)
NOV4 Oh (SEQ ID NO 500)
NOV40i (SEQ ID O 502)
NOV40J (SEQ ID NO 504)
NOV4Ok (SEQ ID NO 506)
NOV401 (SEQ ID NO 508)
NOV4Om (SEQ ID NO 510)
NOV40n (SEQ ID NO 512)
NOV4Oo (SEQ ID NO 514)
NOV4Op (SEQ ID NO 516)
NOV40q (SEQ ID NO 518)
NOV40r (SEQ ID NO 520) NOV40S (SEQ ID NO 522)
NOV40t (SEQ ID NO 524)
NOV4 Ou (SEQ ID NO 526)
NOV4 Ov (SEQ ID NO 528)
NOV4 Ow (SEQ ID NO 530)
NOV4 Ox (SEQ ID NO 532)
NOV4 Oy (SEQ ID NO 534)
NOV40z (SEQ ID NO 536)
NOV40aa (SEQ ID NC ): 538)
NOV4 Oab (SEQ ID NC ): 540)
NOV40ac (SEQ ID NC ): 542)
Further analysis ofthe NOV40a protein yielded the following properties shown in Table 40C.
Figure imgf000634_0001
cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: RRPYCSLTKSRREKERR at 6 bipartite: RKEQAQGKVNVFGRKLR at 1778 content of basic residues: 9.9% NLS Score: 0.51
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none .
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 57 checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LTPLRYDLRDRITRLGDVQYRL at 2196 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues Final Results (k = 9/23) :
34.8 % nuclear
26.1 % mitochondrial
13.0 % Golgi
8.7 % cytoplasmic
4.3 % plasma membrane
4.3 % vesicles of secretory system
4.3 % extracellular, including cell wall
4.3 % peroxisomal
>> prediction for CG55069-01 is nuc (k=23)
A search ofthe NOV40a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 40D.
Figure imgf000636_0001
In a BLAST search of public sequence databases, the NOV40a protein was found to have homology to the proteins shown in the BLASTP data in Table 40E.
Figure imgf000637_0001
PFam analysis indicates that the NOV40a protein contains the domains shown in the Table 40F.
Figure imgf000637_0002
Example 41.
The NOV41 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 41 A.
Figure imgf000638_0001
Figure imgf000639_0001
NOV41e, CG55343-01 SEQ ID NO: 562 313 aa MW at 35443.7kD Protein Sequence
MNWVNDS11QEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLT11LVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDWFVAICRPLHYSVIM HQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGK MVSLFYGIIAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV41f, CG55343-02 SEQ ID NO: 563 993 bp DNA Sequence ORF Start: ATG at 15 ORF Stop: TAA at 954
TTGAAACATTAATCATGAATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCA
GATCGACCTTGGCTGGAGTTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGG CAATCTGACCATTATTCTAGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTA CCAATCTATCACTCCTGGATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGC AGCATCAGGAAAGTAATCAGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGC TACTGAATATCTTCTCCTGGCCGTCATGTCCTTTGATAGGTTTGTAGCTATTTGTCGGCCTCTCCATT ACTCAGTTATCATGCACCAGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGT AACTCAGTGTGGTTGTCTACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTT TCTCTGTGAAGTCCCTGCACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTAT TCCTTGTCAGTGAGCTCTTCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTC CGAGCAGTATTGAGGATACAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCT AATTGTGGTGTCTCTTTTTTATAGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCA AGGACCAAGGAAAGATGGTTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATAT ACACTTAGGAACAAGGAGGTAAAGGAAGGCTTTAAAAGGTTGGTTGCAAGAGTCTTCTTAATCAAGAA ATAAGAAATATGCAAATGATAAGCTTTGCTAAAGACAAAAT
NOV41f, CG55343-02 SEQ ID NO: 564 313 aa MW at 35413.7kD Protein Sequence
MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDRFVAICRPLHYSVIM HQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGK MVSLFYGIIAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV41g, CG55343-04 SEQ ID NO: 565 60 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGCTGGAGTTT
NOV41g, CG55343-04 SEQ ID NO: 566 20 aa| MW at 2425.7kD Protein Sequence
DSIIQEFILLGFSDRPWLEF
NOV41h, CG55343-05 SEQ ID NO: 567 60 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GAAGTCCCTGCACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTA
NOV41h, CG55343-05 SEQ ID NO: 568 20 aa MW at 2130.4kD Protein Sequence
EVPALLKLSCVETTANEAEL
NOV41i, CG55343-06 SEQ ID NO: 569 946 bp DNA Sequence ORF Start: at 3 ORF Stop: TAG at 936
ATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGCTGGAG TTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGGCAATCTGACCATTATTCT AGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTACCAATCTATCACTCCTGG ATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGCAGCATCAGGAAAGTAATC AGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGCTACTGAATATCTTCTCCT GGCCGTCATGTCCTTTGATAGGTTTGTAGCTATTTGTCGGCCTCTCCATTACTCAGTTATCATGCACC AGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGTAACTCAGTGTGGTTGTCT ACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTTTCTCTGTGAAGTCCCTGC ACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTATTCCTTGTCAGTGAGCTCT TCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTCCGAGCAGTATTGAGGATA CAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCTAATTGTGGTGTCTCTTTT TTATAGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCAAGGACCAAGGAAAGATGG TTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATATACACTTAGGAACAAGGAG GTAAAGGAAGGCTTTAAAAGGTTGGTTGCAAGAGTCTTCTTAATCAAGAAATAGGGATTCGG
NOV4H, CG55343-06 SEQ ID NO: 570 311 aa MW at 35168.4kD Protein Sequence
WVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSLLD LCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDRFVAICRPLHYSVIMHQ RLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSELF HLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMV SLFYGIIAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV41J, SNP13373740 of SEQ ID NO: 571 943 bp CG55343-03, DNA Sequence ORF Start: ATG at 2 ORF Stop: TAA at 941
SNP Pos: 56δ SNP Change: T to C
TATGAATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGC TGGAGTTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGGCAATCTGACCATT ATTCTAGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTACCAATCTATCACT CCTGGATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGCAGCATCAGGAAAG TAATCAGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGCTACTGAATATCTT CTCCTGGCCGTCATGTCCTTTGATTGGTTTGTAGCTATTTGTCGGCCTCTCCATTACTCAGTTATCAT GCACCAGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGTAACTCAGTGTGGT TGTCTACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTTTCTCTGTGAAGTC CCTGCACTGCTCAAGTTATCTTGCGTTGAGACAACAGCAAATGAGGCTGAACTATTCCTTGTCAGTGA GCTCTTCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTCCGAGCAGTATTGA GGATACAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCTAATTGTGGTGTCT CTTTTTTATAGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCAAGGACCAAGGAAA GATGGTTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATATACACTTAGGAACA AGGAGGTAAAGGAAGGCTTTAAAAGGTTGGTTGCAAGAGTCTTCTTAATCAAGAAATAA
NOV41J, SNP 13373740 of SEQ ID NO: 572 313 aa MW at 35443.7kD CG55343-03, Protein Sequence SNP Pos: 189 ISNP Change: Cys to Cys
MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDWFVAICRPLHYSVIM HQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGK MVSLFYGIIAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV41k, SNP13376425 of SEQ ID NO: 573 943 bp CG55343-03, DNA Sequence ORF Start: ATG at 2 ORF Stop: TAA at 941
SNP Pos: 758 SNP Change: A to G
TATGAATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGC TGGAGTTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGGCAATCTGACCATT ATTCTAGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTACCAATCTATCACT CCTGGATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGCAGCATCAGGAAAG TAATCAGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGCTACTGAATATCTT CTCCTGGCCGTCATGTCCTTTGATTGGTTTGTAGCTATTTGTCGGCCTCTCCATTACTCAGTTATCAT GCACCAGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGTAACTCAGTGTGGT TGTCTACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTTTCTCTGTGAAGTC CCTGCACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTATTCCTTGTCAGTGA GCTCTTCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTCCGAGCAGTATTGA GGATACAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCTAATTGTGGTGTCT CTTTTTTATGGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCAAGGACCAAGGAAA GATGGTTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATATACACTTAGGAACA AGGAGGTAAAGGAAGGCTTTAAAAGGTTGGTTGCAAGAGTCTTCTTAATCAAGAAATAA
NOV41k, SNP13376425 of SEQ ID NO: 574 313 aa MW at 35413.7kD CG55343-03, Protein Sequence SNP Pos: 253 SNP Change: Ser to Gly
MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDWFVAICRPLHYSVIM HQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYGTAVSVYLQPPSPSSKDQGK MVSLFYGIIAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV411, SNP13376424 of SEQ ID NO: 575 943 bp CG55343-03, DNA Sequence ORF Start: ATG at 2 ORF Stop: TAA at 941
SNP Pos: δlO SNP Change: A to G
TATGAATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGC TGGAGTTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGGCAATCTGACCATT ATTCTAGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTACCAATCTATCACT CCTGGATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGCAGCATCAGGAAAG TAATCAGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGCTACTGAATATCTT CTCCTGGCCGTCATGTCCTTTGATTGGTTTGTAGCTATTTGTCGGCCTCTCCATTACTCAGTTATCAT GCACCAGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGTAACTCAGTGTGGT TGTCTACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTTTCTCTGTGAAGTC CCTGCACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTATTCCTTGTCAGTGA GCTCTTCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTCCGAGCAGTATTGA GGATACAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCTAATTGTGGTGTCT CTTTTTTATAGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCAAGGACCGAGGAAA GATGGTTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATATACACTTAGGAACA AGGAGGTAAAGGAAGGCTTTAAAAGGTTGGTTGCAAGAGTCTTCTTAATCAAGAAATAA
NOV411, SNP 13376424 of SEQ ID NO: 576 313 aa MW at 35471.δkD CG55343-03, Protein Sequence SNP Pos: 270 SNP Change: Gin to Arg
MNWVNDSI IQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSI RKVI SYRGCVAQLFI FLALGATEYLLLAVMSFDWFVAI CRPLHYSVIM HQRLCLQLAAASVAΓΓGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDRGK MVSLFYGI IAPMLNPLIYTLRNKEVKEGFKRLVARVFLIKK
NOV41m, SNPl 3376423 of SEQ ID NO: 577 943 bp CG55343-03, DNA Sequence ORF Start: ATG at 2 ORF Stop: TAA at 941
SNP Pos: 90δ SNP Change: A to G
TATGAATTGGGTAAATGACAGCATCATACAGGAGTTTATTCTGCTGGGTTTCTCAGATCGACCTTGGC TGGAGTTTCCACTCCTTGTGGTCTTCTTGATTTCTTACACTGTGACCATCTTTGGCAATCTGACCATT ATTCTAGTGTCACGCCTGGACACCAAACTTCATACCCCCATGTATTTTTTTCTTACCAATCTATCACT CCTGGATCTTTGTTACACCACATGTACAGTCCCACAAATGCTAGTAAATTTATGCAGCATCAGGAAAG TAATCAGTTATCGTGGCTGTGTAGCCCAGCTTTTCATATTTCTGGCCTTGGGGGCTACTGAATATCTT CTCCTGGCCGTCATGTCCTTTGATTGGTTTGTAGCTATTTGTCGGCCTCTCCATTACTCAGTTATCAT GCACCAGAGACTCTGCCTCCAGTTGGCAGCTGCATCCTGGGTTACTGGTTTTAGTAACTCAGTGTGGT TGTCTACCCTGACTCTCCAGCTGCCACTCTGTGACCCCTATGTGATAGATCACTTTCTCTGTGAAGTC CCTGCACTGCTCAAGTTATCTTGTGTTGAGACAACAGCAAATGAGGCTGAACTATTCCTTGTCAGTGA GCTCTTCCATCTAATACCCCTGACACTCATCCTTATATCATATGCTTTTATTGTCCGAGCAGTATTGA GGATACAGTCTGCTGAAGGTCGACAAAAAGCATTTGGGACATGTGGTTCCCATCTAATTGTGGTGTCT CTTTTTTATAGTACAGCCGTCTCTGTGTACCTGCAACCACCTTCGCCCAGCTCCAAGGACCAAGGAAA GATGGTTTCTCTCTTCTATGGAATCATTGCACCCATGCTGAATCCCCTTATATATACACTTAGGAACA AGGAGGTAAAGGAAGGCTTTAAAGGGTTGGTTGCAAGAGTCTTCTTAATCAAGAAATAA
63δ NOV41m, SNPl 3376423 of SEQ ID NO: 57 313 aa MW at 35344.6kD CG55343-03, Protein Sequence SNP Pos: 303 SNP Change: Arg to Gly
MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLHTPMYFFLTNLSL LDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLAVMSFDWFVAICRPLHYSVIM HQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDHFLCEVPALLKLSCVETTANEAELFLVSE LFHLIPLTLILISYAFIVRAVLRIQSAEGRQKAFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGK MVSLFYGIIAPMLNPLIYTLRNKEVKEGFKGLVARVFLIKK
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 4 IB.
Table 41B. Comparison ofthe NOV41 protein sequences.
NOV41a MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH NOV4 lb WVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH NOV41C RGSTMNWVNDS11QEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLT11LVSRLDTKLH N0V41d RGSTMNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH NOV41e MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH NOV41f MNWVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH N0V4lg DSIIQEFILLGFSDRPWLEF NOV41h NOV4U WVNDSIIQEFILLGFSDRPWLEFPLLWFLISYTVTIFGNLTIILVSRLDTKLH
NOV41a TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA N0V4 lb TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA N0V41C TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA N0V41d TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLEA NOV41e TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA NOV41f TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA NOV4 lg NOV41 N0V41i TPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLFIFLALGATEYLLLA
N0V4 la VMSFDWFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
N0V4lb VMSFDRFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
N0V4 lc VMSFDRFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
NOV4Id
N0V4 le VMSFDWFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
N0V41f VMSFDRFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
NOV4 lg
NOV4 lh
NOV4 li VMSFDRFVAICRPLHYSVIMHQRLCLQLAAASWVTGFSNSVWLSTLTLQLPLCDPYVIDH
NOV4 la FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK
NOV4 lb FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK
NOV4 lc FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK
NOV4 Id
NOV4 le FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK
NOV41f FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK
NOV4 lg
NOV4 lh EVPALLKLSCVETTANEAEL
NOV4 li FLCEVPALLKLSCVETTANEAELFLVSELFHLIPLTLILISYAFIVRAVLRIQSAEGRQK NOV41a AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
NOV4lb AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
NOV4IC AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
NOV4Id
NOV4le AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
NOV41f AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
NOV41g
N0V4lh
N0V41Ϊ AFGTCGSHLIWSLFYSTAVSVYLQPPSPSSKDQGKMVSLFYGIIAPMLNPLIYTLRNKE
N0V41a VKEGFKRLVARVFLIKK
N0V4lb VKEGFKRLVARVFLIKK
NOV41c VKEGFKRLVARVFLIKKLEA
NOV41d
NOV41e VKEGFKRLVARVFLIKK
NOV41f VKEGFKRLVARVFLIKK
NOV41g
NOV41h
NOV41i VKEGFKRLVARVFLIKK
NOV41a (SEQ ID NO 554)
NOV4lb (SEQ ID NO 556)
NOV41C (SEQ ID O 558)
NOV4 Id (SEQ ID NO 560)
NOV41e (SEQ ID NO 562)
NOV41f (SEQ ID NO 564)
NOV41g (SEQ ID NO 566)
NOV41h (SEQ ID NO 568)
NOV41i (SEQ ID NO 570)
Further analysis ofthe NOV4 la protein yielded the following properties shown in Table 41C.
Table 41C. Protein Sequence Properties NOV41a
SignalP analysis: Cleavage site between residues 39 and 40
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 0; neg.chg 2 H-region: length 7; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -4.39 possible cleavage site: between 38 and 39
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: INTEGRAL Likelihood = -4.78 Transmembrane 25 41 INTEGRAL Likelihood = -5.15 Transmembrane 101 - 117
INTEGRAL Likelihood = -5.47 Transmembrane 206 - 222
INTEGRAL Likelihood = -0.80 Transmembrane 244 - 260
INTEGRAL Likelihood = -0.75 Transmembrane 273 - 289
PERIPHERAL Likelihood = 3.02 (at 173)
ALOM score: -5.47 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 32 Charge difference: 3.5 C( 1.5) - N(-2.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.26 Hyd Moment (95) : 10.83 G content: 0 D/E content : 2 S/T content : 1 Score: -5.89
Gavel : prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 7.3% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: FLIK
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1.- none type : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: mitochondrial
>> prediction for CG55343-03 is end (k=9)
A search ofthe NOV41 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4 ID.
Figure imgf000647_0001
In a BLAST search of public sequence databases, the NOV4 la protein was found to have homology to the proteins shown in the BLASTP data in Table 4 IE.
Figure imgf000648_0001
PFam analysis indicates that the NOV4 la protein contains the domains shown in the Table 41F.
Figure imgf000648_0002
Example 42.
The NOV42 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 42A. Table 42A. NOV42 Sequence Analysis
NOV42a, CG5535δ-04 ^SEQ ID NO: 579 |947 bp" DNA Sequence ORF Start: ATG at 2 ORF Stop: TAG at 93δ
TATGGAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACC TAGAGCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATT GTCTTGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATT CCTGGACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGA CCATCAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTC CTCCTGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCAT GCACCCACGTCTCTGTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAA TGGCACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATG CCAGCACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAAT CTTTATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTA GGATCAAGTCAGCTGCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCT CTCTTCTATGGTACAATCATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAA GTTTCTTACCCTTTTCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACA AAGATGTTAAAGAGGCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGGA
NOV42a, CG55358-04 SEQ ID NO: 580 312 aa MW at 34640.9kD Protein Sequence
MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSF LDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIM HPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAI FIVLAPLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGK FLTLFYTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42b, CG55358-03 SEQ ID NO: 581 932 bp DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42b, CG55358-03 SEQ ID NO: 5δ2 307 aa MW at 34051.3kD Protein Sequence
TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLC GQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NO V42c, 317863291 SEQ ID NO: 583 693 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CGCGGATCCACCATGTACAAGTTCTTTCGAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCT AGAGCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTG TCTTGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTC CTGGACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGAC CATCAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCC TCCTGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATG CACCCACGTCTCTGTGGACAGCTGGTTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAAT GGCACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGC CAGCACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATC TTTATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAG GATCCTCGAGGCG
NOV42c, 317863291 SEQ ID NO: 584 231 aa MW at 25750.8kD Protein Sequence
RGSTMYKFFRGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSF LDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIM HPRLCGQLVSVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAI FIILAPLILILISYGYVGGTVLRILEA
NOV42d, 317δ6332δ SEQ ID NO: 5δ5 609 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CGCGGATCCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGCTCT GGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTTTCA CCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTGGGT TGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCATGGC ATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCTGTG GACAGCTGGTTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACATTG ATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGGTAT GGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGGCAC CACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCCTCGAGGCG
NOV42d, 317δ6332δ SEQ ID NO: 5δ6 203 aa MW at 22437.δkD Protein Sequence
RGSLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVG CAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLCGQLVSVAWLSGFGNSLIMAPQTL MLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRILEA
NOV42e, 317δ63350 SEQ ID NO: 5δ7 433 bp DNA Sequence ORF Start: at 1 ORF Stop: at 433
CGCGGATCCGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGT CATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTC TCTGTGGACAGCTGGTTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAG ACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAAT TGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCC TGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCCTCGAG GCGAAGGGCGAATTCCAGCACACTG
NOV42e, 317δ63350 SEQ ID NO: 5δδ 144 aa MW at l57δ3.9kD Protein Sequence
RGSAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLCGQLVSVAWLSGFGNSLIMAPQ TLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRILE AKGEFQHT
NO V42f, 271624076 SEQ ID NO: 5δ9 953 bp DNA Sequence ORF Start: at 1 ORF Stop: TAG at 934
GAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGA GCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCT TGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTG GACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCAT CAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCC TGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCAC CCACGTCTCTGTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGC ACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAG CACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTT ATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGAT CAAGTCAGCTGCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCT TCTATGGTACAATCATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTT CTTACCCTTTTCTACACAATCGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGA TGTTAAAGAGGCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGGAATTCGGAAGGGCGA A
NOV42f, 271624076 SEQ ID NO: 590 311 aa MW at 34523.7kD Protein Sequence
ENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFL DMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMH PRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIF IILAPLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKF LTLFYTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42g, CG5535δ-01 SEQ ID NO: 591 945 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAG at 937
ATGGAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCT AGAGCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTG TCTTGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTC CTGGACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGAC CATCAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCC TCCTGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATG CACCCACGTCTCTGTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAAT GGCACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGC CAGCACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATC TTTATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAG GATCAAGTCAGCTGCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTC TCTTCTATGGTACAATCATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAG TTTCTTACCCTTTTCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAA AGATGTTAAAGAGGCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42g, CG5535δ-01 SEQ ID NO: 592 312 aa MW at 34654.9kD Protein Sequence
MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSF LDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIM HPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAI FIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGK FLTLFYTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42h, CG55358-02 SEQ ID NO: 593 947 bp DNA Sequence ORF Start: ATG at 3 ORF Stop: TAG at 939
GTATGGAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCAC CTAGAGCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCAT TGTCTTGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCAT TCCTGGACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAG ACCATCAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGT CCTCCTGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCA TGCACCCACGTCTCTGTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATA ATGGCACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGAT GCCAGCACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAA TCTTTATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTT AGGATCAAGTCAGCTGCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTC TCTCTTCTATGGTACAATCATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCA AGTTTCTTACCCTTTTCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAAC AAAGATGTTAAAGAGGCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42h, CG55358-02 SEQ ID NO: 594 312 aa MW at 34654.9kD Protein Sequence
MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSF LDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIM HPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAI FIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGK FLTLFYTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42i, CG5535δ-05 SEQ ID NO: 595 63 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: end of sequence
ATGGAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCC
NOV42i, CG5535δ-05 SEQ ID NO: 596 21 aa MW at 2362.5kD Protein Sequence
MENDNTSSFEGFILVGFSDRP
NOV42J, CG5535δ-06 SEQ ID NO: 597 60 bp DNA Sequence ORF Start: at 1 JORF Stop: end of sequence
ACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCA
NOV42J, CG5535δ-06 SEQ ID NO: 598 20 aa; MW at 2411.9kD Protein Sequence
TLMLPRCGHRRVDHFLCEMP
|NOV42k, CG55358-07 SEQ ID NO: 599 953 bp DNA Sequence ORF Start: at 1 JORF Stop: TAG at 934
GAAAACGATAATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGA GCTGATCGTCTTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCT TGCTTTCAGCTCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTG GACATGTGTTTCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCAT CAGCTATGTGGGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCC TGGCTGTCATGGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCAC CCACGTCTCTGTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGC ACCCCAGACATTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAG CACTAATTGGTATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTT ATCATCCTGGCACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGAT CAAGTCAGCTGCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCT TCTATGGTACAATCATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTT CTTACCCTTTTCTACACAATCGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGA TGTTAAAGAGGCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGGAATTCGGAAGGGCGA A
NOV42k, CG5535δ-07 SEQ ID NO: 600 311 aa MW at 34523.7kD Protein Sequence
ENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFL DMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMH PRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIF IILAPLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKF LTLFYTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV421, SNPl 3375122 of SEQ ID NO: 601 932 bp CG5535δ-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 64 SNP Change: T to C
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGACCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC
64δ TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV421, SNP 13375122 of SEQ ID NO: 602 307 aa MW at 34039.2kD CG5535δ-03, Protein Sequence SNP Pos: 21 SNP Change: He to Thr
TSSFEGFILVGFSDRPHLELTVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLC GQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42m, SNPl 3375123 of SEQ ID NO: 603 932 bp CG5535δ-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 124 SNP Change: T to C
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGCCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42m, SNP13375123 of SEQ ID NO: 604|307 aa MW at 34023.2kD CG5535δ-03, Protein Sequence SNP Pos: 41 SNP Change: Val to Ala
TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIALLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLC GQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42n, SNP133δ2494 of SEQ ID NO: 605 932 bp CG5535δ-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 254 SNP Change: T to C
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGACAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42n, SNP133δ2494 of SEQ ID NO: 606 307 aa jMW at 34051.3kD CG5535δ-03, Protein Sequence SNP Pos: δ4 jSNP Change: Asp to Asp
TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLC GQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42o, SNPl 3375124 of SEQ ID NO: 607 932 bp CG5535δ-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 2δ3 SNP Change: T to C
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCACCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42o, SNP 13375124 of SEQ ID NO: 608 307 aa MW at 34039.2kD CG5535δ-03, Protein Sequence SNP Pos: 94 SNP Change: He to Thr
TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGS I PQMLYNLWGPDKTI SYVGCATQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTI IMHPRLC GQLASVAWLSGFGNSL I MAPQTLMLPRCGHRRVDHFLCEMPAL I GMACVDTMMLEALAFALAI F I I LA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42p, SNP13375125 of SEQ ID NO: 609 932 bp CG55358-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 336 SNP Change: G to A
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTATCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42p, SNP13375125 of [SEQ ID NO: 610 307 aa MW at 34065.3kD
CG55358-03, Protein Sequence SNP Pos: 112 SNP Change: Val to He
TSSFEGFILVGFSDRPHLELIVFWVLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAIMAYDRYAAVCKPLHYTIIMHPRLC GQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42q, SNPl 3376426 of SEQ ID NO: 611 932 bp CG55358-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 415 SNP Change: A to G
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACGGCTGGCTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
NOV42q, SNPl 3376426 of SEQ ID NO: 612 307 aa MW at 34079.3kD CG5535δ-03, Protein Sequence SNP Pos: 138 |SNP Change: Gin to Arg
TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMYFFLANLSFLDMCF TTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAYDRYAAVCKPLHYTIIMHPRLC GRLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCEMPALIGMACVDTMMLEALAFALAIFIILA PLILILISYGYVGGTVLRIKSAAGRKKAFNTCSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLF YTIVTPSVNPLIYTLRNKDVKEAMKKVLGKGSAEI
NOV42r, SNP13376427 of SEQ ID NO: 613 932 bp CG55358-03, DNA Sequence ORF Start: at 3 ORF Stop: TAG at 924
SNP Pos: 421 SNP Change: C to T
ATACAAGTTCTTTCGAAGGCTTCATCCTGGTGGGCTTCTCTGATCGTCCCCACCTAGAGCTGATCGTC TTTGTGGTTGTCCTCATCTTTTATCTGCTGACTCTTCTTGGCAACATGACCATTGTCTTGCTTTCAGC TCTGGATTCCCGGCTGCACACACCAATGTATTTCTTTTTGGCAAACCTCTCATTCCTGGACATGTGTT TCACCACAGGTTCCATCCCTCAGATGCTCTACAACCTTTGGGGTCCAGATAAGACCATCAGCTATGTG GGTTGTGCCATCCAGCTGTACTTTGTCCTGGCCCTGGGAGGGGTGGAGTGTGTCCTCCTGGCTGTCAT GGCATATGACCGCTATGCTGCAGTCTGCAAACCCCTGCACTACACCATCATCATGCACCCACGTCTCT GTGGACAGCTGGTTTCAGTGGCATGGCTGAGTGGCTTTGGCAATTCTCTCATAATGGCACCCCAGACA TTGATGCTACCCCGCTGTGGGCACAGACGAGTTGACCACTTTCTCTGTGAGATGCCAGCACTAATTGG TATGGCCTGTGTAGACACCATGATGCTTGAGGCACTGGCTTTTGCCCTGGCAATCTTTATCATCCTGG CACCACTCATCCTCATTCTCATTTCTTATGGTTACGTTGGAGGAACAGTGCTTAGGATCAAGTCAGCT GCTGGGCGAAAGAAAGCCTTCAACACTTGCAGCTCGCATCTAATTGTTGTCTCTCTCTTCTATGGTAC AATTATATACATGTACCTCCAGCCAGCAAATACTTATTCCCAGGACCAGGGCAAGTTTCTTACCCTTT TCTACACAATTGTCACTCCCAGTGTTAACCCCCTGATCTATACACTAAGAAACAAAGATGTTAAAGAG GCCATGAAGAAGGTGCTAGGGAAGGGGAGTGCAGAAATATAGTAAGGG
Figure imgf000656_0001
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 42B.
Table 42B. Comparison of the NOV42 protein sequences.
N0V42a MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
N0V42b TSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
N0V42C RGSTMYKFFRGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
N0V42d RGSLIFYLLTLLGNMTIVLLSALDSRLHTPMY
N0V42e
N0V42f -ENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
N0V42g MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
NOV42h MENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
NOV42i
NOV42J
NOV42k -ENDNTSSFEGFILVGFSDRPHLELIVFVWLIFYLLTLLGNMTIVLLSALDSRLHTPMY
NOV42a FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY NOV42b FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY NOV42C FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42d FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42e RGSAIQLYFVLALGGVECVLLAVMAY
NOV42f FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42g FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42h FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42i
NOV42j
NOV42k FFLANLSFLDMCFTTGSIPQMLYNLWGPDKTISYVGCAIQLYFVLALGGVECVLLAVMAY
NOV42a DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42b DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42C DRYAAVCKPLHYTIIMHPRLCGQLVSVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42d DRYAAVCKPLHYTIIMHPRLCGQLVSVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42e DRYAAVCKPLHYTIIMHPRLCGQLVSVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42f DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42g DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42h DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE NOV42i MENDNTSSFEGFILVGFSDRP NOV42J TLMLPRCGHRRVDHFLCE NOV42k DRYAAVCKPLHYTIIMHPRLCGQLASVAWLSGFGNSLIMAPQTLMLPRCGHRRVDHFLCE
NOV42a MPALIGMACVDTMMLEALAFALAIFIVLAPLILILISYGYVGGTVLRIKSAAGRKKAFNT NOV42b MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNT NOV42C MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRILEA NOV42d MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRILEA NOV42e MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRILEAKGEFQHT-- NOV42f MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNT NOV42g MPA IGMACVDTMMLEALAFALAIF11LAPLILILISYGYVGGTVLRIKSAAGRKKAFNT NOV42h MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNT NOV42i NOV42J Mp NOV42k MPALIGMACVDTMMLEALAFALAIFIILAPLILILISYGYVGGTVLRIKSAAGRKKAFNT
NOV42a CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42b CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42C
NOV42d
NOV42e
NOV42f CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42g CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42h CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42i
NOV42j
NOV42k CSSHLIWSLFYGTIIYMYLQPANTYSQDQGKFLTLFYTIVTPSVNPLIYTLRNKDVKEA
NOV42a MKKVLGKGSAEI
NOV42b MKKVLGKGSAEI
NOV42C
NOV42d
NOV42e
NOV42f MKKVLGKGSAEI
NOV42g MKKVLGKGSAEI
NOV42h MKKVLGKGSAEI NOV42i
NOV42k MKKVLGKGSAEI
NOV42a (SEQ ID O 580)
NOV42b (SEQ ID NO 582)
NOV42C (SEQ ID NO 584)
NOV42d (SEQ ID NO 586)
NOV42e (SEQ ID NO 588)
NOV42f (SEQ ID NO 590)
NOV42g (SEQ ID O 592)
NOV42h (SEQ ID NO 594)
NOV42i (SEQ ID NO 596)
NOV42J (SEQ ID NO 598)
NOV42k (SEQ ID O 600)
Further analysis ofthe NOV42a protein yielded the following properties shown in Table 42C.
Table 42C. Protein Sequence Properties NOV42a
SignalP analysis: Cleavage site between residues 42 and 43
PSORT II analysis:
PSG: a new signal peptide prediction method
N- region: length 10; pos . chg 0; neg.chg 3 H- region: length 8; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1) : -2.80 possible cleavage site: between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5:
INTEGRAL Likelihood =-13.21 Transmembrane 25 41
INTEGRAL Likelihood = -7.11 Transmembrane 103 119
INTEGRAL Likelihood = -0.27 Transmembrane 183 199
INTEGRAL Likelihood =-14.97 Transmembrane 200 216
INTEGRAL Likelihood = -1.12 Transmembrane 244 260
PERIPHERAL Likelihood = 1.80 (at 273)
ALOM score: -14.97 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 32 Charge difference: 2.0 C( 0.5) - N(-1.5) C > N: C-terminal side will be inside
>>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 6.56 Hyd Moment(95): 3.47 G content: 0 D/E content: 2 S/T content: 0 Score: -7.29
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 6.7% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail : none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Figure imgf000660_0001
A search ofthe NOV42a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 42D.
Figure imgf000660_0002
In a BLAST search of public sequence databases, the NOV42a protein was found to have homology to the proteins shown in the BLASTP data in Table 42E.
Figure imgf000661_0001
PFam analysis indicates that the NOV42a protein contains the domains shown in the Table 42F.
Figure imgf000661_0002
Example 43.
The NOV43 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 43A. Table 43A. NOV43 Sequence Analysis
NOV43a, CG55604-04 SEQ ID NO: 617 968 bp DNA Sequence ORF Start: ATG at 8 JORF Stop: TGA at 950
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43a, CG55604-04 SEQ ID NO: 618 314 aa MW at 35728.1kD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43b, CG55604-01 SEQ ID NO: 619 J840 bp DNA Sequence ORF Start: ATG at 42 ORF Stop: TGA at 810
TCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATCTCTCC
TTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGAGGAA AACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAGTGTG CGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTACCATC ATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTTTAGT AGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGTGAAC CTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAATGGGC GTGGTAATCCTCCTGGCCCCTGTCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTGTTAT CCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTTGTTG TCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACTGGAT AAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGAGGAA CAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGACCTC TGAGTCTGACTTTTAGAGCTATGG
NOV43b, CG55604-01 SEQ ID NO: 620 256 aa MW at 29023. lkD Protein Sequence
MYFFLRNLSFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAV CKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYS TEMAIFSMGWILLAPVSLILGSYWNI ISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRP NSKTTKELDKMISVFYTAVTPMLNPI IYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43c, CG55604-02 SEQ ID NO: 621 994 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TGA at 973
TGCCAAACAGGTAAACAGGCAAAAATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTAT
CTTCCTGGGTCTTTCACAGGACTTGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATC TGCTGACCGTGCTTGGAAACCAGCTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCC ATGTATTTTTTTCTTAGAAATATCTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGT GTTGGTTCACTTCTTGGTAAAGAGGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCT TTCTTCTGGTTGGGTGTACAGAGTGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTC TGCAAGCCCCTGTACTACTCTACCATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTG GGCCAGTGGGGCACTAGTGTCTTTAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGA ATATAATCAATCACTACTTTTGTGAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGC ACAGAAATGGCCATCTTTTCAATGGGCGTGGTAATCCTCCTGGCCCCTGTCTCCCTGATTCTTGGTTC TTATTGGAATATTATCTCCACTGTTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCA CCTGTGGCTCCCATCTTATTGTTGTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCA AACTCCAAGACTACAAAAGAACTGGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTT GAACCCCATAATTTATAGCTTGAGGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAA AGTGCTTCTCTCATAGGCAGTGACCTCTGAGTCTGACTTTTA
NOV43c, CG55604-02 SEQ ID NO: 622 314 aa lMW at 35714.1kD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPVSLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43d, CG55604-03 SEQ ID NO: 623 960 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 943
ATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACTTGCAGAC CCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAGCTCATCA TCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATATCTCCTTT GCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGAGGAAAAC CATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAGTGTGCGC TGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTACCATCATG ACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTTTAGTAGA TACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGTGAACCTC CTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAATGGGCGTG GTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTGTTATCCA GATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTTGTTGTCC TCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACTGGATAAA ATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGAGGAACAA AGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGACCTCTGA GTCTGACT
NOV43d, CG55604-03 SEQ ID NO: 624 314 aa MW at 35728.1kD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43e, CG55604-05 SEQ ID NO: 625 995 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TGA at 973
TGCCAAACAGGTAAACAGGCAAAAATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTAT
CTTCCTGGGTCTTTCACAGGACTTGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATC TGCTGACCGTGCTTGGAAACCAGCTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCC ATGTATTTTTTTCTTAGAAATCTCTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGT GTTGGTTCACTTCTTGGTAAAGAGGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCT TTCTTCTGGTTGGGTGTACAGAGTGTGCGCTGCTGGCCGTGATGTCCTATGACCGGTATGTGGCTGTC TGCAAGCCCCTGTACTACTCTACCATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTG GGCCAGTGGGGCACTAGTGTCTTTAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGA ATATAATCAATCACTACTTTTGTGAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGC ACAGAAATGGCCATCTTTTCAATGGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTC TTATTGGAATATTATCTCCACTGTTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCA CCTGTGGCTCCCATCTTATTGTTGTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCA AACTCCAAGACTACAAAAGAACTGGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTT GAACCCCATAATTTATAGCTTGAGGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAA AGTGCTTCTCTCATAGGCAGTGACCTCTGAGTCTGACTTTTAA
NOV43e, CG55604-05 SEQ ID NO: 626 314 aa MW at 35728. lkD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNLSF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43f, CG55604-06 SEQ ID NO: 627 946 bp DNA Sequence ORF Start: ATG at 2 JORF Stop: TGA at 944
TATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACTTGCAGA CCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAGCTCATC ATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATATCTCCTT TGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGAGGAAAA CCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAGTGTGCG CTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTACCATCAT GACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTCGGCCAGTGGGGCACTAGTGTCTTTAGTAG ATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGTGAACCT CCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAATGGGCGT GGTAATCCTCCTGGCCCCTGTCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTGTTATCC AGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTTGTTGTC CTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACTGGATAA AATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGAGGAACA AAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA
NOV43f, CG55604-06 SEQ ID NO: 628 314 aa MW at 35614.9kD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSSASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPVSLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43g, CG55604-07 SEQ ID NO: 629 962 bp DNA Sequence ORF Start: ATG at 2 ORF Stop: TGA at 944
TATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACTTGCAGA CCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAGCTCATC ATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATATCTCCTT TGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGAGGAAAA CCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAGTGTGCG CTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTACCATCAT GACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTTTAGTAG ATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGTGAACCT CCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAATGGGCGT GGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTGTTATCC AGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTTGTTGTC CTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACTGGATAA AATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGAGGAACA AAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGACCTCTG AGTCTGACTA NOV43g, CG55604-07 SEQ ID NO: 630 314 aa MW at 35728. lkD Protein Sequence
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIWVLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43h, SNP13019742 of SEQ ID NO: 631 968 bp CG55604-04, DNA Sequence ORF Start: ATG at 8 ORF Stop: TGA at 950
SNP Pos: 203 SNP Change: A to C
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATCT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43h, SNP 13019742 of SEQ ID NO: 632 314 aa MW at 3572δ.lkD CG55604-04, Protein Sequence SNP Pos: 66 SNP Change: He to Leu
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNLSF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPII SLRNKDVKGALRKLVGRKCFSHRQ
NOV43i, SNPl 3373776 of SEQ ID NO: 633 96δ bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: 355 SNP Change: A to C
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCCGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA NOV43i, SNPl 3373776 of SEQ ID NO: 6341314 aa MW at 35728.1kD CG55604-04, Protein Sequence SNP Pos: 116 SNP Change: Ala to Ala
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43J, SNPl 3373777 of SEQ ID NO: 635 968 bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: 372 SNP Change: G to A
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCAGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43J, SNPl 3373777 of SEQ ID NO: 636 314 aa MW at 35700.0kD CG55604-04, Protein Sequence SNP Pos: 122 SNP Change: Arg to Gin
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDQYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIWVLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43k, SNPl 3373778 of SEQ ID NO: 637 968 bp CG55604-04, DNA Sequence ORF Start: ATG at 8 ORF Stop: TGA at 950
SNP Pos: 422 SNP Change: C to T
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAATGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
Figure imgf000667_0001
NOV43m, SNPl 3373837 of SEQ ID NO: 642314 aa MW at 35827.2kD CG55604-04, Protein Sequence SNP Pos: 152 SNP Change: Gly to Arg
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASRALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43n, SNPl 3373836 of SEQ ID NO: 643 96 bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: 5δ7 SNP Change: A to G
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACGGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43n, SNP13373δ36 of SEQ ID NO: 644 314 aa MW at 35698. lkD CG55604-04, Protein Sequence SNP Pos: 194 SNP Change: Ser to Gly
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYGTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43o, SNP13373780 of SEQ ID NO: 645 968 bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: 615 SNP Change: G to A
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGACGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
Figure imgf000669_0001
NOV43q, SNP133737δ2 of SEQ ID NO: 650 314 aa MW at 35728.1kD CG55604-04, Protein Sequence SNP Pos: 224 SNP Change: Thr to Thr
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIWVLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43r, SNP 13373783 of SEQ ID NO: 651 968 bp CG55604-04, DNA Sequence ORF Start: ATG at 8 ORF Stop: TGA at 950
SNP Pos: 844 SNP Change: A to G
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACGGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43r, SNP133737δ3 of SEQ ID NO: 652 314 aa MW at 35728. lkD CG55604-04, Protein Sequence SNP Pos: 279 SNP Change: Thr to Thr
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43s, SNP13373δ33 of SEQ ID NO: 653 968 bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: 850 SNP Change: G to A
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTAACTCCAATGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA NOV43s, SNP13373δ33 of SEQ ID NO: 654)314 aa MW at 3572δ.lkD CG55604-04, Protein Sequence SNP Pos: 281 SNP Change: Val to Val
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43t, SNP133737δ4 of SEQ ID NO: 655 96δ bp CG55604-04, DNA Sequence ORF Start: ATG at δ ORF Stop: TGA at 950
SNP Pos: δ57 SNP Change: A to G
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAGTGTTGAACCCCATAATTTATAGCTTGA GGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA
NOV43t, SNP133737δ4 of SEQ ID NO: 656 314 aa MW at 35696.0kD CG55604-04, Protein Sequence SNP Pos: 2δ4 SNP Change: Met to Val
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPVLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
NOV43u, SNP13373δ32 of SEQ ID NO: 657 96 bp CG55604-04, DNA Sequence ORF Start: ATG at 8 ORF Stop: TGA at 950
SNP Pos: 8δ5 SNP Change: G to A
TATATCAATGGGAGAAGAAAACCAAACCTTTGTGTCCAAGTTTATCTTCCTGGGTCTTTCACAGGACT
TGCAGACCCAGATCCTGCTATTTATCCTTTTCCTCATCATTTATCTGCTGACCGTGCTTGGAAACCAG CTCATCATCATTCTCATCTTCCTGGATTCTCGCCTTCACACTCCCATGTATTTTTTTCTTAGAAATAT CTCCTTTGCAGATCTCTGTTTCTCTACTAGCATTGTCCCTCAAGTGTTGGTTCACTTCTTGGTAAAGA GGAAAACCATTTCTTTTTATGGGTGTATGACACAGATAATTGTCTTTCTTCTGGTTGGGTGTACAGAG TGTGCGCTGCTGGCAGTGATGTCCTATGACCGGTATGTGGCTGTCTGCAAGCCCCTGTACTACTCTAC CATCATGACACAACGGGTGTGTCTCTGGCTGTCCTTCAGGTCCTGGGCCAGTGGGGCACTAGTGTCTT TAGTAGATACCAGCTTTACTTTCCATCTTCCCTACTGGGGACAGAATATAATCAATCACTACTTTTGT GAACCTCCTGCCCTCCTGAAGCTGGCTTCCATAGACACTTACAGCACAGAAATGGCCATCTTTTCAAT GGGCGTGGTAATCCTCCTGGCCCCTATCTCCCTGATTCTTGGTTCTTATTGGAATATTATCTCCACTG TTATCCAGATGCAGTCTGGGGAAGGGAGACTCAAGGCTTTTTCCACCTGTGGCTCCCATCTTATTGTT GTTGTCCTCTTCTATGGGTCAGGAATATTCACCTACATGCGACCAAACTCCAAGACTACAAAAGAACT GGATAAAATGATATCTGTGTTCTATACAGCGGTGACTCCAATGTTGAACCCCATAATTTATAGCTTGA AGAACAAAGATGTCAAAGGGGCTCTCAGGAAACTAGTTGGGAGAAAGTGCTTCTCTCATAGGCAGTGA CCTCTGAGTCTGACTA NOV43u, SNP13373δ32 of SEQ ID NO: 65δ 314 aa MW at 35700. lkD CG55604-04, Protein Sequence SNP Pos: 293 SNP Change: Arg to Lys
MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMYFFLRNISF ADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSYDRYVAVCKPLYYSTIM TQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCEPPALLKLASIDTYSTEMAIFSMGV VILLAPISLILGSYWNIISTVIQMQSGEGRLKAFSTCGSHLIVWLFYGSGIFTYMRPNSKTTKELDK MISVFYTAVTPMLNPIIYSLRNKDVKGALRKLVGRKCFSHRQ
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 43B.
Table 43B. Comparison of the NOV43 protein sequences.
NOV43a MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLIIILIFLDSRLHTPMY NOV43b MY NOV43c MGEENQTFVSKFIFLGLSQDLQTQILLFILFLII LLTVLGNQLII [I]LIFLDSRLHTPMY NOV43d MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLII[I]LIFLDSRLHTPMY NOV43e MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLII[I]LIFLDSRLHTPMY NOV43f MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLII[I]LIFLDSRLHTPMY NOV43g MGEENQTFVSKFIFLGLSQDLQTQILLFILFLIIYLLTVLGNQLII[I]LIFLDSRLHTPMY
NOV43a FFLRNISFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQI IVFLLVGCTECALLAVMSY NOV43b FFLRNLSFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY NOV43c FFLRNISFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY NOV43d FFLRNISFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY NOV43e FFLRNLSFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY NOV43f FFLRNISFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY NOV43g FFLRNISFADLCFSTSIVPQVLVHFLVKRKTISFYGCMTQIIVFLLVGCTECALLAVMSY
NOV43a DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43b DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43C DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43d DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43e DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43f DRYVAVCKPLYYSTIMTQRVCLWLSFRSSASGALVSLVDTSFTFHLPYWGQNIINHYFCE NOV43g DRYVAVCKPLYYSTIMTQRVCLWLSFRSWASGALVSLVDTSFTFHLPYWGQNIINHYFCE
NOV43a PPALLKLASIDTYSTEMAIFSMGWILLAPISLILGSYWNI ISTVIQMQSGEGRLKAFST NOV43b PPALLKLASIDTYSTEMAIFSMGWILLAPVSLILGSYWNIISTVIQMQSGEGRLKAFST NOV43c PPALLKLASIDTYSTEMAIFSMGWILLAPVSLILGSYWNIISTVIQMQSGEGRLKAFST NOV43d PPALLKLASIDTYSTEMAIFSMGWILLAPISLILGSYWNIISTVIQMQSGEGRLKAFST NOV43e PPALLKLASIDTYSTEMAIFSMGWILLAPISLILGSYWNIISTVIQMQSGEGRLKAFST NOV43f PPALLKLASIDTYSTEMAIFSMGWILLAPVSLILGSYWNIISTVIQMQSGEGRLKAFST NOV43g PPALLKLASIDTYSTEMAIFSMGWILLAPISLILGSYWNIISTVIQMQSGEGRLKAFST
NOV43a CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43b CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43c CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43d CGSHLIWVLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43e CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43f CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA NOV43g CGSHLIVWLFYGSGIFTYMRPNSKTTKELDKMISVFYTAVTPMLNPIIYSLRNKDVKGA
66δ NOV43a LRKLVGRKCFSHRQ
NOV43b LRKLVGRKCFSHRQ
NOV43C LRKLVGRKCFSHRQ
NOV43d LRKLVGRKCFSHRQ
NOV43e LRKLVGRKCFSHRQ
NOV43f LRKLVGRKCFSHRQ
NOV43g LRKLVGRKCFSHRQ
NOV43a (SEQ ID NO 618)
NOV43b (SEQ ID NO 620)
NOV43C (SEQ ID NO 622)
NOV43d (SEQ ID NO 624)
NOV43e (SEQ ID NO 626)
NOV43f (SEQ ID NO 628)
NOV43g (SEQ ID NO 630)
Further analysis ofthe NOV43a protein yielded the following properties shown in Table 43C.
Table 43C. Protein Sequence Properties NOV43a
SignalP analysis: Cleavage site between residues 42 and 43
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 1; neg.chg 2 H-region: length 8; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 0.24 possible cleavage site: between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood =-13 .32 Transmembrane 25 - - 41
INTEGRAL Likelihood = -1 75 Transmembrane 71 - - 87
INTEGRAL Likelihood = -8 86 Transmembrane 101 - - 117
INTEGRAL Likelihood = -9 34 Transmembrane 199 - - 215
INTEGRAL Likelihood = -1 65 Transmembrane 241 - - 257
PERIPHERAL Likelihood = 1 59 (at 273)
ALOM score : -13.32 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 32 Charge difference: 1.5 C( 1.5) - N( 0.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.77 Hyd Moment(95): 7.26 G content: 1 D/E content : 2 S/T content : 0 Score: -7.02
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 8.0% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LFLIIYLLTVLGNQLIIILIFL at 30 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliabil ity: 94.1
COIL: Lupas s algorithm to detect coiled-coil regions total c residues
Final Results (k = 9/23) :
44.4 %: endoplasmic reticulum 22.2 %: vacuolar 11.1 %: Golgi 11.1 %: vesicles of secretory system 11.1 %: mitochondrial
>> prediction for CG55604- D4 is end (k=9)
A search ofthe NOV43a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 43D.
Figure imgf000676_0001
In a BLAST search of public sequence databases, the NOV43a protein was found to have homology to the proteins shown in the BLASTP data in Table 43E.
Figure imgf000677_0001
PFam analysis indicates that the NOV43a protein contains the domains shown in the Table 43F.
Figure imgf000677_0002
Example 44.
The NOV44 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 44A. Table 44A. NOV44 Sequence Analysis
NOV44a, CG55752-07 SEQ ID NO: 659 199 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 19691
ATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTG GCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGA TGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGC ATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTAC AGGTACACAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATG AGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTG GACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAG GATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGCTTGTGGTCATCAGTGATCCCCACATCAAGATTG ATCCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGGGAA GACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAGAGA GTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGAATG ACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCATGGC AATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGGACT GATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCACAAA AGTATGGTGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCA ATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAA TCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATG CCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAA GCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTC CCAACCTGTCATGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAGATG AATACATGCTGGGTAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACAGTTGATGTG TTTCTTCCAGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGGAGGGTGTAC TGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGATACCAATAA AGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTTGCTCTAAGC ACTAAGGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCACCAGAA GCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATTCCAGTTTTGCTGACCAGA GGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAGCCATCT TCTGTGACTACCCACTCATCTGGTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAAAAC ATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATATGAC AAAGAACTGCCCCTGGTGATGTGAGC
NOV44a, CG55752-07 SEQ ID NO: 660 656 aa MW at 74971.6kD Protein Sequence
MGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVH MSESG IIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWL DIEHTEGKRYFTWDKNRFPNPKRMQELLRSKKRKLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGE DFEGVCWPGLSSYLDFTNPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHG N EHRELHNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGGAV TGDNTAEWSNLKISIP MLLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREP LFGEEHTRLIRE AIRERYGLLPYWYSLFYHAHVASQPVMRPLWVEFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDV FLPGSNEVWYDYKTFAH EGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRVALS TKGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSVLINSSFADQRGHYPSKCWEKILVLGFRKEPS SVTTHSSGDGKDQPVAFTYCAKTSILSLEKLSLNIATDWEVRII
NOV44b, CG55752-06 SEQ ID NO: 661 2001 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1972
ATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTG GCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGA TGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGC ATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTAC AGGTATTCAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATG AGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTG GACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAG GATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGGTACTTGTGGTCATCAGTGATCCCCACATCAAGA TTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGG GAAGACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAG AGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGA ATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCAT GGCAATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGG ACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCAC AAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCA ATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAA TCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATG CCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAA GCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTC CCAACCTGTCATGAGGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAG ATGAATACATGCTGGGTTTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACA GTTGATGTGTTTCTTCCAGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGG AGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGA TACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTT GCTCTAAGCACTGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCA CCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATTCCAGTTTTGCTG ACCAGAGGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAG CCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAA AACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATAT GACAAAGAACTGCCCCTGGTGATGTGAGC
NOV44b, CG55752-06 SEQ ID NO: 662 657 aa MW at 75166.9kD Protein Sequence
MGIYGSVPYLLAHKLGRTIGIF LNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVHWMSESG IIDVFLLTGPTPSDVFKQYSHLTGIQAMPPLFSLGYHQCR NYEDEQDVKAVDAGFDEHDIPYDAMWL DIEHTEGKRYFT DKNRFPNPKRMQELLRSKKRKVLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEG EDFEGVCWPGLSSYLDFTNPKVREWYSSLFAFPVYQGSTDILFL NDMNEPSVFRGPEQTMQKNAIHH GN EHRELHNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAV TGDNTAE SNLKISIP MLLTLSITGISFCGADIGGFIGNPETELLVR YQAGAYQPFFRGHATMNTKRREP LFGEEHTRLIRE AIRERYGLLPY YSLFYHAHVASQPVMRRPL VEFPDELKTFDMEDEYMLGLGSALLVHPVTEPKATT VDVFLPGSNEV YDYKTFAHWEGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRV ALSTGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSVLINSSFADQRGHYPSKCWEKILVLGFRKE PSSVTTHSSDGKDQPVAFTYCAKTSILSLEKLSLNIATD EVRII
NOV44c, CG55752-01 SEQ ID NO: 663 3025 bp DNA Sequence ORF Start: ATG at 2δ ORF Stop: TGA at 2929
ACAGGTGCCTGGGGGTCAGGCTTCCGCATGCGGGCTGCAGTTGCTGGCATTGCCTTCCGCAGGAGGCG
TCAGAAACAGTGGCTTTCCAAGAAGTCCACCTATCAGGCATTATTGGATTCAGTCACAACAGATGAAG ACAGCACCAGGTTCCAAATCATCAATGAAGCAAGTAAGGTGAGGCGTCAGAAACAGTGGCTTTCCAAG AAGTCCACCTATCAGGCATTATTGGATTCAGTCACAACAGATGAAGACAGCACCAGGTTCCAAATCAT CAATGAAGCAAGTAAGGTGCCTCTCCTGGCTGAAATTTATGGTATAGAAGGAAACATTTTCAGGCTTA AAATTAATGAAGAGACTCCTCTAAAACCCAGATTTGAAGTTCCGGATGTCCTCACAAGCAAGCCAAGC ACTGTAAGGATTTCATGCTCTGGGGACACAGGCAGTCTGATATTGGCAGATGGAAAAGGAGACCTGAA GTGCCATATCACAGCAAACCCATTCAAGGTAGACTTGGTGTCTGAAGAAGAGGTTGTGATTAGCATAA ATTCCCTGGGCCAATTATACTTTGAGCATGGCAGGGCCCCTAGGGTCTCTTTCTCGGATAAGGTTAAT CTCACGCTTGGTAGCATATGGGATAAGATCAAGAACCTTTTCTCTAGGCAAGGATCAAAAGACCCAGC TGAGGGCGATGGGGCCCAGCCTGAGGAAACACCCAGGGATGGCGACAAGCCAGAGGAGACTCAGGGGA AGGCAGAGAAAGATGAGCCAGGAGCCTGGGAGGAGACATTCAAAACTCACTCTGACAGCAAGCCGTAT GGCCCTTCTTCTATTGGTTTGGATTTCTCCTTGCATGGATTTGAGCATCTTTATGGGATCCCACAACA TGCAGAATCACACCAACTTAAAAATACTGGGGATGGAGATGCTTACCGTCTTTATAACCTGGATGTCT ATGGATACCAAATATATGATAAAATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTG GGCAGAACTATAGGTATTTTCTGGCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGC AGGGATAGTCATCTTTGGTCCTGTCTCTTTGATTTATCAAAGCCAGGGAGATACACCTCTAACAACTC ATGTGCACTGGATGTCAGAGAGTGGCATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGAT GTCTTCAAACAGTACTCACACCTTACAGGTACACAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCA CCAGTGCCGCTGGAACTATGAAGATGAGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATG ACATTCCTTATGATGCCATGTGGCTGGACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGAC AAAAACAGATTCCCAAACCCCAAGAGGATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGCTTGTGGT CATCAGTGATCCCCACATCAAGATTGAACCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCT TCTTTGTGAAGAATCAGGAAGGGGAAGACTTTGAAGGGGTGTGTTGGCCAGGTATGAAATCATACCTG GATTTCACCAATCCCAAGGTCAGAGAGTGGTATTCAAGTATGTTCAGTTCCAATTGTGATGGATCTAC GGACATCCTCTTCCTTTGGAATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGC AGAAGAATGCCATTCATCATGGCAATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATATG GCTACTGCAGAAGGACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTT CTTTGCTGGATCACAAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGA AAATTTCTATCCCAATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGC GGGTTCATTGGGAATCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTT CTTCCGTGGCCATGCCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCC GACTCATCCGAGAAGCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCAT GCACACGTGGCTTCCCAACCTGTCATGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTT TGATATGGAAGATGAATACATGTTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCA CCACAGTTGATGTGTTTCTTCCAGGATCAAATGAGGTAGTCTGGTATGACTATAAGACATTTGCTCAT TGGGAAGGAGGGTGTACTGTAAAGATCCCAGTACTGTTACAGATTCCAGTGTTTCAGCGAGGTGGAAG TGTGATACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCC GGGTTGCTCTAAGCACTCTCCAGGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTC CAATACCTCCACCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGGTGGCCTC CTCTCCAGTATCTCAAGGACACTTACATACCCCACTCAGCATGACAAAAGCCCTGCTTTTCACTGTAT CGTCTCCAGCCAGCGTGAAAATGCGGCTTCACTACAGCCCAGAGAAAAGGGCCAGGTTTAGTCATTGT GCCAAAACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCAT CATATGACAAAGAACTGCCCCTGGTGATGTGAGCAGGGACCTGCCTGCCCCTTTCAACCTTTCCCCTC
ACCTTTTTTGAGATTTTTGCTGCAATCTGTTTG
NOV44c, CG55752-01 SEQ ID NO: 664 967 aa MW at l09δ01.3kD Protein Sequence
MRAAVAGIAFRRRRQKQWLSKKSTYQALLDSVTTDEDSTRFQIINEASKVRRQKQ LSKKSTYQALLD SVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPDVLTSKPSTVRISCSGD TGSLILADGKGDLKCHITANPFKVDLVSEEEWISINSLGQLYFEHGRAPRVSFSDKVNLTLGSI DK IKNLFSRQGSKDPAEGDGAQPEETPRDGDKPEETQGKAEKDEPGAWEETFKTHSDSKPYGPSSIGLDF SLHGFEHLYGIPQHAESHQLKNTGDGDAYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWL NASETLVEINTEPAGIVIFGPVSLIYQSQGDTPLTTHVHMSESGIIDVFLLTGPTPSDVFKQYSHLT GTQAMPPLFSLGYHQCR NYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKR MQELLRSKKRKLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGMKSYLDFTNPKVRE WYSSMFSSNCDGSTDILFL NDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHNIYGFYMATAEGLIKR SKGKERPFVLTRSFFAGSQKYGAVWTGDNTAE SNLKISIPMLLTLSITGISFCGADIGGFIGNPETE LLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEEHTRLIREAIRERYGLLPY YSLFYHAHVASQPVM RPLWVEFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDVFLPGSNEW YDYKTFAHWEGGCTVKI PVLLQIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRVALSTLQGSSVGELYLDDGHSFQYLHQKQFL HRKFSFCSSVLVASSPVSQGHLHTPLSMTKALLFTVSSPASVKMRLHYSPEKRARFSHCAKTSILSLE KLSLNIATD EVRII
NOV44d, CG55752-02 SEQ ID NO: 665 44δ3 bp DNA Sequence ORF Start: ATG at 204 ORF Stop: TGA at 2946
AACGCTAGTTTGGGCCTGAAAAATTCCAGGAGCAAGAGTCAAGATTTGTCACTCCATGAGAATCTGGA
GGGGACTCCCTTCCCAGAAACTTGACGATGAAGTACTGGTTGTAATTTTAGAAAGACACCCAATCGGC
TTTTTTAAAAGATCGCCCAGGGCCCTTGTCCTGAGAGCTGGGAGCTGGTCGGAGTGACAGAGAAGCCA
TGGAAGCAGCAGTGAAAGAGGAAATAAGTGTTGAAGATGAAGCTGTAGATAAAAACATTTTCAGAGAC TGTAACAAGATCGCATTTTACAGGCGTCAGAAACAGTGGCTTTCCAAGAAGTCCACCTATCAGGCATT ATTGGATTCAGTCACAACAGATGAAGACAGCACCAGGTTCCAAATCATCAATGAAGCAAGTAAGGTTC CTCTCCTGGCTGAAATTTATGGTATAGAAGGAAACATTTTCAGGCTTAAAATTAACGAAGAGACTCCT CTAAAACCCAGATTTGAAGTTCCGGATGTCCTCACAAGCAAGCCAAGCACTGTAAGGCTGATTTCATG CTCTGGGGACACAGGCAGTCTGATATTGGCAGATGGAAAAGGAGACCTGAAGTGCCATATCACAGCAA ACCCATTCAAGGTAGACTTGGTGTCTGAAGAAGAGGTTGTGATTAGCATAAATTCCCTGGGCCAATTA TACTTTGAGCATCTACAGATTCTTCACAAACAAAGAGCTGCTAAAGAAAATGAGGAGGAGACATCAGT GGACACCTCTCAGGAAAATCAAGAAGATCTGGGCCTGTGGGAAGAGAAATTTGGAAAATTTGTGGATA TCAAAGCTAATGGCCCTTCTTCTATTGGTTTGGATTTCTCCTTGCATGGATTTGAGCATCTTTATGGG ATCCCACAACATGCAGAATCACACCAACTTAAAAATACTGGTGATGGAGATGCTTACCGTCTTTATAA CCTGGATGTCTATGGATACCAAATATATGATAAAATGGGCATTTATGGTTCAGTACCTTATCTCCTGG CCCACAAACTGGGCAGAACTATAGGTATTTTCTGGCTGAATGCCTCGGAAACACTGGTGGAGATCAAT ACAGAGCCTGCAGTAGAGTACACACTGACCCAGATGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATC TCGCACTCATGTGCACTGGATGTCAGAGAGTGGCATCATTGATGTTTTTCTGCTGACAGGACCTACAC CTTCTGATGTCTTCAAACAGTACTCACACCTTACAGGCACACAAGCCATGCCCCCTCTTTTCTCTTTG GGATACCACCAGTGCCGCTGGAACTATGAAGATGAGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGA TGAGCATGACATTCCTTATGATGCCATGTGGCTGGACATAGAGCACACTGAGGGCAAGAGGTACTTCA CCTGGGACAAAAACAGATTCCCAAACCCCAAGAGGATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAG CTTGTGGTCATCAGTGATCCCCACATCAAGATTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGA TCAGGGCTTCTTTGTGAAGAATCAGGAAGGGGAAGACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCT CTTACCTGGATTTCACCAATCCCAAGGTCAGAGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTAT CAGGGATCTACGGACATCCTCTTCCTTTGGAATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGA GCAAACCATGCAGAAGAATGCCATTCATCATGGCAATTGGGAGCACAGAGAGCTCCACAACATCTACG GTTTTTATCATCAAATGGCTACTGCAGAAGGACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTT GTTCTTACACGTTCTTTCTTTGCTGGATCACAAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGC AGAATGGAGCAACTTGAAAATTTCTATCCCAATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTT GCGGAGCTGACATAGGCGGGTTCATTGGGAATCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCT GGAGCCTACCAGCCCTTCTTCCGTGGCCATGCCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTT TGGGGAGGAACACACCCGACTCATCCGAGAAGCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGT ATTCTCTGTTCTACCATGCACACGTGGCTTCCCAACCTGTCATGAGGCCTCTGTGGGTAGAGTTCCCT GATGAACTAAAGACTTTTGATATGGAAGATGAATACATGCTGGGGAGTGCATTATTGGTTCATCCAGT CACAGAACCAAAAGCCACCACAGTTGATGTGTTTCTTCCAGGATCAAATGAGGTCTGGTATGACTATA AGACATTTGCTCATTGGGAAGGAGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTG TTTCAGCGAGGTGGAAGTGTGATACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGA ATCCTCCTATGGACTCCGGGTTGCTCTAAGCACTAAGGGTTCTTCAGTGGGTGAGTTATATCTTGATG ATGGCCATTCATTCCAATACCTCCACCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGT GTTCTGATCAATAGTTTTGCTGACCAGAGGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTT GGTCTTAGGCTTCAGGAAGGAGCCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTG TGGCTTTTACGTATTGTGCCAAAACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACT GACTGGGAGGTCCGCATCATATGACAAAGAACTGCCCCTGGTGATGTGAGCAGGGACCTGCCTGCCCC
TTTCAACCTTTCCCCTCACCTTTTTTGAGATTTTTGCTGCAATCTGTTTGCCTTCCCTGAATCAAAAT
AATCTTTCATTCGTCACCATTATACTAATGAACAATAGATTTCATGTTTCAAAATTTCAGATTTTACA
TGTTAAGATGTACTAACAATATTCCTTGTATCAAACATCTCCTTTTCTCCCTGATACATAGCCCTGAG
ACATTTATAGCGTTCAGGAGTCTTCTATTGCTTCCATTCCTTCAGCAGGGCTGCGTGGGTCTGTTTTA!
ACGTGGGCCAAGCCTACCTGGGCAGCCCATTTGCCAGGGCTTGCCTCAGGCCATGCAGCATTGGCGCTj
CTGGCTGCAGCAGCTGAGTTGCTCAAGGCCAGTGTCCAAGTGGACAGCAGCCTCTGGTACTCCCCCCA
GTTATCTTCCACCCACATGGACTGGGCAGAGCAGCCCTCTTCTGTGTGCACTGCATACGCTGCAGCCG iTGGGAGTTATTCTCCCCTAGAGATCGACTTGGCAGCACGAAGGATTCTTTTCTCTTTCATGCTTCTCA
GGCTCAATAGTTTCTAATTAATCTTAAAATCCATGTCTTTTACATTGTTTTTTTAATTAAGTGCTGTT
TACTAACCAAATAATATTTATAACATGAGTAAGCTATAATTAATAACAATGAAATAAATACCCATGTA
CCCACCACTGGACTTCAGAAGTAGAACTCATGACTGGGACTAGGATGAGGCAAGGGAGACCCTGGCCT;
ITGGGCACAAAATGTAAGGGATGCCAAAAAAATACAGTAATCAAAGTAAGTAATATTTCAATCCAATAT jTTTTAAAAATCAGAATTAATGCAAAAAAAACCATGATGAACAAAATATTAAAATTTAAAATAAAGACA1
GGATTAGTATTACTGAGTTTTCCTTTTGTCCCAGGCTTTAATATGGCTTGGCATGGGGCAGAACATTAI
CAACATACCAGTCGTGTCATGGTGCCCAAGGCTCCACAGACCTCAGTGGCTCCCTGCTGCCTGCCACA
;GCATCTGTTTTAGCAGCCTCGACTCCTCAGCACTCCTCAGCACACACCTCTTCTTATCAGGCTTCCTC
CACTTAGCAACTTGCTAACGGCCACCTCTGTGCCTTCTGATCCCTGGGCGCCAATATCCTCCTGCCCT
TACCATCCTTCCAGGCCCAACTTAAATCCCACTTTCCCATGAAGCCTAACTGCGTGAACACCCCTACC
CCCATACCCATTAGCAGTGATTTTGCCCTTCCCCGTAATGCTGTCCCACTTATAACTGTGCTCTACTT
AGCATTCTCAGGGATCATACCTTAATGTTTTCAGTATGTCTGCGTTCTCCTACTAGATTGTATGTCCC!
TCAAGAGCATGTTCTGTTTCTCTTCTGTCTGACAGAGCACTATTATACCTGACTTTCAGTAACTGTTA,
GCTGTGATTAGTTAGCTGGTGGATTTAATTGATTAAAAAATTACGATTGAATGTAAAAAAAAA
NOV44d, CG55752-02 SEQ ID NO: 666 914 aa MW at l04319.2kD Protein Sequence
MEAAVKEEISVEDEAVDKNIFRDCNKIAFYRRQKQWLSKKSTYQALLDSVTTDEDSTRFQIINEASKV PLLAEIYGIEGNIFRLKINEETPLKPRFEVPDVLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITA NPFKVDLVSEEEWISINSLGQLYFEHLQILHKQRAAKENEEETSVDTSQENQEDLGLWEEKFGKFVD IKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDGDAYRLYNLDVYGYQIYDKMGIYGSVPYLL AHKLGRTIGIF LNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVH MSESGIIDVFLLTGPT PSDVFKQYSHLTGTQAMPPLFSLGYHQCR NYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYF TWDKNRFPNPKRMQELLRSKKRKLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLS SYLDFTNPKVREWYSSLFAFPVYQGSTDILFLNDMNEPSVFRGPEQTMQKNAIHHGN EHRELHNIY GFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAEWSNLKISIPMLLTLSITGISF CGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREP LFGEEHTRLIREAIRERYGLLPY YSLFYHAHVASQPVMRPL VEFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDVFLPGSNEVWYDY KTFAH EGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTGWMTESSYGLRVALSTKGSSVGELYLD DGHSFQYLHQKQFLHRKFSFCSSVLINSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSSDGKDQP VAFTYCAKTSILSLEKLSLNIATDWEVRII
NOV44e, CG55752-03 SEQ ID NO: 667 3015 bp DNA Sequence ORF Start: ATG at 204 ORF Stop: TGA at 2946
AACGCTAGTTTGGGCCTGAAAAATTCCAGGAGCAAGAGTCAAGATTTGTCACTCCATGAGAATCTGGA
GGGGACTCCCTTCCCAGAAACTTGACGATGAAGTACTGGTTGTAATTTTAGAAAGACACCCAATCGGC
TTTTTTAAAAGATCGCCCAGGGCCCTTGTCCTGAGAGCTGGGAGCTGGTCGGAGTGACAGAGAAGCCA
TGGAAGCAGCAGTGAAAGAGGAAATAAGTGTTGAAGATGAAGCTGTAGATAAAAACATTTTCAGAGAC TGTAACAAGATCGCATTTTACAGGCGTCAGAAACAGTGGCTTTCCAAGAAGTCCACCTATCAGGCATT ATTGGATTCAGTCACAACAGATGAAGACAGCACCAGGTTCCAAATCATCAATGAAGCAAGTAAGGTTC CTCTCCTGGCTGAAATTTATGGTATAGAAGGAAACATTTTCAGGCTTAAAATTAACGAAGAGACTCCT CTAAAACCCAGATTTGAAGTTCCGGATGTCCTCACAAGCAAGCCAAGCACTGTAAGGCTGATTTCATG CTCTGGGGACACAGGCAGTCTGATATTGGCAGATGGAAAAGGAGACCTGAAGTGCCATATCACAGCAA ACCCATTCAAGGTAGACTTGGTGTCTGAAGAAGAGGTTGTGATTAGCATAAATTCCCTGGGCCAATTA TACTTTGAGCATCTACAGATTCTTCACAAACAAAGAGCTGCTAAAGAAAATGAGGAGGAGACATCAGT GGACACCTCTCAGGAAAATCAAGAAGATCTGGGCCTGTGGGAAGAGAAATTTGGAAAATTTGTGGATA TCAAAGCTAATGGCCCTTCTTCTATTGGTTTGGATTTCTCCTTGCATGGATTTGAGCATCTTTATGGG ATCCCACAACATGCAGAATCACACCAACTTAAAAATACTGGTGATGGAGATGCTTACCGTCTTTATAA CCTGGATGTCTATGGATACCAAATATATGATAAAATGGGCATTTATGGTTCAGTACCTTATCTCCTGG CCCACAAACTGGGCAGAACTATAGGTATTTTCTGGCTGAATGCCTCGGAAACACTGGTGGAGATCAAT ACAGAGCCTGCAGTAGAGTACACACTGACCCAGATGGGCCCAGTTGCTGCTAAACAAAAGGTCGGATC TCGCACTCATGTGCACTGGATGTCAGAGAGTGGCATCATTGATGTTTTTCTGCTGACAGGACCTACAC CTTCTGATGTCTTCAAACAGTACTCACACCTTACAGGCACACAAGCCATGCCCCCTCTTTTCTCTTTG GGATACCACCAGTGCCGCTGGAACTATGAAGATGAGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGA TGAGCATGACATTCCTTATGATGCCATGTGGCTGGACATAGAGCACACTGAGGGCAAGAGGTACTTCA CCTGGGACAAAAACAGATTCCCAAACCCCAAGAGGATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAG CTTGTGGTCATCAGTGATCCCCACATCAAGATTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGA TCAGGGCTTCTTTGTGAAGAATCAGGAAGGGGAAGACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCT CTTACCTGGATTTCACCAATCCCAAGGTCAGAGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTAT CAGGGATCTACGGACATCCTCTTCCTTTGGAATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGA GCAAACCATGCAGAAGAATGCCATTCATCATGGCAATTGGGAGCACAGAGAGCTCCACAACATCTACG GTTTTTATCATCAAATGGCTACTGCAGAAGGACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTT GTTCTTACACGTTCTTTCTTTGCTGGATCACAAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGC AGAATGGAGCAACTTGAAAATTTCTATCCCAATGTTACTCACTCTCAGCATTACTGGGGTCTCTTTTT GCGGAGCTGACATAGGCGGGTTCATTGGGAATCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCT GGAGCCTACCAGCCCTTCTTCCGTGGCCATGCCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTT TGGGGAGGAACACACCCGACTCATCCGAGAAGCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGT ATTCTCTGTTCTACCATGCACACGTGGCTTCCCAACCTGTCATGAGGCCTCTGTGGGTAGAGTTCCCT GATGAACTAAAGACTTTTGATATGGAAGATGAATACATGCTGGGGAGTGCATTATTGGTTCATCCAGT CACAGAACCAAAAGCCACCACAGTTGATGTGTTTCTTCCAGGATCAAATGAGGTCTGGTATGACTATA AGACATTTGCTCATTGGGAAGGAGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTG TTTCAGCGAGGTGGAAGTGTGATACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGA ATCCTCCTATGGACTCCGGGTTGCTCTAAGCACTAAGGGTTCTTCAGTGGGTGAGTTATATCTTGATG ATGGCCATTCATTCCAATACCTCCACCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGT GTTCTGATCAATAGTTTTGCTGACCAGAGGGGTCACTATCCCAGCAAGTGTGTGGTGGAGAAGATCTT GGTCTTAGGCTTCAGGAAGGAGCCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTG TGGCTTTTACGTATTGTGCCAAAACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACT GACTGGGAGGTCCGCATCATATGACAAAGAACTGCCCCTGGTGATGTGAGCAGGGACCTGCCTGCCCC TTTCAACCTTTCCCCTCACCTTT
67δ NOV44e, CG55752-03 SEQ ID NO: 66δ 914 aa MW at 104206.0kD Protein Sequence
MEAAVKEEISVEDEAVDKNIFRDCNKIAFYRRQKQ LSKKSTYQALLDSVTTDEDSTRFQIINEASKV PLLAEIYGIEGNIFRLKINEETPLKPRFEVPDVLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITA NPFKVDLVSEEEWISINSLGQLYFEHLQILHKQRAAKENEEETSVDTSQENQEDLGLWEEKFGKFVD IKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDGDAYRLYNLDVYGYQIYDKMGIYGSVPYLL AHKLGRTIGIFWLNASETLVEINTEPAVEYTLTQMGPVAAKQKVGSRTHVHWMSESGIIDVFLLTGPT PSDVFKQYSHLTGTQAMPPLFSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAM LDIEHTEGKRYF T DKNRFPNPKRMQELLRSKKRKLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLS SYLDFTNPKVRE YSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHNIY GFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAEWSNLKISIPMLLTLSITGVSF CGADIGGFIGNPETELLVR YQAGAYQPFFRGHATMNTKRREPWLFGEEHTRLIREAIRERYGLLPYW YSLFYHAHVASQPVMRPLWVEFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDVFLPGSNEVWYDY KTFAHWEGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRVALSTKGSSVGELYLD DGHSFQYLHQKQFLHRKFSFCSSVLINSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSSDGKDQP VAFTYCAKTSILSLEKLSLNIATDWEVRII
NOV44f, CG55752-04 SEQ ID NO: 669 3102 bp DNA Sequence ORF Start: ATG at 103 ORF Stop: TGA at 2839
TACTGGTTGTAATTTTAGAAAGACACCCAATCGGCTTTTTTAAAAGATCGCCCAGGGCCCTTGTCCTGl
AGAGCTGGGAGCTGGTCGGAGTGACAGAGAAGCCATGGAAGCAGCAGTGAAAGAGGAAATAAGTGTTG
AAGATGAAGCTGTAGATAAAAACATTTTCAGAGACTGTAACAAGATCGCATTTTACAGGCGTCAGAAA CAGTGGCTTTCCAAGAAGTCCACCTATCGGGCATTATTGGATTCAGTCACAACAGATGAAGACAGCAC CAGGTTCCAAATCATCAATGAAGCAAGTAAGGTTCCTCTCCTGGCTGAAATTTATGGTATAGAAGGAA ACATTTTCAGGCTTAAAATTAACGAAGAGACTCCTCTAAAACCCAGATTTGAAGTTCCGGATGTCCTC ACAAGCAAGCCAAGCACTGTAAGGCTGATTTCATGCTCTGGGGACACAGGCAGTCTGATATTGGCAGA TGGAAAAGGAGACCTGAAGTGCCATATCACAGCAAACCCATTCAAGGTAGACTTGGTGTCTGAAGAAG AGGTTGTGATTAGCATAAATTCCCTGGGCCAATTATACTTTGAGCATCTACAGATTCTTCACAAACAA AGAGCTGCTAAAGAAAATGAGGAGGAGACATCAGTGGACACCTCTCAGGAAAATCAAGAAGATCTGGG CCTGTGGGAAGAGAAATTTGGAAAATTTGTGGATATCAAAGCTAATGGCCCTTCTTCTATTGGTTTGG ATTTCTCCTTGCATGGATTTGAGCATCTTTATGGGATCCCACAACATGCAGAATCACACCAACTTAAA AATACTGGAGATGCTTACCGTCTTTATAACCTGGATGTCTATGGATACCAAATATATGATAAAATGGG CATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTGGCTGA ATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGATGGGC CCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGCATCAT TGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTACAGGTA CGCAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATGAGCAG GATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTGGACAT AGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAGGATGC AAGAGCTGCTCAGGAGCAAAAAGCGTAAGCTTGTGGTCATCAGTGATCCCCACATCAAGATTGAACCT GACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGGGAAGACTT TGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAGAGAGTGGT ATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGAATGACATG AATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCATGGCAATTG GGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGGACTGATAA AACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCACAAAAGTAT GGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCAATGTTACT CACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAATCCAGAGA CAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATGCCACCATG AACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAAGCCATCAG AGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTCCCAACCTG TCATGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAGATGAATACATG TTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACAGTTGATGTGTTTCTTCC AGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGGAGGGTGTACTGTAAAGA TCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGATACCAATAAAGACAACT GTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTTGCTCTAAGCACTCAGGG TTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCACCAGAAGCAATTTT TGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATAGTTTTGCTGACCAGAGGGGTCATTAT CCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAGCCATCTTCTGTGACTAC CCACTCATCTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAAAACATCCATCCTGAGCC TGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATATGACAAAGAACTGCCCCT
GGTGATGTGAGCAGGGACCTGCCTGCCCCTTTCAACCTTTCCCCTCACCTTTTTTGAGATTTTTGCTG
CAATCTGTTTGTCTTCCCTGAATCAAAATAATCTTTCATTCGTCACCATTATACTAATGAACAATAGA
TTTCATGTTTCAAAATTTCAGATTTTACATGTTAAGATGTACTAACAATATTCCTTGTATCAAACATC
TCCTTTTCTCCCTGATACATAGCCCTGAGACATTATAGCGTC
NOV44f, CG55752-04 SEQ ID NO: 670 912 aa MW at l041 δ9.1kD Protein Sequence
MEAAVKEEISVEDEAVDKNIFRDCNKIAFYRRQKQ LSKKSTYRALLDSVTTDEDSTRFQIINEASKV PLLAEIYGIEGNIFRLKINEETPLKPRFEVPDVLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITA NPFKVDLVSEEEWISINSLGQLYFEHLQILHKQRAAKENEEETSVDTSQENQEDLGL EEKFGKFVD IKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDAYRLYNLDVYGYQIYDKMGIYGSVPYLLAH KLGRTIGIFWLNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVH MSESGIIDVFLLTGPTPS DVFKQYSHLTGTQAMPPLFSLGYHQCR NYEDEQDVKAVDAGFDEHDIPYDAM LDIEHTEGKRYFTW DKNRFPNPKRMQELLRSKKRKLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSY LDFTNPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHNIYGF YHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAEWSNLKISIPMLLTLSITGISFCG ADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEEHTRLIREAIRERYGLLPYWYS LFYHAHVASQPVMRPLWVEFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDVFLPGSNEV YDYKT FAHWEGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRVALSTQGSSVGELYLDDG HSFQYLHQKQFLHRKFSFCSSVLINSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSSDGKDQPVA FTYCAKTSILSLEKLSLNIATDWEVRII
NOV44g, CG55752-05 SEQ ID NO: 671 2951 bp DNA Sequence ORF Start: ATG at 210 ORF Stop: TGA at 268δ
TACTGGTTGTAATTTTAGAAAGACACCCAATCGGCTTTTTTAAAAGATCGCCCAGGGCCCTTGTCCTG
AGAGCTGGGAGCTGGTCGGAGTGACAGAGAAGCCATGGAAGCAGCAGTGAAAGAGGAAATAAGTGTTG
AAGATGAAGCTGTAGATAAAAACATTTTCAGAGACTGTAACAAGATCGCATTTTACAGGAAGAAAAGCi
GTATTATGTTAATTCTGAACAGGCGTCAGAAACAGTGGCTTTCCAAGAAGTCCACCTATCGGGCATTAi
TTGGATTCAGTCACAACAGATGAAGACAGCACCAGGTTCCAAATCATCAATGAAGCAAGTAAGGTTCC TCTCCTGGCTGAAATTTATGGTATAGAAGGAAACATTTTCAGGCTTAAAATTAACGAAGAGACTCCTC TAAAACCCAGATTTGAAGTTCCGGATGTCCTCACAAGCAAGCCAAGCACTGTAAGAGCTGCTAAAGAA AATGAGGAGGAGACATCAGTGGACACCTCTCAGGAAAATCAAGAAGATCTGGGCCTGTGGGAAGAGAA ATTTGGAAAATTTGTGGATATCACAGCTAATGGCCCTTCTTCTATTGGTTTGGATTTCTCCTTGCATG GATTTGAGCATCTTTATGGGATCCCACAACATGCAGAATCACACCAACTTAAAAATACTGGAGATGCT TACCGTCTTTATAACCTGGATGTCTATGGATACCAAATATATGATAAAATGGGCATTTATGGTTCAGT ACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTGGCTGAATGCCTCGGAAACAC TGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGATGGGCCCAGTTGCTGCTAAA CAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGCATCATTGATGTTTTTCTGCT GACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTACAGGTACGCAAGCCATGCCCC CTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATGAGCAGGATGTAAAAGCAGTG GATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTGGACATAGAGCACACTGAGGG CAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAGGATGCAAGAGCTGCTCAGGA GCAAAAAGCGTAAGCTTGTGGTCATCAGTGATCCCCACATCAAGATTGAACCTGACTACTCAGTATAT GTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGGGAAGACTTTGAAGGGGTGTGTTG GCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAGAGAGTGGTATTCAAGTCTTTTTG CTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGAATGACATGAATGAGCCTTCTGTC TTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCATGGCAATTGGGAGCACAGAGAGCT CCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGGACTGATAAAACGATCTAAAGGGA AGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCACAAAAGTATGGTGCCGTGTGGACA GGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCAATGTTACTCACTCTCAGCATTAC TGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAATCCAGAGACAGAGCTGCTAGTGC GTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATGCCACCATGAACACCAAGCGACGA GAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAAGCCATCAGAGAGCGCTATGGCCT CCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTCCCAACCTGTCATGAGGCCTCTGT GGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAGATGAATACATGTTAGGGAGTGCATTA TTGGTTCATCCAGTCACAGAACCAAAAGCCACCACAGTTGATGTGTTTCTTCCAGGATCAAATGAGGT
6δ0 ATGGTATGACTATAAGACATTTGCTCATTGGGAAGGAGGGTGTACTGTAAAGATCCCAGTAGCCTTGG ACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGATACCAATAAAGACAACTGTAGGAAAATCCACA GGCTGGATGACTGAATCCTCCTATGGACTCCGGGTTGCTCTAAGCACTCAGGGTTCTTCAGTGGGTGA GTTATATCTTGATGATGGCCATTCATTCCAATACCTCCACCAGAAGCAATTTTTGCACAGGAAGTTTT CATTCTGTTCCAGTGTTCTGATCAATAGTTTTGCTGACCAGAGGGGTCATTATCCCAGCAAGTGTGTG GTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAGCCATCTTCTGTGACTACCCACTCATCTGATGG TAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAAAACATCCATCCTGAGCCTGGAGAAGCTCTCAC TCAACATTGCCACTGACTGGGAGGTCCGCATCATATGACAAAGAACTGCCCCTGGTGATGTGAGCAGG
GACCTGCCTGCCCCTTTCAACCTTTCCCCTCACCTTTTTTGAGATTTTTGCTGCAATCTGTTTGTCTT
CCCTGAATCAAAATAATCTTTCATTCGTCACCATTATACTAATGAACAATAGATTTCATGTTTCAAAA
TTTCAGATTTTACATGTTAAGATGTACTAACAATATTCCTTGTATCAAACATCTCCTTTTCTCCCTGA
TACATAGCCCTGAGACATTATAGCGTC
NOV44g, CG55752-05 SEQ ID NO: 672 δ26 aa MW at 94610.4kD Protein Sequence
MLILNRRQKQWLSKKSTYRALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLK PRFEVPDVLTSKPSTVRAAKENEEETSVDTSQENQEDLGLWEEKFGKFVDITANGPSSIGLDFSLHGF EHLYGIPQHAESHQLKNTGDAYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLV EINTEPAVEYTLTQMGPVAAKQKVRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPL FSLGYHQCR NYEDEQDVKAVDAGFDEHDIPYDAM LDIEHTEGKRYFTWDKNRFPNPKRMQELLRSK KRKLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFTNPKVRE YSSLFAF PVYQGSTDILFL NDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHNIYGFYHQMATAEGLIKRSKGKE RPFVLTRSFFAGSQKYGAV TGDNTAEWSNLKISIPMLLTLSITGISFCGADIGGFIGNPETELLVR YQAGAYQPFFRGHATMNTKRREPWLFGEEHTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMRPLWV EFPDELKTFDMEDEYMLGSALLVHPVTEPKATTVDVFLPGSNEVWYDYKTFAHWEGGCTVKIPVALDT IPVFQRGGSVIPIKTTVGKSTG MTESSYGLRVALSTQGSSVGELYLDDGHSFQYLHQKQFLHRKFSF CSSVLINSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSSDGKDQPVAFTYCAKTSILSLEKLSLN IATD EVRII
NOV44h, SNP 13379656 of SEQ ID NO: 673 2001 bp CG55752-06, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1972
SNP Pos: 617 SNP Change: A to G
ATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTG GCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGA TGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGC ATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTAC AGGTATTCAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATG AGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTG GACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAG GATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGGTACTTGTGGTCATCAGTGATCCCCACATCAAGA TTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGG GAAGGCTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAG AGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGA ATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCAT GGCAATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGG ACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCAC AAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCA ATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAA TCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATG CCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAA GCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTC CCAACCTGTCATGAGGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAG ATGAATACATGCTGGGTTTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACA GTTGATGTGTTTCTTCCAGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGG AGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGA TACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTT GCTCTAAGCACTGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCA CCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATTCCAGTTTTGCTG ACCAGAGGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAG CCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAA AACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATAT GACAAAGAACTGCCCCTGGTGATGTGAGC
NOV44h, SNPl 3379656 of SEQ ID NO: 674 657 aa MW at 7510δ.9kD CG55752-06, Protein Sequence SNP Pos: 206 SNP Change: Asp to Gly
MGIYGSVPYLLAHKLGRTIGIF LNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVH MSESG IIDVFLLTGPTPSDVFKQYSHLTGIQAMPPLFSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWL DIEHTEGKRYFTWDKNRFPNPKRMQELLRSKKRKVLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEG EGFEGVCWPGLSSYLDFTNPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHH GNWEHRELHNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAE SNLKISIP MLLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEEHTRLIRE AIRERYGLLPYWYSLFYHAHVASQPVMRRPLWVEFPDELKTFDMEDEYMLGLGSALLVHPVTEPKATT VDVFLPGSNEVWYDYKTFAH EGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTG MTESSYGLRV ALSTGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSVLINSSFADQRGHYPSKCWEKILVLGFRKE PSSVTTHSSDGKDQPVAFTYCAKTSILSLEKLSLNIATD EVRII
NOV44i, SNPl 3379655 of SEQ ID NO: 675 2001 bp CG55752-06, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1972
SNP Pos: 1763 SNP Change: T to C
ATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTG GCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGA TGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGC ATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTAC AGGTATTCAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATG AGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTG GACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAG GATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGGTACTTGTGGTCATCAGTGATCCCCACATCAAGA TTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGG GAAGACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAG AGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGA ATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCAT GGCAATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGG ACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCAC AAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCA ATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAA TCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATG CCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAA GCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTC CCAACCTGTCATGAGGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAG ATGAATACATGCTGGGTTTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACA GTTGATGTGTTTCTTCCAGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGG AGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGA TACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTT GCTCTAAGCACTGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCA CCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATTCCAGTTCTGCTG ACCAGAGGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAG CCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAA AACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATAT GACAAAGAACTGCCCCTGGTGATGTGAGC
NOV44i, SNP 13379655 of SEQ ID NO: 676 657 aa MW at 75106.δkD CG55752-06, Protein Sequence SNP Pos: 5δ8 SNP Change: Phe to Ser
MGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVHWMSESG IIDVFLLTGPTPSDVFKQYSHLTGIQAMPPLFSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWL DIEHTEGKRYFTWDKNRFPNPKRMQELLRSKKRKVLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEG EDFEGVCWPGLSSYLDFTNPKVREVJYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHH GNWEHRELHNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAV TGDNTAEWSNLKISIP MLLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREP LFGEEHTRLIRE AIRERYGLLPY YSLFYHAHVASQPVMRRPL VEFPDELKTFDMEDEYMLGLGSALLVHPVTEPKATT VDVFLPGSNEVWYDYKTFAH EGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTGWMTESSYGLRV ALSTGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSVLINSSSADQRGHYPSKCWEKILVLGFRKE PSSVTTHSSDGKDQPVAFTYCAKTSILSLEKLSLNIATDWEVRII
NOV44J, SNPl 3379654 of SEQ ID NO: 677 2001 bp CG55752-06, DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1972
SNP Pos: 1772 SNP Change: A to G
ATGGGCATTTATGGTTCAGTACCTTATCTCCTGGCCCACAAACTGGGCAGAACTATAGGTATTTTCTG GCTGAATGCCTCGGAAACACTGGTGGAGATCAATACAGAGCCTGCAGTAGAGTACACACTGACCCAGA TGGGCCCAGTTGCTGCTAAACAAAAGGTCAGATCTCGCACTCATGTGCACTGGATGTCAGAGAGTGGC ATCATTGATGTTTTTCTGCTGACAGGACCTACACCTTCTGATGTCTTCAAACAGTACTCACACCTTAC AGGTATTCAAGCCATGCCCCCTCTTTTCTCTTTGGGATACCACCAGTGCCGCTGGAACTATGAAGATG AGCAGGATGTAAAAGCAGTGGATGCAGGGTTTGATGAGCATGACATTCCTTATGATGCCATGTGGCTG GACATAGAGCACACTGAGGGCAAGAGGTACTTCACCTGGGACAAAAACAGATTCCCAAACCCCAAGAG GATGCAAGAGCTGCTCAGGAGCAAAAAGCGTAAGGTACTTGTGGTCATCAGTGATCCCCACATCAAGA TTGATCCTGACTACTCAGTATATGTGAAGGCCAAAGATCAGGGCTTCTTTGTGAAGAATCAGGAAGGG GAAGACTTTGAAGGGGTGTGTTGGCCAGGTCTCTCCTCTTACCTGGATTTCACCAATCCCAAGGTCAG AGAGTGGTATTCAAGTCTTTTTGCTTTCCCTGTTTATCAGGGATCTACGGACATCCTCTTCCTTTGGA ATGACATGAATGAGCCTTCTGTCTTTAGAGGGCCAGAGCAAACCATGCAGAAGAATGCCATTCATCAT GGCAATTGGGAGCACAGAGAGCTCCACAACATCTACGGTTTTTATCATCAAATGGCTACTGCAGAAGG ACTGATAAAACGATCTAAAGGGAAGGAGAGACCCTTTGTTCTTACACGTTCTTTCTTTGCTGGATCAC AAAAGTATGGTGCCGTGTGGACAGGCGACAACACAGCAGAATGGAGCAACTTGAAAATTTCTATCCCA ATGTTACTCACTCTCAGCATTACTGGGATCTCTTTTTGCGGAGCTGACATAGGCGGGTTCATTGGGAA TCCAGAGACAGAGCTGCTAGTGCGTTGGTACCAGGCTGGAGCCTACCAGCCCTTCTTCCGTGGCCATG CCACCATGAACACCAAGCGACGAGAGCCCTGGCTCTTTGGGGAGGAACACACCCGACTCATCCGAGAA GCCATCAGAGAGCGCTATGGCCTCCTGCCATATTGGTATTCTCTGTTCTACCATGCACACGTGGCTTC CCAACCTGTCATGAGGAGGCCTCTGTGGGTAGAGTTCCCTGATGAACTAAAGACTTTTGATATGGAAG ATGAATACATGCTGGGTTTAGGGAGTGCATTATTGGTTCATCCAGTCACAGAACCAAAAGCCACCACA GTTGATGTGTTTCTTCCAGGATCAAATGAGGTATGGTATGACTATAAGACATTTGCTCATTGGGAAGG AGGGTGTACTGTAAAGATCCCAGTAGCCTTGGACACTATTCCAGTGTTTCAGCGAGGTGGAAGTGTGA TACCAATAAAGACAACTGTAGGAAAATCCACAGGCTGGATGACTGAATCCTCCTATGGACTCCGGGTT GCTCTAAGCACTGGTTCTTCAGTGGGTGAGTTATATCTTGATGATGGCCATTCATTCCAATACCTCCA CCAGAAGCAATTTTTGCACAGGAAGTTTTCATTCTGTTCCAGTGTTCTGATCAATTCCAGTTTTGCTG ACCGGAGGGGTCATTATCCCAGCAAGTGTGTGGTGGAGAAGATCTTGGTCTTAGGCTTCAGGAAGGAG CCATCTTCTGTGACTACCCACTCATCTGATGGTAAAGATCAGCCTGTGGCTTTTACGTATTGTGCCAA AACATCCATCCTGAGCCTGGAGAAGCTCTCACTCAACATTGCCACTGACTGGGAGGTCCGCATCATAT GACAAAGAACTGCCCCTGGTGATGTGAGC
NOV44J, SNPl 3379654 of SEQ ID NO: 67δ 657 aa MW at 75194.9kD CG55752-06, Protein Sequence SNP Pos: 591 SNP Change: Gin to Arg
MGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTLTQMGPVAAKQKVRSRTHVH MSESG IIDVFLLTGPTPSDVFKQYSHLTGIQAMPPLFSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAM L DIEHTEGKRYFTWDKNRFPNPKRMQELLRSKKRKVLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEG EDFEGVCWPGLSSYLDFTNPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHH GNWEHRELHNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAEWSNLKISIP MLLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREP LFGEEHTRLIRE AIRERYGLLPY YSLFYHAHVASQPVMRRPL VEFPDELKTFDMEDEYMLGLGSALLVHPVTEPKATT VDVFLPGSNEVWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGSVIPIKTTVGKSTGWMTESSYGLRV ALSTGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSVLINSSFADRRGHYPSKCWEKILVLGFRKE PSSVTTHSSDGKDQPVAFTYCAKTSILSLEKLSLNIATDWEVRII
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 44B.
6δ3 Table 44B. Comparison of the NOV44 protein sequences.
N0V44a
N0V44b
N0V44c MRAAVAGIAFRRRRQKQWLSKKSTYQALLDSVTTDEDSTRFQIINEASKVRRQKQWLSKK
N0V44d MEAAVKEEIS VEDEAVDKN- -IFRDCNKIAFYRRQKQWLSKK
NOV44e MEAAVKEEIS VEDEAVDKN- -IFRDCNKIAFYRRQKQWLSKK
NOV44f MEAAVKEEIS VEDEAVDKN- -IFRDCNKIAFYRRQKQWLSKK
NOV 4g -MLILNRRQKQWLSKK
NOV44a NOV 4b NOV 4C STYQALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPD NOV44d STYQALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPD NOV44e STYQALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPD NOV 4f STYRALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPD NOV 4g STYRALLDSVTTDEDSTRFQIINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPD
NOV 4a NOV44b NOV 4c VLTSKPSTVR-ISCSGDTGSLILADGKGDLKCHITANPFKVDLVSEEEWISINSLGQLY NOV44d VLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITANPFKVDLVSEEEWISINSLGQLY NOV44e VLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITANPFKVDLVSEEEWISINSLGQLY NOV44f VLTSKPSTVRLISCSGDTGSLILADGKGDLKCHITANPFKVDLVSEEEWISINSLGQLY NOV44g VLTSKP
NOV44a NOV44b NOV44c FEHGRAPRVSFSDKVNLTLGSIWDKIKNLFSRQGSKDPAEGDGAQPEETPRDGDKPEETQ NOV44d FEH LQILHKQRAAKENEE ETSVDTS- -QENQ NOV44e FEH LQILHKQRAAKENEE ETSVDTS- -QENQ NOV44f FEH LQILHKQRAAKENEE ETSVDTS- -QENQ NOV44g S- -TVRAAKENEE ETSVDTS- -QENQ
NOV44a NOV44b NOV44C GKAEKDEPGAWEETFKTHSDSKPYGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDGD NOV4 d EDLGLWEEKFGKFVDIKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDGD NOV44e EDLGLWEEKFGKFVDIKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTGDGD NOV44f EDLGLWEEKFGKFVDIKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTG- -D NOV44g EDLGLWEEKFGKFVDITANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNTG- -D
NOV44a MGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL NOV44b MGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL NOV44C AYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAGIVIF NOV44d AYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL NOV44e AYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL NOV44f AYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL NOV44g AYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAVEYTL
NOV44a TQMGPVAAKQK-VRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL NOV44b TQMGPVAAKQK-VRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGIQAMPPLFSL NOV44C GPVSLIYQSQGDTPLTTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL NOV44d TQMGPVAAKQK-VRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL
6δ4 NOV44e TQMGPVAAKQK-VGSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL
NOV44f TQMGPVAAKQK-VRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL
NOV44g TQMGPVAAKQK-VRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPLFSL
NOV44a GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44b GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44c GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44d GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44e GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44f GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44g GYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKRMQE
NOV44a LLRSKKR-KLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44b LLRSKKRKVLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44C LLRSKKR-KLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGMKSYLDFT
NOV44d LLRSKKR-KLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44e LLRSKKR-KLWISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44f LLRSKKR-KLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44g LLRSKKR-KLWISDPHIKIEPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLDFT
NOV44a NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44b NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44C NPKVREWYSSMFSS-NCDGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44d NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44e NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44f NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44g NPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHRELHN
NOV44a IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGGAVWTGDNTAEWSNLKISIPM
NOV44b IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44C IYGFY- -MATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44d IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44e IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44 f IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44g IYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYG-AVWTGDNTAEWSNLKISIPM
NOV44a LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44b LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44C LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44d LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44e LLTLSITGVSFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44f LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44g LLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGEE
NOV44a HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG--
NOV44b HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMRRPLWVEFPDELKTFDMEDEYMLGLG
NOV44C HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG--
NOV44d HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG- -
NOV44e HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG- -
NOV44f HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG--
NOV44g HTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMR-PLWVEFPDELKTFDMEDEYMLG--
NOV44a SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS NOV44b SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS
6δ5 NOV44C SALLVHPVTEPKATTVDVFLPGSNEWWYDYKTFAHWEGGCTVKIPVLLQ-IPVFQRGGS NOV44d SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS NOV44e SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS NOV 4f SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS NOV44g SALLVHPVTEPKATTVDVFLPGSNE-VWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGS
NOV44a VIPIKTTVGKSTGWMTESSYGLRVALSTK-GSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV44b VIPIKTTVGKSTGWMTESSYGLRVALST--GSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV44C VIPIKTTVGKSTGWMTESSYGLRVALSTLQGSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV44d VIPIKTTVGKSTGWMTESSYGLRVALSTK-GSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV4 e VIPIKTTVGKSTGWMTESSYGLRVALSTK-GSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV44f VIPIKTTVGKSTGWMTESSYGLRVALSTQ-GSSVGELYLDDGHSFQYLHQKQFLHRKFSF NOV44g VIPIKTTVGKSTGWMTESSYGLRVALSTQ-GSSVGELYLDDGHSFQYLHQKQFLHRKFSF
NOV44a CSSVLINSSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSSGDGKDQPVAFTYCAKTS NOV44b CSSVLINSSFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSS-DGKDQPVAFTYCAKTS NOV44C CSSVLVA-SSPVSQGHLHTPLSMTKALLFTVSS-PASVKMRLH-YSPEKRARFSHCAKTS NOV44d CSSVLIN-SFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSS-DGKDQPVAFTYCAKTS NOV44e CSSVLIN-SFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSS-DGKDQPVAFTYCAKTS NOV44f CSSVLIN-SFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSS-DGKDQPVAFTYCAKTS NOV44g CSSVLIN-SFADQRGHYPSKCWEKILVLGFRKEPSSVTTHSS-DGKDQPVAFTYCAKTS
NOV44a ILSLEKLSLNIATDWEVRII NOV44b ILSLEKLSLNIATDWEVRII NOV44C ILSLEKLSLNIATDWEVRII NOV44d ILSLEKLSLNIATDWEVRII NOV44e ILSLEKLSLNIATDWEVRII NOV 4f ILSLEKLSLNIATDWEVRII NOV44g ILSLEKLSLNIATDWEVRII
NOV44a (SEQ ID NO 660) NOV44b (SEQ ID NO 662) NOV44c (SEQ ID NO 664) NOV44d (SEQ ID NO 666) NOV44e (SEQ ID NO 668) NOV44f (SEQ ID NO 670) NOV44g (SEQ ID NO 672)
Further analysis ofthe NOV44a protein yielded the following properties shown in Table
44C.
Figure imgf000690_0001
possible cleavage site: between 51 and 52
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -2.07 Transmembrane 337 - 353 PERIPHERAL Likelihood = 3.82 (at 496) ALOM score: -2.07 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 344 Charge difference: -2.0 C(-3.0) - N(-1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 2 (cytoplasmic tail 1 to 337)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 2.91 Hyd Moment (95): 0.96 G content: 4 D/E content: 1 S/T content: 3 Score: -6.13
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 27 GRT | IG
NUCDISC: discrimination of nuclear localization signals pat4: KKRK (5) at 167 pat7: none bipartite: none content of basic residues: 10.4% NLS Score: -0.16
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : MGIYGSV
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 10 LL at 74 LL at 163 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhard 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
30.4 %: cytoplasmic
30.4 %: mitochondrial
17.4 %: Golgi
8.7 %: endoplasmic reticulum
4.3 %: extracellular, including cell wall
4.3 %: nuclear
4.3 %: vesicles of secretory system
>> prediction for CG55752-07 is cyt (k=23)
A search ofthe NOV44a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 44D.
6δ8
Figure imgf000693_0001
In a BLAST search of public sequence databases, the NOV44a protein was found to have homology to the proteins shown in the BLASTP data in Table 44E.
6δ9
Figure imgf000694_0001
PFam analysis indicates that the NOV44a protein contains the domains shown in the Table 44F.
Figure imgf000694_0002
Example 45.
The NOV45 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 45A.
Table 45A. NOV45 Sequence Analysis
NOV45a, CG55778-03 SEQ ID NO: 679 752 bp DNA Sequence ORF Start: ATG at 23 ORF Stop: TAA at 653
GGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGCAGGCTT
CTCCAGGTAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCT TACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAG ACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTGGAAACAG CATGCAGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTGGCCCATG GGTTTCAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCC TCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTCCTGGACA CGTGGGAGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCA AGTCACATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCT CAGCCTAAACAAGAATCTCCGACTGGCCATGTTCCCCATGTAAATATGGCTCCTTCTTTTTAAAACAG
AGGGAAGAATATACAGATTGAATGATTGGTGTCTGAATAGAACTAAAAATCACAAAGACTATCCTTTC
CACA
NOV45a, CG5577δ-03 SEQ ID NO: 6δ0 210 aa MW at 24136JkD Protein Sequence
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRVQDLPL DESNMVIPSDTDFLDTWEILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSLNKNLR LAMFPM
NOV45b, CG5577δ-06 SEQ ID NO: 6δl 569 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 550
ATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGGCTTCTCCAGGAAAAGTGACCGAGGCAGT GAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCTTACTTTTACCACAATGAGAGGGAGG TTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAGACGGGAGGATCTGTTCATTGCCACT AAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCCTCGAGT GCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTCCTGGACACGTGGG AGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCAAGTCAC ATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCTCAGCCT AAACAGGAATCTCCGACTGGCCATGTTCCCCATAACTAAAAATCACAAAGACTATCCTTTCCACATAG AATACTGAGGACGCTTCCCCTTCCT
NOV45b, CG5577δ-06 SEQ ID NO: 682 Ϊ183 aa M at 21057.δkD Protein Sequence
MGDIPAVGLSSWKASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIAT KPPHPEWIMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEILIRFQIQRNVIVIPGSITPSH IKENIQVFDFELTQHDMDNILSLNRNLRLAMFPITKNHKDYPFHIEY
NOV45c, 2754δ09δ4 SEQ ID NO: 6δ3 655 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCAGATCTCCCACCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGCAGGCTTCTCCAG GGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCTTACTTT TACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAGACGGGA GGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTGGAAACAGCATGCA GAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTGGCCCATGGGTTTC AAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCCTCGAGT GCAGGACTTGCCTCTGGACGAGAGCAACGTGGTTATTCCCAGTGACACGGACTTCCTGGACACGTGGG AGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCAAGTCAC ATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCTCAGCCT AAACAGGAACCTCCGACTGGCCATGTTCCCCATGGTCGACGGC
NOV45c, 2754δ09δ4 SEQ ID NO: 6δ4 21 δ aa MW at 24946.5kD Protein Sequence
TRSPTMGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRRE DLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRV QDLPLDESNWIPSDTDFLDTWEILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSL NRNLRLAMFPMVDG
NOV45d, CG5577δ-01 SEQ ID NO: 6δ5 956 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TGA at 937
GGCGGGGCGGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAA
GCAGGCTTCTCCAGGGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCG ACTGTGCTTACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGC GCTGTAAGACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGT GGAAACAGCATGCAGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACT GGCCCATGGGTTTCAAGCCTCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGT GACACGGACTTCCTGGACACGTGGGAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTGAAGAACAT CGGGGTGTCAAACTTCAACCATGAACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAGGTTCAAGC CACTAACCAACCAGATTGAGTGCCACCCATATCTTACTCAGAAGAATCTGATCAGTTTTTGCCAATCC AGAGATGTGTCCGTGACTGCTTACCGTCCTCTTGGTGGCTCTAGTGAGGGGGTTGACCTGATAGACAA CCCTGTGATCAAGAGGATTGCAAAGGAGCACGGCAAGTCTCCTGCTCAGATTTTGATCCGATTTCAAA TCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCAAGTCACATTAAAGAGAATATCCAGGTG TTTGATTTTGAATTAACACAGCACGATATGGATAACATCCTCAGCCTAAACAGGAATCTCCGACTGGC CATGTTCCCCAGAACTAAAAATCACAAAGACTATCCTTTCCACATAGAATACTGAGGACGCTTCCCCT TCCT
NOV45d, CG5577δ-01 SEQ ID NO: 6δ6 302 aa MW at 34561.5kD Protein Sequence
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPRVQDLPLDESNMVIPSDTDFLDTWEA MEDLVITGLVKNIGVSNFNHEQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRP LGGSSEGVDLIDNPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDM DNILSLNRNLRLAMFPRTKNHKDYPFHIEY
NOV45e, CG5577δ-02 SEQ ID NO: 6δ7 875 bp DNA Sequence ORF Start: ATG at 23 JORF Stop: TAA at 776
GGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGCAGGCTT
CTCCAGGAAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCT TACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAG ACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTGGAAACAG CATGCAGAAAGGGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTGGCCCATG GGTTTCAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCC TCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTCCTGGACA CGTGGGAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTGAAGAACATCGGGGTGTCAAACTTCAAC CATGAACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAGGTTCAAGCCACTAACCAACCAGATTTT GATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCAAGTCACATTAAAG AGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCTCAGCCTAAACAGG AATCTCCGACTGGCCATGTTCCCCATGTAAATATGGCTCCTTCTTTTTAAAACAGAGGGAAGAATATA
CAGATTGAATGATTGGTGTCTGAATAGAACTAAAAATCACAAAGACTATCCTTTCCACA
NOV45e, CG5577δ-02 SEQ ID NO: 6δδ 251 aa MW at 2δ765.1kD Protein Sequence
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKLWCTCHKKSLVETACRKGLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRVQDLPL DESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNHEQLERLLNKPGLRFKPLTNQILIRFQIQR NVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSLNRNLRLAMFPM
NOV45f, CG5577δ-04 SEQ ID NO: 689 785 bp DNA Sequence ORF Start: ATG at 31 |ORF Stop: TGA at 766
GGCGGGGCGGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAA
GCAGGCTTCTCCAGGGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCG ACTGTGCTTACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGC GCTGTAAGACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGT GGAAACAGCATGCAGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACT GGCCCATGGGTTTCAAGCCTCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGT GACACGGACTTCCTGGACACGTGGGAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTGAAGAACAT CGGGGTGTCAAACTTCAACCATGAACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAGGTTCAAGC CACTAACCAACCAGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATC ACCCCAAGTCACATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAA CATCCTCAGCCTAAACAGGAATCTCCGACTGGCCATGTTCCCCAGAACTAAAAATCACAAAGACTATC CTTTCCACATAGAATACTGAGGACGCTTCCCCTTCCT NOV45f, CG55778-04 SEQ ID NO: 690 245 aa MW at 28311.4kD Protein Sequence
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPRVQDLPLDESNMVIPSDTDFLDTWEA MEDLVITGLVKNIGVSNFNHEQLERLLNKPGLRFKPLTNQILIRFQIQRNVIVIPGSITPSHIKENIQ VFDFELTQHDMDNILSLNRNLRLAMFPRTKNHKDYPFHIEY
NOV45g, CG5577δ-05 SEQ ID NO: 691 937 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAA at δ3δ
GGCGGGGCGGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAA
GCAGGCTTCTCCAGGGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCG ACTGTGCTTACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGC GCTGTAAGACGGGAGGATCTGTTCATTGCCACTAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAG TGAACTTTCCTTCTGCCTCTCACATCCTCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTA TTCCCAGTGACACGGACTTCCTGGACACGTGGGAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTG AAGAACATCGGGGTGTCAAACTTCAACCATGAACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAG GTTCAAGCCACTAACCAACCAGATTGAGTGCCACCCATATCTTACTCAGAAGAATCTGATCAGTTTTT GCCAATCCAGAGATGTGTCCGTGACTGCTTACCGTCCTCTTGGTGGCTCGTGTGAGGGGGTTGACCTG ATAGACAACCCTGTGATCAAGAGGATTGCAAAGGAGCACGGCAAGTCTCCTGCTCAGATTTTGATCCG ATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCAAGTCACATTAAAGAGAATA TCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCTCAGCCTAAACAGGAATCTC CGACTGGCCATGTTCCCCATGTAAATATGGCTCCTTCTTTTTAAAACAGAGGGAAGAATATACAGATT
GAATGATTGGTGTCTGAATAGAACTAAAAATCACAAAGACTATCCTTTCCACA
NOV45g, CG5577δ-05 SEQ ID NO: 692 269 aa MW at 30426.6kD Protein Sequence
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKPPHPEWIMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH EQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSCEGVDLIDNPVIKRIA KEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSLNRNLRLAMFPM
NOV45h, CG5577δ-07 SEQ ID NO: 693 1527 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TGA at 981
CGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGGCTTCTCCA!
GGGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCTTACTT TTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAGACGGG AGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTGGAAACAGCATGC AGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTGGCCCATGGGTTT CAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCCTCGAG TGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTCCTGGACACGTGG GAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTGAAGAACATCGGGGTGTCAAACTTCAACCATGA ACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAGGTTCAAGCCACTAACCAACCAGATTGAGTGCC ACCCATATCTTACTCAGAAGAATCTGATCAGTTTTTGCCAATCCAGAGATGTGTCCGTGACTGCTTAC CGTCCTCTTGGTGGCTCGTGTGAGGGGGTTGACCTGATAGACAACCCTGTGATCAAGAGGATTGCAAA GGAGCACGGCAAGTCTCCTGCTCAGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCC CCGGATCTATCACCCCAAGTCACATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCAC GATATGGATAACATCCTCAGCCTAAACAGGAATCTCCGACTGGCCATGTTCCCCATAACTAAAAATCA CAATGACTATCCTTTCCACATAGAATACTGAGGACGCTTCCCCTTCCTTGTTTCTGCTCAGCCCAGAT GCACAGACACTATTGGCAATGTTGACCCTCCTCTGTCATCACAGCGCCAGGGCAGCTGTGCCTGGGAC AGGAGCCACACAGTCAGAGGGGGATGTAAGAGCCACCTTCTCTGACAAATCTGGAGAATTGAGTGTGT TCTAAGTGAAGGCAATGGGGTTTCTCCAAGACAGCCTGTGTGGCCTCTACTCTGAACAAATACACTGA TGAGTCATCAGTGAAATTTGCCTTCACATTTTAAGAAAACTTTATCTTATGGAGTTATTTAAGCCATC TACAGAGCTGAGGAAACAGTGTAATGTGTCTCTGCCCCATTGCGCAGCTCCACCCATTGTGCCCCAGG CCAGCCCGCGTCACCTACACTTCCTTCTGTGCCCTGCCAGTGACCCCCAGGTTATTCTAAAGCAGAGT CCTTCCCTTCCCCCAGTGAGAAGGAAAATGGGATAAGTCTGGGACACTGTTTCAGTTCAATAAAGAGG CTTTTTTCTTCCTTAAAAAAAAAAAAAAAAA NOV45h, CG55778-07 SEQ ID NO: 694 320 aa MW at 36574.δkD Protein Sequence
MGDIPAVGLSSWKASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIAT KLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRVQDLPLD ESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNHEQLERLLNKPGLRFKPLTNQIECHPYLTQK NLISFCQSRDVSVTAYRPLGGSCEGVDLIDNPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPS HIKENIQVFDFELTQHDMDNILSLNRNLRLAMFPITKNHNDYPFHIEY
NOV45i, CG5577δ-0δ SEQ ID NO: 695 1680 bp DNA Sequence ORF Start: ATG at 101 ORF Stop: TAA at 1022
GGCACGAGGACGGCGGGTCGCCAGCGCCTCAGTAGCTCGCGCGGTGCCTGTCGGTAGTCGCGTGCGGG
GCGGCGGGGCGGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGG
AAGGCTTCTCCAGGGAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGA CTGTGCTTACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCG CTGTAAGACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTG GAAACAGCATGCAGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTG GCCCATGGGTTTCAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCT CACATCCTCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTC CTGGACACGTGGGAGGCCATGGAGGACCTGGTGATCACCGGGCTGGTGAAGAACATCGGGGTGTCAAA CTTCAACCATGAACAGCTTGAGAGGCTTTTGAATAAGCCTGGGTTGAGGTTCAAGCCACTAACCAACC AGATTGAGTGCCACCCATATCTTACTCAGAAGAATCTGATCAGTTTTTGCCAATCCAGAGATGTGTCC GTGACTGCTTACCGTCCTCTTGGTGGCTCGTGTGAGGGGGTTGACCTGATAGACAACCCTGTGATCAA GAGGATTGCAAAGGAGCACGGCAAGTCTCCTGCTCAGATTTTGATCCGATTTCAAATCCAGAGGAATG TGATAGTGATCCCCGGATCTATCACCCCAAGTCACATTAAAGAGAATATCCAGGTGTTTGATTTTGAA TTAACACAGCACGATATGGATAACATCCTCAGCCTAAACAGGAATCTCCGACTGGCCATGTTCCCCAT GTAAATATGGCTCCTTCTTTTTAAAACAGAGGGAAGAATATACAGATTGAATGATTGGTGTCTGAATA
GAACTAAAAATCACAAAGACTATCCTTTCCACATAGAATACTGAGGACGCTTCCCCTTCCTTGTTTCT
GCTCAGCCCAGATGCACAGACACTATTGGCAATGTTGACCCTCCTCTGTCATCACAGCGCCAGGGCAG
CTGTGCCTGGGACAGGAGCCACACAGTCAGAGGGGGATGTAAGAGCCACCTTCTCTGACAAATCTGGA
GAATTGAGTGTGTTCTAAGTGAAGGCAATGGGGTTTCTCCAAGACAGCCTGTGTGGCCTCTACTCTGA lACAAATACACTGATGAGTCATCAGTGAAATTTGCCTTCACATTTTAAGAAAACTTTATCTTATGGAGT jTATTTAAGCCATCTACAGAGCTGAGGAAACAGTGTAATGTGTCTCTGCCCCATTGCGCAGCTCCACCC lATTGTGCCCCAGGCCAGCCCGCGTCACCTACACTTCCTTCTGTGCCCTGCCAGTGACCCCCAGGTTAT
ITCTAAAGCAGAGTCCTTCCCTTCCCCCAGTGAGAAGGAAAATGGGATAAGTCTGGGACACTGTTTCAG iTTCAATAAAGAGGCTTTTTTCTTCCTTAAAAAAAAAAAAAAAAAAAAA
NOV45i, CG55778-0δ SEQ ID NO: 696 307 aa MW at 34933. OkD Protein Sequence
MGDIPAVGLSSWKASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIAT KLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRVQDLPLD ESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNHEQLERLLNKPGLRFKPLTNQIECHPYLTQK NLISFCQSRDVSVTAYRPLGGSCEGVDLIDNPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPS HIKENIQVFDFELTQHDMDNILSLNRNLRLAMFPM
NOV45J, SNP13375δl3 of SEQ ID NO: 697 752 bp CG5577δ-03, DNA Sequence ORF Start: ATG at 23 ORF Stop: TAA at 653
SNP Pos: 624 SNP Change: A to G
GGCGGGGCGGCCGGCGGCGGCCATGGGAGATATCCCAGCCGTGGGCCTCAGCTCCTGGAAGCAGGCTT
CTCCAGGTAAAGTGACCGAGGCAGTGAAAGAGGCCATTGACGCAGGGTACCGGCACTTCGACTGTGCT TACTTTTACCACAATGAGAGGGAGGTTGGAGCAGGGATCCGTTGCAAGATCAAGGAAGGCGCTGTAAG ACGGGAGGATCTGTTCATTGCCACTAAGCTGTGGTGCACCTGCCATAAGAAGTCCTTGGTGGAAACAG CATGCAGAAAGAGTCTCAAGGCCTTGAAGCTGAACTATTTGGACCTCTACCTCATACACTGGCCCATG GGTTTCAAGCCTCCTCATCCAGAATGGATCATGAGCTGCAGTGAACTTTCCTTCTGCCTCTCACATCC TCGAGTGCAGGACTTGCCTCTGGACGAGAGCAACATGGTTATTCCCAGTGACACGGACTTCCTGGACA CGTGGGAGATTTTGATCCGATTTCAAATCCAGAGGAATGTGATAGTGATCCCCGGATCTATCACCCCA AGTCACATTAAAGAGAATATCCAGGTGTTTGATTTTGAATTAACACAGCACGATATGGATAACATCCT CAGCCTAAACAGGAATCTCCGACTGGCCATGTTCCCCATGTAAATATGGCTCCTTCTTTTTAAAACAG
AGGGAAGAATATACAGATTGAATGATTGGTGTCTGAATAGAACTAAAAATCACAAAGACTATCCTTTC
CACA
NOV45J, SNP13375δl3 of SEQ ID NO: 69δ 210 aa MW at 24164 JkD CG5577δ-03, Protein Sequence SNP Pos: 201 SNP Change: Lys to Arg
MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVRREDLFIA TKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSELSFCLSHPRVQDLPL DESNMVIPSDTDFLDTWEILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSLNRNLR LAMFPM
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 45B.
Table 45B. Comparison of the NOV45 protein sequences.
NOV45a MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45b MGDIPAVGLSSWKAS-PGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45C TRSPTMGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45d MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45e MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45f MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45g MGDIPAVGLSSWKQASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45h MGDIPAVGLSSWKAS-PGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45i MGDIPAVGLSSWKAS-PGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKI
NOV45a KEGAVRREDLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEW
NOV45b KEGAVRREDLFIAT KPPHPEW
NOV45C KEGAVRREDLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEW
NOV45d KEGAVRREDLFIATKLWCTCHKKSLVETACR KSLKALKLNY
NOV45e KEGAVRREDLFIATKLWCTCHKKSLVETACRKGLKALKLNYLDLYLIHWPMGFKPPHPEW
NOV45f KEGAVRREDLFIATKLWCTCHKKSLVETACR KSLKALKLNY
NOV45g KEGAVRREDLFIAT KPPHPEW
NOV45h KEGAVRREDLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEW
NOV45i KEGAVRREDLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEW
NOV45a IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWE
NOV45b IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWE
NOV45c IMSCSELSFCLSHPRVQDLPLDESNWIPSDTDFLDTWE
NOV45d LDLYLIHWPMGFKPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45e IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45f LDLYLIHWPMGFKPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45g IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45h IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45i IMSCSELSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNH
NOV45a
NOV45b IL-
NOV45c
NOV45d EQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSSEGVDLID
NOV45e EQLERLLNKPGLRFKPLTN
NOV45f EQLERLLNKPGLRFKPLT
NOV45g EQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSCEGVDLID
NOV45h EQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSCEGVDLID NOV45i EQLERLLNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSCEGVDLID
NOV45a ILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45b 1- -RFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45C ILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45d NPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45e QILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45f N QILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45g NPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45h NPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45i NPVIKRIAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNIL
NOV45a SLNKNLRLAMFPM NOV45b SLNRNLRLAMFPITKNHKDYPFHIEY NOV45C SLNRNLRLAMFPMVDG NOV45d SLNRNLRLAMFPRTKNHKDYPFHIEY NOV45e SLNRNLRLAMFPM NOV45f SLNRNLRLAMFPRTKNHKDYPFHIEY NOV45g SLNRNLRLAMFPM NOV45h SLNRNLRLAMFPITKNHNDYPFHIEY NOV45i SLNRNLRLAMFPM
NOV45a (SEQ ID NO 680) NOV45b (SEQ ID NO 682) NOV45C (SEQ ID NO 684) NOV45d (SEQ ID NO 686) NOV45e (SEQ ID NO 688) NOV45f (SEQ ID NO 690) NOV 5g (SEQ ID NO 692) NOV45h (SEQ ID NO 694) NOV45i (SEQ ID NO 696)
Further analysis ofthe NOV45a protein yielded the following properties shown in Table
45C.
Table 45C. Protein Sequence Properties NOV45a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 3; pos . chg 0; neg.chg 1
H-region: length 9; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.56 possible cleavage site: between 18 and 19
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed
PERIPHERAL Likelihood = 6.21 (at 155)
ALOM score: 6.21 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 5.33 Hyd Moment(95): 5.59 G content: 3 D/E content: 2 S/T content: 4 Score: -7.44
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 11.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
52.2 %: cytoplasmic
34.8 %: nuclear
13.0 %: mitochondrial
>> prediction for CG55778-03 is cyt (k=23)
A search ofthe NOV45a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 45D.
Figure imgf000702_0001
69δ In a BLAST search of public sequence databases, the NOV45a protein was found to have homology to the proteins shown in the BLASTP data in Table 45E.
Figure imgf000703_0001
PFam analysis indicates that the NOV45a protein contains the domains shown in the Table 45F.
Figure imgf000703_0002
Example 46.
The NOV46 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 46A. Table 46A. NOV46 Sequence Analysis
NOV46a, CG55794-03 SEQ ID NO: 699 1222 bp DNA Sequence ORF Start: ATG at 41 ORF Stop: TAA at 1163
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAG AGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCAC TCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAAT GATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGAT CGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCC TTCTCATATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCA GCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGC ACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCT CTTCTCTAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTTGGAGGAACG
NOV46a, CG55794-03 SEQ ID NO: 700 374 aa MW at 425δ0.0kD Protein Sequence
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46b, 210223559 SEQ ID NO: 701 1579 bp DNA Sequence ORF Start: at 67 ORF Stop: TAA at 1396
CCAATTGACAAGCTTTTGATTTTAACGACTTTTAACGACAACTTGAGAAGATCAAAAAACAACTAATT:
ATTCGAAACGATGAGATTTCCTTCAATTTTTACTGCTGTTTTATTCGCAGCATCCTCCGCATTAGCTG CTCCAGTCAACACTACAACAGAAGATGAAACGGCACAAATTCCGGCTGAAGCTGTCATCGGTTACTCA GATTTAGAAGGGGATTTCGATGTTGCTGTTTTGCCATTTTCCAACAGCACAAATAACGGGTTATTGTT TATAAATACTACTATTGCCAGCATTGCTGCTAAAGAAGAAGGGGTATCTCTCGAGAAAAGATATGATA GATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTAT TCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAA GGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGATCA GCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATT GCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTATACG CAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTT GGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACGGAT CTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATT CTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGG ATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACC AAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGC AAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAA GAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGTAT GGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGT CCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGC TGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGCGGCCGCCAGCTTTCTAGAACAAAAACTC ATCTCAGAAGAGGATCTGAATAGCGCCGTCGACCATCATCATCATCATCATTGAGTTTGTAGCCTTAG ACATGACTGTTCCTCAGTTCAAGTTGGGCACTTACGAGAAGACCGGTCTTGCTAGATTCTAATCAAGA GGATGTCAGAATGCC
NOV46b, 210223559 SEQ ID NO: 702 443 aa MW at 49δ42.7kD Protein Sequence
LFETMRFPSIFTAVLFAASSALAAPVNTTTEDETAQIPAEAVIGYSDLEGDFDVAVLPFSNSTNNGLL FINTTIASIAAKEEGVSLEKRYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46c, 210223626 SEQ ID NO: 703 1607 bp DNA Sequence ORF Start: at 74 ORF Stop: TAA at 1421
ACTGGTTCCAATTGACAAGCTTTTGATTTTAACGACTTTTAACGACAACTTGAGAAGATCAAAAAACA
ACTAATTATTCGAAACGATGAGATTTCCTTCAATTTTTACTGCTGTTTTATTCGCAGCATCCTCCGCA
TTAGCTGCTCCAGTCAACACTACAACAGAAGATGAAACGGCACAAATTCCGGCTGAAGCTGTCATCGG TTACTCAGATTTAGAAGGGGATTTCGATGTTGCTGTTTTGCCATTTTCCAACAGCACAAATAACGGGT TATTGTTTATAAATACTACTATTGCCAGCATTGCTGCTAAAGAAGAAGGGGTATCTCTCGAGAAAAGA TATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGA GACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGA AGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTG AAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGA ATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAA GTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATC TACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGG GACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATC AAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGC AAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGG CTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCAT TGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGG TCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGG AACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGC TGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCC ACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCCACCATCACCACCATCACTAAGCGGC
CGCCAGCTTTCTAGAACAAAAACTCATCTCAGAAGAGGATCTGAATAGCGCCGTCGACCATCATCATC
ATCATCATTGAGTTTGTAGCCTTAGACATGACTGTTCCTCAGTTCAAGTTGGGCACTTACGAGAAGAC
CGGTCTTGCTAGATTCTAATCAAGAGGATGTCAGAATGCCATT
NOV46c, 210223626 SEQ ID NO: 704 1449 aa MW at 50665.6kD Protein Sequence
LFETMRFPSIFTAVLFAASSALAAPVNTTTEDETAQIPAEAVIGYSDLEGDFDVAVLPFSNSTNNGLL FINTTIASIAAKEEGVSLEKRYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46d, 171095097 SEQ ID NO: 705 114 bp DNA Sequence ORF Start: at 2 iORF Stop: TAA at 1127
CACCATGAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATG ATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACG TATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTA CAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGA TCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGG ATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTAT ACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACA CTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACG GATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAAC ATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGA AGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTAC ACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAA AGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTT CAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACG TATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTC AGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTA TGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGCGGCCGCTCGAGTCTAGA
NOV46d, 171095097 SEQ ID NO: 706 375 aa MW at 42630.1kD Protein Sequence
TMKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46e, I δ3δ52229 SEQ ID NO: 707 114δ bp DNA Sequence ORF Start: at 3 ORF Stop: TAA at 1146
CCACCATGAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATAT GATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGAC GTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGT ACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAG ATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATG GATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTA TACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTAC ACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGAC GGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAA CATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAG AAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTA CACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGA AAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCT TCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAAC GTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGT CAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACT ATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCCACCATCACCACCATCACTAA
NOV46e, I δ3δ52229 SEQ ID NO: 70δ 3δl aa MW at 43452.9kD Protein Sequence
TMKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46f, I δ3δ52264 SEQ ID NO: 709 1151 bp DNA Sequence ORF Start: at 3 ORF Stop: TAA at 1149
CCACCATGGGCCACCATCACCACCATCACAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTG GTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGT GAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGA TGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACC CACCCCATGTATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTG TGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAA ACCATAAAGACAACTCAAGTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTT AACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAA TAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCT CTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTT GCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTT AATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGAC AGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATT TTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTT TGAGCTGAGGGACAGTGGAACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGG AGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCT GGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAA
NOV46f, Iδ3δ52264 SEQ ID NO: 710 382 aa MW at 43510.0kD Protein Sequence
TMGHHHHHHKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWM REISEKYKEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQN HKDNSSIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGAS RNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQ KAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEE TMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46g, Iδ3δ52410 SEQ ID NO: 711 1162 bp DNA Sequence ORF Start: at 2 [ORF Stop: TAA at 1148
CACCATGGGCCACCATCACCACCATCACAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGG TTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTG AGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGAT GAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCC ACCCCATGTATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGT GGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAA CCATAAAGACAACTCAAGTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTA ACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAAT AATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTC TAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTG CCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTA ATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACA GAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTT TATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTT GAGCTGAGGGACAGTGGAACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGA GACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTG GAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGCGGCC GCTTTC
NOV46g, 183δ52410 SEQ ID NO: 712 382 aa MW at 43510.0kD Protein Sequence
TMGHHHHHHKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWM REISEKYKEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQN HKDNSSIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGAS RNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQ KAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEE TMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46h, 183523337 SEQ ID NO: 713 1 162 bp DNA Sequence ORF Start: at 2 ORF Stop: TAA at 1148
CACCATGGGCCACCATCACCACCATCACAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGG TTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTG AGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGAT GAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCC ACCCCATGTATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGT GGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAA CCATAAAGACAACTCAAGTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTA ACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAAT AATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTC TAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTG CCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTA ATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACA GAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTT TATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTT GAGCTGAGGGACAGTGGAACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGA GACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTG GAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGCGGCC GCTTTC
NOV46h, lδ3523337 SEQ ID NO: 714 3δ2 aa MW at43510.0kD Protein Sequence
TMGHHHHHHKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWM REISEKYKEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQN HKDNSSIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGAS RNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQ KAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEE TMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46i, CG55794-01 SEQ ID NO: 715 1196 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAA at 113δ
TTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGGTTCCTGGAGG
GCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGA GCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATCAATGAGTGGATGAGAGAGATC AGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATATA TTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGGCTGTGGAATTCACG CCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGAC AACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGG TTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACAT GTTTTGGGACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGC CAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCAT AGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACAC CTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCA AATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTC ATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGG ACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAG GCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGAC ATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGTGCATCCTGCCCAGG CCTGCTCAACCCCAGTGGCATGAGTGTGGCTGGAGGAACG
NOV46i, CG55794-01 SEQ ID NO: 716 374 aa MW at 42472.9kD Protein Sequence
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEINEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMGCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46J, CG55794-02 SEQ ID NO: 717 lOOδ bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGA GACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGA AGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTG AAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGA ATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAA GTATACGCAAGCTCCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATC TACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGG GACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATC AAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGC AAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGG CTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCAT TGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGG TCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGG AACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGC TGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGG
NOV46J, CG55794-02 SEQ ID NO: 718 336 aa MW at 3δ597.1kD Protein Sequence
YDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYL KISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETKAVASFIES KKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGTNYRVGSSADILYASSG SSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSVLDDVYAKHWHSDSAGR
NOV46k, CG55794-04 SEQ ID NO: 719 1579 bp DNA Sequence ORF Start: at 334 ORF Stop: TAA at 1396
CCAATTGACAAGCTTTTGATTTTAACGACTTTTAACGACAACTTGAGAAGATCAAAAAACAACTAATT
ATTCGAAACGATGAGATTTCCTTCAATTTTTACTGCTGTTTTATTCGCAGCATCCTCCGCATTAGCTG
CTCCAGTCAACACTACAACAGAAGATGAAACGGCACAAATTCCGGCTGAAGCTGTCATCGGTTACTCA
GATTTAGAAGGGGATTTCGATGTTGCTGTTTTGCCATTTTCCAACAGCACAAATAACGGGTTATTGTT
TATAAATACTACTATTGCCAGCATTGCTGCTAAAGAAGAAGGGGTATCTCTCGAGAAAAGATATGATA
GATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTAT TCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAA GGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGATCA GCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATT GCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTATACG CAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTT GGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACGGAT CTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATT CTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGG ATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACC AAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGC AAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAA GAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGTAT GGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGT CCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGC TGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAAGCGGCCGCCAGCTTTCTAGAACAAAAACTC
ATCTCAGAAGAGGATCTGAATAGCGCCGTCGACCATCATCATCATCATCATTGAGTTTGTAGCCTTAG
ACATGACTGTTCCTCAGTTCAAGTTGGGCACTTACGAGAAGACCGGTCTTGCTAGATTCTAATCAAGA
GGATGTCAGAATGCC
NOV46k, CG55794-04 SEQ ID NO: 720 354 aa MW at 40431.3kD Protein Sequence
YDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYL KISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETKAVASFIES KKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGTNYRVGSSADILYASSG SSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSVLDDVYAKHWHSDSAGRVTSA TMLLGLLVSCMSLL NOV461, CG55794-05 SEQ ID NO: 721 1607 bp DNA Sequence ORF Start: at 341 ORF Stop: at 1403
ACTGGTTCCAATTGACAAGCTTTTGATTTTAACGACTTTTAACGACAACTTGAGAAGATCAAAAAACAj
ACTAATTATTCGAAACGATGAGATTTCCTTCAATTTTTACTGCTGTTTTATTCGCAGCATCCTCCGCAi
TTAGCTGCTCCAGTCAACACTACAACAGAAGATGAAACGGCACAAATTCCGGCTGAAGCTGTCATCGG
TTACTCAGATTTAGAAGGGGATTTCGATGTTGCTGTTTTGCCATTTTCCAACAGCACAAATAACGGGT
TATTGTTTATAAATACTACTATTGCCAGCATTGCTGCTAAAGAAGAAGGGGTATCTCTCGAGAAAAGA
TATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGA GACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGA AGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTG AAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGA ATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAA GTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATC TACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGG GACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATC AAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGC AAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGG CTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCAT TGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGG TCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGG AACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGC TGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCC ACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCCACCATCACCACCATCACTAAGCGGC
CGCCAGCTTTCTAGAACAAAAACTCATCTCAGAAGAGGATCTGAATAGCGCCGTCGACCATCATCATC
'ATCATCATTGAGTTTGTAGCCTTAGACATGACTGTTCCTCAGTTCAAGTTGGGCACTTACGAGAAGAC
CGGTCTTGCTAGATTCTAATCAAGAGGATGTCAGAATGCCATT
NOV461, CG55794-05 SEQ ID NO: 722 354 aa MW at 40431.3kD Protein Sequence
YDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYL KISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETKAVASFIES KKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGTNYRVGSSADILYASSG SSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSVLDDVYAKHWHSDSAGRVTSA TMLLGLLVSCMSLL
NOV46m, CG55794-06 SEQ ID NO: 723 977 bp DNA Sequence ORF Start: ATG at 41 ORF Stop: TAG at 671
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAAACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGA
TCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCC
CTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCC
AGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGG
CACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTC
TCTTCTCTAAGTGCATCCTGCCCAG
NOV46m, CG55794-06 SEQ ID NO: 724 210 aa MW at 2484δ.2kD Protein Sequence
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCNSSWTEGSKCIES KVWNQL
NOV46n, CG55794-07 SEQ ID NO: 725 137δ bp DNA Sequence ORF Start: ATG at 259 ORF Stop: TAA at 1225
IACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAGGTGAAAATACATCAGCATGTGGGAAAGAGCAACG
TTGATCGTCTTCACGGAAAGGCTGAGGACCCTGCGCCTACCACATGTTGGCCAGGGTGAGCAAGCAGT
GAAAGAGAAAACACTTTTTTCAAAAAGCCAACTGATCCTTAGCCCAACACAGACAAGAGATTGTGGAC
AAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATCTA
TGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCT ATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGG ATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAAT TCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATGTCCTTC CAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCA CCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTGTAGTAT TGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTA AAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTTAT GGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATTCA AGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTG CAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCA TATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCAC CTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTCGG ACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTC TAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTGGAGGAACGGTGTGTTAT
GGTTGTAAAGAAACCAAATAATTTAACTAAAAATACTTCCTATTTCAATAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAA
NOV46n, CG55794-07 SEQ ID NO: 726 322 aa MW at 36617.2kD Protein Sequence
MGEIYEWMREISEKYKEWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQW FVKEILQNHKDNSRIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNA SWCSIGASRNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNH PEMIQVGQKAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEA QIQPTCEETMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46o, CG55794-08 SEQ ID NO: 727 112δ bp DNA Sequence ORF Start: at 1 ORF Stop: TAA at 1126
ACCATGAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGA TAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGT ATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTAC AAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGAT CAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGA TTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTATA CGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACAC TTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACGG ATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACA TTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAA GGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTACA CCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAA GCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTC AAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGT ATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCA GTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTAT GCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCTAA
Figure imgf000712_0001
NOV46q, CG55794-10 SEQ ID NO: 732 381 aa MW at 43452.9kD Protein Sequence
TMKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46r, CG55794-11 SEQ ID NO: 733 1146 bp DNA Sequence ORF Start: at 1 ORF Stop: TAA at 1144
ACCATGGTAAGCGCTATTGTTTTATATGTGCTTTTGGCGGCGGCGGCGCATTCTGCCTTTGCGTATGA TAGATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGT ATTCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTAC AAGGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGAT CAGCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGA TTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTATA CGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACAC TTGGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACGG ATCTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACA TTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAA GGATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTACA CCAAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAA GCAAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTC AAGAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGT ATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCA GTCCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTAT GCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCCACCATCACCACCATCACTAA
NOV46r, CG55794-l l SEQ ID NO: 734 381 aa MW at 43355.7kD Protein Sequence
TMVS AI VLYVLLAAAAHSAFAYDRSLAQHRQE I VDKS VS P WSLETYS Y I YHPMGE I E WMRE I SEKY KEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSI RKLLRNLDFYVLPVLN I DGY I YTWTTDRLWRKSRS PHNNGTCFGTDLNRNFNAS WCS I GASRNCQDQT FCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALK AKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLS VLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46s, CG55794-12 SEQ ID NO: 735 1161 bp DNA Sequence ORF Start: at 1 ORF Stop: TAA at 1159
ATTATTATACCTCCCACCATCGGGCGCGGATCCACCATGGTAAGCGCTATTGTTTTATATGTGCTTTT GGCGGCGGCGGCGCATTCTGCCTTTGCGTATGATAGATCCTTAGCCCAACACAGACAAGAGATTGTGG ACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGAGATC TATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAGTGAC CTATGAGACCCACCCCATGTATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATCATTT GGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAA ATTCTACAAAACCATAAAGACAACTCAAGTATACGCAAGCTTCTTAGGAACCTGGACTTCTATGTCCT TCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCCCGTT CACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCATCTTGGTGTAGT ATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAGAGAC TAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCACTCTT ATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAATGATT CAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGATCGAG TGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCCTTCT CATATACGTTTGAGCTGAGGGACAGTGGAACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCC ACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGCACTC GGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTC TCTAA NOV46s, CG55794-12 SEQ ID NO: 736 386 aa MW at 43638. lkD Protein Sequence
IIIPPTIGRGSTMVSAIVLYVLLAAAAHSAFAYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEI YEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKE ILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCS IGASRNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMI QVGQKAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQP TCEETMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46t, CG55794-13 SEQ ID NO: 737 1212 bp DNA Sequence ORF Start: at 1 ORF Stop: TAA at 1210
CGCGGATCCACCATGGTAAGCGCTATTGTTTTATATGTGCTTTTGGCGGCGGCGGCGCATTCTGCCTT TGCGAAGCCTCTGCTTGAAACCCTTTATCTTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATA GATCCTTAGCCCAACACAGACAAGAGATTGTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTAT TCCTATAACATATACCACCCCATGGGAGAGATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAA GGAAGTGGTGACACAGCATTTCCTAGGAGTGACCTATGAGACCCACCCCATGTATTATCTGAAGATCA GCCAACCATCTGGTAATCCCAAGAAAATCATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATT GCTCCTGCTTTTTGCCAATGGTTCGTCAAAGAAATTCTACAAAACCATAAAGACAACTCAAGTATACG CAAGCTTCTTAGGAACCTGGACTTCTATGTCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTT GGACAACTGATCGTCTTTGGAGGAAATCCCGTTCACCCCATAATAATGGCACATGTTTTGGGACGGAT CTCAATCGAAATTTCAATGCATCTTGGTGTAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATT CTGTGGGACAGGGCCAGTGTCTGAACCAGAGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGG ATGATATTTTGTGCTTCCTGACCATGCACTCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACC AAAAATAAATCAAGTAACCACCCAGAAATGATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGC AAAGTATGGAACCAATTATAGAGTTGGATCGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAA GAGATTGGGCCCGAGACATTGGGATTCCCTTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGTAT GGGTTTGTTCTGCCAGAAGCTCAGATCCAGCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGT CCTGGATGATGTGTATGCGAAACACTGGCACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGC TGCTGGGCCTGCTGGTGTCCTGCATGTCTCTTCTCCACCATCACCACCATCACTAA
NOV46t, CG55794-13 SEQ ID NO: 738 403 aa MW at 45622.4kD Protein Sequence
RGSTMVSAIVLYVLLAAAAHSAFAKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETY SYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGNPKKIIWMDCGIHAREWI APAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTD LNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYT KNKSSNHPEMIQVGQKAANALKAKYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTY GFVLPEAQIQPTCEETMEAVLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46u, SNPl 3375362 of SEQ ID NO: 739 1222 bp CG55794-03, DNA Sequence ORF Start: ATG at 41 ORF Stop: TAA at 1 163
SNP Pos: 240 SNP Change: A to G
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTGCAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAG AGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCAC TCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAAT GATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGAT CGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCC TTCTCATATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCA GCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGC ACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCT CTTCTCTAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTTGGAGGAACG
NOV46u, SNPl 3375362 of SEQ ID NO: 740 374 aa MW at 42520.0kD CG55794-03, Protein Sequence SNP Pos: 67 SNP Change: Tyr to CyjT
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKCK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46v, SNP1337959δ of SEQ ID NO: 741 1222 bp CG55794-03, DNA Sequence ORF Start: ATG at 41 ORF Stop: TAA at 1163
SNP Pos: 9δδ SNP Change: A to G
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAG AGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCAC TCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAAT GATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGAT CGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCC TTCTCATATACGTTTGAGCTGAGGGACAGTGGAACGTATGGGTTTGTTCTGCCAGAAGCTCAGATCCA GCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGC ACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCT CTTCTCTAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTTGGAGGAACG
NOV46v, SNP1337959δ of SEQ ID NO: 742 374 aa MW at 425δ0.0kD CG55794-03, Protein Sequence SNP Pos: 316 SNP Change: Thr to Thr
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46w, SNPl 3375066 of SEQ ID NO: 743 1222 bp CG55794-03, DNA Sequence ORF Start: ATG at 41 ORF Stop: TAA at 1163
SNP Pos: 1152 SNP Change: T to C
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAG AGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCAC TCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAAT GATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGAT CGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCC TTCTCATATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCA GCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGC ACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCACGTCT CTTCTCTAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTTGGAGGAACG
NOV46w, SNPl 3375066 of SEQ ID NO: 744 374 aa MW at 42549.9kD CG55794-03, Protein Sequence SNP Pos: 371 SNP Change: Met to Thr
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCTSLL
NOV46x, SNPl 3375067 of SEQ ID NO: 745 1222 bp CG55794-03, DNA Sequence ORF Start: ATG at 41 ORF Stop: TAA at 1163
SNP Pos: 1161 SNP Change: T to C
CCAGAGAGGCCCAGAATTTTCTAACTTACTGTGTGGCAGAATGAAGCCTCTGCTTGAAACCCTTTATC
TTTTGGGGATGCTGGTTCCTGGAGGGCTGGGATATGATAGATCCTTAGCCCAACACAGACAAGAGATT GTGGACAAGTCAGTGAGTCCATGGAGCCTGGAGACGTATTCCTATAACATATACCACCCCATGGGAGA GATCTATGAGTGGATGAGAGAGATCAGTGAGAAGTACAAGGAAGTGGTGACACAGCATTTCCTAGGAG TGACCTATGAGACCCACCCCATATATTATCTGAAGATCAGCCAACCATCTGGTAATCCCAAGAAAATC ATTTGGATGGACTGTGGAATTCACGCCAGAGAATGGATTGCTCCTGCTTTTTGCCAATGGTTCGTCAA AGAAATTCTACAAAACCATAAAGACAACTCAAGGATACGCAAGCTCCTTAGGAACCTGGACTTCTATG TCCTTCCAGTTCTTAACATAGATGGTTATATCTACACTTGGACAACTGATCGTCTTTGGAGGAAATCC CGTTCACCCCATAATAATGGCACATGTTTTGGGACGGATCTCAATCGAAATTTCAATGCTTCTTGGTG TAGTATTGGTGCCTCTAGAAACTGCCAAGATCAAACATTCTGTGGGACAGGGCCAGTGTCTGAACCAG AGACTAAAGCTGTTGCCAGCTTCATAGAGAGCAAGAAGGATGATATTTTGTGCTTCCTGACCATGCAC TCTTATGGGCAGTTAATTCTCACACCTTACGGCTACACCAAAAATAAATCAAGTAACCACCCAGAAAT GATTCAAGTTGGACAGAAGGCAGCAAATGCATTGAAAGCAAAGTATGGAACCAATTATAGAGTTGGAT CGAGTGCAGATATTTTATATGCCTCATCAGGGTCTTCAAGAGATTGGGCCCGAGACATTGGGATTCCC TTCTCATATACGTTTGAGCTGAGGGACAGTGGAACATATGGGTTTGTTCTGCCAGAAGCTCAGATCCA GCCCACCTGTGAGGAGACCATGGAGGCTGTGCTGTCAGTCCTGGATGATGTGTATGCGAAACACTGGC ACTCGGACAGTGCTGGAAGGGTGACATCTGCCACTATGCTGCTGGGCCTGCTGGTGTCCTGCATGTCT CTTCCCTAAGTGCATTCTGCCCAGGCCTGCTCAACCCCAGTGGCATGAGTGTGGCTTGGAGGAACG
NOV46x, SNPl 3375067 of SEQ ID NO: 746 374 aa MW at 42564.0kD CG55794-03, Protein Sequence SNP Pos: 374 SNP Change: Leu to Pro
MKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKSVSPWSLETYSYNIYHPMGEIYEWMREISEKYK EWTQHFLGVTYETHPIYYLKISQPSGNPKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIR KLLRNLDFYVLPVLNIDGYIYTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTF CGTGPVSEPETKAVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKA KYGTNYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEAVLSV LDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLP
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 46B.
Table 46B. Comparison of the NOV46 protein sequences.
NOV46a
NOV46b LFETMRFPSIFTAVLFAASSALAAPVNTTTEDETAQIPAEAVIGYSDLEGDFDVAVLPFS NOV46C LFETMRFPSIFTAVLFAASSALAAPVNTTTEDETAQIPAEAVIGYSDLEGDFDVAVLPFS
NOV46d
NOV46e
NOV46f -TM
NOV46g -TM NOV46h -TM NOV46i NOV46J NOV46k NOV461 NOV46m NOV46n N0V46O NOV46p -TM NOV46q N0V46r NOV46S IIIPPTI N0V46t
NOV46a MKPLLETLYLLGMLVPG -GLGYDRSLAQHRQEIVDKS NOV46b NSTNNGLLFINTTIASIAAKEEGVSL- -EKRYDRSLAQHRQEIVDKS NOV46C NSTNNGLLFINTTIASIAAKEEGVSL- -EKRYDRSLAQHRQEIVDKS NOV46d TMKPLLETLYLLGMLVPGG - -LGYDRSLAQHRQEIVDKS NOV46e TMKPLLETLYLLGMLVPGG - -LGYDRSLAQHRQEIVDKS NOV46f GHHHHHHKPLLETLYLLGMLVPG -GLGYDRSLAQHRQEIVDKS NOV46g GHHHHHHKPLLETLYLLGMLVPG -GLGYDRSLAQHRQEIVDKS NOV46h GHHHHHHKPLLETLYLLGMLVPG -GLGYDRSLAQHRQEIVDKS NOV46i MKPLLETLYLLGMLVPG -GLGYDRSLAQHRQEIVDKS NOV46J YDRSLAQHRQEIVDKS NOV46k YDRSLAQHRQEIVDKS NOV461 YDRSLAQHRQEIVDKS NOV46m -MKPLLETLYLLGMLVPG- -GLGYDRSLAQHRQEIVDKS NOV46n N0V46O TMKPLLETLYLLGMLVPGG- LGYDRSLAQHRQEIVDKS NOV46p GHHHHHHKPLLETLYLLGMLVPG- GLGYDRSLAQHRQEIVDKS NOV46 TMKPLLETLYLLGMLVPGG- LGYDRSLAQHRQEIVDKS NOV46r TMVSAIVLYVLLAAAAHS- - AFAYDRSLAQHRQEIVDKS NOV46S GRGSTMVSAIVLYVLLAAAAHS- - AFAYDRSLAQHRQEIVDKS NOV46t -RGSTMVSAIVLYVLLAAAAHSAFAKPLLETLYLLGMLVPGGLGYDRSLAQHRQEIVDKS
NOV46a VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPIYYLKISQPSGN NOV46b VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46C VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46d VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46e VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46f VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46g VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46h VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46i VSPWSLETYSYNIYHPMGEINEWMREISEKYKEWTQHFLGVTYETHPIYYLKISQPSGN NOV46J VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46k VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV461 VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN NOV46m VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPIYYLKISQPSGN NOV46n MGEIYEWMREISEKYKEWTQHFLGVTYETHPIYYLKISQPSGN N0V46O VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46p VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46q VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46r VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46S VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46t VSPWSLETYSYNIYHPMGEIYEWMREISEKYKEWTQHFLGVTYETHPMYYLKISQPSGN
NOV46a PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIRKLLRNLDFYVLPVLNIDGYI
NOV46b PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46C PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46d PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46e PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46f PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46g PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46h PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46i PKKIIWMGCGIHAREWIAPAFCQWFVKEILQNHKDNSRIRKLLRNLDFYVLPVLNIDGYI
NOV46J PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46k PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV461 PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46m PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIRKLLRNLDFYVLPVLNIDGYI
NOV46n PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSRIRKLLRNLDFYVLPVLNIDGYI
N0V46O PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46p PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46q PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46r PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46S PKKII MDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46 PKKIIWMDCGIHAREWIAPAFCQWFVKEILQNHKDNSSIRKLLRNLDFYVLPVLNIDGYI
NOV46a YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46b YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46C YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46d YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46e YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46f YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46g YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46h YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46i YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46J YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46k YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV461 YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46m YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCNSSWTEGSKCIESKVWNQL
NOV46n YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46o YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46p YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46q YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46r YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46S YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV461 YTWTTDRLWRKSRSPHNNGTCFGTDLNRNFNASWCSIGASRNCQDQTFCGTGPVSEPETK
NOV46a AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT
NOV46b AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT
NOV46C AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT
NOV46d AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT
NOV46e AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46f AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46g AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46h AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46i AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46J AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46k AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV461 AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46m NOV46n AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT N0V46O AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46p AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46q AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46r AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46S AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT NOV46 AVASFIESKKDDILCFLTMHSYGQLILTPYGYTKNKSSNHPEMIQVGQKAANALKAKYGT
NOV46a NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46b NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46c NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46d NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46e NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46f NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46g NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46h NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46i NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46J NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46k NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV461 NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46m NOV46n NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA N0V46O NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46p NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46q NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46r NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV 6s NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA NOV46t NYRVGSSADILYASSGSSRDWARDIGIPFSYTFELRDSGTYGFVLPEAQIQPTCEETMEA
NOV46a VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46b VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46c VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46d VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46e VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46f VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46g VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46h VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46i VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46j VLSVLDDVYAKHWHSDSAGR
NOV46k VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV461 VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46m
NOV46n VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46o VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46p VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46q VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH NOV46r VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46s VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLL
NOV46t VLSVLDDVYAKHWHSDSAGRVTSATMLLGLLVSCMSLLHHHHHH
NOV46a (SEQ ID NO: 700)
NOV46b (SEQ ID NO 702)
NOV46c (SEQ ID NO 704)
NOV46 (SEQ ID NO 706)
NOV46e (SEQ ID NO 708)
NOV46f (SEQ ID NO 710)
NOV46g (SEQ ID NO 712)
NOV46h (SEQ ID NO 714)
NOV46i (SEQ ID NO 716)
Figure imgf000720_0001
NOV46k (SEQ ID NO 720)
NOV461 (SEQ ID NO 722)
NOV46m (SEQ ID NO 724)
NOV46n (SEQ ID NO 726)
N0V46O (SEQ ID NO 728)
NOV46p (SEQ ID NO 730)
NOV46q (SEQ ID NO 732)
NOV46r (SEQ ID NO 734)
NOV46s (SEQ ID NO 736)
NOV46 (SEQ ID NO 738)
Further analysis ofthe NOV46a protein yielded the following properties shown in Table 46C.
Figure imgf000720_0002
Center position for calculation: 10
Charge difference: -0.5 C( 0.5) - N( 1.0)
N >= C: N-terminal side will be inside
>>> membrane topology: type la (cytoplasmic tail 374 to 374)
>>> Seems to be GPI anchored
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.63 Hyd Moment(95): 12.49 G content: 4 D/E content: 2 S/T content: 1 Score: -7.55
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 9.9% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
55.6 % extracellular, including cell wall 22.2 % endoplasmic reticulum 11.1 % Golgi 11.1 % plasma membrane
>> prediction for CG55794 - 03 is exc (k=9)
A search ofthe NOV46a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 46D.
Figure imgf000723_0001
In a BLAST search of public sequence databases, the NOV46a protein was found to have homology to the proteins shown in the BLASTP data in Table 46E.
Figure imgf000724_0001
PFam analysis indicates that the NOV46a protein contains the domains shown in the Table 46F.
Table 46F. Domain Analysis of NOV46a
Identities/
Pfam Domain NOV46a Match Region Similarities Expect Value for the Matched Region
Zn carbOpept 4δ..249 δ2/215 (3δ%) 1.2e-74 168/215 (78%)
Example 47.
The NOV47 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 47A. Table 47A. NOV47 Sequence Analysis
NOV47a, CG55δ06-04 SEQ ID NO: 747 1300 bp DNA Sequence ORF Start: ATG at 20 ORF Stop: TGA at 1274
TGACTGTATCGCCGGATTCATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCATCACCA
TCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAA ATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAGGAGTTTGTTCATGGGAACCTTGAGAG AGAATGTATGGAAGAAAAGTGCAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAA CTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGT TGCAAGGATGTCATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT AGTGCCATTTCCATGTGGAAGAGTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGACTGTTT TTCCTGATGTGGACTATGTAAATTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACC CAATCATTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCA GGTTGTTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGGATTGTAA CTGCTGCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAG ACAGAACATACAGAGCAAAAGCGAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTAT TAATAAGTACAACCATGACATTGCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTA CACCTATTTGCATTGCTGACAAGGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGT GGCTGGGGAAGAGTCTTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGT TGACCGAGCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCC ATGAAGGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACC AGTTTCTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATAC CAAGGTATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAGCTCACTTGACTGCAGCCAAGCTAAT TCCGGAAG
NOV47a, CG55δ06-04 SEQ ID NO: 748 418 aa M at47031.δkD Protein Sequence
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVHGNLERECMEEK CSFEEAREVFENTERTTEF KQYVDGDQCESNPCLNGGSCKDVINSYECWCPFGFEGKNCELVPFPCG RVSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPWQWLNGK VDAFCGGSIVNEKWIVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHD IALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSG GRVFHKGRSALVLQYLRVPLVDRATCL RSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTIVSRYV NWIKEKTKLT
NOV47b, CG55δ06-01 SEQ ID NO: 749 1438 bp DNA Sequence ORF Start: ATG at 2 ORF Stop: TAA at 1184
TATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCATCACCATCTGCCTTTTAGGATATC TACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAG AGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTCTGGAGGAAAA GTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAACTGAATTTTGGAAGCAGT ATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAAT TCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGATGTGGACTATGTAAA TTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACCCAATCATTTAATGACTTCACTC GGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCAGGTTGTTTTGAATGGTAAAGTT GATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGGATTGTAACTGCTGCCCACTGTGTTGAAAC TGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAGACAGAACATACAGAGCAAAAGC GAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTATTAATAAGTACAACCATGACATT GCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTACACCTATTTGCATTGCTGACAA GGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGTGGCTGGGGAAGAGTCTTCCACA AAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGTTGACCGAGCCACATGTCTTCGA TCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCCATGAAGGAGGTAGAGATTCATG TCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACCAGTTTCTTAACTGGAATTATTA GCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATACCAAGGTATCCCGGTATGTCAAC TGGATTAAGGAAAAAACAAAGCTCACTTAATGAAAGATGGATTTCCAAGGTTAATTCATTGGAATTGA AAATTAACAGGGCCTCTCACTAACTAATCACTTTCCCATCTTTTGTTAGATTTGAATATATACATTCT ATGATCATTGCTTTTTCTCTTTACAGGGGAGAATTTCATATTTTACCTGAGCAAATTGATTAGAAAAT GGAACCACTAGAGGAATATAATGTGTTAGGAAATTACAGTCATTTCTAAGGGCCCAGCCTTGACAAAT
ITGTGAGTAAA
NOV47b, CG55806-01 SEQ ID NO: 750 394 aa MW at 44431.7kD Protein Sequence
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECLEEK CSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCPFGFEGKNCELDVDYVN STEAETILDNITQSTQSFNDFTRWGGEDAKPGQFP QWLNGKVDAFCGGSIVNEPCWIVTAAHCVET GVKITWAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADK EYTNIFLKFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSC QGDSGGPHOTEVEGTSFLTGI ISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
NOV47c, CG55δ06-02 SEQ ID NO: 751 2δ07 bp DNA Sequence ORF Start: ATG at 20 ORF Stop: TAA at 1403
CAATCTGCTAGCAAAGGTTATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTGATCACCAi
TCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAA ATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAG AGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAA CTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGT TGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT AGATGTAACATGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAAGG TGGTTTGCTCCTGTACTGAGGGATATCGACTTGCAGAAAACCAGAAGTCCTGTGAACCAGCAGTGCCA TTTCCATGTGGAAGAGTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGACTGTTTTTCCTGA TGTGGACTATGTAAATTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACCCAATCAT TTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCAGGTTGTT TTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGGATTGTAACTGCTGC CCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAGACAGAAC ATACAGAGCAAAAGCGAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTATTAATAAG TACAACCATGACATTGCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTACACCTAT TTGCATTGCTGACAAGGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGTGGCTGGG GAAGAGTCTTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGTTGACCGA GCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCCATGAAGG AGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACCAGTTTCT TAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATACCAAGGTA TCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAGCTCACTTAATGAAAGATGGATTTCCAAGGTTA ATTCATTGGAATTGAAAATTAACAGGGCCTCTCACTAACTAATCACTTTCCCATCTTTTGTTAGATTT GAATATATACATTCTATGATCATTGCTTTTTCTCTTTACAGGGGAGAATTTCATATTTTACCTGAGCA AATTGATTAGAAAATGGAACCACTAGAGGAATATAATGTGTTAGGAAATTACAGTCATTTCTGAAGCC CAGCCCTTGACAAAATTGTGAAGTTAAATTCTCCACTCTGTCCATCAGATACTATGGTTCTCCACTAT GGCAACTAACTCACTCAATTTTCCCTCCTTAGCAGCATTCCATCTTCCCGATCTTCTTTGCTTCTCCA ACCAAAACATCATGTTTATTAGTTCTGTATACAGTACAGGATCTTTGGTCTACTCTATCACGAGAAGG CTCAGTACCACACTCATGAAGAAAGAACACAGGAGTAGCTGAGAGGCTAAAACTCATCAAAAACACTA CTCCTTTTCCTCTACCCTATTCCTCAATCTTTTACCTTTTCCAAATTCCCAATTCCCCAAATCAGTTT TTCTCTTTCTTACTCCCTCTCTCCCTTTTACCCTCCATGGTCGTTAAAGGAGAGATGGGGAGCATCAT TCTGTTATACTTCTGTACACAGTTATACATGTCTATCAAACCCAGACTTGCTTCCATAGTGGAGACTT GCTTTTCAGAACATAGGGATGAAGTAAGGTGCCTGAAAAGTTTGGGGGAAAAGTTTCTTTCAGAGAGT TAAGTTATTTTATATATATAATATATATATAAAATATATAATATACAATATAAATATATAGTGTGTGT GTGTATGCGTGTGTGTAGACACACACGCATACACACATATAATGGAAGCAATAAGCCATTCTTAAGAG CTTGTATGGTTATGCAGGTCTGACTAGGCATGATTTCACGAAGGCAAGATTGGCATATCAGTTGTAAC TAAAAAAGCTGACATTGACCCAGACATATTGTACTCTTTCTAAAAATAATAATAATAATGCTAACAGA AAGAAGAGAACCGTTCGTTTGCAATCTACAGCTAGTAGAGACTTGAGGAAGAATTCAACAGTGTGTCT TCAGCAGTGTTCAGAGCCAAGCAAGAAGTTGAAGTTGCCTAGACCAGAGGACATAAGTATCATGTCTC CTTTAACTAGCATACCCCGAAGTGGAGAAGGATGCAGCAGGCTCAAAGGCATAAGTCATTCCAATCAG CCAACTAAGTTGTCCTTTTCTGGTTTCGTGTTCACCATGGAACATTTTGATTATAGTTAATCCTTCTA TCTTGAATCTTCTAGAGAGTTGCTGACCAACTGACGTATGTTTCCCTTTGTGAATTAATAAACTGGTG TTCTGGTTCAAAAAAAAAA NOV47c, CG55806-02 SEQ ID NO: 752 461 aa MW at 51778.0kD Protein Sequence
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECMEEK CSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYEC CPFGFEGKNCELDVTCNI KNGRCEQFCKNSADNKWCSCTEGYRLAENQKSCEPAVPFPCGRVSVSQTSKLTRAETVFPDVDYVNS TEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPWQWLNGKVDAFCGGSIVNEK IVTAAHCVETG VKITWAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKE YTNIFLKFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQ GDSGGPHVTEVEGTSFLTGI IS GEECAMKGKYGIYTKVSRYVN IKEKTKLT
NOV47d, CG55806-03 SEQ ID NO: 753 1612 bp DNA Sequence ORF Start: ATG at 22 ORF Stop: TAA at 1405
TTGACTGTATCGCCGGAATTCATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCATCAC
CATCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACA AAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAG AGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAAC AACTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCA GTTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAA TTAGATGTAACATGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAA GGTGGTTTGCTCCTGTACTGAGGGATATCGACTTGCAGAAAACCAGAAGTCCTGTGAACCAGCAGTGC CATTTCCATGTGGAAGAGTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGACTGTTTTTCCT GATGTGGACTATGTAAATTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACCCAATC ATTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCAGGTTG TTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGGATTGTAACTGCT GCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAGACAGA ACATACAGAGCAAAAGCGAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTATTAATA AGTACAACCATGACATTGCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTACACCT ATTTGCATTGCTGACAAGGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGTGGCTG GGGAAGAGTCTTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGTTGACC GAGCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCCATGAA GGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACCAGTTT CTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATACCAAGG TATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAGCTCACTTAATGAAAGATGGATTTCCAAGGT
TAATTCATTGAAATTGAAAATTAATAGGGCCTCTCACTAACTAATCACTTTCCCATCTTTTGTTAGAT
TTGAATATATACATTCTATGATCATTGCTTTTTCTCTTTACAGGGGAGAATTTCATATTTTACCTGAG
CAAATTGATTAGAAAATGGAACCACTAGAGGAATATAATGTGTTAGGA
NOV47d, CG55δ06-03 SEQ ID NO: 754 461 aa MW at 5177δ.0kD Protein Sequence
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECMEEK CSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCPFGFEGKNCELDVTCNI KNGRCEQFCKNSADNKVVCSCTEGYRLAENQKSCEPAVPFPCGRVSVSQTSKLTRAETVFPDVDYVNS TEAETILDNITQSTQSFNDFTRWGGEDAKPGQFP QWLNG VDAFCGGSIVNEKWIVTAAHCVETG VKITWAGEHNIEETEHTEQKRNVIRI IPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKE YTNIFLKFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQ GDSGGPHVTEVEGTSFLTGI ISWGEECAMKGKYGIYTKVSRYVN IKEKTKLT
NOV47e, SNP133δ2503 of SEQ ID NO: 755 1300 bp CG55δ06-04, DNA Sequence ORF Start: ATG at 20 ORF Stop: TGA at 1274
SNP Pos: 470 SNP Change: A to G
TGACTGTATCGCCGGATTCATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCATCACCA
TCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAA ATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAGGAGTTTGTTCATGGGAACCTTGAGAG AGAATGTATGGAAGAAAAGTGCAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAA CTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGT TGCAAGGATGTCATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT AGTGCCATTTCCATGTGGAAGAGTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGGCTGTTT TTCCTGATGTGGACTATGTAAATTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACC CAATCATTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCA GGTTGTTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGGATTGTAA CTGCTGCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAG ACAGAACATACAGAGCAAAAGCGAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTAT TAATAAGTACAACCATGACATTGCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTA CACCTATTTGCATTGCTGACAAGGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGT GGCTGGGGAAGAGTCTTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGT TGACCGAGCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCC ATGAAGGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACC AGTTTCTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATAC CAAGGTATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAGCTCACTTGACTGCAGCCAAGCTAAT TCCGGAAG
NOV47e, SNPl 3382503 of SEQ ID NO: 756|418 aa MW at 47001. δkD CG55806-04, Protein Sequence SNP Pos: 151 SNP Change: Thr to Ala
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVHGNLERECMEEK CSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDVINSYECWCPFGFEGKNCELVPFPCG RVSVSQTSKLTRAEAVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFP QWLNGK VDAFCGGSIVNEKWIVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHD IALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCL RSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYV NWIKEΪTKLT
NOV47f, SNP133δ2492 of SEQ ID NO: 757 1300 bp CG55δ06-04, DNA Sequence ORF Start: at 2 ORF Stop: at 1253
SNP Pos: 673 SNP Change: G to A
TGACTGTATCGCCGGATTCATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCATCACCA TCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAA ATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAGGAGTTTGTTCATGGGAACCTTGAGAG AGAATGTATGGAAGAAAAGTGCAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAA CTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGT TGCAAGGATGTCATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT AGTGCCATTTCCATGTGGAAGAGTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGACTGTTT TTCCTGATGTGGACTATGTAAATTCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAAGCACC CAATCATTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGGCA GGTTGTTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAATGAATTGTAA CTGCTGCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGTGAACATAATATTGAGGAG ACAGAACATACAGAGCAAAAGCGAAATGTGATTCGAATTATTCCTCACCACAACTACAATGCAGCTAT TAATAAGTACAACCATGACATTGCCCTTCTGGAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTA CACCTATTTGCATTGCTGACAAGGAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGT GGCTGGGGAAGAGTCTTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGT TGACCGAGCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTCC ATGAAGGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTGGAAGGGACC AGTTTCTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGCAAATATGGAATATATAC CAAGGTATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAGCTCACTTGACTGCAGCCAAGCTAAT TCCGGAAG
NOV47f, SNP133δ2492 of SEQ ID NO: 758 417 aa M at 46845.6kD CG55806-04, Protein Sequence SNP Pos: 218 SNP Change: Trp to End
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVHGNLERECMEEK CSFEEAREVFENTERTTEF KQYVDGDQCESNPCLNGGSCKDVINSYEC CPFGFEGKNCELVPFPCG RVSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPWQWLNGK VDAFCGGSIVNEKIVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHDI ALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSG GRVFHKGRSALVLQYLRVPLVDRATCLR STKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYVN WIKEKTKLT A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 47B.
Table 47B. Comparison of the NOV47 protein sequences.
NOV47a MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVHGNL
NOV47b MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
NOV47c MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
NOV47d MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
NOV47a ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDVINSYECWCP
NOV47b ERECLEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP
NOV47C ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP
NOV47d ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP
NOV47a FGFEGKNCELVP FP- -CGR
NOV47b FGFEGKNCELDV D
NOV47c FGFEGKNCELDVTCNIKNGRCEQFCKNSADNKWCSCTEGYRLAENQKSCEPAVPFPCGR
NOV47d FGFEGKNCELDVTCNIKNGRCEQFCKNSADNKWCSCTEGYRLAENQKSCEPAVPFPCGR
NOV47a VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPW
NOV47b YVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPW
NOV47c VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFPW
NOV47d VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRWGGEDAKPGQFP
NOV47a QWLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITWAGEHNIEETEHTEQIRNVIRII
NOV47b QWLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRII
NOV47C QWLNGIVDAFCGGSIVNEK IVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRII
NOV47d QWLNGKVDAFCGGSIVNEK IVTAAHCVETGVKITWAGEHNIEETEHTEQKRNVIRII
NOV47a PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIAD EYTNIFLKFGSGYVSGWGRVF
NOV47b PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF
NOV47c PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF
NOV47d PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF
NOV47a HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE
NOV47b HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE
NOV47c HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE
NOV47d HKGRSALVLQYLRVPLVDRATCLRSTKFTI NNMFCAGFHEGGRDSCQGDSGGPHVTEVE
NOV47a GTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
NOV47b GTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
NOV47C GTSFLTGIIS GEECAMKGKYGIYTKVSRYVN IKEKTKLT
NOV47d GTSFLTGIISWGEECAMKGKYGIYTKVSRYVN IKEKTKLT
NOV47a (SEQ ID NO 748)
NOV47b (SEQ ID NO 750)
NOV47C (SEQ ID NO 752)
NOV47d (SEQ ID NO 754)
Further analysis ofthe NOV47a protein yielded the following properties shown in Table 47C. Table 47C. Protein Sequence Properties NOV47a
SignalP analysis: Cleavage site between residues 26 and 27
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 1; neg.chg 1 H-region: length 16; peak value 9.84 PSG score: 5.44
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -2.46 possible cleavage site: between 25 and 26
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -2.50 Transmembrane 14 - 30 PERIPHERAL Likelihood = 2.07 (at 219) ALOM score: -2.50 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 21 Charge difference: -2.5 C(-1.5) - N( 1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 2 (cytoplasmic tail 1 to 14)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 4.83 Hyd Moment(95): 6.44 G content: 2 D/E content : 2 S/T content : 3 Score: -6.32
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 13 QRV|NM
NUCDISC: discrimination of nuclear localization signals pat4: RPKR (4) at 43 pat7: none bipartite: none content of basic residues: 10.0% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: QRVN KKXX-like motif in the C-terminus: KTKL
SKL: peroxisomal targeting signal in the C- terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail : none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions
58 N 0.51
59 L 0.51
60 E 0.51
61 R 0.51
62 E 0.51
63 C 0.51
64 M 0.51
65 E 0.51
66 E 0.51
67 K 0.51
68 C 0.51
69 S 0.51
70 F 0.51
71 E 0.51
72 E 0.51
73 A 0.51
74 R 0.51
75 E 0.51
76 V 0.51 77 F 0.51
78 E 0.51
79 N 0.51
80 T 0.51
81 E 0.51
82 R 0.51
83 T 0.51
84 T 0.51
85 E 0.51 total: 28 residues
Final Results (k = 9/23) :
34.8 % mitochondrial
30.4 % cytoplasmic
8.7 % Golgi
8.7 % nuclear
4.3 % vacuolar
4.3 % extracellular, including cell wall
4.3 % vesicles of secretory system
4.3 % endoplasmic reticulum
>> prediction for CG55806-04 is mit (k=23)
A search ofthe NOV47a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 47D.
72δ
Figure imgf000733_0001
In a BLAST search of public sequence databases, the NOV47a protein was found to have homology to the proteins shown in the BLASTP data in Table 47E.
Figure imgf000734_0001
PFam analysis indicates that the NOV47a protein contains the domains shown in the Table 47F.
Figure imgf000734_0002
Example 48.
The NOV4δ clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4δA. Table 48A. NOV48 Sequence Analysis
NOV4δa, CG55δ2δ-02 SEQ ID NO: 759 1439 bp DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1406
TCATCCACAGCCATCATATAAAGGTTTTGGCATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATAT
CTGGCCCGTCCAACTTTGAACACAGGGTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGC CTTCCCCAGCAGTGGCACAGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTC ATGCATCACACCCATCCAGCTGGCTCCTATGAAGGTGGATTACGATCGAGCACAGATGGTCCTCAGCC CTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAAGCAAATCG GGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCATCACCCCTC CCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTCATCCAGCA CCTACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTT CGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAAT CGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGA AGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGTGGTCAT GGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAACAGATAG CTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCACAGGGAC ATAAAAAGTGACTCCATTCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTTCTGTGC TCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGG TGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATG ATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTT ACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATGTTGG TGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTAGCAGGT CCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTGTAGGTG GCAAAGCTAGA
NOV48a, CG55δ2δ-02 SEQ ID NO: 760 457 aa MW at 51352.3kD Protein Sequence
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQWHSLLADTANRPKPMVDPSCITPIQLAPMK VDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTA SYLSSLSLSSSTYPPPSWGSSSDQQPSRVSHEQFRAALQLWSPGDPREYLANFIKIGEGSTGIVCIA TEKHTGKQVAVKKMDLRKQQRRELLFNEWIMRDYHHDNWDMYSSYLVGDELWWMEFLEGGALTDI VTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKS LVGTPY MAPEVISRLPYGTEVDI SLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVS SVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
NOV48b, CG5582δ-01 SEQ ID NO: 761 4796 bp DNA Sequence ORF Start: ATG at 549 ORF Stop: TGA at 1833
INCGAAAACCCGGAGCAGCTGCGTACGCTCATGGACAGTCCTCCGAGGGGCGAAGCCGGGCAGCTGGGC lATGCTCAGTAGCTGGGGGAGGTTTGGGTGGAGAGTAGAAAGCTGTGGCTCTGCCTCTCATCCCCTCCC
IGCTGGCCCCCGCCCCCCTTGCCCCTACCCAGCCAGTAGTAGTTCCCCAGCGTGCGCCCGGGGAGACCG
GGAACATGGCGCTGGGAGCGCTGTAGCAGCTGAGAAGGGGCTGAGGCACCGCCGCTTCGCTGACAGCC
IGGCCACCAGATGTTCATGCATTCTAGAGAAAGTGGAAAACTTAGAAGCCTAATTAATGACTGTCTTCT
IGGACCTCTGAGACCATGTTTCTAGTGTTTTCCGTGGAATATTATCAGAAATACACTGTGGTGAAATGC
TTCCACCTCTTGCTAAAATGAACACTGAGGAAAAATGAAGAAGACTGACAAGCACCAGCGAAAAGTTG
CAGAATAGAAATAGCCACACTCCTCTGGAGTCTTTAATTCATCCACAGCCATCATATAAAGGTTTTGG
CATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATATCTGGCCCGTCCAACTTTGAACACAGGGTTC
ATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGCCTTCCCCAGCAGTGGCACAGCCTGTTAGCA GATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTCATGCATCACACCCATCCAGCTGGCTCCTAT GAAGACAATCGTTAGAGGAAACAAACCCTGCAAGGAAACCTCCATCAACGGCCTGCTAGAGGATTTTG ACAACATCTCGGTGACTCGCTCCAACTCCCTAAGGAAAGAAAGCCCACCCACCCCAGATCAGGGAGCC TCCAGCCACGGTCCAGGCCACGCGGAAGAAAATGGCTTCATCACCTTCTCCCAGTATTCCAGCGAATC CGATACTACTGCTGACTACACGACCGAAAAGTACAGGGAGAAGAGTCTCTATGGAGATGATCTGGATC CGTATTATAGAGGCAGCCACGCAGCCAAGCAAAATGGGCACGTAATGAAAATGAAGCACGGGGAGGCC TACTATTCTGAGGTGAAGCCTTTGAAATCCGATTTTGCCAGATTTTCTGCCGATTATCACTCACATTT GGACTCACTGAGCAAACCAAGTGAATACAGTGACCTCAAGTGGGAGTATCAGAGAGCCTCGAGTAGCT CCCCTCTGGATTATTCATTCCAATTCACACCTTCTAGAACTGCAGGGACCAGCGGGTGCTCCAAGGAG AGCCTGGCGTACAGTGAAAGTGAATGGGGACCCAGCCTGGATGACTATGACAGGAGGCCAAAGTCTTC GTACCTGAATCAGACAAGCCCTCAGCCCACCATGCGGCAGAGGTCCAGGTCAGGCTCGGGACTCCAGG AACCGATGATGCCATTTGGAGCAAGTGCATTTAAAACCCATCCCCAAGGACACTCCTACAACTCCTAC ACCTACCCTCGCTTGTCCGAGCCCACAATGTGCATTCCAAAGGTGGATTACGATCCAGCACAGATGGT CCTCAGCCCTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAA GCAAATCGGGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCAT CACCCCTCCCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTC ATCCAGCATACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAA CAGTTTCGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTAT
CAAAATCGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTG
CAGTGAAGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATG
CGGGATTACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGT
GGTCATGGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAAC
AGATAGCTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCAC
AGGGACATAAAAAGTGACTCCATCCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTT
CTGTGCTCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCC
CTGAGGTGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATA
GAAATGATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGA
CAGTTTACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGA
TGTTGGTGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTA
GCAGGTCCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTG jTAGGTGGCAAAGCTAGATGAGGACATGAGAATAATTCAGGAGAACAAAAGGAAACACAGAACATGCAA
AAGGCCTGTGCATTCTAGACCAGCCAATTGGTGGGACAGCGTGATGACCGGCAGGGTTCAACAGACCA
GGGCATCTTCTTGTGTCTTAAACAGGCATCTCTCCACTGACAGCCGGTGTGGTCACTTGGAGCACGGC;
TT AATAAGTCATTATTATATTTTTCAGCCCTTCATCCAGCAAATCAGAAGGACTCAGTACAAACTCC;
GTTATGATATATCCTAGCCACATGCAGGGTAACATGTAGGATTTTCTATATTGAAAGAATACTTTTCT
GGCAAAAAAAAAAAAAAAAAGAAAGAAAGGAAAACAAAAAGCACTTTTTTCTTAATGGTAGCAGTATA: lATGTATTTTGCAACGAATTTGTAATTTTTCTGTACGATAGTTTTGATAATTTATAGTACTTTGATGTC:
ATGTAGCCATTGTATCAGTTGAAGTAATACTTGTTTACTAGAGGAGTTTGAACAAAGCCTTTCCTACT
TTTTTATCCCTTTAAGAGAACCAATGATTCTTTAGGAACTTTGAATACTGAATGACTCTCAATCACCG iTCAGCTTTAGTAAAATCTCTTTCTTATCCTAACAAGTGTCTTATTTGGTGGAAGAAGAATTAAGAGTG
ATGGTGATGGTGTGCACGTTTCATTAATCCAACCAAAAATAATGAAATAAAATTTGAGCCACAGTATAI
CCACTCCTTGGGATAAAGTTAAATATTTTTAAAGATCACATTTTCCATGAACGCCTCTAGTAGCAAAC
CATTCTTTTGCACACCACAATGTTTCCCTCAGTGCCCTTTCTCAAATGGGTACAATGTTCCCTTGTGG
CCAAATTTCCCTCCCAGGGAGCAATTTCAGTGCTAGGATCATTGGATTCAGTTCCCAAAATAGAATGT
TTCAGTGAGACCATGAGAATTCCAGGCTCACAGAGGGAGAGGAGAGAACAGGGCAAGACGTTTGGTTT
CATTTGTCACCATTTTTAAAACTCTGTATGCTAGCACACCAAACTCTTGTCTATATTTACCTTTGTAC
CACAGTATTAATCGCTATTGTTCATGTATCGTGCTGGAAGTCTGAACTGACTCTAGAGGATGAATTAG!
CAAGAGGGTATTTTACCAGGTATGATCTGACTTCAGTTGTGCCCATGTTATAATGTGTTTCCGACATA!
GGAGAGTCGTGCTGCTGTCTAGATCTTCTTGAATGTTGATAAAAATGAATGACTACTACAATACATTT!
TGTGTTGCTTGTTGGATGAATTTGCATGTTAACTGTAGGCCAATATAGATTTGCCTTTAAAACTCTGG
AAGAGCTACATAGTCATCATTAGTTTCTATTAATTATGCATCAGACAAAAGCCATTTGTTACCAAACT
GGGAAAACAGAGGCTTTTCTTAACTATTTCACATACTGTAACAAATATGAATTTAAATTTGTGATAGC
GCTCTGGTTGCTCTAAGCATAATTAAGAATTTTTGTAATTAATAGGTTGCTAATTATTTATCACTGCT
AAAAAGGAAAAAAGGCATAAAATGACCTTCTACTGATTAGATTTTCAGTTTTCTTTCAAACTGGAAAT
GCCTCCATAAATATGATCTATGATTTTGCTTCATAAAACAGCAAATCAATGTTTTATGTAAAATATTA iAAGCATTAATATAAATATGTGAGAATAAAAACAATCTAAATCCAGAAAATGGCAGTCCTAAATGTTCA iTGAGACAGATTGTATTAATTTAACCAGGACTATGTAGAAGTAGAAAGAAAAGAAAAAGAAAATCTTTT!
!TTAAACCAGAATAAACATTAAAAACTATTGCAGAAAATAGTGGATTTTGGATTCCAAACATTTTCGAC| lAGTGTAATGGAAATTTTTCTGTAATTTTCTTACCATCGGGTATTTTTTAAAGTATTCATTGAGTTTAC
CAAAAGTTACTGTAGCTTAAAAGGTTTTGTGAGCACTAACTATTGGCAGAAACTGCATTTGCAAATAAI
AAATAAATGTTTGCCTTTTAAAAAAAAAAAAAAAAA
NOV48b, CG5582δ-01 SEQ ID NO: 762 42δ aa MW at 47439.0kD Protein Sequence
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQWHSLLADTANRPKPMVDPSCITPIQLAPMK TIVRGNKPCKETSINGLLEDFDNISVTRSNSLRKESPPTPDQGASSHGPGHAEENGFITFSQYSSESD TTADYTTEKYREKSLYGDDLDPYYRGSHAAKQNGHVMKMKHGEAYYSEVKPLKSDFARFSADYHSHLD SLSKPSEYSDLKWEYQRASSSSPLDYSFQFTPSRTAGTSGCSKESLAYSESEWGPSLDDYDRRPKSSY LNQTSPQPTMRQRSRSGSGLQEPMMPFGASAFKTHPQGHSYNSYTYPRLSEPTMCIPKVDYDPAQMVL SPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTASYLSSLSLSS SIPAAQLGLLLRPAALQGVP
NOV4δc, SNP13379517 of SEQ ID NO: 763 1439 bp CG55δ2δ-02, DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1406
SNP Pos: 149 SNP Change: T to C
TCATCCACAGCCATCATATAAAGGTTTTGGCATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATAT
CTGGCCCGTCCAACTTTGAACACAGGGTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGC CTTCCCCAGCAGCGGCACAGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTC ATGCATCACACCCATCCAGCTGGCTCCTATGAAGGTGGATTACGATCGAGCACAGATGGTCCTCAGCC CTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAAGCAAATCG GGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCATCACCCCTC CCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTCATCCAGCA CCTACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTT CGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAAT CGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGA AGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGTGGTCAT GGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAACAGATAG CTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCACAGGGAC ATAAAAAGTGACTCCATTCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTTCTGTGC TCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGG TGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATG ATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTT ACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATGTTGG TGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTAGCAGGT CCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTGTAGGTG GCAAAGCTAGA
NOV4δc, SNP13379517 of 1SEQ ID NO: 764 457 aa M at51322.3kD
CG5582δ-02, Protein Sequence SNP Pos: 39 SNP Change: Trp to Arg
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQRHSLLADTANRPKPMVDPSCITPIQLAPMK VDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTA SYLSSLSLSSSTYPPPSWGSSSDQQPSRVSHEQFRAALQLWSPGDPREYLANFIKIGEGSTGIVCIA TEKHTGKQVAVKKMDLRKQQRRELLFNEWIMRDYHHDNWDMYSSYLVGDELWWMEFLEGGALTDI VTΉTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKS LVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVS SVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
NOV48d, SNPl3376535 of SEQ ID NO: 765 1439 bp CG55828-02, DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1406
SNP Pos: 222 SNP Change: A to G
TCATCCACAGCCATCATATAAAGGTTTTGGCATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATAT
CTGGCCCGTCCAACTTTGAACACAGGGTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGC CTTCCCCAGCAGTGGCACAGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTC ATGCATCACACCCATCCGGCTGGCTCCTATGAAGGTGGATTACGATCGAGCACAGATGGTCCTCAGCC CTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAAGCAAATCG GGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCATCACCCCTC CCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTCATCCAGCA CCTACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTT CGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAAT CGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGA AGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGTGGTCAT GGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAACAGATAG CTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCACAGGGAC ATAAAAAGTGACTCCATTCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTTCTGTGC TCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGG TGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATG ATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTT ACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATGTTGG TGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTAGCAGGT CCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTGTAGGTG GCAAAGCTAGA
NOV48d, SNP13376535 of SEQ ID NO: 766 457 aa MWat513δ0.3kD CG5582δ-02, Protein Sequence SNP Pos: 63 SNP Change: Gin to Arg
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQ HSLLADTANRPKPMVDPSCITPIRLAPMK VDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTA SYLSSLSLSSSTYPPPSWGSSSDQQPSRVSHEQFRAALQLWSPGDPREYLA FIKIGEGSTGIVCIA TEKHTGKQVAVKKMDLRKQQRRELLFNEWIMRDYHHDNWDMYSSYLVGDELWWMEFLEGGALTDI VTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKS LVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVS SVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
NOV48e, SNPl 3382500 of SEQ ID NO: 767 1439 bp CG55828-02, DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1406
SNP Pos: 970 SNP Change: T to C
TCATCCACAGCCATCATATAAAGGTTTTGGCATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATAT
CTGGCCCGTCCAACTTTGAACACAGGGTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGC CTTCCCCAGCAGTGGCACAGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTC ATGCATCACACCCATCCAGCTGGCTCCTATGAAGGTGGATTACGATCGAGCACAGATGGTCCTCAGCC CTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAAGCAAATCG GGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCATCACCCCTC CCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTCATCCAGCA CCTACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTT CGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAAT CGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGA AGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGTGGTCAT GGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAACAGATAG CTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCACAGGGAC ATAAAAAGTGACTCCATCCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTTCTGTGC TCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGG TGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATG ATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTT ACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATGTTGG TGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTAGCAGGT CCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTGTAGGTG GCAAAGCTAGA
NOV4δe, SNP133δ2500 of SEQ ID NO: 768 457 aa M at 51352.3kD CG55δ2δ-02, Protein Sequence SNP Pos: 312 SNP Change: He to He
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQVfHSLLADTANRPKPMVDPSCITEIQLAPMK VDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTA SYLSSLSLSSSTYPPPSWGSSSDQQPSRVSHEQFRAALQLWSPGDPREYLANFIKIGEGSTGIVCIA TEKHTGKQVAVKKMDLRKQQRRELLFNEWIMRDYHHD WDMYSSYLVGDELWWMEFLEGGALTDI VTHTRMNEEQIATVCLSVLRALSYLH QGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKS LVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVS SVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH NOV48f, SNP 13375705 of SEQ ID NO: 769 1439 bp CG55δ2δ-02, DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1406
SNP Pos: 1375 SNP Change: C to T
TCATCCACAGCCATCATATAAAGGTTTTGGCATCATGTTTGGGAAGAAAAAGAAAAAGATTGAAATAT
CTGGCCCGTCCAACTTTGAACACAGGGTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGC CTTCCCCAGCAGTGGCACAGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTC ATGCATCACACCCATCCAGCTGGCTCCTATGAAGGTGGATTACGATCGAGCACAGATGGTCCTCAGCC CTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGTCAAAGCAAATCG GGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCCACCTTGTACCATCACCCCTC CCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTACCTGAGCTCCCTCAGCCTCTCATCCAGCA CCTACCCGCCGCCCAGCTGGGGCTCCTCCTCCGACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTT CGGGCGGCCCTGCAGCTGGTGGTCAGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAAT CGGGGAAGGCTCAACCGGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGA AGAAAATGGACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGGGTGGTCAT GGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATGAATGAAGAACAGATAG CTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCATAACCAAGGAGTGATTCACAGGGAC ATAAAAAGTGACTCCATTCTCCTGACAAGCGATGGCCGGATAAAGTTGTCTGATTTTGGTTTCTGTGC TCAAGTTTCCAAAGAGGTGCCGAAGAGGAAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGG TGATTTCTAGGCTACCTTATGGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATG ATTGATGGCGAGCCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTT ACCTCCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATGTTGG TGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTAAAACTAGCAGGT CCACCGTCTTGCATTGTCCCCCTCATGAGACAATACAGGCATCACTGAGCAGAGGATTCGTGTAGGTG GCAAAGCTAGA
NOV4δf, SNP13375705 of SEQ ID NO: 770 457 aa MW at 51352.3kD CG55δ2δ-02, Protein Sequence SNP Pos: 447 SNP Change: He to He
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQWHSLLADTANRPKPMVDPSCITPIQLAPMK VDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTA SYLSSLSLSSSTYPPPS GSSSDQQPSRVSHEQFRAALQLWSPGDPREYLANFIKIGEGSTGIVCIA TEKHTGKQVAVKKMDLRKQQRRELLF EWIMRDYHHD WDMYSSYLVGDELWWMEFLEGGALTDI VTHTRM EEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKS LVGTPY MAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVS SVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 4δB.
Table 48B. Comparison of the NOV48 protein sequences.
NOV48a MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQ HSLLADTANRPKPMVDPSCIT
NOV48b MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQWHSLLADTANRPKPMVDPSCIT
NOV48a PIQLAPMKVDYDRAQMVLSPPLSGSDTYPRGPAKLPQSQSKSGYSSSSHQYPSGYHKATL
NOV48b PIQLAPMKTIVRGNKPCKETSING-LLEDFDNISVTRSNSLRKESPPTPDQGASSHGPGH
NOV48a YHHPSLQSSSQYISTASYLSSLSLSSSTYPPPS GSSSDQQPSRVSHEQFRAALQLWSP
NOV48b AEENGFITFSQYSSESD- -TTADYTTEKYREKSLYGDDLDPYYRGSHAAKQNGHVMKMKH
NOV48a GDPREYLANFIKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLFNEWIMRDYH
NOV48b G EAYYSEVKPLKSDFARFSADYHSHLDSLSKPSEYS-DLK EYQRASSSSPLDYS NOV48a HDNWDMYS-SYLVGDEL WMEFLEGGALTDIVTHTRM EEQIATVCLSVLRALSYLHN
NOV48b FQFTPSRTAGTSGCSKESLAYSESE GPSLDDYDRRPKSS YLNQTSP
NOV48a QGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKSLVGTPY MAPEVISRLPYG
NOV48b QPTMRQRSRS GSG-LQEPMMPFGASAFKTHPQGHSYNSYTYPRLSEPTMCIP--
NOV48a TEVDI SLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLPPRVKDLHKVSSVLRGFLDLML
NOV48b -KVDYDPAQMVLSPPLSGSDTYPRGP- -AKLPQSQSKSGYSSSSHQYPSGYHKATLYHHP
NOV48a VREPS-QRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
NOV48b SLQSSSQYISTASYLSSLSLSSSIPAAQLGLLLRPAALQGVP
NOV48a (SEQ ID NO: 760)
NOV48b (SEQ ID NO: 762)
Further analysis ofthe NOV48a protein yielded the following properties shown in Table
4δC.
Table 48C. Protein Sequence Properties NOV48a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 5; neg.chg 1 H-region: length 7; peak value -2.19 PSG score: -6.59
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.22 possible cleavage site: between 44 and 45
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 2.54 (at 257) ALOM score: 2.54 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.66 Hyd Moment(95): 6.70 G content: 2 D/E content: 2 S/T content: 2 Score: -7.66
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: KKKK (5) at 4 pat4: KKKK (5) at 5 pat4: PKRK (4) at 336 pat7: PKRKSLV (5) at 336 bipartite: none content of basic residues: 11.2% NLS Score: 0.84
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) : 78 .3 % : nuclear
13 0 % • cytoplasmic
4 3 % mitochondrial
4 .3 % : peroxisomal
>> prediction for CG55828 - 02 is nuc (k= =23 )
A search ofthe NOV4δa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4δD.
Figure imgf000742_0001
In a BLAST search of public sequence databases, the NOV4δa protein was found to have homology to the proteins shown in the BLASTP data in Table 4δE.
73 δ
Figure imgf000743_0001
PFam analysis indicates that the NOV48a protein contains the domains shown in the Table 48F.
Figure imgf000743_0002
Example 49.
The NOV49 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 49A. Table 49A. NOV49 Sequence Analysis
NOV49a, CG55980-02 SEQ ID NO: 771 972 bp DNA Sequence ORF Start: ATG at 18 ORF Stop: TAA at 954
CTCATATCTCCCTCATTATGTCTGTTCTCAATAACTCCGAAGTCAAGCTTTTCCTTCTGATTGGGATC
CCAGGACTGGAACATGCCCACATTTGGTTCTCCATCCCCATTTGCCTCATGTACCTGCTTGCCATCAT GGGCAACTGCACCATTCTCTTTATTATAAAGACAGAGCCCTCGCTTCATGAGCCCATGTATTATTTCC TTGCCATGTTGGCTGTCTCTGACATGGGCCTGTCCCTCTCCTCCCTTCCTACCATGTTGAGGGTCTTC TTGTTCAATGCCATGGGAATTTCACCTAATGCCTGCTTTGCTCAAGAATTCTTCATTCATGGATTCAC TGTCATGGAATCCTCAGTACTTCTAATTATGTCTTTGGACCGCTTTCTTGCCATTCACAATCCCTTAA GATACAGTTCTATCCTCACTAGCAACAGGGTTGCTAAAATGGGACTTATTTTAGCCATTAGGAGCATT CTCTTAGTGATTCCATTTCCCTTCACCTTAAGGAGATTAAAATATTGTCAAAAGAATCTTCTTTCTCA CTCATACTGTCTTCATCAGGATACCATGAAGCTGGCCTGCTCTGACAACAAGACCAATGTCATCTATG GCTTCTTCATTGCTCTCTGTACTATGCTGGACTTGGCACTGATTGTTTTGTCTTATGTGCTGATCTTG AAGACTATACTCAGCATTGCATCTTTGGCAGAGAGGCTTAAGGCCCTAAATACCTGTGTCTCCCACAT CTGTGCTGTGCTCACCTTCTATGTGCCCATCATCACCCTGGCTGCCATGCATCACTTTGCCAAGCACA AAAGCCCTCTTGTTGTGATCCTTATTGCAGATATGTTCTTGTTGGTGCCGCCCCTTATGAACCCCATT GTGTACTGTGTAAAGACTCGACAAATCTGGGAGAAGATCTTGGGGAAGTTGCTTAATGTATGTGGGAG ATAAGAACTTGAACAATTAG
NOV49a, CG55980-02 SEQ ID NO: 772 312 aa MW at 35131. lkD Protein Sequence
MSVLNNSEVKLFLLIGIPGLEHAHIWFSIPICLMYLLAIMGNCTILFIIKTEPSLHEPMYYFLAMLAV SDMGLSLSSLPTMLRVFLFNAMGISPNACFAQEFFIHGFTVMESSVLLIMSLDRFLAIHNPLRYSSIL TSNRVAKMGLILAIRSILLVIPFPFTLRRLKYCQKNLLSHSYCLHQDTMKLACSDNKTNVIYGFFIAL CTMLDLALIVLSYVLILKTILSIASLAERLKALNTCVSHICAVLTFYVPIITLAAMHHFAKHKSPLVV ILIADMFLLVPPLMNPIVYCVKTRQIWEKILGKLLNVCGR
NOV49b, CG55980-01 SEQ ID NO: 773 1972 bp DNA Sequence ORF Start: ATG at 18 ORF Stop: TAA at 954
CTCATATCTCCCTCATTATGTCTGTTCTCAATAACTCCGAAGTCAAGCTTTTCCTTCTGATTGGGATC
CCAGGACTGGAACATGCCCACATTTGGTTCTCCATCCCCATTTGCCTCATGTACCTGCTTGCCATCAT GGGCAACTGCACCATTCTCTTTATTATAAAGACAGAGCCCTCGCTTCATGAGCCCATGTATTATTTCC TTGCCATGTTGGCTGTCTCTGACATGGGCCTGTCCCTCTCCTCCCTTCCTACCATGTTGAGGGTCTTC TTGTTCAATGCCATGGGAATTTCACCTAATGCCTGCTTTGCTCAAGAATTCTTCATTCATGGATTCAC TGTCATGGAATCCTCAGTACTTCTAATTATGTCTTTGGACCGCTTTCTTGCCATTCACAATCCCTTAA GATACAGTTCTATCCTCACTAGCAACAGGGTTGCTAAAATGGGACTTATTTTAGCCATTAGGAGCATT CTCTTAGTGATTCCATTTCCCTTCACCTTAAGGAGATTAAAATATTGTCAAAAGAATCTTCTTTCTCA CTCATACTGTCTTCATCAGGATACCATGAAGCTGGCCTGCTCTGACAACAAGACCAATGTCATCTATG GCTTCTTCATTGCTCTCTGTACTATGCTGGACTTGGCACTGATTGTTTTGTCTTATGTGCTGATCTTG AAGACTATACTCAGCATTGCATCTTTGGCAGAGAGGCTTAAGGCCCTAAATACCTGTGTCTCCCACAT CTGTGCTGTGCTCACCTTCTATGTGCCCATCATCACCCTGGCTGCCATGCATCACTTTGCCAAGCACA AAAGCCCTCTTGTTGTGATCCTTATTGCAGATATGTTCTTGTTGGTGCCGCCCCTTATGAACCCCATT GTGTACTGTGTAAAGACTCGACAAATCTGGGAGAAGATCTTGGGGAAGTTGCTTAATGTATGTGGGAG ATAAGAACTTGAACAATTAG
NOV49b, CG559δ0-01 SEQ ID NO: 774 312 aa MW at 35131. lkD Protein Sequence
MSVLNNSEVKLFLLIGIPGLEHAHIWFSIPICLMYLLAIMGNCTILFIIKTEPSLHEPMYYFLAMLAV SDMGLSLSSLPTMLRVFLFNAMGISPNACFAQEFFIHGFTVMESSVLLIMSLDRFLAIHNPLRYSSIL TSNRVAKMGLILAIRSILLVIPFPFTLRRLKYCQKNLLSHSYCLHQDTMKLACSDNKTNVIYGFFIAL CTMLDLALIVLSYVLILI ΓILSIASLAERLKALNTCVSHICAVLTFYVPI ITLAAMHHFAKHKSPLW ILIADMFLLVPPLMNPIVYCVKTRQI EKILGKLLNVCGR
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 49B. Table 49B. Comparison of the NOV49 protein sequences.
N0V49a MSVLNNSEVKLFLLIGIPGLEHAHIWFSIPICLMYLLAIMGNCTILFIIKTEPSLHEPMY
NOV49b MSVLNNSEVKLFLLIGIPGLEHAHI FSIPICLMYLLAIMGNCTILFIIKTEPSLHEPMY
NOV49a YFLAMLAVSDMGLSLSSLPTMLRVFLFNAMGISPNACFAQEFFIHGFTVMESSVLLIMSL
NOV49b YFLAMLAVSDMGLSLSSLPTMLRVFLFNAMGISPNACFAQEFFIHGFTVMESSVLLIMSL
NOV49a DRFLAIHNPLRYSSILTSNRVAKMGLILAIRSILLVIPFPFTLRRLKYCQKNLLSHSYCL
NOV49b DRFLAIHNPLRYSSILTSNRVAKMGLILAIRSILLVIPFPFTLRRLKYCQKNLLSHSYCL
NOV49a HQDTMKLACSDNKTNVIYGFFIALCTMLDLALIVLSYVLILKTILSIASLAERLKALNTC
NOV49b HQDTMKLACSDNKTNVIYGFFIALCTMLDLALIVLSYVLILKTILSIASLAERLKALNTC
NOV49a VSHICAVLTFYVPIITLAAMHHFAKHKSPLWILIADMFLLVPPLMNPIVYCVKTRQIWE
NOV49b VSHICAVLTFYVPIITLAAMHHFAKHKSPLWILIADMFLLVPPLMNPIVYCVKTRQIWE
NOV49a KILGKLLNVCGR
NOV49b KILGKLLNVCGR
NOV49a (SEQ ID NO: 772)
NOV49b (SEQ ID NO: 774)
Further analysis of the NOV49a protein yielded the following properties shown in Table 49C.
Table 49C. Protein Sequence Properties NOV49a
SignalP analysis: Cleavage site between residues 42 and 43
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos . chg 1; neg.chg 1 H-region: length 10; peak value 10.00 PSG score: 5.60
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.28 possible cleavage site: between 23 and 24
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5: 8
INTEGRAL Likelihood -6.00 Transmembrane 33 - 49 INTEGRAL Likelihood 0.32 Transmembrane 62 - 78 INTEGRAL Likelihood -0.48 Transmembrane 102 - 118 INTEGRAL Likelihood -5.63 Transmembrane 141 - 157 INTEGRAL Likelihood -7.59 Transmembrane 199 - 215 INTEGRAL Likelihood 0.42 Transmembrane 218 - 234 INTEGRAL Likelihood = -5.79 Transmembrane 244 - 260
INTEGRAL Likelihood = -8.17 Transmembrane 270 - 286
PERIPHERAL Likelihood = 2.12 (at 11)
ALOM score: -8.17 (number of TMSs: 8)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 40 Charge difference: -1.5 C(-0.5) - N( 1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75) : 0.68 Hyd Moment(95): 3.43 G content: 2 D/E content : 2 S/T content : 2 Score: -8.46
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 7.7% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LKYCQKNLLSHSYCLHQDTMKL at 166 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum
22.2 %: mitochondrial
11.1 %: vesicles of secretory system
>> prediction for CG55980-02 is end (k=9)
A search ofthe NOV49a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 49D.
Figure imgf000748_0001
In a BLAST search of public sequence databases, the NOV49a protein was found to have homology to the proteins shown in the BLASTP data in Table 49E.
Figure imgf000749_0001
PFam analysis indicates that the NOV49a protein contains the domains shown in the Table 49F.
Figure imgf000749_0002
Example 50.
The NOV50 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 50A. Table 50A. NOV50 Sequence Analysis
NOV50a, CG55988-03 SEQ ID NO: 775 1630 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1528
ATGGGGTCCCGCCACTTCGAGGGGATTTATGACCACGTGGGGCACTTCGGCAGATTCCAGAGAGTCCT CTATTTCATATGTGCCTTCCAGAACATCTCTTGTGGTATTCACTACTTGGCTTCTGTGTTCATGGGAG TCACCCCTCATCATGTCTGCAGGCCCCCAGGCAATGTGAGTCAGGTTGTTTTCCATAATCACTCTAAT TGGAGTTTGGAGGACACCGGGGCCCTGTTGTCTTCAGGCCAGAAAGATTATGTTACGGTGCAGTTGCA GAATGGTGAGATCTGGGAGCTCTCAAGGTGTAGCAGGAATAAGAGGGAGAACACATCGAGTTTGGGCT ATGAATACACTGGCAGTAAGAAAGAGTTTCCTTGTGTGGATGGCTACATATATGACCAGAACACATGG AAAAGCACTGCGGTGACCCAGTGGAACCTGGTCTGTGACCGAAAATGGCTTGCAATGCTGATCCAGCC CCTATTTATGTTTGGAGTCCTACTGGGATCGGTGACTTTTGGCTACTTTTCTGACAGGCTAGGACGCC GGGTGGTCTTGTGGGCCACAAGCAGTAGCATGTTTTTGTTTGGAATAGCAGCGGCGTTTGCAGTTGAT TATTACACCTTCATGGCTGCTCGCTTTTTTCTTGCCATGGTTGCAAGTGGCTATCTTGTGGTGGGGTT TGTCTATGTGATGGAATTCATTGGCATGAAGTCTCGGACATGGGCGTCTGTCCATTTGCATTCCTTTT TTGCAGTTGGAACCCTGCTGGTGGCTTTGACAGGATACTTGGTCAGGACCTGGTGGCTTTACCAGATG ATCCTCTCCACAGTGACTGTCCCCTTTATCCTGTGCTGTTGGGTGCTCCCAGAGACACCTTTTTGGCT TCTCTCAGAGGGACGATATGAAGAAGCACAAAAAATAGTTGACATCATGGCCAAGTGGAACAGGGCAA GCTCCTGTAAACTGTCAGAACTTTTATCACTGGACCTACAAGGTCCTGTTAGTAATAGCCCCACTGAA GTTCAGAAGCACAACCTATCATATCTGTTTTATAACTGGAGCATTACGAAAAGGACACTTACCGTTTG GCTAATCTGGTTCACTGGAAGTTTGGGATTCTACTCGTTTTCCTTGAATTCTGTTAACTTAGGAGGCA ATGAATACTTAAACCTCTTCCTCCTGGGTGTAGTGGAAATTCCCGCCTACACCTTCGTGTGCATCGCC ACGGACAAGGTCGGGAGGAGAACAGTCCTGGCCTACTCTCTTTTCTGCAGTGCACTGGCCTGTGGTGT CGTTATGGTGATCCCCCAGATCGCTGGCTGTGGGAAGCGGCAGCATGGTGTGTCGCCTGGCCAGCATC CTGGCGCCGTTCTCTGTGGACCTCAGCAGCATTTGGATCTTCATACCACAGTTGTTTGTTGGGACTAT GGCCCTCCTGAGTGGAGTGTTAACACTAAAGCTTCCAGAAACCCTTGGGAAACGGCTAGCAACTACTT GGGAGGAGGCTGCAAAACTGGAGTCAGAGAATGAAAGCAAGTCAAGCAAATTACTTCTCACAACTAAT
AATAGTGGGCTGGAAAAAACGGAAGCGATTACCCCCAGGGATTCTGGTCTTGGTGAATAAATGTGC
NOV50a, CG5598δ-03 SEQ ID NO: 776 509 aa MW at 57300.6kD Protein Sequence
MGSRHFEGIYDHVGHFGRFQRVLYFICAFQNISCGIHYLASVFMGVTPHHVCRPPG VSQWFHNHSN WSLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNKRENTSSLGYEYTGSKKEFPCVDGYIYDQNT KSTAVTQWNLVCDRK LAMLIQPLFMFGVLLGSVTFGYFSDRLGRRWLWATSSSMFLFGIAAAFAVD YYTFMAARFFLAMVASGYLWGFVYVMEFIGMKSRTWASVHLHSFFAVGTLLVALTGYLVRT LYQM ILSTVTVPFILCC VLPETPFWLLSEGRYEEAQKIVDIMAKVJNRASSCKLSELLSLDLQGPVSNSPTE VQKHNLSYLFYNWSITKRTLTVWLIWFTGSLGFYSFSLNSVNLGGNEYLNLFLLGWEIPAYTFVCIA TDKVGRRTVLAYSLFCSALACGWMVIPQIAGCGKRQHGVSPGQHPGAVLCGPQQHLDLHTTWCWDY GPPEWSVNTKASRNPWETASNYLGGGCKTGVRE
NOV50b, CG559δδ-04 SEQ ID NO: 777 1599 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 1546
ATGGGGTCCCGCCACTTCGAGGGGATTTATGACCACGTGGGGCACTTCGGCAGATTCCAGAGAGTCCT CTATTTCATATGTGCCTTCCAGAACATCTCTTGTGGTATTCACTACTTGGCTTCTGTGTTCATGGGAG TCACCCCTCATCATGTCTGCAGGCCCCCAGGCAATGTGAGTCAGGTTGTTTTCCATAATCACTCTAAT TGGAGTTTGGAGGACACCGGGGCCCTGTTGTCTTCAGGCCAGAAAGATTATGTTACGGTGCAGTTGCA GAATGGTGAGATCTGGGAGCTCTCAAGGTGTAGCAGGAATAAGAGGGAGAACACATCGAGTTTGGGCT ATGAATACACTGGCAGTAAGAAAGAGTTTCCTTGTGTGGATGGCTACATATATGACCAGAACACATGG AAAAGCACTGCGGTGACCCAGTGGAACCTGGTCTGTGACCGAAAATGGCTTGCAATGCTGATCCAGCC CCTATTTATGTTTGGAGTCCTACTGGGATCGGTGACTTTTGGCTACTTTTCTGACAGGCTAGGACGCC GGGTGGTCTTGTGGGCCACAAGCAGTAGCATGTTTTTGTTTGGAATAGCAGCGGCGTTTGCAGTTGAT TATTACACCTTCATGGCTGCTCGCTTTTTTCTTGCCATGGTTGCAAGTGGCTATCTTGTGGTGGGGTT TGTCTATGTGATGGAATTCATTGGCATGAAGTCTCGGACATGGGCGTCTGTCCATTTGCATTCCTTTT TTGCAGTTGGAACCCTGCTGGTGGCTTTGACAGGATACTTGGTCAGGACCTGGTGGCTTTACCAGATG ATCCTCTCCACAGTGACTGTCCCCTTTATCCTGTGCTGTTGGGTGCTCCCAGAGACACCTTTTTGGCT TCTCTCAGAGGGACGATATGAAGAAGCACAAAAAATAGTTGACATCATGGCCAAGTGGAACAGGGCAA GCTCCTGTAAACTGTCAGAACTTTTATCACTGGACCTACAAGGTCCTGTTAGTAATAGCCCCACTGAA
Figure imgf000751_0001
GRRWLWATSSSMFLFGIAAAFAVDYYTFMAARFFLAMVASGYLWGFVYVMEFIGMKSRTWASVHLH SFFAVGTLLVALTGYLVRT WLYQMILSTVTVPFILCCWVLPETPFWLLSEGRYEEAQKIVυiMAK N RASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYNWSITKRTLTVWLI FTGSLGFYSFSLNSVNL GGNEYLNLFLLGVVEIPAYTFVCIAMDKVGRRTVLAYSLFCSALACGVVMVIPQKHYILGVVTAMVGK FAIGAAFGLIYLYTAELYPTIVRSLAVGSGSMVCRLASILAPFSVDLSSIWIFIPQLFVGTMALLSGV LTLKLPETLGKRLATTWEEAAKLESENESKSSKLLLTT SGLEKTEAITPRDSGLGE
NOV50d, CG55988-02 SEQ ID NO: 781 1666 bp DNA Sequence ORF Start: ATG at 76 ORF Stop: TAA at 1654
TTCCAGAGAGTCCTCTATTTCATATGTGCCTTCCAGAACATCTCTTGTGGTATTCACTACTTGGCTTC
TGTGTTCATGGGAGTCACCCCTCATCATGTCTGCAGGCCCCCAGGCAATGTGAGTCAGGTTGTTTTCC
ATAATCACTCTAATTGGAGTTTGGAGGACACCGGGGCCCTGTTGTCTTCAGGCCAGAAAGATTATGTT ACGGTGCAGTTGCAGAATGGTGAGATCTGGGAGCTCTCAAGGTGTAGCAGGAATAAGAGGGAGAACAC ATCGAGTTTGGGCTATGAATACACTGGCAGTAAGAAAGAGTTTCCTTGTGTGGATGGCTACATATATG ACCAGAACACATGGAAAAGCACTGCGGTGACCCAGTGGAACCTGGTCTGTGACCGAAAATGGCTTGCA ATGCTGATCCAGCCCCTATTTATGTTTGGAGTCCTACTGGGATCGGTGACTTTTGGCTACTTTTCTGA CAGGCTTTTTTGCCTATATGTGATTTGCAATGGGGTCAGACTCCTCAATAGTTATAAATGTGACCTTG AATATAAATCCCTATTATTTGTTTTTCAGGTTGCAAGTGGCTATCTTGTGGTGGGGTTTGTCTATGTG ATGGAATTCATTGGCATGAAGTCTCGGACATGGGCGTCTGTCCATTTGCATTCCTTTTTTGCAGTTGG AACCCTGCTGGTGGCTTTGACAGGATACTTGGTCAGGACCTGGTGGCTTTACCAGATGATCCTCTCCA CAGTGACTGTCCCCTTTATCCTGTGCTGTTGGGTGCTCCCAGAGACACCTTTTTGGCTTCTCTCAGAG GGACGATATGAAGAAGCACAAAAAATAGTTGACATCATGGCCAAGTGGAACAGGGCAAGCTCCTGTAA ACTGTCAGAACTTTTATCACTGGACCTACAAGGTCCTGTTAGTAATAGCCCCACTGAAGTTCAGAAGC ACAACCTATCATATCTGTTTTATAACTGGAGCATTACGAAAAGGACACTTACCGT TGGCTAATCTGG TTCACTGGAAGTTTGGGATTCTACTCGTTTTCCTTGAATTCTGTTAACTTAGGAGGCAATGAATACTT AAACCTCTTCCTCACAGGTGTAGTGGAAATTCCCGCCTACACCTTCGTGTGCATCGCCATGGACAAGG TCGGGAGGAGAACAGTCCTGGCCTACTCTCTTTTCTGCAGTGCACTGGCCTGTGGTGTCGTTATGGTG ATCCCCCAGGTGAGTTATCTTCTGGGTGTGGTGACAGCTATGGTTGGAAAATTTGCCATCGGGGCAGC ATTTGGCCTCATTTATCTTTATACAGCTGAGCTGTATCCAACCATTGTAAGGTCGCTGGCTGTGGGAA GCGGCAGCATGGTGTGTCGCCTGGCCAGCATCCTGGCGCCGTTCTCTGTGGACCTCAGCAGCATTTGG ATCTTCATACCACAGTTGTTTGTTGGGACTATGGCCCTCCTGAGTGGAGTGTTAACACTAAAGCTTCC AGAAACCCTTGGGAAACGGCTAGCAACTACTTGGGAGGAGGCTGCAAAACTGGAGTCAGAGAATGAAA GCAAGTCAAGCAAATTACTTCTCACAACTAATAATAGTGGGCTGGAAAAAACGGAAGCGATTACCCCC AGGGATTCTGGTCTTGGTGAATAAATGTGCCATG
NOV50d, CG5598δ-02 SEQ ID NO: 782 526 aa MW at 58820.δkD Protein Sequence
MGVTPHHVCRPPGNVSQWFHNHSN SLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNKRENTSS LGYEYTGSKKEFPCVDGYIYDQNT KSTAVTQ NLVCDRK LAMLIQPLF FGVLLGSVTFGYFSDRL FCLYVICNGVRLLNSYKCDLEYKSLLFVFQVASGYLWGFVYVMEFIGMKSRTWASVHLHSFFAVGTL LVALTGYLVRT WLYQMILSTVTVPFILCCWVLPETPFWLLSEGRYEEAQKIVDIMAKWNRASSCKLS ELLSLDLQGPVSNSPTEVQKHNLSYLFYNWSITKRTLTVWLIWFTGSLGFYSFSLNSVNLGGNEYLNL FLTGWEIPAYTFVCIAMDKVGRRTVLAYSLFCSALACGWMVIPQVSYLLGWTAMVGKFAIGAAFG LIYLYTAELYPTIVRSLAVGSGSMVCRLASILAPFSVDLSSI IFIPQLFVGT ALLSGVLTLKLPET LGKRLATTWEEAAKLESENESKSSKLLLTTNNSGLEKTEAITPRDSGLGE
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 50B.
Table 50B. Comparison of the NOV50 protein sequences.
NOV50a MGSRHFEGIYDHVGHFGRFQRVLYFICAFQNISCGIHYLASVFMGVTPHHVCRPPG VSQ
NOV50b MGSRHFEGIYDHVGHFGRFQRVLYFICAFQNISCGIHYLASVFMGVTPHHVCRPPG VSQ
NOV5 Oc MGVTPHHVCRPPGNVSQ
NOV50d MGVTPHHVCRPPGNVSQ
NOV50a WFHNHSN SLEDTGALLSSGQKDYVTVQLQNGEI ELSRCSRNKRENTSSLGYEYTGSK NOV50b WFHNHSNWSLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNKRENTSSLGYEYTGSK
NOV50C WFHNHSNWSLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNKRENTSSLGYEYTGSK
NOV50d WFHNHSNWSLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNICRENTSSLGYEYTGSK
NOV5Oa KEFPCVDGYIYDQNTWKSTAVTQWNLVCDRKWLAMLIQPLFMFGVLLGSVTFGYFSDRLG
NOV5Ob KEFPCVDGYIYDQNTWKSTAVTQWNLVCDRKWLAMLIQPLFMFGVLLGSVTFGYFSDRLG
NOV5Oc KEFPCVDGYIYDQNTWKSTAVTQWNLVCDRKWLAMLIQPLFMFGVLLGSVTFGYFSDRLG
NOV5Od KEFPCVDGYIYDQNTWKSTAVTQWNLVCDRKWLAMLIQPLFMFGVLLGSVTFGYFSDRLF
NOV5Oa RRWL ATSSSMFLFGIAAAFAVDYYTFMAARFFLAMVASGYLWGFVYVMEFIGMKSRT
NOV5Ob RRWL ATSSSMFLFGIAAAFAVDYYTFMAARFFLAMVASGYLWGFVYVMEFIGMKSRT
NOV50C RRWLWATSSSMFLFGIAAAFAVDYYTFMAARFFLAMVASGYLWGFVYVMEFIGMKSRT
NOV50d CLYVICN GVRLLNSYKCDLEYKSLLFVFQVASGYLWGFVYVMEFIGMKSRT
NOV5Oa ASVHLHSFFAVGTLLVALTGYLVRTW LYQMILSTVTVPFILCC VLPETPF LLSEGR
NOV50b WASVHLHSFFAVGTLLVALTGYLVRT WLYQMILSTVTVPFILCC VLPETPF LLSEGR
NOV5Oc ASVHLHSFFAVGTLLVALTGYLVRT WLYQMILSTVTVPFILCC VLPETPFWLLSEGR
NOV5Od ASVHLHSFFAVGTLLVALTGYLVRT LYQMILSTVTVPFILCCWVLPETPFWLLSEGR
NOV5Oa YEEAQKIVDIMAKWNRASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYN SITKRTL
NOVSOb YEEAQKIVDIMAKWNRASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYN SITKRTL
NOV50C YEEAQKIVDIMAK NRASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYNWSITKRTL
NOV5Od YEEAQKIVDIMAKWNRASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYN SITKRTL
NOV5Oa TVWLIWFTGSLGFYSFSLNSV LGGNEYLNLFLLGWEIPAYTFVCIATDKVGRRTVLAY
NOV5Ob TV LI FTGSLGFYSFSLNSV LGGNEYLNLFLLGWEIPAYTFVCIATDKVGRRTVLAY
NOV50c TVWLIWFTGSLGFYSFSLNSVNLGGNEYLNLFLLGWEIPAYTFVCIAMDKVGRRTVLAY
NOV50d TWLIWFTGSLGFYSFSLNSVNLGGNEYLNLFLTGVVEIPAYTFVCIAMDKVGRRTVLAY
NOV50a SLFCSALACGWMVIPQI AGCGKRQHGVSPG QHP G-
NOV50b SLFCSALACGWMVIPQKHYILGWTAMVGKFAIGAAFGLIYLYTAELYPTIVRSLAVGS
NOV5Oc SLFCSALACGWMVIPQKHYILGWTAMVGKFAIGAAFGLIYLYTAELYPTIVRSLAVGS
NOV5Od SLFCSALACGWMVIPQVSYLLGWTAMVGKFAIGAAFGLIYLYTAELYPTIVRSLAVGS
NOV50a -AVLCGPQQHLDLHTTWC- -WDYGP PE WSV T
NOV50b GSMVCRLASILAPFSVDLSSIWIFIPQLLGQHLQE
NOV50C GSMVCRLASILAPFSVDLSSIWIFIPQLFVGTMALLSGVLTLKLPETLGKRLATTWEEAA
NOV50d GSMVCRLASILAPFSVDLSSIWIFIPQLFVGTMALLSGVLTLKLPETLGKRLATTWEEAA
NOV5Oa KASRNPWETASNYLGGGCKTGVRE
NOV50b
NOV50c KLESENESKSSKLLLTTNNSGLEKTEAITPRDSGLGE
NOV50d KLESENESKSSKLLLTTNNSGLEKTEAITPRDSGLGE
NOV50a (SEQ ID NO 776)
NOV50b (SEQ ID NO 778)
NOV50C (SEQ ID NO 780)
NOV50d (SEQ ID NO 782)
Further analysis ofthe NOV50a protein yielded the following properties shown in Table 50C. Table 50C. Protein Sequence Properties NOV50a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 1; neg.chg 2 H-region: length 6; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.51 possible cleavage site: between 34 and 35
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 7
INTEGRAL Likelihood -3, .03 Transmembrane 154 - 170
INTEGRAL Likelihood -1 .12 Transmembrane 183 - 199
INTEGRAL Likelihood -4. .57 Transmembrane 214 - 230
INTEGRAL Likelihood -3 .08 Transmembrane 248 - 264
INTEGRAL Likelihood -5. .89 Transmembrane 272 - 288
INTEGRAL Likelihood -4. .51 Transmembrane 391 - 407
INTEGRAL Likelihood -5. .10 Transmembrane 419 - 435
PERIPHERAL Likelihood 2. .81 (at 360)
ALOM score : -5.89 (number of TMSs: 7)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 161 Charge difference: 0.0 C( 2.0) - N( 2.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 7.38 Hyd Moment(95): 9.73 G content: 2 D/E content: 2 S/T content: 1 Score: -6.19
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 14 SRH | FE
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 7.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: GSRH none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LVCDRKWLAMLIQPLFMFGVLL at 146 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
77.8 %: endoplasmic reticulum 22.2 %: mitochondrial
>> prediction for CG55988-03 is end (k=9) A search ofthe NOV50a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 50D.
Figure imgf000756_0001
In a BLAST search of public sequence databases, the NOV50a protein was found to have homology to the proteins shown in the BLASTP data in Table 50E.
Figure imgf000757_0001
PFam analysis indicates that the NOV50a protein contains the domains shown in the Table 50F.
Figure imgf000757_0002
Example 51.
The NOV51 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 51 A.
Figure imgf000757_0003
CGAGGGCTGGTGGACCGGGCAGCTGAACCAGCGGGTGGGCATCTTCCCCAGCAACTACGTGACCCCGC GCAGCGCCTTCTCCAGCCGCTGCCAGCCCGGCGGCGAAATTGATTTTGCGGAGCTCACCTTGGAAGAG ATTATTGGCATCGGGGGCTTTGGGAAGGTCTATCGTGCTTTCTGGATAGGGGATGAGGTTGCTGTGAA AGCAGCTCGCCACGACCCTGATGAGGACATCAGCCAGACCATAGAGAATGTTCGCCAAGAGGCCAAGC TCTTCGCCATGCTGAAGCACCCCAACATCATTGCCCTAAGAGGGGTATGTCTGAAGGAGCCCAACCTC TGCTTGGTCATGGAGTTTGCTCGTGGAGGACCTTTGAATAGAGTGTTATCTGGGAAAAGGATTCCCCC AGACATCCTGGTGAATTGGGCTGTGCAGATTGCCAGAGGGATGAACTACTTACATGATGAGGCAATTG TTCCCATCATCCACCGCGACCTTAAGTCCAGCAACGTATTGATCCTCCAGAAGGTGGAGAATGGAGAC CTGAGCAACAAGATTCTGAAGATCACTGATTTTGGCCTGGCTCGGGAATGGCACCGAACCACCAAGAT GAGTGCGGCAGGGACGTATGCTTGGATGGCACCCGAAGTCATCCGGGCCTCCATGTTTTCCAAAGGCA GTGATGTGTGGAGCTATGGGGTGCTACTTTGGGAGTTGCTGACTGGTGAGGTGCCCTTTCGAGGCATT GATGGCTTAGCAGTCGCTTATGGAGTGGCCATGAACAAACTCGCCCTTCCTATTCCTTCTACGTGCCC AGAACCTTTTGCCAAACTCATGGAAGACTGCTGGAATCCTGATCCCCACTCACGACCATCTTTCACGA ATATCCTGGACCAGCTAACCACCATAGAGGAGTCTGGTTTCTTTGAAATGCCCAAGGACTCCTTCCAC TGCCTGCAGGACAACTGGAAACACGAGATTCAGGAGATGTTTGACCAACTCAGGGCCAAAGAAAAGGA ACTTCGCACCTGGGAGGAGGAGCTGACGCGGGCTGCACTGCAGCAGAAGAACCAGGAGGAACTGCTGC GGCGTCGGGAGCAGGAGCTGGCCGAGCGGGAGATTGACATCCTGGAACGGGAGCTCAACATCATCATC CACCAGCTGTGCCAGGAGAAGCCCCGGGTGAAGAAACGCAAGGGCAAGTTCAGGAAGAGCCGGCTGAA GCTCAAGGATGGCAACCGCATCAGCCTCCCTTCTGGTTTCCAGCACAAGTTCACGGTGCAGGCCTCCC CTACCATGGATAAAAGGAAGAGTCTTATCAACAGCCGCTCCAGTCCTCCTGCAAGCCCCACCATCATT CCTCGCCTTCGAGCCATCCAGTGTGAGACTGTTTCCCAAATTAGCTGGGGCCAGAACACACAGGGGCA CCTGTCCGAAAGCAGCAAAACCTGGGGCAGGAGCTCAGTCGTCCCAAAGGAGGAAGGGGAGGAGGAGG AGAAGAGGGCCCCAAAGAAGAAGGGACGGACGTGGGGGCCAGGGACGCTTGGTCAGAAGGAGCTTGCC TCGGGAGATGAACTCAAGTCCCTGGTAGATGGATATAAGCAGTGGTCGTCCAGTGCCCCCAACCTGGT GAAGGGCCCAAGGAGTACCCCGGCCCTGCCAGGGTTCACCAGCCTTATGGAGATGGAGGATGAGGACA GTGAAGGCCCAGGGAGTGGAGAGAGTCGCCTACAGCATTCACCCAGCCAGTCCTACCTCTGTATCCCA TTCCCTCGTGGAGAGCCCACCCCAGTCAACTCGGCCACGAGTACCCCTCAGCTGACGCCAACCAACAG CCTCAAGCGGGGCGGTGCCCACCACCGCCGCTGCGAGGTGGCTCTGCTCGGCTGTGGGGCTGTTCTGG CAGCCACAGGCCTAGGGTTTGACTTGCTGGAAGCTGGCAAGTGCCAGCTGCTTCCCCTGGAGGAGCCT GAGCCACCAGCCCGGGAGGAGAAGAAAAGACGGGAGGGTCTTTTTCAGAGGTCCAGCCGTCCTCGTCG GAGCACCAGCCCCCCATCCCGAAAGCTTTTCAAGAAGGAGGAGCCCATGCTGTTGCTAGGAGACCCCT CTGCCTCCCTGACGCTGCTCTCCCTCTCCTCCATCTCCGAGTGCAACTCCACACGCTCCCTGCTGCAG TCCGACAGCGATGAAATTGTCGTGTATGAGATGCCAGTCAGCCCAGTCGAGGCCCCTCCCCTGAGTCC ATGTACCCACAACCCCCTGGTCAATGTCCGAGTAGAGCGCTTCAAACGAGATCCTAACCAATCTCTGA CTCCCACCCATGTCACCCTCACCACCCCCTCGCAGCCCAGCAGTCACCGGCGGACTCCTTCTGATGGG GCCCTTAAGCCAGAGACTCTCCTAGCCAGCAGGAGCCCCAGTCCCAGCCGAGACCCAGGTGAATTCCC CCGTCTCCCTGACCCCAATGTGGTCTTCCCCCCAACCCCAAGGCGCTGGAACACTCAGCAGGACTCTA CCTTGGAGAGACCCAAGACTCTGGAGTTTCTGCCTCGGCCGCGTCCTTCTGCCAACCGGCAACGGCTG GACCCTTGGTGGTTTGTGTCCCCCAGCCATGCCCGCAGCACCTCCCCAGCCAACAGCTCCAGCACAGA GACGCCCGGGCCGCTGCCCCCGACTGAGCGGACGCTCCTGGACCTGGATGCAGAGGGGCAGAGTCAGG ACAGCACCGTGCCGCTGTGCAGAGCGGAACTGAACACACACAGGCCTGCCCCTTATGAGATCCAGCAG GAGTTCTGGTCTTAGCACGAAAAGGATTGGGG
NOV51a, CG56071-01 SEQ ID NO: 784 1024 aa IMW at 113682. lkD Protein Sequence
MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPY TAVFEYEAAGE DELTLRLGDWEVLSKDSQVSGDEG WTGQLNQRVGIFPSNYVTPRSAFSSRCQPGGEIDFAELTLEE IIGIGGFGKVYRAF IGDEVAVKAARHDPDEDISQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNL CLVMEFARGGPLNRVLSGKRIPPDILVNWAVQIARGMNYLHDEAIVPIIHRDLKSSNVLILQKVENGD LSNKILKITDFGLARE HRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLL ELLTGEVPFRGI DGLAVAYGVAMNKLALPIPSTCPEPFAKLMEDC NPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFH CLQDN KHEIQEMFDQLRAKEKELRTWEEELTRAALQQKNQEELLRRREQELAEREIDILERELNIII HQLCQEKPRVKKRKGKFRKSRLKLKDGNRISLPSGFQHKFTVQASPTMDKRKSLINSRSSPPASPTII PRLRAIQCETVSQISWGQNTQGHLSESSKTWGRSSWPKEEGEEEEKRAPKKKGRTWGPGTLGQKELA SGDELKSLVDGYKQWSSSAPNLVKGPRSTPALPGFTSLMEMEDEDSEGPGSGESRLQHSPSQSYLCIP FPRGEPTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLGCGAVLAATGLGFDLLEAGKCQLLPLEEP EPPAREEKKRREGLFQRSSRPRRSTSPPSRKLFKKEEPMLLLGDPSASLTLLSLSSISECNSTRSLLQ SDSDEIWYEMPVSPVEAPPLSPCTHNPLVNVRVERFKRDPNQSLTPTHVTLTTPSQPSSHRRTPSDG ALKPETLLASRSPSPSRDPGEFPRLPDPNWFPPTPRR NTQQDSTLERPKTLEFLPRPRPSANRQRL DP FVSPSHARSTSPANSSSTETPGPLPPTERTLLDLDAEGQSQDSTVPLCRAELNTHRPAPYEIQQ EF S
NOV51b, 2740δ2270 SEQ ID NO: 7δ5 δ07 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
ACCGGATCCCTCACCTTGGAAGAGATTATTGGCATCGGGGGCTTTGGGAAGGTCTATCGTGCTTTCTG GATAGGGGATGAGGTTGCTGTGAAAGCAGCTCGCCACGACCCTGATGAGGACATCAGCCAGACCATAG AGAATGTTCGCCAAGAGGCCAAGCTCTTCGCCATGCTGAAGCACCCCAACATCATTGCCCTAAGAGGG GTATGTCTGAAGGAGCCCAACCTCTGCTTGGTCATGGAGTTTGCTCGTGGAGGACCTTTGAATAGAGT GTTATCTGGGAAAAGGATTCCCCCAGACATCCTGGTGAATTGGGCTGTGCAGATTGCCAGAGGGATGA ACTACTTACATGATGAGGCAATTGTTCCCATCATCCACCGCGACCTTAAGTCCAGCAACATATTGATC CTCCAGAAGGTGGAGAATGGAGACCTGAGCAACAAGATTCTGAAGATCACTGATTTTGGCCTGGCTCG GGAATGGCACCGAACCACCAAGATGAGTGCGGCAGGGACGTATGCTTGGATGGCACCCGAAGTCATCC GGGCCTCCATGTTTTCCAAAGGCAGTGATGTGTGGAGCTATGGGGTGCTACTTTGGGAGTTGCTGACT GGTGAGGTGCCCTTTCGAGGCATTGATGGCTTAGCAGTCGCTTATGGAGTGGCCATGAACAAACTCGC CCTTCCTATTCCTTCTACGTGCCCAGAACCTTTTGCCAAACTCATGGAAGACTGCTGGAATCCTGATC CCCACTCACGACCATCTTTCACGAATATCCTGGACCAGCTAACCACCATACTCGAGGGC
NOV51b, 2740δ2270 SEQ ID NO: 7δ6 269 aa MW at 29δ61.3kD Protein Sequence
TGSLTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDEDISQTIENVRQEAKLFAMLKHPNIIALRG VCLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVN AVQIARGMNYLHDEAIVPIIHRDLKSSNILI LQKVENGDLSNKILKITDFGLARE HRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLLWELLT GEVPFRGIDGLAVAYGVAMNKLALPIPSTCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTILEG
NOV51c, SNP13376041 of SEQ ID NO: 7δ7 3092 bp CG56071-01, DNA Sequence ORF Start: ATG at 1 ORF Stop: TAG at 3073
SNP Pos: 2712 SNP Change: T to C
ATGGAGCCCTCCAGAGCGCTTCTCGGCTGCCTAGCGAGCGCCGCCGCTGCCGCCCCGCCGGGGGAGGA TGGAGCAGGGGCCGGGGCCGAGGAGGAGGAGGAGGAGGAGGAGGAGGCGGCGGCGGCGGTGGGCCCCG GGGAGCTGGGCTGCGACGCGCCGCTGCCCTACTGGACGGCCGTGTTCGAGTACGAGGCGGCGGGCGAG GACGAGCTGACCCTGCGGCTGGGCGACGTGGTGGAGGTGCTGTCCAAGGACTCGCAGGTGTCCGGCGA CGAGGGCTGGTGGACCGGGCAGCTGAACCAGCGGGTGGGCATCTTCCCCAGCAACTACGTGACCCCGC GCAGCGCCTTCTCCAGCCGCTGCCAGCCCGGCGGCGAAATTGATTTTGCGGAGCTCACCTTGGAAGAG ATTATTGGCATCGGGGGCTTTGGGAAGGTCTATCGTGCTTTCTGGATAGGGGATGAGGTTGCTGTGAA AGCAGCTCGCCACGACCCTGATGAGGACATCAGCCAGACCATAGAGAATGTTCGCCAAGAGGCCAAGC TCTTCGCCATGCTGAAGCACCCCAACATCATTGCCCTAAGAGGGGTATGTCTGAAGGAGCCCAACCTC TGCTTGGTCATGGAGTTTGCTCGTGGAGGACCTTTGAATAGAGTGTTATCTGGGAAAAGGATTCCCCC AGACATCCTGGTGAATTGGGCTGTGCAGATTGCCAGAGGGATGAACTACTTACATGATGAGGCAATTG TTCCCATCATCCACCGCGACCTTAAGTCCAGCAACGTATTGATCCTCCAGAAGGTGGAGAATGGAGAC CTGAGCAACAAGATTCTGAAGATCACTGATTTTGGCCTGGCTCGGGAATGGCACCGAACCACCAAGAT GAGTGCGGCAGGGACGTATGCTTGGATGGCACCCGAAGTCATCCGGGCCTCCATGTTTTCCAAAGGCA GTGATGTGTGGAGCTATGGGGTGCTACTTTGGGAGTTGCTGACTGGTGAGGTGCCCTTTCGAGGCATT GATGGCTTAGCAGTCGCTTATGGAGTGGCCATGAACAAACTCGCCCTTCCTATTCCTTCTACGTGCCC AGAACCTTTTGCCAAACTCATGGAAGACTGCTGGAATCCTGATCCCCACTCACGACCATCTTTCACGA ATATCCTGGACCAGCTAACCACCATAGAGGAGTCTGGTTTCTTTGAAATGCCCAAGGACTCCTTCCAC TGCCTGCAGGACAACTGGAAACACGAGATTCAGGAGATGTTTGACCAACTCAGGGCCAAAGAAAAGGA ACTTCGCACCTGGGAGGAGGAGCTGACGCGGGCTGCACTGCAGCAGAAGAACCAGGAGGAACTGCTGC GGCGTCGGGAGCAGGAGCTGGCCGAGCGGGAGATTGACATCCTGGAACGGGAGCTCAACATCATCATC CACCAGCTGTGCCAGGAGAAGCCCCGGGTGAAGAAACGCAAGGGCAAGTTCAGGAAGAGCCGGCTGAA GCTCAAGGATGGCAACCGCATCAGCCTCCCTTCTGGTTTCCAGCACAAGTTCACGGTGCAGGCCTCCC CTACCATGGATAAAAGGAAGAGTCTTATCAACAGCCGCTCCAGTCCTCCTGCAAGCCCCACCATCATT CCTCGCCTTCGAGCCATCCAGTGTGAGACTGTTTCCCAAATTAGCTGGGGCCAGAACACACAGGGGCA CCTGTCCGAAAGCAGCAAAACCTGGGGCAGGAGCTCAGTCGTCCCAAAGGAGGAAGGGGAGGAGGAGG AGAAGAGGGCCCCAAAGAAGAAGGGACGGACGTGGGGGCCAGGGACGCTTGGTCAGAAGGAGCTTGCC TCGGGAGATGAACTCAAGTCCCTGGTAGATGGATATAAGCAGTGGTCGTCCAGTGCCCCCAACCTGGT GAAGGGCCCAAGGAGTACCCCGGCCCTGCCAGGGTTCACCAGCCTTATGGAGATGGAGGATGAGGACA GTGAAGGCCCAGGGAGTGGAGAGAGTCGCCTACAGCATTCACCCAGCCAGTCCTACCTCTGTATCCCA TTCCCTCGTGGAGAGCCCACCCCAGTCAACTCGGCCACGAGTACCCCTCAGCTGACGCCAACCAACAG CCTCAAGCGGGGCGGTGCCCACCACCGCCGCTGCGAGGTGGCTCTGCTCGGCTGTGGGGCTGTTCTGG CAGCCACAGGCCTAGGGTTTGACTTGCTGGAAGCTGGCAAGTGCCAGCTGCTTCCCCTGGAGGAGCCT GAGCCACCAGCCCGGGAGGAGAAGAAAAGACGGGAGGGTCTTTTTCAGAGGTCCAGCCGTCCTCGTCG GAGCACCAGCCCCCCATCCCGAAAGCTTTTCAAGAAGGAGGAGCCCATGCTGTTGCTAGGAGACCCCT CTGCCTCCCTGACGCTGCTCTCCCTCTCCTCCATCTCCGAGTGCAACTCCACACGCTCCCTGCTGCAG TCCGACAGCGATGAAATTGTCGTGTATGAGATGCCAGTCAGCCCAGTCGAGGCCCCTCCCCTGAGTCC ATGTACCCACAACCCCCTGGTCAATGTCCGAGTAGAGCGCTTCAAACGAGATCCTAACCAATCTCTGA CTCCCACCCATGTCACCCTCACCACCCCCTCGCAGCCCAGCAGTCACCGGCGGACTCCTTCTGATGGG GCCCTTAAGCCAGAGACTCTCCTAGCCAGCAGGAGCCCCAGTCCCAGCCGAGACCCAGGCGAATTCCC CCGTCTCCCTGACCCCAATGTGGTCTTCCCCCCAACCCCAAGGCGCTGGAACACTCAGCAGGACTCTA CCTTGGAGAGACCCAAGACTCTGGAGTTTCTGCCTCGGCCGCGTCCTTCTGCCAACCGGCAACGGCTG GACCCTTGGTGGTTTGTGTCCCCCAGCCATGCCCGCAGCACCTCCCCAGCCAACAGCTCCAGCACAGA GACGCCCGGGCCGCTGCCCCCGACTGAGCGGACGCTCCTGGACCTGGATGCAGAGGGGCAGAGTCAGG ACAGCACCGTGCCGCTGTGCAGAGCGGAACTGAACACACACAGGCCTGCCCCTTATGAGATCCAGCAG GAGTTCTGGTCTTAGCACGAAAAGGATTGGGG
NOV51c, SNP13376041 of SEQ ID NO: 7δδ 1024 aa MW at l l36δ2.1kD CG56071-01, Protein Sequence SNP Pos: 904 SNP Change: Gly to Gly
MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPYWTAVFEYEAAGE DELTLRLGDWEVLSKDSQVSGDEGWWTGQLNQRVGIFPSNYVTPRSAFSSRCQPGGEIDFAELTLEE IIGIGGFGKVYRAFWIGDEVAVKAARHDPDEDISQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNL CLVMEFARGGPLNRVLSGKRIPPDILVNWAVQIARGMNYLHDEAIVPIIHRDLKSSNVLILQKVENGD LSNKILKITDFGLARE HRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLLWELLTGEVPFRGI DGLAVAYGVAMNKLALPIPSTCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFH CLQDNWKHEIQEMFDQLRAKEKELRT EEELTRAALQQKNQEELLRRREQELAEREIDILERELNIII HQLCQEKPRVKKRKGKFRKSRLKLKDGNRISLPSGFQHKFTVQASPTMDKRKSLINSRSSPPASPTII PRLRAIQCETVSQIS GQNTQGHLSESSKTWGRSSWPKEEGEEEEKRAPKKKGRTWGPGTLGQKELA SGDELKSLVDGYKQWSSSAPNLVKGPRSTPALPGFTSLMEMEDEDSEGPGSGESRLQHSPSQSYLCIP FPRGEPTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLGCGAVLAATGLGFDLLEAGKCQLLPLEEP EPPAREEKKRREGLFQRSSRPRRSTSPPSRKLFKKEEPMLLLGDPSASLTLLSLSSISECNSTRSLLQ SDSDEIWYEMPVSPVEAPPLSPCTHNPLVNVRVERFKRDPNQSLTPTHVTLTTPSQPSSHRRTPSDG ALKPETLLASRSPSPSRDPGEFPRLPDPNWFPPTPRRWNTQQDSTLERPKTLEFLPRPRPSANRQRL DP WFVSPSHARSTSPANSSSTETPGPLPPTERTLLDLDAEGQSQDSTVPLCRAELNTHRPAPYEIQQ EF S
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 5 IB.
Table 51B. Comparison of the NOV51 protein sequences.
NOV5la MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPYWTAV
NOV5lb
NOV5la FEYEAAGEDELTLRLGDWEVLSKDSQVSGDEGW TGQLNQRVGIFPSNYVTPRSAFSSR
NOV51b
NOV51a CQPGGEIDFAELTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDEDISQTIENVRQEA
NOV5lb TGSLTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDEDISQTIENVRQEA
NOV51a KLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVNWAVQIARG
NOV51b KLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVNWAVQIARG
NOV5la MNYLHDEAIVPIIHRDLKSSNVLILQKVENGDLSNKILKITDFGLARE HRTTKMSAAGT
NOV51b MNYLHDEAIVPIIHRDLKSS ILILQKVENGDLSNKILKITDFGLARE HRTTKMSAAGT NOV5la YA MAPEVIRASMFSKGSDV SYGVLL ELLTGEVPFRGIDGLAVAYGVAMNKLALPIPS
NOV5lb YAWMAPEVIRASMFSKGSDVWSYGVLL ELLTGEVPFRGIDGLAVAYGVAMNKLALPIPS
NOV5la TCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFHCLQDNWKHEIQE
NOV5lb TCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTILEG
NOV51a MFDQLRAKEKELRTWEEELTRAALQQKNQEELLRRREQELAEREIDILERELNIIIHQLC
NOV51b
NOV5la QEKPRVKKRKGKFRKSRLKLKDGNRISLPSGFQHKFTVQASPTMDKRKSLINSRSSPPAS
NOV51b
NOV51a PTIIPRLRAIQCETVSQISWGQNTQGHLSESSKTWGRSSWPKEEGEEEEKRAPKKKGRT
NOV5lb
NOV51a WGPGTLGQKELASGDELKSLVDGYKQWSSSAPNLVKGPRSTPALPGFTSLMEMEDEDSEG
NOV5lb
NOV5la PGSGESRLQHSPSQSYLCIPFPRGEPTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLG
NOV51b
NOV51a CGAVLAATGLGFDLLEAGKCQLLPLEEPEPPAREEKKRREGLFQRSSRPRRSTSPPSRKL
NOV5lb
NOV51a FKKEEPMLLLGDPSASLTLLSLSSISECNSTRSLLQSDSDEIWYEMPVSPVEAPPLSPC
NOV5lb
NOV51a THNPLVNVRVERFKRDPNQSLTPTHVTLTTPSQPSSHRRTPSDGALKPETLLASRSPSPS
NOV5lb
NOV51a RDPGEFPRLPDPNWFPPTPRRW TQQDSTLERPKTLEFLPRPRPSANRQRLDP WFVSP
NOV51b
NOV51a SHARSTSPANSSSTETPGPLPPTERTLLDLDAEGQSQDSTVPLCRAELNTHRPAPYEIQQ
NOV51b
NOV51a EF S
NOV51b
NOV51a (SEQ ID NO: 784) NOV51b (SEQ ID NO: 786)
Further analysis ofthe NOV5 la protein yielded the following properties shown in Table 51C.
Table 51 C. Protein Sequence Properties NOV51a
SignalP analysis: Cleavage site between residues 18 and 19
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 5; pos. chg 1; neg.chg 1 H-region: length 16; peak value 7.95 PSG score: 3.55
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 0.45 possible cleavage site: between 17 and 18
>>> Seems to have a cleavable signal peptide (1 to 17)
ALOM: Klein et al's method for TM region allocation Init position for calculation: 18
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -3.66 Transmembrane 716 - 732 PERIPHERAL Likelihood = 2.44 (at 342) ALOM score: -3.66 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 8 Charge difference: -10.0 C(-9.0) - N( 1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type la (cytoplasmic tail 733 to 1024)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 4.60 Hyd Moment (95): 9.12 G content: 2 D/E content: 2 S/T content: 2 Score: -6.34
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 15 SRA|LL
NUCDISC: discrimination of nuclear localization signals pat4: KKRK (5) at 487 pat4: PKKK (4) at 594 pat4: KKRR (5) at 756 pat4: RPRR (4) at 768 pat7: PRVKKRK (5) at 484 pat7: PTMDKRK (3) at 522 pat7: PKKKGRT (5) at 594 bipartite: KKRREGLFQRSSRPRRS at 756 content of basic residues: 12.1% NLS Score: 2.27
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: EPSR none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS : 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 734 LL at 742 LL at 788 LL at 789 LL at 799 LL at 814 LL at 891 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions
409 L 0.51
410 Q 0.87
411 D 0.99
412 N 0.99
413 W 0.99
414 K 1.00
415 H 1.00
416 E 1.00
417 I 1.00
418 Q 1.00
419 E 1.00
420 M 1.00
421 F 1.00
422 D 1.00
423 Q 1.00
424 L 1.00
425 R 1.00 426 A 1.00
427 K 1.00
428 E 1.00
429 K 1.00
430 E 1.00
431 L 1.00
432 R 1.00
433 T 1.00
434 W 1.00
435 E 1.00
436 E 1.00
437 E 1.00
438 L 1.00
439 T 1.00
440 R 1.00
441 A 1.00
442 A 0.97
443 L 0.97
444 Q 0.96
445 Q 0.96
446 K 0.96
447 N 0.96
448 Q 0.96
449 E 0.96
450 E 0.96
451 L 0.81
452 L 0.81
453 R 0.81
454 R 0.81
455 R 0.71
456 E 0.71
457 Q 0.71
458 E 0.71
459 L 0.71
460 A 0.71
461 E 0.71
462 R 0.64
463 E 0.64
464 I 0.64
465 D 0.64
466 I 0.64
467 L 0.64
468 E 0.64
469 R 0.64
470 E 0.64
471 L 0.64
472 N 0.64
473 I 0.64
474 I 0.64
475 I 0.64
476 H 0.64
477 Q 0.64
478 L 0.64
479 C 0.64 480 Q 0 64
481 E 0 64
482 K 0 64 total: 74 residues
Final Results (k = 9/23) :
44 4 % extracellular, including ce 11 wall
22 2 % Golgi
22 2 % endoplasmic reticulum
11 1 % plasma membrane
>> prediction for CG56071-01 is exc (k= 9)
A search ofthe NOV5 la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5 ID.
Figure imgf000766_0001
In a BLAST search of public sequence databases, the NOV51a protein was found to have homology to the proteins shown in the BLASTP data in Table 5 IE.
Figure imgf000767_0001
PFam analysis indicates that the NOV51a protein contains the domains shown in the Table 5 IF.
Figure imgf000767_0002
Example 52.
The NOV52 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 52A.
Table 52A. NOV52 Sequence Analysis
NOV52a, CG56142-01 SEQ ID NO: 7δ9 866 bp DNA Sequence ORF Start: ATG at 19 ORF Stop: TGA at 820
CCCAGCCTTGAAGACAGAATGAGAGGGGTTTCCTGTCTCCAGGTCCTGCTCCTTCTGGTGCTGGCCTG
CGGGCAGCCCCGCATGTCCAGTCGGATCGTTGGGGGCCGGGATGGCCGGGACGGAGAGTGGCCGTGGC AGGCGAGCATCCAGCATCGTGGGGCACACGTGTGCGGGGGGTCGCTCATCGCCCCCCAGTGGGTGCTG ACAGCGGCGCACTGCTTCCCCAGGGCACTGCCAGCTGAGTACCGCGTGCGCCTGGGGGCGCTGCGTCT GGGCTCCACCTCGCCCCGCACGCTCTCGGTGCCCGTGCGACGGGTGCTGCTGCCCCCGGACTACTCCG AGGACGGGGCCCGCGGCGACCTGGCACTGCTGCAGCTGCGTCGCCCGGTGCCCCTGAGCGCTCGCGTC CAACCCGTCTGCCTGCCCGTGCCCGGCGCCCGCCCGCCGCCCGGCACACCATGCCGGGTCACCGGCTG GGGCAGCCTCCGCCCAGGAGTGCCCCTCCCAGAGTGGCGACCGCTACAAGGAGTAAGGGTGCCGCTGC TGGACTCGCGCACCTGCGACGGCCTCTACCACGTGGGCGCGGACGTGCCCCAGGCTGAGCGCATTGTG CTGCCTGGGAGTCTGTGTGCCGGCTACCCCCAGGGCCACAAGGACGCCTGCCAGGTGTGCACCCAGCC TCCCCAGCCTCCGGAGTCCCCTCCCTGTGCCCAGCACCCTCCCTCCCTGAACTCCAGGACCCAGGACA TCCCAACTCAGGCTCAGGATCCTGGCCTCCAACCTAGAGGCACCACGCCAGGGGTCTGGAACCCTGAG AACTGAAGTCCTGGGAGGGCTGGGACTTAGGCTCCTCTTTCTCCTGCAGG
NOV52a, CG56142-01 SEQ ID NO: 790 267 aa MW at 28699.8kD Protein Sequence
MRGVSCLQVLLLLVLACGQPRMSSRIVGGRDGRDGEWP QASIQHRGAHVCGGSLIAPQWVLTAAHCF PRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSEDGARGDLALLQLRRPVPLSARVQPVCLP VPGARPPPGTPCRVTGWGSLRPGVPLPE RPLQGVRVPLLDSRTCDGLYHVGADVPQAERIVLPGSLC AGYPQGHKDACQVCTQPPQPPESPPCAQHPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN
NOV52b, CG56142-04 SEQ ID NO: 791 638 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TGA at 57δ
CCTTGAAGACAGAATGAGAGGGGTTTCCTGTCTCCAGGTCCTGCTCCTTCTGGTGCTGGGAGCTGCTG
GGACTCAGGGAAGGAAGTCTGCAGCCTGCGGGCAGCCCCGCATGTCCAGTCGGATCGTTGGGGGCCGG GATGGCCGGGACGGAGAGTGGCCGTGGCAGGCGAGCATCCAGCATCGTGGGGCACACGTGTGCGGGGG GTCGCTCATCGCCCCCCAGTGGGTGCTGACAGCGGCGCACTGCTTCCCCAGTGCCCCTCCAGAGTGGC GACCGCTACAAGGAGTAAGGGTGCCGCTGCTGGACTCGCGCACCTGCGACGGCCTCTACCACGTGGGC GCGGACGTGCCCCAGGCTGAGCGCATTGTGCTGCCTGGGAGTCTGTGTGCCGGCTACCCCCAGGGCCA CAAGGACGCCTGCCAGGTGTGCACCCAGCCTCCCCAGCCTCCGGAGTCCCCTCCCTGTGCCCAGCACC CTCCCTCCCTGAACTCCAGGACCCAGGACATCCCAACTCAGGCTCAGGATCCTGGCCTCCAACCTAGA GGCACCACGCCAGGGGTCTGGAACCCTGAGAACTGAAGTCCTGGGAGGGCTGGGACTTAGGCTCCTCT TTCTCCTGGAGGGTGATTCTGGGGGA
NOV52b, CG56142-04 SEQ ID NO: 792 188 aa MW at 19994.5kD Protein Sequence
MRGVSCLQVLLLLVLGAAGTQGRKSAACGQPRMSSRIVGGRDGRDGEWPWQASIQHRGAHVCGGSLIA PQWVLTAAHCFPSAPPE RPLQGVRVPLLDSRTCDGLYHVGADVPQAERIVLPGSLCAGYPQGHKDAC QVCTQPPQPPESPPCAQHPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN
NOV52c, 276873337 SEQ ID NO: 793 1165 bp DNA Sequence ORF Start: at 606 ORF Stop: TGA at 948
CACCAAGCTTTGGGACTACGAGACGCCCAAGGTGATCGTGGTGAGGAACCGGCGCCTGGGGGTCCTGT ACCGCGCCGTGCAGCTGCTCATCCTGCTCTACTTCGTGTGGTACGTATTCATCGTGCAGAAAAGCTAC CAGGAGAGCGAGACGGGCCCCGAGAGCTCCATCATCACCAAGGTCAAGGGGATCACCACGTCCGAGCA CAAAGTGTGGGACGTGGAGGAGTACGTGAAGCCCCCCGAGGGGGGCAGCGTGTTCAGCATCATCACCA GGGTCGAGGCCACCCACTCCCAGACCCAGGGAACCTGCCCCGAGAGCATAAGGGTCCACAACGCCACC
TGCCTCTCCGACGCCGACTGCGTGGCTGGGGAGCTGGACATGCTGGGAAACGGCCTGAGGACCGGGCG
CTGTGTGCCCTATTACCAGGGGCCCTCCAAGACCTGCGAGGTGTTCGGCTGGTGCCCGGTGGAAGATG
GGGCCTCTGTCAGCCAATTTCTGGGTACGATGGCCCCAAATTTCACCATCCTCATCAAGAACAGCATC
CACTACCCCAAATTCCACTTCTCCAAGGGCAACATCGCCGACCGCACAGACGGGTACCTGAAGCGCTG CACGTTCCACGAGGCCTCCGACCTCTACTGCCCCATCTTCAAGCTGGGCTTTATCGTGGAGAAGGCTG GGGAGAGCTTCACAGAGCTCGCACACAAGGGTGGTGTCATCGGGGTCATTATCAACTGGGACTGTGAC CTGGACCTGCCTGCATCGGAGTGCAACCCCAAGTACTCCTTCCGGAGGCTTGACCCCAAGCACGTGCC TGCCTCGTCAGGCTACAACTTCAGGTTTGCCAAATACTACAAGATCAATGGCACCACCACCCGCACGC TCATCAAGGCCTACGGGATCCACATTGACGTCATTGTGCATGGACAGGTCGGGAAGTTCAGCCTGATT CCCACCATTATTAATCTGGCCACAGCTCTGACTTCCGTCGGGGTGGTAAGGAACCCTCTCTGGGGTCC
CAGCGGGTGCGGGGGGTCCACCAGGCCCTTACACACCGGTCTCTGCTGGCCCCAGGGCTCCTTCCTGT
GCGACTGGATCTTGCTAACATTCATGAACAAAAACAAGGTCTACAGCCATAAGAAATTTGACAAGGTG
GTCGACGGC
NOV52c, 276873337 SEQ ID NO: 794 114 aa MW at ll702.8kD Protein Sequence
SAARSTRPPTSTAPSSSWALSWRRLGRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPS TCLPRQATTSGLPNTTRSMAPPPARSSRPTGSTLTSLCMDRSGSSA
NOV52d, 276δ63970 SEQ ID NO: 795 1164 bp DNA Sequence ORF Start: at 605 ORF Stop: TGA at 947
CACAAGCTTTGGGACTACGAGACGCCCAAGGTGATCGTGGTGAGGAACCGGCGCCTGGGGGTCCTGTA
CCGCGCCGTGCAGCTGCTCATCCTGCTCTACTTCGTGTGGTACGTATTCATCGTGCAGAAAAGCTACC;
AGGAGAGCGAGACGGGCCCCGAGAGCTCCATCATCACCAAGGTCAAGGGGATCACCACGTCCGAGCAC
AAAGTGTGGGACGTGGAGGAGTACGTGAAGCCCCCCGAGGGGGGCAGCGTGTTCAGCATCATCACCAG
GGTCGAGGCCACCCACTCCCAGACCCAGGGAACCTGCCCCGAGAGCATAAGGGTCCACAACGCCACCT
GCCTCTCCGACGCCGACTGCGTGGCTGGGGAGCTGGACATGCTGGGAAACGGCCTGAGGACCGGGCGC
TGTGTGCCCTATTACCAGGGGCCCTCCAAGACCTGCGAGGTGTTCGGCTGGTGCCCGGTGGAAGATGG
GGCCTCTGTCAGCCAATTTCTGGGTACGATGGCCCCAAATTTCACCATCCTCATCAAGAACAGCATCC
ACTACCCCAAATTCCACTTCTCCAAGGGCAACATCGCCGACCGCACAGACGGGTACCTGAAGCGCTGC
ACGTTCCACGAGGCCTCCGACCTCTACTGCCCCATCTTCAAGCTGGGCTTTATCGTGGAGAAGGCTGG GGAGAGCTTCACAGAGCTCGCACACAAGGGTGGTGTCATCGGGGTCATTATCAACTGGGACTGTGACC TGGACCTGCCTGCATCGGAGTGCAACCCCAAGTACTCCTTCCGGAGGCTTGACCCCAAGCACGTGCCT GCCTCGTCAGGCTACAACTTCAGGTTTGCCAAATACTACAAGATCAATGGCACCACCACCCGCACGCT CATCAAGGCCTACGGGATCCGCATTGACGTCATTGTGCATGGACAGGTCGGGAAGTTCAGCCTGATTC CCACCATTATTAATCTGGCCACAGCTCTGACTTCCGTCGGGGTGGTAAGGAACCCTCTCTGGGGTCCC
AGCGGGTGCGGGGGGTCCACCAGGCCCTTACACACCGGTCTCTGCTGGCCCCAGGGCTCCTTCCTGTG
CGACTGGATCTTGCTAACATTCATGAACAAAAACAAGGTCTACAGCCATAAGAAATTTGACAAGGTGG
TCGACGGC
NOV52d, 276863970 SEQ ID NO: 796 114 aa MW at ll672.δkD Protein Sequence
SAARSTRPPTSTAPSSS ALSWRRLGRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPS TCLPRQATTSGLPNTTRSMAPPPARSSRPTGSALTSLCMDRSGSSA
NOV52e, 276δ63992 SEQ ID NO: 797 10δ7 bp DNA Sequence ORF Start: at 606 ORF Stop: TGA at 94δ
CACCAAGCTTTGGGACTACGAGACGCCCAAGGTGATCGTGGTGAGGAACCGGCGCCTGGGGGTCCTGT ACCGCGCCGTGCAGCTGCTCATCCTGCTCTACTTCGTGTGGTACGTATTCATCGTGCAGAAAAGCTAC CAGGAGAGCGAGACGGGCCCCGAGAGCTCCATCATCACCAAGGTCAAGGGGATCACCACGTCCGAGCA CAAAGTGTGGGACGTGGAGGAGTACGTGAAGCCCCCCGAGGGGGGCAGCGTGTTCAGCATCATCACCA GGGTCGAGGCCACCCACTCCCAGACCCAGGGAACCTGCCCCGAGAGCATAAGGGTCCACAACGCCACC TGCCTCTCCGACGCCGACTGCGTGGCTGGGGAGCTGGACATGCTGGGAAACGGCCTGAGGACCGGGCG CTGTGTGCCCTATTACCAGGGGCCCTCCAAGACCTGCGAGGTGTTCGGCTGGTGCCCGGTGGAAGATG GGGCCTCTGTCAGCCAATTTCTGGGTACGATGGCCCCAAATTTCACCATCCTCATCAAGAACAGCATC CACTACCCCAAATTCCACTTCTCCAAGGGCAACATCGCCGACCGCACAGACGGGTACCTGAAGCGCTG CACGTTCCACGAGGCCTCCGACCTCTACTGCCCCATCTTCAAGCTGGGCTTTATCGTGGAGAAGGCTG
Figure imgf000770_0001
PLSARVQPVCLPVPGARPPPGTPCRVTG GSLRPGVPLPE RPLQGVRVPLLDSRTCDGLYHVGADVP QAERIVLPGSLCAGYPQGHKDACQGDSGGPLTCLQSGS VLVGWSWGKGCALPNRPGVYTSVATYSP WIQARVSF
NOV52h, CG56142-03 SEQ ID NO: δ03 11606 bp DNA Sequence ORF Start: ATG at 69 JORF Stop: TGA at 921
CCACGCGTCCGACCAGAGTCCAAGCCCTAGGCAGTGCCACCCTTACCCAGCCCAGCCTTGAAGACAGA
ATGAGAGGGGTTTCCTGTCTCCAGGTCCTGCTCCTTCTGGTGCTGGGAGCTGCTGGGACTCAGGGAAG GAAGTCTGCAGCCTGCGGGCAGCCCCGCATGTCCAGTCGGATCGTTGGGGGCCGGGATGGCCGGGACG GAGAGTGGCCGTGGCAGGCGAGCATCCAGCATCCTGGGGCACACGTGTGCGGGGGGTCGCTCATCGCC CCCCAGTGGGTGCTGACAGCGGCGCACTGCTTCCCCAGGAGGGCACTGCCAGCTGAGTACCGCGTGCG CCTGGGGGCGCTGCGTCTGGGCTCCACCTCGCCCCGCACGCTCTCGGTGCCCGTGCGACGGGTGCTGC TGCCCCCGGACTACTCCGAGGACGGGGCCCGCGGCGACCTGGCACTGCTGCAGCTGCGTCGCCCGGTG CCCCTGAGCGCTCGCGTCCAACCCGTCTGCCTGCCCGTGCCCGGCGCCCGCCCGCCGCCCGGCACACC ATGCCGGGTCACCGGCTGGGGCAGCCTCCGCCCAGGAGTGCCCCTCCCAGAGTGGCGACCGCTACAAG GAGTAAGGGTGCCGCTGCTGGACTCGCGCACCTGCGACGGCCTCTACCACGTGGGCGCGGACGTGCCC CAGGCTGAGCGCATTGTGCTGCCTGGGAGTCTGTGTGCCGGCTACCCCCAGGGCCACAAGGACGCCTG CCAGGGTGATTCTGGGGGACCTCTGACCTGCCTGCAGTCTGGGAGCTGGGTCCTGGTGGGCGTGGTGA GCTGGGGCAAGGGTTGTGCCCTGCCCAACCGTCCAGGGGTCTACACCAGTGTGGCCACATATAGCCCC TGGATTCAGGCTCGCGTCACTTCTAATGCTAGCCGGTGAGGCTGACCTGGAGCCAGCTGCTGGGGTCC
CTCAGCCTCCTGGTTCATCCAGGCACCTGCCTATACCCCACATCCCTTCTGCCTCGAGGCCAAGATGC
CTAAAAAAGCTAAAGGCCACCCCACCCCCCACCCACCACCTTCTGGCTCCTCTCCTCTTTGGGGATCA
CCAGCTCTGACTCCACCAACCCTCATCCAGGAATCTGCCATGAGTCCCAGGGAGTCACACTCCCCACT
CCCTTCCTGGCTTGTATTTACTTTTCTTGGCCCTGGCCAGGGCTGGGCGCAAGGCACGCAGTGATGGG
CAAACCAATTGCTGCCCATCTGGCCTGTGTGCCCATCTTTTTCTGGAGAAAGTCAGATTCACAGCATG
ACAGAGATTTGACACCAGGGAGATCCTCCATAGCTGGCTTTGAGGACACGGGGACCACAGCCATGAGC
GGCCTCTAAGAGCTGAGAGACAGCCGGCAGGGAATCGGAACCCTCAGACCCACAGCCGCAAGGCACTG jGATTCTGGCAGCACCCTGAAGGAGCTGGGAAGTAAGTTCTTCCCCAGCCTCCAGATAAGAGCCCCGCC
GGCCAATCCCTTCATTTCAACCTAAAGAGACCCTAAGCAGAGAACCTAGCTGAGCCACTCCTGACCTA
CAAAGTTGTGACTTAATAAATGTGTGCTTTAAGCTGCCAAAA
NOV52h, CG56142-03 SEQ ID NO: δ04 284 aa MW at 30109.5kD Protein Sequence
MRGVSCLQVLLLLVLGAAGTQGRKSAACGQPRMSSRIVGGRDGRDGEWPWQASIQHPGAHVCGGSLIA PQWVLTAAHCFPRRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSEDGARGDLALLQLRRPV PLSARVQPVCLPVPGARPPPGTPCRVTGWGSLRPGVPLPE RPLQGVRVPLLDSRTCDGLYHVGADVP QAERIVLPGSLCAGYPQGHKDACQGDSGGPLTCLQSGS VLVGWS GKGCALPNRPGVYTSVATYSP WIQARVTSNASR
NOV52i, CG56142-05 SEQ ID NO: 805 1762 bp DNA Sequence ORF Start: at 7 ORF Stop: at 757
AGATCTCAGCCCCGCATGTCCAGTCGGATCGTTGGGGGCCGGGATGGCCGGGACGGAGAGTGGCCGTG
GCAGGCGAGCATCCAGCATCGTGGGGCACACGTGTGCGGGGGGTCGCTCATCGCCCCCCAGTGGGTGC TGACAGCGGCGCACTGCTTCCCCAGGAGGGCACTGCCAGCTGAGTACCGCGTGCGCCTGGGGGCGCTG CGTCTGGGCTCCACCTCGCCCCGCACGCTCTCGGTGCCCGTGCGACGGGTGCTGCTGCCCCCGGACTA CTCCGAGGACGGGGCCCGCGGCGACCTGGCACTGCTGCAGCTGCGTCGCCCGGTGCCCCTGAGCGCTC GCGTCCAACCCGTCTGCCTGCCCGTGCCCGCCGCCCGCCCGCCGCCCGGCACACCATGCCGGGTCACC GGCTGGGGCAGCCTCCGCCCAGGAGTGCCCCTCCCAGAGGGGCGACCGCTACAAGGAGTAAGGGTGCC GCTGCTGGACTCGCGCACCTGCGACGGCCTCTACCACGTGGGCGCGGACGTGCCCCAGGCTGAGCGCA TTGTGCTGCCTGGGAGTCTGTGTGCCGGCTACCCCCAGGTCCACAAGGACGCCTGCCAGGTGTGCACC CAGCCTCCCCAGCCTCCGGAGTCCCCTCCCTGTGCCCAGCTCCCTCCCTCCCTGAACTCCAGGACCCA GGACATCCCAACTCAGGCTCAGGATCCTGGCCTCCAACCTAGAGGCACCACGCCAGGGGTCTGGAACC CTGAGAACCTCGAG
NOV52i, CG56142-05 SEQ ID NO: 806 250 aa MW at 2688δ.5kD Protein Sequence
QPRMSSRIVGGRDGRDGEWPWQASIQHRGAHVCGGSLIAPQWVLTAAHCFPRRALPAEYRVRLGALRL GSTSPRTLSVPVRRVLLPPDYSEDGARGDLALLQLRRPVPLSARVQPVCLPVPAARPPPGTPCRVTGW GSLRPGVPLPEGRPLQGVRVPLLDSRTCDGLYHVGADVPQAERIVLPGSLCAGYPQVHKDACQVCTQP PQPPESPPCAQLPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN
NOV52J, CG56142-06 SEQ ID NO: δ07 DNA Sequence ORF Start: at 7 ORF Stop: at 757
AGATCTCAGCCCCGCATGTCCAGTCGGATCGTTGGGGGCCGGGATGGCCGGGACGGAGAGTGGCCGTG
GCAGGCGAGCATCCAGCATCGTGGGGCACACGTGTGCGGGGGGTCGCTCATCGCCCCCCAGTGGGTGC TGACAGCGGCGCACTGCTTCCCCAGGAGGGCACTGCCAGCTGAGTACCGCGTGCGCCTGGGGGCGCTG CGTCTGGGCTCCACCTCGCCCCGCACGCTCTCGGTGCCCGTGCGACGGGTGCTGCTGCCCCCGGACTA CTCCGAGGACGGGGCCCGCGGCGACCTGGCACTGCTGCAGCTGCGTCGCCCGGTGCCCCTGAGCGCTC GCGTCCAACCCGTCTGCCTGCCCGTGCCCGGCGCCCGCCCGCCGCCCGGCACACCATGCCGGGTCACC GGCTGGGGCAGCCTCCGCCCAGGAGTGCCCCTCCCAGAGTGGCGACCGCTACAAGGAGTAAGGGTGCC GCTGCTGGACTCGCGCACCTGCGACGGCCTCTACCACGTGGGCGCGGACGTGCCCCAGGCTGAGCGCA TTGTGCTGCCTGGGAGTCTGTGTGCCGGCTACCCCCAGGGCCACAAGGACGCCTGCCAGGTGTGCACC CAGCCTCCCCAGCCTCCGGAGTCCCCTCCCTGTGCCCAGCTCCCTCCCTCCCTGAACTCCAGGACCCA GGACATCCCAACTCAGGCTCAGGATCCTGGCCTCCAACCTAGAGGCACCACGCCAGGGGTCTGGAACC CTGAGAACCTCGAG
NOV52j, CG56142-06 SEQ ID NO: 808 250 aa M at 26961.6kD Protein Sequence
QPRMSSRIVGGRDGRDGE P QASIQHRGAHVCGGSLIAPQWVLTAAHCFPRRALPAEYRVRLGALRL GSTSPRTLSVPVRRVLLPPDYSEDGARGDLALLQLRRPVPLSARVQPVCLPVPGARPPPGTPCRVTGW GSLRPGVPLPE RPLQGVRVPLLDSRTCDGLYHVGADVPQAERIVLPGSLCAGYPQGHKDACQVCTQP PQPPESPPCAQLPPSLNSRTQDIPTQAQDPGLQPRGTTPGV NPEN
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 52B.
Table 52B. Comparison of the NOV52 protein sequences.
NOV52a MRGVSCLQVLLLLVL ACGQPRMSSRIVGGRDGRDGEWPWQASIQHRGAH
NOV52b MRGVSCLQVLLLLVLGAAGTQGRKSAACGQPRMSSRIVGGRDGRDGEWP QASIQHRGAH
NOV52c
NOV52d
NOV52Θ
NOV52f
NOV52g MRGVSCLQVLLLLVLGAAGTQGRKSAACGQPRMSSRIVGGRDGRDGEWP QASIQHRGAH
NOV52h MRGVSCLQVLLLLVLGAAGTQGRKSAACGQPRMSSRIVGGRDGRDGEWPWQASIQHPGAH
NOV52i QPR SSRIVGGRDGRDGEWPWQASIQHRGAH
NOV52j QPRMSSRIVGGRDGRDGEWPWQASIQHRGAH
NOV52a VCGGSLIAPQWVLTAAHCFPR-ALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSE
NOV52b VCGGSLIAPQ VLTAAHCFPS
NOV52c
NOV52d
NOV52e
NOV52f
NOV52g VCGGSLIAPQWVLTAAHCFPRRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSE
NOV52h VCGGSLIAPQ VLTAAHCFPRRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSE
N0V52i VCGGSLIAPQ VLTAAHCFPRRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSE
NOV52J VCGGSLIAPQ VLTAAHCFPRRALPAEYRVRLGALRLGSTSPRTLSVPVRRVLLPPDYSE
NOV52a DGARGDLALLQLRRPVPLSARVQPVCLPVPGARPPPGTPCRVTGWGSLRPGVPLPE RPL
N0V52b AP PEWRPL
N0V52C SAARSTRPPTST-APSSSWA LSWRRL
76δ N0V52d SAARSTRPPTST-APSSS A LSWRRL N0V52e SAARSTRPPTST-APSSSWA LSWRRL N0V52f SAARSTRPPTST-APSSSWA LSWRRL NOV52g DGARGDLALLQLRRPVPLSARVQPVCLPVPGARPPPGTPCRVTGWGSLRPGVPLPEWRPL NOV52h DGARGDLALLQLRRPVPLSARVQPVCLPVPGARPPPGTPCRVTGWGSLRPGVPLPEWRPL NOV52i DGARGDLALLQLRRPVPLSARVQPVCLPVPAARPPPGTPCRVTGWGSLRPGVPLPEGRPL NOV52J DGARGDLALLQLRRPVPLSARVQPVCLPVPGARPPPGTPCRVTGWGSLRPGVPLPEWRPL
NOV52a QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQGHKDACQVCTQ-PPQPPE NOV52b QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQGHKDACQVCTQ-PPQPPE NOV52C GRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPSTCLPRQATTSGLPNTTR NOV52 GRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPSTCLPRQATTSGLPNTTR NOV52e GRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPSTCLPRQATTSGLPNTTR NOV52f GRASQSSHTRWSSGSLSTGTVTWTCLHRSATPSTPSGGLTPSTCLPRQATTSGLPNTTR NOV52g QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQGHKDACQGDSGGPLTCLQ NOV52h QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQGHKDACQGDSGGPLTCLQ NOV52i QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQVHKDACQVCTQ-PPQPPE NOV52J QGVRVPLLDSRTCDGLYHVG-ADVPQAERIVLPGSLCAGYPQGHKDACQVCTQ-PPQPPE
NOV52a SPPCAQHPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN NOV52b SPPCAQHPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN NOV52c SM- -APP-PARSSRPTGSTLTSL-CMDRSGSSA NOV52d SM- -APP-PARSSRPTGSALTSL-CMDRSGSSA NOV52e SM- -APP-PARSSRPTGSALTSL-CMDRPGSSA NOV52f SM- -APP-PARSSRPTGSALTSL-CMDRPGSSS NOV52g SG- -SWVLVGWSWGKGCALPNR-PGVYTSVATYSPWIQARVSF NOV52h SG- -SWVLVGWSWGKGCALPNR- PGVYTSVATYSPWIQARVTSNASR NOV52i SPPCAQLPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN NOV52J SPPCAQLPPSLNSRTQDIPTQAQDPGLQPRGTTPGVWNPEN
NOV52a (SEQ ID NO 790) NOV52b (SEQ ID NO 792) NOV52c (SEQ ID NO 79 ) NOV52d (SEQ ID NO 796) NOV52e (SEQ ID NO 798) NOV52f (SEQ ID NO 800) NOV52g (SEQ ID NO 802) NOV52h (SEQ ID NO 804) NOV52i (SEQ ID NO 806)
Figure imgf000773_0001
Further analysis ofthe NOV52a protein yielded the following properties shown in Table 52C.
Table 52C. Protein Sequence Properties NOV52a
SignalP analysis: Cleavage site between residues 19 and 20
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 2 ; pos . chg 1 ; neg . chg 0 H-region : length 18 ; peak value 10 .88 PSG score : 6 .48 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.06 possible cleavage site: between 18 and 19
>>> Seems to have a cleavable signal peptide (1 to 18)
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 19
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 5.30 (at 48) ALOM score: 5.30 (number of TMSs: 0)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 9 Charge difference: 0.0 C( 2.0) - N( 2.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq R content: 4 Hyd Moment (75): 6.32 Hyd Moment (95): 5.75 G content: 4 D/E content: 1 S/T content: 3 Score: -2.36
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 35 SRl|VG
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 10.1% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: RGVS none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
55.6 % extracellular, including cell wall 33.3 % mitochondrial 11.1 % nuclear
>> prediction for CG56142-01 is exc (k=9)
A search ofthe NOV52a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 52D.
Figure imgf000776_0001
In a BLAST search of public sequence databases, the NOV52a protein was found to have homology to the proteins shown in the BLASTP data in Table 52E.
Figure imgf000777_0001
PFam analysis indicates that the NOV52a protein contains the domains shown in the Table 52F.
Table 52F. Domain Analysis of NOV52a
Identities/
Pfam Domain NOV52a Match Region Similarities Expect Value for the Matched Region trypsin 26..241 δ3/269 (31%) le-3δ 165/269 (61%)
Example 53.
The NOV53 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 53A.
Table 53A. NOV53 Sequence Analysis
NOV53a, CG56144-01 SEQ ID NO: δ09 jl l51 bp DNA Sequence ORF Start: ATG at 90 ORF Stop: TAG at 1056
TAATCTTTGCAGGTGGGATAGCACAGGTTGAACTCTAATCATATATACTGTAGAAGGTATATATAGAA
GGTGAAGAAGCCCTGTAAAAAATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTC
AACACATCCAGCTGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCA TCCCCTTCTGCTTTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCT GATGCAGCCCTCCATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTC TTCTACAACGCTGCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCT GTCTGGTCCAGATGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCC TTTGACCGCTATGTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCAC CAAGATTGGCATGGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGAC GCTTCCACTACTGCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTG GCGTGTGGGGACACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTAGTGTGGTGTTGGA CCTGCTCTTTGTTATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGG CCCGCTACAAAGCATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTA GTCATCTCTTCAGTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTAT TTTCTATCTCCTTTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTG AGTATGTGCTCAGTCTATTCCAGAGAAAGAACATGTAGATGGATAGTTCTCTTTTTTTATCCCACTTG
CCAAGTAATGAGAATGCTGGATTGGGGTTGAGGGGAAAAATCTAAATAGGAAAATTGCAGAGT
NOV53a, CG56144-01 SEQ ID NO: δl0 322 aa MW at 36121.9kD Protein Sequence
MTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLFIIQADAALHEP MYLFLAMLATIDLVLSSTTLPK LAIF FRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRYVAI CKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGDTSF NNIYGIAVAMFSWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWISSVMH RVARHAAPRVHILLAIFYLLFPPMVNPIIYGVKTKQIREYVLSLFQRKNM
NOV53b, 170645965 SEQ ID NO: δl l 9δl bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGC TGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCTTCTGCT TTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCTGATGCAGCCCTC CATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCT GCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGA TGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTAT GTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCAT GGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACT GCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGAC ACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGT TATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGG CATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCA GTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTATCTCCT TTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCA GTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53b, 170645965 SEQ ID NO: δl2 327 aa MW at 36635.5kD Protein Sequence
GSTMTRRFPGAMLPSNITSTHPAVFLLVGI PGLEHLHAWI S I PFCFAYTLALLGNCTLLFI IQADAAL HEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRY VAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGD TSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWISS VMHRVARHAAPRVHILI.AIFYLLFPP.WNPI IYGVKTKQIREYVLSLFQRKNMLE
NOV53c, 16δδ69277 SEQ ID NO: δl 3 9δl bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGC TGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCTTCTGCT TTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCTGATGCAGCCCTC CATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCT GCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGA TGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTAT GTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCAT GGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACT GCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGAC ACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGT TATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGG CATTTGGGACATGTGCGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCA GTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTATCTCCT TTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCA GTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53c, 16δδ69277 SEQ ID NO: 814 327 aa MW at 36607.4kD Protein Sequence
GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLFI IQADAAL HEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRY VAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGD TSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCASHIGAILSTYTPWISS VMHRVARHAAPRVHILLAIFYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKNMLE
NOV53d, 170645981 SEQ ID NO: 815 981 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCAAGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGC TGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCTTCTGCT TTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCTGATGCAGCCCTC CATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCT GCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGA TGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTAT GTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCAT GGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACT GCCGAGACCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGAC ACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGT TATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGG CATTTGGGACATGTGTGTCTCACATAGGTACCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCA GTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTATCTCCT TTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCA GTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53d, 1706459δl SEQ ID NO: 816 327 aa MW at 36720.5kD Protein Sequence
GSTKTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLFIIQADAAL HEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRY VAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRDPVIAHCYCEHMAWRLACGD TSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGTILSTYTPWISS VMHRVARHAAPRVHILLAIFYLLFPPMVNPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53e, 168δ69262 SEQ ID NO: δl 7 9δl bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGC TGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCTTCTGCT TTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCGGGCTGATGCAGCCCTC CATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCT GCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGA TGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTAT GTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCAT GGCTGCTGTGGCCTGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACT GCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGAC ACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGT TATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGG CATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCA GTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTATCTCCT TTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCA GTCTATTCCAGAGAAAGAACATGCTCGAG NOV53e, 16δ869262 SEQ ID NO: 818 327 aa MW at 36693.5kD Protein Sequence
GSTMTRRFPGAMLPSNITSTHPAVFLLVGI PGLEHLHAWISI PFCFAYTLALLGNCTLLFI IRADAAL HEPMYLFLAMLATIDLVLSSTTLPK LAIF FRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRY VAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGD TSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWISS VMHRVARHAAPRVHILLAIFYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKNMLE
NOV53f, 168δ69254 SEQ ID NO: δl 9 9δl bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGC TGTCTTTTTGTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCCTCTGCT TTGCTTATACTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCTGATGCAGCCCTC CATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCT GCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGA TGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTAT GTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCAT GGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACT GCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGAC ACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGT TATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGG CATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCA GTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTATCTCCT TTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCA GTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53f, 16δδ69254 SEQ ID NO: δ20 327 aa MW at 36601.4kD Protein Sequence
GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPLCFAYTLALLGNCTLLFIIQADAAL HEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRY VAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGD TSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWISS VMHRVARHAAPRVHILLAIFYLLFPPMVNPIIYGVKTKQIREYVLSLFQRKN LE
NOV53g, CG56144-02 SEQ ID NO: δ21 966 bp DNA Sequence ORF Start: ATG at 1 JORF Stop: end of sequence
ATGACAAGGAGATTTCCAGGAGCCATGCTTCCCTCTAATATCACCTCAACACATCCAGCTGTCTTTTT GTTGGTAGGAATTCCTGGTTTGGAACACCTGCATGCCTGGATCTCCATCCCCTTCTGCTTTGCTTATA CTCTGGCCCTGCTAGGCAACTGTACCCTTCTCTTCATTATCCAGGCTGATGCAGCCCTCCATGAACCC ATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTACAACGCTGCCCAAAAT GCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGGTCCAGATGTTCTTCC TTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGACCGCTATGTGGCCATC TGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGATTGGCATGGCTGCTGT GGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCCACTACTGCCGAGGCC CAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGTGGGGACACTAGCTTC AACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGACCTGCTCTTTGTTATCCTGTC TTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCTACAAGGCATTTGGGA CATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATCTCTTCAGTCATGCAC CGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTTCTTGCTATTTTCTATCTCCTTTTCCCACC CATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATGTGCTCAGTCTATTCC AGAGAAAGAACATG
NOV53g, CG56144-02 SEQ ID NO: δ22 322 aa MW at 3614δ.0kD Protein Sequence
MTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLFI IQADAALHEP MYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFDRYVAI CKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLACGDTSF NNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWISSVMH RVARHAAPRVHILLAIFYLLFPPMVNPIIYGVKTKQIREYVLSLFQRKNM
NOV53h, CG56144-03 SEQ ID NO: 823 777 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GCCCTCCATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTAC AACGCTGCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGG TCCAGATGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGAC CGCTATGTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGAT TGGCATGGCTGCTGTGGCCTGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCC ACTACTGCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGT GGGGACACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTCTATTGTGGTGTTGGACCTGCT CTTTGTTATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCT ACAAGGCATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATC TCTTCAGTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTA TCTCCTTTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATG TGCTCAGTCTATTCCAGAGAAAGAACATG
NOV53h, CG56144-03 SEQ ID NO: 824 259 aa MW at 29252.8kD Protein Sequence
ALHEPMYLFLAMIATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFD RYVAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLAC GDTSFNNIYGIAVAMSIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWI SSVMHRVARHAAPRVHILLAIFYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKNM
NOV53i, CG56144-04 SEQ ID NO: δ25 777 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GCCCTCCATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTCTTCTAC AACGCTGCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCTGTCTGG TCCAGATGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCCTTTGAC CGCTATGTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCACCAAGAT TGGCATGGCTGCTGTGGCCTGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGACGCTTCC ACTACTGCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTGGCGTGT GGGGACACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTCTATTGTGGTGTTGGACCTGCT CTTTGTTATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGGCCCGCT ACAAGGCATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTAGTCATC TCTTCAGTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTATTTTCTA TCTCCTTTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTGAGTATG TGCTCAGTCTATTCCAGAGAAAGAACATG
NOV53i, CG56144-04 SEQ ID NO: δ26 259 aa MW at 29252. δkD Protein Sequence
ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQ FFLHSFSIMESAVLLAMAFD RYVAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLAC GDTSFNNIYGIAVAMSIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWI SSVMHRVARHAAPRVHILLAI FYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKNM
NOV53J, CG56144-05 SEQ ID NO: δ27 7δ9 bp DNA Sequence ORF Start: at 7 JORF Stop: at 7δ4
GGATCCGCCCTCCATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTC
TTCTACAACGCTGCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCT GTCTGGTCCAGATGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCC TTTGACCGCTATGTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCAC CAAGATTGGCATGGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGAC GCTTCCACTACTGCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTG GCGTGTGGGGACACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGA CCTGCTCTTTGTTATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGG CCCGCTACAAGGCATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTA GTCATCTCTTCAGTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTAT TTTCTATCTCCTTTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTG AGTATGTGCTCAGTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53J, CG56144-05 SEQ ID NO: δ2δ 259 aa MW at 292δ2.9kD Protein Sequence
ALHEP^TΪ'LFLAMLATIDLVLSSTTLPKMLAIF FRDQEI FFACLVQMFFLHSFSIMESAVLLAMAFD RYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLAC GDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWI SSVMHRVARHAAPRVHILLAIFYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKN
NOV53k, CG56144-06 SEQ ID NO: δ29 789 bp DNA Sequence ORF Start: at 7 ORF Stop: at 784
GGATCCGCCCTCCATGAACCCATGTACCTCTTTCTGGCCATGTTGGCAACCATTGACTTGGTTCTTTC
TTCTACAACGCTGCCCAAAATGCTTGCCATATTCTGGTTCAGGGATCAGGAGATCAACTTCTTTGCCT GTCTGGTCCAGATGTTCTTCCTTCACTCCTTCTCCATCATGGAGTCAGCAGTGCTGCTGGCCATGGCC TTTGACCGCTATGTGGCCATCTGCAAGCCATTGCACTACACGACGGTCCTGACTGGGTCCCTCATCAC CAAGATTGGCATGGCTGCTGTGGCCCGGGCTGTGACACTAATGACTCCACTCCCCTTCCTGCTCAGAC GCTTCCACTACTGCCGAGGCCCAGTGATTGCCCATTGCTACTGTGAACACATGGCTGTGGTAAGGCTG GCGTGTGGGGACACTAGCTTCAACAATATCTATGGCATTGCTGTGGCCATGTTTATTGTGGTGTTGGA CCTGCTCTTTGTTATCCTGTCTTATGTCTTCATCCTTCAGGCAGTTCTCCAGCTTGCCTCTCAGGAGG CCCGCTACAAGGCATTTGGGACATGTGTGTCTCACATAGGTGCCATCCTGTCCACCTACACTCCAGTA GTCATCTCTTCAGTCATGCACCGTGTAGCCCGCCATGCTGCCCCTCGTGTCCACATACTCCTTGCTAT TTTCTATCTCCTTTTCCCACCCATGGTCAATCCTATCATATATGGAGTCAAGACCAAGCAGATTCGTG AGTATGTGCTCAGTCTATTCCAGAGAAAGAACATGCTCGAG
NOV53k, CG56144-06 SEQ ID NO: 830 259 aa MW at 29282.9kD Protein Sequence
ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSFSIMESAVLLAMAFD RYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFHYCRGPVIAHCYCEHMAWRLAC GDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPWI SSVMHRVARHAAPRVHILLAIFYLLFPPMVNPI IYGVKTKQIREYVLSLFQRKNM A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 53B.
Table 53B. Comparison of the NOV53 protein sequences.
NOV53a MTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHA ISIPFCFAYTLALLGNCTLLF
NOV53b GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLF
NOV53C GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLF
NOV53d GSTKTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLF
NOV53e GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLF
NOV53f GSTMTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHA ISIPLCFAYTLALLGNCTLLF
NOV53g MTRRFPGAMLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLF
NOV53h
NOV53i
NOV53J
NOV53k
NOV53a IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF
NOV53b IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF
NOV53C IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSF
NOV53d IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF
NOV53e IIRADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSF
NOV53f IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF NOV53g IIQADAALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF
N0V53h ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSF
NOV53i ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSF
NOV53j ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIF FRDQEINFFACLVQMFFLHSF
NOV53k ALHEPMYLFLAMLATIDLVLSSTTLPKMLAIFWFRDQEINFFACLVQMFFLHSF
NOV53a SI ESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53b SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53C SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53d SIMESAVLLA AFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53e SIMESAVLLA AFDRYVAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFH
NOV53f SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53g SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53h SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFH
NOV53i SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVAWAVTLMTPLPFLLRRFH
NOV53J SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53k SIMESAVLLAMAFDRYVAICKPLHYTTVLTGSLITKIGMAAVARAVTLMTPLPFLLRRFH
NOV53a YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFSWLDLLFVILSYVFILQAVLQ
NOV53b YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53C YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53d YCRDPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53e YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53f YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53g YCRGPVIAHCYCEHMAWRLACGDTSFN IYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53h YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMSIWLDLLFVILSYVFILQAVLQ
NOV53i YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMSIWLDLLFVILSYVFILQAVLQ
NOV53J YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53k YCRGPVIAHCYCEHMAWRLACGDTSFNNIYGIAVAMFIWLDLLFVILSYVFILQAVLQ
NOV53a LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53b LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53c LASQEARYKAFGTCASHIGAI STYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53d LASQEARYKAFGTCVSHIGTILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53e LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53f LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53g LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53h LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53i LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53J LASQEARYKAFGTCVSHIGAILSTYTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53k LASQEARYKAFGTCVSHIGAI S YTPWISSVMHRVARHAAPRVHILLAIFYLLFPPMV
NOV53a NPIIYGVKTKQIREYVLSLFQRKNM--
NOV53b NPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53C NPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53d NPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53e NPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53f NPIIYGVKTKQIREYVLSLFQRKNMLE
NOV53g NPIIYGVKTKQIREYVLSLFQRKNM--
NOV53h NPIIYGVKTKQIREYVLSLFQRKNM--
NOV53i NPIIYGVKTKQIREYVLSLFQRKNM--
NOV53J NPIIYGVKTKQIREYVLSLFQRKNM--
NOV53k NPIIYGVKTKQIREYVLSLFQRKNM-- NOV53a (SEQ ID NO 810)
NOV53b (SEQ ID NO 812)
NOV53C (SEQ ID NO 814)
NOV53d (SEQ ID NO 816)
NOV53e (SEQ ID NO 818)
NOV53f (SEQ ID NO 820)
NOV53g (SEQ ID NO 822)
NOV53h (SEQ ID NO 824)
NOV53i (SEQ ID NO 826)
NOV53J (SEQ ID NO 828)
NOV53k (SEQ ID NO 830)
Further analysis ofthe NOV53a protein yielded the following properties shown in Table 53C.
Table 53C. Protein Sequence Properties NOV53a
SignalP analysis: Cleavage site between residues 64 and 65
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 4 ; pos . chg 2 ; neg . chg 0 H-region : length 26 ; peak value 10 .58 PSG score : 6 . 18
GvH : von Heij ne ' s method for signal seq . recognition GvH score (threshold : -2 . 1) : -3 .34 possible cleavage site : between 61 and 62
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation
Init position for calculation : Tentative number of TMS ( s) for the threshold 0.5 :
INTEGRAL Likelihood = -3 29 Transmembrane 43 - 59
INTEGRAL Likelihood = -2 07 Transmembrane 69 • - 85
INTEGRAL Likelihood = -1 .70 Transmembrane 104 ■ - 120
INTEGRAL Likelihood = 0 26 Transmembrane 157 - - 173
INTEGRAL Likelihood =-11 09 Transmembrane 210 - • 226
INTEGRAL Likelihood = 0 21 Transmembrane 255 - • 271
INTEGRAL Likelihood = -3 03 Transmembrane 284 - • 300
PERIPHERAL Likelihood = 1 54 (at 21)
ALOM score : -11.09 (number of TMSs : 7 )
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 50 Charge difference: -1.5 C(-1.5) - N( 0.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 12.17 Hyd Moment(95): 11.23 G content: 3 D/E content: 1 S/T content: 5 Score: -1.65
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 14 RRF | PG
NUCDISC: discrimination of nuclear localization signals pat4 : none pa 7: none bipartite: none content of basic residues: 6.8% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : TRRF
KKXX-like motif in the C-terminus : QRKN
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: found TLPK at 87
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
77.8 %: endoplasmic reticulum
11.1 %: nuclear
11.1 %: mitochondrial
>> prediction for CG56144-01 is end (k=9)
A search ofthe NOV53a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 53D.
Figure imgf000786_0001
In a BLAST search of public sequence databases, the NOV53a protein was found to have homology to the proteins shown in the BLASTP data in Table 53E.
Figure imgf000787_0001
PFam analysis indicates that the NOV53a protein contains the domains shown in the Table 53F.
Figure imgf000787_0002
Example 54.
The NOV54 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 54 A. Table 54A. NOV54 Sequence Analysis
NOV54a, CG56146-02 SEQ ID NO: 831 807 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: end of sequence
ATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTTAGACCT GTGTCTCATTTCTGACACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCATCTCCT TCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATCCTTACT GCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAGCAGAGG GCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACACAGCTG GAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCTGCCCTA CTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTGTTATGC ATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGATATCAC AGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTGTTTCTT GTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCTGGTGTC TGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGGACATTA AATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGAC
NOV54a, CG56146-02 SEQ ID NO: 832 269 aa M at 29515.5kD Protein Sequence
MILDHRLHMAMYFFLRHLSFLDLCLISDTVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILT AMSYDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPAL LKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFL VTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDD
NOV54b, CG56146-01 SEQ ID NO: 833 995 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TAA at 966
GGCGCTTATAATTTTGAACTATGACCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACT
GAGAATTGGGTGCTCCTGAGGCTGCATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGAT GAATTTAGTCATCATTCTCCTCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCC GACATTTGTCCTTCTTAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTC GCCTCCACTGACTCCATCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGG ATCAGAGATTGGCATCCTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACT GTGAGGCTGTCATGAGCAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCC TTGGGACTCTTGTACACAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTT CTTCTGCGATGTCCCTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTG TGGCCATTGGGGTCTGTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTC TCTGCTGTGTTAAGGATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCT CATTGTTGTCACTGTGTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTT CTATTCTAGACTTGCTGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTAC TGTCTGAAGAACAAGGACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGT AATGAAAGATGACTAAAGTTGAAGATGGGAAGTACTTTTTTTG
NOV54b, CG56146-01 SEQ ID NO: 834 315 aa MW at 34934.2kD Protein Sequence
MTNQTQMME FLLVRFTEN VLLRLHALLFSL I YLTAVLMNLVI I LLMI LDHRLHMAMY FFLRHLS FLD LCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDRYAAICCPLHCEAVMSR GLCVQLMALSWLNRGALGLL YTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAI ISVSVAIGVCY AFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLV SVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDD
NOV54c, 170646057 SEQ ID NO: δ35 δl9 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT AGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATC CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA CAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCT GCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTG TTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGA TATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTG TTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATACACCTTCTATTCTAGACTTGCT GGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGG ACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCTC GAG
NOV54c, 170646057 SEQ ID NO: 836 273 aa MW at 298δδ.0kD Protein Sequence
GSMILDHRLHMAMYFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGI LTAMSYDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTV FLVTGAVAYLKPGSDTPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVL NVRSSGVMKDDL
E
NOV54d, 170646049 SEQ ID NO: δ37 819 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT AGACCTGTGTCTCATTTCTGCCGCAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATC CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA CAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCT GCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTG TTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGA TATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTG TTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCT GGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGG ACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCTC GAG
NOV54d, 170646049 SEQ ID NO: 83δ 273 aa MW at 29δ27.9kD Protein Sequence
GSMILDHRLHMAMYFFLRHLSFLDLCLISAAVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGI LTAMSYDRYAAICCPLHCEAVMSRGLCVQLMALS LNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTV FLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVL NVRSSGVMKDDL E
NOV54e, 170646053 SEQ ID NO: δ39 δl9 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT AGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCCGGCTGGATCAGAGATTGGCATC CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA CAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCT GCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGGGGCCATTGGGGTCTG TTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGA TATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTG TTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCT GGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGG ACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCTC GAG
7δ5 NOV54e, 170646053 SEQ ID NO: δ40 273 aa MW at 29799.δkD Protein Sequence
GSMILDHRLHMAMYFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLPAGSEIGI LTAMSYDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAIISVSGAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTV FLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDDL E
NOV54f, 174307717 SEQ ID NO: δ41 960 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGACCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACTGAGAATTGGGT GCTCCTGAGGCTGCATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGATGAATTTAGTCA TCATTCTCCTCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCC TTCTTAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGA CTCCATCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTG GCATCCCTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTAAGGCTGTC ATGAGCAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTT GTACACAGCTGGAACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATG TCCCTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGG GTCTGTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTT AAGGATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCA CTGTGTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGAC TTGCTGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAA CAAGGACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATG ACCTCGAG
NOV54f, 174307717 SEQ ID NO: δ42 320 aa MW at 35404 JkD Protein Sequence
GSTMTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFFLRHLS FLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGIPTAMSYDRYAAICCPLHCKAV MSRGLCVQLMALS LNRGALGLLYTAGTFSLNFYGSDELHQFFCDVPALLKLTCSKEHAIISVSVAIG VCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILD LLVSVFYS VAP PTLNPVI YCLKNKDI KS ALS KVLWNVRS SGVMKDDLE
NOV54g, 16δδ693δ3 SEQ ID NO: 843 820 bp DNA Sequence ORF Start: at 296 ORF Stop: end of sequence
GGATCCATGATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTT lAGACCTGTGTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCA,
TCTCCTTCCTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATC
CTTACTGCCATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAG
CAGAGGGCTCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACA
CAGCTGGAACATTCTCTTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCC TGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCT GTTATGCATTTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGG ATATCACAGAGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGT GTTTCTTGTAACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGC TGGTGTCTGTGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAG GACATTAAATCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACCT CGAG
NOV54g, 168869383 SEQ ID NO: 844 175 aa MW at l9239.2kD Protein Sequence
WLCPGSTEGPWDSCTQLEHSLLNFYGSDELHQFFCDVPALLKLTCSKEHAIISVSVAIGVCYAFSCLV CIWSYVYIFSAVLRISQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSV APPTLNPVIYCLKNKDIKSALSKVLWNVRSSGVMKDDLE
Figure imgf000791_0001
7δ7 NOV54J, CG56146-04 SEQ ID NO: δ50 20 aa MW at 2519.0kD Protein Sequence
MMEFLLVRFTEN VLLRLHA
NOV54k, CG56146-05 SEQ ID NO: δ51 60 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GATGTCCCTGCCCTACTAAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGT;
NOV54k, CG56146-05 SEQ ID NO: δ52 20 aa MW at 2124.5kD Protein Sequence
DVPALLKLTCS KEHAI I S VS
NOV541, CG56146-06 SEQ ID NO: δ53 952 bp DNA Sequence ORF Start: at 3 ORF Stop: TAG at 942
CCAATCAGACACAGATGATGGAATTCTTGCTTGTGAGATTTACTGAGAATTGGGTGCTCCTGAGGCTG CATGCTTTGCTCTTCTCACTGATCTACCTCACGGCTGTGCTGATGAATTTAGTCATCATTCTCCTCAT GATTCTGGACCATCGTCTCCACATGGCAATGTACTTTTTCCTCCGACATTTGTCCTTCTTAGACCTGT GTCTCATTTCTGCCACAGTCCCCAAATCCATCCTCAACTCTGTCGCCTCCACTGACTCCATCTCCTTC CTGGGGTGTGTGTTGCAGCTCTTCTTGGTGGTACTGCTGGCTGGATCAGAGATTGGCATCCTTACTGC CATGTCCTATGACCGCTATGCTGCCATCTGCTGCCCCCTACACTGTGAGGCTGTCATGAGCAGAGGGC TCTGTGTCCAGTTGATGGCTCTGTCCTGGCTCAACAGAGGGGCCTTGGGACTCTTGTACACAGCTGGA ACATTCTCTCTGAATTTTTATGGCTCTGATGAGCTACATCAGTTCTTCTGCGATGTCCCTGCCCTACT AAAGCTCACTTGTTCTAAAGAACATGCCATCATTAGTGTCAGTGTGGCCATTGGGGTCTGTTATGCAT TTTCATGTTTAGTTTGCATTGTAGTTTCCTATGTGTACATTTTCTCTGCTGTGTTAAGGATATCACAG AGACAGAGACAATCCAAAGCCTTTTCCAACTGTGTGCCTCACCTCATTGTTGTCACTGTGTTTCTTGT AACAGGTGCTGTTGCTTATTTAAAGCCAGGGTCTGATGCACCTTCTATTCTAGACTTGCTGGTGTCTG TGTTCTATTCTGTCGCACCTCCAACCTTGAACCCTGTTATCTACTGTCTGAAGAACAAGGACATTAAA TCCGCTCTGAGTAAAGTCCTGTGGAATGTTAGAAGCAGTGGGGTAATGAAAGATGACTAGCAATTGGG
NOV541, CG56146-06 SEQ ID NO: 854 313 aa MW at 34701.9kD Protein Sequence
NQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAMYFFLRHLSFLDLC LISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMSYDRYAAICCPLHCEAVMSRGL CVQLMALS LNRGALGLLYTAGTFSLNFYGSDELHQFFCDVP ALLKLTCSKEHAI I SVSVAIGVCYAF SCLVCI WSYVYI FSAVLRI SQRQRQSKAFSNCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSV FYSVAPPTLNPVIYCLKNKDIKSALSKVL NVRSSGVMKDD
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 54B.
Table 54B. Comparison of the NOV54 protein sequences.
NOV54a MILDHRLHMAM
NOV54b MTNQTQMMEFLLVRFTEN VLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAM
NOV54C GSMILDHRLHMAM
NOV54d GSMILDHRLHMAM
NOV54e GSMILDHRLHMAM
NOV54f GSTMTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAM
NOV54g
NOV54h MTNQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAM
NOV54i NQTQMMEFLLVRFTENWVLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAM
NOV54J
NOV54k
NOV541 NQTQMMEFLLVRFTEN VLLRLHALLFSLIYLTAVLMNLVIILLMILDHRLHMAM
78δ N0V54a YFFLRHLSFLDLCLISDTVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
N0V54b YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54C YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54d YFFLRHLSFLDLCLISAAVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54e YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLPAGSEIGILTAMS
NOV54f YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGIPTAMS
NOV54g
NOV54h YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54i YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54j
NOV54k
NOV541 YFFLRHLSFLDLCLISATVPKSILNSVASTDSISFLGCVLQLFLWLLAGSEIGILTAMS
NOV54a YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54b YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54C YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54d YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV5 e YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54f YDRYAAICCPLHCKAVMSRGLCVQLMALS LNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54g WLCPGSTEGPWDS- -CTQLEHS LLNFYGSDELHQFFC NOV54h YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54i YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC NOV54J MMEFLLVRFT NOV54k NOV541 YDRYAAICCPLHCEAVMSRGLCVQLMALSWLNRGALGLLYTAGTFSLNFYGSDELHQFFC
NOV54a DVPALLKLTCSKEHAI ISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54b DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54C DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54d DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54e DVPALLKLTCSKEHAIISVSGAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54f DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54g DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54h DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54i DVPALLKLTCSKEHAIISVSVAIGVCYAFSCLVCIWSYVYIFSAVLRISQRQRQSKAFS NOV54J EN VLLRLHA NOV5 k DVPALLKLTCSKEHAI ISVS NOV541 DVPALLKLTCSKEHAI ISVSVAIGVCYAFSCLVCI SYVYIFSAVLRISQRQRQSKAFS
NOV54a NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54b NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54C NCVPHLIWTVFLVTGAVAYLKPGSDTPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54d NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54e NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54f NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54g NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54h NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54i NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS NOV54k NOV541 NCVPHLIWTVFLVTGAVAYLKPGSDAPSILDLLVSVFYSVAPPTLNPVIYCLKNKDIKS
NOV54a ALSKVLWNVRSSGVMKDD--
7δ9 NOV54b ALSKVLWNVRSSGVMKDD- -
NOV54C ALSKVL NVRSSGVMKDDLE
NOV54d ALSKVL NVRSSGVMKDDLE
NOV54e ALSKVLWNVRSSGVMKDDLE
NOV54f ALSKVLWNVRSSGVMKDDLE
NOV54g ALSKVLWNVRSSGVMKDDLE
NOV54h ALSKVLWNVRSSGVMKDD- -
NOV54i ALSKVLWNVRSSGVMKDD- -
NOV54J
NOV54k NOV541 ALSKVLWNVRSSGVMKDD- -
NOV54a (SEQ ID NO 832)
NOV54b (SEQ ID NO 834)
NOV54C (SEQ ID NO 836)
NOV54d (SEQ ID NO 838)
NOV54e (SEQ ID O 840)
NOV54f (SEQ ID NO 842)
NOV54g (SEQ ID O 844)
NOV54h (SEQ ID NO 846)
NOV54i (SEQ ID NO 848)
Figure imgf000794_0001
NOV54k (SEQ ID NO 852)
NOV541 (SEQ ID NO 854)
Further analysis ofthe NOV54a protein yielded the following properties shown in Table 54C.
Figure imgf000794_0002
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 51 Charge difference: 0.0 C(-1.0) - N(-1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.56 Hyd Moment(95): 1.99 G content: 0 D/E content: 2 S/T content: 1 Score: -5.34
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 26 LRH|LS
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 7.1% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: VMKD
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 %: endoplasmic reticulum 33.3 %: mitochondrial
>> prediction for CG56146-02 is end (k=9)
A search ofthe NOV54a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 54D.
Figure imgf000797_0001
In a BLAST search of public sequence databases, the NOV54a protein was found to have homology to the proteins shown in the BLASTP data in Table 54E.
Figure imgf000798_0001
PFam analysis indicates that the NOV54a protein contains the domains shown in the Table 54F.
Figure imgf000798_0002
Example 55.
The NOV55 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 55A.
Table 55A. NOV55 Sequence Analysis
NOV55a, CG5625δ-04 SEQ ID NO: δ55 2δ2δ bp DNA Sequence ORF Start: ATG at 63 ORF Stop: TAA at 2δ26
GTCTCTGGCCTATCAGGAGGACAACTGGTGCTGCAATAGAAGCCAGTGGCTAAGTCTCGTGTATGGCG
TGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTACCTTTGTGCTCTTCCT GAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCAGAACAATGAGTCCT IGTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTT GGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCAT CATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAATTAAGA AACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCTCCAACCTGACCCTT ATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGTGGTCATGGGTTCAT TGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTTCATCATCATTGGCA TCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAACATCTACGAGTCTTCTTCATCACC GCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGT CCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTGGGTGGCAG ATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAACACCGAGGAATTATC ATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATGAATTCCCATTTTCT AGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGAGATGATCCGGATTC TCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGATGGCCAATTACTAT GCTCTTTCCCACCAACAGAAGAGCCGCGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGC AGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGCGAGGTGCACA CCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACCAGTGCCTGGAGAAC TGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACCATGTATGTGGACTA CAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGGCACGGTGGTTCTGA AGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAA CACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCAGC AATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCACAGTTACCATCT TGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCAGTGAGAGTATTGGT GTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTCCCCTTTAGGACAGT AGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATG ATGAAACTGTGAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATACGAAAGGCAAGAGAATTTC TTCATTGCCCTTGGTGAACCGAAATGGATGGAACGTGGAATATCAGATGTGACAGACAGGAAGCTGAC TATGGAAGAAGAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGGGTGAACACCCCAAAC TAGAAGTCATCATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTGATCAAGAAGACAAAC CTGGCCTTGGTTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCATCACCGTCAGTGCAGC AGGGGATGAGGATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACTACGTCATGCACT TCCTGACTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTACTGCCACGGCTGGGCC TGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGACCTGGCCTCGCACTT CGGCTGCACCATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCATTTGGCACCTCTGTCC CAGATACGTTTGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCCTCCATTGGCAACGTG ACGGGCAGCAACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGTGGCCGCCATCTACTG GGCTCTGCAGGGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCACCCTCTTCACCA TCTTTGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTGGGAGGGGAGCTTGGT GGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCTCCTCTACATACTCTT TGCCACACTAGAGGCCTATTGCTACATCAAGGGGTTCTAA
NOV55a, CG5625δ-04 SEQ ID NO: δ56 921 aa MW at l02413.7kD Protein Sequence
MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENP SLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNL TLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFF ITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRG IIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMAN YYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCL ENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEE DEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSES IGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEYERQE NFFIALGEPKWMERGISDVTDRKLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKLIKK TNLALWGTHSWRDQFMEAITVSAAGDEDEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHG WACFAVSILIIGMLTAIIGDLASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIG NVTGSNAVNVFLGIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGE LGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGF NOV55b, CG5625δ-02 SEQ ID NO: 857 2840 bp DNA Sequence ORF Start: ATG at 63 ORF Stop: TAA at 2838
GTCTCTGGCCTATCAGGAGGACAACTGGTGCTGCAATAGAAGCCAGTGGCTAAGTCTCGTGTATGGCG
TGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTACCTTTGTGCTCTTCCT GAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCAGAACAATGAGTCCT GTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTT GGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCAT CATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAATTAAGA AACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCTCCAACCTGACCCTT ATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGTGGTCATGGGTTCAT TGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTTCATCATCATTGGCA TCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAGCATCTACGAGTCTTCTTCATCACC GCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGT CCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTGGGTGGCAG ATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAACACCGAGGAATTATC ATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATGAATTCCCATTTTCT AGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGAGATGATCCGGATTC TCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGATGGCCAATTACTAT GCTCTTTCCCACCAACAGAAGAGCCGTGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGC AGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGCGAGGTGCACA CCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACCAGTGCCTGGAGAAC TGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACCATGTATGTGGACTA CAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGGCACGGTGGTTCTGA AGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAA CACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCAGC AATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCACAGTTACCATCT TGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCAGTGAGAGTATTGGT GTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTCCCCTTTAGGACAGT AGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATG ATGAAACTGTCAAAACAATTCACATCAAGGTAATTGATGATGAGGCATATGAGAAAAACAAGAATTAC TTCATTGAGATGATGGGCCCCCGCATGGTGGATATGAGTTTTCAGAAAGCGCTCCTGTTATCTCCAGA CAGGAAGCTGACTATGGAAGAAGAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGGGTG AACACCCCAAACTAGAAGTCATCATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTGATC AAGAAGACAAACCTGGCCTTGGTTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCATCAC CGTCAGTGCAGCAGGGGATGAGGATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACT ACGTCATGCACTTCCTGACTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTACTGC CACGGCTGGGCCTGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGACCT GGCCTCGCACTTCGGCTGCACCATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCATTTG GCACCTCTGTCCCAGATACGTTTGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCCTCC ATTGGCAACGTGACGGGCAGCAACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGTGGC CGCCATCTACTGGGCTCTGCAGGGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCA CCCTCTTCACCATCTTTGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTGGGA GGGGAGCTTGGTGGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCTCCT CTACATACTCTTTGCCACACTAGAGGCCTATTGCTACATCAAGGGGTTCTAA
NOV55b, CG56258-02 SEQ ID NO: 858 925 aa MW at l02802.3kD Protein Sequence
MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENP SLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNL TLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFF ITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRG IIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMAN YYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCL ENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEE DEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSES IGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTIHIKVIDDEAYEKNK NYFIEMMGPRMVDMSFQKALLLSPDRKLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDK LIKKTNLALWGTHSWRDQFMEAITVSAAGDEDEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTE YCHGWACFAVSILIIGMLTAI IGDLASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYAD ASIGNVTGSNAVNVFLGIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPH LGGELGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGF
NOV55c, 258076220 SEQ ID NO: 859 2778 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGGCGTGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTAC CTTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGC AGAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCG GAGAACCCTTCCCTTGGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTT CCTTGGGGTGTCCATCATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGG AGGTGACAATTAAGAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTC TCCAACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTG TGGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGT TCATCATCATTGGCATCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAGCATCTACGA GTCTTCTTCATCACCGCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTT CTCCCCTGGTGTGGTCCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTC TGGCCTGGGTGGCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAA CACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGAT GAATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAG AGATGATCCGGATTCTCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAG ATGGCCAATTACTATGCTCTTTCCCACCAACAGAAGAGCCGCGCCTTCTACCGTATCCAAGCCACTCG TATGATGACTGGTGCAGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCA TGAGCGAGGTGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTAC CAGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGAC CATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGG GCACGGTGGTTCTGAAGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATT TTTGAGGAGGATGAACACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGA GGGGATGCCTCCAGCAATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGG CCACAGTTACCATCTTGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTC AGTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGT CCCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGT TGGAATTCAAGAATGATGAAACTGTGAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATACGAA AGGCAAGAGAATTTCTTCATTGCCCTTGGTGAACCGAAATGGATGGAACGTGGAATATCAGATGTGAC AGACAGGAAGCTGACTATGGAAGAAGAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGG GTGAACACCCCAAACTAGAAGTCATCATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTG ATCAAGAAGACAAACCTGGCCTTGGTTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCAT CACCGTCAGTGCAGCAGGGGATGAGGATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTG ACTACGTCATGCACTTCCTGACTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTAC TGCCACGGCTGGGCCTGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGA CCTGGCCTCGCACTTCGGCTGCACCATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCAT TTGGCACCTCTGTCCCAGATACGTTTGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCC TCCATTGGCAACGTGACGGGCAGCAACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGT GGCCGCCATCTACTGGGCTCTGCAGGGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCG TCACCCTCTTCACCATCTTTGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTG GGAGGGGAGCTTGGTGGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCT CCTCTACATACTCTTTGCCACACTAGAGGCCTATTGCTACATCAAGGGGTTCCTCGAG
NOV55c, 258076220 SEQ ID NO: 860 926 aa MW at 102901.2kD Protein Sequence
GSTMAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYP ENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETV SNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLR VFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDK HRGIIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVE MANYYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSY QCLENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDI FEEDEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHV SESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEYE RQENFFIALGEPKWMERGISDVTDRKLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKL IKKTNLALWGTHSWRDQFMEAITVSAAGDEDEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEY CHGWACFAVSILIIGMLTAIIGDLASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADA SIGNVTGSNAVNVFLGIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHL GGELGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGFLE
NOV55d, 248057963 SEQ ID NO: 861 2685 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCAGAACAATGAGTCCTGTTCAGGGTC ATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTTGGGGACAAGA TTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCATCATTGCTGAC CGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAATTAAGAAACCCAATGG AGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCTCCAACCTGACCCTTATGGCCCTGG GTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGTGGTCATGGGTTCATTGCTGGTGAT CTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTTCATCATCATTGGCATCTGTGTCTA CGTGATCCCAGACGGAGAGACTCGCAAGATCAAACATCTACGAGTCTTCTTCATCACCGCTGCTTGGA GTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGTCCAGGTTTGG GAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTGGGTGGCAGATAAACGACT GCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAACACCGAGGAATTATCATAGAGACAG AGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATGAATTCCCATTTTCTAGATGGGAAC CTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGAGATGATCCGGATTCTCAAGGATCT GAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGATGGCCAATTACTATGCTCTTTCCC ACCAACAGAAGAGCCGCGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGCAGGCAATATC CTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGCGAGGTGCACACCGATGAGCC TGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACCAGTGCCTGGAGAACTGTGGGGCTG TACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACCATGTATGTGGACTACAAAACAGAG GATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGGCACGGTGGTTCTGAAGCCAGGAGA GACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAACACTTCTTTG TAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCAGCAATATTCAAC AGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCACAGTTACCATCTTGGATGATGA CCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCAGTGAGAGTATTGGTGTTATGGAGG TCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTCCCCTTTAGGACAGTAGAAGGGACA GCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATGATGAAACTGT GAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATACGAAAGGCAAGAGAATTTCTTCATTGCCC TTGGTGAACCGAAATGGATGGAACGTGGAATATCAGATGTGACAGACAGGAAGCTGACTATGGAAGAA GAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGGGTGAACACCCCAAACTAGAAGTCAT CATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTGATCAAGAAGACAAACCTGGCCTTGG TTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCATCACCGTCAGTGCAGCAGGGGATGAG GATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACTACGTCATGCACTTCCTGACTGT CTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTACTGCCACGGCTGGGCCTGCTTCGCCG TCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGACCTGGCCTCGCACTTCGGCTGCACC ATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCATTTGGCACCTCTGTCCCAGATACGTT TGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCCTCCATTGGCAACGTGACGGGCAGCA ACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGTGGCCGCCATCTACTGGGCTCTGCAG GGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCACCCTCTTCACCATCTTTGCATT TGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTGGGAGGGGAGCTTGGTGGCCCCCGTG GCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCTCCTCTACATACTCTTTGCCACACTA GAGGCCTATTGCTACATCAAGGGGTTCCTCGAG
NOV55d, 24δ057963 SEQ ID NO: δ62 895 aa MW at 99385.0kD Protein Sequence
GSEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIAD RFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGD LGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVW EGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFLDGN LVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQATRMMTGAGNI LKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLTWRKGGDMSKTMYVDYKTE DGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEEDEHFFVRLSNVRIEEEQPEEGMPPAIFN SLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGT AKGGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEYERQENFFIALGEPKWMERGISDVTDRKLTMEE EEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDE DEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGDLASHFGCT IGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFLGIGLAWSVAAIYWALQ GQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGPRGCKLATTWLFVSLWLLYILFATL EAYCYIKGFLE
NOV55e, CG56258-01 SEQ ID NO: 863 2813 bp DNA Sequence ORF Start: ATG at 9 JORF Stop: TAG at 2793
TCTCGTGTATGGCGTGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTACC
TTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCA GAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGG AGAACCCTTCCCTTGGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTC CTTGGGGTGTCCATCATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGA GGTGACAATTAAGAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCT CCAACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGT GGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTT CATCATCATTGGCATCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAGCATCTACGAG TCTTCTTCATCACCGCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTC TCCCCTGGTGTGGTCCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCT GGCCTGGGTGGCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAAC ACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATG AATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGA GATGATCCGGATTCTCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGA TGGCCAATTACTATGCTCTTTCCCACCAACAGAAGAGCCGTGCCTTCTACCGTATCCAAGCCACTCGT ATGATGACTGGTGCAGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCAT GAGCGAGGTGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACC AGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACC ATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGG CACGGTGGTTCTGAAGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTT TTGAGGAGGATGAACACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAG GGGATGCCTCCAGCAATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGC CACAGTTACCATCTTGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCA GTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTC CCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTT GGAATTCAAGAATGATGAAACTGTGAAAACTCTTCAGGTGAAGATAGTTGATGACGAGGAATATGAGA AAAAGGATAATTTCTTCATTGAGCTGGGCCAGCCCCAGTGGCTTAAGCGAGGGATTTCAGCTCTGCTA CTCAATCAAGGGGATGGGGACAGGAAGCTAACAGCCGAGGAGGAGGAGGCTCGGAGGATAGCAGAGAT GGGCAAGCCAGTTCTTGGGGAGAACTGCCGGCTGGAGGTCATCATCGAGGAGTCATATGATTTTAAGA ACACGGTGGATAAACTCATCAAGAAAACGAACTTGGCCTTGGTAATTGGGACCCATTCATGGAGGGAG CAGTTTTTAGAGGCAATTACGGTGAGCGCAGGGGACGAGGAGGAGGAGGAGGACGGGTCCCGGGAGGA GCGGCTGCCGTCGTGCTTTGACTACGTGATGCACTTCCTGACGGTGTTCTGGAAGGTGCTCTTCGCCT GTGTGCCCCCCACCGAGTACTGCCACGGCTGGGCCTGCTTTGGTGTCTCCATCCTGGTCATCGGCCTG CTCACCGCCCTCATTGGGGACCTCGCCTCCCACTTCGGCTGCACCGTTGGCCTCAAGGACTCTGTCAA TGCTGTTGTCTTCGTTGCCCTGGGCACCTCCATCCCTGACACGTTCGCCAGCAAGGTGGCGGCGCTGC AGGACCAGTGCGCCGACGCGTCCATCGGCAACGTGACCGGCTCCAACGCGGTGAACGTGTTCCTTGGC CTGGGCGTCGCCTGGTCTGTGGCCGCCGTGTACTGGGCGGTGCAGGGCCGCCCCTTCGAGGTGCGCAC TGGCACGCTGGCCTTCTCCGTCACGCTCTTCACCGTCTTCGCCTTCGTGGGCATTGCCGTGCTGCTGT ACCGGCGCCGGCCGCACATCGGCGGCGAGCTGGGCGGCCCGCGCGGACCCAAGCTCGCCACCACCGCG CTCTTCCTGGGCCTCTGGCTCCTGTACATCCTCTTCGCCAGCCTGGAGGCGTACTGCCACATCCGGGG CTTCTAGGGCCTCGCGCAGAGACTC
NOV55e, CG5625δ-01 SEQ ID NO: δ64 92 aa MW at 102900. lkD Protein Sequence
MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENP SLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNL TLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFF ITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRG IIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMAN YYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCL ENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEE DEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSES IGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTLQVKIVDDEEYEKKD NFFIELGQPQWLKRGISALLLNQGDGDRKLTAEEEEARRIAEMGKPVLGENCRLEVIIEESYDFKNTV DKLIKKTNLALVIGTHSWREQFLEAITVSAGDEEEEEDGSREERLPSCFDYVMHFLTVFWKVLFACVP PTEYCHGWACFGVSILVIGLLTALIGDLASHFGCTVGLKDSVNAWFVALGTSIPDTFASKVAALQDQ CADASIGNVTGSNAVNVFLGLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFTVFAFVGIAVLLYRR RPHIGGELGGPRGPKLATTALFLGLWLLYILFASLEAYCHIRGF
NOV55f, CG56258-03 SEQ ID NO: 865 12685 bp DNA Sequence ORF Start: at 7 ORF Stop: at 2680
GGATCCGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCAGAACAATGAGTCCTGTTCAGGGTC
ATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTTGGGGACAAGA TTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCATCATTGCTGAC CGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAATTAAGAAACCCAATGG AGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCTCCAACCTGACCCTTATGGCCCTGG GTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGTGGTCATGGGTTCATTGCTGGTGAT CTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTTCATCATCATTGGCATCTGTGTCTA CGTGATCCCAGACGGAGAGACTCGCAAGATCAAACATCTACGAGTCTTCTTCATCACCGCTGCTTGGA GTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGTCCAGGTTTGG GAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTGGGTGGCAGATAAACGACT GCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAACACCGAGGAATTATCATAGAGACAG AGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATGAATTCCCATTTTCTAGATGGGAAC CTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGAGATGATCCGGATTCTCAAGGATCT GAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGATGGCCAATTACTATGCTCTTTCCC ACCAACAGAAGAGCCGCGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGCAGGCAATATC CTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGCGAGGTGCACACCGATGAGCC TGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACCAGTGCCTGGAGAACTGTGGGGCTG TACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACCATGTATGTGGACTACAAAACAGAG GATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGGCACGGTGGTTCTGAAGCCAGGAGA GACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAACACTTCTTTG TAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCAGCAATATTCAAC AGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCACAGTTACCATCTTGGATGATGA CCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCAGTGAGAGTATTGGTGTTATGGAGG TCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTCCCCTTTAGGACAGTAGAAGGGACA GCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATGATGAAACTGT GAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATACGAAAGGCAAGAGAATTTCTTCATTGCCC TTGGTGAACCGAAATGGATGGAACGTGGAATATCAGATGTGACAGACAGGAAGCTGACTATGGAAGAA GAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGGGTGAACACCCCAAACTAGAAGTCAT CATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTGATCAAGAAGACAAACCTGGCCTTGG TTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCATCACCGTCAGTGCAGCAGGGGATGAG GATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACTACGTCATGCACTTCCTGACTGT CTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTACTGCCACGGCTGGGCCTGCTTCGCCG TCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGACCTGGCCTCGCACTTCGGCTGCACC ATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCATTTGGCACCTCTGTCCCAGATACGTT TGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCCTCCATTGGCAACGTGACGGGCAGCA ACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGTGGCCGCCATCTACTGGGCTCTGCAG GGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCACCCTCTTCACCATCTTTGCATT TGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTGGGAGGGGAGCTTGGTGGCCCCCGTG GCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCTCCTCTACATACTCTTTGCCACACTA GAGGCCTATTGCTACATCAAGGGGTTCCTCGAG
NOV55f, CG5625δ-03 SEQ ID NO: δ66 891 aa MW at 9899δ.6kD Protein Sequence
EAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRF MASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLG PSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEG LLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFLDGNLV PLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQATRMMTGAGNILK KHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLTWRKGGDMSKTMYVDYKTEDG SANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEEDEHFFVRLSNVRIEEEQPEEGMPPAIFNSL PLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAK GGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEYERQENFFIALGEPKWMERGISDVTDRKLTMEEEE AKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALVVGTHSWRDQFMEAITVSAAGDEDE DESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGDLASHFGCTIG LKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFLGIGLAWSVAAIYWALQGQ EFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGPRGCKLATTWLFVSLWLLYILFATLEA YC IKGF
NOV55g, CG5625δ-05 SEQ ID NO: 867 2778 bp DNA Sequence ORF Start: ATG at 10 ORF Stop: at 2773
GGATCCACCATGGCGTGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTAC
CTTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGC AGAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCG GAGAACCCTTCCCTTGGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTT CCTTGGGGTGTCCATCATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGG AGGTGACAATTAAGAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTC TCCAACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTG TGGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGT TCATCATCATTGGCATCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAGCATCTACGA GTCTTCTTCATCACCGCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTT CTCCCCTGGTGTGGTCCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTC TGGCCTGGGTGGCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAA CACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGAT GAATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAG AGATGATCCGGATTCTCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAG ATGGCCAATTACTATGCTCTTTCCCACCAACAGAAGAGCCGCGCCTTCTACCGTATCCAAGCCACTCG TATGATGACTGGTGCAGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCA TGAGCGAGGTGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTAC CAGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGAC CATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGG GCACGGTGGTTCTGAAGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATT TTTGAGGAGGATGAACACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGA GGGGATGCCTCCAGCAATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGG CCACAGTTACCATCTTGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTC AGTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGT CCCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGT TGGAATTCAAGAATGATGAAACTGTGAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATACGAA AGGCAAGAGAATTTCTTCATTGCCCTTGGTGAACCGAAATGGATGGAACGTGGAATATCAGATGTGAC AGACAGGAAGCTGACTATGGAAGAAGAGGAGGCCAAGAGGATAGCAGAGATGGGAAAGCCAGTATTGG GTGAACACCCCAAACTAGAAGTCATCATTGAAGAGTCCTATGAGTTCAAGACTACGGTGGACAAACTG ATCAAGAAGACAAACCTGGCCTTGGTTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCAT CACCGTCAGTGCAGCAGGGGATGAGGATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTG ACTACGTCATGCACTTCCTGACTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTAC TGCCACGGCTGGGCCTGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGA CCTGGCCTCGCACTTCGGCTGCACCATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTTTCGTGGCAT TTGGCACCTCTGTCCCAGATACGTTTGCCAGCAAAGCTGCTGCCCTCCAGGATGTATATGCAGACGCC TCCATTGGCAACGTGACGGGCAGCAACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGT GGCCGCCATCTACTGGGCTCTGCAGGGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCG TCACCCTCTTCACCATCTTTGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTG GGAGGGGAGCTTGGTGGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGCT CCTCTACATACTCTTTGCCACACTAGAGGCCTATTGCTACATCAAGGGGTTCCTCGAG
NOV55g, CG56258-05 SEQ ID NO: 868 921 aa MW at l02413.7kD Protein Sequence
MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENP SLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNL TLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFF ITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRG IIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMAN YYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCL ENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEE DEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSES IGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEYERQE NFFIALGEPKWMERGISDVTDRKLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKLIKK TNLALWGTHSWRDQFMEAITVSAAGDEDEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHG WACFAVSILIIGMLTAIIGDLASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIG NVTGSNAVNVFLGIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGE LGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGF
NOV55h, CG5625δ-06 SEQ ID NO: δ69 2δl3 bp DNA Sequence ORF Start: ATG at 9 ORF Stop: TAG at 2793
TCTCGTGTATGGCGTGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTGGTTACC!
TTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCA GAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGG AGAACCCTTCCCTTGGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTC CTTGGGGTGTCCATCATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGA GGTGACAATTAAGAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCT CCAACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGT GGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTT CATCATCATTGGCATCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAGCATCTACGAG TCTTCTTCATCACCGCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTC TCCCCTGGTGTGGTCCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCT GGCCTGGGTGGCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAAC ACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATG AATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGA GATGATCCGGATTCTCAAGGATCTGAAGCAAAAACACCCAGAGAAGGACTTAGATCAGCTGGTGGAGA TGGCCAATTACTATGCTCTTTCCCACCAACAGAAGAGCCGTGCCTTCTACCGTATCCAAGCCACTCGT ATGATGACTGGTGCAGGCAATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCAT GAGCGAGGTGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTACC AGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACC ATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGG CACGGTGGTTCTGAAGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACATTT TTGAGGAGGATGAACACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAG GGGATGCCTCCAGCAATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGC CACAGTTACCATCTTGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTATTCATGTCA GTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTC CCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTT GGAATTCAAGAATGATGAAACTGTGAAAACTCTTCAGGTGAAGATAGTTGATGACGAGGAATATGAGA AAAAGGATAATTTCTTCATTGAGCTGGGCCAGCCCCAGTGGCTTAAGCGAGGGATTTCAGCTCTGCTA CTCAATCAAGGGGATGGGGACAGGAAGCTAACAGCCGAGGAGGAGGAGGCTCGGAGGATAGCAGAGAT GGGCAAGCCAGTTCTTGGGGAGAACTGCCGGCTGGAGGTCATCATCGAGGAGTCATATGATTTTAAGA ACACGGTGGATAAACTCATCAAGAAAACGAACTTGGCCTTGGTAATTGGGACCCATTCATGGAGGGAG CAGTTTTTAGAGGCAATTACGGTGAGCGCAGGGGACGAGGAGGAGGAGGAGGACGGGTCCCGGGAGGA GCGGCTGCCGTCGTGCTTTGACTACGTGATGCACTTCCTGACGGTGTTCTGGAAGGTGCTCTTCGCCT GTGTGCCCCCCACCGAGTACTGCCACGGCTGGGCCTGCTTTGGTGTCTCCATCCTGGTCATCGGCCTG CTCACCGCCCTCATTGGGGACCTCGCCTCCCACTTCGGCTGCACCGTTGGCCTCAAGGACTCTGTCAA TGCTGTTGTCTTCGTTGCCCTGGGCACCTCCATCCCTGACACGTTCGCCAGCAAGGTGGCGGCGCTGC AGGACCAGTGCGCCGACGCGTCCATCGGCAACGTGACCGGCTCCAACGCGGTGAACGTGTTCCTTGGC CTGGGCGTCGCCTGGTCTGTGGCCGCCGTGTACTGGGCGGTGCAGGGCCGCCCCTTCGAGGTGCGCAC TGGCACGCTGGCCTTCTCCGTCACGCTCTTCACCGTCTTCGCCTTCGTGGGCATTGCCGTGCTGCTGT ACCGGCGCCGGCCGCACATCGGCGGCGAGCTGGGCGGCCCGCGCGGACCCAAGCTCGCCACCACCGCG CTCTTCCTGGGCCTCTGGCTCCTGTACATCCTCTTCGCCAGCCTGGAGGCGTACTGCCACATCCGGGG CTTCTAGGGCCTCGCGCAGAGACTC
δ02 NOV55h, CG5625δ-06 SEQ ID NO: 870 928 aa MW at 102900. lkD Protein Sequence
MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENP SLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNL TLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFF ITAAWSIFAYIWLYMILAVFSPGWQVWEGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRG IIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMAN YYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCL ENCGAVLLTWRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEE DEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSES IGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTLQVKIVDDEEYEKKD NFFIELGQPQWLKRGISALLLNQGDGDRKLTAEEEEARRIAEMGKPVLGENCRLEVIIEESYDFKNTV DKLIKKTNLALVIGTHSWREQFLEAITVSAGDEEEEEDGSREERLPSCFDYVMHFLTVFWKVLFACVP PTEYCHGWACFGVSILVIGLLTALIGDLASHFGCTVGLKDSVNAWFVALGTSIPDTFASKVAALQDQ CADASIGNVTGSNAVNVFLGLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFTVFAFVGIAVLLYRR RPHIGGELGGPRGPKLATTALFLGLWLLYILFASLEAYCHIRGF
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 55B.
Table 55B. Comparison of the NOV55 protein sequences.
NOV55a MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55b MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55C GSTMAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55d GSEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55e MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55f EAGGSGDVPSTGQNNESCSGSSDCKEG NOV55g MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG NOV55h MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEG
NOV55a VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSI IADRFMASIEVITSQEREVTIKKP NOV55b VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP NOV55C VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP NOV55d VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP NOV55e VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP NOV55f VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSII DRFMASIEVITSQEREVTIKKP NOV55g VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP NOV55h VILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKP
NOV55a NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55b NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55c NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55d NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55e NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55f NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55g NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN NOV55h NGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSAAFN
NOV55a MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55b MFIIIGICVYVTPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55C MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55d MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55e MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55f MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55g MFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT NOV55h MF111GICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGWQVWEGLLT
NOV55a LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGI IIETEGDHPKGIEMDGKMMNSHFL NOV55b LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFL NOV55c LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFL NOV55 LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFL NOV55e LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFL NOV55f LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFL NOV55g LFFFPVCVIiLAWVADKRLLFYKYMHKKYRTDKHRGI11ETEGDHPKGIEMDGKMMNSHFL NOV55h LFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGI IIETEGDHPKGIEMDGKMMNSHFL
NOV55a DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55b DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55c DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55d DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55e DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55f DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55g DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ NOV55h DGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQ
NOV55a ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55b ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55c ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55d ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55e ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55f ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55g ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT NOV55h ATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLT
NOV55a WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55b WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55c WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55d WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55e WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55f WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55g WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED NOV55h WRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTWLKPGETQKEFSVGIIDDDIFEED
NOV55a EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55b EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55c EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55 EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55e EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55f EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55g EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD NOV55h EHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECD
NOV55a TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT NOV55b TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT NOV55C TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT NOV55d TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT NOV55e TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT δ04 NOV55f TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT
NOV55g TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT
NOV55h TIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKT
NOV55a IRVKIVDEEEYERQENFFIALGEP KWMERGISDVT DRKLTMEEEEAKRIAEMG
NOV55b IHIKVIDDEAYEKNKNYFIEMMGPRMVDMSFQKALLLSP DRKLTMEEEEAKRIAEMG
NOV55C IRVKIVDEEEYERQENFFIALGEP KWMERGISDVT DRKLTMEEEEAKRIAEMG
NOV55d IRVKIVDEEEYERQENFFIALGEP KWMERGISDVT DRKLTMEEEEAKRIAEMG
NOV55e LQVKIVDDEEYEKKDNFFIELGQPQ-WLKRGISALLLNQGDGDRKLTAEEEEARRIAEMG
NOV55f IRVKIVDEEEYERQENFFIALGEP KWMERGISDVT DRKLTMEEEEAKRIAEMG
NOV55g IRVKIVDEEEYERQENFFIALGEP KWMERGISDVT DRKLTMEEEEAKRIAEMG
NOV55h LQVKIVDDEEYEKKDNFFIELGQPQ-WLKRGISALLLNQGDGDRKLTAEEEEARRIAEMG
NOV55a KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55b KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55C KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55d KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55e KPVLGENCRLEVIIEESYDFKNTVDKLIKKTNLALVIGTHSWREQFLEAITVSAG-DEEE
NOV55f KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55g KPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALWGTHSWRDQFMEAITVSAAGDEDE
NOV55h KPVLGENCRLEVIIEESYDFKNTVDKLIKKTNLALVIGTHSWREQFLEAITVSAG-DEEE
NOV55a DESG- -EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55b DESG--EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55C DESG- -EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55d DESG- -EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55e EEDGSREERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFGVSILVIGLLTALIGD
NOV55f DESG--EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55g DESG--EERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGD
NOV55h EEDGSREERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFGVSILVIGLLTALIGD
NOV55a LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55b LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55c LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55d LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55e LASHFGCTVGLKDSVNAWFVALGTSIPDTFASKVAALQDQCADASIGNVTGSNAVNVFL
NOV55f LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55g LASHFGCTIGLKDSVTAWFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFL
NOV55h LASHFGCTVGLKDSVNAWFVALGTSIPDTFASKVAALQDQCADASIGNVTGSNAVNVFL
NOV55a GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55b GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55C GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55d GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55e GLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFTVFAFVGIAVLLYRRRPHIGGELGGP
NOV55f GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55g GIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGP
NOV55h GLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFTVFAFVGIAVLLYRRRPHIGGELGGP
NOV55a RGCKLATTWLFVSLWLLYILFATLEAYCYIKGF- -
NOV55b RGCKLATTWLFVSLWLLYILFATLEAYCYIKGF- -
NOV55c RGCKLATTWLFVSLWLLYILFATLEAYCYIKGFLE
NOV55d RGCKLATTWLFVSLWLLYILFATLEAYCYIKGFLE
NOV55e RGPKLATTALFLGLWLLYILFASLEAYCHIRGF- - NOV55f RGCKLATTWLFVSLWLLYILFATLEAYCYIKGF--
NOV55g RGCKLATTWLFVSLWLLYILFATLEAYCYIKGF- -
NOV55h RGPKLATTALFLGLWLL ILFASLEAYCHIRGF- -
NOV55a (SEQ ID NO 856)
NOV55b (SEQ ID NO 858)
NOV55c (SEQ ID NO 860)
NOV55d (SEQ ID NO 862)
NOV55e (SEQ ID NO 864)
NOV55f (SEQ ID NO 866)
NOV55g (SEQ ID NO 868)
NOV55h (SEQ ID NO 870)
Further analysis ofthe NOV55a protein yielded the following properties shown in Table 55C.
Figure imgf000810_0001
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 4.35 Hyd Moment(95): 3.78 G content: 2 D/E content: 1 S/T content: 3 Score: -3.73
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 39 LRA|EA
NUCDISC: discrimination of nuclear localization signals pat4: RRRP (4) at 876 pat7: none bipartite: none content of basic residues: 9.0% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: AWLR
KKXX-like motif in the C-terminus: YIKG
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: found ILPI at 59
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
66.7 % endoplasmic reticulum 11.1 % nuclear 11.1 % vesicles of secretory system 11.1 % mitochondrial
>> prediction for CG56258-04 is end (k=9)
A search ofthe NOV55a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 55D.
80δ
Figure imgf000813_0001
In a BLAST search of public sequence databases, the NOV55a protein was found to have homology to the proteins shown in the BLASTP data in Table 55E.
Figure imgf000814_0001
PFam analysis indicates that the NOV55a protein contains the domains shown in the Table 55F.
Figure imgf000815_0001
Example 56.
The NOV56 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 56 A.
Table 56A. NOV56 Sequence Analysis
KOV56a, CG56262-01 SEQ ID NO: δ71 1551 bp DNA Sequence ORF Start: ATG at 108 ORF Stop: TGA at 1512
GCGGCCGCGGGAGCTGACCCTGCGGGGTCCCGGGGGGGGAGGGGGAGCCGCGAAGCCCCCACTGAGGC
CGCCGCTGCCGGGCCTCCCCTCCCCCCCGGGCGGGCGCCATGCGGGGGAGCCCGGGCGACGCGGAGCG
GCGGCAGCGCTGGGGTCGCCTGTTCGAGGAGCTGGACAGTAACAAGGATGGCCGCGTGGACGTGCACG AGTTGCGCCAGGGGCTGGCCAGGCTGGGCGGGGGCAACCCAGACCCCGGCGCCCAACAGGGTATCTCC TCTGAGGGTGATGCTGACCCAGATGGCGGGCTCGACCTGGAGGAATTTTCCCGCTATCTGCAGGAGCG GGAACAGCGTCTGCTGCTCATGTTTCACAGTCTTGACCGGAACCAGGATGGTCACATTGATGTCTCTG AGATCCAACAGAGTTTCCGAGCTCTGGGCATTTCCATCTCGCTGGAGCAGGCTGAGAAAATTTTGCAC AGCATGGACCGAGACGGCACAATGACCATTGACTGGCAAGAATGGCGCGACCACTTCCTGTTGCATTC GCTGGAAAATGTGGAGGACGTGCTGTATTTCTGGAAGCATTCCACGGTCCTGGACATTGGCGAGTGCC TGACAGTGCCGGACGAGTTCTCAAAGCAAGAGAAGCTGACGGGCATGTGGTGGAAACAGCTGGTGGCC GGCGCAGTGGCAGGTGCCGTGTCACGGACAGGCACGGCCCCTCTGGACCGCCTCAAGGTCTTCATTCA GGTCCATGCCTCAAAGACCAACCGGCTGAACATCCTTGGGGGGCTTCGAAGCATGGTCCTTGAGGGAG GCATCCGCTGCCTGTGGCGCGGCAATGGTATTAATGTACTCAAGATTGCCCCCGAGTCAGCTATCAAG TTCATGGCCTATGAACAGGTGAGGAGGGCCATCCTGGGGCAGCAGGAGACACTGCATGTGCAGGAGCG CTTCGTGGCTGGCTCCCTGGCTGGTGCCACAGCCCAAACCATCATTTACCCTATGGAGGTGCTGAAGA CGCGGCTGACCTTGCGCCGGACGGGCCAGTATAAGGGGCTGCTGGACTGCGCCAGGCGTATCCTGGAG AGGGAGGGGCCCCGTGCCTTCTACCGCGGCTACCTCCCCAACGTGCTGGGCATCATCCCCTATGCGGG CATCGACCTGGCCGTCTACGAGGTCCTGAAGAACTGGTGGCTTCAGCAGTACAGCCACGACTCGGCAG ACCCAGGCATCCTCGTGCTCCTGGCCTGCGGTACCATATCCAGCACCTGCGGCCAGATAGCCAGTTAC CCGCTGGCCCTGGTCCGGACCCGCATGCAGGCACAAGCCTCCATCGAGGGTGGCCCCCAGCTGTCCAT GCTGGGTCTGCTACGTCACATCCTGTCCCAGGAGGGCATGCGGGGCCTCTACCGGGGGATCGCCCCCA ACTTCATGAAGGTTATTCCAGCTGTGAGCATCTCCTATGTGGTCTACGAGAACATGAAGCAGGCCTTG GGGGTCACGTCCAGGTGAGGGACCCGGAGCCCGTCCCCCCAATCCCTCACCCCCC NOV56a, CG56262-01 SEQ ID NO: 872 468 aa MW at 523δ7.5kD Protein Sequence
MRGSPGDAERRQRWGRLFEELDSNKDGRVDVHELRQGLARLGGGNPDPGAQQGISSEGDADPDGGLDL EEFSRYLQEREQRLLLMFHSLDRNQDGHIDVSEIQQSFRALGISISLEQAEKILHSMDRDGTMTIDWQ EWRDHFLLHSLENVEDVLYFWKHSTVLDIGECLTVPDEFSKQEKLTGM WKQLVAGAVAGAVSRTGTA PLDRLKVFIQVHASKTNRLNILGGLRSMVLEGGIRCLWRGNGINVLKIAPESAIKFMAYEQVRRAILG QQETLHVQERFVAGSLAGATAQTIIYPMEVLKTRLTLRRTGQYKGLLDCARRILEREGPRAFYRGYLP NVLGIIPYAGIDLAVYEVLKN LQQYSHDSADPGILVLLACGTISSTCGQIASYPLALVRTRMQAQA SIEGGPQLSMLGLLRHILSQEGMRGLYRGIAPNFMKVIPAVSISYWYENMKQALGVTSR
NOV56b, 266120550 SEQ ID NO: 873 1426 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCACCATGCGGGGGAGCCCGGGCGACGCGGAGCGGCGGCAGCGCTGGGGTCGCCTGTTCG AGGAGCTGGACAGTAACAAGGATGGCCGCGTGGACGTGCACGAGTTGCGCCAGGGGCTGGCCAGGCTG GGCGGGGGCAACCCAGACCCCGGCGCCCAACAGGGTATCTCCTCTGAGGGTGATGCTGACCCAGATGG CGGGCTCGACCTGGAGGAATTTTCCCGCTATCTGCAGGAGCGGGAACAGCGTCTGCTGCTCATGTTTC ACAGTCTTGACCGGAACCAGGATGGTCACATTGATGTCTCTGAGATCCAACAGAGTTTCCGAGCTCTG GGCATTTCCATCTCGCTGGAGCAGGCTGAGAAAATTTTGCACAGCATGGACCGAGACGGCACAATGAC CATTGACTGGCAAGAATGGCGCGACCACTTCCTGTTGCATTCGCTGGAAAATGTGGAGGACGTGCTGT ATTTCTGGAAGCATTCCACGGTCCTGGACATTGGCGAGTGCCTGACAGTGCCGGACGAGTTCTCAAAG CAAGAGAAGCTGACGGGCATGTGGTGGAAACAGCTGGTGGCCGGCGCAGTGGCAGGTGCCGTGTCACG GACAGGCACGGCCCCTCTGGACCGCCTCAAGGTCTTCATGCAGGTCCATGCCTCAAAGACCAACCGGC TGAACATCCTTGGGGGGCTTCGAAGCATGGTCCTTGAGGGAGGCATCCGCTCCCTGTGGCGCGGCAAT GGTATTAATGTACTCAAGATTGCCCCCGAGTCAGCTATCAAGTTCATGGCCTATGAACAGATCAAGAG GGCCATCCTGGGGCAGCAGGAGACACTGCATGTGCAGGAGCGCTTCGTGGCTGGCTCCCTGGCTGGTG CCACAGCCCAAACCATCATTTACCCTATGGAGGTGCTGAAGACGCGGCTGACCTTGCGCCGGACGGGC CAGTATAAGGGGCTGCTGGACTGCGCCAGGCGTATCCTGGAGAGGGAGGGGCCCCGTGCCTTCTACCG CGGCTACCTCCCCAACGTGCTGGGCATCATCCCCTATGCGGGCATCGACCTGGCCGTCTACGAGACTC TGAAGAACTGGTGGCTTCAGCAGTACAGCCACGACTCGGCAGACCCAGGCATCCTCGTGCTCCTGGCC TGCGGTACCATATCCAGCACCTGCGGCCAGATAGCCAGTTACCCGCTGGCCCTGGTCCGGACCCGCAT GCAGGCACAAGCCTCCATCGAGGGTGGCCCCCAGCTGTCCATGCTGGGTCTGCTACGTCACATCCTGT CCCAGGAGGGCATGCGGGGCCTCTACCGGGGGATCGCCCCCAACTTCATGAAGGTTATTCCAGCTGTG AGCATCTCCTATGTGGTCTACGAGAACATGAAGCAGGCCTTGGGGGTCACGTCCAGGCTCGAGGGC
NOV56b, 266120550 SEQ ID NO: δ74 475 aa MW at 53023. lkD Protein Sequence
TGSTMRGSPGDAERRQRWGRLFEELDSNKDGRVDVHELRQGLARLGGGNPDPGAQQGISSEGDADPDG GLDLEEFSRYLQEREQRLLLMFHSLDRNQDGHIDVSEIQQSFRALGISISLEQAEKILHSMDRDGTMT IDWQEWRDHFLLHSLENVEDVLYF KHSTVLDIGECLTVPDEFSKQEKLTGMWWKQLVAGAVAGAVSR TGTAPLDRLKVFMQVHASKTNRLNILGGLRSMVLEGGIRSL RGNGINVLKIAPESAIKFMAYEQIKR AILGQQETLHVQERFVAGSLAGATAQTIIYPMEVLKTRLTLRRTGQYKGLLDCARRILEREGPRAFYR GYLPNVLGIIPYAGIDLAVYETLKNW LQQYSHDSADPGILVLLACGTISSTCGQIASYPLALVRTRM QAQASIEGGPQLSMLGLLRHILSQEGMRGLYRGIAPNFMKVIPAVSISYWYENMKQALGVTSRLEG A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 56B.
Table 56B. Comparison of the NOV56 protein sequences.
N0V56a MRGSPGDAERRQRWGRLFEELDSNKDGRVDVHELRQGLARLGGGNPDPGAQQGISS
NOV56b TGSTMRGSPGDAERRQR GRLFEELDSNKDGRVDVHELRQGLARLGGGNPDPGAQQGISS
NOV56a EGDADPDGGLDLEEFSRYLQEREQRLLLMFHSLDRNQDGHIDVSEIQQSFRALGISISLE
NOV56b EGDADPDGGLDLEEFSRYLQEREQRLLLMFHSLDRNQDGHIDVSEIQQSFRALGISISLE NOV56a QAEKILHSMDRDGTMTID QE RDHFLLHSLENVEDVLYF KHSTVLDIGECLTVPDEFS
NOV56b QAEKILHSMDRDGTMTIDWQEWRDHFLLHSLENVEDVLYFWKHSTVLDIGECLTVPDEFS
NOV56a KQEKLTGMWWKQLVAGAVAGAVSRTGTAPLDRLKVFIQVHASKTNRLNILGGLRSMVLEG
NOV56b KQEKLTGM KQLVAGAVAGAVSRTGTAPLDRLKVFMQVHASKTNRLNILGGLRSMVLEG
NOV56a GIRCLWRGNGINVLKIAPESAIKFMAYEQVRRAILGQQETLHVQERFVAGSLAGATAQTI
NOV56b GIRSLWRGNGINVLKIAPESAIKFMAYEQIKRAILGQQETLHVQERFVAGSLAGATAQTI
NOV56a IYPMEVLKTRLTLRRTGQYKGLLDCARRILEREGPRAFYRGYLPNVLG11PYAGIDLAVY
NOV56b IYPMEVLKTRLTLRRTGQYKGLLDCARRILEREGPRAFYRGYLPNVLGIIPYAGIDLAVY
NOV56a EVLKN LQQYSHDSADPGILVLLACGTISSTCGQIASYPLALVRTRMQAQASIEGGPQL
NOV56b ETLKNWWLQQYSHDSADPGILVLLACGTISSTCGQIASYPLALVRTRMQAQASIEGGPQL
NOV56a SMLGLLRHILSQEGMRGLYRGIAPNFMKVIPAVSISYWYENMKQALGVTSR
NOV56b SMLGLLRHILSQEGMRGLYRGIAPNFMKVIPAVSISYWYENMKQALGVTSRLEG
NOV56a (SEQ ID NO: 872) NOV56b (SEQ ID NO: 874)
Further analysis of the NOV56a protein yielded the following properties shown in Table 56C.
Table 56C. Protein Sequence Properties NOV56a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos . chg 3; neg . chg 2 H-region: length 1; peak value -14.40 PSG score: -18.80
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.60 possible cleavage site: between 46 and 47
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 0.85 (at 342) ALOM score: -0.90 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 10.59 Hyd Moment(95): 7.77 G content: 2 D/E content: 2 S/T content: 1 Score: -5.97 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 12 MRG | SP
NUCDISC: discrimination of nuclear localization signals pat4 : none pat : none bipartite: none content of basic residues: 11.3% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : RGSP none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LEEFSRYLQEREQRLLLMFHSL at 68 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues Final Results (k = 9/23) :
52.2 %: cytoplasmic
30.4 %: nuclear
8.7 %: mitochondrial
4.3 % : vacuolar
4.3 %: vesicles of secretory system
>> prediction for CG56262-01 is cyt (k=23)
A search ofthe NOV56a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 56D.
Figure imgf000819_0001
In a BLAST search of public sequence databases, the NOV56a protein was found to have homology to the proteins shown in the BLASTP data in Table 56E.
Figure imgf000820_0001
PFam analysis indicates that the NOV56a protein contains the domains shown in the Table 56F.
Figure imgf000820_0002
Example 57.
The NOV57 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 57A.
Figure imgf000821_0001
TGATAATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAA AGGCACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTAT CAGCCTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCT TTAGTGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCC AAACCCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGCGTATTGTGTTGAA TTCCATTGAACTGAGTTTTTTGGTTCTCAAGTGCCTTATTAAGTGCTGTCTCCAAAAATATTTAAAAA AACCTCAAGTCCTCAGTGTGCTCGAGGGCAAGGGTGGGCGCGCC
NOV57c, 247678321 SEQ ID NO: 880 241 aa MW at 27446.4kD Protein Sequence
GSAAAPFTGSMSWMFLRDLLSGVNKYSTGIGWIWLAWFVFRLLVYMVAAEHVWKDEQKEFECNSRQP GCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGLWYAYLI SLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKTIFILFLVITSCLRIVLN SIELSFLVLKCLIKCCLQKYLKKPQVLSVLEGKGGRA
NOV57d, 247679418 SEQ ID NO: 881 538 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGT GCAACAGTAGACAGCCCGGTTGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGA CTTTGGGCCTTACAACTGATAATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCA TGAGGGTAGAGAGAAAAGGCACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTAT GGTACGCTTATCTTATCAGCCTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTAT AAGCTATATGATGGCTTTAGTGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGT GGACTGCTTCATCTCCAAACCCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCT TGCGTATTGTGTTGAATTTCATTGAACTGAGTTTTTTGCTCGAGGGCAAGGGTGGGCGCGCC
NO V57d, 2476794 lδ SEQ ID NO: δδ2 179 aa MW at 20339.7kD Protein Sequence
GSAAAPFTGSEHV KDEQKEFECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYH EGREKRHRKKLYVSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTV DCFISKPTEKTIFILFLVITSCLRIVLNFIELSFLLEGKGGRA
NOV57e, 247679395 SEQ ID NO: 883 65δ bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
AGGCTCCGCGGCCGCCCCCTTCACCGGATCCATGAGTTGGATGTTCCTCAGAGATCTCCTGAGTGGAG TAAATAAATACTCCACTGGGATTGGATGGATTTGGCTGGCTGTCGTGTTTGTCTTCCGTTTGCTGGTC TACATGGTGGCAGCAGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGTGCAACAGTAGACAGCC CGGTTGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGACTTTGGGCCTTACAAC TGATAATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAA AGGCACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTAT CAGCCTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCT TTAGTGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCC AAACCCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGCGTATTGTGTTGAA TTTCATTGAACTGAGTTTTTTGCTCGAGGGCAAGGGTGGGCGCGCC
NOV57e, 247679395 SEQ ID NO: δ84 219 aa MW at 24976.2kD Protein Sequence
GSAAAPFTGSMSWMFLRDLLSGVNKYSTGIGWIWLAWFVFRLLVYMVAAEHVWKDEQKEFECNSRQP GCKNVCFDDFFPISQVRL ALQLIMVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGLWYAYLI SLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKTIFILFLVITSCLRIVLN FIELSFLLEGKGGRA
NOV57f, 247679328 SEQ ID NO: 8δ5 604 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGT GCAACAGTAGACAGCCCGGTTGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGA CTTTGGGCCTTACAACTGATAATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCA TGAGGGTAGAGAGAAAAGGCACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTAT δiδ
Figure imgf000823_0001
NOV57k, CG56315-06 SEQ ID NO: 895 24 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
ITTTGAGTGCAACAGTAGACAGCCC
NOV57k, CG56315-06 SEQ ID NO: 896| 8 aa MW at 980.1kDι Protein Sequence
FECNSRQP
NOV571, CG56315-07 SEQ ID NO: 897 24 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TTTGAGCAAAACAGTAGACAGGCC
NOV571, CG56315-07 SEQ ID NO: 898 8 aa MW at 979.0kD Protein Sequence
FEQNSRQA
NOV57m, CG56315-08 SEQ ID NO: 899 24 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TTTGAGTGCAACAGTAGACAGGCC
NOV57m, CG56315-08 SEQ ID NO: 900 8 aa MW at 954.0kD Protein Sequence
FECNSRQA
NOV57n, SNP13381650 of SEQ ID NO: 901 72δ bp CG56315-01, DNA Sequence ORF Start: ATG at 2δ ORF Stop: TGA at 697
SNP Pos: δ6 SNP Change: C to T
AGTCTTGCCTTCTTTTGAGCCTAAGTCATGAGTTGGATGTTCCTCAGAGATCTCCTGAGTGGAGTAAA
TAAATACTCCACTGGGATTGGATGGATTTGGCTGGCTGTCGTGTTTGTCTTCCGTTTGCTGGTCTACA TGGTGGCAGCAGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGTGCAACAGTAGACAGCCCGGT TGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGACTTTGGGCCTTACAACTGAT AATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAAAGGC ACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTATCAGC CTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCTTTAG TGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCCAAAC CCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGTGTATTGTGTTGAATTTC ATTGAACTGAGTTTTTTGGTTCTCAAGTGCTTTATTAAGTGCTGTCTCCAAAAATATTTAAAAAAACC TCAAGTCCTCAGTGTGTGAGTGCCACAGCCTCAGATATGTTGAATGTG
NOV57n, SNPl 33δ 1650 of SEQ ID NO: 902 223 aa MW at 25δ71.7kD CG56315-01, Protein Sequence SNP Pos: 20 SNP Change: Thr to He
MSWMFLRDLLSGVNKYSTGIG IWLAWFVFRLLVYMVAAEHVWKDEQI EFECNSRQPGCKNVCFDDF FPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGL YAYLISLIVKTGFEI GFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKTIFILFLVITSCLCIVLNFIELSFLVLK CFIKCCLQKYLKKPQVLSV
NOV57o, SNP133δl651 of SEQ ID NO: 903 72δ bp CG56315-01, DNA Sequence ORF Start: ATG at 28 ORF Stop: TGA at 697
SNP Pos: 154 SNP Change: G to A
AGTCTTGCCTTCTTTTGAGCCTAAGTCATGAGTTGGATGTTCCTCAGAGATCTCCTGAGTGGAGTAAA
TAAATACTCCACTGGGACTGGATGGATTTGGCTGGCTGTCGTGTTTGTCTTCCGTTTGCTGGTCTACA TGGTGGCAGCAGAGCACATGTGGAAAGATGAGCAGAAAGAGTTTGAGTGCAACAGTAGACAGCCCGGT TGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGACTTTGGGCCTTACAACTGAT AATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAAAGGC ACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTATCAGC CTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCTTTAG TGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCCAAAC CCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGTGTATTGTGTTGAATTTC ATTGAACTGAGTTTTTTGGTTCTCAAGTGCTTTATTAAGTGCTGTCTCCAAAAATATTTAAAAAAACC TCAAGTCCTCAGTGTGTGAGTGCCACAGCCTCAGATATGTTGAATGTG
NOV57o, SNP133δl651 of SEQ ID NO: 904 223 aa MW at 25δ91.7kD CG56315-01, Protein Sequence SNP Pos: 43 SNP Change: Val to Met
MS MFLRDLLSGVNKYSTGTG IWLAWFVFRLLVYMVAAEHMWKDEQKEFECNSRQPGCKNVCFDDF FPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGLWYAYLISLIVKTGFEI GFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKTIFILFLVITSCLCIVLNFIELSFLVLK CFIKCCLQKYLKKPQVLSV
NOV57p, SNP133δl652 of SEQ ID NO: 905 72δ bp CG56315-01, DNA Sequence ORF Start: ATG at 28 ORF Stop: TGA at 697
SNP Pos: 276 SNP Change: G to A
AGTCTTGCCTTCTTTTGAGCCTAAGTCATGAGTTGGATGTTCCTCAGAGATCTCCTGAGTGGAGTAAA
TAAATACTCCACTGGGACTGGATGGATTTGGCTGGCTGTCGTGTTTGTCTTCCGTTTGCTGGTCTACA TGGTGGCAGCAGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGTGCAACAGTAGACAGCCCGGT TGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGACTTTGGGCCTTACAACTGAT AATAGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAAAGGC ACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTATCAGC CTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCTTTAG TGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCCAAAC CCACTGAGAAGACGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGTGTATTGTGTTGAATTTC ATTGAACTGAGTTTTTTGGTTCTCAAGTGCTTTATTAAGTGCTGTCTCCAAAAATATTTAAAAAAACC TCAAGTCCTCAGTGTGTGAGTGCCACAGCCTCAGATATGTTGAATGTG
NOV57p, SNP 13381652 of SEQ ID NO: 906 223 aa JMW at 25841.6kD CG56315-01, Protein Sequence SNP Change: Met to He
MSWMFLRDLLSGVNKYSTGTGWIWLAWFVFRLLVYMVAAEH KDEQKEFECNSRQPGCKNVCFDDF FPISQVRLWALQLIIVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGLWYAYLISLIVKTGFEI GFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKTIFILFLVITSCLCIVLNFIELSFLVLK CFI KCCLQKYLKKPQVLSV
NOV57q, SNP13381653 of SEQ ID NO: 907 72 bp CG56315-01, DNA Sequence ORF Start: ATG at 2δ ORF Stop: TGA at 697
SNP Pos: 557 SNP Change: C to T
AGTCTTGCCTTCTTTTGAGCCTAAGTCATGAGTTGGATGTTCCTCAGAGATCTCCTGAGTGGAGTAAA
TAAATACTCCACTGGGACTGGATGGATTTGGCTGGCTGTCGTGTTTGTCTTCCGTTTGCTGGTCTACA TGGTGGCAGCAGAGCACGTGTGGAAAGATGAGCAGAAAGAGTTTGAGTGCAACAGTAGACAGCCCGGT TGCAAAAATGTGTGTTTTGATGACTTCTTCCCCATTTCCCAAGTCAGACTTTGGGCCTTACAACTGAT AATGGTCTCCACACCTTCACTTCTGGTGGTTTTACATGTAGCCTATCATGAGGGTAGAGAGAAAAGGC ACAGAAAGAAACTCTATGTCAGCCCAGGTACAATGGATGGGGGCCTATGGTACGCTTATCTTATCAGC CTCATTGTTAAAACTGGTTTTGAAATTGGCTTCCTTGTTTTATTTTATAAGCTATATGATGGCTTTAG TGTTCCCTACCTTATAAAGTGTGATTTGAAGCCTTGTCCCAACACTGTGGACTGCTTCATCTCCAAAC CCACTGAGAAGATGATCTTCATCCTCTTCTTGGTCATCACCTCATGCTTGTGTATTGTGTTGAATTTC ATTGAACTGAGTTTTTTGGTTCTCAAGTGCTTTATTAAGTGCTGTCTCCAAAAATATTTAAAAAAACC TCAAGTCCTCAGTGTGTGAGTGCCACAGCCTCAGATATGTTGAATGTG
NOV57q, SNP133δl653 of SEQ ID NO: 90δ|223 aa MW at 25δδ9.δkD CG56315-01, Protein Sequence SNP Pos: 177 SNP Change: Thr to Met
MS MFLRDLLSGVNKYSTGTGWIWLAWFVFRLLVYMVAAEHVWKDEQICEFECNSRQPGCKNVCFDDF FPISQVRL ALQLIMVSTPSLLWLHVAYHEGREKRHRKKLYVSPGTMDGGLWYAYLISLIVKTGFEI GFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFISKPTEKMIFILFLVITSCLCIVLNFIELSFLVLK CFIKCCLQKYLKKPQVLSV
Figure imgf000826_0001
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 57B.
Table 57B. Comparison of the NOV57 protein sequences.
NOV57a MSWMFLRDLLSGVNKYSTGTGWIWLAWFVFRLLVYMVAAEHVWKDEQKE
NOV57b GSAAAPFTGSMS MFLRDLLSGVNKYSTGIG IWLAWFVFRLLVYMVAAEHVWKDEQKE
NOV57C GSAAAPFTGSMSWMFLRDLLSGVNKYSTGIGWIWLAWFVFRLLVYMVAAEHVWKDEQKE
NOV57d GSAAAPFTG SEHVWKDEQKE
NOV57e GSAAAPFTGSMS MFLRDLLSGVNKYSTGIGWI LAWFVFRLLVYMVAAEHVWKDEQKE
NOV57f GSAAAPFTG SEHVWKDEQKE
NOV57g MS MFLRDLLSGVNKYSTGIG IWLAWFVFRLLVYMVAAEHVWKDEQKE
NOV57h
NOV57i
NOV57J
NOV57k
NOV571
NOV57m
NOV57a FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57b FECNSRQPGCKNVCFDDFFPISQVRLWAVQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57C FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57d FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57e FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57f FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57g FECNSRQPGCKNVCFDDFFPISQVRLWALQLIMVSTPSLLWLHVAYHEGREKRHRKKLY
NOV57h FEQNRRQP
NOV57i FECNRRQP
NOV57j FEQNSRQP
NOV57k FECNSRQP
NOV571 FEQNSRQA NOV57m FECNSRQA-
NOV57a VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57b VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57C VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57d VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57e VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57f VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57g VSPGTMDGGLWYAYLISLIVKTGFEIGFLVLFYKLYDGFSVPYLIKCDLKPCPNTVDCFI
NOV57h
NOV57i
NOV57k
NOV571
NOV57m
NOV57a SKPTEKTIFILFLVITSCLCIVLNFIELSFLVLKCFIKCCLQKYLKKPQVLSV
NOV57b SKPTEKTIFILFLVITSCLRIVLNFIELSFLLEGKGGRADPAFLYKSWHFIRK
NOV57C SKPTEKTIFILFLVITSCLRIVLNSIELSFLVLKCLIKCCLQKYLKKPQVLSVLEGKGGR
NOV57d SKPTEKTIFILFLVITSCLRIVLNFIELSFLLEGKGGRA
NOV57e SKPTEKTIFILFLVITSCLRIVLNFIELSFLLEGKGGRA
NOV57f SKPTEKTIFILFLVITSCLRIVLNSIELSFLVLKCLIKCCLQKYLKKPQVLSVLEGKGGR
NOV57g SKPTEKTIFILFLVITSCLCIVLNFIELSFLVLKCFIKCCLQKYLKKPQVLSV
NOV57h
NOV57i
NOV57
NOV57k
NOV571
NOV57m
NOV57a -
NOV57b -
NOV57c A
NOV57 -
NOV57e -
NOV57f A
NOV57g -
NOV57h -
NOV57i -
NOV57J -
NOV57k -
NOV571 -
NOV57m -
NOV57a (SEQ ID NO 876)
NOV57b (SEQ ID NO 878)
NOV57C (SEQ ID NO 880)
NOV57d (SEQ ID NO 882)
NOV57e (SEQ ID NO 884)
NOV57f (SEQ ID NO 886)
NOV57g (SEQ ID NO 888)
NOV57h (SEQ ID O 890)
NOV57i (SEQ ID NO 892)
NOV57J (SEQ ID NO 894) N0V57k (SEQ ID NO: 896)
N0V571 (SEQ ID NO: 898)
N0V57m (SEQ ID NO: 900)
Further analysis ofthe NOV57a protein yielded the following properties shown in Table 57C.
Table 57C. Protein Sequence Properties NOV57a
SignalP analysis: Cleavage site between residues 41 and 42
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region : length 8 ; pos . chg 1 ; neg . chg 1 H-region : length 6 ; peak value -2 .35 PSG score : -6 . 75
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 .1) : -4 .71 possible cleavage site : between 40 and 41
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -7 .64 Transmembrane 23 - 39
INTEGRAL Likelihood = -2 60 Transmembrane 81 - 97
INTEGRAL Likelihood = -3 24 Transmembrane 125 - 141
INTEGRAL Likelihood =-12 26 Transmembrane 177 - 193
INTEGRAL Likelihood = -2 81 Transmembrane 195 - 211
PERIPHERAL Likelihood = 6 36 (at 63)
ALOM score : -12.26 (number of TMSs: 5)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 30 Charge difference: -1.5 C( 0.5) - N ( 2.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 11.62 Hyd Moment(95): 9.22 G content: 3 D/E content: 2 S/T content: 5 Score: -4.01
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 42 FRL|LV
NUCDISC: discrimination of nuclear localization signals pat4: KRHR (3) at 103 pat4: RHRK (3) at 104 pat4 : HRKK ( 3 ) at 105 pat 7 : none bipartite: none content of basic residues: 11.2%
NLS Score: 0.09
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum 33.3 %: mitochondrial 11.1 %: nuclear
>> prediction for CG56315-01 is end (k=9) A search ofthe NOV57a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 57D.
Figure imgf000830_0001
In a BLAST search of public sequence databases, the NOV57a protein was found to have homology to the proteins shown in the BLASTP data in Table 57E.
Figure imgf000831_0001
PFam analysis indicates that the NOV57a protein contains the domains shown in the Table 57F.
Figure imgf000831_0002
Example 58.
The NOV58 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5δA.
Figure imgf000831_0003
δ27 AGATCCCCTGGATGCGTTTCCCCAGAAGGGCTTGGAGCCTGGGGACATCGCGGTGCTAGTTCTGTACT TCCTCTTTGTCCTGGCTGTTGGACTATGGTCCACAGTGAAGACCAAAAGAGACACAGTGAAAGGCTAC TTCCTGGCTGGAGGGGACATGGTGTGGTGGCCAGTGGGTGCATCCTTGTTTGCCAGCAATGTTGGAAG TGGACATTTCATTGGCCTGGCAGGGTCAGGTGCTGCTACGGGCATTTCTGTATCAGCTTATGAACTTA ATGGCTTGTTTTCTGTGCTGATGTTGGCCTGGATCTTCCTACCCATCTACATTGCTGGTCAGGTGACC ACGATGCCAGAATACCTACGGAAGCGCTTCGGTGGCATCAGAATCCCCATCATCCTGGCTGTACTCTA CCTATTTATCTACATCTTCACCAAGATCTCGGTAGACATGTATGCAGGTGCCATCTTCATCCAGCAGT CTTTGCACCTGGATCTGTACCTGGCCATAGTTGGGCTACTGGCCATCACTGCTGTATACACGGTTGCT GGTGGCCTGGCTGCTGTGATCTACACGGATGCCCTGCAGACGCTGATCATGCTTATAGGAGCGCTCAC CTTGATGGGCTACAGTTTCGCCGCGGTTGGTGGGATGGAAGGACTGAAGGAGAAGTACTTCTTGGCCC TGGCTAGCAACCGGAGTGAGAACAGCAGCTGCGGGCTGCCCCGGGAAGATGCCTTCCATATTTTCCGA GATCCGCTGACATCTGATCTCCCGTGGCCGGGGGTCCTATTTGGAATGTCCATCCCATCCCTCTGGTA CTGGTGCACGGATCAGGTAATTGTCCAGCGGACTCTGGCTGCCAAGAACCTGTCCCATGCCAAAGGAG GTGCTCTGATGGCTGCATACCTGAAGGTGCTGCCCCTCTTCATAATGGTGTTCCCTGGGATGGTCAGC CGCATCCTCTTCCCAGATCAAGTGGCCTGTGCAGATCCAGAGATCTGCCAGAAGATCTGCAGCAACCC CTCAGGCTGTTCGGACATCGCGTATCCCAAACTCGTGCTGGAACTCCTGCCCACAGGTCTCCGTGGGC TGATGATGGCTGTGATGGTGGCGGCTCTCATGTCCTCCCTCACCTCCATCTTTAACAGTGCCAGCACC ATCTTCACCATGGACCTCTGGAATCACCTCCGGCCTCGGGCATCTGAGAAGGAGCTCATGATTGTGGG CAGGGTGTTTGTGCTGCTGCTGGTCCTGGTCTCCATCCTCTGGATCCCTGTGGTCCAGGCCAGCCAGG GCGGCCAGCTCTTCATCTATATCCAGTCCATCAGCTCCTACCTGCAGCCGCCTGTGGCGGTGGTCTTC ATCATGGGATGTTTCTGGAAGAGGACCAATGAAAAGGGTGCCTTCTGGGGCCTGATCTCGGGCCTGCT CCTGGGCTTGGTTAGGCTGGTCCTGGACTTTATTTACGTGCAGCCTCGATGCGACCAGCCAGATGAGC GCCCGGTCCTGGTGAAGAGCATTCACTACCTCTACTTCTCCATGATCCTGTCCACGGTCACCCTCATC ACTGTCTCCACCGTGAGCTGGTTCACAGAGCCACCCTCCAAGGAGATGGTCAGCCACCTGACCTGGTT TACTCGTCACGACCCCGTGGTCCAGAAGGAACAAGCACCACCAGCAGCTCCCTTGTCTCTTACCCTCT CTCAGAACGGGATGCCAGAGGCCAGCAGCAGCAGCAGCGTCCAGTTCGAGATGGTTCAAGAAAACACG TCTAAAACCCACAGCGGTGACATGACCCCAAAGCAGTCCAAAGTGGTGAAGGCCATCCTGTGGCTCTG TGGAATACAGGAGAAGGGCAAGGAAGAGCTCCCGGCCAGAGCAGAAGCCATCATAGTTTCCCTGGAAG AAAACCCCTTGGTGAAGACCCTCCTGGACGTCAACCTCATTTTCTGCGTGAGCTGCGCCATCTTTATC TGGGGCTATTTTGCTTAGTGTGGGGTGAACCCAGGGGTCCAAACTCTGTTTCTCTTCAGTGCTCC
NOV5δa, CG5639δ-01 SEQ ID NO: 912 675 aa MW at 739δ9.3kD
Protein Sequence
MESGTSSPQPPQLDPLDAFPQKGLEPGDIAVLVLYFLFVLAVGLWSTVKTKRDTVKGYFLAGGDMVWW PVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLA IFLPIYIAGQVTTMPEYLRKRF GGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLAIVGLLAITAVYTVAGGLAAVIYTD ALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLALASNRSENSSCGLPREDAFHIFRDPLTSDLPWP GVLFGMSIPSL YWCTDQVIVQRTLAAKNLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVAC ADPEICQKICSNPSGCSDIAYPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDLWNHL RPRASEKELMIVGRVFVLLLVLVSIL IPWQASQGGQLFIYIQSISSYLQPPVAWFIMGCF KRTN EKGAFWGLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSIHYLYFSMILSTVTLITVSTVSWFTE PPSKEMVSHLTWFTRHDPWQKEQAPPAAPLSLTLSQNGMPEASSSSSVQFEMVQENTSKTHSGDMTP KQSKWKAILWLCGIQEKGKEELPARAEAIIVSLEENPLVKTLLDVNLIFCVSCAIFIWGYFA
NOV5δb, 265726152 SEQ ID NO: 913 1309 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCTACTTCCTGGCTGGAGGGGACATGGTGTGGTGGCCAGTGGGTGCATCCTTGTTTGCCA GCAATGTTGGAAGTGGACATTTCATTGGCCTGGCAGGGTCAGGTGCTGCTACGGGCATTTCTGTATCA GCTTATGAACTTAATGGCTTGTTTTCTGTGCTGATGTTGGCCTGGATCTTCCTACCCATCTACATTGC TGGTCAGGTCACCACGATGCCAGAATACCTACGGAAGCGCTTCGGTGGCATCAGAATCCCCATCATCC TGGCTGTACTCTACCTATTTATCTACATCTTCACCAAGATCTCGGTAGACATGTATGCAGGTGCCATC TTCATCCAGCAGTCTTTGCACCTGGATCTGTACCTGGCCATAGTTGGGCTACTGGCCATCACTGCTGT ATACACGGTTGCTGGTGGCCTGGCTGCTGTGATCTACACGGATGCCCTGCAGACGCTGATCATGCTTA TAGGAGCGCTCACCTTGATGGGCTACAGTTTCGCCGCGGTTGGTGGGATGGAAGGACTGAAGGAGAAG TACTTCTTGGCCCTGGCTAGCAACCGGAGTGAGAACAGCAGCTGCGGGCTGCCCCGGGAAGATGCCTT CCATATTTTCCGAGATCCGCTGACATCTGATCTCCCGTGGCCGGGGGTCCTATTTGGAATGTCCATCC CATCCCTCTGGTACTGGTGCACGGATCAGGTGATTGTCCAGCGGACTCTGGCTGCCAAGAACCTGTCC CATGCCAAAGGAGGTGCTCTGATGGCTGCATACCTGAAGGTGCTGCCCCTCTTCATAATGGTGTTCCC TGGGATGGTCAGCCGCATCCTCTTCCCAGATCAAGTGGCCTGTGCAGATCCAGAGATCTGCCAGAAGA δ28 TCTGCAGCAACCCCTCAGGCTGTTCGGACATCGCGTATCCCAAACTCGTGCTGGAACTCCTGCCCACA GGGCTCCGTGGGCTGATGATGGCTGTGATGGTGGCGGCTCTCATGTCCTCCCTCACCTCCATCTTTAA CAGTGCCAGCACCATCTTCACCATGGACCTCTGGAATCACCTCCGGCCTCGGGCATCTGAGAAGGAGC TCATGATTGTGGGCAGGGTGTTTGTGCTGCTGCTGGTCCTGGTCTCCATCCTCTGGATCCCTGTGGTC CAGGCCAGCCAGGGCGGCCAGCTCTTCATCTATATCCAGTCCATCAGCTCCTACCTGCAGCCGCCTGT GGCGGTGGTCTTCATCATGGGATGTTTCTGGAAGAGGACCAATGAAAAGGGTGCCTTCTGGGGCCTGA TCTCGGGCCTCGAGGGC
NOV58b, 265726152 SEQ ID NO: 914 436 aa MW at 4735δ.5kD Protein Sequence
TGSYFLAGGDMV PVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLA IFLPIYIA GQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLAIVGLLAITAV YTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLALASNRSENSSCGLPREDAF HIFRDPLTSDLPWPGVLFGMSIPSLWY CTDQVIVQRTLAAKNLSHAKGGALMAAYLKVLPLFIMVFP GMVSRILFPDQVACADPEICQKICSNPSGCSDIAYPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFN SASTIFTMDLWNHLRPRASEKELMIVGRVFVLLLVLVSIL IPWQASQGGQLFIYIQSISSYLQPPV AWFIMGCFWKRTNEKGAFWGLISGLEG
NOV5δc, 267254040 SEQ ID NO: 915 [1912 bp DNA Sequence JORF Start: at 2 ORF Stop: end of sequence
AGAATTCGCCTTCACCGGATCCAAAAGAGACACAGTGAAAGGCTACTTCCTGGCTGGAGGGGACATGG TGTGGTGGCCAGTGGGTGCATCCTTGTTTGCCAGCAATGTTGGAAGTGGACATTTCATTGGCCTGGCA GGGTCAGGTGCTGCTACGGGCATTTCTGTATCAGCTTATGAACTTAATGGCTTGTTTTCTGTGCTGAT GTTGGCCTGGATCTTCCTACCCATCTACATTGCTGGTCAGGTCACCACGATGCCAGAATACCTACGGA AGCGCTTCGGTGGCATCAGAATCCCCATCATCCTGGCTGTACTCTACCTATTTATCTACATCTTCACC AAGATCTCGGTAGACATGTATGCAGGTGCCATCTTCATCCAGCAGTCTTTGCACCTGGATCTGTACCT GGCCATAGTTGGGCTACTGGCCATCACTGCTGTATACACGGTTGCTGGTGGCCTGGCTGCTGTGATCT ACACGGATGCCCTGCAGACGCTGATCATGCTTATAGGAGCGCTCACCTTGATGGGCTACAGTTTCGCC GCGGTTGGTGGGATGGAAGGACTGAAGGAGAAGTACTTCTTGGCCCTGGCTAGCAACCGGAGTGAGAA CAGCAGCTGCGGGCTGCCCCGGGAAGATGCCTTCCATATTTTCCGAGATCCGCTGACATCTGATCTCC CGTGGCCGGGGGTCCTATTTGGAATGTCCATCCCATCCCTCTGGTACTGGTGCACGGATCAGGTGATT GTCCAGCGGACTCTGGCTGCCAAGAACCTGTCCCATGCCAAAGGAGGTGCTCTGATGGCTGCATACCT GAAGGTGCTGCCCCTCTTCATAATGGTGTTCCCTGGGATGGTCAGCCGCATCCTCTTCCCAGATCAAG TGGCCTGTGCAGATCCAGAGATCTGCCAGAAGATCTGCAGCAACCCCTCAGGCTGTTCGGACATCGCG TATCCCAAACTCGTGCTGGAACTCCTGCCCACAGGGCTCCGTGGGCTGATGATGGCTGTGATGGTGGC GGCTCTCATGTCCTCCCTCACCTCCATCTTTAACAGTGCCAGCACCATCTTCACCATGGACCTCTGGA ATCACCTCCGGCCTCGGGCATCTGAGAAGGAGCTCATGATTGTGGGCAGGGTGTTTGTGCTGCTGCTG GTCCTGGTCTCCATCCTCTGGATCCCTGTGGTCCAGGCCAGCCAGGGCGGCCAGCTCTTCATCTATAT CCAGTCCATCAGCTCCTACCTGCAGCCGCCTGTGGCGGTGGTCTTCATCATGGGATGTTTCTGGAAGA GGACCAATGAAAAGGGTGCCTTCTGGGGCCTGATCTCGGGCCTGCTCCTGGGCTTGGTTAGGCTGGTC CTGGACTTTATTTACGTGCAGCCTCGATGCGACCAGCCAGATGAGCGCCCGGTCCTGGTGAAGAGCAT TCACTACCTCTACTTCTCCATGATCCTGTCCACGGTCACCCTCATCACTGTCTCCACCGTGAGCTGGT TCACAGAGCCACCCTCCAAGGAGATGGTCAGCCACCTGACCTGGTTTACTCGTCACGACCCCGTGGTC CAGAAGGAACAAGCACCACCAGCAGCTCCCTTGTCTCTTACCCTCTCTCAGAACGGGATGCCAGAGGC CAGCAGCAGCAGCAGCGTCCAGTTCGAGATGGTTCAAGAAAACACGTCTAAAACCCACAGCTGTGACA TGACCCCAAAGCAGTCCAAAGTGGTGAAGGCCATCCTGTGGCTCTGTGGAATACAGGAGAAGGGCAAG GAAGAGCTCCCGGCCAGAGCAGAAGCCATCATAGTTTCCCTGGAAGAAAACCCCTTGGTGAAGACCCT CCTGGACGTCAACCTCATTTTCTGCGTGAGCTGCGCCATCTTTATCTGGGGCTATTTTGCTCTCGAGG GCAGGGCG
NOV5δc, 267254040 SEQ ID NO: 916 637 aa MW at 69945.6kD Protein Sequence
EFAFTGSKRDTVKGYFLAGGDMWWPVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLM LAWIFLPIYIAGQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYL AlVGLLAITAVYTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLALASNRSEN SSCGLPREDAFHIFRDPLTSDLP PGVLFGMSIPSL YWCTDQVIVQRTLAAKNLSHAKGGALMAAYL KVLPLFIMVFPGMVSRILFPDQVACADPEICQKICSNPSGCSDIAYPKLVLELLPTGLRGLMMAVMVA ALMSSLTSIFNSASTIFTMDLWNHLRPRASEKELMIVGRVFVLLLVLVSILWIPWQASQGGQLFIYI QSISSYLQPPVAWFIMGCFWKRTNEKGAFWGLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSI δ29 HYLYFSMILSTVTLITVSTVSWFTEPPSKEMVSHLTWFTRHDPWQKEQAPPAAPLSLTLSQNGMPEA SSSSSVQFEMVQENTSKTHSCDMTPKQSKWKAILWLCGIQEKGKEELPARAEAIIVSLEENPLVKTL LDVNLIFCVSCAIFI GYFALEGRA
NOV5δd, SNP 13379242 of SEQ ID NO: 917 2105 bp CG5639δ-01, DNA Sequence ORF Start: ATG at 31 ORF Stop: TAG at 2056
SNP Pos: δ04 SNP Change: C to G
CCTCAGGATCCAGAGGTCTCGTTCAGGACCATGGAGAGCGGCACCAGCAGCCCTCAGCCTCCACAGTT
AGATCCCCTGGATGCGTTTCCCCAGAAGGGCTTGGAGCCTGGGGACATCGCGGTGCTAGTTCTGTACT TCCTCTTTGTCCTGGCTGTTGGACTATGGTCCACAGTGAAGACCAAAAGAGACACAGTGAAAGGCTAC TTCCTGGCTGGAGGGGACATGGTGTGGTGGCCAGTGGGTGCATCCTTGTTTGCCAGCAATGTTGGAAG TGGACATTTCATTGGCCTGGCAGGGTCAGGTGCTGCTACGGGCATTTCTGTATCAGCTTATGAACTTA ATGGCTTGTTTTCTGTGCTGATGTTGGCCTGGATCTTCCTACCCATCTACATTGCTGGTCAGGTGACC ACGATGCCAGAATACCTACGGAAGCGCTTCGGTGGCATCAGAATCCCCATCATCCTGGCTGTACTCTA CCTATTTATCTACATCTTCACCAAGATCTCGGTAGACATGTATGCAGGTGCCATCTTCATCCAGCAGT CTTTGCACCTGGATCTGTACCTGGCCATAGTTGGGCTACTGGCCATCACTGCTGTATACACGGTTGCT GGTGGCCTGGCTGCTGTGATCTACACGGATGCCCTGCAGACGCTGATCATGCTTATAGGAGCGCTCAC CTTGATGGGCTACAGTTTCGCCGCGGTTGGTGGGATGGAAGGACTGAAGGAGAAGTACTTCTTGGCCC TGGCTAGCAACCGGAGTGAGAACAGCAGCTGCGGGCTGCCCCGGGAAGATGCCTTGCATATTTTCCGA GATCCGCTGACATCTGATCTCCCGTGGCCGGGGGTCCTATTTGGAATGTCCATCCCATCCCTCTGGTA CTGGTGCACGGATCAGGTAATTGTCCAGCGGACTCTGGCTGCCAAGAACCTGTCCCATGCCAAAGGAG GTGCTCTGATGGCTGCATACCTGAAGGTGCTGCCCCTCTTCATAATGGTGTTCCCTGGGATGGTCAGC CGCATCCTCTTCCCAGATCAAGTGGCCTGTGCAGATCCAGAGATCTGCCAGAAGATCTGCAGCAACCC CTCAGGCTGTTCGGACATCGCGTATCCCAAACTCGTGCTGGAACTCCTGCCCACAGGTCTCCGTGGGC TGATGATGGCTGTGATGGTGGCGGCTCTCATGTCCTCCCTCACCTCCATCTTTAACAGTGCCAGCACC ATCTTCACCATGGACCTCTGGAATCACCTCCGGCCTCGGGCATCTGAGAAGGAGCTCATGATTGTGGG CAGGGTGTTTGTGCTGCTGCTGGTCCTGGTCTCCATCCTCTGGATCCCTGTGGTCCAGGCCAGCCAGG GCGGCCAGCTCTTCATCTATATCCAGTCCATCAGCTCCTACCTGCAGCCGCCTGTGGCGGTGGTCTTC ATCATGGGATGTTTCTGGAAGAGGACCAATGAAAAGGGTGCCTTCTGGGGCCTGATCTCGGGCCTGCT CCTGGGCTTGGTTAGGCTGGTCCTGGACTTTATTTACGTGCAGCCTCGATGCGACCAGCCAGATGAGC GCCCGGTCCTGGTGAAGAGCATTCACTACCTCTACTTCTCCATGATCCTGTCCACGGTCACCCTCATC ACTGTCTCCACCGTGAGCTGGTTCACAGAGCCACCCTCCAAGGAGATGGTCAGCCACCTGACCTGGTT TACTCGTCACGACCCCGTGGTCCAGAAGGAACAAGCACCACCAGCAGCTCCCTTGTCTCTTACCCTCT CTCAGAACGGGATGCCAGAGGCCAGCAGCAGCAGCAGCGTCCAGTTCGAGATGGTTCAAGAAAACACG TCTAAAACCCACAGCGGTGACATGACCCCAAAGCAGTCCAAAGTGGTGAAGGCCATCCTGTGGCTCTG TGGAATACAGGAGAAGGGCAAGGAAGAGCTCCCGGCCAGAGCAGAAGCCATCATAGTTTCCCTGGAAG AAAACCCCTTGGTGAAGACCCTCCTGGACGTCAACCTCATTTTCTGCGTGAGCTGCGCCATCTTTATC TGGGGCTATTTTGCTTAGTGTGGGGTGAACCCAGGGGTCCAAACTCTGTTTCTCTTCAGTGCTCC
NOV5δd, SNP13379242 of SEQ ID NO: 918 675 aa MW at 73955.2kD CG5639δ-01, Protein Sequence SNP Pos: 258 SNP Change: Phe to Leu
MESGTSSPQPPQLDPLDAFPQKGLEPGDIAVLVLYFLFVLAVGLWSTVKTKRDTVKGYFLAGGDM W PVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLAWIFLPIYIAGQVTTMPEYLRKRF GGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLAIVGLLAITAVYTVAGGLAAVIYTD ALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLALASNRSENSSCGLPREDALHIFRDPLTSDLPWP GVLFGMSIPSLWYWCTDQVIVQRTLAAKNLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVAC ADPEICQKICSNPSGCSDIAYPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDL NHL RPRASEKELMIVGRVFVLLLVLVSILWIPWQASQGGQLFIYIQSISSYLQPPVAWFIMGCFWKRTN EKGAF GLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSIHYLYFSMILSTVTLITVSTVS FTE PPSKEMVSHLT FTRHDPWQKEQAPPAAPLSLTLSQNGMPEASSSSSVQFEMVQENTSKTHSGDMTP KQSKWKAILWLCGIQEKGKEELPARAEAIIVSLEENPLVKTLLDVNLIFCVSCAIFI GYFA
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 58B. Table 58B. Comparison of the NOV58 protein sequences.
NOV58a MESGTSSPQPPQLDPLDAFPQKGLEPGDIAVLVLYFLFVLAVGLWSTVKTKRDTVKGYFL
NOV58b TGSYFL
NOV58C EFAFTGSKRDTVKGYFL
NOV58a AGGDMVW PVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLA IFLPIY
NOV58b AGGDMVWWPVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLAWIFLPIY
NOV58C AGGDMVWWPVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLAWIFLPIY
NOV58a IAGQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLA
NOV58b IAGQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLA
NOV58C IAGQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLA
NOV58a IVGLLAITAVYTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLAL
NOV58b IVGLLAITAVYTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLAL
NOV58c IVGLLAITAVYTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLAL
NOV58a ASNRSENSSCGLPREDAFHIFRDPLTSDLPWPGVLFGMSIPSLWY CTDQVIVQRTLAAK
NOV58b ASNRSENSSCGLPREDAFHIFRDPLTSDLPWPGVLFGMSIPSLWYWCTDQVIVQRTLAAK
NOV58C ASNRSENSSCGLPREDAFHIFRDPLTSDLPWPGVLFGMSIPSL YWCTDQVIVQRTLAAK
NOV58a NLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVACADPEICQKICSNPSGCSDIA
NOV58b NLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVACADPEICQKICSNPSGCSDIA
NOV58C NLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVACADPEICQKICSNPSGCSDIA
NOV58a YPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDLWNHLRPRASEKELMIV
NOV58b YPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDLWNHLRPRASEKELMIV
NOV58c YPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDLWNHLRPRASEKELMIV
NOV58a GRVFVLLLVLVSILWIPWQASQGGQLFIYIQSISSYLQPPVAWFIMGCF KRTNEKGA
NOV58b GRVFVLLLVLVSIL IPWQASQGGQLFIYIQSISSYLQPPVAWFIMGCF KRTNEKGA
NOV58C GRVFVLLLVLVSILWIPWQASQGGQLFIYIQSISSYLQPPVAWFIMGCFWKRTNEKGA
NOV58a FWGLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSIHYLYFSMILSTVTLITVSTVS
NOV58b FWGLISGLEG
NOV58c FWGLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSIHYLYFSMILSTVTLITVSTVS
NOV58a FTEPPSKEMVSHLT FTRHDPWQKEQAPPAAPLSLTLSQNGMPEASSSSSVQFEMVQE
NOV58b
NOV58C WFTEPPSKEMVSHLT FTRHDPWQKEQAPPAAPLSLTLSQNGMPEASSSSSVQFEMVQE
NOV58a NTSKTHSGDMTPKQSKWKAIL LCGIQEKGKEELPARAEAIIVSLEENPLVKTLLDVNL
NOV58b
NOV58C NTSKTHSCDMTPKQSKWKAILWLCGIQEKGKEELPARAEAIIVSLEENPLVKTLLDVNL
NOV58a IFCVSCAIFIWGYFA
NOV58b
NOV58C IFCVSCAIFI GYFALEGRA
NOV58a (SEQ ID NO 912) NOV58b (SEQ ID NO 914) NOV58c (SEQ ID NO 916) Further analysis ofthe NOV5δa protein yielded the following properties shown in Table 5δC.
Table 58C. Protein Sequence Properties NOV58a
SignalP analysis: Cleavage site between residues 51 and 52
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 2 ; pos . chg 0 ; neg . chg 1 H-region : length 11 ; peak value 0. 00 PSG score : -4 .40
GvH : von Heij ne ' s method for signal seq. recognition GvH score (threshold : -2 . 1) : -0. 94 possible cleavage site : between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0, 5: 11
I INNTTEEGGRRAALL Likelihood =-10.61 Transmembrane 29 - 45
I INNTTEEGGRRAALL Likelihood = -6.64 Transmembrane 106 - 122
I INNTTEEGGRRAALL Likelihood = -7.64 Transmembrane 139 - 155
I INNTTEEGGRRAALL Likelihood = -5.79 Transmembrane 177 - 193
I INNTTEEGGRRAALL Likelihood = -3.24 Transmembrane 210 - 226
I INNTTEEGGRRAALL Likelihood = -4.88 Transmembrane 309 - 325
I INNTTEEGGRRAALL Likelihood = -3.88 Transmembrane 376 - 392
I INNTTEEGGRRAALL Likelihood =-13.69 Transmembrane 423 - 439
I INNTTEEGGRRAALL Likelihood = -5.47 Transmembrane 484 - 500
I INNTTEEGGRRAALL Likelihood = -0.53 Transmembrane 524 - 540
I INNTTEEGGRRAALL Likelihood = -5.47 Transmembrane 654 - 670
P PEERRIIPPHHEERRAALL Likelihood = 1.32 (at 454)
ALOM score : -13.69 (number of TMSs: 11)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 36 Charge difference: 6.0 C( 3.0) - N(-3.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 4.59 Hyd Moment (95): 4.89 G content: 1 D/E content: 2 S/T content: 4 Score: -6.67
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
δ32 NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PEYLRKR (3) at 129 bipartite: none content of basic residues: 6.7% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2: 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
66.7 % endoplasmic reticulum
11.1 % vacuolar
11.1 % mitochondrial
11.1 % Golgi δ33 >> prediction for CG56398-01 is end (k=9)
A search ofthe NOV58a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 58D.
Figure imgf000838_0001
In a BLAST search of public sequence databases, the NOV5δa protein was found to have homology to the proteins shown in the BLASTP data in Table 5δE.
δ34
Figure imgf000839_0001
PFam analysis indicates that the NOV58a protein contains the domains shown in the Table 58F.
Figure imgf000839_0002
Example 59.
The NOV59 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 59A.
Table 59A. NOV59 Sequence Analysis
NOV59a, CG56605-03 SEQ ID NO: 919 557 bp DNA Sequence ORF Start: ATG at 26 ORF Stop: TAG at 524
ATGGTGGCAGAGTCTACATAGAACTATGCTTCGTGGTGTTCTGGGGAAAACCTTTCGACTTGTTGGCT ATACTATTCAATATGGCTGTATAGCTCATTGTGCTTTTGAATACGTTGGTGGTGTTGTCATGTGTTCT GGACCATCAATGGAGCCTACAATTCAAAATTCAGATATTGTCTTTGCAGAAAATCTTAGTCGACATTT TTATGGTATCCAAAGAGGTGACATTGTGATTGCAAAAAGCCCAAGTGATCCAAAATCAAATATTTGTA AAAGAGTAATTGGTTTGGAAGGAGACAAAATCCTCACCACTAGTCCATCAGATTTCTTTAAAAGCCAT AGTTATGTGCCAATGGGTCATGTTTGGTTAGAAGGTGACAATCTACAGAATTCTACAGATTCCAGGTG CTATGGACCTATTCCATATGGACTAATAAGAGGACGAATCTTCTTTAAGATTTGGCCTCTGAGTGATT TTGGATTTTTACGTGCCAGCCCTAATGGCCACAGATTTTCTGATGATTAGTAAGCATTTATTCTTTTG ACTTGATTATTGT
NOV59a, CG56605-03 SEQ ID NO: 920 166 aa MW at l8504.0kD Protein Sequence
MLRGVLGKTFRLVGYTIQYGCIAHCAFEYVGGWMCSGPSMEPTIQNSDIVFAENLSRHFYGIQRGDI VIAKSPSDPKSNICKRVIGLEGDKILTTSPSDFFKSHSYVPMGHWLEGDNLQNSTDSRCYGPIPYGL IRGRIFFKIWPLSDFGFLRASPNGHRFSDD
NOV59b, CG56605-01 SEQ ID NO: 921 513 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAA at 445
AGTCTACATAGAACTATGCTTCGTGGTGCTCTGGGGAAACCTTCTGACCTTGTTGGCTATGCTATTCA
GTATGGCTGTATAGCTCACTGTGCTTCTGAATACGTTGGTGGTGTTGTCATGTGTTCTGGACCATCAA TGGAGCCTACAATTCAAAATTCAGATACTGTCTTTGCACAAAATCTTAGTCGACATTTTGATAGTATC CAAAGAGGTGACATTGTGATTGCAAAAAGCCCAAGTGATCCAACATCAAATATTTGTAAAAGAGTAAC TGGTTTGGAAGGAGACAAAATCCTCACCACTAGTCCATCAGATTTCTTTAAAAGCTACAGTTATGTCC CAGTGGGTCATGTTTGGTTAGAAGGTGATAATCTACAGAATTCTACAGATTCCAGTTACTATGGACCT ATTCCATATGAACTAATAAGAGGACGAATCTTCTTTTAAGATTCGGCCTCTGAGTGATTTTGGATTTT TATGTGCCAGCCTTAATGGCCACAGATTTTCTGATGA
NOV59b, CG56605-01 SEQ ID NO: 922 143 aa MW at l5622.4 D Protein Sequence
MLRGALGKPSDLVGYAIQYGCIAHCASEYVGGWMCSGPSMEPTIQNSDTVFAQNLSRHFDSIQRGDI VIAKSPSDPTSNICKRVTGLEGDKILTTSPSDFFKSYSYVPVGHVWLEGDNLQNSTDSSYYGPIPYEL IRGRIFF
NOV59c, CG56605-02 SEQ ID NO: 923 507 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: at 506
ACATAGAACTATGCTTCGTGGTGCTCTGGGGAAAACCTTTCGACTTGTTGGCTATACTATTCAATATG
GCTGTATAGCTCATTGTGCTTTTGAATACGTTGGTGGTGTTGTCATGTGTTCTGGACCATCAATGGAG CCTACAATTCAAAATTCAGATATTGTCTTTGCAGAAAATCTTAGTCGACATTTTTATGGTATCCAAAG AGGTGACATTGTGATTGCAAAAAGCCCAAGTGATCCAAAATCAAATATTTGTAAAAGAGTAATTGGTT TGGAAGGAGACAAAATCCTCACCACTAGTCCATCAGATTTCTTTAAAAGCCATAGTTATGTGCCAATG GGTCATGTTTGGTTAGAAGGTGACAATCTACAGAATTCTACAGATTCCAGGTGCTATGGACCTATTCC ATATGGACTAATAAGAGGACGAATCTTCTTTAAGATTTGGCCTCTGAGTGATTTTGGATTTTTACGTG CCAGCCTTAATGGCCACAGATTTTCTGATGA
NOV59c, CG56605-02 SEQ ID NO: 924 165 aa MW at l8376.9kD Protein Sequence
MLRGALGKTFRLVGYTIQYGCIAHCAFEYVGGWMCSGPSMEPTIQNSDIVFAENLSRHFYGIQRGDI VIAKSPSDPKSNICKRVIGLEGDKILTTSPSDFFKSHSYVPMGHVWLEGDNLQNSTDSRCYGPIPYGL IRGRIFFKIWPLSDFGFLRASLNGHRFSD
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 59B.
Table 59B. Comparison of the NOV59 protein sequences.
NOV59a MLRGVLGKTFRLVGYTIQYGCIAHCAFEYVGGWMCSGPS EPTIQNSDIVFAENLSRHF NOV59b MLRGALGKPSDLVGYAIQYGCIAHCASEYVGGWMCSGPSMEPTIQNSDTVFAQNLSRHF δ36 NOV59c MLRGALGKTFRLVGYTIQYGCIAHCAFEYVGGWMCSGPSMEPTIQNSDIVFAENLSRHF
NOV59a YGIQRGDIVIAKSPSDPKSNICKRVIGLEGDKILTTSPSDFFKSHSYVPMGHV LEGDNL
NOV59b DSIQRGDIVIAKSPSDPTSNICKRVTGLEGDKILTTSPSDFFKSYSYVPVGHVWLEGDNL
NOV59c YGIQRGDIVIAKSPSDPKSNICKRVIGLEGDKILTTSPSDFFKSHSYVPMGHVWLEGDNL
NOV59a QNSTDSRCYGPIPYGLIRGRIFFKIWPLSDFGFLRASPNGHRFSDD
NOV59b QNSTDSSYYGPIPYELIRGRIFF
NOV59C QNSTDSRCYGPIPYGLIRGRIFFKIWPLSDFGFLRASLNGHRFSD-
NOV59a (SEQ ID NO 920) NOV59b (SEQ ID NO 922) NOV59C (SEQ ID NO 924)
Further analysis ofthe NOV59a protein yielded the following properties shown in Table 59C.
Table 59C. Protein Sequence Properties NOV59a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 11 ; pos . chg 3 ; neg . chg 0 H-region : length 16 ; peak value 6 .29 PSG score : 1 .89
GvH : von Heijne ' s method for signal seq . recognition GvH score ( threshold : -2 . 1 ) : -7 .69 possible cleavage site : between 32 and 33
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation Init position for calculation : 1 Tentative number of TMS ( s) for the threshold 0 . 5: number of TMS (s) . . fixed PERIPHERAL Likelihood = 1. 70 (at 20) ALOM score : 1 .70 (number of TMSs : 0 )
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 6 Charge difference: 0.0 C( 2.0) - N( 2.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq
R content : 2 Hyd Moment (75) : 14.36
Hyd Momen (95): 9.31 G content : 4
D/E content: 1 S/T content: 2 Score: -2.96
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 21 FRL|VG NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : LRGV
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
δ3δ 43.5 %: cytoplasmic
34.8 %: mitochondrial
8.7 %: nuclear
8.7 %: peroxisomal
4.3 %: plasma membrane
>> prediction for CG56605-03 is cyt (k=23)
A search ofthe NOV59a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 59D.
Figure imgf000843_0001
In a BLAST search of public sequence databases, the NOV59a protein was found to have homology to the proteins shown in the BLASTP data in Table 59E.
Figure imgf000844_0001
PFam analysis indicates that the NOV59a protein contains the domains shown in the Table 59F.
Table 59F. Domain Analysis of NOV59a
Identities/
Pfam Domain NOV59a Match Region Similarities Expect Value for the Matched Region
Peptidase_S26 1..152 37/221 (17%) 9.1e-07 104/221 (47%)
Example 60.
The NOV60 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 60A.
δ40 Table 60A. NOV60 Sequence Analysis
NOV60a, CG56645-03 SEQ ID NO: 925 lδ62 bp DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1829
CGGGCTCATACCTAGTGCCTGCGGCAGGACAGCCATGGCCGCCAACTCCACCAGCGACCTCCACACTC
CCGGGACGCAGCTGAGCGTGGCTGACATCATCGTCATCACTGTGTATTTTGCTCTGAACGTGGCCGTG GGCATATGGTCCTCTTGTCGGGCCAGTAGGAACACGGTGAATGGCTACTTCCTGGCAGGCCGGGACAT GACGTGGTGGCCGATTGGAGCCTCCCTCTTCGCCAGCAGCGAGGGCTCTGGCCTCTTCATTGGACTGG CGGGCTCAGGCGCGGCAGGAGGTCTGGCCGTGGCAGGCTTCGAGTGGAATGCCACGTACGTGCTGCTG GCACTGGCATGGGTGTTCGTGCCCATCTACATCTCCTCAGAGATCGTCACCTTACCTGAGTACATTCA GAAGCGCTACGGGGGCCAGCGGATCCGCATGTACCTGTCTGTCCTGTCCCTGCTACTGTCTGTCTTCA CCAAGATATCGCTGGACCTGTACGCGGGGGCTCTGTTTGTGCACATCTGCCTGGGCTGGAACTTCTAC CTCTCCACCATCCTCACGCTCGGCATCACAGCCCTGTACACCATCGCAGGGGGCCTGGCTGCTGTAAT CTACACGGACGCCCTGCAGACGCTCATCATGGTGGTGGGGGCTGTCATCCTGACAATCAAAGCTTTTG ACCAGATCGGTGGTTACGGGCAGCTGGAGGCAGCCTACGCCCAGGCCATTCCCTCCAGGACCATTGCC AACACCACCTGCCACCTGCCACGTACAGACGCCATGCACATGTTTCGAGACCCCCACACAGGGGACCT GCCGTGGACCGGGATGACCTTTGGCCTGACCATCATGGCCACCTGGTACTGGTGCACCGACCAGGTCA TCGTGCAGCGATCACTGTCAGCCCGGGACCTGAACCATGCCAAGGCGGGCTCCATCCTGGCCAGCTAC CTCAAGATGCTCCCCATGGGCCTGATCATCATGCCGGGCATGATCAGCCGCGCATTGTTCCCAGGTGC TCATGTCTATGAGGAGAGACACCAAGTGTCCGTCTCTCGAACAGATGATGTGGGCTGCGTGGTGCCGT CCGAGTGCCTGCGGGCCTGCGGGGCCGAGGTCGGCTGCTCCAACATCGCCTACCCCAAGCTGGTCATG GAACTGATGCCCATCGGTCTGCGGGGGCTGATGATCGCAGTGATGCTGGCGGCGCTCATGTCGTCGCT GACCTCCATCTTCAACAGCAGCAGCACCCTCTTCACTATGGACATCTGGAGGCGGCTGCGTCCCCGCT CCGGCGAGCGGGAGCTCCTGCTGGTGGGACGGCTGGTCATAGTGGCACTCATCGGCGTGAGTGTGGCC TGGATCCCCGTCCTGCAGGACTCCAACAGCGGGCAACTCTTCATCTACATGCAGTCAGTGACCAGCTC CCTGGCCCCACCAGTGACTGCAGTCTTTGTCCTGGGCCTGATAGCAGGGCTGGTGGTGGGGGCCACGA GGCTGGTCCTGGAATTCCTGAACCCAGCCCCACCGTGCGGAGAGCCAGACACGCGGCCAGCCGTCCTG GGGAGCATCCACTACCTGCACTTCGCTGTCGCCCTCTTTGCACTCAGTGGTGCTGTTGTGGTGGCTGG AAGCCTGCTGACCCCACCCCCACAGAGTGTCCAGATTGAGAACCTTACCTGGTGGAACCTGGCTCAGG ATGTGCCCTTGGGAACTAAAGCAGGTGATGGCCAAACACCCCAGAAACACGCCTTCTGGGCCCGTGTC TGTGGCTTCAATGCCATCCTCCTCATGTGTGTCAACATATTCTTTTATGCCTACTTCGCCTGACACTG CCATCCTGGACAGAAAGGCAGGAGCT
NOV60a, CG56645-03 SEQ ID NO: 926 59δ aa MW at 644δ5.7kD Protein Sequence
MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTW PIGASLFA SSEGSGLFIGLAGSGAAGGLAVAGFE NATYVLLALAWVFVPIYISSEIVTLPEYIQKRYGGQRIRMY LSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGITALYTIAGGLAAVIYTDALQTLIMV VGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANTTCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTI MATWY CTDQVIVQRSLSARDLNHAKAGSILASYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSV SRTDDVGCWPSECLRACGAEVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLF TMDIWRRLRPRSGERELLLVGRLVIVALIGVSVA IPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVL GLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALSGAVWAGSLLTPPPQSVQ IENLTW NLAQDVPLGTKAGDGQTPQKHAFWARVCGFNAILLMCVNIFFYAYFA
NOV60b, CG56645-04 SEQ ID NO: 927 lδOl bp DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1790
CGGGCTCATACCTAGTGCCTGCGGCAGGACAGCCATGGCCGCCAACTCCACCAGCGACCTCCACACTC
CCGGGACGCAGCTGAGCGTGGCTGACATCATCGTCATCACTGTGTATTTTGCTCTGAACGTGGCCGTG GGCATATGGTCCTCTTGTCGGGCCAGTAGGAACACGGTGAATGGCTACTTCCTGGCAGGCCGGGACAT GACGTGGTGGCCGATTGGAGCCTCCCTCTTCGCCAGCAGCGAGGGCTCTGGCCTCTTCATTGGACTGG CGGGCTCAGGCGCGGCAGGAGGTCTGGCCGTGGCAGGCTTCGAGTGGAATGCCACGTACGTGCTGCTG GCACTGGCATGGGTGTTCGTGCCCATCTACATCTCCTCAGAGATCGTCACCTTACCTGAGTACATTCA GAAGCGCTACGGGGGCCAGCGGATCCGCATGTACCTGTCTGTCCTGTCCCTGCTACTGTCTGTCTTCA CCAAGATATCGCTGGACCTGTACGCGGGGGCTCTGTTTGTGCACATCTGCCTGGGCTGGAACTTCTAC CTCTCCACCATCCTCACGCTCGGCATCACAGCCCTGTACACCATCGCAGCTTTTGACCAGATCGGTGG δ41 TTACGGGCAGCTGGAGGCAGCCTACGCCCAGGCCATTCCCTCCAGGACCATTGCCAACACCACCTGCC AGCTGCCACGTACAGACGCCATGCACATGTTTCGAGACCCCCACACAGGGGACCTGCCGTGGACCGGG ATGACCTTTGGCCTGACCATCATGGCCACCTGGTACTGGTGCACCGACCAGGTCATCGTGGAGGGATC ACTGTCAGCCCGGGACCTGAACCATGCCAAGGGGGGCTCCATCCTGGGCAGCTACCTCAAGATGCTCC CCATGGGCCTGATCATCATGCCGGGCATGATCAGCCGCGCATTGTTCCCAGGTGCTCATGTCTATGAG GAGAGACACCAAGTGTCCGTCTCTCGAACAGATGATGTGGGCTGCGTGGTGCCGTCCGAGTGCCTGCG GGCCTGCGGGGCCGAGGTCGGCTGCTCCAACATCGCCTACCCCAAGCTGGTCATGGAACTGATGCCCA TCGGTCTGCGGGGGCTGATGATCGCAGTGATGCTGGCGGCGCTCATGTCGTCGCTGACCTCCATCTTC AACAGCAGCAGCACCCTCTTCACTATGGACATCTGGAGGCGGCTGCGTCCCCGCTCCGGCGAGCGGGA GCTCCTGCTGGTGGGACGGCTGGTCATAGTGGCACTCATCGGCGTGAGTGTGGCCTGGATCCCCGTCC TGCAGGACTCCAACAGCGGGCAACTCTTCATCTACATGCAGTCAGTGACCAGCTCCCTGGCCCCACCA GTGACTGCAGTCTTTGTCCTGGGCGTCTTCTGGCGACGTGCCAACGAGCAGGGGGCCTTCTGGGGCCT GATAGCAGGGCTGGTGGTGGGGGCCACGAGGCTGGTCCTGGAATTCCTGAACCCGGCCCCACCGTGCG GAGAGCCAGACACGCGGCCAGCCGTCCTGGGGAGCATCCACTACCTGCACTTCGCTGTCGCCCTCTTT GCACTCAGTGGTGCTGTTGTGGTGGCTGGAAGCCTGCTGACCCCACCCCCACAGAGTGTCCAGATTGA GAACCTTACCTGGTGGACCCTGGCTCAGGATGTGCCCTTGGGAACTAAAGCAGGTGATGGCCAAACAC CCCAGAAACACGCCTTCTGGGCCCGTGTCTGTGGCTTCAATGCCATCCTCCTCATGTGTGTCAACATA TTCTTTTATGCCTACTTCGCCTGACACTGCCAT
NOV60b, CG56645-04 SEQ ID NO: 92δ 585 aa MW at 63317.1kD Protein Sequence
MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTWWPIGASLFA SSEGSGLFIGLAGSGAAGGI^VAGFEWNATYVLLALAWVFVPIYISSEIVTLPEYIQKRYGGQRIRMY LSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGITALYTIAAFDQIGGYGQLEAAYAQA IPSRTIANTTCQLPRTDAMHMFRDPHTGDLPWTGMTFGLTIMATWYWCTDQVIVEGSLSARDLNHAKG GSILGSYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSVSRTDDVGCWPSECLRACGAEVGCSNI AYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRSGERELLLVGRLVIVA LIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVLGVF RRANEQGAF GLIAGLWGATRL VLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALSGAVWAGSLLTPPPQSVQIENLT WTLAQDV PLGTKAGDGQTPQKHAF ARVCGFNAILLMCVNIFFYAYFA
NOV60c, CG56645-01 SEQ ID NO: 929 1914 bp
DNA Sequence ORF Start: ATG at 51 ORF Stop: TGA at 1839
TTGCCCCTCAGTCCCTCGGGCTCATACCTAGTGCCTGCGGCAGGACAGCCATGGCCGCCAACTCCACC
AGCGACCTCCACACTCCCGGGACGCAGCTGAGCGTGGCTGACATCATCGTCATCACTGTGTATTTTGC TCTGAACGTGGCCGTGGGCATATGGTCCTCTTGTCGGGCCAGTAGGAACACGGTGAATGGCTACTTCC TGGCAGGCCGGGACATGACGTGGTGGCCGATTGGAGCCTCCCTCTTCGCCAGCAGCGAGGGCTCTGGC CTCTTCATTGGACTGGCGGGCTCAGGCGCGGCAGGAGGTCTGGCCGTGGCAGGCTTCGAGTGGAATGC CACGTACGTGCTGCTGGCACTGGCATGGGTGTTCGTGCCCATCTACATCTCCTCAGAGATCGTCACCT TACCTGAGTACATTCAGAAGCGCTACGGGGGCCAGCGGATCCGCATGTACCTGTCTGTCCTGTCCCTG CTACTGTCTGTCTTCACCAAGATATCGCTGGACCTGTACGCGGGGGCTCTGTTTGTGCACATCTGCCT GGGCTGGAACTTCTACCTCTCCACCATCCTCACGCTCGGCATCACAGCCCTGTACACCATCGCAGGGG GCCTGGCTGCTGTAATCTACACGGACGCCCTGCAGACGCTCATCATGGTGGTGGGGGCTGTCATCCTG ACAATCAAAGCTTTTGACCAGATCGGTGGTTACGGGCAGCTGGAGGCAGCCTACGCCCAGGCCATTCC CTCCAGGACCATTGCCAACACCACCTGCCACCTGCCACGTACAGACGCCATGCACATGTTTCGAGACC CCCACACAGGGGACCTGCCGTGGACCGGGATGACCTTTGGCCTGACCATCATGGCCACCTGGTACTGG TGCACCGACCAGGTGATCGTGCAGCGATCACTGTCAGCCCGGGACCTGAACCATGCCAAGGCGGGCTC CATCCTGGCCAGCTACCTCAAGATGCTCCCCATGGGCCTGATCATAATGCCGGGCATGATCAGCCGCG CATTGTTCCCAGATGATGTGGGCTGCGTGGTGCCGTCCGAGTGCCTGCGGGCCTGCGGGGCCGAGGTC GGCTGCTCCAACATCGCCTACCCCAAGCTGGTCATGGAACTGATGCCCATCGGTCTGCGGGGGCTGAT GATCGCAGTGATGCTGGCGGCGCTCATGTCGTCGCTGACCTCCATCTTCAACAGCAGCAGCACCCTCT TCACTATGGACATCTGGAGGCGGCTGCGTCCCCGCTCCGGCGAGCGGGAGCTCCTGCTGGTGGGACGG CTGGTCATAGTGGCACTCATCGGCGTGAGTGTGGCCTGGATCCCCGTCCTGCAGGACTCCAACAGCGG GCAACTCTTCATCTACATGCAGTCAGTGACCAGCTCCCTGGCCCCACCAGTGACTGCAGTCTTTGTCC TGGGCGTCTTCTGGCGACGTGCCAACGAGCAGGGGGCCTTCTGGGGCCTGATAGCAGGGCTGGTGGTG GGGGCCACGAGGCTGGTCCTGGAATTCCTGAACCCAGCCCCACCGTGCGGAGAGCCAGACACGCGGCC AGCCGTCCTGGGGAGCATCCACTACCTGCACTTCGCTGTCGCCCTCTTTGCACTCAGTGGTGCTGTTG TGGTGGCTGGAAGCCTGCTGACCCCACCCCCACAGAGTGTCCAGATTGAGAACCTTACCTGGTGGACC CTGGCTCAGGATGTGCCCTTGGGAACTAAAGCAGGTGATGGCCAAACACCCCAGAAACACGCCTTCTG GGCCCGTGTCTGTGGCTTCAATGCCATCCTCCTCATGTGTGTCAACATATTCTTTTATGCCTACTTCG CCTGACACTGCCATCCTGGACAGAAAGGCAGGAGCTCTGAGTCCTCAGGTCCACCCATTTCCCTCATG
GGGATCCCGA
NOV60c, CG56645-01 SEQ ID NO: 930 596 aa MW at 64341.6kD Protein Sequence
MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMT PIGASLFA SSEGSGLFIGLAGSGAAGGLAVAGFEWNATYVLLALAWVFVPIYISSEIVTLPEYIQKRYGGQRIRMY LSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGITALYTIAGGLAAVIYTDALQTLIMV VGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANTTCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTI MATWYWCTDQVIVQRSLSARDLNHAKAGSILASYLKMLPMGLIIMPGMISRALFPDDVGCWPSECLR ACGAEVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRSGERE LLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVLGVF RRANEQGAF GL IAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALSGAVWAGSLLTPPPQSVQIE NLT TLAQDVPLGTKAGDGQTPQKHAFWARVCGFNAILLMCVNIFFYAYFA
NOV60d, CG56645-02 SEQ ID NO: 931 1912 bp DNA Sequence ORF Start: ATG at 35 ORF Stop: TGA at 1871
CGGGCTCATACCTAGTGCCTGCGGCAGGACAGCCATGGCCGCCAACTCCACCAGCGACCTCCACACTC
CCGGGACGCAGCTGAGCGTGGCTGACATCATCGTCATCACTGTGTATTTTGCTCTGAACGTGGCCGTG GGCATATGGTCCTCTTGTCGGGCCAGTAGGAACACGGTGAATGGCTACTTCCTGGCAGGCCGGGACAT GACGTGGTGGCCGATTGGAGCCTCCCTCTTCGCCAGCAGCGAGGGCTCTGGCCTCTTCATTGGACTGG CGGGCTCAGGCGCGGCAGGAGGTCTGGCCGTGGCAGGCTTCGAGTGGAATGCCACGTACGTGCTGCTG GCACTGGCATGGGTGTTCGTGCCCATCTACATCTCCTCAGAGATCGTCACCTTACCTGAGTACATTCA GAAGCGCTACGGGGGCCAGCGGATCCGCATGTACCTGTCTGTCCTGTCCCTGCTACTGTCTGTCTTCA CCAAGATATCGCTGGACCTGTACGCGGGGGCTCTGTTTGTGCACATCTGCCTGGGCTGGAACTTCTAC CTCTCCACCATCCTCACGCTCGGCATCACAGCCCTGTACACCATCGCAGGGGGCCTGGCTGCTGTAAT CTACACGGACGCCCTGCAGACGCTCATCATGGTGGTGGGGGCTGTCATCCTGACAATCAAAGCTTTTG ACCAGATCGGTGGTTACGGGCAGCTGGAGGCAGCCTACGCCCAGGCCATTCCCTCCAGGACCATTGCC AACACCACCTGCCACCTGCCACGTACAGACGCCATGCACATGTTTCGAGACCCCCACACAGGGGACCT GCCGTGGACCGGGATGACCTTTGGCCTGACCATCATGGCCACCTGGTACTGGTGCACCGACCAGGTCA TCGTGCAGCGATCACTGTCAGCCCGGGACCTGAACCATGCCAAGGCGGGCTCCATCCTGGCCAGCTAC CTCAAGATGCTCCCCATGGGCCTGATCATCATGCCGGGCATGATCAGCCGCGCATTGTTCCCAGGTGC TCATGTCTATGAGGAGAGACACCAAGTGTCCGTCTCTCGAACAGATGATGTGGGCTGCGTGGTGCCGT CCGAGTGCCTGCGGGCCTGCGGGGCCGAGGTCGGCTGCTCCAACATCGCCTACCCCAAGCTGGTCATG GAACTGATGCCCATCGGTCTGCGGGGGCTGATGATCGCAGTGATGCTGGCGGCGCTCATGTCGTCGCT GACCTCCATCTTCAACAGCAGCAGCACCCTCTTCACTATGGACATCTGGAGGCGGCTGCGTCCCCGCT CCGGCGAGCGGGAGCTCCTGCTGGTGGGACGGCTGGTCATAGTGGCACTCATCGGCGTGAGTGTGGCC TGGATCCCCGTCCTGCAGGACTCCAACAGCGGGCAACTCTTCATCTACATGCAGTCAGTGACCAGCTC CCTGGCCCCACCAGTGACTGCAGTCTTTGTCCTGGGCGTCTTCTGGCGACGTGCCAACGAGCAGGGGG CCTTCTGGGGCCTGATAGCAGGGCTGGTGGTGGGGGCCACGAGGCTGGTCCTGGAATTCCTGAACCCA GCCCCACCGTGCGGAGAGCCAGACACGCGGCCAGCCGTCCTGGGGAGCATCCACTACCTGCACTTCGC TGTCGCCCTCTTTGCACTCAGTGGTGCTGTTGTGGTGGCTGGAAGCCTGCTGACCCCACCCCCACAGA GTGTCCAGATTGAGAACCTTACCTGGTGGACCCTGGCTCAGGATGTGCCCTTGGGAACTAAAGCAGGT GATGGCCAAACACTCCAGAAACACGCCTTCTGGGCCCGTGTCTGTGGCTTCAATGCCATCCTCCTCAT GTGTGTCAACATATTCTTTTATGCCTACTTCGCCTGACACTGCCATCCTGGACAGAAAGGCAGGAGCT CTGAGTCC
NOV60d, CG56645-02 SEQ ID NO: 932 612 aa MW at 66194.7kD Protein Sequence
MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMT WPIGASLFA SSEGSGLFIGLAGSGAAGGLAVAGFE NATYVLLALA VFVPIYISSEIVTLPEYIQKRYGGQRIRMY LSVLSLLLSVFTKISLDLYAGALFVHICLG NFYLSTILTLGITALYTIAGGLAAVIYTDALQTLIMV VGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANTTCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTI MAT YWCTDQVIVQRSLSARDLNHAKAGSILASYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSV SRTDDVGCWPSECLRACGAEVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLF TMDIWRRLRPRSGERELLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVL GVFWRRANEQGAFWGLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALSGAW VAGSLLTPPPQSVQIENLTWWTLAQDVPLGTKAGDGQTLQKHAFWARVCGFNAILLMCVNIFFYAYFA A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 60B.
Table 60B. Comparison of the NOV60 protein sequences.
NOV6Oa MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTWW
NOV6Ob MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTWW
NOV6Oc MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTWW
NOV6Od MAANSTSDLHTPGTQLSVADIIVITVYFALNVAVGIWSSCRASRNTVNGYFLAGRDMTWW
NOV6Oa PIGASLFASSEGSGLFIGLAGSGAAGGLAVAGFEWNATYVLLALAWVFVPIYISSEIVTL
NOV60b PIGASLFASSEGSGLFIGLAGSGAAGGLAVAGFEWNATYVLLALAWVFVPIYISSEIVTL
NOV60C PIGASLFASSEGSGLFIGLAGSGAAGGLAVAGFEWNATYVLLALAWVFVPIYISSEIVTL
NOV6Od PIGASLFASSEGSGLFIGLAGSGAAGGLAVAGFEWNATYVLLALAWVFVPIYISSEIVTL
NOV6Oa PEYIQKRYGGQRIRMYLSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGIT
NOV60b PEYIQKRYGGQRIRMYLSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGIT
NOV60C PEYIQKRYGGQRIRMYLSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGIT
NOV60d PEYIQKRYGGQRIRMYLSVLSLLLSVFTKISLDLYAGALFVHICLGWNFYLSTILTLGIT
NOV60a ALYTIAGGLAAVIYTDALQTLIMWGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANT
NOV6Ob ALYTIA AFDQIGGYGQLEAAYAQAIPSRTIANT
NOV6Oc ALYTIAGGLAAVIYTDALQTLIMWGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANT
NOV60d ALYTIAGGLAAVIYTDALQTLIMWGAVILTIKAFDQIGGYGQLEAAYAQAIPSRTIANT
NOV6Oa TCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTIMATWYWCTDQVIVQRSLSARDLNHAKAG
NOV6Ob TCQLPRTDAMHMFRDPHTGDLPWTGMTFGLTIMATWYWCTDQVIVEGSLSARDLNHAKGG
NOV6Oc TCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTIMATWYWCTDQVIVQRSLSARDLNHAKAG
NOV6Od TCHLPRTDAMHMFRDPHTGDLPWTGMTFGLTIMATWYWCTDQVIVQRSLSARDLNHAKAG
NOV60a SILASYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSVSRTDDVGCWPSECLRACGA
NOV60b SILGSYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSVSRTDDVGCWPSECLRACGA
NOV6Oc SILASYLKMLPMGLIIMPGMISRALFP DDVGCWPSECLRACGA
NOV60d SILASYLKMLPMGLIIMPGMISRALFPGAHVYEERHQVSVSRTDDVGCWPSECLRACGA
NOV60a EVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRS
NOV6Ob EVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRS
NOV60C EVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRS
NOV60d EVGCSNIAYPKLVMELMPIGLRGLMIAVMLAALMSSLTSIFNSSSTLFTMDIWRRLRPRS
NOV6Oa GERELLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVL
NOV60b GERELLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVLGVFW
NOV60C GERELLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVLGVFW
NOV6Od GERELLLVGRLVIVALIGVSVAWIPVLQDSNSGQLFIYMQSVTSSLAPPVTAVFVLGVFW
NOV6Oa GLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALS
NOV6Ob RRANEQGAFWGLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALS
NOV6Oc RRANEQGAFWGLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALS
NOV6Od RRANEQGAFWGLIAGLWGATRLVLEFLNPAPPCGEPDTRPAVLGSIHYLHFAVALFALS
NOV6Oa GAVWAGSLLTPPPQSVQIENLTWWNLAQDVPLGTKAGDGQTPQKHAFWARVCGFNAILL NOV6Ob GAVWAGSLLTPPPQSVQIENLTWWTLAQDVPLGTKAGDGQTPQKHAFWARVCGFNAILL NOV60C GAVWAGSLLTPPPQSVQIENLTWWTLAQDVPLGTKAGDGQTPQKHAFWARVCGFNAILL NOV60d GAVWAGSLLTPPPQSVQIENLTWWTLAQDVPLGTKAGDGQTLQKHAFWARVCGFNAILL
NOV60a MCVNIFFYAYFA
NOV60b MCVNIFFYAYFA
NOV60C MCVNIFFYAYFA
NOV60d MCVNIFFYAYFA
NOV60a (SEQ ID NO: 926)
NOV60b (SEQ ID NO: 928)
NOVβOc (SEQ ID NO: 930)
NOV60d (SEQ ID NO: 932)
Further analysis ofthe NOV60a protein yielded the following properties shown in Table 60C.
Figure imgf000849_0001
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.68 Hyd Moment (95): 8.07 G content: 1 D/E content: 2 S/T content: 6 Score: -5.13
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 5.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regie total: 0 residues
Final Results (k = 9/23) :
77.8 %: endoplasmic reticulum 11.1 %: mitochondrial 11.1 %: vacuolar
>> prediction for CG56645-03 is end (k=9)
A search ofthe NOV60a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 60D.
Figure imgf000851_0001
In a BLAST search of public sequence databases, the NOV60a protein was found to have homology to the proteins shown in the BLASTP data in Table 60E.
Figure imgf000852_0001
PFam analysis indicates that the NOV60a protein contains the domains shown in the Table 60F.
Figure imgf000852_0002
Example 61. The NOV61 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 61 A.
Figure imgf000852_0003
δ4δ TGCTCCTCGGGAGCAAGGGCTGTTTCTGCTGATTTATCTGGCAGTGCTGGTGGGGAACCTGCTCATCA TTGCAGTCATCACTCTCGATCAGCATCTTCACACACCCATGTACTTCTTCCTGAAGAACCTCTCCGTT TTGGATCTGTGCTACATCTCAGTCACTGTGCCTAAATCCATCCGTAACTCCCTGACTCGCAGAAGCTC CATCTCTTATCTTGGCTGTGTGGCTCAAGTCTATTTTTTCTCTGCCTTTGCATCTGCTGAGCTGGCCT TCCTTACTGTCATGTCTTATGACCGCTATGTTGCCATTTGCCACCCCCTCCAATACAGAGCCGTGATG ACATCAGGAGGGTGCTATCAGATGGCAGTCACCACCTGGCTAAGCTGCTTTTCCTACGCAGCCGTCCA CACTGGCAACATGTTTCGGGAGCACGTTTGCAGATCCAGTGTGATCCACCAGTTCTTCCGTGACATCC CTCATGTGTTGGCCCTGGTTTCCTGTGAGGTTTTCTTTGTAGAGTTTTTGACCCTGGCCCTGAGCTCA TGCTTGGTTCTGGGATGCTTTATTCTCATGATGATCTCCTATTTCCAAATCTTCTCAACGGTGCTCAG AATCCCTTCAGGACAGAGTCGAGCAAAAGCCTTCTCCACCTGCTCCCCCCAGCTCATTGTCATCATGC TCTTTCTTACCACAGGGCTCTTTGCTGCCTTAGGACCAATTGCAAAAGCTCTGTCCATTCAGGATTTA GTGATTGCTCTGACATACACAGTTTTGCCTCCCTTCCTCAATCCCATCATATATAGTCTTAGGAATAA GGAGATTAAAACAGCCATGTGGAGACTCTTTGTGAAGATATATTTTCTGCAAAAGTAGAACATCCTGG
TCTTTACTATAGAAGATCTGCAACAAAACCCCAAAAAAGCATAAATACTTTATGACAAAAAAAGATGA
AAAAATT
NOV61a, CG56667-01 SEQ ID NO: 934 313 aa MWat35319.9kD Protein Sequence
MICSAINLHLLLAVKMIHPV ILAPREQGLFLLIYLAVLVGNLLIIAVITLDQHLHTPMYFFLKNLSV LDLCYISVTVPKSIRNSLTRRSSISYLGCVAQVYFFSAFASAELAFLTVMSYDRYVAICHPLQYRAVM TSGGCYQMAVTT LSCFSYAAVΉTGNMFREHVCRSSVIHQFFRDIPHVLALVSCEVFFVEFLTLALSS CLVLGCFILMMISYFQIFSTVLRIPSGQSRAKAFSTCSPQLIVIMLFLTTGLFAALGPIAKALSIQDL VIALTYTVLPPFLNPIIYSLRNKEIKTAMWRLFVKIYFLQK
NOV61b,26δ952113 SEQ ID NO: 935 δl7bp DNA Sequence ORF Start: at 2 ORF Stop: end ofsequence
CACCGGATCCGTCATCACTCTCGATCAGCATCTTCACACACCCATGTACTTCTTCCTGAAGAACCTCT CTGTTTTGGATCTGTGCTACATCTCAGTCACTGTGCCTAAATCCATCCGTAACTCCCTGACTCGCAGA AGCTCCATCTCTTATCTTGGCTGTGTGGCTCAAGTCTATTTTTTCTCTGCCTTTGCATCTGCTGAGCT GGCCTTCCTTACTGTCATGTCTTATGACCGCTATGTTGCCATTTGCCACCCCCTCCAATACAGAGCCG TGATGACATCAGGAGGGTGCTATCAGATGGCAGTCACCACCTGGCTAAGCTGCTTTTCCTACGCAGCC GTCCACACTGGCAACATGTTTCGGGAGCACGTTTGCAGATCCAATGTGATCCACCAGTTCTTCCGTGA CATCCCTCATGTGTTGGCCCTGGTTTCCTGTGAGGTTTTCTTTGTAGAGTTTTTGACCCTGGCCCTGA GCTCATGCTTGGTTCTGGGATGCTTTATTCTCATGATGATCTCCTATTTCCAAATCTTCTCAACGGTG CTCAGAATCCCTTCAGGACAGAGTCGAGCAAAAGCCTTCTCCACCTGCTCCCCCCAGCTCATTGTCAT CATGCTCTTTCTTACCACAGGGCTCTTTGCTGCCTTAGGACCAATTGCAAAAGCTCTGTCCATTCAGG ATTTAGTGATTGCTCTGACATACACAGTTTTGCCTCCCTTCCTCAATCCCATCATATATAGTCTTAGG AATAAGGAGATTAAAACAGCCATGTGGAGACTCTTTGTGAAGATATATTTTCTGCAAAAGCTCGAGGG C
NOV61b, 26δ952113 SEQ ID NO: 936 272 aa MW at 30688.0kD Protein Sequence
TGSVITLDQHLHTPMYFFLKNLSV DLCYISVTVPKSIRNSLTRRSSISYLGCVAQVYFFSAFASAEL AFLTVMSYDRYVAICHPLQYRAVMTSGGCYQMAVTTWLSCFSYAAVHTGNMFREHVCRSNVIHQFFRD IPHVLALVSCEVFFVEFLTLALSSCLVT-GCFILMMISYFQIFSTVLRIPSGQSRAKAFSTCSPQLIVI MLFLTTGLFAALGPIAKALSIQDLVIALTYTVLPPFLNPIIYSLRNKEIKTAMWRLFVKIYFLQKLEG A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 6 IB.
Table 61B. Comparison of the NOV61 protein sequences.
NOV6 la MICSAINLHLLLAVKMIHPVWILAPREQGLFLLIYLAVLVGNLLI IAVITLDQHLHTPMY NOV61b TGSVITLDQHLHTPMY
NOV61a FFLKNLSVXiDLCYISvTVPKSIRNSLTRRSSISYLGCVAQVYFFSAFASAELAFLTVMSY NOV61b FFLKNLSVLDLCYISVTVPKSIRNSLTRRSSISYLGCVAQVYFFSAFASAELAFLTVMSY NOV6 la DRYVAICHPLQYRAVMTSGGCYQMAVTT LSCFSYAAVHTGNMFREHVCRSSVIHQFFRD
NOV6 lb DRYVAICHPLQYRAVMTSGGCYQMAVTTWLSCFSYAAVHTGNMFREHVCRSNVIHQFFRD
NOV61a IPHΛΠJALVSCEVFFVEFLTLALSSCLVLGCFILMMI SYFQIFSTVLRIPSGQSRAKAFST
NOVδlb IPHVLALVSCEVFFVΈFLTLALSSCLVLGCFILMMISYFQIFSTVLRIPSGQSRAKAFST
NOV61a CSPQLIVIMLFLTTGLFAALGPIAKALSIQDLVIALTYTVLPPFLNPIIYSLRNKEIKTA
NOV61b CSPQLIVIMLFLTTGLFAALGPIAKALSIQDLVIALTYTVLPPFLNPIIYSLRNKEIKTA
NOV6la MWRLFVKIYFLQK
NOV61b M RLFVKIYFLQKLEG
NOV61a (SEQ ID NO: 934) NOV61b (SEQ ID NO: 936)
Further analysis ofthe NOV61a protein yielded the following properties shown in Table 61C.
Table 61 C. Protein Sequence Properties NOV61a
SignalP analysis: Cleavage site between residues 48 and 49
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos . chg 0; neg.chg 0 H-region: length 14; peak value 6.18 PSG score: 1.78
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.68 possible cleavage site: between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. 5: 7
INTEGRAL Likelihood = -2.39 Transmembrane 1 - 17
INTEGRAL Likelihood =-11.20 Transmembrane 33 - 49
INTEGRAL Likelihood -0.22 Transmembrane 101 - 117
INTEGRAL Likelihood -1.22 Transmembrane 183 - 199
INTEGRAL Likelihood -8.86 Transmembrane 200 - 216
INTEGRAL Likelihood -7.54 Transmembrane 245 - 261
INTEGRAL Likelihood -0.00 Transmembrane 273 - 289
PERIPHERAL Likelihood 2.01 (at 62)
ALOM score : -11.20 (number of TMSs : 7)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 8 Charge difference: 0.5 C( 2.0) - N( 1.5) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75): 1.74 Hyd Moment (95): 4.81 G content: 0 D/E content : 1 S/T content : 1 Score: -4.54
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 99 RRS|SI
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 7.0% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas s algorithm to detect coiled-coil regions total C residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
11.1 %: mitochondri al
11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: Golgi
>> prediction for CG56667- 01 is end (k=9)
A search ofthe NOV61a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6 ID.
Figure imgf000857_0001
In a BLAST search of public sequence databases, the NOV6 la protein was found to have homology to the proteins shown in the BLASTP data in Table 6 IE.
δ53
Figure imgf000858_0001
PFam analysis indicates that the NOVόla protein contains the domains shown in the Table 6 IF.
Figure imgf000858_0002
Example 62.
The NOV62 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 62A.
Table 62A. NOV62 Sequence Analysis
NOV62a, CG5686δ-01 SEQ ID NO: 937 2422 bp DNA Sequence ORF Start: ATG at 51 ORF Stop: TAG at 23δ2
GAACTCCTTTTCTCAAGCACTTCTGCTCTCCTCTACCAGAATCACTCAGAATGCTTCCCGGGTGTATAI δ54 TTCTTGATGATTTTACTCATTCCTCAGGTTAAAGAAAAGTTCATCCTTGGAGTAGAGGGTCAACAACT GGTTCGTCCTAAAAAGCTTCCTCTGATACAGAAGCGAGATACTGGACACACCCATGATGATGACATAC TGAAAACGTATGAAGAAGAATTGTTGTATGAAATAAAACTAAATAGAAAAACCTTAGTCCTTCATCTT CTAAGATCCAGGGAGTTCCTAGGCTCAAATTACAGTGAAACATTCTACTCCATGAAAGGAGAAGCGTT CACCAGGCATCCTCAGATCATGGAACACTGTTACTATAAAGGAAACATCCTAAATGAAAAGAATTCTG TTGCCAGCATCAGTACTTGTGACGGGTTGAGGGGATTCTTCAGAATAAACGACCAAAGATACCTCATT GAACCAGTGAAATACTCAGATGAGGGAGAACATTTGGTGTTCAAATATAACCTGAGGGTGCCGTATGG TGCCAATTATTCCTGTACAGAGCTTAATTTTACCAGAAAAACTGTTCCAGGGGATAATGAATCTGAAG AAGACTCCAAAATAAAAGGCATCCATGATGAAAAGTATGTTGAATTGTTCATTGTTGCTGATGATACT GTGTATCGCAGAAATGGTCATCCTCACAATAAACTAAGGAACCGAATTTGGGGAATGGTCAATTTTGT CAACATGATTTATAAAACCTTAAACATCCATGTGACGTTGGTTGGCATTGAAATATGGACACATGAAG ATAAAATAGAACTATATTCAAATATAGAAACTACCTTATTGCGTTTTTCATTTTGGCAAGAAAAGATC CTTAAAACACGGAAGGATTTTGATCATGTTGTATTACTCAGTGGGAAGTGGCTCTACTCACATGTGCA AGGAATTTCTTATCCAGGGGGTATGTGCCTGCCCTATTATTCCACCAGTATCATTAAGGATCTTTTAC CTGACACAAACATAATTGCAAACAGAATGGCACATCAACTGGGGCATAACCTTGGGATGCAGCATGAC GAGTTCCCATGCACCTGTCCTTCAGGAAAATGCGTGATGGACAGTGATGGAAGCATTCCTGCACTGAA ATTCAGTAAATGCAGCCAAAACCAATACCACCAGTACTTGAAGGATTATAAGCCAACATGCATGCTCA ACATTCCATTTCCTTACAATTTTCATGATTTCCAATTTTGTGGAAACAAGAAGTTGGATGAGGGTGAA GAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTGATGCACACACATGTGTACTGAA GCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAGATAAAAAAAGCAGGGTCCATAT GCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGGCCACTCGCCTGCCTGTCCTAAG GACCAGTTCAGGGTCAATGGATTTCCTTGCAAGAACTCAGAAGGCTACTGTTTCATGGGGAAATGTCC AACTCGTGAGGATCAGTGCTCTGAACTATTTGATGATGAGGCAATAGAGAGTCATGATATCTGCTACA AGATGAATACAAAAGGAAATAAATTTGGATACTGCAAAAACAAGGAAAACAGATTTCTTCCCTGTGAG GAGAAGGATGTCAGATGTGGAAAGATCTACTGCACTGGAGGGGAGCTTTCCTCTCTCCTTGGAGAAGA CAAGACTTATCACCTTAAGGATCCCCAGAAGAATGCTACTGTCAAATGCAAAACTATTTTTTTATACC ATGATTCTACAGACATTGGCCTGGTGGCGTCAGGAACAAAATGTGGAGAGGGAATGGTGTGCAACAAT GGTGAATGTCTAAACATGGAAAAGGTCTATATCTCAACCAATTGCCCCTCTCAGTGCAATGAAAATCC TGTGGATGGCCACGGACTCCAGTGCCACTGTGAGGAAGGACAGGCACCTGTAGCCTGTGAAGAAACCT TACATGTTACCAGTATCACCATCTTGGTTGTTGTGCTTGTCCTGGTTATTGTCGGTATCGGAGTTCTT ATACTATTAGTTCGTTACCGAAAATGTATCAAGTTGAAGCAAGTTCAGAGCCCACCTACAGAAACCCT GGGAGTGGAGAACAAAGGATACTTTGGTGATGAGCAGCAGATAAGGACTGAGCCAATCCTGCCAGAAA TTCATTTCCTAAATCAGAGAACTCCAGAATCCTTGGAAAGCCTGCCCACTAGTTTTTCAAGTCCCCAC TACATCACACTGAAACCTGCAAGTAAAGATTCAAGAGGAATCGCAGATCCCAATCAAAGTGCCAAGTG GTAGGTTACCCTGACAGATAGTACCTCCCTTTTTTATTTTTC
NOV62a, CG56δ6δ-01 SEQ ID NO: 93δ 777 aa MW at δδ341.2kD Protein Sequence
MLPGCIFLMILLIPQVKEKFILGVΕGQQL PKKLPLIQKRDTGHTHDDDILKTYEEELLYEIKLNRK TLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMEHCYYKGNILNEKNSVASISTCDGLRGFFRIN DQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTVPGDNESEEDSKIKGIHDEKYVELF IVADDTVYRRNGHPHNKLRNRI GMV FVNMIYKTLNIHVTLVGIEIWTHEDKIELYSNIETTLLRFS FWQE ILKTRKDFDHWLLSGKWLYSHVQGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHN LGMQHDEFPCTCPSGKCVMDSDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNK KLDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGH SPACPKDQFRVNGFPCKNSEGYCF GKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCKNKEN RFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTDIGLVASGTKCGE GMVCNNGECLN EKVYISTNCPSQCNENPVUGHGLQCHCEEGQAPVACEETLHVTSITILVVVLVLVI VGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDEQQIRTEPILPEIHFLNQRTPESLESLPT SFSSPHYITLKPASKDSRGIADPNQSAK
NOV62b, 2765δ0332 SEQ ID NO: 939 247 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGTACCGATGAGGGTGAAGAGTGTGACTGTGGCCCTGCTCAGGAGTGTACTAATCCTTGCTGTG ATGCACACACATGTGTACTGAAGCCAGGATTTACTTGTGCAGAAGGAGAATGCTGTGAATCTTGTCAG ATAAAAAAAGCAGGGTCCATATGCAGACCGGCGAAAGATGAATGTGATTTTCCTGAGATGTGCACTGG CCACTCGCCTGCCTGTCCTAAGGACCAGTTCAGGGTCGACGGC
δ55 NOV62b, 2765δ0332 SEQ ID NO: 940 δ2 aa MW at δ696.6kD Protein Sequence
TGTDEGEECDCGPAQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTG HSPACPKDQFRVDG
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 62B.
Table 62B. Comparison of the NOV62 protein sequences.
NOV62a MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL
NOV62b
NOV62a YEIKLNRKTLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMEHCYYKGNILNEKNSV
NOV62b
NOV62a ASISTCDGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTV
NOV62b
NOV62a PGDNESEEDSKIKGIHDEKYVELFIVADDTVYRRNGHPHNKLRNRIWGMVNFVN IYKTL
NOV62b
NOV62a NIHVTLVGIEIWTHEDKIELYSNIETTLLRFSF QEKILKTRKDFDHWLLSGKWLYSHV
NOV62b
NOV62a QGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCVMD
NOV62b
NOV62a SDGSIPALKFSKCSQNQYHQYLKDYKPTC LNIPFPYNFHDFQFCGNKKLDEGEECDCGP
NOV62b TGTDEGEECDCGP
NOV62a AQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSPAC
NOV62b AQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSPAC
NOV62a PKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCK
NOV62b PKDQFRVDG
NOV62a NKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTD
NOV62b
NOV62a IGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVAC
NOV62b
NOV62a EETLHVTSITILVWLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDE
NOV62b
NOV62a QQIRTEPILPEIHFLNQRTPESLESLPTSFSSPHYITLKPASKDSRGIADPNQSAKW
NOV62b
NOV62a (SEQ ID NO: 938)
NOV62b (SEQ ID NO: 940)
δ56 Further analysis ofthe NOV62a protein yielded the following properties shown in Table 62C.
Table 62C. Protein Sequence Properties NOV62a
SignalP analysis: Cleavage site between residues 19 and 20
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos . chg 0; neg.chg 0 H-region: length 16; peak value 12.97 PSG score: 8.57
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.58 possible cleavage site: between 18 and 19
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 2 INTEGRAL Likelihood = -2.18 Transmembrane 1 - 17 INTEGRAL Likelihood =-18.52 Transmembrane 671 - 687 PERIPHERAL Likelihood = 4.35 (at 235) ALOM score: -18.52 (number of TMSs: 2)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 8 Charge difference: 0.0 C( 1.0) - N ( 1.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.80 Hyd Moment(95): 1.48 G content: 1 D/E content: 1 S/T content: 0 Score: -6.33
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: RPKK (4) at 31 pat7 : none bipartite: none content of basic residues: 11.3% NLS Score: -0.22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: KKXX-like motif in the C-terminus: QSAK
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs:
Bacterial regulatory proteins, gntR family signature (PS00043) *** found ***
EEELL EIKLNRKTLVLHLLRS at 56
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
34.8 % nuclear
30.4 % endoplasmic reticulum
21.7 % mitochondrial
4.3 % vesicles of secretory system
4.3 % cytoplasmic
4.3 % peroxisomal
>> prediction for CG56868-01 is nuc (k=23)
85δ A search ofthe NOV62a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 62D.
Figure imgf000863_0001
In a BLAST search of public sequence databases, the NOV62a protein was found to have homology to the proteins shown in the BLASTP data in Table 62E.
δ59
Figure imgf000864_0001
PFam analysis indicates that the NOV62a protein contains the domains shown in the Table 62F.
Figure imgf000864_0002
Example 63.
The NOV63 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 63A.
Figure imgf000865_0001
CTCCATAATATAACATTTCAT
NOV63b, CG56870-06 SEQ ID NO: 944 2δ3 aa MW at 31109.1kD Protein Sequence
MIRMVQETSRTLTVRYQYPTMDELAEMLPPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVL INVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNS YNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQV VQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDV LDRHQTMEVSC
NOV63c, 2765δ5681 SEQ ID NO: 945 994 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCAAGCTTACAAGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTG TGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATT GGCCTCAACCATAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCA CTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATC AGTACCCCACAATGGATGAGCTGGCTGAAGTGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGC ATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCT TGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCA AACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTA CAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCT GCAGCTCTTCTTGAATTCCTACAATGGACGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAA ATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTT GAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTG TGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAA TGGGCTACATACCATCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGC CTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCGACGGC
NOV63c, 2765856δl SEQ ID NO: 946 331 aa MW at 3642δ.9kD Protein Sequence
TKLTRNFQDFDCQEHDIETTHGWΉVTIRGLPKGNRPVILTYHDIGLNHKSCFNAFFNFEDMQEITQH FAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEVLPPVLTHLSLKSIIGIGVGAGAYILSRFALNHPEL VEGLVLINVDPCAKG ID AASKLSGLTTNWDI ILAHHFGQEELQANLDLIQTYRMHIAQDINQDNL QLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAWΈCNSRLNPINTTLLKMADC GGLPQWQPGKLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGESPFSRSVDG
NOV63d, CG56870-02 SEQ ID NO: 947 1175 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAA at 1141
TCGTTATCTGACCTCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGA
TAAGAATGGTACAAGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTG TGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATT GGCCTCAACCATAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCA CTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATC AGTACCCCACAATGGATGAGCTGGCTGAAGTGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGC ATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCT TGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCA AACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTA CAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCT GCAGCTCTTCTTGAATTCCTACAATGGACGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAA ATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTT GAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTG TGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAA TGGGCTACATACCATCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGC CTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATC CTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTC CCCTGGACCATTGCAAGTC NOV63d, CG56870-02 SEQ ID NO: 94δ 375 aa !MW at 41376.2kD Protein Sequence
MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTYHDIGLNHK SCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEVLPPVLTHLSLKSIIGIG VGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSGLTTNWDIILAHHFGQEELQANLD LIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAWE CNSRLNPINTTLLKMADCGGLPQWQPGKLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGE SPFSRSVTSNQSDGTQESCESPDVLDRHQTMEVSC
NOV63e, CG56δ70-03 SEQ ID NO: 949 1232 bp DNA Sequence ORF Start: ATG at 71 ORF Stop: TAA at 1160
ACTTCTTTCTTTTCTGTTTCAGAGTTACTGATTTATTCTTGAGATTCCTCTACTCTCGTTATCTGACC
TCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGGAACATGAT ATAGAAACAACTCATGGTGTGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTAT ACTAACATATCATGACATTGGCCTCAACCATAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATA TGCAAGAGATCACCCAGCACTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCC TCTTTCCCAACAGGGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTAC CCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTG CACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGG ATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCA CTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAG ACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGGCGCAGAGACCTGGAGATCGAA AGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGG GGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTT TGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTC AAGTACTTTTTGCAGGGAATGGGCTACGTCCCGTCTGCCAGCATGACTCGGCTCGCCCGATCACGAAC CCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGT CAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCC TGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAA CATTTCAT
NOV63e, CG56δ70-03 SEQ ID NO: 950 363 aa MW at 39967.δkD Protein Sequence
MDELQDVQLTEIKPLLNDKEHDIETTHGWHVTIRGLPKGNRPVILTYHDIGLNHKSCFNAFFNFEDM QEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEMLPPVLTHLSLKSIIGIGVGAGAYILSRFA LNHPELVEGLVLINVDPCAKG IDWAASKLSGLTTNWDI ILAHHFGQEELQANLDLIQTYRMHIAQD INQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTL LKMADCGGLPQWQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQS DGTQESCESPDVLDRHQTMEVSC
NOV63f, CG56870-04 SEQ ID NO: 951 1220 bp DNA Sequence ORF Start: ATG at 71 ORF Stop: TAA at 1148
ACTTCTTTCTTTTCTGTTTCAGAGTTACTGATTTATTCTTGAGATTCCTCTACTCTCGTTATCTGACC
TCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGAATGGTACA AGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTGTGGTCCACGTCAC TATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATTGGCCTCAACCGTA AATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCACTTTGCTGTCTGT CATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATCAGTACCCCACAAT GGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTG GAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTT GTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCT GACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGG ACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTG AATTCCTACAATGGACGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATC AAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGATGG CGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGTTCACCGAGGCCTTCAAGTACTTTTTG CAGGGAATGGGCTACACACCATCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTC GAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTC AAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGAT GCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAACATTTCAT
NOV63f, CG56870-04 SEQ ID NO: 952 359 aa MW at 39652.2kD Protein Sequence
MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTYHDIGLNRK SCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEMLPPVLTHLSLKSIIGIG VGAGAYILSRFALNHPELVEGLVLINVDPCAKG IDWAASKLSGLTTNWDIILAHHFGQEELQANLD LIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAVMA DCGGLPQWQPGKFTEAFKYFLQGMGYTPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQ ESCESPDVLDRHQTMEVSC
NOV63g, CG56870-05 SEQ ID NO: 953 970 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 898
ATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGAATGGTACAAG AAACTTCCAGGACTTTGACTGTCAGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTC CTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTC AGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGC TAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTT TGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCAT ATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGGCGCAGAGACCT GGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTAC TGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATA AATACAACTTTGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCAC CGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACGTCCCGTCTGCCAGCATGACTCGGCTCGCCC GATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACC AGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCAT GGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTC CATAATATAACATTTCAT
NOV63g, CG56870-05 SEQ ID NO: 954 299 aa MW at 32956.9kD Protein Sequence
MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQYQYPTMDELAEMLPPVLTHLSLKSI IGIGVGAGAYIL SRFALNHPELVEGLVLINVDPCAKG IDWAASKLSGLTTNWDIILAHHFGQEELQANLDLIQTYRMH IAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPI NTTLLKMADCGGLPQWQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVT SNQSDGTQESCESPDVLDRHQTMEVSC
A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 63B.
Table 63B. Comparison of the NOV63 protein sequences.
NOV63a MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTY NOV63b NOV63C TKLTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTY NOV63d MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTY NOV63e MDELQDVQLTEIKPLLNDKEHDIETTHGWHVTIRGLPKGNRPVILTY NOV63f MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGWHVTIRGLPKGNRPVILTY NOV63g
NOV63a HDIGLNRKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEML
NOV63b MIRMVQETS RTLTVRYQYPTMDELAEML
NOV63C HDIGLNHKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEVL
NOV63d HDIGLNHKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEVL NOV63e HDIGLNHKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEML NOV63f HDIGLNRKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEML NOV63g MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQYQYPTMDELAEML
NOV63a PPVLTHLSLKSI IGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSG NOV63b PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSG NOV63c PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSG NOV63d PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSG NOV63e PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSG NOV63f PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSG NOV63g PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWID AASKLSG
NOV63a LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63b LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63c LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63d LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63e LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63f LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP NOV63g LTTNWDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP
NOV63a ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG NOV63b ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG NOV63c ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG NOV63d ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG NOV63e ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG NOV63f ILGQNDNKSKTLKCSTLLWGDNSPAVEAV ,-MADCGGLPQWQPG NOV63g ILGQNDNKSKTLKCSTLLWGDNSPAVEAWECNSRLNPINTTLLKMADCGGLPQWQPG
NOV63a KLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE NOV63b KLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE NOV63c KLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGESPFSRSVDG NOV63d KLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE NOV63e KLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE NOV63f KFTEAFKYFLQGMGYTPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE NOV63g KLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE
NOV63a SPDVLDRHQTMEVSC NOV63b SPDVLDRHQTMEVSC NOV63c NOV63d SPDVLDRHQTMEVSC NOV63e SPDVLDRHQTMEVSC NOV6 f SPDVLDRHQTMEVSC NOV63g SPDVLDRHQTMEVSC
NOV63a (SEQ ID NO 942) NOV63b (SEQ ID O 944) NOV63c (SEQ ID O 946) NOV63d (SEQ ID NO 948) NOV63e (SEQ ID O 950) NOV6 f (SEQ ID NO 952) NOV63g (SEQ ID NO 954)
Further analysis ofthe NOV63a protein yielded the following properties shown in Table 63C. Table 63C. Protein Sequence Properties NOV63a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 11; pos. chg 0; neg.chg 4 H-region: length 1; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -14.03 possible cleavage site: between 48 and 49
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 4.67 (at 174) ALOM score: 0.47 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.01 Hyd Moment(95): 7.59 G content: 0 D/E content: 2 S/T content: 0 Score: -6.61
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals ρat4 : none pat7: none bipartite: none content of basic residues: 7.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 55.5
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
39.1 %: cytoplasmic
39.1 %: nuclear
13.0 %: mitochondrial
4.3 %: Golgi
4.3 %: endoplasmic reticulum
>> prediction for CG56870-01 is cyt (k=23)
A search ofthe NOV63a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 63D.
Figure imgf000872_0001
In a BLAST search of public sequence databases, the NOV63a protein was found to have homology to the proteins shown in the BLASTP data in Table 63E.
86δ
Figure imgf000873_0001
PFam analysis indicates that the NOV63a protein contains the domains shown in the Table 63F.
Figure imgf000873_0002
Example 64.
The NOV64 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 64A.
Table 64A. NOV64 Sequence Analysis
NOV64a, CG57109-01 SEQ ID NO: 955 2536 bp DNA Sequence ORF Start: ATG at 150 ORF Stop: TAG at 2094
GGGACACTGACATGGACTGAAGGAGTAGAAAAGAAGCCTTGGGCTCTCCCAGATGGAAGAATGACCGT
IGTGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGATTTCTTCAGGGAAGGGGAj δ69 TGCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGGTGGCTGTAGAAGAACTGT
ACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCTTCTCCAAGGCTGAGGAGC AGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGAGACCCCCAAGAGCTGCAG CGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCGAGGAGCTTTCACTAGATG ACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAACCCAGTAGCAAGCCCCCC AGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGGGGTGGAGATTGAAAAGAC CTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTTCAGCAGAGCCTGGAGCGTG AGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATGTATGATGTGGAGAAGCTG GTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGGGGAGGAAGGGTGGAAGGG TGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGACCCAGCAAGAGCATGGACA AGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCAGCCAAGGCCAAGAAGGAC CTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGGGAGGTGAAGAAGGACACCAGGCCCATGAG CAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTGAGAAGCTCCGCAGGACCC GAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGATGACTCTC AGAGATGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAGCCAGAGCG GCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTATGAGACTG GCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCAGGCAGGCC TATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGTGAGATCTT GATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTCTACGAAACAGACATGGAAA TCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTGTGAAGTTC CCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCACGACAAGAG CATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATCTACTACCT TGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTGGGACCCCA ACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGGTGGACATGTGGGCGGCTGG CGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCCTGAGAGGGACCAGGACGAGC TCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACTGGGACAATATCTCTGATGCT GCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCATCAGGTTCT TCAGCACCCCTGGATCGAAACAGCTGGCAAGACCAATACAGTGAAACGACAGAAGCAGGTGTCCCCCA GCAGCGAGGGTCACTTCCGGAGCCAGCACAAGAGGGTTGTGGAGCAGGTATCATAGTCACCACCTTGG
GAATCTGTCCAGCCCCCAGTTCTGCTCAAGGACAGAGAAAAGGATAGAAGTTTGAGAGAAAAACAATG
AAAGAGGCTTCTTCACATAATTGGTGAATCAGAGGGAGAGACACTGAGTATATTTTAAAGCATATTAA
AAAAATTAAGTCAATGTTAAATGTCACAACATATTTTTAGATTTGTATATTTAAAGCCTTTAATACAT
TTTTGGGGGGTAAGCATTGTCATCAGTGAGGAATTTTGGTAATAATGATGTGTTTTGCTTCCCCTTTG
TAACCAAGTTTATTCTGTACTACAGGAGTGGTGCTTACCAGGGTCTAAACTCCCCCTGTGAGATTAAT
AAGGTGCATTGTGGTCTTTCTGTGTTAATAAAATGTGCTCTGAATAACAGAAAAAAAAAAAAAAAAAA:
AAAAAAAAAAAAAAAAAAGG
NO V64a, CG57109-01 SEQ ID NO: 956 64δ aa MW at 73δl3.6kD Protein Sequence
MGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAG CKAAMRHQGKIPEELSLDDRARTQKK GRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEI IRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KGDSHR SSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMSRSKH GGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPERPSGR KPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILIIQS LSHPNIVKLHEVYETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHR DLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILY ILLCGFPPFRSPERDQDELFNIIQLGHFEFLPPY DNISDAAKDLVSRLLWDPKKRYTAHQVLQHPW IETAGKTNTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64b, 260457400 SEQ ID NO: 957 793 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCTATGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGAC ACCGCGAGACCAGGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGAC ATGGTGGACAGTGAGATCTTGATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGT CTACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCA TCATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTC GTCCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAA TGAGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATAT δ70 TTACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAG GTGGACATGTGGGCTGCTGGCGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCC TGAGAGGGACCAGGACGAGCTCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACT GGGACAATATCTCTGATGCTGCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGC TACACAGCTCATCAGGTTCTTCAGCACCCCTGGATCCTCGAGGGC
NOV64b, 260457400 SEQ ID NO: 95δ 264 aa MW at 30106.4kD Protein Sequence
TGSYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILI IQSLSHPNIVKLHEV YETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRN EDKSTTLKLADFGLAKHVVRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSP ERDQDELFNIIQLGHFEFLPPYWDNISDAAKDLVSRLLWDPKKRYTAHQVLQHP ILEG
NOV64c, 260457409 SEQ ID NO: 959 625 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCTATGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGAC ACCGCGAGACCAGGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGAC ATGGTGGACAGTGAGATCTTGATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGT CTACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCA TCATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTC GTCCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAA TGAGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATAT TTACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGCTGCTAAAGATCTG GTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCATCAGGTTCTTCAGCACCCCTG GATCCTCGAGGGC
NOV64c, 260457409 SEQ ID NO: 960 20δ aa MW at 23605. lkD Protein Sequence
TGSYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEV YETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRN EDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKAAKDLVSRLLWDPKKRYTAHQVLQHPW I LEG
NOV64d, CG57109-05 SEQ ID NO: 961 2133 bp DNA Sequence ORF Start: ATG at 90 ORF Stop: TAG at 2034
TTOACCGTGTGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGATTTCTTCAGG
GAAGGGGATGCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGGTGGCTGTAGA
AGAACTGTACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCTTCTCCAAGGC TGAGGAGCAGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGAGACCCCCAAG AGCTGCAGCGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCGAGGAGCTTTC ACTAGATGACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAACCCAGTAGCA AGCCCCCCAGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGGGGTGGAGATT GAAAAGACCTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTCCAGCAGAGCCT GGAGCGTGAGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATGTATGATGTGG AGAAGCTGGTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGGGGAGGAAGGG TGGAAGGGTGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGACCCAGCAAGAG CATGGACAAGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCGGCCAAGGCCA AGAAGGACCTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGAGAGGTGAAGAAGGACACCAGG CCCATGAGCAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTGAGAAGCTCCG CAGGACCCGAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGA TGACTCTCAGAGACGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAG CCAGAGCGGCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTA TGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCA GGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGT GAGATCTTGATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTCTACGAAACAGA CATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTG TGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCAC GACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATC TACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTG GGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGGTGGACATGTGG GCTGCTGGCGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCCTGAGAGGGACCA GGACGAGCTCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACTGGGACAATATCT CTGATGCTGCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCAT CAGGTTCTTCAGCACCCCTGGATCGAAACAGCTGGCAAGACCAATACAGTGAAACGACAGAAGCAGGT GTCCCCCAGCAGCGAGGGTCACTTCCGGAGCCAGCACAAGAGGGTTGTGGAGCAGGTATCATAGTCAC
CACCTTGGGAATCTGTCCAGCCCCCAGTTCTGCTCAAGGACAGAGAAAAGGATAGAAGTTTGAGAGAA
AAACAATGAAAGAGGCTTCTTCACA
NOV64d, CG57109-05 SEQ ID NO: 962 648 aa MW at 73δl3.6kD Protein Sequence
MGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAG CKAAMRHQGKIPEELSLDDRARTQKK GRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEI IRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KGDSHR SSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMSRSKH GGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPERPSGR KPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILIIQS LSHPNIVKLHEVYETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHR DLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILY ILLCGFPPFRSPERDQDELFNIIQLGHFEFLPPYWDNISDAAKDLVSRLLWDPKKRYTAHQVLQHPW IETAGKTNTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64e, 267253965 SEQ ID NO: 963 1966 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCACCATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGGTGGCTGTAGAAGAACTGT ACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCTTCTCCAAGGCTGAGGAGC AGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGAGACCCCCAAGAGCTGCAG CGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCGAGGAGCTTTCACTAGATG ACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAACCCAGTAGCAAGCCCCCC AGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGGGGTGGAGATTGAAAAGAC CTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTCCAGCAGAGCCTGGAGCGTG AGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATGTATGATGTGGAGAAGCTG GTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGGGGAGGAAGGGTGGAAGGG TGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGACCCAGCAAGAGCATGGACA AGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCGGCCAAGGCCAAGAAGGAC CTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGAGAGGTGAAGAAGGACACCAGGCCCATGAG CAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTGAGAAGCTCCGCAGGACCC GAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGATGACTCTC AGAGACGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAGCCAGAGCG GCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTATGAGACTG GCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCAGGCAGGCC TATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGTGAGATCTT GATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTCTACGAAACAGACATGGAAA TCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTGTGAAGTTC CCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCACGACAAGAG CATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATCTACTACCT TGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTGGGACCCCA ACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGGTGGACATGTGGGCTGCTGG CGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCCTGAGAGGGACCAGGACGAGC TCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACTGGGACAATATCTCTGATGCT GCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCATCAGGTTCT TCAGCACCCCTGGATCGAAACAGCTGGCAAGACCAATACAGTGAAACGACAGAAGCAGGTGTCCCCCA GCAGCGAGGGTCACTTCCGGAGCCAGCACAAGAGGGTTGTGGAGCAGGTATCACTCGAGGGC
NOV64e, 267253965 SEQ ID NO: 964 655 aa MW at 74459.2kD Protein Sequence
TGSTMGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCS EVAGCKAAMRHQGKIPEELSLDDRARTQKK GRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKT δ72 SGEIIRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMS RSKHGG LLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPER PSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEIL IIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKS IVHRDLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMAAG VILYILLCGFPPFRSPERDQDELFNIIQLGHFEFLPPYWDNISDAAKDLVSRLLWDPKKRYTAHQVL QHPWIETAGKTNTVKRQKQVSPSSEGHFRSQHKRWEQVSLEG
NOV64f, 267254000 SEQ ID NO: 965 1621 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCACCATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGGTGGCTGTAGAAGAACTGT ACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCTTCTCCAAGGCTGAGGAGC AGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGAGACCCCCAAGAGCTGCAG CGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCGAGGAGCTTTCACTAGATG ACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAACCCAGTAGCAAGCCCCCC AGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGGGGTGGAGATTGAAAAGAC CTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTCCAGCAGAGCCTGGAGCGTG AGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATGTATGATGTGGAGAAGCTG GTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGGGGAGGAAGGGTGGAAGGG TGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGACCCAGCAAGAGCATGGACA AGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCGGCCAAGGCCAAGAAGGAC CTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGAGAGGTGAAGAAGGACACCAGGCCCATGAG CAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTGAGAAGCTCCGCAGGACCC GAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGATGACTCTC AGAGACGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAGCCAGAGCG GCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTATGAGACTG GCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCAGGCAGGCC TATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGTGAGATCTT GATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTCTACGAAACAGACATGGAAA TCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTGTGAAGTTC CCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCACGACAAGAG CATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATCTACTACCT TGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTGGGACCCCA ACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGCTCGAGGGC
NOV64f, 267254000 SEQ ID NO: 966 540 aa MW at 61179.2kD Protein Sequence
TGSTMGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCS EVAGCKAAMRHQGKIPEELSLDDRARTQKK GRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKT SGEIIRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KG DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMS RSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPER PSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEIL IIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKS IVHRDLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLELEG
NOV64g, 2672539δ7 SEQ ID NO: 967 793 bp DNA Sequence ORF Start: at 1 ORF Stop: at 793
ACCGGATCCTATGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACA CCGCGAGACCAGGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACA TGGTGGACAGTGAGATCTTGATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTC TACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCAT CATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCG TCCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAAT GAGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATT TACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGG TGGACATGTGGGCTGCTGGCGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCCT GAGAGGGACCAGGACGAGCTCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACTG GGACAATATCTCTGATGCTGCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCT ACACAGCTCATCAGGTTCTTCAGCACCCCTGGATCCTCGAGGGCC
NOV64g, 267253987 SEQ ID NO: 968 264 aa MW at 30106.4kD Protein Sequence
TGSYETGRVIGDGNFAWKECRHRETRQAYAMKI IDKSRLKGKEDMVDSEILI IQSLSHPNIVKLHEV YETDMEIYLILEYVQGGDLFDAI IESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRN EDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSP ERDQDELFNIIQLGHFEFLPPY DNISDAAKDLVSRLLWDPKKRYTAHQVLQHPWILEG
NOV64h, CG57109-02 SEQ ID NO: 969 280δ bp DNA Sequence ORF Start: ATG at 151 ORF Stop: TAG at 2659
TTTACAGAGTCAGGCCTCACCGTGAGAGGGCTCCTGTATTAGTCCCTTTTCATGCTGCTTATAGAGAC
ATACCTGAGACTGGGCAATTTGCAGAGAAAGGTTTTCTTGGACTTACAGTTAGTTCCACGTGGCTGGG
GAAGCCTCACAATCATGGCGGAAGGCAAGGAAGGGCAAGTCCCATCTTACATGGATGGCAGCAGGCAA
AGAGAGAATGAGGAAGATGCAAAAGCGGAAACCCCTGATGTAACCATCAGATCTTATGAGATTTATTC ACTACCATGGAACAGACAGCAAGGCGTATGTGACCATTCTCTAGAATATTTAAGCTCGAGAATCTCAG AGCGGAAGCTGCAAGGCTCCTGGCTGCCTGCCAGCCGAGGGAATCTGGAGAAACCATTCCTGGGGCCG CGTGGCCCCGTCGTGCCCTTGTTCTGCCCTCGGAATGGCCTTCACTCAGCACATCCTGAGAACAGCCC TCTGAAGCCCAGGGTCGTGACCGTAGTGAAGCTGGGTGGGCAGCGCCCCCGAAAGATCACTCTGCTCC TCAACAGGCGATCAGTGCAGACGTTCGAGCAGCTCTTAGCTGACATCTCAGAAGCCTTGGGCTCTCCC AGATGGAAGAATGACCGTGTGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGA TTTCTTCAGGGAAGGGGATGCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGG TGGCTGTAGAAGAACTGTACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCT TCTCCAAGGCTGAGGAGCAGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGA GACCCCCAAGAGCTGCAGCGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCG AGGAGCTTTCACTAGATGACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAA CCCAGTAGCAAGCCCCCCAGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGG GGTGGAGATTGAAAAGACCTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTCC AGCAGAGCCTGGAGCGTGAGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATG TATGATGTGGAGAAGCTGGTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGG GGAGGAAGGGTGGAAGGGTGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGAC CCAGCAAGAGCATGGACAAGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCA GCCAAGGCCAAGAAGGACCTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGGGAGGTGAAGAA GGACACCAGGCCCATGAGCAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTG AGAAGCTCCGCAGGACCCGAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGA GGCAGAAGGATGACTCTCAGAGATGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGA AGAGAACAAGCCAGAGCGGCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGG AAAAGCATTATGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACAC CGCGAGACCAGGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACAT GGTGGACAGTGAGATCTTGATCATCCAGAGCCTCTCTCACCCCAACATCGTGAAATTGCATGAAGTCT ACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTTTGACGCCATC ATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCAAAGCCCTCGT CCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTTCAGCGAAATG AGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAGACCTATATTT ACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTTATGGACTGGAGGT GGACATGTGGGCTGCTGGCGTGATCCTCTATATCCTGCTGTGTGGCTTTCCCCCATTCCGCAGCCCTG AGAGGGACCAGGACGAGCTCTTTAACATCATCCAGCTGGGCCACTTTGAGTTCCTCCCCCCTTACTGG GACAATATCTCTGATACAGCTGCTAAAGATCTGGTGAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCG CTACACAGCTCATCAGGTTCTTCAGCACCCCTGGATCGAAACAGCTGGCAAGACCAATACAGTGAAAC GACAGAAGCAGGTGTCCCCCAGCAGCGAGGGTCACTTCCGGAGCCAGCACAAGAGGGTTGTGGAGCAG GTATCATAGTCACCACCTTGGGAATCTGTCCAGCCCCCAGTTCTGCTCAAGGACAGAGAAAAGGATAG
AAGTTTGAGAGAAAAACAATGAAAGAGGCTTCTTCACATAATTGGTGAATCAGAGGGAGAGACACTGA
GTATATTTTAAAGCATATTA
NOV64h, CG57109-02 SEQ ID NO: 970 δ36 aa MW at 95152.6kD Protein Sequence
MAEGKEGQVPSYMDGSRQRENEEDAKAETPDVTIRSYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQ δ74 GS LPASRGNLEKPFLGPRGPWPLFCPRNGLHSAHPENSPLKPRWTWKLGGQRPRKITLLLNRRS VQTFEQLLADISEALGSPR KNDRVRKLFNLKGREIRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEE LYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIPEELSL DDRARTQKKWGRGK EPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCEKCKRERELQQSLE RERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KGDSHRSSPRNPTQELRRPSKSM DKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMSRSKHGGWLLREHQAGFEKLRR TRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYE TGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDM EIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKST TLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPERDQD ELFNIIQLGHFEFLPPY DNISDTAAKDLVSRLLWDPKKRYTAHQVLQHPWIETAGKTNTVKRQKQV SPSSEGHFRSQHKRWEQVS
NOV64i, CG57109-03 SEQ ID NO: 971 3016 bp DNA Sequence ORF Start: ATG at 52 ORF Stop: TAG at 2617
TTTACAGAGTCAGGCCTCACCGTGAGAGGGCTCCTGTATTAGTCCCTTTTCATGCTGCTTATAGAGAC
ATACCTGAGACTGGGCAATTTGCAGAGAAAGGTTTTCTTGGACTTACAGTTAGTTCCACGTGGCTGGG GAAGCCTCACAATCATGGCGGAAGGCAAGGAAGGGCAAGTCCCATCTTACATGGATGGCAGCAGGCAA AGAGAGAATGAGGAAGATGCAAAAGCGGAAACCCCTGATGTAACCATCAGATCTTATGAGATTTATTC ACTACCATG^AACAGACAGCAAGGCGTATGTGACCATTCTCTAGAATATTTAAGCTCGAGAATCTCAG AGCGGAAGCTGCAAGGCTCCTGGCTGCCTGCCAGCCGAGGGAATCTGGAGAAACCATTCCTGGGGCCG CGTGGCCCCGTCGTGCCCTTGTTCTGCCCTCGGAATGGCCTTCACTCAGCACATCCTGAGAACAGCCC TCTGAAGCCCAGGGTCGTGACCGTAGTGAAGCTGGGTGGGCAGCGCCCCCGAAAGATCACTCTGCTCC TCAACAGGCGATCAGTGCAGACGTTCGAGCAGCTCTTAGCTGACATCTCAGAAGCCTTGGGCTCTCCC AGATGGAAGAATGACCGTGTGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGA TTTCTTCAGGGAAGGGGATGCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGG TGGCTGTAGAAGAACTGTACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCT TCTCCAAGGCTGAGGAGCAGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGA GACCCCCAAGAGCTGCAGCGAAGTTGCAGGATGCAAGGCAGCTATGAGGCACCAGGGGAAGATCCCCG AGGAGCTTTCACTAGATGACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAA CCCAGTAGCAAGCCCCCCAGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGG GGTGGAGATTGAAAAGACCTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTTC AGCAGAGCCTGGAGCGTGAGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATG TATGATGTGGAGAAGCTGGTGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGG GGAGGAAGGGTGGAAGGGTGACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGAC CCAGCAAGAGCATGGACAAGAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCA GCCAAGGCCAAGAAGGACCTTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGGGAGGTGAAGAA GGACACCAGGCCCATGAGCAGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTG AGAAGCTCCGCAGGACCCGAGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGA GGCAGAAGGATGACTCTCAGAGATGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGA AGAGAACAAGCCAGAGCGGCCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGG AAAAGCATTATGAGACTGGCCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACAC CGCGAGACCAGGCAGGCCTATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACAT GGTGGACAGTGAGATCTTGCATGAAGTCTACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACG TGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTC ATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAA GCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGAC TTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATT CTTTCTGAGAAAGGTTATGGACTGGAGGTGGACATGTGGGCTGCTGGCGTGATCCTCTATATCCTGCT GTGTGGCTTTCCCCCATTCCGCAGCCCTGAGAGGGACCAGGACGAGCTCTTTAACATCATCCAGCTGG GCCACTTTGAGTTCCTCCCCCCTTACTGGGACAATATCTCTGATGCTGCTAAAGATCTGGTGAGCCGG TTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCATCAGGTTCTTCAGCACCCCTGGATCGAAAC AGCTGGCAAGACCAATACAGTGAAACGACAGAAGCAGGTGTCCCCCAGCAGCGAGGGTCACTTCCGGA GCCAGCACAAGAGGGTTGTGGAGCAGGTATCATAGTCACCACCTTGGGAATCTGTCCAGCCCCCAGTT CTGCTCAAGGACAGAGAAAAGGATAGAAGTTTGAGAGAAAAACAATGAAAGAGGCTTCTTCACATAAT TGGTGAATCAGAGGGAGAGACACTGAGTATATTTTAAAGCATATTAAAAAAATTAAGTCAATGTTAAA TGTCACAACATATTTTTAGATTTGTATATTTAAAGCCTTTAATACATTTTTGGGGGGTAAGCATTGTC ATCAGTGAGGAATTTTGGTAATAATGATGTGTTTTGCTTCCCCTTTGTAACCAAGTTTATTCTGTACT ACAGGAGTGGTGCTTACCAGGGTCTAAACTCCCCCTGTGAGATTAATAAGGTGCACTGTGGTCTTTCT GTGTTAATAAAATGTGCTCTGAAT
NOV64i, CG57109-03 SEQ ID NO: 972 855 aa MW at 97447.3kD Protein Sequence
MLLIETYLRLGNLQRKVFLDLQLVPRGWGSLTIMAEGKEGQVPSYMDGSRQRENEEDAKAETPDVTIR SYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQGS LPASRGNLEKPFLGPRGPWPLFCPRNGLHSA HPENSPLKPRWTWKLGGQRPRKITLLLNRRSVQTFEQLLADISEALGSPRWKNDRVRKLFNLKGRE IRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDH RCGETETPKSCSEVAGCKAAMRHQGKIPEELSLDDRARTQKK GRGKWEPEPSSKPPREATLEERHAR GEKHLGVEIEKTSGEIIRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPE ANPASGEEGWKGDSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEG LREVKKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKE PKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRL KGKEDMVDSEILHEVYETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSI VHRDLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMAAGV ILYILLCGFPPFRSPERDQDELFNIIQLGHFEFLPPYWDNISDAAKDLVSRLLWDPKKRYTAHQVLQ HPWIETAGKTNTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64J, CG57109-04 SEQ ID NO: 973 2433 bp DNA Sequence ORF Start: ATG at 52 ORF Stop: TAG at 2284
TTTACAGAGTCAGGCCTCACCGTGAGAGGGCTCCTGTATTAGTCCCTTTTCATGCTGCTTATAGAGAC
ATACCTGAGACTGGGCAATTTGCAGAGAAAGGTTTTCTTGGACTTACAGTTAGTTCCACGTGGCTGGG GAAGCCTCACAATCATGGCGGAAGGCAAGGAAGGGCAAGTCCCATCTTACATGGATGGCAGCAGGCAA AGAGAGAATGAGGAAGATGCAAAAGCGGAAACCCCTGATGTAACCATCAGATCTTATGAGATTTATTC ACTACCATGGAACAGACAGCAAGGCGTATGTGACCATTCTCTAGAATATTTAAGCTCGAGAATCTCAG AGCGGAAGCTGCAAGGCTCCTGGCTGCCTGCCAGCCGAGGGAATCTGGAGAAACCATTCCTGGGGCCG CGTGGCCCCGTCGTGCCCTTGTTCTGCCCTCGGAATGGCCTTCACTCAGCACATCCTGAGAACAGCCC TCTGAAGCCCAGGGTCGTGACCGTAGTGAAGCTGGGTGGGCAGCGCCCCCGAAAGATCACTCTGCTCC TCAACAGGCGATCAGTGCAGACGTTCGAGCAGCTCTTAGCTGACATCTCAGAAGCCTTGGGCTCTCCC AGATGGAAGAATGACCGTGTGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGA TTTCTTCAGGGAAGGGGATGCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGG TGGCTGTAGAAGAACTGTACCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCT TCTCCAAGGCTGAGGAGCAGGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGA GACCCCCAAGAGCTGCAGCGAAGTTGCAGGATGCAAGGCAGCCATGAGGCACCAGGGGAAGATCCCCG AGGAGCTTTCACTAGATGACAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAA CCCAGTAGCAAGCCCCCCAGGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGG GGTGGAGATTGAAAAGACCTCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTCC AGCAGAGCCTGGAGCGTGAGAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATG TATGATGTGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGATGACTCTCAGAGATGACCAACCTGC AAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAGCCAGAGCGGCCCAGCGGTCGGAAGC CACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTATGAGACTGGCCGGGTCATTGGGGAT GGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCAGGCAGGCCTATGCGATGAAGATCAT TGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGTGAGATCTTGATCATCCAGAGCCTCT CTCACCCCAACATCGTGAAATTGCATGAAGTTTACGAAACAGACATGGAAATCTACCTGATCCTGGAG TACGTGCAGGGAGGAGACCTTTTTGACGCCATCATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGC CCTCATGATCATGGACTTATGCAAAGCCCTCGTCCACATGCACGACAAGAGCATTGTCCACCGGGACC TCAAGCCGGAAAACCTTTTGGTTCAGCGAAATGAGGACAAATCTACTACCTTGAAATTGGCTGATTTT GGACTTGCAAAGCATGTGGTGAGACCTATATTTACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGA AATTCTTTCTGAGAAAGGTTATGGACTGGAGGTGGACATGTGGGCTGCTGGCGTGATCCTCTATATCC TGCTGTGTGGCTTTCCCCCATTCCGCAGCCCTGAGAGGGACCAGGACGAGCTCTTTAACATCATCCAG CTGGGCCACTTTGAGTTCCTCCCCCCTTACTGGGACAATATCTCTGATACAGCTGCTAAAGATCTGGT GAGCCGGTTGCTGGTGGTAGACCCCAAAAAGCGCTACACAGCTCATCAGGTTCTTCAGCACCCCTGGA TCGAAACAGCTGGCAAGACCAATACAGTGAAACGACAGAAGCAGGTGTCCCCCAGCAGCGAGGGTCAC TTCCGGAGCCAGCACAAGAGGGTTGTGGAGCAGGTATCATAGTCACCACCTTGGGAATCTGTCCAGCC CCCAGTTCTGCTCAAGGACAGAGAAAAGGATAGAAGTTTGAGAGAAAAACAATGAAAGAGGCTTCTTC ACATAATTGGTGAATCAGAGGGAGAGACACTGAGTATATTTTAAAGCATATTA NOV64J, CG57109-04 SEQ ID NO: 974 744 aa MW at 84729.4kD Protein Sequence
MLLIETYLRLGNLQRKVFLDLQLVPRGWGSLTIMAEGKEGQVPSYMDGSRQRENEEDAKAETPDVTIR SYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQGSWLPASRGNLEKPFLGPRGPWPLFCPRNGLHSA HPENSPLKPRWTWKLGGQRPRKITLLLNRRSVQTFEQLLADISEALGSPRWKNDRVRKLFNLKGRE IRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDH RCGETETPKSCSEVAGCKAAMRHQGKIPEELSLDDRARTQKK GRGK EPEPSSKPPREATLEERHAR GEKHLGVEIEKTSGEIIRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKKPCMSGGRRMTL RDDQPAKLEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQA YAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLFDAIIESVKF PEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADFGLAKHWRPIFTVCGTP TYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQDELFNIIQLGHFEFLPPY DNISDT AAKDLVSRLLWDPKKRYTAHQVLQHPWIETAGKTNTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64k, CG57109-06 SEQ ID NO: 975 2720 bp DNA Sequence ORF Start: ATG at 149 ORF Stop: TGA at 1826
GGACACTGACATGGACTGAAGGAGTAGAAAAGAAGCCTTGGGCTCTCCCAGATGGAAGAATGACCGTG
TGAGGAAACTGTTTAACCTCAAGGGCAGGGAAATCAGGAGCGTCTCTGATTTCTTCAGGGAAGGGGAT
GCTTTCATAGCTATGGGCAAAGAACCACTGACACTGAAGAGCATTCAGGTGGCTGTAGAAGAACTGTA
CCCCAACAAAGCCCGGGCCCTGACACTGGCCCAGCACAGCCGTGCCCCTTCTCCAAGGCTGAGGAGCA GGCTGTTTAGCAAGGCTCTGAAAGGAGACCACCGCTGTGGGGAGACCGAGACCCCCAAGAGCTGCAGC GAAGTTGCAGGATGCAAGGCAGCTATGAGGCACCAGGGGAAGATCCCCGAGGAGCTTTCACTAGATGA CAGAGCGAGGACCCAGAAGAAGTGGGGGAGGGGGAAATGGGAGCCAGAACCCAGTAGCAAGCCCCCCA GGGAAGCCACTCTGGAAGAGAGGCACGCAAGGGGAGAGAAGCATCTTGGGGTGGAGATTGAAAAGACC TCGGGTGAAATTATCAGATGCGAGAAGTGCAAGAGAGAGAGGGAGCTTCAGCAGAGCCTGGAGCGTGA GAGGCTTTCTCTGGGGACCAGTGAGCTGGATATGGGGAAGGGCCCAATGTATGATGTGGAGAAGCTGG TGAGGACCAGAAGCTGCAGGAGGTCTCCCGAGGCAAATCCTGCAAGTGGGGAGGAAGGGTGGAAGGGT GACAGCCACAGGAGCAGCCCCAGGAATCCCACTCAAGAGCTGAGGAGACCCAGCAAGAGCATGGACAA GAAAGAGGACAGAGGCCCAGAGGATCAAGAAAGCCATGCTCAGGGAGCAGCCAAGGCCAAGAAGGACC TTGTGGAAGTTCTTCCTGTCACAGAGGAGGGGCTGAGGGAGGTGAAGAAGGACACCAGGCCCATGAGC AGGAGCAAACATGGTGGCTGGCTCCTGAGAGAGCACCAGGCGGGCTTTGAGAAGCTCCGCAGGACCCG AGGAGAAGAGAAGGAGGCAGAGAAGGAGAAAAAGCCATGTATGTCTGGAGGCAGAAGGATGACTCTCA GAGATGACCAACCTGCAAAGCTAGAAAAGGAGCCCAAGACGAGGCCAGAAGAGAACAAGCCAGAGCGG CCCAGCGGTCGGAAGCCACGGCCCATGGGCATCATTGCCGCCAATGTGGAAAAGCATTATGAGACTGG CCGGGTCATTGGGGATGGGAACTTTGCTGTCGTGAAGGAGTGCAGACACCGCGAGACCAGGCAGGCCT ATGCGATGAAGATCATTGACAAGTCCAGACTCAAGGGCAAGGAGGACATGGTGGACAGTGAGATCTTG CATGAAGTCTACGAAACAGACATGGAAATCTACCTGATCCTGGAGTACGTGCAGGGAGGAGACCTTTT TGACGCCATCATAGAAAGTGTGAAGTTCCCGGAGCCCGATGCTGCCCTCATGATCATGGACTTATGCA AAGCCCTCGTCCACATGCACGACAAGAGCATTGTCCACCGGGACCTCAAGCCGGAAAACCTTTTGGTT CAGCGAAATGAGGACAAATCTACTACCTTGAAATTGGCTGATTTTGGACTTGCAAAGCATGTGGTGAG ACCTATATTTACTGTGTGTGGGACCCCAACTTACGTAGCTCCCGAAATTCTTTCTGAGAAAGGTAAGT GTTACACATCGATCTGTGGGACTCTAGTTCCCTTACTAACAAATGTTTCATTTGTCATATTTACTAGT TTTCAATATGGAATAAATCTCAGAGAACTGACACTTAGGCTTGGATTTGGACTTCAATGAAAATATTT GAAGTAGGCTTGACCAAAGCATGAGAGCTTTCTCCTCATTAGGGCTGCCCTTGTTACAGTCAATGGAT CAGTGTGTGTGCATGTGTGTGTGTGTGTGTGTGTTTATTGTGTTTAGGCAGGACAGTGAGATGAAAGA TGATGGAGAATTGGGTGGGGAACTCAAGCAAGCAAGGCTACTTGACCCAAGGCTATCTCTAATAGGAG AGAATTGAAGCAGTCCTTATGGTACTTGGTTTAAAAATTTCTTCACCAACCTTGCATTTAAAGGAAAA GGATCCCATTTTCCTCCATGAACTCTATGAATATTTATTACCTACTTGTATATTATGCAAGGATCCAA TGAGCTGTTTTAGTGACAAACTTTCTAAAACATTTAAAAAGGAAATAATAGTTATGATATGGCTCTAA ATATATGAATGACTATTTGACTACTGTGGCACTCCAGGAGAAACCAATTTACCCACCATTGGTAAGAT GGGAAGACTCTCATTGGGTTGCAGGGTTGGTGACAGGGAGAAGGGATGGACGGATAGTTTCCCAGCAG CAGAAGCATCAGGATAATTAAGATGAGGAGATGGCCAGGGATGGTGGCTCATGCCTGTAATCCCAGCT CTTTGGGAGGCTGAGGCAGGTGGATCACCTGAGGTCAGGCGTTTGAAACCATCCTGGCCAACATGGTG AAACCCTGTCTGTACTAAAACTACAAAAAAATTAGCTGGGCGTGGTGGCACATGCCTGTAATCTGAGC TACTCGGGAGGCTGAGGCAGGAGAATTGCTTGAACCGGGGAGGTGGAGTTTGCAGTGAGCCAAGATCG TGCCATTGCACTCCAGCCTGGGCAACAAGAGTGAAACTTCATCTCAAAAAAAAAAAAAAAAAAAAAAC NOV64k, CG57109-06 SEQ ID NO: 976 559 aa MW at 63436.9kD Protein Sequence
MGKEPLTLKSIQVAVEELYPNKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAG CKAAMRHQGKIPEELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEI IRCEKCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KGDSHR SSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREVKKDTRPMSRSKH GGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAKLEKEPKTRPEENKPERPSGR KPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQAYAMKIIDKSRLKGKEDMVDSEILHEVY ETDMEIYLILEYVQGGDLFDAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNE DKSTTLKLADFGLAKHWRPIFTVCGTPTYVAPEILSEKGKCYTSICGTLVPLLTNVSFVIFTSFQYG INLRELTLRLGFGLQ
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 64B.
Table 64B. Comparison of the NOV64 protein sequences.
NOV64a
NOV64b
NOV64c
NOV64d
NOV64e
NOV64f
NOV64g
NOV64h MAEGKEGQVPSYMDGSRQRENEEDAKA
NOV64i MLLIETYLRLGNLQRKVFLDLQLVPRG GSLTIMAEGKEGQVPSYMDGSRQRENEEDAKA
NOV64J MLLIETYLRLGNLQRKVFLDLQLVPRG GSLTIMAEGKEGQVPSYMDGSRQRENEEDAKA
NOV64k
NOV64a
NOV64b
NOV64c
NOV64d
NOV64e
NOV64f
NOV64g
NOV64h ETPDVTIRSYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQGS LPASRGNLEKPFLGPR
NOV64i ETPDVTIRSYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQGSWLPASRGNLEKPFLGPR
NOV64J ETPDVTIRSYEIYSLPWNRQQGVCDHSLEYLSSRISERKLQGSWLPASRGNLEKPFLGPR
NOV64k
NOV64a
NOV64b
NOV64c
NOV64d
NOV64e
NOV64f
NOV64g
NOV64h GPVVPLFCPRNGLHSAHPENSPLKPRVVTVVKLGGQRPRKITLLLNRRSVQTFEQLLADI
NOV64i GPVVPLFCPRNGLHSAHPENSPLKPRVVTWKLGGQRPRKITLLLNRRSVQTFEQLLADI
NOV64J GPWPLFCPRNGLHSAHPENSPLKPRWTWKLGGQRPRKITLLLNRRSVQTFEQLLADI
NOV64k
NOV64a MGKEPLTLKSIQVAVEELYP
87δ NOV64b
NOV64c
NOV64d MGKEPLTLKSIQVAVEELYP
NOV64e TGSTMGKEPLTLKSIQVAVEELYP
NOV64f TGSTMGKEPLTLKSIQVAVEELYP
NOV64g
NOV64h SEALGSPRWKNDRVRKLFNLKGREIRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEELYP
NOV64i SEALGSPRWKNDRVRKLFNLKGREIRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEELYP
NOV64J SEALGSPRWKNDRVRKLFNLKGREIRSVSDFFREGDAFIAMGKEPLTLKSIQVAVEELYP
NOV64k MGKEPLTLKSIQVAVEELYP
NOV64a NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64b
NOV64c
NOV64d NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64e NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64f NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64g
NOV64h NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64i NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64J NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64k NKARALTLAQHSRAPSPRLRSRLFSKALKGDHRCGETETPKSCSEVAGCKAAMRHQGKIP
NOV64a EELSLDDRARTQKK GRGK EPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64b
NOV64c
NOV64d EELSLDDRARTQKKWGRGK EPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64e EELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64f EELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64g
NOV64h EELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64i EELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64J EELSLDDRARTQKKWGRGKWEPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64k EELSLDDRARTQKKWGRGK EPEPSSKPPREATLEERHARGEKHLGVEIEKTSGEIIRCE
NOV64a KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG
NOV64b
NOV64c
NOV64d KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG
NOV64e KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG
NOV64f KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KG
NOV64g
NOV64h KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG
NOV64i KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEG KG
NOV64j KCKRERELQQSLERERLSLGTSELDMGKGPMYDVE
NOV64k KCKRERELQQSLERERLSLGTSELDMGKGPMYDVEKLVRTRSCRRSPEANPASGEEGWKG
NOV64a DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64b
NOV64C
NOV64d DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64e DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64f DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64g NOV64h DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64i DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64J
NOV64k DSHRSSPRNPTQELRRPSKSMDKKEDRGPEDQESHAQGAAKAKKDLVEVLPVTEEGLREV
NOV64a KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64b
NOV64C
NOV64d KKDTRPMSRSKHGG LLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64e KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64f KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64g
NOV64h KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64i KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64j KKPCMSGGRRMTLRDDQPAK
NOV64k KKDTRPMSRSKHGGWLLREHQAGFEKLRRTRGEEKEAEKEKKPCMSGGRRMTLRDDQPAK
NOV64a LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64b TGSYETGRVIGDGNFAWKECRHRETRQ
NOV64C TGSYETGRVIGDGNFAWKECRHRETRQ
NOV64d LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64e LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64f LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64g TGSYETGRVIGDGNFAWKECRHRETRQ
NOV64h LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64 i LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64j LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64k LEKEPKTRPEENKPERPSGRKPRPMGIIAANVEKHYETGRVIGDGNFAWKECRHRETRQ
NOV64a AYAMKIIDKSRLKGKEDMVDSEILI IQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64b AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64C AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64d AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64e AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64f AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64g AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64h AYAMKIIDKSRLKGKEDMVDSEILIIQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64i AYAMKIIDKSRLKGKEDMVDSEI - - LHEVYETDMEIYLILEYVQGGDLF NOV64J AYAMKIIDKSRLKGKEDMVDSEILI IQSLSHPNIVKLHEVYETDMEIYLILEYVQGGDLF NOV64k AYAMKIIDKSRLKGKEDMVDSEIL- HEVYETDMEIYLILEYVQGGDLF
NOV64a DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64b DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64C DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64d DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64e DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64f DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64g DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64h DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64i DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64J DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF NOV64k DAIIESVKFPEPDAALMIMDLCKALVHMHDKSIVHRDLKPENLLVQRNEDKSTTLKLADF
NOV64a GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQ
8δ0 NOV64b GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQ NOV64C GLAKHWRPIFTVCGTPTYVAPEILSEK NOV64d GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPERDQ NOV64e GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQ NOV64f GLAKHWRPIFTVCGTPTYVAPEILSEKG NOV64g GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPERDQ NOV64h GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQ NOV64i GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDM AAGVILYILLCGFPPFRSPERDQ NOV64J GLAKHWRPIFTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPERDQ NOV64 GLAKHWRPIFTVCGTPTYVAPEILSEKGK CYTSICG
NOV64a DELFNI IQLGHFEFLPPY DNISD-AAKDLVSRLLWDPKKRYTAHQVLQHP IETAGKT NOV64b DELFNI IQLGHFEFLPPYWDNISD-AAKDLVSRLLWDPKKRYTAHQVLQHP ILEG NOV64C AAK DLVSRLLWDPKKRYTAHQVLQHPWILEG NOV64 DELFNI IQLGHFEFLPPYWDNISD-AAKDLVSRLLWDPKKRYTAHQVLQHP IETAGKT NOV64e DELFNIIQLGHFEFLPPYWDNISD-AAKDLVSRLLWDPKKRYTAHQVLQHPWIETAGKT NOV64f YGLELEG NOV64g DELFNI IQLGHFEFLPPYWDNISD-AAKDLVSRLLWDPKKRYTAHQVLQHPWILEG NOV64h DELFNI IQLGHFEFLPPY DNISDTAAKDLVSRLLWDPKKRYTAHQVLQHP IETAGKT NOV64i DELFNIIQLGHFEFLPPY DNISD-AAKDLVSRLLWDPKKRYTAHQVLQHPWIETAGKT NOV64J DELFNIIQLGHFEFLPPYWDNISDTAAKDLVSRLLWDPKKRYTAHQVLQHPWIETAGKT NOV6 k _ -T LVPLLTNVSFVIFTSFQYGINLRELTLRLGFGLQ
NOV64a NTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64b
NOV64C
NOV64d NTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64e NTVKRQKQVSPSSEGHFRSQHKRWEQVSLEG
NOV64f
NOV64g
NOV64h NTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64i NTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64j NTVKRQKQVSPSSEGHFRSQHKRWEQVS
NOV64k
NOV64a (SEQ ID NO 956)
NOV64b (SEQ ID NO 958)
NOV64C (SEQ ID NO 960)
NOV64d (SEQ ID NO 962)
NOV64e (SEQ ID NO 964)
NOV64f (SEQ ID NO 966)
NOV64g (SEQ ID NO 968)
NOV64h (SEQ ID NO 970)
NOV64i (SEQ ID NO 972)
NOV64J (SEQ ID NO 974)
NOV64k (SEQ ID O 976)
Further analysis ofthe NOV64a protein yielded the following properties shown in Table 64C. Table 64C. Protein Sequence Properties NOV64a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos. chg 2; neg.chg 1 H-region: length 6; peak value -5.22 PSG score: -9.62
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.85 possible cleavage site: between 34 and 35
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -3.29 Transmembrane 534 - 550 PERIPHERAL Likelihood = 4.72 (at 452) ALOM score: -3.29 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 541 Charge difference: 1.0 C(-2.0) - N(-3.0) C > N: C-terminal side will be inside
>>> Single TMS is located near the C-terminus
>>> membrane topology: type Nt (cytoplasmic tail 1 to 533)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 9.28 Hyd Moment(95): 7.07 G content: 1 D/E content: 2 S/T content: 2 Score: -6.37
Gavel: prediction of cleavage sites for mitochondrial preseq R-10 motif at 52 SRL FS
NUCDISC: discrimination of nuclear localization signals pat4 RKPR (4) at 340 pat4 PKKR (4) at 598 pat7 PSGRKPR (3) at 337 pat7 PKKRYTA (5) at 598 bipartite: none content of basic residues: 17.9% NLS Score: 0.72
KDEL: ER retention motif in the C-terminus: none
8δ2 ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 276 LL at 483 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhard 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
30.4 %: nuclear
26.1 %: cytoplasmic
13.0 %: Golgi
8.7 %: mitochondrial
8.7 %: vesicles of secretory system
8.7 %: endoplasmic reticulum
4.3 %: peroxisomal
>> prediction for CG57109-01 is nuc (k=23)
δ83 A search ofthe NOV64a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 64D.
Figure imgf000888_0001
In a BLAST search of public sequence databases, the NOV64a protein was found to have homology to the proteins shown in the BLASTP data in Table 64E.
8δ4
Figure imgf000889_0001
PFam analysis indicates that the NOV64a protein contains the domains shown in the Table 64F.
Figure imgf000889_0002
Example 65.
The NOV65 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 65A. δδ5 Table 65A. NOV65 Sequence Analysis
NOV65a, CG57399-04 SEQ ID NO: 977 947 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: TGA at 937
GACCTGATGAAGAATGACACGAGGATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGG
CGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTCCACTATTCTCCCCAGAACTTCACAGACAACA TTGGAAAGGCCCTGGACATCCTCCATGCTGAGGTTCCTCGGGCATTTGTGAACCTGGTGACGGTGCTT GAGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAAAAAGTCTACTGCCCAAGGATGATCCTCAGGTC TCTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACTTGCTACCCTCATCGAATTCAACA AGAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGATATGACACAAGGGAAGATTTTACT GTGGTTGTGCGGCCGTTCTTTGAAAACGTGGACATGCCAAAGACCTCGGAAGGATTGCCTGACAACTC TTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTCCCGAGCAGCCAGTGCTCTCTGGA ACAATATGCTGGAGCCTGTTGGCCAGAAGACGACTCGTCATAAGTTTGAAAACAAGATCAATATCACA TGTCCGAACCAGGTCCAGCCGTTTCTGAGGACCTACAAGAACAGCATGCAGGGTCATGGGACCTGGCT GCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTCAGTGCATGCCCTGAGACCTGCAGACA TCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCAATGGAATTGGCTCCAAACCAGACGAC CTCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGAGAAAGTAAACCAGGGTTCTTATCAGA CTCCTGGGTCAGCAAATCCAACAGGAAATGCACCAGAAAAGCACCAAATCCCTGAATCTACAC
NOV65a, CG57399-04 SEQ ID NO: 97δ 310 aa MW at 3526δ.7kD Protein Sequence
MKNDTRIHFQEDWKIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAEVPRAFVNLVTVLEI VNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQEKTHQLIESGRYDTREDFTW VRPFFENVDMPKTSEGLPDNSFFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCP NQVQPFLRTYKNSMQGHGT LPCRDRAPSALHPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLP DVTTQYRGLSYRESKPGFLSDS VSKSNRKCTRKAPNP
NOV65b, CG57399-01 SEQ ID NO: 979 426δ bp
DNA Sequence lORF Start: ATG at 1 JORF Stop: TAG at 425δ
ATGACCTGGGACACAGCTCTCTGGACCTCAGTTTTTCTGATTGGGCTCCTTCCTACCCTTGGTTTCGC TAATTGCATCCTCCAGACTTCTGGTAAAATGTGTACTTTAAGAGGTAGATACCCCCAGCCCCCACAAC CACCTCTCTGCTTGTCTCCCCTAGTCCACCAGCTCCGACCAGCAGACATCAAAGTGGTGGCCGCCCTG GGTAATGATGAAACCTTCCAGGAAAGTGGTGCAGGGCAGCTAAGTGAGCCTGACCCCAGGCAGTGGTC CTGGCCACAGGCCTGCTTGCCTGGGGTAAAAAAGGAAATGCAAGATGTGGTAGGTGAGAGAACGCCGA GCCGTCGCCGCAGCCTCCGCCGCCGAGAAGCCCTTGTTCCCGCTGCTGGGAAGGAGAGTCTGTGCCGA CAAGATATTTTCATTTCCTTGTTGGAAATTATCAAGCATTTTCCTCCCTCCCCTCAGGACATCAACCT GGAGAAAGACTGGAAGCTGGTCACACTCTTCATTGGGGTCAACGACTTGTGTCATTACTGTCCACTTG TTCAGGGCCCCGTTATAGACCTGGGTGGGATGGATACCCTCCACTCCCTGCAGCTCCCAAGGGCTTTC GTCAACGTGGTGGAGGTCATGGAGCTGGCTAGCCTGTACCAGGGCCAAGGCGGGAAATGTGCCATGCT GGCAGCTCAGGAAGCCTGGAACAGCCTCCTGGCCTCCAGCAGGTACAGTGAGCAGGAGTCCTTCACCG TGGTTTTCCAGCCTTTCTTCTATGAGACCACCCCATCTGACCCCCGACTCCAGGATTCTACCACGCTG GCCTGGCATCTCTGGAATAGGATGATGGAGCCAGCAGGAGAGAAAGATGAGCCATTGAGTGTAAAACA CGGGAGGCCAATGAAGTGTCCCTCTCAGGAGAGCCCCTATCTGTTCAGCTACAGAAACAGCAACTACC TGACCAGACTGCAGAAACCCCAAGACAAGCTTGTAAGAGAAGGAGCGGAAATCAGATGTCCTGACAAA GACCCCTCCGATACGGTTCCCACCTCAGTTCATAGGCTGAAGCCGGCTGACATCAACGTAATTGGAGC CCTGGGTGACTCTCTCACGGCAGGCAATGGGGCCGGGTCCACACCTGGGAACGTCTTGGACGTCTTGA CTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGATGAGAACATCGGCACCGTTACCACCCTGGCA GACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTTCTCTGTTGGCACTGGGAAAGAAACCAGTCC TAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAGCTGAGCAGGCCAGGAGGCTGGTGGACCTGA TGAAGAATGACACGAGGATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAAT GACCTCTGTGATTTCTGCAATGATCTGGTACACTATTCTCCCCAGAACTTCACAGACAACATTGGAAA GGCCCTGGACATCCTCCATGCTGAGTCTCAGGTTCCTCGGGCATTTGTGAACCTGGTGACGGTGCTTG AGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAAAAAGTCTACTGCCCAAGGATGATCCTCAGGTCA CTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACTTGCTACCCTCATCGAATTCAACAA GAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGATATGACACAAGGGAAGATTTTACTG TGGTTGTGCAGCCGTTCTTTGAAAACGTGGACATGCCAAAGACCCAGGAAGGATTGCCTGACAACTCT TTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTCCCGAGCAGCCAGTGCTCTCTGGAA δδ6 CAATATGCTGGAGCCTGTTGGCCAGAAGACGACTCGTCATAAGTTTGAAAACAAGATCAATATCACAT GTCCGTCACAGGTCCAGCCGTTTCTGAGGACCTACAAGAACAGCATGCAGGGTCATGGGACCTGGCTG CCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTCAGTGCATGCCCTGAGACCTGCAGACAT CCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCAATGGAATTGGCTCCAAACCAGACGACC TCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGTGCAGGAGGGGACGGCTCCCTGGAGAAT GTGACCACCTTACCTAGTTCTATCCTTCGGGAGTTTAACAGAAACCTCACAGGCTACGCCGTGGGCAC GGGTGATGCCAATGACACGAATGCATTCCTCAATCAAGCTGTTCCCGGAGCAAAGGCTAGGGATCTTA TGAGCCAAGTCCAAACTCTGATGCAGAAGATGAAAGATGATCATAGAGTAAATTTCCATGAAGACTGG AAGGTCATCACAGTGCTGATCGGAGGCAGCGATTTATGTGACTACTGCACAGATTCGAATCTGTATTC TGCAGCCAACTTTGTTCACCATCTCCGCAATGCCTTGGACGTCCTGCATAGAGAGGTGCCCAGAGTCC TGGTCAACCTCGTGGACTTCCTGAACCCCACTATCATGCGGCAGGTGTTCCTGGGAAACCCAGACAAG TGCCCAGTGCAGCAGGCCAGCGTTTTGTGTAACTGCGTTCTGACCCTGCGGGAGAACTCCCAAGAGCT AGCCAGGCTGGAGGCCTTCAGCCGAGCCTACCAGAGCAGCATGCGCGAGCTGGTGGGGTCAGGCCGCT ATGACACGCAGGAGGACTTCTCTGTGGTGCTGCAGCCCTTCTTCCAGAACATCCAGCTCCCTGTCCTG CAGGATGGGCTCCCAGATACGTCCTTCTTTGCCCCAGACTGCATCCACCCAAATCAGAAATTCCACTC CCAGCTGGCCAGAGCCCTTTGGACCAATATGCTTGAACCACTTGGAAGCAAAACAGAGACCCTGGACC TGAGAGCAGAGATGCCCATCACCTGTCCCACTCAGAATGAGCCCTTCCTGAGAACCCCTCGGAATAGT AACTACACGTACCCCATCAAGCCAGCCATTGAGAACTGGGGCAGTGACTTCCTGTGTACAGAGTGGAA GGCTTCCAATAGTGTTCCAACCTCTGTCCACCAGCTCCGACCAGCAGACATCAAAGTGGTGGCCGCCC TGGGTGACTCTCTGACTACAGCAGTGGGAGCTCGACCAAACAACTCCAGTGACCTACCCACATCTTGG AGGGGACTCTCTTGGAGCATTGGAGGGGATGGGAACTTGGAGACTCACACCACACTGCCCAGTATTCT
GAAGAAGTTCAACCCTTACCTCCTTGGCTTCTCTACCAGCACCTGGGAGGGGACAGCAGGACTAAATG TGGCAGCGGAAGGGGCCAGAGCTAGGAGGGACATGCCAGCCCAGGCCTGGGACCTGGTAGAGCGAATG AAAAACAGCCCCATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAATGACCT CTGTGATTTCTGCAATGATCTGGTAGGTGAATATGTTCAGCACATCCAACAGGCCCTGGACATCCTCT CTGAGGAGCTCCCAAGGGCTTTCGTCAACGTGGTGGAGGTCATGGAGCTGGCTAGCCTGTACCAGGGC CAAGGCGGGAAATGTGCCATGCTGGCAGCTCAGAACAACTGCACTTGCCTCAGACACTCGCAAAGCTC CCTGGAGAAGCAAGAACTGAAGAAAGTGAACTGGAACCTCCAGCATGGCATCTCCAGTTTCTCCTACT GGCACCAATACACACAGCGTGAGGACTTTGCGGTTGTGGTGCAGCCTTTCTTCCAAAACACACTCACC CCACTGAACAGAGGGGACACTGACCTCACCTTCTTCTCCGAGGACTGTTTTCACTTCTCAGACCGCGG GCATGCCGAGATGGCCATCGCACTCTGGAACAACATGCTGGAACCAGTGGGCCGCAAGACTACCTCCA ACAACTTCACCCACAGCCGAGCCAAACTCAAGTGCCCCTCTCCTGTGAGTCCTTACCTCTACACCCTG CGGAACAGCCGATTGCTCCCAGACCAGGCTGAAGAAGCCCCCGAGGTGCTCTACTGGGCTGTCCCAGT GGCAGCGGGAGTCGGCCTTGTGGTGGGCATCATCGGGACAGTGGTCTGGAGGTGCAGGAGAGGTGGCC GGAGGGAAGATCCTCCAATGAGCCTGCGCACTGTGGCCCTCTAGGCCCGGGG
NOV65b, CG57399-01 SEQ ID NO: 9δ0 1419 aa MW at l58435.1kD Protein Sequence
MTWDTAL TSVFLIGLLPTLGFANCILQTSGKMCTLRGRYPQPPQPPLCLSPLVHQLRPADIKWAAL GNDETFQESGAGQLSEPDPRQ SWPQACLPGVKKEMQDWGERTPSRRRSLRRREALVPAAGKESLCR QDIFISLLEIIKHFPPSPQDINLEKDWKLVTLFIGVNDLCHYCPLVQGPVIDLGGMDTLHSLQLPRAF VNWEVMELASLYQGQGGKCAMLAAQEAWNSLLASSRYSEQESFTWFQPFFYETTPSDPRLQDSTTL AWHL NRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDKLVREGAEIRCPDK DPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGLSWSVGGDENIGTVTTLA DILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLVDLMKNDTRIHFQEDWKIITLFIGGN DLCDFCNDLVHYSPQNFTDNIGKALDILHAESQVPRAFVNLVTVLEIVNLRELYQEKKVYCPRMILRS LCPCVLKFDDNSTELATLIEFNKKFQEKTHQLIESGRYDTREDFTVWQPFFENVDMPKTQEGLPDNS FFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCPSQVQPFLRTYKNSMQGHGT L PCRDRAPSALHPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDGSLEN VTTLPSSILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRVNFHEDW KVITVLIGGSDLCDYCTDSNLYSAANFVHHLRNALDVLHREVPRVLVNLVDFLNPTIMRQVFLGNPDK CPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRYDTQEDFSWLQPFFQNIQLPVL QDGLPDTSFFAPDCIHPNQKFHSQLARALWTNMLEPLGSKTETLDLRAEMPITCPTQNEPFLRTPRNS NYTYPIKPAIENWGSDFLCTEWKASNSVPTSVHQLRPADIKWAALGDSLTTAVGARPNNSSDLPTSW RGLS SIGGDGNLETHTTLPSILKKFNPYLLGFSTST EGTAGLNVAAEGARARRDMPAQAWDLVERM KNSPIHFQEDWKIITLFIGGNDLCDFCNDLVGEYVQHIQQALDILSEELPRAFVNWEVMELASLYQG QGGKCAMLAAQNNCTCLRHSQSSLEKQELKKVN NLQHGISSFSY HQYTQREDFAVWQPFFQNTLT PLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLKCPSPVSPYLYTL RNSRLLPDQAEEAPEVLY AVPVAAGVGLWGIIGTW RCRRGGRREDPPMSLRTVAL NOV65c, CG57399-02 SEQ ID NO: 981 1624 bp DNA Sequence ORF Start: ATG at 311 JORF Stop: TGA at 1241
GCCGGCTGACATCAATGTAATTGGAGCCCTGGGTGACTCTCTCACGGCAGGCAATGGGGCCGGGTCCA
CACCTGGGAACGTCTTGGACGTCTTGACTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGATGAG
AACATCGGCACCGTTACCACCCTGGCGAACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTTCTCI
TGTTGGCACTGGGAAAGAAACCAGTCCTAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAGCTG
AGGATCTACCTGTCCAGGCCAGGAGGCTGGTGGACCTGATGAAGAATGACACGAGGATACACTTTCAG
GAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGT CCACTATTCTCCCCAGAACTTCACAGACAACATTGGAAAGGCCCTGGACATCCTCCATGCTGAGGTTC CTCGGGCATTTGTGAACCTGGTGACGGTGCTTGAGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAA AAAGTCTACTGCCCAAGGATGATCCTCAGGTCTCTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTC AACAGAACTTGCTACCCTCATCGAATTCAACAAGAAGTTTCAGGAGAAGACCCACCAACTGATTGAGA GTGGGCGATATGACACAAGGGAAGATTTTACTGTGGTTGTGCAGCCGTTCTTTGAAAACGTGGACATG CCAAAGACCTCGGAAGGATTGCCTGACAACTCTTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAA GTCTCACTCCCGAGCAGCCAGTGCTCTCTGGAACAATATGCTGGAGCCTGTTGGCCAGAAGACGACTC GTCATAAGTTTGAAAACAAGATCAATATCACATGTCCGAACCAGGTCCAGCCGTTTCTGAGGACCTAC AAGAACAGCATGCAGGGTCATGGGACCTGGCTGCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCC TACCTCAGTGCATGCCCTGAGACCTGCAGACATCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCG CTGGCAATGGAATTGGCTCCAAACCAGACGACCTCCCCGATGTCACCACACAGTATCGGGGACTGTCA TACAGAGAAAGTAAACCAGGGTTCTTATCAGACTCCTGGGTCAGCAAATCCAACAGGAAATGCACCAG AAAAGCACCAAATCCCTGAATCTTCACCTCCCCGCTTGCATGTATACGTGTACACGTGGTGTTCCTAC
GTCTCTGTTTACTGTCTTTATGTGTTTATTCATGTTGTCTTGTAGTCACACAGCTGCCTTTACATATA
TGTACACATCTGCACAGAAAACCTCTGAAACCCATCGCACACTTCGAGAGGCCATAACCAAGACACAA
TCACAATCAGCCATGTCTTGAAAGATTAGCAATTCGACAAGAGGAAAGGGTGAGAAAGGGCATCCCGA
ACACGGAAGTGGAGAAGCTCAGGGTGTGTCAGGCGAGCGGTTGCGTGTAGATATTCTCAAGTTTCTTT
CTCTCCTAATAAAGTTCTCATTCCTGTAGGCTTCAAAGTAAGTGGCGAGTAGCTCAGAAT
NOV65c, CG57399-02 SEQ ID NO: 982 310 aa MW at 35240.6kD Protein Sequence
MKNDTRIHFQEDWKIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAEVPRAFVNLVTVLEI VNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQEKTHQLIESGRYDTREDFTW VQPFFENVDMPKTSEGLPDNSFFAPDCFHFSSKSHSRAASAL NNMLEPVGQKTTRHKFENKINITCP NQVQPFLRTYKNSMQGHGTWLPCRDRAPSALHPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLP DVTTQYRGLSYRESKPGFLSDSWVSKSNRKCTRKAPNP
NOV65d, CG57399-03 SEQ ID NO: 9δ3 4425 bp
DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 42δ5
CTGGAGCATTCTGGCATGGGGCTGCGGCCAGGCATTTTCCTCCTGGAGCTGCTGCTGCTTCTGGGGCA
AGGTACCCCTCAGATCCATACCTCTCCTAGAAAGAGTACATTGGAAGGGCAGCTATGGCCAGAGACAG TTCACTCTCTGAAGCCTTCTGATATTAAATTTGTGGCAGCCATTGGCAATCTGGAAATTGTGCCAGAC CCAGGGACGGGCGATCTGGAGAAGCAAGACGAAAGGCCACAGCAGGTGTGCATGGGAGTGATGACAGT CCTTTCAGACATCATCAGATATTTCAGTCCTTCTGTTCCAATGCCTGTGTGCCACACTGGAAAGAGAG TCATACCCCACGATGGTGCTGAGGACTTGTGGATTCAGGCTCAAGAACTGGTGAGAAACATGAAAGAG AACCAACTTGACTTTCAATTTGACTGGAAGCTCATCAATGTGTTCTTCAGTAATGCAAGCCAGTGTTA CCTGTGCCCCTCTGCTCAACAGAATGGGCTTGCGGCGGGCGGCGTGGATGAGCTGATGGGGGTGCTGG ACTACCTGCAGCAGGAGGTGCCCAGAGCATTTGTAAACCTGGTGGACCTCTCTGAGGTTGCAGAGGTC TCTCGTCAGTATCACGGCACTTGGCTCAGCCCTGCACCAGAGCCCTGTAATTGCTCAGAGGAGACCAC CCGGCTGGCCAAGGTGGTGATGCAGTGGTCTTATCAGGAAGCCTGGAACAGCCTCCTGGCCTCCAGCA GGTACAGTGAGCAGGAGTCCTTCACCGTGGTTTTCCAGCCTTTCTTCTATGAGACCACCCCATCTGAC CCCCGACTCCAGGATTCTACCACGCTGGCCTGGCATCTCTGGAATAGGATGATGGAGCCAGCAGGAGA GAAAGATGAGCCATTGAGTGTAAAACACGGGAGGCCAATGAAGTGTCCCTCTCAGGAGAGCCCCTATC TGTTCAGCTACAGAAACAGCAACTACCTGACCAGACTGCAGAAACCCCAAGACAAGCTTGAGGTAAGA GAAGGAGCGGAAATCAGATGTCCTGACAAAGACCCCTCCGATACGGTTCCCACCTCAGTTCATAGGCT GAAGCCGGCTGACATCAACGTAATTGGAGCCCTGGGTGACTCTCTCACGGCAGGCAATGGGGCCGGGT CCACACCTGGGAACGTCTTGGACGTCTTGACTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGAT GAGAACATCGGCACCGTTACCACCCTGGCGGACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTT CTCTGTTGGCACTGGGAAAGAAACCAGTCCTAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAG CTGAGCAGGCCAGGAGGCTGGTGGACCTGATGAAGAATGACACGAGGATACACTTTCAGGAAGACTGG δ88 AAGATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTACACTATTC TCCCCAGAACTTCACAGACAACATTGGAAAGGCCCTGGACATCCTCCATGCTGAGGTTCCTCGGGCAT TTGTGAACCTGGTGACGGTGCTTGAGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAAAAAGTCTAC TGCCCAAGGATGATCCTCAGGTCACTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACT TGCTACCCTCATCGAATTCAACAAGAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGAT ATGACACAAGGGAAGATTTTACTGTGGTTGTGCAGCCGTTCTTTGAAAACGTGGACATGCCAAAGACC CAGGAAGGATTGCCTGACAACTCTTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTC CCGAGCAGCCAGTGCTCTCTGGAACAATATGCTGGAGCCTGTTGGCCAGAAGACGACTCGTCATAAGT TTGAAAACAAGATCAATATCACATGTCCGAACCAGGTAGAGTGGCCGTTTCTGAGGACCTACAAGAAC AGCATGCAGGGTCATGGGACCTGGCTGCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTC AGTGCATGCCCTGAGACCTGCAGACATCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCA ATGGAATTGGCTCCAAACCAGACGACCTCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGT GCAGGAGGGGACGGCTCCCTGGAGAATGTGACCACCTTACCTGATATCCTTCGGGAGTTTAACAGAAA CCTCACAGGCTACGCCGTGGGCACGGGTGATGCCAATGACACGAATGCATTCCTCAATCAAGCTGTTC CCGGAGCAAAGGCTAGGGATCTTATGAGCCAAGTCCAAACTCTGATGCAGAAGATGAAAGATGATCAT AGAGTAAATTTCCATGAAGACTGGAAGGTCATCACAGTGCTGATCGGAGGCAGCGATTTATGTGACTA CTGCACAGATTCGAATCTGTATTCTGCAGCCAACTTTGTTCACCATCTCCGCAATGCCTTGGACGTCC TGCATAGAGAGGTGCCCAGAGTCCTGGTCAACCTCGTGGACTTCCTGAACCCCACTATCATGCGGCAG GTGTTCCTGGGAAACCCAGACAAGTGCCCAGTGCAGCAGGCCAGCGTTTTGTGTAACTGCGTTCTGAC CCTGCGGGAGAACTCCCAAGAGCTAGCCAGGCTGGAGGCCTTCAGCCGAGCCTACCAGAGCAGCATGC GCGAGCTGGTGGGGTCAGGCCGCTATGACACGCAGGAGGACTTCTCTGTGGTGCTGCAGCCCTTCTTC CAGAACATCCAGCTCCCTGTCCTGCAGGATGGGCTCCCAGATACGTCCTTCTTTGCCCCAGACTGCAT CCACCCAAATCAGAAATTCCACTCCCAGCTGGCCAGAGCCCTTTGGACCAATATGCTTGAACCACTTG GAAGCAAAACAGAGACCCTGGACCTGAGAGCAGAGATGCCCATCACCTGTCCCACTCAGAATGAGCCC TTCCTGAGAACCCCTCGGAATAGTAACTACACGTACCCCATCAAGCCAGCCATTGAGAACTGGGGCAG TGACTTCCTGTGTACAGAGTGGAAGGCTTCCAATAGTGTTCCAACCTCTGTCCACCAGCTCCGACCAG CAGACATCAAAGTGGTGGCCGCCCTGGGTGACTCTCTGACTGTGGCAGTGGGAGCTCGACCAAACAAC TCCAGTGACCTACCCACATCTTGGAGGGGACTCTCTTGGAGCATTGGAGGGGATGGGAACTTGGAGAC
TCACACCACACTGCCCGACATTCTGAAGAAGTTCAACCCTTACCTCCTTGGCTTCTCTACCAGCACCT GGGAGGGGACAGCAGGACTAAATGTGGCAGCGGAAGGGGCCAGAGCTAGGGACATGCCAGCCCAGGCC TGGGACCTGGTAGAGCGAATGAAAAACAGCCCCCAGGACATCAACCTGGAGAAAGACTGGAAGCTGGT CACACTCTTCATTGGGGTCAACGACTTGTGTCATTACTGTGAGAATCCGGTAGGCGAATATGTTCAGC ACATCCAACAGGCCCTGGACATCCTCTCTGAGGAGCTCCCAAGGGCTTTCGTCAACGTGGTGGAGGTC ATGGAGCTGGCTAGCCTGTACCAGGGCCAAGGCGGGAAATGTGCCATGCTGGCAGCTCAGAACAACTG CACTTGCCTCAGACACTCGCAAAGCTCCCTGGAGAAGCAAGAACTGAAGAAAGTGAACTGGAACCTCC AGCATGGCATCTCCAGTTTCTCCTACTGGCACCAATACACACAGCGTGAGGACTTTGCGGTTGTGGTG CAGCCTTTCTTCCAAAACACACTCACCCCACTGAACAGAGGGGACACTGACCTCACCTTCTTCTCCGA GGACTGTTTTCACTTCTCAGACCGCGGGCATGCCGAGATGGCCATCGCACTCTGGAACAACATGCTGG AACCAGTGGGCCGCAAGACTACCTCCAACAACTTCACCCACAGCCGAGCCAAACTCAAGTGCCCCTCT CCTGAGAGCCCTTACCTCTACACCCTGCGGAACAGCCGATTGCTCCCAGACCAGGCTGAAGAAGCCCC CGAGGTGCTCTACTGGGCTGTCCCAGTGGCAGCGGGAGTCGGCCTTGTGGTGGGCATCATCGGGACAG TGGTCTGGAGGTGCAGGAGAGGTGGCCGGAGGGAAGATCCTCCAATGAGCCTGCGCACTGTGGCCCTC TAGGCCCGGGGGTGGGTCCTCACCCTAAACTCCCTATAGCCACTCTCTTCACCGCCCTCTGCCCCAGC
CACTCCCGGCCACCAGGACATGCTTCAATGCCTGGTGCCATAGGAAGCCCAGGGGACAGTCACAACTT
CTTGG
NOV65d, CG57399-03 SEQ ID NO: 9δ4 1423 aa MW at 159352/7kD Protein Sequence
MGLRPGIFLLELLLLLGQGTPQIHTSPRKSTLEGQLWPETVHSLKPSDIKFVAAIGNLEIVPDPGTGD LEKQDERPQQVCMGVMTVLSDIIRYFSPSVPMPVCHTGKRVIPHDGAEDLWIQAQELVRNMKENQLDF QFD KLINVFFSNASQCYLCPSAQQNGLAAGGVDELMGVLDYLQQEVPRAFVNLVDLSEVAEVSRQYH GT LSPAPEPCNCSEETTRLAKWMQ SYQEAWNSLLASSRYSEQESFTWFQPFFYETTPSDPRLQD STTLAWHLWNRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDKLEVREGAEI RCPDKDPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGLSWSVGGDENIGT VTTLADILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLVDLMKNDTRIHFQEDWKIITL FIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAEVPRAFVlsrLVTVLEIVNLRELYQEKKVYCPRMI LRSLCPCNflLKFDDNSTEI-ATLIEFNKKFQEKTHQLIESGRYDTREDFTV QPFFENVDMPKTQEGLP DNSFFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCPNQVEWPFLRTYKNSMQGH GTWLPCRDRAPSALHPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDG δδ9 SLENVTTLPDILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRVNFH EDWKVITVLIGGSDLCDYCTDSNLYSAANFVHHLRNALDVLHREVPRVLVNLVDFLNPTIMRQVFLGN PDKCPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRYDTQEDFSWLQPFFQNIQL PVLQDGLPDTSFFAPDCIHPNQKFHSQLARAL TNMLEPLGSKTETLDLRAEMPITCPTQNEPFLRTP RNSNYTYPIKPAIENWGSDFLCTE KASNSVPTSVHQLRPADIKWAALGDSLTVAVGARPNNSSDLP TS RGLS SIGGDGNLETHTTLPDILKKFNPYLLGFSTSTWEGTAGLNVAAEGARARDMPAQAWDLVE RMKNSPQDINLEKD KLVTLFIGVNDLCHYCENPVGEYVQHIQQALDILSEELPRAFVNVVEVMELAS LYQGQGGKCAMLAAQNNCTCLRHSQSSLEKQELKKVNWNLQHGISSFSYWHQYTQREDFAVWQPFFQ NTLTPLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLKCPSPESPY LYTLRNSRLLPDQAEEAPEVLYWAVPVAAGVGLWGIIGTWWRCRRGGRREDPPMSLRTVAL
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 65B.
Table 65B. Comparison of he NOV65 protein sequences.
NOV65a
NOV65b MTWDTAL TSVFLIGLLPTLGFANCILQTSGKMCTLRGRYPQPPQPPLCLSPLVHQLRPA
NOV65C
NOV65d MGLRPGIFLLELLLLLGQGTPQIHTSPRKSTLEGQLWP ETVHSLKPS
NOV65a
NOV65b DIKWAALGNDETFQESGAGQLSEPDPRQWSWPQACLPGVKKEMQDWGERTPSRRRSLR
NOV65C
NOV65d DIKFVAAIGNLEIVPDPGTGDLEKQDER PQQVCMGVMTVLSDIIRYFSPSVPMPVC
NOV65a
NOV65b RR-EALVPAAGKESLCRQDIFISLLEIIKHFPPSPQDINLEKD KLVTLFIGVNDLCHYC
NOV65C
NOV65d HTGKRVIPHDG AEDLWIQAQELVRNMKEN- -QLDFQFD KLINVFFSNASQCYLC
NOV65a
NOV65b PLVQGPVIDLGGMDTLH S-LQLPRAFVNWEVMELASLYQGQGG
NOV65C
NOV65d PSAQQNGLAAGGVDELMGVLDYLQQEVPRAFVNLVDLSEVAEVSRQYHGTWLSPAPEPCN
NOV65a
NOV65b K CAMLAAQEAWNSLLASSRYSEQESFTWFQPFFYETTPSDPRLQDSTTL
NOV65C
NOV65d CSEETTRLAKWMQWSYQEAWNSLLASSRYSEQESFTWFQPFFYETTPSDPRLQDSTTL
NOV65a
NOV65b AWHL NRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDK-LVRE
NOV65C
NOV65d A HLWNRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDKLEVRE
NOV65a
NOV65b GAEIRCPDKDPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGL
NOV65C
NOV65d GAEIRCPDKDPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGL
NOV65a
NOV65b S SVGGDENIGTVTTLADILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLV
NOV65C δ90 NOV65d S SVGGDENIGTVTTLADILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLV
NOV65a - -MKNDTRIHFQEDWKIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAE- -VP
NOV65b DLMKNDTRIHFQED KIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAESQVP
NOV65c - -MKNDTRIHFQEDWKIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAE- -VP
NOV65d DLMKNDTRIHFQED KIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAE- -VP
NOV65a RAFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQE
NOV65b RAFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQE
NOV65C RAFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQE
NOV65d RAFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQE
NOV65a KTHQLIESGRYDTREDFTWVRPFFENVDMPKTSEGLPDNSFFAPDCFHFSSKSHSRAAS
NOV65b KTHQLIESGRYDTREDFTVWQPFFENVDMPKTQEGLPDNSFFAPDCFHFSSKSHSRAAS
NOV65C KTHQLIESGRYDTREDFTVWQPFFENVDMPKTSEGLPDNSFFAPDCFHFSSKSHSRAAS
NOV65d KTHQLIESGRYDTREDFTVWQPFFENVDMPKTQEGLPDNSFFAPDCFHFSSKSHSRAAS
NOV65a AL NNMLEPVGQKTTRHKFENKINITCPNQVQP-FLRTYKNSMQGHGT LPCRDRAPSAL
NOV65b AL NNMLEPVGQKTTRHKFENKINITCPSQVQP-FLRTYKNSMQGHGTWLPCRDRAPSAL
NOV65C ALWNNMLEPVGQKTTRHKFENKINITCPNQVQP-FLRTYKNSMQGHGTWLPCRDRAPSAL
NOV65d ALWNNMLEPVGQKTTRHKFENKINITCPNQVEWPFLRTYKNSMQGHGTWLPCRDRAPSAL
NOV65a HPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYRESKPG
NOV65b HPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDGSLENVT
NOV65C HPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYRESKPG
NOV65d HPTSVHALRPADIQWAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDGSLENV-
NOV65a FLSDSWVSKSNRKCTRKAPNP
NOV65b TLPSSILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRV
NOV65C FLSDSWVSKSNRKCTRKAPNP
NOV65d TTLPDILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRV
NOV65a
NOV65b NFHEDWKVITVLIGGSDLCDYCTDSNLYSAANFVHHLRNALDVLHREVPRVLVNLVDFLN
NOV65C
NOV65d NFHEDWKVITVLIGGSDLCDYCTDSNLYSAANFVHHLRNALDVLHREVPRVLVNLVDFLN
NOV65a
NOV65b PTIMRQVFLGNPDKCPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRY
NOV65c
NOV65d PTIMRQVFLGNPDKCPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRY
NOV65a
NOV65b DTQEDFSWLQPFFQNIQLPVLQDGLPDTSFFAPDCIHPNQKFHSQLARALWTNMLEPLG
NOV65C
NOV65d DTQEDFSWLQPFFQNIQLPVLQDGLPDTSFFAPDCIHPNQKFHSQLARALWTNMLEPLG
NOV65a
NOV65b SKTETLDLRAEMPITCPTQNEPFLRTPRNSNYTYPIKPAIENWGSDFLCTEWKASNSVPT
NOV65c
NOV65d SKTETLDLRAEMPITCPTQNEPFLRTPRNSNYTYPIKPAIENWGSDFLCTEWKASNSVPT
NOV65a
NOV65b SVHQLRPADIKWAALGDSLTTAVGARPNNSSDLPTSWRGLSWSIGGDGNLETHTTLPSI N0V65c
NOV65d SVHQLRPADIKWAALGDSLTVAVGARPNNSSDLPTSWRGLSWSIGGDGNLETHTTLPDI
NOV65a
NOV65b LKKFNPYLLGFSTSTWEGTAGLNVAAEGARARRDMPAQAWDLVERMKNSP--IHFQEDWK
NOV65c
NOV65d LKKFNPYLLGFSTSTWEGTAGLNVAAEGARAR-DMPAQAWDLVERMKNSPQDINLEKDWK
NOV65a
NOV65b IITLFIGGNDLCDFCNDLVGEYVQHIQQALDILSEELPRAFVNWEVMELASLYQGQGGK
NOV65c
NOV65d LVTLFIGVNDLCHYCENPVGEYVQHIQQALDILSEELPRAFVNWEVMELASLYQGQGGK
NOV65a
NOV65b CAMLAAQNNCTCLRHSQSSLEKQELKKVNWNLQHGISSFSYWHQYTQREDFAVWQPFFQ
NOV65C
NOV65d CAMLAAQNNCTCLRHSQSSLEKQELKKVNWNLQHGISSFSYWHQYTQREDFAVWQPFFQ
NOV65a
NOV65b NTLTPLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLK
NOV65c
NOV65d NTLTPLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLK
NOV65a
NOV65b CPSPVSPYLYTLRNSRLLPDQAEEAPEVLYWAVPVAAGVGLWGIIGTWWRCRRGGRRE
NOV65C
NOV65d CPSPESPYLYTLRNSRLLPDQAEEAPEVLYWAVPVAAGVGLWGIIGTWWRCRRGGRRE
NOV65a
NOV65b DPPMSLRTVAL
NOV65C
NOV65d DPPMSLRTVAL
NOV65a (SEQ ID NO 978)
NOV65b (SEQ ID NO 980)
NOV65C (SEQ ID NO 982)
NOV65d (SEQ ID NO 984)
Further analysis ofthe NOV65a protein yielded the following properties shown in Table 65C.
Figure imgf000896_0001
possible cleavage site: between 28 and 29
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 1.43 (at 55) ALOM score: 1.43 (number of TMSs : 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 3.74 Hyd Moment(95): 6.40 G content: 0 D/E content: 2 S/T content: 1 Score: -6.13
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 12.3% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus : KAPN
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
87.0 %: nuclear 8.7 %: mitochondrial 4.3 %: peroxisomal
>> prediction for CG57399-04 is nuc (k=23)
A search ofthe NOV65a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 65D.
Figure imgf000899_0001
In a BLAST search of public sequence databases, the NOV65a protein was found to have homology to the proteins shown in the BLASTP data in Table 65E.
δ95
Figure imgf000900_0001
PFam analysis indicates that the NOV65a protein contains the domains shown in the Table 65F.
Figure imgf000900_0002
Example 66.
The NOV66 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 66A.
Table 66A. NOV66 Sequence Analysis
NOV66a, CG57562-02 SEQ ID NO: 985 3517 bp
DNA Sequence ORF Start: ATG at 5 ORF Stop: TGA at 3506
AAAGATGGCGGCAGCGGCGGCGGTGC 5GCAACGCGGTGCCCTGCGGGGCCCGGCCTTGCGGGGTCCGGC
CTGACGGGCAGCCCAAGCCCGGGCCC 5CAGCCGCGCGCGCTCCTTGC CGCCGGGCCGGCGCTCATAGCG AACGGTGACGAGCTGGTGGCTGCCGT 'GTGGCCGTACCGGCGGTTGG CGCTGTTGCGGCGCCTCACGGT GCTGCCATTCGCCGGGCTGCTTTACC :CGGCCTGGTTGGGTGCCGCΛGCCGCTGGCTGCTGGGGCTGGG GCAGCAGTTGGGTGCAGATCCCCGA2.GCTGCGCTGCTCGTGCTTGC CACCATCTGCCTCGCGCACGCG CTCACTGTCCTCTCGGGGCATTGGTCTGTGCACGCGCATTGCGCGCTCACCTGCACCCCGGAGTACGA CCCCAGCAAAGCGACCTTTGTGAAGGTGGTGCCAACCCCCAACAATGGCTCCACGGAGCTCGTGGCCC TGCACCGCAATGAGGGCGAAGACGGGCTTGAGGTGCTGTCCTTCGAATTCCAGAAGATCAAGTATTCC TACGATGCCCTGGAGAAGAAGCAGTTTCTCCCCGTGGCCTTTCCTGTGGGAAACGCCTTCTCATACTA TCAGAGCAACAGAGGCTTCCAGGAAGACTCAGAGATCCGAGCAGCTGAGAAGAAATTTGGGAGCAACA AGGCCGAGATGGTGGTGCCTGACTTCTCGGAGCTTTTCAAGGAGAGAGCCACAGCCCCCTTCTTTGTA TTTCAGGTGTTCTGTGTGGGGCTCTGGTGCCTGGATGAGTACTGGTACTACAGCGTCTTTACGCTATC CATGCTGGTGGCGTTCGAGGCCTCGCTGGTGCAGCAGCAGATGCGGAACATGTCGGAGATCCGGAAGA TGGGCAACAAGCCCCACATGATCCAGGTCTACCGAAGCCGCAAGTGGAGGCCCATTGCCAGTGATGAG ATCGTACCAGGGGACATCGTCTCCATCGGCCGCTCCCCACAGGAGAACCTGGTGCCATGTGACGTGCT TCTGCTGCGAGGCCGCTGCATCGTAGACGAGGCCATGCTCACGGGGGAGTCCGTGCCACAGATGAAGG AGCCCATCGAAGACCTCAGCCCAGACCGGGTGCTGGACCTCCAGGCTGATTCCCGGCTGCACGTCATC TTCGGGGGCACCAAGGTGGTGCAGCACATCCCCCCACAGAAAGCCACCACGGGCCTGAAGCCGGTTGA CAGCGGGTGCGTGGCCTACGTCCTGCGGACCGGATTCAACACATCCCAGGGCAAGCTGCTGCGCACCA TCCTCTTCGGGGTCAAGAGGGTGACTGCGAACAACCTGGAGACCTTCATCTTCATCCTCTTCCTCCTG GTGTTTGCCATCGCTGCAGCTGCCTATGTATGGATTGAAGGTACCAAGGACCCCAGCCGGAACCGCTA CAAGCTGTTTCTGGAGTGCACCCTGATCCTCACCTCGGTCGTGCCTCCTGAGCTGCCCATCGAGCTGT CCCTGGCCGTCAACACCTCCCTCATCGCCCTGGCCAAGCTCTACATGTACTGCACAGAGCCCTTCCGG ATCCCCTTTGCTGGCAAGGTCGAGGTGTGCTGCTTTGACAAGACGGGGACGTTGACCAGTGACAGCCT GGTGGTGCGCGGTGTGGCCGGGCTGAGAGACGGGAAGGAGGTGACCCCAGTGTCCAGCATCCCTGTAG AAACACACCGGGCCCTGGCCTCGTGCCACTCGCTCATGCAGCTGGACGACGGCACCCTCGTGGGTGAC CCTCTAGAGAAGGCCATGCTGACGGCCGTGGACTGGACGCTGACCAAAGATGAGAAAGTATTCCCCCG AAGTATTAAAACTCAGGGGCTGAAAATTCACCAGCGCTTTCATTTTGCCAGTGCCCTGAAGCGAATGT CCGTGCTTGCCTCGTATGAGAAGCTGGGCTCCACCGACCTTTGTTACATCGCGGCCGTGAAGGGGGCC CCCGAAACTCTGCACTCCATGGCCCGGGAGGTCAAGCGGGAGGCCCTGGAGTGCAGCCTCAAGTTCGT CGGCTTCATTGTGGTCTCCTGCCCGCTCAAGGCTGACTCGAAGGCCGTGATCCGGGAGATCCAGAATG CGTCCCACCGGGTGTTCATGATCACGGGAGACAACCCGCTCACTGCATGCCACGTGGCCCAGGAGCTG CACTTCATTGAAAAGGCCCACACGCTGATCCTGCAGCCTCCCTCCGAGAAAGGCCGGCAGTGCGAGTG GCGCTCCATTGACGGCAGCATCGTGCTGCCCCTGGCCCGGGGCTCCCCAAAGGCACTGGCCCTGGAGT ACGCACTGTGCCTCACAGGCGACGGCTTGGCCCACCTGCAGGCCACCGACCCCCAGCAGCTGCTCCGC CTCATCCCCCATGTGCAGGTGTTCGCCCGTGTGGCTCCCAAGCAGAAGGAGTTTGTCATCACCAGCCT GAAGGAGCTGGGCTACGTGACCCTCATGTGTGGGGATGGCACCAACGACGTGGGCGCCCTGAAGCATG CTGACGTGGGTGTGGCGCTCTTGGCCAATGCCCCTGAGCGGGTTGTCGAGCGGCGACGGCGGCCCCGG GACAGCCCAACCCTGAGCAACAGTGGCATCAGAGCCACCTCCAGGACAGCCAAGCAGCGGTCGGGGCT CCCTCCCTCCGAGGAGCAGCCAACCTCCCAGAGGGACCGCCTGAGCCAGGTGCTGCGAGACCTCGAGG ACGAGAGTACGCCCATTGTGAAACTGGGGGATGCCAGCATCGCAGCACCCTTCACCTCCAAGCTCTCA TCCATCCAGTGCATCTGCCACGTGATCAAGCAGGGCCGCTGCACGCTGGTGACCACGCTACAGATGTT CAAGATCCTGGCGCTCAATGCCCTCATCCTGGCCTACAGCCAGAGCGTCCTCTACCTGGAGGGAGTCA AGTTCAGTGACTTCCAGGCCACCCTACAGGGGCTGCTGCTGGCCGGCTGCTTCCTCTTCATCTCCCGT TCCAAGCCCCTCAAGACCCTCTCCCGAGAACGGCCCCTGCCCAACATCTTCAACCTGTACACCATCCT CACCGTCATGCTCCAGTTCTTTGTGCACTTCCTGAGCCTTGTCTACCTGTACCGTGAGGCCCAGGCCC GGAGCCCCGAGAAGCAGGAGCAGTTCGTGGACTTGTACAAGGAGTTTGAGCCAAGCCTGGTCAACAGC ACCGTCTACATCATGGCCATGGCCATGCAGATGGCCACCTTCGCCATCAATTACAAAGGCCCGCCCTT CATGGAGAGCCTGCCCGAGAACAAGCCCCTGGTGTGGAGTCTGGCAGTTTCACTCCTGGCCATCATTG
GCCTGCTCCTCGGCTCCTCGCCCGACTTCAACAGCCAGTTTGGCCTCGTGGACATCCCTGTGGAGTTC AAGCTGGTCATTGCCCAGGTCCTGCTCCTGGACTTCTGCCTGGCGCTCCTGGCCGACCGCGTCCTGCA GTTCTTCCTGGGGACCCCGAAGCTGAAAGTGCCTTCCTGAGATGGCAGT
NOV66a, CG57562-02 SEQ ID NO: 986 1167 aa MW at 128749.4kD Protein Sequence
MAAAAAVGNAVPCGARPCGVRPDGQPKPGPQPRALLAAGPALIANGDELVAAVWPYRRLALLRRLTVL PFAGLLYPA LGAAAAGC GWGSS VQIPEAALLVLATICLAHALTVLSGHWSVHAHCALTCTPEYDP SKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYSYDALEKKQFLPVAFPVGNAFSYYQ SNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKERATAPFFVFQVFCVGLWCLDEYWYYSVFTLSM LVAFEASLVQQQMRNMSEIRKMGNKPHMIQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLL LRGRCIVDEAMLTGESVPQMKEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDS GCVAYVLRTGFNTSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYK LFLECTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTSDSLV VRGVAGLRDGKEVTPVSS I PVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVD TLTKDEKVFPRS IKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETLHSMAREVKREALECSLKFVG FIWSCPLKADSKAVIREIQNASHRVFMITGDNPLTACHVAQELHFIEKAHTLILQPPSEKGRQCE R SIDGSIVLPLARGSPKALALEYALCLTGDGLAHLQATDPQQLLRLIPHVQVFARVAPKQKEFVITSLK ELGYVTLMCGDGTNDVGALKHADVGVALLANAPERWERRRRPRDSPTLSNSGIRATSRTAKQRSGLP PSEEQPTSQRDRLSQVLRDLEDESTPIVKLGDASIAAPFTSKLSSIQCICHVIKQGRCTLVTTLQMFK ILALNALILAYSQSVLYLEGVKFSDFQATLQGLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILT VMLQFFVHFLSLVYLYREAQARSPEKQEQFVDLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFM ESLPENKPLVWSLAVSLLAIIGLLLGSSPDFNSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQF FLGTPKLKVPS
NOV66b, CG57562-01 SEQ ID NO: 987 3904 bp DNA Sequence ORF Start: ATG at 68 ORF Stop: TGA at 3680
TTACCGGAAGTAAAACTTCGGAAGTGAGGCGTTCCTCTGCCCGGAAGTGAGCGCGGCGCTAGGAAAGA
TGGCGGCAGCGGCGGCGGTGGGCAACGCGGTGCCCTGCGGGGCCCGGCCTTGCGGGGTCCGGCCTGAC GGGCAGCCCAAGCCCGGGCGCAGCCGGCGCGCGCTCCTTGCCGCCGGGCCGGCGCTCATAGCGAACGG TGACGAGCTGGTGGCTGCCGTGTGGCCGTACCGGCGGTTGGCGCTGTTGCGGCGCCTCACGGTGCTGC CATTCGCCGGGCTGCTTTACCCGGCCTGGTTGGGTGCCGCAGCCGCTGGCTGCTGGGGCTGGGGCAGC AGTTGGGTGCAGATCCCCGAAGCTGCGCTGCTCGTGCTTGCCACCATCTGCCTCGCGCACGCGCTCAC TGTCCTCTCGGGGCATTGGTCTGTGCACGCGCATTGCGCGCTCACCTGCACCCCGGAGTACGACCCCA GCAAAGCGACCTTTGTGAAGGTGGTGCCAACCCCCAACAATGGCTCCACGGAGCTCGTGGCCCTGCAC CGCAATGAGGGCGAAGACGGGCTTGAGGTGCTGTCCTTCGAATTCCAGAAGATCAAGTATTCCTACGA TGCCCTGGAGAAGAAGCAGTTTCTCCCCGTGGCCTTTCCTGTGGGAAACGCCTTCTCATACTATCAGA GCAACAGAGGCTTCCAGGAAGACTCAGAGATCCGAGCAGCTGAGAAGAAATTTGGGAGCAACAAGGCC GAGATGGTGGTGCCTGACTTCTCGGAGCTTTTCAAGGAGAGAGCCACAGCCCCCTTCTTTGTATTTCA GGTGTTCTGTGTGGGGCTCTGGTGCCTGGATGAGTACTGGTACTACAGCGTCTTTACGCTATCCATGC TGGTGGCGTTCGAGGCCTCGCTGGTGCAGCAGCAGATGCGGAACATGTCGGAGATCCGGAAGATGGGC AACAAGCCCCACATGATCCAGGTCTACCGAAGCCGCAAGTGGAGGCCCATTGCCAGTGATGAGATCGT ACCAGGGGACATCGTCTCCATCGGCCGCTCCCCACAGGAGAACCTGGTGCCATGTGACGTGCTTCTGC TGCGAGGCCGCTGCATCGTAGACGAGGCCATGCTCACGGGGGAGTCCGTGCCACAGATGAAGGAGCCC ATCGAAGACCTCAGCCCAGACCGGGTGCTGGACCTCCAGGCTGATTCCCGGCTGCACGTCATCTTCGG GGGCACCAAGGTGGTGCAGCACATCCCCCCACAGAAAGCCACCACGGGCCTGAAGCCGGTTGACAGCG GGTGCGTGGCCTACGTCCTGCGGACCGGATTCAACACATCCCAGGGCAAGCTGCTGCGCACCATCCTC TTCGGGGTCAAGAGGGTGACTGCGAACAACCTGGAGACCTTCATCTTCATCCTCTTCCTCCTGGTGTT TGCCATCGCTGCAGCTGCCTATGTATGGATTGAAGGTACCAAGGACCCCAGCCGGAACCGCTACAAGC TGTTTCTGGAGTGCACCCTGATCCTCACCTCGGTCGTGCCTCCTGAGCTGCCCATCGAGCTGTCCCTG GCCGTCAACACCTCCCTCATCGCCCTGGCCAAGCTCTACATGTACTGCACAGAGCCCTTCCGGATCCC CTTTGCTGGCAAGGTCGAGGTGTGCTGCTTTGACAAGACGGGGACGTTGACCAGTGACAGCCTGGTGG TGCGCGGTGTGGCCGGGCTGAGAGACGGGAAGGAGGTGACCCCAGTGTCCAGCATCCCTGTAGAAACA CACCGGGCCCTGGCCTCGTGCCACTCGCTCATGCAGCTGGACGACGGCACCCTCGTGGGTGACCCTCT AGAGAAGGCCATGCTGACGGCCGTGGACTGGACGCTGACCAAAGATGAGAAAGTATTCCCCCGAAGTA TTAAAACTCAGGGGCTGAAAATTCACCAGCGCTTTCATTTTGCCAGTGCCCTGAAGCGAATGTCCGTG CTTGCCTCGTATGAGAAGCTGGGCTCCACCGACCTCTGCTACATCGCGGCCGTGAAGGGGGCCCCCGA AACTCTGCACTCCATGTTCTCCCAGTGCCCGCCCGACTACCACCACATCCACACCGAGATCTCCCGGG AAGGAGCCCGCGTCCTGGCGCTGGGGTACAAGGAGCTGGGACACCTCACTCACCAGCAGGCCCGGGAG GTCAAGCGGGAGGCCCTGGAGTGCAGCCTCAAGTTCGTCGGCTTCATTGTGGTCTCCTGCCCGCTCAA GGCTGACTCCAAGGCCGTGATCCGGGAGATCCAGAATGCGTCCCACCGGGTGGTCATGATCACGGGAG ACAACCCGCTCACTGCATGCCACGTGGCCCAGGAGCTGCACTTCATTGAAAAGGCCCACACGCTGATC CTGCAGCCTCCCTCCGAGAAAGGCCGGCAGTGCGAGTGGCGCTCCATTGACGGCAGCATCGTGCTGCC CCTGGCCCGGGGCTCCCCAAAGGCACTGGCCCTGGAGTACGCACTGTGCCTCACAGGCGACGGCTTGG CCCACCTGCAGGCCACCGACCCCCAGCAGCTGCTCCGCCTCATCCCCCATGTGCAGGTGTTCGCCCGT GTGGCTCCCAAGCAGAAGGAGTTTGTCATCACCAGCCTGAAGGAGCTGGGCTACGTGACCCTCATGTG TGGGGATGGCACCAACGACGTGGGCGCCCTGAAGCATGCTGACGTGGGTGTGGCGCTCTTGGCCAATG CCCCTGAGCGGGTTGTCGAGCGGCGACGGCGGCCCCGGGACAGCCCAACCCTGAGCAACAGTGGCATC AGAGCCACCTCCAGGACAGCCAAGCAGCGGTCGGGGCTCCCTCCCTCCGAGGAGCAGCCAACCTCCCA GAGGGACCGCCTGAGCCAGGTGCTGCGAGACCTCGAGGACGAGAGTACGCCCATTGTGAAACTGGGGG ATGCCAGCATCGCAGCACCCTTCACCTCCAAGCTCTCATCCATCCAGTGCATCTGCCACGTGATCAAG CAGGGCCGCTGCACGCTGGTGACCACGCTACAGATGTTCAAGATCCTGGCGCTCAATGCCCTCATCCT GGCCTACAGCCAGAGCGTCCTCTACCTGGAGGGAGTCAAGTTCAGTGACTTCCAGGCCACCCTACAGG GGCTGCTGCTGGCCGGCTGCTTCCTCTTCATCTCCCGTTCCAAGCCCCTCAAGACCCTCTCCCGAGAA
89δ CGGCCCCTGCCCAACATCTTCAACCTGTACACCATCCTCACCGTCATGCTCCAGTTCTTTGTGCACTT CCTGAGCCTTGTCTACCTGTACCGTGAGGCCCAGGCCCGGAGCCCCGAGAAGCAGGAGCAGTTCGTGG
ACTTGTACAAGGAGTTTGAGCCAAGCCTGGTCAACAGCACCGTCTACATCATGGCCATGGCCATGCAG ATGGCCACCTTCGCCATCAATTACAAAGGCCCGCCCTTCATGGAGAGCCTGCCCGAGAACAAGCCCCT GGTGTGGAGTCTGGCAGTTTCACTCCTGGCCATCATTGGCCTGCTCCTCGGCTCCTCGCCCGACTTCA ACAGCCAGTTTGGCCTCGTGGACATCCCTGTGGAGTTCAAGCTGGTCATTGCCCAGGTCCTGCTCCTG GACTTCTGCCTGGCGCTCCTGGCCGACCGCGTCCTGCAGTTCTTCCTGGGGACCCCGAAGCTGAAAGT GCCTTCCTGAGATGGCAGTGCTGGTACCCACTGCCCACCCTGGCTGCCGCTGGGCGGGAACCCCAACA
GGGCCCCGGGAGGGAACCCTGCCCCCAACCCCCCACAGCAAGGCTGTACAGTCTCGCCCTTGGAAGAC
TGAGCTGGGACCCCCACAGCCATCCGCTGGCTTGGCCAGCAGAACCAGCCCCAAGCCAGCACCTTTGG
TAAATAAAGCAGCATCTGAGATTTTAAA
NOV66b, CG57562-01 SEQ ID NO: 9δ8 1204 aa MW at l33030.2kD Protein Sequence
MAAAAAVGNAVPCGARPCGVRPDGQPKPGRSRRALLAAGPALIANGDELVAAVWPYRRLALLRRLTVL PFAGLLYPA LGAAAAGC GWGSSWVQIPEAALLVLATICLAHALTVLSGHWSVHAHCALTCTPEYDP SKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYSYDALEKKQFLPVAFPVGNAFSYYQ SNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKERATAPFFVFQVFCVGLWCLDEYWYYSVFTLSM LVAFEASLVQQQMRNMSEIRKMGNKPHMIQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLL LRGRCIVDEAMLTGESVPQMKEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDS GCVAYVLRTGFNTSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYK LFLECTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTSDSLV VRGVAGLRDGKEVTPVSSIPVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVD TLTKDEKVFPRS IKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETLHSMFSQCPPDYHHIHTEISR EGARVLALGYKELGHLTHQQAREVKREALECSLKFVGFIWSCPLKADSKAVIREIQNASHRWMITG DNPLTACHVAQELHFIEKAHTLILQPPSEKGRQCE RSIDGSIVLPLARGSPKALALEYALCLTGDGL AHLQATDPQQLLRLIPHVQVFARVAPKQKEFVITSLKELGYVTLMCGDGTNDVGALKHADVGVALLAN APERWERRRRPRDSPTLSNSGIRATSRTAKQRSGLPPSEEQPTSQRDRLSQVLRDLEDESTPIVKLG DASIAAPFTSKLSSIQCICHVIKQGRCTLVTTLQMFKILALNALILAYSQSVLYLEGVKFSDFQATLQ GLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILTVMLQFFVHFLSLVYLYREAQARSPEKQEQFV DLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFMESLPENKPLV SLAVSLLAIIGLLLGSSPDF NSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQFFLGTPKLKVPS
NOV66c, SNPl 3380762 of SEQ ID NO: 989 3517 bp CG57562-02, DNA Sequence ORF Start: ATG at 5 ORF Stop: TGA at 3506
SNP Pos: 756 SNP Change: T to C
AAAGATGGCGGCAGCGGCGGCGGTGGGCAACGCGGTGCCCTGCGGGGCCCGGCCTTGCGGGGTCCGGC
CTGACGGGCAGCCCAAGCCCGGGCCGCAGCCGCGCGCGCTCCTTGCCGCCGGGCCGGCGCTCATAGCG AACGGTGACGAGCTGGTGGCTGCCGTGTGGCCGTACCGGCGGTTGGCGCTGTTGCGGCGCCTCACGGT GCTGCCATTCGCCGGGCTGCTTTACCCGGCCTGGTTGGGTGCCGCAGCCGCTGGCTGCTGGGGCTGGG GCAGCAGTTGGGTGCAGATCCCCGAAGCTGCGCTGCTCGTGCTTGCCACCATCTGCCTCGCGCACGCG CTCACTGTCCTCTCGGGGCATTGGTCTGTGCACGCGCATTGCGCGCTCACCTGCACCCCGGAGTACGA CCCCAGCAAAGCGACCTTTGTGAAGGTGGTGCCAACCCCCAACAATGGCTCCACGGAGCTCGTGGCCC TGCACCGCAATGAGGGCGAAGACGGGCTTGAGGTGCTGTCCTTCGAATTCCAGAAGATCAAGTATTCC TACGATGCCCTGGAGAAGAAGCAGTTTCTCCCCGTGGCCTTTCCTGTGGGAAACGCCTTCTCATACTA TCAGAGCAACAGAGGCTTCCAGGAAGACTCAGAGATCCGAGCAGCTGAGAAGAAATTTGGGAGCAACA AGGCCGAGATGGTGGTGCCTGACTTCTCGGAGCTTTTCAAGGAGAGAGCCACAGCCCCCTTCTTTGTA TTTCAGGCGTTCTGTGTGGGGCTCTGGTGCCTGGATGAGTACTGGTACTACAGCGTCTTTACGCTATC CATGCTGGTGGCGTTCGAGGCCTCGCTGGTGCAGCAGCAGATGCGGAACATGTCGGAGATCCGGAAGA TGGGCAACAAGCCCCACATGATCCAGGTCTACCGAAGCCGCAAGTGGAGGCCCATTGCCAGTGATGAG ATCGTACCAGGGGACATCGTCTCCATCGGCCGCTCCCCACAGGAGAACCTGGTGCCATGTGACGTGCT TCTGCTGCGAGGCCGCTGCATCGTAGACGAGGCCATGCTCACGGGGGAGTCCGTGCCACAGATGAAGG AGCCCATCGAAGACCTCAGCCCAGACCGGGTGCTGGACCTCCAGGCTGATTCCCGGCTGCACGTCATC TTCGGGGGCACCAAGGTGGTGCAGCACATCCCCCCACAGAAAGCCACCACGGGCCTGAAGCCGGTTGA CAGCGGGTGCGTGGCCTACGTCCTGCGGACCGGATTCAACACATCCCAGGGCAAGCTGCTGCGCACCA TCCTCTTCGGGGTCAAGAGGGTGACTGCGAACAACCTGGAGACCTTCATCTTCATCCTCTTCCTCCTG GTGTTTGCCATCGCTGCAGCTGCCTATGTATGGATTGAAGGTACCAAGGACCCCAGCCGGAACCGCTA CAAGCTGTTTCTGGAGTGCACCCTGATCCTCACCTCGGTCGTGCCTCCTGAGCTGCCCATCGAGCTGT CCCTGGCCGTCAACACCTCCCTCATCGCCCTGGCCAAGCTCTACATGTACTGCACAGAGCCCTTCCGG ATCCCCTTTGCTGGCAAGGTCGAGGTGTGCTGCTTTGACAAGACGGGGACGTTGACCAGTGACAGCCT GGTGGTGCGCGGTGTGGCCGGGCTGAGAGACGGGAAGGAGGTGACCCCAGTGTCCAGCATCCCTGTAG AAACACACCGGGCCCTGGCCTCGTGCCACTCGCTCATGCAGCTGGACGACGGCACCCTCGTGGGTGAC CCTCTAGAGAAGGCCATGCTGACGGCCGTGGACTGGACGCTGACCAAAGATGAGAAAGTATTCCCCCG AAGTATTAAAACTCAGGGGCTGAAAATTCACCAGCGCTTTCATTTTGCCAGTGCCCTGAAGCGAATGT CCGTGCTTGCCTCGTATGAGAAGCTGGGCTCCACCGACCTTTGTTACATCGCGGCCGTGAAGGGGGCC CCCGAAACTCTGCACTCCATGGCCCGGGAGGTCAAGCGGGAGGCCCTGGAGTGCAGCCTCAAGTTCGT CGGCTTCATTGTGGTCTCCTGCCCGCTCAAGGCTGACTCGAAGGCCGTGATCCGGGAGATCCAGAATG CGTCCCACCGGGTGTTCATGATCACGGGAGACAACCCGCTCACTGCATGCCACGTGGCCCAGGAGCTG CACTTCATTGAAAAGGCCCACACGCTGATCCTGCAGCCTCCCTCCGAGAAAGGCCGGCAGTGCGAGTG GCGCTCCATTGACGGCAGCATCGTGCTGCCCCTGGCCCGGGGCTCCCCAAAGGCACTGGCCCTGGAGT ACGCACTGTGCCTCACAGGCGACGGCTTGGCCCACCTGCAGGCCACCGACCCCCAGCAGCTGCTCCGC CTCATCCCCCATGTGCAGGTGTTCGCCCGTGTGGCTCCCAAGCAGAAGGAGTTTGTCATCACCAGCCT GAAGGAGCTGGGCTACGTGACCCTCATGTGTGGGGATGGCACCAACGACGTGGGCGCCCTGAAGCATG CTGACGTGGGTGTGGCGCTCTTGGCCAATGCCCCTGAGCGGGTTGTCGAGCGGCGACGGCGGCCCCGG GACAGCCCAACCCTGAGCAACAGTGGCATCAGAGCCACCTCCAGGACAGCCAAGCAGCGGTCGGGGCT CCCTCCCTCCGAGGAGCAGCCAACCTCCCAGAGGGACCGCCTGAGCCAGGTGCTGCGAGACCTCGAGG ACGAGAGTACGCCCATTGTGAAACTGGGGGATGCCAGCATCGCAGCACCCTTCACCTCCAAGCTCTCA TCCATCCAGTGCATCTGCCACGTGATCAAGCAGGGCCGCTGCACGCTGGTGACCACGCTACAGATGTT CAAGATCCTGGCGCTCAATGCCCTCATCCTGGCCTACAGCCAGAGCGTCCTCTACCTGGAGGGAGTCA AGTTCAGTGACTTCCAGGCCACCCTACAGGGGCTGCTGCTGGCCGGCTGCTTCCTCTTCATCTCCCGT TCCAAGCCCCTCAAGACCCTCTCCCGAGAACGGCCCCTGCCCAACATCTTCAACCTGTACACCATCCT CACCGTCATGCTCCAGTTCTTTGTGCACTTCCTGAGCCTTGTCTACCTGTACCGTGAGGCCCAGGCCC GGAGCCCCGAGAAGCAGGAGCAGTTCGTGGACTTGTACAAGGAGTTTGAGCCAAGCCTGGTCAACAGC ACCGTCTACATCATGGCCATGGCCATGCAGATGGCCACCTTCGCCATCAATTACAAAGGCCCGCCCTT CATGGAGAGCCTGCCCGAGAACAAGCCCCTGGTGTGGAGTCTGGCAGTTTCACTCCTGGCCATCATTG
GCCTGCTCCTCGGCTCCTCGCCCGACTTCAACAGCCAGTTTGGCCTCGTGGACATCCCTGTGGAGTTC AAGCTGGTCATTGCCCAGGTCCTGCTCCTGGACTTCTGCCTGGCGCTCCTGGCCGACCGCGTCCTGCA GTTCTTCCTGGGGACCCCGAAGCTGAAAGTGCCTTCCTGAGATGGCAGT
NOV66c, SNP13380762 of SEQ ID NO: 990 1167 aa MW at l2δ721.4kD CG57562-02, Protein Sequence SNP Pos: 251 SNP Change: Val to Ala
MAAAAAVGNAVPCGARPCGVRPDGQPKPGPQPRALLAAGPALIANGDELVAAV PYRRLALLRRLTVL PFAGLLYPAWLGAAAAGCWGWGSSWVQIPEAALLVLATICLAHALTVLSGHWSVHAHCALTCTPEYDP SKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYSYDALEKKQFLPVAFPVGNAFSYYQ SNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKERATAPFFVFQAFCVGLWCLDEYWYYSVFTLSM LVAFEASLVQQQMRNMSEIRKMGNKPHMIQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLL LRGRCIVDEAMLTGESVPQMKEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDS GCVAYVLRTGFNTSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYK LFLECTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTSDSLV VRGVAGLRDGKEVTPVSSIPVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVDWTLTKDEKVFPRS IKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETLHSMAREVKREALECSLKFVG FIWSCPLKADSKAVIREIQNASHRVFMITGDNPLTACHVAQELHFIEKAHTLILQPPSEKGRQCEWR SIDGSIVLPLARGSPKALALEYALCLTGDGLAHLQATDPQQLLRLIPHVQVFARVAPKQKEFVITSLK ELGYVTLMCGDGTNDVGALKHADVGVALLANAPERWERRRRPRDSPTLSNSGIRATSRTAKQRSGLP PSEEQPTSQRDRLSQVLRDLEDESTPIVKLGDASIAAPFTSKLSSIQCICHVIKQGRCTLVTTLQMFK ILALNALILAYSQSVLYLEGVKFSDFQATLQGLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILT VMLQFFVHFLSLVYLYREAQARSPEKQEQFVDLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFM ESLPENKPLVWSLAVSLLAIIGLLLGSSPDFNSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQF FLGTPKLKVPS
NOV66d, SNP133δ07δ7 of SEQ ID NO: 991 3517 bp CG57562-02, DNA Sequence ORF Start: ATG at 5 ORF Stop: TGA at 3506
SNP Pos: 2732 SNP Change: C to A
AAAGATGGCGGCAGCGGCGGCGGTGGGCAACGCGGTGCCCTGCGGGGCCCGGCCTTGCGGGGTCCGGC
CTGACGGGCAGCCCAAGCCCGGGCCGCAGCCGCGCGCGCTCCTTGCCGCCGGGCCGGCGCTCATAGCG AACGGTGACGAGCTGGTGGCTGCCGTGTGGCCGTACCGGCGGTTGGCGCTGTTGCGGCGCCTCACGGT GCTGCCATTCGCCGGGCTGCTTTACCCGGCCTGGTTGGGTGCCGCAGCCGCTGGCTGCTGGGGCTGGG GCAGCAGTTGGGTGCAGATCCCCGAAGCTGCGCTGCTCGTGCTTGCCACCATCTGCCTCGCGCACGCG CTCACTGTCCTCTCGGGGCATTGGTCTGTGCACGCGCATTGCGCGCTCACCTGCACCCCGGAGTACGA CCCCAGCAAAGCGACCTTTGTGAAGGTGGTGCCAACCCCCAACAATGGCTCCACGGAGCTCGTGGCCC TGCACCGCAATGAGGGCGAAGACGGGCTTGAGGTGCTGTCCTTCGAATTCCAGAAGATCAAGTATTCC TACGATGCCCTGGAGAAGAAGCAGTTTCTCCCCGTGGCCTTTCCTGTGGGAAACGCCTTCTCATACTA TCAGAGCAACAGAGGCTTCCAGGAAGACTCAGAGATCCGAGCAGCTGAGAAGAAATTTGGGAGCAACA AGGCCGAGATGGTGGTGCCTGACTTCTCGGAGCTTTTCAAGGAGAGAGCCACAGCCCCCTTCTTTGTA TTTCAGGTGTTCTGTGTGGGGCTCTGGTGCCTGGATGAGTACTGGTACTACAGCGTCTTTACGCTATC CATGCTGGTGGCGTTCGAGGCCTCGCTGGTGCAGCAGCAGATGCGGAACATGTCGGAGATCCGGAAGA TGGGCAACAAGCCCCACATGATCCAGGTCTACCGAAGCCGCAAGTGGAGGCCCATTGCCAGTGATGAG ATCGTACCAGGGGACATCGTCTCCATCGGCCGCTCCCCACAGGAGAACCTGGTGCCATGTGACGTGCT TCTGCTGCGAGGCCGCTGCATCGTAGACGAGGCCATGCTCACGGGGGAGTCCGTGCCACAGATGAAGG AGCCCATCGAAGACCTCAGCCCAGACCGGGTGCTGGACCTCCAGGCTGATTCCCGGCTGCACGTCATC TTCGGGGGCACCAAGGTGGTGCAGCACATCCCCCCACAGAAAGCCACCACGGGCCTGAAGCCGGTTGA CAGCGGGTGCGTGGCCTACGTCCTGCGGACCGGATTCAACACATCCCAGGGCAAGCTGCTGCGCACCA TCCTCTTCGGGGTCAAGAGGGTGACTGCGAACAACCTGGAGACCTTCATCTTCATCCTCTTCCTCCTG GTGTTTGCCATCGCTGCAGCTGCCTATGTATGGATTGAAGGTACCAAGGACCCCAGCCGGAACCGCTA CAAGCTGTTTCTGGAGTGCACCCTGATCCTCACCTCGGTCGTGCCTCCTGAGCTGCCCATCGAGCTGT CCCTGGCCGTCAACACCTCCCTCATCGCCCTGGCCAAGCTCTACATGTACTGCACAGAGCCCTTCCGG ATCCCCTTTGCTGGCAAGGTCGAGGTGTGCTGCTTTGACAAGACGGGGACGTTGACCAGTGACAGCCT GGTGGTGCGCGGTGTGGCCGGGCTGAGAGACGGGAAGGAGGTGACCCCAGTGTCCAGCATCCCTGTAG AAACACACCGGGCCCTGGCCTCGTGCCACTCGCTCATGCAGCTGGACGACGGCACCCTCGTGGGTGAC CCTCTAGAGAAGGCCATGCTGACGGCCGTGGACTGGACGCTGACCAAAGATGAGAAAGTATTCCCCCG AAGTATTAAAACTCAGGGGCTGAAAATTCACCAGCGCTTTCATTTTGCCAGTGCCCTGAAGCGAATGT CCGTGCTTGCCTCGTATGAGAAGCTGGGCTCCACCGACCTTTGTTACATCGCGGCCGTGAAGGGGGCC CCCGAAACTCTGCACTCCATGGCCCGGGAGGTCAAGCGGGAGGCCCTGGAGTGCAGCCTCAAGTTCGT CGGCTTCATTGTGGTCTCCTGCCCGCTCAAGGCTGACTCGAAGGCCGTGATCCGGGAGATCCAGAATG CGTCCCACCGGGTGTTCATGATCACGGGAGACAACCCGCTCACTGCATGCCACGTGGCCCAGGAGCTG CACTTCATTGAAAAGGCCCACACGCTGATCCTGCAGCCTCCCTCCGAGAAAGGCCGGCAGTGCGAGTG GCGCTCCATTGACGGCAGCATCGTGCTGCCCCTGGCCCGGGGCTCCCCAAAGGCACTGGCCCTGGAGT ACGCACTGTGCCTCACAGGCGACGGCTTGGCCCACCTGCAGGCCACCGACCCCCAGCAGCTGCTCCGC CTCATCCCCCATGTGCAGGTGTTCGCCCGTGTGGCTCCCAAGCAGAAGGAGTTTGTCATCACCAGCCT GAAGGAGCTGGGCTACGTGACCCTCATGTGTGGGGATGGCACCAACGACGTGGGCGCCCTGAAGCATG CTGACGTGGGTGTGGCGCTCTTGGCCAATGCCCCTGAGCGGGTTGTCGAGCGGCGACGGCGGCCCCGG GACAGCCCAACCCTGAGCAACAGTGGCATCAGAGCCACCTCCAGGACAGCCAAGCAGCGGTCGGGGCT CCCTCCCTCCGAGGAGCAGCCAACCTCCCAGAGGGACCGCCTGAGCCAGGTGCTGCGAGACCTCGAGG ACGAGAGTACGACCATTGTGAAACTGGGGGATGCCAGCATCGCAGCACCCTTCACCTCCAAGCTCTCA TCCATCCAGTGCATCTGCCACGTGATCAAGCAGGGCCGCTGCACGCTGGTGACCACGCTACAGATGTT CAAGATCCTGGCGCTCAATGCCCTCATCCTGGCCTACAGCCAGAGCGTCCTCTACCTGGAGGGAGTCA AGTTCAGTGACTTCCAGGCCACCCTACAGGGGCTGCTGCTGGCCGGCTGCTTCCTCTTCATCTCCCGT TCCAAGCCCCTCAAGACCCTCTCCCGAGAACGGCCCCTGCCCAACATCTTCAACCTGTACACCATCCT CACCGTCATGCTCCAGTTCTTTGTGCACTTCCTGAGCCTTGTCTACCTGTACCGTGAGGCCCAGGCCC GGAGCCCCGAGAAGCAGGAGCAGTTCGTGGACTTGTACAAGGAGTTTGAGCCAAGCCTGGTCAACAGC ACCGTCTACATCATGGCCATGGCCATGCAGATGGCCACCTTCGCCATCAATTACAAAGGCCCGCCCTT CATGGAGAGCCTGCCCGAGAACAAGCCCCTGGTGTGGAGTCTGGCAGTTTCACTCCTGGCCATCATTG
GCCTGCTCCTCGGCTCCTCGCCCGACTTCAACAGCCAGTTTGGCCTCGTGGACATCCCTGTGGAGTTC AAGCTGGTCATTGCCCAGGTCCTGCTCCTGGACTTCTGCCTGGCGCTCCTGGCCGACCGCGTCCTGCA GTTCTTCCTGGGGACCCCGAAGCTGAAAGTGCCTTCCTGAGATGGCAGT
NOV66d, SNPl 3380787 of SEQ ID NO: 992 1167 aa MW at 128753.4kD CG57562-02, Protein Sequence SNP Pos: 910 SNP Change: Pro to Thr
MAAAAAVGNAVPCGARPCGVRPDGQPKPGPQPRALLAAGPALIANGDELVAAVWPYRRLALLRRLTVL PFAGLLYPAWLGAAAAGCWGWGSSWVQIPEAALLVLATICLAHALTVLSGHWSVHAHCALTCTPEYDP SKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYSYDALEKKQFLPVAFPVGNAFSYYQ SNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKERATAPFFVFQVFCVGLWCLDEYWYYSVFTLSM LVAFEASLVQQQMRNMSEIRKMGNKPHMIQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLL LRGRCIVDEAMLTGESVPQMKEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDS GCVAYVLRTGFNTSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYK LFLECTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTSDSLV VRGVAGLRDGKEVTPVSSIPVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVDWTLTKDEKVFPRS IKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETLHSMAREVKREALECSLKFVG FIWSCPLKADSKAVIREIQNASHRVFMITGDNPLTACHVAQELHFIEKAHTLILQPPSEKGRQCEWR SIDGSIVLPLARGSPKALALEYALCLTGDGLAHLQATDPQQLLRLIPHVQVFARVAPKQKEFVITSLK ELGYVTLMCGDGTNDVGALKHADVGVALLANAPERWERRRRPRDSPTLSNSGIRATSRTAKQRSGLP PSEEQPTSQRDRLSQVLRDLEDESTTIVKLGDASIAAPFTSKLSSIQCICHVIKQGRCTLVTTLQMFK ILALNALILAYSQSVLYLEGVKFSDFQATLQGLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILT VMLQFFVHFLSLVYLYREAQARSPEKQEQFVDLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFM ESLPENKPLVWSLAVSLLAIIGLLLGSSPDFNSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQF FLGTPKLKVPS
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 66B.
Table 66B. Comparison of the NOV66 protein sequences.
NOV66a MAAAAAVGNAVPCGARPCGVRPDGQPKPGPQPRALLAAGPALIANGDELVAAVWPYRRLA
NOV66b MAAAAAVGNAVPCGARPCGVRPDGQPKPGRSRRALLAAGPALIANGDELVAAVWPYRRLA
NOV66a LLRRLTVLPFAGLLYPAWLGAAAAGC GWGSSWVQIPEAALLVLATICLAHALTVLSGHW
NOV66b LLRRLTVLPFAGLLYPA LGAAAAGCWG GSSWVQIPEAALLVLATICLAHALTVLSGHW
NOV66a SVHAHCALTCTPEYDPSKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYS
NOV66b SVHAHCALTCTPEYDPSKATFVKWPTPNNGSTELVALHRNEGEDGLEVLSFEFQKIKYS
NOV66a YDALEKKQFLPVAFPVGNAFSYYQSNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKE
NOV66b YDALEKKQFLPVAFPVGNAFSYYQSNRGFQEDSEIRAAEKKFGSNKAEMWPDFSELFKE
NOV66a RATAPFFVFQVFCVGLWCLDEYWYYSVFTLSMLVAFEASLVQQQMRNMSEIRKMGNKPHM
NOV66b RATAPFFVFQVFCVGLWCLDEYWYYSVFTLSMLVAFEASLVQQQMRNMSEIRKMGNKPHM
NOV66a IQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLLLRGRCIVDEAMLTGESVPQM
NOV66b IQVYRSRKWRPIASDEIVPGDIVSIGRSPQENLVPCDVLLLRGRCIVDEAMLTGESVPQM
NOV66a KEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDSGCVAYVLRTGFN
NOV66b KEPIEDLSPDRVLDLQADSRLHVIFGGTKWQHIPPQKATTGLKPVDSGCVAYVLRTGFN
NOV66a TSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYKLFLE
NOV66b TSQGKLLRTILFGVKRVTANNLETFIFILFLLVFAIAAAAYVWIEGTKDPSRNRYKLFLE
NOV66a CTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTS
NOV66b CTLILTSWPPELPIELSLAVNTSLIALAKLYMYCTEPFRIPFAGKVEVCCFDKTGTLTS
NOV66a DSLWRGVAGLRDGKEVTPVSSIPVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVDW
NOV66b DSLWRGVAGLRDGKEVTPVSSIPVETHRALASCHSLMQLDDGTLVGDPLEKAMLTAVDW
NOV66a TLTKDEKVFPRSIKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETL
NOV66b TLTKDEKVFPRSIKTQGLKIHQRFHFASALKRMSVLASYEKLGSTDLCYIAAVKGAPETL
NOV66a HSM AREVKREALECSLKFVGFIV
NOV66b HSMFSQCPPDYHHIHTEISREGARVLALGYKELGHLTHQQAREVKREALECSLKFVGFIV
NOV66a VSCPLKADSKAVIREIQNASHRVFMITGDNPLTACHVAQELHFIEKAHTLILQPPSEKGR NOV66b VSCPLKADSKAVIREIQNASHRWMITGDNPLTACHVAQELHFIEKAHTLILQPPSEKGR
NOV66a QCEWRSIDGSIVLPLARGSPKALALEYALCLTGDGLAHLQATDPQQLLRLIPHVQVFARV
NOV66b QCEWRSIDGSIVLPLARGSPKALALEYALCLTGDGLAHLQATDPQQLLRLIPHVQVFARV
NOV66a APKQKEFVITSLKELGYVTLMCGDGTNDVGALKHADVGVALLANAPERWERRRRPRDSP
NOV66b APKQKEFVITSLKELGYVTLMCGDGTNDVGALKHADVGVALLANAPERWERRRRPRDSP
NOV66a TLSNSGIRATSRTAKQRSGLPPSEEQPTSQRDRLSQVLRDLEDESTPIVKLGDASIAAPF
NOV66b TLSNSGIRATSRTAKQRSGLPPSEEQPTSQRDRLSQVLRDLEDESTPIVKLGDASIAAPF
NOV66a TSKLSSIQCICHVIKQGRCTLVTTLQMFKILALNALILAYSQSVLYLEGVKFSDFQATLQ
NOV66b TSKLSSIQCICHVIKQGRCTLVTTLQMFKILALNALILAYSQSVLYLEGVKFSDFQATLQ
NOV66a GLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILTVMLQFFVHFLSLVYLYREAQARS
NOV66b GLLLAGCFLFISRSKPLKTLSRERPLPNIFNLYTILTVMLQFFVHFLSLVYLYREAQARS
NOV66a PEKQEQFVDLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFMESLPENKPLVWSLAV
NOV66b PEKQEQFVDLYKEFEPSLVNSTVYIMAMAMQMATFAINYKGPPFMESLPENKPLVWSLAV
NOV66a SLLAIIGLLLGSSPDFNSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQFFLGTPKL NOV66b SLLAIIGLLLGSSPDFNSQFGLVDIPVEFKLVIAQVLLLDFCLALLADRVLQFFLGTPKL
NOV66a KVPS
NOV66b KVPS
NOV66a (SEQ ID NO: 986)
NOV66b (SEQ ID NO: 988)
Further analysis ofthe NOV66a protein yielded the following properties shown in Table 66C.
Figure imgf000907_0001
INTEGRAL Likelihood = -0,.16 Transmembrane 265 - 281
INTEGRAL Likelihood =- -11. .94 Transmembrane 446 - 462
INTEGRAL Likelihood = 0, .10 Transmembrane 493 - 509
INTEGRAL Likelihood = -0, .64 Transmembrane 672 - 688
INTEGRAL Likelihood = -0, .69 Transmembrane 944 - 960
INTEGRAL Likelihood = -1. .38 Transmembrane 978 - 994
INTEGRAL Likelihood = -3. .61 Transmembrane 1017 -1033
INTEGRAL Likelihood = -9, .45 Transmembrane 1097 -1113
INTEGRAL Likelihood = -8. .65 Transmembrane 1134 -1150
PERIPHERAL Likelihood = 1. .01 (at 67)
ALOM score: -11.94 (number of TMSs: 11)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 107 Charge difference: 3.0 C( 2.0) - N(-1.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment (75): 2.14 Hyd Moment(95): 0.67 G content: 3 D/E content: 1 S/T content: 0 Score: -5.79
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 43 PRA|LL
NUCDISC: discrimination of nuclear localization signals pat4: RRRR (5) at 855 pat4 : RRRP (4) at 856 pat : RRPR (4) at 857 pat7: none bipartite: RKMGNKPHMIQVYRSRK at 292 content of basic residues: 10.4% NLS Score: 0.83
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus : LKVP
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt τs method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
77.8 %: endoplasmic reticulum 11.1 %: mitochondrial 11.1 %: vacuolar
>> prediction for CG57562-02 is end (k=9)
A search ofthe NOV66a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 66D.
Figure imgf000910_0001
In a BLAST search of public sequence databases, the NOV66a protein was found to have homology to the proteins shown in the BLASTP data in Table 66E.
Figure imgf000911_0001
PFam analysis indicates that the NOV66a protein contains the domains shown in the Table 66F.
Figure imgf000911_0002
Example 67.
The NOV67 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 67A. Table 67A. NOV67 Sequence Analysis
NOV67a, CG57758-03 SEQ ID NO: 993 3147 bp DNA Sequence ORF Start: ATG at 2 ORF Stop: TAG at 1706
GATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTTCGTCACCCCGCTCC TGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTACGTCATCATCCTCATG GCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCC ACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCC TGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACG CTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTC CATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGA TGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTG CCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTT GTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGA CGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAAC TTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCT CCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACG AGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTGTCCTTCGCGGAGATC AACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGG CTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTG TGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAA GAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTG GGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCG TGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCC TTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTT TGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCT CCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAG GTTGCTGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGT CAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTG AGACTTAGGAAGAGCCACAAGACCACACACACAGCCCTTACCCTCCTCAGGACTACCGAACCTTCTGG
CACACCTTGTACAGAGTTTTGGGGTTCACACCCCAAAATGACCCAACGATGTCCACACACCACCAAAA
CCCAGCCAATGGGCCACCTCTTCCTCCAAGCCCAGATGCAGAGATGGTCATGGGCAGCTGGAGGGTAG
GCTCAGAAATGAAGGGAACCCCTCAGTGGGCTGCTGGACCCATCTTTCCCAAGCCTTGCCATTATCTC
TGTGAGGGAGGCCAGGTAGCCGAGGGATCAGGATGCAGGCTGCTGTACCCGCTCTGCCTCAAGCATCC
CCCACACAGGGCTCTGGTTTTCACTCGCTTCGTCCTAGATAGTTTAAATGGGAATCGGATCCCCTGGT
TGAGAGCTAAGACAACCACCTACCAGTGCCCATGTCCCTTCCAGCTCACCTTGAGCAGCCTCAGATCA
TCTCTGTCACTCTGGAAGGGACACCCCAGCCAGGGACGGAATGCCTGGTCTTGAGCAACCTCCCACTG
CTGGAGTGCGAGTGGGAATCAGAGCCTCCTGAAGCCTCTGGGAACTCCTCCTGTGGCCACCACCAAAG
GATGAGGAATCTGAGTTGCCAACTTCAGGACGACACCTGGCTTGCCACCCACAGTGCACCACAGGCCA
ACCTACGCCCTTCATCACTTGGTTCTGTTTTAATCGACTGGCCCCCTGTCCCACCTCTCCAGTGAGCC
TCCTTCAACTCCTTGGTCCCCTGTTGTCTGGGTCAACATTTGCCGAGACGCCTTGGCTGGCACCCTCT
GGGGTCCCCCTTTTCTCCCAGGCAGGTCATCTTTTCTGGGAGATGCTTCCCCTGCCATCCCCAAATAG
CTAGGATCACACTCCAAGTATGGGCAGTGATGGCGCTCTGGGGGCCACAGTGGGCTATCTAGGCCCTC:
CCTCACCTGAGGCCCAGAGTGGACACAGCTGTTAATTTCCACTGGCTATGCCACTTCAGAGTCTTTCA!
TGCCAGCGTTTGAGCTCCTCTGGGTAAAATCTTCCCTTTGTTGACTGGCCTTCACAGCCATGGCTGGT
GACAACAGAGGATCGTTGAGATTGAGCAGCGCTTGGTGATCTCTCAGCAAACAACCCCTGCCCGTGGG
CCAATCTACTTGAAGTTACTCGGACAAAGACCCCAAAGTGGGGCAACAACTCCAGAGAGGCTGTGGGA
ATCTTCAGAAGCCCCCCTGTAAGAGACAGACATGAGAGACAAGCATCTTCTTTCCCCCGCAAGTCCAT
TTTATTTCCTTCTTGTGCTGCTCTGGAAGAGAGGCAGTAGCAAAGAGATGAGCTCCTGGATGGCATTT
TCCAGGGCAGGAGAAAGTATGAGAGCCTCAGGAAACCCCATCAAGGACCGAGTATGTGTCTGGTTCCT
TTGGTGGTTGGCTTCTGGC
NOV67a, CG5775δ-03 SEQ ID NO: 994 56δ aa MW at 63061.4kD Protein Sequence
MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIPLAVTSLMPVLLFP LFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL VGAKPARLMLGFMGVTALLS M ISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRL CKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWL QFVYMRFNFKKS GCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPG
90δ LTVAVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQEKVPW GIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIF ASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV NT GRAIFDLDHFPDWANVTHIET
NOV67b, 30δ537δ54 SEQ ID NO: 995 1729 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCAGATCTCCCACCATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGT TCGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTAC GTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCC TGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACA CCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGG ATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGT CACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGG CCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGC AAGGCCAAGGAGCTGCCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCA AGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCG CCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGC AAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTT CGCCTGGCTGTGGCTCCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAG AGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTG TCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCC CGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCA CTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGC AGCCAGACTGAGGAAGAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCA GGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGG CCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATC ACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTT GTTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCT GTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACC TATGGGCACCTCAAGGTTGCTGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTG TGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTA ATGTGACACATATTGAGACTCTCGAGGGC
NOV67b, 30δ537δ54 SEQ ID NO: 996 576 aa MW at 63903.4kD Protein Sequence
TRSPTMASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIPLAVTSLMP VLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGV TALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQ ERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLF AWL LQFVYMRFNFKKS GCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDP GFMPGWLTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQ EKVPWGIVLLLGGGFALAKGSEASGLSV MGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTL FLPIFASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFC VFLAVNT GRAIFDLDHFPDWANVTHIETLEG
NOV67c, CG5775δ-01 SEQ ID NO: 997 1790 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 1720
TCTCCCTCCCGCGCGATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTT
CGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGGTCAGTTGTGCCTACGTCA TCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTC TTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAA CATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCG CCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACA GCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCAT ATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGG CCAAGGAGCTGCCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAG CGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCAC CCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGG ACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCC TGGCTGTGGCTCCAGTTTGTTTACATGTTCTCCAGTTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAG CAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGCTGGGGCCCTTGTCCT TCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGC TTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGT GGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCC AGACTGAGGAAGGTAAGTCTCCTGTTCTGATCGCCCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAG GAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGC CTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCA CCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTG TTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTG TACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCT ATGGGCACCTCAAGGTTGCTGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGT GTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAA TGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCACACACACAGCCCTTACCCTCCTCAGGACT ACCGAACCTTCTGGCACACCTT
NOV67c, CG5775δ-01 SEQ ID NO: 99δ 56δ aa MW at 62592.9kD Protein Sequence
MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCAYVIILMAIY CTEVIPLAVTSLMPVLLFPL FQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWGAKPARLMLGFMGVTALLSM WISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRLC KAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQ FVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPG LTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPW GIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIF ASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV NTWGRAIFDLDHFPDWANVTHIET
NOV67d, CG5775δ-02 SEQ ID NO: 999 lδ99 bp DNA Sequence ORF Start: ATG at 31 ORF Stop: TAG at lδ79
CGTCTCGCCCGCCAGTCTCCCTCCCGCGCGATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTC
CTTCGTGATCTTGTTCGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGGTCA GTTGCTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTC ACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCA GTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGA ACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTG GGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGT GCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGG GACAAGGTACCACAATAAACAACCTGAATGCACTGGAGGATGATACAGTGAAAGCAGTACTAGGAGGA AAGTGTGTAGCTATAATAAGCACTTACGTCAAAAAAGTAGAAAAACTTCAAATAAACAATCTAATGAC ACCTCTTAAAAAACTAGAAAAGCAAGAGCAACAGGACCTAGGGCCTGGCATCAGGCCTCAGGACTCTG CCCAGTGCCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCG GCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAA CGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACA TGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGTTCTCCAGTTTTAAAAAG TCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTA CCGGAAGCTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCC TGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACA AAGTCAGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAA GCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGGTAAGTCTCCTGTTCTGATCGCCCCCCCTCCCC TGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTT GCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCA CGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAA GCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAAT CCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCC TCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCTGACATGGTAAAAACAGGAGTCATAA TGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTG GATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCAC
NOV67d, CG5775δ-02 SEQ ID NO: 1000 616 aa MW at 67δl6.9kD Protein Sequence
MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCCAYVIILMAIYWCTEVIPLAVTSLMPVLLFP LFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLS MWISNTATTAMMVPIVEAILQQMEATSAATEAGLEGQGTTINNLNALEDDTVKAVLGGKCVAIISTYV KKVEKLQINNLMTPLKKLEKQEQQDLGPGIRPQDSAQCQEDQERKRLCKAMTLCICYAASIGGTATLT GTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKK NEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKSVSDATVAI FVATLLFIVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASG LSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSRSIGLNPLYIMLPCTL SASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVT HIET
NOV67e, CG5775δ-04 SEQ ID NO: 1001 1606 bp DNA Sequence ORF Start: ATG at 2 ORF Stop: TAG at 1568
GATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTTCGTCACCCCGCTCC TGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTACGTCATCATCCTCATG GCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCC ACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCC TGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACG CTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTC CATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGA TGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTG CCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTT GTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGA CGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAAC TTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCT CCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACG AGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTGTCCTTCGCGGAGATC AACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGG CTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTG TGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAA GAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTG GGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCG TGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCC TTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTT TGCCTCCATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCA ACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAG ACTTAGGAAGAGCCACAAGACCACACACATAGCCCTTACCCT
NOV67e, CG57758-04 SEQ ID NO: 1002 522 aa M at 5δl09.6kD Protein Sequence
MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIPLAVTSLMPVLLFP LFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVER NLHKRIALRTLLWVGAKPARLMLGFMGVTALLS MWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRL CKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWL QFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPG WLTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQEKVPW GIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIF ASMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIET
NOV67f, CG5775δ-05 SEQ ID NO: 1003 1781 bp DNA Sequence ORF Start: ATG at 2 ORF Stop: TGA at 1550
GATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTTCGTCACCCCGCTCC TGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTACGTCATCATCCTCATG GCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCC ACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCC TGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACG CTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTC CATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGA TGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTG CCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTT GTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGA CGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAAC TTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCT CCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACG AGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTGTCCTTCGCGGAGATC AACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGG CTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTG TGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAA GAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTG GGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCG TGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCC TTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTT TGCCTCCATGAATCACGTCCCCAAGAGCTTCTGTGTTCTGTACGGTGATGTTGCAGTGCTGTCTTTCC GCAGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTG
CCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCT iGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACAC
CTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTT
AGGAAGAGCCACA
NOV67f, CG57758-05 SEQ ID NO: 1004 516 aa MW at 57173.5kD Protein Sequence
MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIPLAVTSLMPVLLFP LFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLS MWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRL CKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWL QFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPG WLTVA VEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQEKVPW GIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIF ASMNHVPKSFCVLYGDVAVLSFRSLAPSASIRCTSCCPVP
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 67B.
Table 67B. Comparison of the NOV67 protein sequences.
NOV67a MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIP
NOV67b TRSPTMASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIP
NOV67C MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVS-CAYVIILMAIYWCTEVIP
NOV67d MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCCAYVIILMAIYWCTEVIP
NOV67e MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIP
NOV67f MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIP
NOV67a LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67b LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67C LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67d LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67e LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67f LAVTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLL
NOV67a WVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDK NOV67b VGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDK
NOV67C WVGAKPARLMLGFMGVTALLSM ISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDK
NOV67d WVGAKPARLMLGFMGVTALLSM ISNTATTAMMVPIVEAILQQMEATSAATEAGLEGQGT
NOV67e WVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDK
NOV67f WVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDK
NOV67a GK AKELPGSQVIFEGPTLG
NOV67b GK AKELPGSQVIFEGPTLG
NOV67c GK AKELPGSQVIFEGPTLG
NOV67d TINNLNALEDDTVKAVLGGKCVAIISTYVKKVEKLQINNLMTPLKKLEKQEQQDLGPGIR
NOV67e GK AKELPGSQVIFEGPTLG
NOV67f GK AKELPGSQVIFEGPTLG
NOV67a -Q QEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67b -Q QEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67C -Q QEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67d PQDSAQCQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67e -Q QEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67f -Q QEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNWLLGQMNELFPDSKDLV
NOV67a NFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67b NFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67C NFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67d NFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67e NFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67f NFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRK
NOV67a LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLF
NOV67b LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLF
NOV67c LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLF
NOV67d LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKSVSDATVAIFVATLLF
NOV67e LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLF
NOV67f LGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLF
NOV67a IVPSQKPKFNFRSQTEEERK-TPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67b IVPSQKPKFNFRSQTEEERK-TPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67C IVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67d IVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67e IVPSQKPKFNFRSQTEEERK-TPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67f IVPSQKPKFNFRSQTEEERK-TPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEAS
NOV67a GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSR SIG
NOV67b GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSR SIG
NOV67C GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSR---SIG
NOV67d GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSR---SIG
NOV67e GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMVKTGVIMN
NOV67f GLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMN H
NOV67a LNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV
NOV67b LNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV
NOV67c LNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV
NOV67d LNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAV
NOV67e IIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIET
NOV67f VPKSFCVLYGD VAVLSFRSLAPSASIRCTSCCPVP NOV67a NTWGRAIFDLDHFPDWANVTHIET NOV67b NTWGRAIFDLDHFPDWANVTHIETLEG NOV67C NTWGRAIFDLDHFPDWANVTHIET NOV67d NTWGRAIFDLDHFPDWANVTHIET NOV67e NOV67f
NOV67a (SEQ ID NO 994) NOV67b (SEQ ID NO 996) NOV67C (SEQ ID NO 998) NOV67d (SEQ ID NO 1000) NOV67e (SEQ ID NO 1002) NOV67f (SEQ ID NO 1004)
Further analysis ofthe NOV67a protein yielded the following properties shown in Table 67C.
Table 67C. Protein Sequence Properties NOV67a
SignalP analysis: Cleavage site between residues 39 and 40
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos . chg 1 ; neg . chg 0
H-region: length 1; peak value 5.97
PSG score: 1.57
GvH: von Heijne's method for signal seq. recognition
GvH score (threshold: - -2.1): - 2.36 possible cleavage site between 30 and 31
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0 .5: 11
INTEGRAL Likelihood =-12.21 Transmembrane 14 - 30
INTEGRAL Likelihood = -1.81 Transmembrane 35 - 51
INTEGRAL Likelihood = -4.99 Transmembrane 53 - 69
INTEGRAL Likelihood = -1.75 Transmembrane 124 - 140
INTEGRAL Likelihood = -3.72 Transmembrane 261 - 277
INTEGRAL Likelihood = -8.01 Transmembrane 312 - 328
INTEGRAL Likelihood = -6.26 Transmembrane 354 - 370
INTEGRAL Likelihood = 0.21 Transmembrane 405 - 421
INTEGRAL Likelihood = -7.11 Transmembrane 443 - 459
INTEGRAL Likelihood = -1.70 Transmembrane 490 - 506
INTEGRAL Likelihood = -7.43 Transmembrane 528 - 544
PERIPHERAL Likelihood = 0.74 (at 89)
ALOM score: -12.21 (number of TMSs: 11)
MTOP: Prediction of membrane topology (Hartmann et al )
Center position for cal culation : 21 Charge difference: -1.0 C ( 2.0) - ( 3.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75) : 1.18 Hyd Moment(95): 3.95 G content: 0 D/E content : 1 S/T conten : 6 Score: -3.21
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 47 VRC|AY
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 7.7% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif .- type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
66.7 %: endoplasmic reticulum
22.2 %: mitochondrial 11.1 %: nuclear
>> prediction for CG57758-03 is end (k=9)
A search ofthe NOV67a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 67D.
Figure imgf000921_0001
In a BLAST search of public sequence databases, the NOV67a protein was found to have homology to the proteins shown in the BLASTP data in Table 67E.
Figure imgf000922_0001
PFam analysis indicates that the NOV67a protein contains the domains shown in the Table 67F.
Figure imgf000922_0002
TRA 1800976v 1 Example 68.
The NOV6δ clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6δA.
Table 68A. NOV68 Sequence Analysis
NOVόδa, CG58504-01 SEQ ID NO: 1005 5115 bp DNA Sequence ORF Start: ATG at 327 ORF Stop: TAA at 5106
GAATTCCGGGAGCGGGCGGGCTGCGAGGCCGCGGGGCATGCGGGAGGCGGAGGGGTGGGACCGGGTGG
CTGCGCCCATTCCACACCCGCCGAAAGCGGACACTGTCAGCTGAATCACTCCCCTTTTAGGAGGAGGG
AGGGGGAAAAGGTGTCTAGCTAATTTCTGCTTAAAAAAGCACAGGAGATCGCGGGTCAGCTTTGCAGT
CGCTGCCTTCTCGCGCCTGACCATGCACCCCTGCATCTTCCTGCTGGGCACAGGCGAGCGCTTTATTT
CTGGAGCTGAGGGCTAAAACTTTTTTCACTTTTCTTCTCCTCAACATCTGAATCATGCCATGTGCCCA
GAGGAGCTGGCTTGCAAACCTTTCCGTGGTGGCTCAGCTCCTTAACTTTGGGGCGCTTTGCTATGGGA GACAGCCTCAGCCAGGCCCGGTTCGCTTCCCGGACAGGAGGCAAGAGCATTTTATCAAGGGCCTGCCA GAATACCACGTGGTGGGTCCAGTCCGAGTAGATGCCAGTGGGCATTTTTTGTCATATGGCTTGCACTA TCCCATCACGAGCAGCAGGAGGAAGAGAGATTTGGATGGCTCAGAGGACTGGGTGTACTACAGAATTT CTCACGAGGAGAAGGACCTGTTTTTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATC ATGGAGAAGAGATATGGGAACCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCT CAGTGGCACGGTTCTACAGCAGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCCTGCCATGGACTGA CTGGATTTTTCCAACTACCACATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAG GGAGGGTACCACCCGCACATCGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGG ATTAAAGGACAGTGTTAACATCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACT TGCCAAGCAGAAGCCTCTCTCGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCC GACACAAAGATGATTGAATACCATGGGAGTGAGAATGTGGAGTCCTACATCCTCACCATCATGAACAT GGTCACTGGGTTGTTCCATAACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTC TACTCGAAGAAGAAGAGCAAGGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGC AAGTGGCAGAAGAGTATCAATCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCT CACCAGAAAGGACATCTGTGCTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAG GAATGTGTCAGCCTCACCGCAGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATT GCCCATGAGCTAGGACACAGCTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGG CAGACATCCGTACATCATGTCCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCA GCGAGGAGTACATCACCCGCTTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTAAAAAG AAAGGCTTGAAGTCCAAGGTCATTGCCCCCGGAGTGATCTATGATGTTCACCACCAGTGCCAGCTACA ATATGGACCCAATGCTACCTTCTGCCAGGAAGTAGAAAACGTCTGCCAGACACTGTGGTGCTCCGTGA AGGGCTTTTGTCGCTCTAAGCTGGACGCTGCTGCAGATGGAACTCAATGTGGTGAGAAGAAGTGGTGT ATGGCAGGCAAGTGCATCACAGTGGGGAAGAAACCAGAGAGCATTCCTGGAGGCTGGGGCCGCTGGTC ACCCTGGTCCCACTGTTCCAGGACCTGTGGGGCTGGAGTCCAGAGCGCAGAGAGGCTCTGCAACAACC CCGAGCCAAAGTTTGGAGGGAAATATTGCACTGGAGAAAGAAAACGCTATCGCTTGTGCAACGTCCAC CCCTGTCGCTCAGAGGCACCAACATTTCGGCAGATGCAGTGCAGTGAATTTGACACTGTTCCCTACAA GAATGAACTCTACCACTGGTTTCCCATTTTTAACCCAGCACATCCTTGTGAGCTCTACTGCCGACCCA TAGATGGCCAGTTTTCTGAGAAAATGCTGGATGCTGTCATTGATGGTACCCCTTGCTTTGAAGGCGGC AACAGCAGAAATGTCTGTATTAATGGCATATGTAAGATGGTTGGCTGTGACTATGAGATCGATTCCAA TGCCACCGAGGATCGCTGCGGTGTGTGCCTGGGAGATGGCTCTTCCTGCCAGACTGTGAGAAAGATGT TTAAGCAGAAGGAAGGATCTGGTTATGTTGACATTGGGCTCATTCCAAAAGGAGCAAGGGACATAAGA GTGATGGAAATTGAGGGAGCTGGAAACTTCCTGGCCATCAGGAGTGAAGATCCTGAAAAATATTACCT GAATGGAGGGTTTATTATCCAGTGGAACGGGAACTATAAGCTGGCAGGGACTGTCTTTCAGTATGACA GGAAAGGAGACCTGGAAAAGCTGATGGCCACAGGTCCCACCAATGAGTCTGTGTGGATCCAGCTTCTA TTCCAGGTGACTAACCCTGGCATCAAGTATGAGTACACAATCCAGAAAGATGGCCTTGACAATGATGT TGAGCAGATGTACTTCTGGCAGTACGGCCACTGGACAGAGTGCAGTGTGACCTGCGGGACAGGTATCC GCCGCCAAACTGCCCATTGCATAAAGAAGGGCCGCGGGATGGTGAAAGCTACATTCTGTGACCCAGAA ACACAGCCCAATGGGAGACAGAAGAAGTGCCATGAAAAGGCTTGTCCACCCAGGTGGTGGGCAGGGGA GTGGGAAGCATGCTCGGCGACATGCGGGCCCCACGGGGAGAAGAAGCGAACCGTGCTGTGCATCCAGA CCATGGTCTCTGACGAGCAGGCTCTCCCGCCCACAGACTGCCAGCACCTGCTGAAGCCCAAGACCCTC CTTTCCTGCAACAGAGACATCCTGTGCCCCTCGGACTGGACAGTGGGCAACTGGAGTGAGTGTTCTGT TTCCTGTGGTGGTGGAGTGCGGATTCGCAGTGTCACATGTGCCAAGAACCATGATGAACCTTGCGATG TGACAAGGAAACCCAACAGCCGAGCTCTGTGTGGCCTCCAGCAATGCCCTTCTAGCCGGAGAGTTCTG
AAACCAAACAAAGGCACTATTTCCAATGGAAAAAACCCACCAACACTAAAGCCCGTCCCTCCACCTAC ATCCAGGCCCAGAATGCTGACCACACCCACAGGGCCTGAGTCTATGAGCACAAGCACTCCAGCAATCA GCAGCCCTAGTCCTACCACAGCCTCCAAAGAAGGAGACCTGGGTGGGAAACAGTGGCAAGATAGCTCA ACCCAACCTGAGCTGAGCTCTCGCTATCTCATTTCCACTGGAAGCACTTCCCAGCCCATCCTCACTTC CCAATCCTTGAGCATTCAGCCAAGTGAGGAAAATGTTTCCAGTTCAGATACTGGTCCTACCTCGGAGG GAGGCCTTGTAGCTACAACAACAAGTGGTTCTGGCTTGTCATCTTCCCGCAACCCTATCACTTGGCCT GTGACTCCATTTTACAATACCTTGACCAAAGGTCCAGAAATGGAGATTCACAGTGGCTCAGGGGAAGA AAGAGAACAGCCTGAGGACAAAGATGAAAGCAATCCTGTAATATGGACCAAGATCAGAGTACCTGGAA ATGACGCTCCAGTGGAAAGTACAGAAATGCCACTTGCACCTCCACTAACACCAGATCTCAGCAGGGAG TCCTGGTGGCCACCCTTCAGCACAGTAATGGAAGGACTGCTCCCCAGCCAAAGGCCCACTACTTCCGA AACTGGGACACCCAGAGTTGAGGGGATGGTTACTGAAAAGCCAGCCAACACTCTGCTCCCTCTGGGAG GAGACCACCAGCCAGAACCCTCAGGAAAGACGGCAAACCGTAACCACCTGAAACTTCCAAACAACATG AACCAAACAAAAAGTTCTGAACCAGTCCTGACTGAGGAGGATGCAACAAGTCTGATTACTGAGGGCTT TTTGCTAAATGCCTCCAATTACAAGCAGCTCACAAACGGCCACGGCTCTGCACACTGGATCGTCGGAA ACTGGAGCGAGTGCTCCACCACATGTGGCCTGGGGGCCTACTGGAAAAGGGTGGAGTGCACCACCCAG ATGGATTCTGACTGTGCGGCCATCCAGAGACCTGACCCTGCAAAAAGATGCCACCTCCGTCCCTGTGC TGGCTGGAAAGTGGGAAACTGGAGCAAGTGCTCCAGAAACTGCAGTGGGGGCTTCAAGATACGCGAGA TTCAGTGCGTGGACAGCCGGGACCACCGGAACCTGAGGCCATTTCACTGCCAGTTCCTGGCCGGCATT CCTCCCCCATTGAGCATGAGCTGTAACCCGGAGCCCTGTGAGGCGTGGCAGGTGGAGCCTTGGAGCCA GTGCTCCAGGTCCTGTGGAGGTGGAGTTCAGGAGAGAGGAGTGTTCTGTCCAGGAGGCCTCTGTGATT GGACAAAAAGACCCACATCCACCATGTCTTGCAATGAGCACCTGTGCTGTCACTGGGCCACTGGGAAC TGGGACCTGTGTTCCACTTCCTGTGGAGGTGGCTTTCAGAAGAGGATTGTCCAATGTGTGCCCTCAGA GGGCAATAAAACTGAAGACCAAGACCAATGTCTATGTGATCACAAACCCAGACCTCCAGAATTCAAAA AATGCAACCAGCAGGCCTGCAAGAAAAGTGCCGATTTACTTTGCACTAAGGACAAACTGTCAGCCAGT TTCTGCCAGACACTGAAAGCCATGAAGAAATGTTCTGTGCCCACCGTGAGGGCTGAGTGCTGCTTCTC GTGTCCCCAGACACACATCACACACACCCAAAGGCAAAGAAGGCAACGGTTGCTCCAAAAGTCAAAAG AACTCTAAGCCCAAA
NOV6δa, CG5δ504-01 SEQ ID NO: 1006 1593 aa MW at 177543.9kD Protein Sequence
MPCAQRS LANLSWAQLLNFGALCYGRQPQPGPVRFPDRRQEHFIKGLPEYHWGPVRVDASGHFLS YGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDLFFNLTV QGFLSNSYIMEKRYGNLSHVKMMASSA PLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETK EPTCGLKDSTOISQKQELWREKWERHNLPSRSLSRRSISKEROTETL ADTKMIEYHGSENVESYIL TIMNMVTGLFHNPSIGNAIHIVVVRLILLEEEEQGLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHD VAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKEND CEPVGRHPYIMSRQLQYDPTPLT SKCSEEYITRFLDRG GFCLDDIPKKKGLKSKVIAPGVIYDVHH QCQLQYGPNATFCQEVE VCQTLWCSVKGFCRSKLDAAADGTQCGEKK CMAGKCITVGKKPESIPGG GR SPWSHCSRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFD TVPYKNELYH FPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICKMVGCDY EIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSEDP EKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVWIQLLFQVTNPGIKYEYTIQKDG LDNDVEQMYFWQYGHWTECSVTCGTGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQKKCHEKACPPR WWAGEWEACSATCGPHGEKKRTVLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNW SECSVSCGGGVRIRSVTCAK HDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKP VPPPTSRPRMLTTPTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQ PILTSQSLSIQPSEE VSSSDTGPTSEGGLVATTTSGSGLSSSRNPIT PVTPFYNTLTKGPEMEIHS GSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQR PTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNNMNQTKSSEPVLTEEDATSL ITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAYWKRVECTTQMDSDCAAIQRPDPAKRCH LRPCAGWKVGN SKCSRNCSGGFKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEA QV EPWSQCSRSCGGGVQERGVFCPGGLCDWTKRPTSTMSCNEHLCCH ATGNWDLCSTSCGGGFQKRIVQ CVPSEGNKTEDQDQCLCDHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRA ECCFSCPQTHITHTQRQRRQRLLQKSKEL
NOV6δb, 16964δ376 SEQ ID NO: 1007 106δ bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGATGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTGCATCCTCACCATCATGAACATGGTCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG CTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGGCAGACATCCGTACATCATGT CCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCAGCGAGGAGTACATCACCCGC TTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTCTCGAG
NOV6δb, 16964δ376 SEQ ID NO: 100δ 356 aa MW at 40336.9kD Protein Sequence
KLNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGMAALSACHGLTGFFQLP HGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLS RRSISKERVWETLVVADTKMIEYHGSENVΕSCILTIMNMVTGLFHNPSIGNAIHIVVVRLILLEEEEQ GLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHR SCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITR FLDRGWGFCLDDIPLE
NOV6δc, 16964δ3δδ SEQ ID NO: 1009 106 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTACATCCTCACCATCATGAACATGATCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG CTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGGCAGACATCCGTACATCATGT CCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCAGCGAGGAGTACATCACCCGC TTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTCTCGAG
NOV6δc, 16964δ388 SEQ ID NO: 1010 356 aa MW at 403δ0.8kD Protein Sequence
KLNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLP HGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLS RRSISKERWVETLWADTK IEYHGSENVESYILTIMNMITGLFHNPSIGNAIHIVWRLILLEEEEQ GLKIVHHAEKTLSSFCK QKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHR SCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITR FLDRGWGFCLDDIPLE
NOV68d, 169648365 SEQ ID NO: 1011 106δ bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTACATCCTCACCATCATGAACATGGTCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG
Figure imgf000926_0001
AGCCCATCCTCACTTCCCAATCCTTGAGCATTCAGCCAAGTGAGGAAAATGTTTCCAGTTCAGATACT GGTCCTACCTCGGAGGGAGGCCTTGTAGCTACAACAACAAGTGGTTCTGGCTTGTCATCTTCCCGCAA
CCCTATCACTTGGCCTGTGACTCCATTTTACAATACCTTGACCAAAGGTCCAGAAATGGAGATTCACA GTGGCTCAGGGGAAGAAAGAGAACAGCCTGAGGACAAAGATGAAAGCAATCCTGTAATATGGACCAAG ATCAGAGTACCTGGAAATGACGCTCCAGTGGAAAGTACAGAAATGCCACTTGCACCTCCACTAACACC AGATCTCAGCAGGGAGTCCTGGTGGCCACCCTTCAGCACAGTAATGGAAGGACTGCTCCCCAGCCAAA GGCCCACTACTTCCGAAACTGGGACACCCAGAGTTGAGGGGATGGTTACTGAAAAGCCAGCCAACACT CTGCTCCCTCTGGGAGGAGACCACCAGCCAGAACCCTCAGGAAAGACGGCAAACCGTAACCACCTGAA ACTTCCAAACAACATGAACCAAACAAAAAGTTCTGAACCAGTCCTGACTGAGGAGGATGCAACAAGTC TGATTACTGAGGGCTTTTTGCTAAATGCCTCCAATTACAAGCAGCTCACAAACGGCCACGGCTCTGCA CACTGGATCGTCGGAAACTGGAGCGAGTGCTCCACCACATGTGGCCTGGGGGCCTACTGGAGAAGGGT GGAGTGCAGCACCCAGATGGATTCTGACTGTGCGGCCATCCAGAGACCTGACCCTGCAAAAAGATGCC ACCTCCGTCCCTGTGCTGGCTGGAAAGTGGGAAACTGGAGCAAGTGCTCCAGAAACTGCAGTGGGGGC TTCAAGATACGCGAGATTCAGTGCGTGGACAGCCGGGACCACCGGAACCTGAGGCCATTTCACTGCCA GTTCCTGGCCGGCATTCCTCCCCCATTGAGCATGAGCTGTAACCCGGAGCCCTGTGAGGCGTGGCAGG TGGAGCCTTGGAGCCAGTGCTCCAGGTCCTGTGGAGGTGGAGTTCAGGAGAGAGGAGTGTTCTGTCCA GGAGGCCTCTGTGATTGGACAAAAAGACCCACATCCACCATGTCTTGCAATGAGCACCTGTGCTGTCA CTGGGCCACTGGGAACTGGGACCTGTGTTCCACTTCCTGTGGAGGTGGCTTTCAGAAGAGGACTGTCC AATGTGTGCCCTCAGAGGGCAATAAAACTGAAGACCAAGACCAATGTCTATGTGATCACAAACCCAGA CCTCCAGAATTCAAAAAATGCAACCAGCAGGCCTGCAAGAAAAGTGCCGATTTACTTTGCACTAAGGA CAAACTGTCAGCCAGTTTCTGCCAGACACTGAAAGCCATGAAGAAATGTTCTGTGCCCACCGTGAGGG CTGAGTGCTGCTTCTCGTGTCCCCAGACACACATCACACACACCCAAAGGCAAAGAAGGCAACGGTTG CTCCAAAAGTCAAAAGAACTCCTCGAGGAGTTCTTTTGACTTTTGGAGCAACCGGGCCTGGCTGAGGC TGTCTCCCATAAGATCT
NOV6δe, 2δ406δ250 SEQ ID NO: 1014 1576 aa M at l75δδ7.8kD Protein Sequence
RSYGRQPQPGPVRFPDRRQEHFIKGLPEYHWGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWV YYRISHEEKDLFFNLTWQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLNGTVIJQQGTRVGTAALSA CHGLTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSV ISQKQELWREKW ERHNLPSRSLSRRSISKEROTETLWADTKMIEYHGSENVΕSYILTI NTWTGLFHNPSIGNAIHIVV VRLILLEEEEQGLKIVΗHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCETLGL SHLSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLT WSKCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATLCQEVE VCQTL WCSVKGFCRSKX.DAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHCSRTCGAGVQSAER LC NPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTVPYKNELYHWFPIFNPAHPCEL YCRPIDGQFSEjLDAVIDGTPCFEGGNSRNVCINGICKMVGCDYEIDSNATEDRCGVCLGDGSSCQT VRK FKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSEDPEKYYLNGGFIIQW GNYKLAGTV FQYDRKGDLEKLMATGPTNES IQLLFQV NPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVT CGTGIRRQTAHCIKKGRGMVIATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRT VLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKNH DEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMST STPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEENVSSSDT GPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEMEIHSGSGEEREQPEDKDESNPVIWTK IRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRPTTSETGTPRVEGMVTEKPANT LLPLGGDHQPEPSGKTANRNHLKLPNNMNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSA HWIVG WSECSTTCGLGAYWRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGG FKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCP GGLCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLCDHKPR PPEF KCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQRL LQKSKELLEEFF
NOV68f, 305δ67δ66 SEQ ID NO: 1015 4777 bp DNA Sequence ORF Start: at 1 ORF Stop: TGA at 4729
AGATCTTATGGGAGACAGCCTCAGCCAGGCCCGGTTCGCTTCCCGGACAGGAGGCAAGAGCATTTTAT CAAGGGCCTGCCAGAATACCACGTGGTGGGTCCAGTCCGAGTAGATGCCAGTGGGCATTTTTTGTCAT ATGGCTTGCACTATCCCATCACGAGCAGCAGGAGGAAGAGAGATTTGGATGGCTCAGAGGACTGGGTG TACTACAGAATTTCTCACGAGGAGAAGGACCTGTTTTTTAACTTGACGGTCAATCAAGGATTTCTTTC CAATAGCTACATCATGGAGAAGAGATATGGGAACCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCC CCCTCTGCCATCTCAGTGGCACGGTTCTACAGCAGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCC TGCCATGGACTGACTGGATTTTTCCAACTACCACATGGAGACTTTTTCATTGAACCCGTGAAGAAGCA TCCACTGGTTGAGGGAGGGTACCACCCGCACATCGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGG AGCCAACCTGTGGATTAAAGGACAGTGTTAACATCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGG GAGAGGCACAACTTGCCAAGCAGAAGCCTCTCTCGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGAC ACTGGTGGTGGCCGACACAAAGATGATTGAATACCATGGGAGTGAGAATGTGGAGTCCTACATCCTCA CCATCATGAACATGGTCACTGGGTTGTTCCATAACCCAAGCATTGGCAATGCAATTCACATTGTTGTG GTTCGGCTCATTCTACTCGAAGAAGAAGAGCAAGGACTGAAAATAGTTCACCATGCAGAAAAGACACT GTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAATCCCAAGAGTGACCTCAATCCTGTTCATCACGACG TGGCTGTCCTTCTCACTAGAAAGGACATCTGTGCTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTG TCTCACCTTTCAGGAATGTGTCAGCCTCACCGCAGTTGTAACATCAATGAAGATTCGGGACTCCCTCT GGCTTTCACAATTGCCCATGAGCTAGGACACAGCTTCGGCATCCAGCATGATGGGAAAGAAAATGACT GTGAGCCTGTGGGCAGACATCCGTACATCATGTCCCGCCAGCTCCAGTACGATCCCACTCCGCTGACA TGGTCCAAGTGCAGCGAGGAGTACATCACCCGCTTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGA CATACCTAAAAAGAAAGGCTTGAAGTCCAAGGTCATTGCCCCCGGAGTGATCTATGATGTTCACCACC AGTGCCAGCTACAATATGGACCCAATGCTACCTTCTGCCAGGAAGTAGAAAACGTCTGCCAGACACTG TGGTGCTCCGTGAAGGGCTTTTGTCGCTCTAAGCTGGACGCTGCTGCAGATGGAACTCAATGTGGTGA GAAGAAGTGGTGTATGGCAGGCAAGTGCATCACAGTGGGGAAGAAACCAGAGAGCATTCCTGGAGGCT GGGGCCGCTGGTCACCCTGGTCCCACTGTTCCAGGACCTGTGGGGCTGGAGTCCAGAGCGCAGAGAGG CTCTGCAACAACCCCGAGCCAAAGTTTGGAGGGAAATATTGCACTGGAGAAAGAAAACGCTATCGCTT GTGCAACGTCCACCCCTGTCGCTCAGAGGCACCAACATTTCGGCAGATGCAGTGCAGTGAATTTGACA CTGTTCCCTACAAGAATGAACTCTACCACTGGTTTCCCATTTTTAACCCAGCACATCCTTGTGAGCTC TACTGCCGACCCATAGATGGCCAGTTTTCTGAGAAAATGCTGGATGCTGTCATTGATGGTACCCCTTG CTTTGAAGGCGGCAACAGCAGAAATGTCTGTATTAATGGCATATGTAAGATGGTTGGCTGTGACTATG AGATCGATTCCAATGCCACCGAGGATCGCTGCGGTGTGTGCCTGGGAGATGGCTCTTCCTGCCAGACT GTGAGAAAGATGTTTAAGCAGAAGGAAGGATCTGGTTATGTTGACATTGGGCTCATTCCAAAAGGAGC AAGGGACATAAGAGTGATGGAAATTGAGGGAGCTGGAAACTTCCTGGCCATCAGGAGTGAAGATCCTG AAAAATATTACCTGAATGGAGGGTTTATTATCCAGTGGAACGGGAACTATAAGCTGGCAGGGACTGTC TTTCAGTATGACAGGAAAGGAGACCTGGAAAAGCTGATGGCCACAGGTCCCACCAATGAGTCTGTGTG GATCCAGCTTCTATTCCAGGTGACTAACCCTGGCATCAAGTATGAGTACACAATCCAGAAAGATGGCC TTGACAATGATGTTGAGCAGCAGATGTACTTCTGGCAGTACGGCCACTGGACAGAGTGCAGTGTGACC TGCGGGACAGGTATCCGCCGCCAAACTGCCCATTGCATAAAGAAGGGCCGCGGGATGGTGAAAGCTAC ATTCTGTGACCCAGAAACACAGCCCAATGGGAGACAGAAGAAGTGCCATGAAAAGGCTTGTCCACCCA GGTGGTGGGCAGGGGAGTGGGAAGCATGCTCGGCGACATGCGGGCCCCACGGGGAGAAGAAGCGAACC GTGCTGTGCATCCAGACCATGGTCTCTGACGAGCAGGCTCTCCCGCCCACAGACTGCCAGCACCTGCT GAAGCCCAAGACCCTCCTTTCCTGCAACAGAGACATCCTGTGCCCCTCGGACTGGACAGTGGGCAACT GGAGTGAGTGTTCTGTTTCCTGTGGTGGTGGAGTGCGGATTCGCAGTGTCACATGTGCCAAGAACCAT GATGAACCTTGCGATGTGACAAGGAAACCCAACAGCCGAGCTCTGTGTGGCCTCCAGCAATGCCCTTC TAGCCGGAGAGTTCTGAAACCAAACAAAGGCACTATTTCCAATGGAAAAAACCCACCAACACTAAAGC CCGTCCCTCCACCTACATCCAGGCCCAGAATGCTGACCACACCCACAGGGCCTGAGTCTATGAGCACA AGCACTCCAGCAATCAGCAGCCCTAGTCCTACCACAGCCTCCAAAGAAGGAGACCTGGGTGGGAAACA GTGGCAAGATAGCTCAACCCAACCTGAGCTGAGCTCTCGCTATCTCATTTCCACTGGAAGCACTTCCC AGCCCATCCTCACTTCCCAATCCTTGAGCATTCAGCCAAGTGAGGAAAATGTTTCCAGTTCAGATACT GGTCCTACCTCGGAGGGAGGCCTTGTAGCTACAACAACAAGTGGTTCTGGCTTGTCATCTTCCCGCAA
CCCTATCACTTGGCCTGTGACTCCATTTTACAATACCTTGACCAAAGGTCCAGAAATGGAGATTCACA GTGGCTCAGGGGAAGAAAGAGAACAGCCTGAGGACAAAGATGAAAGCAATCCTGTAATATGGACCAAG ATCAGAGTACCTGGAAATGACGCTCCAGTGGAAAGTACAGAAATGCCACTTGCACCTCCACTAACACC AGATCTCAGCAGGGAGTCCTGGTGGCCACCCTTCAGCACAGTAATGGAAGGACTGCTCCCCAGCCAAA GGCCCACTACTTCCGAAACTGGGACACCCAGAGTTGAGGGGATGGTTACTGAAAAGCCAGCCAACACT CTGCTCCCTCTGGGAGGAGACCACCAGCCAGAACCCTCAGGAAAGACGGCAAACCGTAACCACCTGAA ACTTCCAAACAACATGAACCAAACAAAAAGTTCTGAACCAGTCCTGACTGAGGAGGATGCAACAAGTC TGATTACTGAGGGCTTTTTGCTAAATGCCTCCAATTACAAGCAGCTCACAAACGGCCACGGCTCTGCA CACTGGATCGTCGGAAACTGGAGCGAGTGCTCCACCACATGTGGCCTGGGGGCCTACTGGAGAAGGGT GGAGTGCAGCACCCAGATGGATTCTGACTGTGCGGCCATCCAGAGACCTGACCCTGCAAAAAGATGCC ACCTCCGTCCCTGTGCTGGCTGGAAAGTGGGAAACTGGAGCAAGTGCTCCAGAAACTGCAGTGGGGGC TTCAAGATACGCGAGATTCAGTGCGTGGACAGCCGGGACCACCGGAACCTGAGGCCATTTCACTGCCA GTTCCTGGCCGGCATTCCTCCCCCATTGAGCATGAGCTGTAACCCGGAGCCCTGTGAGGCGTGGCAGG TGGAGCCTTGGAGCCAGTGCTCCAGGTCCTGTGGAGGTGGAGTTCAGGAGAGAGGAGTGTTCTGTCCA GGAGGCCTCTGTGATTGGACAAAAAGACCCACATCCACCATGTCTTGCAATGAGCACCTGTGCTGTCA CTGGGCCACTGGGAACTGGGACCTGTGTTCCACTTCCTGTGGAGGTGGCTTTCAGAAGAGGACTGTCC AATGTGTGCCCTCAGAGGGCAATAAAACTGAAGACCAAGACCAATGTCTATGTGATCACAAACCCAGA CCTCCAGAATTCAAAAAATGCAACCAGCAGGCCTGCAAGAAAAGTGCCGATTTACTTTGCACTAAGGA CAAACTGTCAGCCAGTTTCTGCCAGACACTGAAAGCCATGAAGAAATGTTCTGTGCCCACCGTGAGGG CTGAGTGCTGCTTCTCGTGTCCCCAGACACACATCACACACACCCAAAGGCAAAGAAGGCAACGGTTG CTCCAAAAGTCAAAAGGACTCCTCGAGGAGTTCTTTTGACTTTTGGAGCAACCGGGCCTGGCTGAGGC TGTCTCCCATAAGATCT
NOV68f, 305867δ66 SEQ ID NO: 1016 1576 aa MW at l75δ22.7kD Protein Sequence
RSYGRQPQPGPVRFPDRRQEHFIKGLPEYHWGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWV YYRISHEEKDLFFNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSA CHGLTGFFQLPHGDFFIEPVKKHPLλ^EGGYHPHIVYRRQKVPETIEPTCGLKDSVNISQKQELWREK ERHNLPSRSLSRRSISKEROTETLWADTKMIEYHGSE VESYILTIMNMOTGLFHNPSIGNAIHIVV VRLILLEEEEQGLKIVHHAEKTLSSFCPWQKSINPKSDLNPVHHDVAVLLTRIDICAGF RPCETLGL SHLSGMCQPHRSC INEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLT WSKCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATFCQEVE VCQTL WCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHCSRTCGAGVQSAER LCNNPEPKFGG YCTGERKRYRLCNVΗPCRSEAPTFRQMQCSEFDTVPYKNELYHWFPIFNPAHPCEL YCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICKMVGCDYEIDSNATEDRCGVCLGDGSSCQT VRKMFKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTV FQYDRKGDLEFCLMATGPTNESVWIQLLFQVTNPGIKYEYTIQPsDGLDNDVEQQMYFWQYGHWTECSVT CGTGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRT VLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKNH DEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMST STPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEENVSSSDT GPTSEGGLVATTTSGSGLSSSR PITWPVTPFYNTLTKGPEMEIHSGSGEEREQPEDKDESNPVIWTK IRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRPTTSETGTPRVEGMVTEKPANT LLPLGGDHQPEPSGKTANR HLKLP NMNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSA HWIVGNWSECSTTCGLGAYWRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGG FKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCP GGLCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLCDHKPR PPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQRL LQKSKGLLEEFF
NOV6δg, 31δl76397 SEQ ID NO: 1017 3174 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
CTGGAATGCGCCCTTAGATCTGGCCGCTGGTCACCCTGGTCCCACTGTTCCAGGACCTGTGGGGCTGG AGTCCAGAGCGCAGAGAGGCTCTGCAACAACCCCGAGCCAAAGTTTGGAGGGAAATATTGCACTGGAG AAAGAAAACGCTATCGCTTGTGCAACGTCCACCCCTGTCGCTCAGAGGCACCAACATTTCGGCAGATG CAGTGCAGTGAATTTGACACTGTTCCCTACAAGAATGAACTCTACCACTGGTTTCCCATTTTTAACCC AGCACATCCTTGTGAGCTCTACTGCCGACCCATAGATGGCCAGTTTTCTGAGAAAATGCTGGATGCTG TCATTGATGGTACCCCTTGCTTTGAAGGCGGCAACAGCAGAAATGTCTGTATTAATGGCATATGTAAG ATGGTTGGCTGTGACTATGAGATCGATTCCAATGCCACCGAGGATCGCTGCGGTGTGTGCCTGGGAGA TGGCTCTTCCTGCCAGACTGCGAGAAAGATGTTTAAGCAGAAGGAAGGATCTGGTTATGTTGACATTG GGCTCATTCCAAAAGGAGCAAGGGACATAAGAGTGATGGAAATTGAGGGAGCTGGAAACTTCCTGGCC ATCAGGAGTGAAGATCCTGAAAAATATTACCTGAATGGAGGGTTTATTATCCAGTGGAACGGGAACTA TAAGCTGGCAGGGACTGTCTTTCAGTATGACAGGAAAGGAGACCTGGAAAAGCTGATGGCCACAGGTC CCACCAATGAGTCTGTGTGGATCCAGCTTCTATTCCAGGTGACTAACCCTGGCATCAAGTATGAGTAC ACAATCCAGAAAGATGGCCTTGACAATGATGTTGAGCAGCAGATGTACTTCTGGCAGTACGGCCACTG GACAGAGTGCAGTGTGACCTGCGGGACAGGTATCCGCCGCCAAACTGCCCATTGCATAAAGAAGGGCC GCGGGATGGTGAAAGCTACATTCTGTGACCCAGAAACACAGCCCAATGGGAGACAGAAGAAGTGCCAT GAAAAGGCTTGTCCACCCAGGTGGTGGGCAGGGGAGTGGGAAGCATGCTCGGCGACATGCGGGCCCCA CGGGGAGAAGAAGCGAACCGTGCTGTGCATCCAGACCATGGTCTCTGACGAGCAGGCTCTCCCGCCCA CAGACTGCCAGCACCTGCTGAAGCCCAAGACCCTCCTTTCCTGCAACAGAGACATCCTGTGCCCCTCG GACTGGACAGTGGGCAACTGGAGTGAGTGTTCTGTTTCCTGTGGTGGTGGAGTGCGGATTCGCAGTGT CACATGTGCCAAGAACCATGATGAACCTTGCGATGTGACAAGGAAACCCAACAGCCGAGCTCTGTGTG GCCTCCAGCAATGCCCTTCTAGCCGGAGAGTTCTGAAACCAAACAAAGGCACTATTTCCAATGGAAAA AACCCACCAACACTAAAGCCCGTCCCTCCACCTACATCCAGGCCCAGAATGCTGACCACACCCACAGG GCCTGAGTCTATGAGCACAAGCACTCCGGCAATCAGCAGCCCTAGTCCTACCACAGCCTCCAAAGAAG GAGACCTGGGTGGGAAACAGTGGCAAGATAGCTCAACCCAACCTGAGCTGAGCTCTCGCTATCTCATT TCCACTGGAAGCACTTCCCAGCCCATCCTCACTTCCCAATCCTTGAGCATTCAGCCAAGTGAGGAAAA TGTTTCCAGTTCAGATACTGGTCCTACCTCGGAGGGAGGCCTTGTAGCTACAACAACAAGTGGTTCTG GCTTGTCATCTTCCCGCAACCCTATCACTTGGCCTGTGACTCCATTTTACAATACCTTGACCAAAGGT CCAGAAATGGAGATTCACAGTGGCTCAGGGGAAGAAAGAGAACAGCCTGAGGACAAAGATGAAAGCAA TCCTGTAATATGGACCAAGATCAGAGTACCTGGAAATGACGCTCCAGTGGAAAGTACAGAAATGCCAC TTGCACCTCCACTAACACCAGATCTCAGCAGGGAGTCCTGGTGGCCACCCTTCAGCACAGTAATGGAA GGACTGCTCCCCAGCCAAAGGCCCACTACTTCCGAAACTGGGACACCCAGAGTTGAGGGGATGGTTAC TGAAAAGCCAGCCAACACTCTGCTCCCTCTGGGAGGAGACCACCAGCCAGAACCCTCAGGAAAGACGG CAAACCGTAACCACCTGAAACTTCCAAACAACATGAACCAAACAAAAAGTTCTGAACCAGTCCTGACT GAGGAGGATGCAACAAGTCTGATTACTGAGGGCTTTTTGCTAAATGCCTCCAATTACAAGCAGCTCAC AAACGGCTACGGCTCTGCACACTGGATCGTCGGAAACTGGAGCGAGTGCTCCACCACATGTGGCCTGG GGGCCTACTGGAGAAGGGTGGAGTGCAGCACCCAGATGGATTCTGACTGTGCGGCCATCCAGAGACCT GACCCTGCAAAAAGATGCCACCTCCGTCCCTGTGCTGGCTGGAAAGTGGGAAACTGGAGCAAGTGCTC CAGAAACTGCAGTGGGGGCTTCAAGATACGCGAGATTCAGTGCGTGGACAGCCGGGACCACCGGAACC TGAGGCCATTTCACTGCCAGTTCCTGGCCGGCATTCCTCCCCCATTGAGCATGAGCTGTAACCCGGAG CCCTGTGAGGCGTGGCAGGTGGAGCCTTGGAGCCAGTGCTCCAGGTCCTGTGGAGGTGGAGTTCAGGA GAGAGGAGTGTTCTGTCCAGGAGGCCTCTGTGATTGGACAAAAAGACCCACATCCACCATGTCTTGCA ATGAGCACCTGTGCTGTCACTGGGCCACTGGGAACTGGGACCTGTGTTCCACTTCCTGTGGAGGCGGC TTTCAGAAGAGGACTGTCCAATGTGTGCCCTCAGAGGGCAATAAAACTGAAGACCAAGACCAATGTCT ATGTGATCACAAACCCAGACCTCCAGAATTCAAAAAATGCAACCAGCAGGCCTGCAAGAAAAGTGCCG ATTTACTTTGCACTAAGGACAAACTGTCAGCCAGTTTCTGCCAGACACTGAAAGCCATGAAGAAATGT TCTGTGCCCACCGTGAGGGCTGAGTGCTGCTTCTCGTGTCCCCAGACACACATCACACACACCCAAAG GCAAAGAAGGCAACGGTTGCTCCAAAAGTCAAAAGAACTCCTCGAG
NOV6δg, 318176397 SEQ ID NO: 1018 1058 aa MW at l l7062.0kD Protein Sequence
LECALRSGRWSPWSHCSRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLC VHPCRSEAPTFRQM QCSEFDTVPYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSR VCINGICK VGCDYEIDSNATEDRCGVCLGDGSSCQTARKMFKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLA IRSEDPEKYYL GGFIIQWNG YKLAGTVFQYDRKGDLEKLMATGPTNESVWIQLLFQVT PGIKYEY TIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQKKCH EKACPPRWWAGEWEACSATCGPHGEKIRTVLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPS DWTVGNWSECSVSCGGGVRIRSVTCAKNHDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGK NPPTLKPVPPPTSRPRMLTTPTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLI STGSTSQPILTSQSLSIQPSEE VSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKG PEMEIHSGSGEEREQPEDPCDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVME GLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNNM QTKSSEPVLT EEDATSLITEGFLLNASNYKQLTNGYGSAHWIVGNWSECSTTCGLGAYWRRVECSTQMDSDCAAIQRP DPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSC PE PCEAWQVEPWSQCSRSCGGGVQERGVFCPGGLCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGG FQKRTVQCVPSEGNKTEDQDQCLCDHKPRPPEF KCNQQACKKSADLLCTΪ03KLSASFCQTLKAMKKC SVPTVRAECCFSCPQTHITHTQRQRRQRLLQKSKELLE
NOV6δh, CG5δ504-02 SEQ ID NO: 1019 106δ bp DNA Sequence ORF Start: at 7 ORF Stop: at 1063
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA
CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGATGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTGCATCCTCACCATCATGAACATGGTCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG CTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGGCAGACATCCGTACATCATGT CCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCAGCGAGGAGTACATCACCCGC TTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTCTCGAG
NOV6δh, CG5δ504-02 SEQ ID NO: 1020 352 aa MW at 39δ53.3kD Protein Sequence
NLTV QGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGMAALSACHGLTGFFQLPHG DFFIEPVKKHPLVEGGYHPHIVΥRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLSRR SISKER n ETLv ADTKMIEYHGSE^rv^SCILTIM MVTGLFH PSIG AIHIVVVRLILLEEEEQGL KIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAV1.LTRI DICAGFNRPCETLGLSHLSGMCQPHRSC NINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITRFL DRGWGFCLDDIP
NOV6δi, CG5δ504-03 SEQ ID NO: 1021 106δ bp DNA Sequence ORF Start: at 7 ORF Stop: at 1063
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA
CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTACATCCTCACCATCATGAACATGATCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG CTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGGCAGACATCCGTACATCATGT CCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCAGCGAGGAGTACATCACCCGC TTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTCTCGAG
NOV6δi, CG5δ504-03 SEQ ID NO: 1022 352 aa MW at 39δ97.2kD Protein Sequence
NLTV QGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLPHG DFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSWISQKQELWREKWERHNLPSRSLSRR SISKERWVETLWADTΪ-MIEYHGSE VESYILTIM MITGLFHNPSIGNAIHIVWRLILLEEEEQGL KIVHHAEKTLSSFCKWQKSINPKSDL PVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSC NINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITRFL DRGWGFCLDDIP
NOV6δj, CG5δ504-04 SEQ ID NO: 1023 1252 bp DNA Sequence ORF Start: at 7 ORF Stop: at 247
AAGCTTCACCAGTGCCAGCTACAATATGGACCCAATGCTACCTTCTGCCAGGAAGTAGAAAACGTCTGi
CCAGACACTGTGGTGCTCCGTGAAGGGCTTTTGTCGCTCTAAGCTGGACGCTGCTGCAGATGGAACTC AATGTGGTGAGAAGAAGTGGTGTATGGCAGGCAAGTGCATCACAGTGGGGAAGAAACCAGAGAGCATT CCTGGAGGCTGCGGCCGCTGGTCACCCTGGTCCCACTGTTCCCTCGAG
NOVόδj, CG58504-04 SEQ ID NO: 1024 80 aa MW at 8757.0kD Protein Sequence
HQCQLQYGPNATFCQEVΈNVCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPG GCGRWSPWSHCS
NOV6δk, CG5δ504-05 SEQ ID NO: 1025 4777 bp ;DNA Sequence ORF Start: at 7 ORF Stop: TGA at 4729
AGATCTTATGGGAGACAGCCTCAGCCAGGCCCGGTTCGCTTCCCGGACAGGAGGCAAGAGCATTTTAT
CAAGGGCCTGCCAGAATACCACGTGGTGGGTCCAGTCCGAGTAGATGCCAGTGGGCATTTTTTGTCAT ATGGCTTGCACTATCCCATCACGAGCAGCAGGAGGAAGAGAGATTTGGATGGCTCAGAGGACTGGGTG TACTACAGAATTTCTCACGAGGAGAAGGACCTGTTTTTTAACTTGACGGTCAATCAAGGATTTCTTTC CAATAGCTACATCATGGAGAAGAGATATGGGAACCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCC CCCTCTGCCATCTCAGTGGCACGGTTCTACAGCAGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCC TGCCATGGACTGACTGGATTTTTCCAACTACCACATGGAGACTTTTTCATTGAACCCGTGAAGAAGCA TCCACTGGTTGAGGGAGGGTACCACCCGCACATCGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGG AGCCAACCTGTGGATTAAAGGACAGTGTTAACATCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGG GAGAGGCACAACTTGCCAAGCAGAAGCCTCTCTCGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGAC ACTGGTGGTGGCCGACACAAAGATGATTGAATACCATGGGAGTGAGAATGTGGAGTCCTACATCCTCA CCATCATGAACATGGTCACTGGGTTGTTCCATAACCCAAGCATTGGCAATGCAATTCACATTGTTGTG GTTCGGCTCATTCTACTCGAAGAAGAAGAGCAAGGACTGAAAATAGTTCACCATGCAGAAAAGACACT GTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAATCCCAAGAGTGACCTCAATCCTGTTCATCACGACG TGGCTGTCCTTCTCACTAGAAAGGACATCTGTGCTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTG TCTCACCTTTCAGGAATGTGTCAGCCTCACCGCAGTTGTAACATCAATGAAGATTCGGGACTCCCTCT GGCTTTCACAATTGCCCATGAGCTAGGACACAGCTTCGGCATCCAGCATGATGGGAAAGAAAATGACT GTGAGCCTGTGGGCAGACATCCGTACATCATGTCCCGCCAGCTCCAGTACGATCCCACTCCGCTGACA TGGTCCAAGTGCAGCGAGGAGTACATCACCCGCTTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGA CATACCTAAAAAGAAAGGCTTGAAGTCCAAGGTCATTGCCCCCGGAGTGATCTATGATGTTCACCACC AGTGCCAGCTACAATATGGACCCAATGCTACCTTCTGCCAGGAAGTAGAAAACGTCTGCCAGACACTG TGGTGCTCCGTGAAGGGCTTTTGTCGCTCTAAGCTGGACGCTGCTGCAGATGGAACTCAATGTGGTGA GAAGAAGTGGTGTATGGCAGGCAAGTGCATCACAGTGGGGAAGAAACCAGAGAGCATTCCTGGAGGCT GGGGCCGCTGGTCACCCTGGTCCCACTGTTCCAGGACCTGTGGGGCTGGAGTCCAGAGCGCAGAGAGG CTCTGCAACAACCCCGAGCCAAAGTTTGGAGGGAAATATTGCACTGGAGAAAGAAAACGCTATCGCTT GTGCAACGTCCACCCCTGTCGCTCAGAGGCACCAACATTTCGGCAGATGCAGTGCAGTGAATTTGACA CTGTTCCCTACAAGAATGAACTCTACCACTGGTTTCCCATTTTTAACCCAGCACATCCTTGTGAGCTC TACTGCCGACCCATAGATGGCCAGTTTTCTGAGAAAATGCTGGATGCTGTCATTGATGGTACCCCTTG CTTTGAAGGCGGCAACAGCAGAAATGTCTGTATTAATGGCATATGTAAGATGGTTGGCTGTGACTATG AGATCGATTCCAATGCCACCGAGGATCGCTGCGGTGTGTGCCTGGGAGATGGCTCTTCCTGCCAGACT GTGAGAAAGATGTTTAAGCAGAAGGAAGGATCTGGTTATGTTGACATTGGGCTCATTCCAAAAGGAGC AAGGGACATAAGAGTGATGGAAATTGAGGGAGCTGGAAACTTCCTGGCCATCAGGAGTGAAGATCCTG AAAAATATTACCTGAATGGAGGGTTTATTATCCAGTGGAACGGGAACTATAAGCTGGCAGGGACTGTC TTTCAGTATGACAGGAAAGGAGACCTGGAAAAGCTGATGGCCACAGGTCCCACCAATGAGTCTGTGTG GATCCAGCTTCTATTCCAGGTGACTAACCCTGGCATCAAGTATGAGTACACAATCCAGAAAGATGGCC TTGACAATGATGTTGAGCAGCAGATGTACTTCTGGCAGTACGGCCACTGGACAGAGTGCAGTGTGACC TGCGGGACAGGTATCCGCCGCCAAACTGCCCATTGCATAAAGAAGGGCCGCGGGATGGTGAAAGCTAC ATTCTGTGACCCAGAAACACAGCCCAATGGGAGACAGAAGAAGTGCCATGAAAAGGCTTGTCCACCCA GGTGGTGGGCAGGGGAGTGGGAAGCATGCTCGGCGACATGCGGGCCCCACGGGGAGAAGAAGCGAACC GTGCTGTGCATCCAGACCATGGTCTCTGACGAGCAGGCTCTCCCGCCCACAGACTGCCAGCACCTGCT GAAGCCCAAGACCCTCCTTTCCTGCAACAGAGACATCCTGTGCCCCTCGGACTGGACAGTGGGCAACT GGAGTGAGTGTTCTGTTTCCTGTGGTGGTGGAGTGCGGATTCGCAGTGTCACATGTGCCAAGAACCAT GATGAACCTTGCGATGTGACAAGGAAACCCAACAGCCGAGCTCTGTGTGGCCTCCAGCAATGCCCTTC TAGCCGGAGAGTTCTGAAACCAAACAAAGGCACTATTTCCAATGGAAAAAACCCACCAACACTAAAGC CCGTCCCTCCACCTACATCCAGGCCCAGAATGCTGACCACACCCACAGGGCCTGAGTCTATGAGCACA AGCACTCCAGCAATCAGCAGCCCTAGTCCTACCACAGCCTCCAAAGAAGGAGACCTGGGTGGGAAACA GTGGCAAGATAGCTCAACCCAACCTGAGCTGAGCTCTCGCTATCTCATTTCCACTGGAAGCACTTCCC AGCCCATCCTCACTTCCCAATCCTTGAGCATTCAGCCAAGTGAGGAAAATGTTTCCAGTTCAGATACT GGTCCTACCTCGGAGGGAGGCCTTGTAGCTACAACAACAAGTGGTTCTGGCTTGTCATCTTCCCGCAA
CCCTATCACTTGGCCTGTGACTCCATTTTACAATACCTTGACCAAAGGTCCAGAAATGGAGATTCACA GTGGCTCAGGGGAAGAAAGAGAACAGCCTGAGGACAAAGATGAAAGCAATCCTGTAATATGGACCAAG ATCAGAGTACCTGGAAATGACGCTCCAGTGGAAAGTACAGAAATGCCACTTGCACCTCCACTAACACC AGATCTCAGCAGGGAGTCCTGGTGGCCACCCTTCAGCACAGTAATGGAAGGACTGCTCCCCAGCCAAA GGCCCACTACTTCCGAAACTGGGACACCCAGAGTTGAGGGGATGGTTACTGAAAAGCCAGCCAACACT CTGCTCCCTCTGGGAGGAGACCACCAGCCAGAACCCTCAGGAAAGACGGCAAACCGTAACCACCTGAA ACTTCCAAACAACATGAACCAAACAAAAAGTTCTGAACCAGTCCTGACTGAGGAGGATGCAACAAGTC TGATTACTGAGGGCTTTTTGCTAAATGCCTCCAATTACAAGCAGCTCACAAACGGCCACGGCTCTGCA CACTGGATCGTCGGAAACTGGAGCGAGTGCTCCACCACATGTGGCCTGGGGGCCTACTGGAGAAGGGT GGAGTGCAGCACCCAGATGGATTCTGACTGTGCGGCCATCCAGAGACCTGACCCTGCAAAAAGATGCC ACCTCCGTCCCTGTGCTGGCTGGAAAGTGGGAAACTGGAGCAAGTGCTCCAGAAACTGCAGTGGGGGC TTCAAGATACGCGAGATTCAGTGCGTGGACAGCCGGGACCACCGGAACCTGAGGCCATTTCACTGCCA GTTCCTGGCCGGCATTCCTCCCCCATTGAGCATGAGCTGTAACCCGGAGCCCTGTGAGGCGTGGCAGG TGGAGCCTTGGAGCCAGTGCTCCAGGTCCTGTGGAGGTGGAGTTCAGGAGAGAGGAGTGTTCTGTCCA GGAGGCCTCTGTGATTGGACAAAAAGACCCACATCCACCATGTCTTGCAATGAGCACCTGTGCTGTCA CTGGGCCACTGGGAACTGGGACCTGTGTTCCACTTCCTGTGGAGGTGGCTTTCAGAAGAGGACTGTCC AATGTGTGCCCTCAGAGGGCAATAAAACTGAAGACCAAGACCAATGTCTATGTGATCACAAACCCAGA CCTCCAGAATTCAAAAAATGCAACCAGCAGGCCTGCAAGAAAAGTGCCGATTTACTTTGCACTAAGGA CAAACTGTCAGCCAGTTTCTGCCAGACACTGAAAGCCATGAAGAAATGTTCTGTGCCCACCGTGAGGG CTGAGTGCTGCTTCTCGTGTCCCCAGACACACATCACACACACCCAAAGGCAAAGAAGGCAACGGTTG CTCCAAAAGTCAAAAGGACTCCTCGAGGAGTTCTTTTGACTTTTGGAGCAACCGGGCCTGGCTGAGGC TGTCTCCCATAAGATCT
NOVόδk, CG58504-05 SEQ ID NO: 1026 1574 aa MW at l75579.4kD Protein Sequence
YGRQPQPGPVRFPDRRQEHFIKGLPEYHWGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWVYY RISHEEKDLFFNLTWQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACH GLTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVΎRRQKVPETKEPTCGLKDSVNISQKQELWREKWER HNLPSRSLSRRSISKERWVETLVVADTKMIEYHGSENVESYILTIMNMVTGLFHNPSIGNAIHIVVVR LILLEEEEQGL IVHHAEKTLSSFCKWQKSINPKSDL P-VTHHDVAVLLTRKDICAGFNRPCETLGLSH LSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWS KCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATFCQEVENVCQTLWC SVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHCSRTCGAGVQSAERLC N PEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTVPYKNELYHWFPIFNPAHPCELYC RPIDGQFSEKMLDAVIDGTPCFEGGNSR VCINGICKMVGCDYEIDSNATEDRCGVCLGDGSSCQTVR KMFKQKEGSGYVDIGLIPKGARDIRλ^MEIEGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQ YDRKGDLEKLMATGPTNESVWIQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCG TGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQ?KCHEKACPPRWWAGEWEACSATCGPHGE?KRTVL CIQTMVSDEQALPPTDCQHLLKPKTLLSCTJRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAK HDE PCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMSTST PAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEE VSSSDTGP TSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEMEIHSGSGEEREQPEDKDESNPVIWTKIR VPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRPTTSETGTPRVEGMVTEKPA TLL PLGGDHQPEPSGKTARNHLΪLP NM QTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHW IVGNWSECSTTCGLGAYWRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFK IREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGG LCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLCDHKPRPP EFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQRLLQ KSKGLLEEFF
NOV681, CG58504-06 SEQ ID NO: 1027 1068 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTAACTTGACGGTCAATCAAGGATTTCTTTCCAATAGCTACATCATGGAGAAGAGATATGGGAA CCTCTCCCATGTTAAGATGATGGCTTCCTCTGCCCCCCTCTGCCATCTCAGTGGCACGGTTCTACAGC AGGGCACCAGAGTTGGGACGGCAGCCCTCAGTGCCTGCCATGGACTGACTGGATTTTTCCAACTACCA CATGGAGACTTTTTCATTGAACCCGTGAAGAAGCATCCACTGGTTGAGGGAGGGTACCACCCGCACAT CGTTTACAGGAGGCAGAAAGTTCCAGAAACCAAGGAGCCAACCTGTGGATTAAAGGACAGTGTTAACA TCTCCCAGAAGCAAGAGCTATGGCGGGAGAAGTGGGAGAGGCACAACTTGCCAAGCAGAAGCCTCTCT CGGCGTTCCATCAGCAAGGAGAGATGGGTGGAGACACTGGTGGTGGCCGACACAAAGATGATTGAATA CCATGGGAGTGAGAATGTGGAGTCCTACATCCTCACCATCATGAACATGGTCACTGGGTTGTTCCATA ACCCAAGCATTGGCAATGCAATTCACATTGTTGTGGTTCGGCTCATTCTACTCGAAGAAGAAGAGCAA GGACTGAAAATAGTTCACCATGCAGAAAAGACACTGTCTAGCTTCTGCAAGTGGCAGAAGAGTATCAA TCCCAAGAGTGACCTCAATCCTGTTCATCACGACGTGGCTGTCCTTCTCACCAGAAAGGACATCTGTG CTGGTTTCAATCGCCCCTGCGAGACCCTGGGCCTGTCTCACCTTTCAGGAATGTGTCAGCCTCACCGC AGTTGTAACATCAATGAAGATTCGGGACTCCCTCTGGCTTTCACAATTGCCCATGAGCTAGGACACAG CTTCGGCATCCAGCATGATGGGAAAGAAAATGACTGTGAGCCTGTGGGCAGACATCCGTACATCATGT CCCGCCAGCTCCAGTACGATCCCACTCCGCTGACATGGTCCAAGTGCAGCGAGGAGTACATCACCCGC TTCTTGGACCGAGGCTGGGGGTTCTGTCTTGATGACATACCTCTCGAG
NOV6δl, CG5δ504-06 SEQ ID NO: 102δ 356 aa MW at 40366.8kD Protein Sequence LNLTV QGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLP HGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLS RRSISKERWVETLWADTKMIEYHGSENVESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEEEQ GLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHR SCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITR FLDRGWGFCLDDIPLE
NOV6δm, CG5δ504-07 SEQ ID NO: 1029 252 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AAGCTTCACCAGTGCCAGCTACAATATGGACCCAATGCTACCTTCTGCCAGGAAGTAGAAAACGTCTG CCAGACACTGTGGTGCTCCGTGAAGGGCTTTTGTCGCTCTAAGCTGGACGCTGCTGCAGATGGAACTC AATGTGGTGAGAAGAAGTGGTGTATGGCAGGCAAGTGCATCACAGTGGGGAAGAAACCAGAGAGCATT CCTGGAGGCTGGGGCCGCTGGTCACCCTGGTCCCACTGTTCCCTCGAG
NOV6δm, CG58504-07 SEQ ID NO: 1030 84 aa MW at 9323.7kD Protein Sequence
KLHQCQLQYGPNATFCQEVE VCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESI PGGWGRWSP SHCSLE A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 6δB.
Table 68B. Comparison of the NOV68 protein sequences.
NOV68a MPCAQRSWLANLSWAQLLNFGALCYGRQPQPGPVRFPDRRQEHFIKGLPEYHWGPVRV
NOV68b
NOV68c
NOV68d
NOV68e
NOV68f
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k
NOV681
NOV68m
NOV68a DASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDLFFNLTVNQGFLSNSYIME
NOV68b
NOV68c
NOV68d
NOV68e
NOV68f
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k
NOV681
NOV68m
NOV68a KRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLPHGDFFIEPVK
NOV68b
NOV68c
NOV68d
NOV68e
NOV68f
NOV68g LECALRSGRWSPWSHCSRTCGAGVQSAE
NOV68h
NOV68i
NOV68J
NOV68k
NOV681
NOV68m
NOV68a KHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLSRR
NOV68b
NOV68C
NOV68d
NOV68e
NOV68f
NOV68g RLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTVPYKNELYHWFPI
NOV68h
NOV68i
NOV68J NOV68k
NOV681
NOV68m
NOV68a SISKERWVΕTLVVADTKMIEYHGSENVESYILTIMNMVTGLFHNPSIGNAIHIVVVRLIL
NOV68b
NOV68C
NOV68d
NOV68e
NOV68f
NOV68g FNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICKMVGCDYEIDSNA
NOV68h
NOV68i
NOV68J
NOV68k
NOV681
NOV68m
NOV68a LEEEEQGLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGF RPCET
NOV68b
NOV68C
NOV68d
NOV68e RSYGRQPQPGPVRFPDRRQ
NOV68f RSYGRQPQPGPVRFPDRRQ
NOV68g TEDRCGVCLGDGSSCQTARKMFKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSE
NOV68h
NOV68i
NOV68k YGRQPQPGPVRFPDRRQ
NOV681
NOV68m
NOV68a LGLSHLSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMS
NOV68b
NOV68c
NOV68d
NOV68e EHFIKGLPEYHWGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDL
NOV68 f EHFI KGLPEYHWGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRI SHEEKDL
NOV68g DPEKYYLNGGFI IQW GNYKLAGTVFQYDRKGDLEKLMATGPTNESVWIQLLFQVTNPGI
NOV68h
NOV68i
NOV68j
NOV68k EHFIKGLPEYHWGP VDASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDL
NOV681
NOV68m
NOV68a RQLQYDPTPLTWSKCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQL
NOV68b KLNLTVNQGFLSNSYIMEKRYGNLSHVK MASSAPLCHLSGTVLQQGTRVGMAALSACHG
NOV68 c KLNLTVNQGFLSNSYIMEKRYGNLSHVICMMASSAPLCHLSGTVLQQGTRVGTAALSACHG
NOV68d P LNLTV QGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHG
NOV68e FFNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLNGTVLQQGTRVGTAALSACHG
NOV68 f FFNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHG
NOV68g KYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKKGRGMVKATFCDP
NOV68h - -NLTVNQGFLSNSYIMEICRYGNLSHVK MASSAPLCHLSGTVLQQGTRVGMAALSACHG
NOV68 i - -NLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHG
NOV68 j HQCQL
NOV68k FFNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHG NOV681 KLNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHG NOV68m KLHQCQL
NOV68a QYGPNATFCQEVENVCQTLWCSVKGFCRSKLDAAA NOV68b LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68C LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68d LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68e LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68f LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68g ETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTMVSDEQALPPTDC NOV68h LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68i LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68J QYGPNATFCQEVENVCQTLWCSVKGFCRSKLDAAA NOV68k LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV681 LTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRR NOV68m QYGPNATFCQEVENVCQTLWCSVKGFCRSKLDAAA
NOV68a DGTQCGEKK- NOV68b QKVPETKEP- NOV68C QKVPETKEP- NOV68d QKVPETKEP- NOV68e QKVPETKEP- NOV68f QKVPETKEP- NOV68g QHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKNHDEPCDVTRKPN NOV68h QKVPETKEP- NOV68i QKVPETKEP- NOV68J DGTQCGEKK- NOV68k QKVPETKEP- NOV681 QKVPETKEP- NOV68m DGTQCGEKK-
NOV68a WCMAGKC NOV68b TCGLKDS NOV68c TCGLKDS NOV68d TCGLKDS NOV68e TCGLKDS NOV68f TCGLKDS NOV68g SRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMSTSTP NOV68h TCGLKDS NOV68i TCGLKDS NOV68J - - -WCMAGKC NOV68k TCGLKDS NOV681 TCGLKDS NOV68m WCMAGKC
NOV68a ITVGKKPESIPGGWGRWSPWSHCSRTCGAGVQSAERLC NPEPKFGGKYCT- - NOV68b VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68C VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68d VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68e VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68f VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68g AISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEE V NOV68h VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68i VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV68J ITVGKKPESIPGGCGRWSPWSHCS NOV68k VNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - NOV681 V ISQKQELWREKWERHNLPSRSLSRRSISKERWVETLWADTKMIEYHGS- - N0V68m - ITVGKKPESIPGGWGRWSPWSHCSLE-
N0V68a GERKRYRLCNVHPCRSEAPTFRQMQCSEFDTVPYKNELYH NOV68b ENVESCILTII VTGLFHNPSIGNAIHIVVVRLILLEEE NOV68C ENVESYILTIM ITGLFHNPSIGNAIHIVWRLILLEEE NOV68d ENVESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEE NOV68e ENVESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEE NOV68f ENVESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEE NOV68g SSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEMEIHSGSGEEREQP NOV68h ENVESCILTIMNMVTGLFHNPSIGNAIHI VRLILLEEE NOV68i ENVESYILTIMN ITGLFHNPSIGNAIHIVWRLILLEEE NOV68J NOV68k -ENVESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEE NOV681 -E VESYILTIMNMVTGLFHNPSIGNAIHIVWRLILLEEE NOV68m
NOV68a WFP
NOV68b EQG
NOV68C EQG
NOV68d EQG
NOV68e EQG
NOV68f EQG
NOV68g E EDDKKJDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRP
NOV68h EQG
NOV68i EQG
NOV68J
NOV68k EQG
NOV681 EQG
NOV68m
NOV68a IFNPAHPCELYCR NOV68b LKIVHHAEKTLSS NOV68C LKIVHHAEKTLSS NOV68d LKIVHHAEKTLSS NOV68e LKIVHHAEKTLSS NOV68f LKIVHHAEKTLSS
NOV68g TTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPN MNQTKSSEPVLT NOV68h LKIVHHAEKTLSS NOV68i LKIVHHAEKTLSS NOV68J NOV68k -LKIVHHAEKTLSS- NOV681 -LKIVHHAEKTLSS- NOV68m
NOV68a -PIDGQFSEKMLD NOV68b -FCKWQKSINPKS NOV68c -FCKWQKSINPKS NOV68d -FCKWQKSINPKS NOV68e -FCKWQKSINPKS NOV68f -FCKWQKSINPKS
NOV68g EEDATSLITEGFLLNASNYKQLTNGYGSAHWIVGNWSECSTTCGLGAYWRRVECSTQMDS
NOV68h -FCKWQKSINPKS NOV68i -FCKWQKSINPKS NOV68J NOV68k -FCKWQKSINPKS NOV681 -FCKWQKSINPKS NOV68m NOV68a AVIDGTPCFEGGNSRNVCINGICKMVGCDYEIDSNATEDRCGVCLGDG-SSCQTVRKMFK
NOV68b DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68c DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68d DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68e DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68f DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68g DCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDSRDHRNLRPFHCQ
NOV68h DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68i DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68J
NOV68k DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV681 DLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINE-DSGLPLAFTIA
NOV68m
NOV68a QKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSE DPEKYY
NOV68b HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68C HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68d HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68e HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68f HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68g FLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGLCDWTKRPTSTMS
NOV68h HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68i HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68j
NOV68k HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV681 HELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPT PLTWSK
NOV68m
NOV68a LNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVWIQLLFQVTNPGIKYEYTI
NOV68b CSEEYITRFLDRGWGFCLDDIPLE
NOV68C CSEEYITRFLDRGWGFCLDDIPLE
NOV68d CSEEYITRFLDRGWGFCLDDIPLE
NOV68e CSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATLCQEVEN
NOV68f CSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATFCQEVEN
NOV68g CNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLCDHKPRPPEFKKC
NOV68h CSEEYITRFLDRGWGFCLDDIP
NOV68i CSEEYITRFLDRGWGFCLDDIP
NOV68J
NOV68k CSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATFCQEVEN
NOV681 CSEEYITRFLDRGWGFCLDDIPLE
NOV68m
NOV68a QKDGLDNDVEQMYFWQYGHWTECSVTCGTGIRRQTAHCIKKGRGMVKATFCDPETQPNGR
NOV68b
NOV68c
NOV68d
NOV68e VCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHC
NOV68f VCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHC
NOV68g NQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQR
NOV68h
NOV68i
NOV68J
NOV68k VCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHC
NOV681
NOV68m NOV68a QKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTMVSDEQALPPTDCQHLLKPK
NOV68b
NOV68c
NOV68d
NOV68e SRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTV
NOV68f SRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTV
NOV68g LLQKSKELLE
NOV68h
NOV68i
NOV68J
NOV68k SRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTV
NOV681
NOV68m
NOV68a TLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKNHDEPCDVTRKPNSRALCGL
NOV68b
NOV68c
NOV68d
NOV68e PYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICK
NOV68f PYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICK
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k PYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICK
NOV681
NOV68m
NOV68a QQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMSTSTPAISSPSP
NOV68b
NOV68c
NOV68d
NOV68e MVGCDYEIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIGLIPKGARDIRVMEI
NOV68f MVGCDYEIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIGLIPKGARDIRVMEI
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k MVGCDYEIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIGLIPKGARDIRVMEI
NOV681
NOV68m
NOV68a TTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEENVSSSDTGP
NOV68b
NOV68c
NOV68d
NOV68e EGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVW
NOV68f EGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVW
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k EGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVW
NOV681
NOV68m
NOV68a TSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEMEIHSGSGEEREQPEDKDESN N0V68b
N0V68c
N0V68d
NOV68e IQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKK
NOV68f IQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKK
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k IQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKK
NOV681
NOV68m
NOV68a PVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRPTTSETGT
NOV68b
NOV68C
NOV68d
NOV68e GRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTM
NOV68f GRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTM
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k GRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTM
NOV681
NOV68m
NOV68a PRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNNMNQTKSSEPVLTEEDATSL
NOV68b
NOV68C
NOV68d
NOV68e VSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKN
NOV68f VSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKN
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k VSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKN
NOV681
NOV68m
NOV68a ITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAYWKRVECTTQMDSDCAAIQR
NOV68b
NOV68C
NOV68d
NOV68e HDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTT
NOV68f HDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTT
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k HDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTT
NOV681
NOV68m
NOV68a PDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDSRDHRNLRPFHCQFLAGIPP
NOV68b NOV68c
NOV68d
NOV68e PTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTS
NOV68f PTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTS
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k PTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTS
NOV681
NOV68m
NOV68a PLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGLCDWTKRPTSTMSCNEHLCC
NOV68b
NOV68c
NOV68d
NOV68e QSLSIQPSEENVSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEME
NOV68f QSLSIQPSEENVSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEME
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k QSLSIQPSEENVSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEME
NOV681
NOV68m
NOV68a HWATGNWDLCSTSCGGGFQKRIVQCVPSEGNKTEDQDQCLCDHKPRPPEFKKCNQQACKK
NOV68b
NOV68c
NOV68d
NOV68e IHSGSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFS
NOV68f IHSGSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFS
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k IHSGSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFS
NOV681
NOV68m
NOV68a SADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQRLLQKSKE
NOV68b
NOV68c
NOV68d
NOV68e TVMEGLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNN
NOV68f TVMEGLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNN
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k TVMEGLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNN
NOV681
NOV68m
NOV68a L
NOV68b
NOV68C N0V68d
NOV68e MNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAY
NOV68f MNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAY
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k MNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAY
NOV681
NOV68m
NOV68a
NOV68b
NOV68C
NOV68d
NOV68e WRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDS
NOV68f WRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDS
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k WRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDS
NOV681
NOV68m
NOV68a
NOV68b
NOV68C
NOV68d
NOV68e RDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGL
NOV68f RDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGL
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k RDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGL
NOV681
NOV68m
NOV68a
NOV68b
NOV68c
NOV68d
NOV68e CDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLC
NOV68f CDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLC
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k CDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLC
NOV681
NOV68m
NOV68a
NOV68b
NOV68c
NOV68d
93δ N0V68e DHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQT
NOV68f DHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQT
NOV68g
NOV68h
NOV68i
NOV68j
NOV68k DHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQT
NOV681
NOV68m
NOV68a
NOV68b
NOV68C
NOV68d
NOV68e HITHTQRQRRQRLLQKSKELLEEFF
NOV68f HITHTQRQRRQRLLQKSKGLLEEFF
NOV68g
NOV68h
NOV68i
NOV68J
NOV68k HITHTQRQRRQRLLQKSKGLLEEFF
NOV681
NOV68m
NOV68a (SEQ ID NO 1006)
NOV68b (SEQ ID NO 1008)
NOV68c (SEQ ID NO 1010)
NOV68d (SEQ ID NO 1012)
NOV68e (SEQ ID NO 1014)
NOV68f (SEQ ID NO 1016)
NOV68g (SEQ ID NO 1018)
NOV68h (SEQ ID NO 1020)
NOV68i (SEQ ID NO 1022)
NOV68J (SEQ ID NO 1024)
NOV68k (SEQ ID NO 1026)
NOV681 (SEQ ID NO 1028)
NOV68m (SEQ ID NO 1030)
Further analysis ofthe NOV6δa protein yielded the following properties shown in Table 68C.
Table 68C. Protein Sequence Properties NOV68a
SignalP analysis: Cleavage site between residues 26 and 27
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 6; pos. chg 1; neg.chg 0 H-region: length 21; peak value 6.23 PSG score: 1.83
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.11 possible cleavage site: between 27 and 28 >>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5-. 2 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 4.98 (at 267) ALOM score: -1.54 (number of TMSs: 0)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 6 Charge difference: 1.0 C( 3.0) - N( 2.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment (75): 8.02 Hyd Moment (95): 8.85 G content: 3 D/E content: 1 S/T content: 2 Score: -2.50
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 46 VRF | PD
NUCDISC: discrimination of nuclear localization signals pat4 : RRKR (5) at 79 pat4: PKKK (4) at 456 pat7: PKKKGLK (5) at 456 pat7: PNGRQKK (3) at 869 pat7: PHGEKKR (3) at 899 bipartite: none content of basic residues: 11.5% NLS Score: 1.04
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: KSKE
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: found KLPN at 1269
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
65.2 %: nuclear
21 .7 % : mitochondrial
13 .0 % : cytoplasmic
>> prediction for CG58504 - 01 is nuc (k=23 )
A search ofthe NOV68a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 68D.
Figure imgf000946_0001
In a BLAST search of public sequence databases, the NOV6δa protein was found to have homology to the proteins shown in the BLASTP data in Table 6δE.
Figure imgf000947_0001
PFam analysis indicates that the NOV68a protein contains the domains shown in the Table 68F.
Figure imgf000948_0001
Example 69.
The NOV69 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 69A.
Figure imgf000948_0002
NOV69a, CG58510-01 SEQ ID NO: 1032 308 aa MW at 34326.6kD Protein Sequence
MENDHNHNHTHGANKKT ISFIIITSYMIVEGLGGFFTNSLALISDAGHMLSDSIS GIALIAFTLG AKQANTNKTFGYKRFEILAAVLNGITLMLIAIYIFYEAIERFKNPPEVASTGMLIIALVGLFINIIVA WIMLRGSDVEENLNMRGAYLHVISDMLGSIGAVIAALLIIFFRWGWADPLASVIVAILVLRSGFYVTK SSLHVLMEGAPSNINTKDIIKTIKKFKEVKNIHDFHWSVTSGLNALSCHIVVEDTMTITENEFLLKR IEHEFNHQNIQHVTIQTETSN NHSEKLFCIVKEED
Further analysis ofthe NOV69a protein yielded the following properties shown in Table 69B.
Table 69B. Protein Sequence Properties NOV69a
SignalP analysis: Cleavage site between residues 34 and 35
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 4; pos. chg 0; neg.chg 2 H-region: length 10; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.24 possible cleavage site: between 43 and 44
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation
Init position for calculation: Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -4 4G Transmembrane 18 - • 34
INTEGRAL Likelihood = -1 65 Transmembrane 51 - - 67
INTEGRAL Likelihood = -6 32 Transmembrane 85 - - 101
INTEGRAL Likelihood =-11 41 Transmembrane 122 - - 138
INTEGRAL Likelihood = -9 55 Transmembrane 162 - - 178
INTEGRAL Likelihood = -4 73 Transmembrane 186 - - 202
PERIPHERAL Likelihood = 2 54 (at 241)
ALOM score : -11.41 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 25 Charge difference: -3.0 C(-1.0) - N( 2.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 6.56 Hyd Moment(95): 3.47 G content: 0 D/E content: 2 S/T content: 0 Score: -7.29
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 7.5% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: VKEE
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhard ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
66.7 % endoplasmic reticulum 22.2 % mitochondrial 11.1 % vesicles of secretory system
>> prediction for CG58510-01 is end (k=9) A search ofthe NOV69a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 69C.
Figure imgf000951_0001
In a BLAST search of public sequence databases, the NOV69a protein was found to have homology to the proteins shown in the BLASTP data in Table 69D.
Figure imgf000952_0002
PFam analysis indicates that the NOV69a protein contains the domains shown in the Table 69E.
Table 69E. Domain Analysis of NOV69a
Identities/
Pfam Domain NOV69a Match Region Similarities Expect Value for the Matched Region
Cation efflux lδ..296 102/303 (34%) 1.5e-106 245/303 (81%)
Example 70.
The NOV70 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 70 A.
Figure imgf000952_0001
GCCGCCAGGTGAGCCTGGACCCTTCCCAGGGATCATTGACATCTTTGGTATTGGAGGGGGCCTCTTGG AATATCGAGCCAGCCTCCTTGCTGGCCATGGCTTTGCCACGTTGGCTCTAGCTTATTATAACTTTGAA GATCTCCCCAATAACATGGACAACATATCCCTGGAGTACTTCGAAGAAGCCGTATGCTACATGCTTCA ACATCCCCAGGTTAAAGGCCCAGGCATTGGGCTTTTGGGCATTTCTCTAGGAGCTGATATTTGTCTCT CAATGGCCTCATTCTTGAAGAATGTCTCAGCCACAGTTTCCATCAATGGATCTGGGATCAGTGGGAAC ACAGCCATCAACTATAAGCACAGTAGCATTCCACCATTGGGCTATGACCTGAGGAGAATCAAGGTAGC TTTCTCAGGCCTCGTGGACATTGTGGATATAAGGAATGCTCTCGTAGGAGGGTACAAGAACCCCAGCA TGATTCCAATAGAGAAGGCCCAGGGGCCCATCCTGCTCATTGTTGGTCAGGATGACCATAACTGGAGA AGTGAGTTGTATGCCCAAACAGTCTCTGAACGGTTACAGGCCCATGGAAAGGAAAAACCCCAGATCAT CTGTTACCCTGGGACTGGGCATTACATCGAGCCTCCTTACTTCCCCCTGTGCCCAGCTTCCCTTCACA GATTACTGAACAAACATGTTATATGGGGTGGGGAGCCCAGGGCTCATTCTAAGGCCCAGGAAGATGCC TGGAAGCAAATTCTAGCCTTCTTCTGCAAACACCTGGGAGGTACCCAGAAAACAGCTGTCCCTAAATT GTAATGCATTTGTCT
NOV70a, CG59309-01 SEQ ID NO: 1034 422 aa MW at 46455. lkD Protein Sequence
MSATLILEPPGRCC NEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADARGELDLERAPAL GGSFAGLEPMGLL ALEPEKPFWRFLKRDVQIPFWELEVLDGHDPEPGRLLCQAQHERHFLPPGVRR QSVRAGRVRATLFLPPGEPGPFPGIIDIFGIGGGLLEYRASLLAGHGFATLALAYYNFEDLPNNMDNI SLEYFEEAVCYMLQHPQVKGPGIGLLGISLGADICLSMASFLKNVSATVSINGSGISGNTAINYKHSS IPPLGYDLRRIKVAFSGLVDIVDIRNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQTVS ERLQAHGKEKPQIICYPGTGHYIEPPYFPLCPASLHRLLNKHVI GGEPRAHSKAQEDA KQILAFFC; KHLGGTQKTAVPKL
NOV70b, 278901386 SEQ ID NO: 1035 1285 bp DNA Sequence ORF Start: at 2 JORF Stop: end of sequence
CACCGGATCCACCATGTCAGCAACGCTGATCCTGGAGCCCCCAGGCCGCTGCTGCTGGAACGAGCCGG TGCGCATTGCCGTGCGCGGCCTGGCCCCGGAGCAGCGGGTTACGCTGCGCGCGTCCCTGCGCGACGAG AAGGGCGCGCTCTTCCGGGCCCACGCGCGCTACTGCGCCGACGCCTGCGGCGAGCTGGACCTGGAGCG CGCACCCGCGCTGGGCGGCAGCTTCGCGGGACTCGAGCCCATGGGGCTGCTCTGGGCCCTGGAACCCG AGAAGCCTTTTTGGCGCTTCCTGAAGCGGGACGTACAGATTCCTTTTGTCGTGGAGTTGGAGGTGCTG GACGGCCACGACCCCGAGCCTGGACGGCTGCTGTGCCAGGCGCAGCACGAGCGCCACTTCCTCCCGCC AGGGGTGCGGCGCCAGTCGGTGCGAGCGGGCCGGGTGCGCGCCACGCTCTTCCTGCCGCCAGGACCTG GACCCTTCCCAGGGATCATTGACATCTTTGGTATTGGAGGGGGCCTCTTGGAATATCGAGCCAGCCTC CTTGCTGGCCATGGCTTTGCCACGTTGGCTCTAGCTTATTATAACTTTGAAGATCTCCCCAATAACAT GGACAACATATCCCTGGAGTACTTCGAAGAAGCCGTATGCTACATGCTTCAACATCCCCAGGTAAAAG GCCCAGGCATTGGGCTTTTGGGCATTTCTCTAGGAGCTGATATTTGTCTCTCAATGGCCTCATTCTTG AAGAATGTCTCAGCCACAGTTTCCATCAATGGATCTGGGATCAGTGGGAACACAGCCATCAACTATAA GCACAGTAGCATTCCACCATTGGGCTATGACCTGAGGAGAATCAAGGTAGCTTTCTCAGGCCTCGTGG ACATCGTGGATATAAGGAATGCTCTCGTAGGAGGGTACAAGAACCCCAGCATGATTCCAATAGAGAAG GCCCAGGGGCCCATCCTGCTCATTGTTGGTCAGGATGACCATAACTGGAGAAGTGAGTTGTATGCCCA AACAGTCTCTGAACGGTTACAGGCCCATGGAAAGGAAAAACCCCAGATCATCTGTTACCCTGGGACTG GGCATTACATCGAGCCTCCTTACTTCCCCCTGTGCCCAGCTTCCCTTCACAGATTACTGAACAAACAT GTTATATGGGGTGGGGAGCCCAGGGCTCATTCTAAGGCCCAGGAAGATGCCTGGAAGCAAATTCTAGC CTTCTTCTGCAAACACCTGGGAGGTACCCAGAAAACAGCTGTCCCTAAATTGGTCGACGGC
NOV70b, 27δ901386 SEQ ID NO: 1036 42δ aa MW at 46δ90.5kD Protein Sequence
TGSTMSATLILEPPGRCCWNEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADACGELDLER APALGGSFAGLEPMGLL ALEPEKPFWRFLKRDVQIPFWELEVLDGHDPEPGRLLCQAQHERHFLPP GVRRQSVRAGRVRATLFLPPGPGPFPGIIDIFGIGGGLLEYRASLLAGHGFATLALAYYNFEDLPNNM DNISLEYFEEAVCYMLQHPQVKGPGIGLLGISLGADICLSMASFLKNVSATVSINGSGISGNTAINYK HSSIPPLGYDLRRIKVAFSGLVDIVDIRNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQ TVSERLQAHGKEKPQIICYPGTGHYIEPPYFPLCPASLHRLLNKHVIWGGEPRAHSKAQEDAWKQILA FFCKHLGGTQKTAVPKLVDG
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 70B. Table 70B. Comparison of the NOV70 protein sequences.
NOV70a MSATLILEPPGRCCWNEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADA
NOV7Ob TGSTMSATLILEPPGRCC NEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADA
NOV70a RGELDLERAPALGGSFAGLEPMGLLWALEPEKPF RFLKRDVQIPFWELEVLDGHDPEP
NOV70b CGELDLERAPALGGSFAGLEPMGLL ALEPEKPFWRFLKRDVQIPFWELEVLDGHDPEP
NOV70a GRLLCQAQHERHFLPPGVRRQSVRAGRVRATLFLPPGEPGPFPGIIDIFGIGGGLLEYRA
NOV70b GRLLCQAQHERHFLPPGVRRQSVRAGRVRATLFLPPG-PGPFPGIIDIFGIGGGLLEYRA
NOV70a SLLAGHGFATLALAYYNFEDLPNNMDNISLEYFEEAVCYMLQHPQVKGPGIGLLGISLGA
NOV70b SLLAGHGFATLALAYYNFEDLPNNMDNISLEYFEEAVCYMLQHPQVKGPGIGLLGISLGA
NOV70a DICLSMASFLKNVSATVSINGSGISGNTAINYKHSSIPPLGYDLRRIKVAFSGLVDIVDI
NOV7Ob DICLSMASFLKNVSATVSINGSGISGNTAINYKHSSIPPLGYDLRRIKVAFSGLVDIVDI
NOV70a RNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQTVSERLQAHGKEKPQIICY
NOV70b RNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQTVSERLQAHGKEKPQIICY
NOV7Oa PGTGHYIEPPYFPLCPASLHRLLNKHVI GGEPRAHSKAQEDA KQILAFFCKHLGGTQK NOV70b PGTGHYIEPPYFPLCPASLHRLLNKHVIWGGEPRAHSKAQEDA KQILAFFCKHLGGTQK
NOV70a TAVPKL
NOV70b TAVPKLVDG
NOV70a (SEQ ID NO: 1034)
NOV70b (SEQ ID NO: 1036)
Further analysis ofthe NOV70a protein yielded the following properties shown in Table 70C.
Table 70C. Protein Sequence Properties NOV70a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 8 ; pos . chg 0 ; neg . chg 1 H-region : length 3 ; peak value 0 . 00 PSG score : -4 .40
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 .1 ) : -7 .81 possible cleavage site : between 13 and 14
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation Init position for calculation : 1
Tentative number of TMS (s) for the threshold 0 .5 : Number of TMS ( s) for threshold 0.5 : 0 PERIPHERAL Likelihood = 1 .75 (at 285 ) ALOM score : - 1 .86 (number of TMSs : 0) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 7.13 Hyd Moment (95): 4.74 G content: 1 D/E content : 2 S/T content : 2 Score: -6.03
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat : none pat7: none bipartite: none content of basic residues: 10.4% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
KKXX-like motif in the C-terminus: AVPK
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhard 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Figure imgf000956_0001
A search ofthe NOV70a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 70D.
Figure imgf000956_0002
In a BLAST search of public sequence databases, the NOV70a protein was found to have homology to the proteins shown in the BLASTP data in Table 70E.
Figure imgf000957_0001
PFam analysis indicates that the NOV70a protein contains the domains shown in the Table 70F.
Figure imgf000957_0002
Example 71.
The NOV71 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 71 A.
Table 71A. NOV71 Sequence Analysis
NOV71a, CG59490-01 SEQ ID NO: 1037 660 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
TCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTGCGCGTT TAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGATCGTCC GTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAGCTGGAG GCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCGGGACGTGCCCTC GGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGCCCCTCA GCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGCCGCTTT CCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGACGGGAA CCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGGTCCAGG TGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGCGTGACG AGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGC
NOV71a, CG59490-01 SEQ ID NO: 1038 220 aa MW at 24527.8kD Protein Sequence
SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLE APVPLSELIHPVSLPSASRDVPSGKTC VTGWGVIGRGELLPWPLSL EATVKVRSNVLCNQTCRRRF PSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVT SYVSWIRQYVPPFPRR
NOV71b, 207639512 SEQ ID NO: 1039 672 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AGATCTTCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTG CGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGA TCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAG CTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGT GCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGC CCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAGCGTCCTCTGTAACCAGACCTGTCGCCGC CGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGA CGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGG TCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGC GTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCCTCGAG
NOV71b, 207639512 SEQ ID NO: 1040 224 aa MW at 24943.3kD Protein Sequence
RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLK LEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEATVKVRSSVLCNQTCRR RFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWS GKLCGLRGYPGMYTR VTSYVSWIRQYVPPFPRRLE
NOV71c, 207639476 SEQ ID NO: 1041 [672 bp
DNA Sequence QRF Start: at 1 ORF Stop: end of sequence
AGATCTTCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTG CGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGA TCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAG CTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGT GCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGC CCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGC CGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGA CGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGG TCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGC GTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCCTCGAG
NOV71c, 207639476 SEQ ID NO: 1042 224 aa MW at 24970.3kD Protein Sequence
RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLK LEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEATVKVRSNVLCNQTCRR RFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCT VQVEWSWGKLCGLRGYPGMYTR VTSYVSWIRQYVPPFPRRLE
NOV7 Id, 207639523 SEQ ID NO: 1043 672 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
AGATCTTCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTG CGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGA TCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGCCGGTGCGGACATCGCCCTGCTGAAG CTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGT GCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGC CCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGC CGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGA CGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCτCCTGTGCAGGCGGAATTGCACCTGGG TCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGC GTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCCTCGAG
NOV7 Id, 207639523 SEQ ID NO: 1044 224 aa MW at 24984.3kD Protein Sequence
RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQAGADIALLK LEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEATVKVRSNVLCNQTCRR RFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTR VTSYVSWIRQYVPPFPRRLE
NOV71e, CG59490-02 SEQ ID NO: 1045 672 bp DNA Sequence ORF Start: at 7 ORF Stop: at 667
AGATCTTCACTGGGGGCTGCGACGTCTCGGCCAGGAGGCACCCCTGGCAGGGAGGAGTTGGAGGCTTG
CGCGTTTAGAGTGCAGGTGGGGCAGCTGAGGCTCTATGAGGACGACCAGCGGACGAAGGTGGTTGAGA TCGTCCGTCACCCCCAGTACAACGAGAGCCTGTCTGCCCAGGGCGGTGCGGACATCGCCCTGCTGAAG CTGGAGGCCCCGGTGCCGCTGTCTGAGCTCATCCACCCGGTCTCGCTCCCGTCTGCCTCCCTGGACGT GCCCTCGGGGAAGACCTGCTGGGTGACCGGCTGGGGTGTCATTGGACGTGGAGAACTACTGCCCTGGC CCCTCAGCTTGTGGGAGGCGACGGTGAAGGTCAGGAGCAACGTCCTCTGTAACCAGACCTGTCGCCGC CGCTTTCCTTCCAACCACACTGAGCGGTTTGAGCGGCTCATCAAGGACGACATGCTGTGTGCCGGGGA CGGGAACCACGGCTCCTGGCCAGGCGACAACGGGGGCCCCCTCCTGTGCAGGCGGAATTGCACCTGGG TCCAGGTGGAGGTGGTGAGCTGGGGCAAACTCTGCGGCCTTCGCGGCTATCCCGGCATGTACACCCGC GTGACGAGCTACGTGTCCTGGATCCGCCAGTACGTCCCGCCGTTCCCCAGACGCCTCGAG
NOV71e, CG59490-02 SEQ ID NO: 1046 220 aa MW at 244δ4.δkD Protein Sequence
SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQGGADIALLKLE APVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEATVKVRSNVLCNQTCRRRF PSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCTWVQVEWSWGKLCGLRGYPGMYTRVT SYVSWIRQYVPPFPRR
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 7 IB.
Table 71B. Comparison of the NOV71 protein sequences.
NOV7la - -SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQG
NOV71b RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQG
N0V71c RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQG
NOV71d RSSLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQA
NOV7le - -SLGAATSRPGGTPGREELEACAFRVQVGQLRLYEDDQRTKWEIVRHPQYNESLSAQG
NOV7la GADIALLKLEAPVPLSELIHPVSLPSASRDVPSGKTCWVTGWGVIGRGELLPWPLSLWEA
NOV71b GADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEA
N0V71C GADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEA
N0V71d GADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEA
NOV71e GADIALLKLEAPVPLSELIHPVSLPSASLDVPSGKTCWVTGWGVIGRGELLPWPLSLWEA
NOV71a TVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCT
NOV71b TVKVRSSVLCNQTCRRRFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRR CT
NOV71C TVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRR CT
N0V7Id TVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCT
NOV71e TVKVRSNVLCNQTCRRRFPSNHTERFERLIKDDMLCAGDGNHGSWPGDNGGPLLCRRNCT
N0V71a WVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR- - NOV7lb WVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRRLE
NOV71c WVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRRLE
NOV7Id WVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRRLE
NOV7le WVQVEWSWGKLCGLRGYPGMYTRVTSYVSWIRQYVPPFPRR- -
NOV71a (SEQ ID NO 1038)
NOV71b (SEQ ID NO 1040)
NOV71C (SEQ ID NO 1042)
NOV71d (SEQ ID NO 1044)
NOV71e (SEQ ID NO 1046)
Further analysis ofthe NOV7 la protein yielded the following properties shown in Table 71C.
Table 71C. Protein Sequence Properties NOV71a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 8; pos. chg 1; neg.chg 0 H-region: length 6; peak value -8.72 PSG score: -13.12
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.58 possible cleavage site: between 14 and 15
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 4.88 (at 62) ALOM score: 4.88 (number of TMSs : 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.94 Hyd Moment(95): 7.43 G content: 4 D/E content : 1 S/T content : 4 Score: -3.60
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 18 SRP|GG
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 12.3% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23)
39.1 %: cytoplasmic
30.4 %: mitochondrial
17.4 %: nuclear
8.7 %: vesicles of secretory system
4.3 %: vacuolar
>> prediction for CG59490-01 is cyt (k=23)
A search ofthe NOV7 la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several h horvmmonllongσonunsc p rvrronttepiinnsc s chlionwnn i inn Taabhllep 7711 D D
Figure imgf000962_0001
In a BLAST search of public sequence databases, the NOV7 la protein was found to have homology to the proteins shown in the BLASTP data in Table 7 IE.
Figure imgf000962_0002
95δ PFam analysis indicates that the NOV7 la protein contains the domains shown in the Table 71F.
Table 71F. Domain Analysis of NOV71a
Identities/
Pfam Domain NOV71a Match Region Similarities Expect Value for the Matched Region trypsin δ..210 δl/272 (30%) 1.9e-32 152/272 (56%)
Example 72.
The NOV72 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 72A.
Table 72A. NOV72 Sequence Analysis
NOV72a, CG59693-01 SEQ ID NO: 1047 972 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 970
ATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGATTTGGCAC CTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTGGCAATTGAAGCTGGCT TCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGGACTGGCCATCCGAAGCAAG ATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGCTTTGGTGCAATTCCCATCG ACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAATTGGATTATGTTGACCTCT ACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAA ATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTGTAAAGATGCAGGATT GGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAACAAGCCAGGGC TCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAGAGAAAACTGCTGGAT TTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGATCCCACCGAGAAGAACCATG GGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCCTTGGCAAAAAAGCACAAGC GAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTAC AATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGC CATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATC CATTTTCTGATGAATATTAA
NOV72a, CG59693-01 SEQ ID NO: 104δ 323 aa MW at 367δ7.9kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWΛΠDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72b, CG59693-03 SEQ ID NO: 1049 972 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 970
ATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGATTTGGCAC CTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTGGCAATTGAAGCTGGCT TCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGGACTGGCCATCCGAAGCAAG ATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGCTTTGGTGCAATTCCCATCG ACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAATTGGATTATGTTGACCTCT ACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAA ATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTGTAAAGATGCAGGATT GGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAACAAGCCAGGGC TCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAGAGAAAACTGCTGGAT TTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGATCCCACCGAGAAGAACCATG GGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCCTTGGCAAAAAAGCACAAGC GAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGTGGTCCTGGCCAAGAGATAC AATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGC CATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATC CATTTTCTGATGAATATTAA
NOV72b, CG59693-03 SEQ ID NO: 1050 323 aa MW at 36δ57.0kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKRY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72c, 277637252 SEQ IDNO: 1051 1001 bp DNA Sequence ORF Start: at δ JORF Stop: TAA at 989
CATCTAGGCCACCATGGCCATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGC
CTGTCCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAA TTGGCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGG ACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGC TTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAA TTGGATTATGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCC AAAAGATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGA AGTGTAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATG ATCCTCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAA CCAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGAT CCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCC TTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGT GGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGA CTTCAGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTT GCTGGCCCCCCTAATTATCCATTTTCTGATGAATATTAAACGCGTGATC
NOV72c, 277637252 SEQ ID NO: 1052 327 aa MW at 37162.4kD Protein Sequence
ATMAMDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLA IRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKD ENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQR KLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWL AKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72d, CG59693-02 SEQ ID NO: 1053 983 bp DNA Sequence ORF Start: ATG at 30 ORF Stop: TAA at 981
ATGGATTCGATATCAGTGTGTGAAGCTGAATGATGGTCACTTCGTGCCTGTCCTGGGATTTGGCACCT
ATGCGCCTGCAGAGGTTACTCCCCCAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTGGCAAT TGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGGACTGGCCA TCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGCTTTGGTGC AATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAATTGGATTA TGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATG AAAGTGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTGTAAA GATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAA CAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAGAGAA AACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGATCCCACCGA GAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCCTTGGCAAA AAAGCACAAGCGAACCCCAGCCCTGGTTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGTGGTCCTGG CCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTCAGAG GAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCC CCCTAATTATCCATTTTCTGATGAATATTAA
NOV72d, CG59693-02 SEQ ID NO: 1054 317 aa MW at 36217.5kD Protein Sequence
MMVTSCLSWDLAPMRLQRLLPQVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSV KREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDESGKILFDTV DLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKD IVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALVALRYQLQRGVWLAKSYNEQRIR QNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72e, CG59693-04 SEQ ID NO: 1055 994 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: at 979
GCCAGATCTCCCACCATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGT
CCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTGG CAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGGACTG GCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGCTTTG GTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAATTGG ATTATGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAA GATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTG TAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCC TCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAG AGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGATCCCA CCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCCTTGG CAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGTGGTC CTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTC AGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTG GCCCCCCTAATTATCCATTTTCTGATGAATATCTCGAGGGTG
NOV72e, CG59693-04 SEQ ID NO: 1056 321 aa MW at 36495.6kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSD
NOV72f, CG59693-05 SEQ ID NO: 1057 1219 bp DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 993
TGCTAACCAGGCCAGTGACAGAAATGGATTCGAAATACCAGTGTGTGAAGCTGAATGATGGTCACTTC
ATGCCTGTCCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTCTAGAGGCCGT CAAATTGGCAATAGAAGCCGGGTTCCACCATATTGATTCTGCACATGTTTACAATAATGAGGAGCAGG TTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCA AAGCTTTGGAGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCT TCAATTGGACTATGTTGACCTCTATCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGA TCCCAAAAGATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCATG GAGAAGTGTAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCACAGGCTGCTGGA GATGATCCTCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACT TCAACCAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTG GGATCCCATCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTG TGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTGCAGCGTGGGG TTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAG TTGACTTCAGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATAT TTTTGCTGGCCCCCCTAATTATCCATTTTCTGATGAATATTAACATGGAGGGCATTGCATGAGGTCTG
CCAGAAGGCCCTGCGTGTGGATGGTGACACAGAGGATGGCTCTATGCTGGTGACTGGACACATCGCCT
CTGGTTAAATCTCTCCTGCTTGGCGACTTCAGTAAGCTACAGCTAAGCCCATCGGCCGGAAAAGAAAG
ACAATAATTTTGTTTTTTCATTTTGAAAAAATTAAATGCTCTCTCCTAAAGATTCTTCACCTA
NOV72f, CG59693-05 SEQ ID NO: 1058 323 aa MW at 36734.9kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY NOV72g, CG59693-06 SEQ ID NO: 1059 1001 bp DNA Sequence ORF Start: at 11 ORF Stop: at 983
CATCTAGGCCACCATGGCCATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGC
CTGTCCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAA TTGGCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGG ACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGC TTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAA TTGGATTATGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCC AAAAGATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGA AGTGTAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATG ATCCTCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAA CCAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGAT CCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCC TTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGT GGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGA CTTCAGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTT GCTGGCCCCCCTAATTATCCATTTTCTGATGAATATTAAACGCGTGATC
NOV72g, CG59693-06 SEQ ID NO: 1060 324 aa MW at 36799.0kD Protein Sequence
TMAMDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAI RSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDE NGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRK LLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLA KSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSD
NOV72h, CG59693-07 SEQ ID NO: 1061 1012 bp DNA Sequence ORF Start: at 1 ORF Stop: at 1012
GCCGGTACCACCATGGGCCACCATCACCACCATCACGATTCGAAATATCAGTGTGTGAAGCTGAATGA TGGTCACTTCATGCCTGTCCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTT TAGAGGCCACCAAATTGGCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAAT GAGGAGCAGGTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATT CTACACTTCAAAGCTTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCAC TGAAAAATCTTCAATTGGATTATGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGT GAGGAAGTGATCCCAAAAGATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTG GGAGGCCGTGGAGAAGTGTAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCA GGCAGCTGGAGATGATCCTCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGT CATCCTTACTTCAACCAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTA TAGTGCTCTGGGATCCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACC CAGTCCTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTA CAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTT TGAATTCCAGTTGACTTCAGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGA CCCTTGATATTTTTGCTGGCCCCCCTAATTATCCATTTTCTGATGAATATCTCGAGGGTG
NOV72h, CG59693-07 SEQ ID NO: 1062 337 aa MW at 3δ297.5kD Protein Sequence
AGTTMGHHHHHHDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNN EEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPG EEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVEC HPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQL QRGVWLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEYLEG
NOV72i, CG59693-08 SEQ ID NO: 1063 1225 bp DNA Sequence ORF Start: ATG at 24 ORF Stop: TAA at 993
TGCTAACCAGGCCAGTGACAGAAATGGATTCGAAATACCAGTGTGTGAAGCTGAATGATGGTCACTTC
ATGCCTGTCCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTCTAGAGGCCGT CAAATTGGCAATAGAAGCCGGGTTCCACCATATTGATTCTGCACATGTTTACAATAATGAGGAGCAGG TTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCA AAGCTTTGGAGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCT TCAATTGGACTATGTTGACCTCTATCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGA TCCCAAAAGATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCATG GAGAAGTGTAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCACAGGCTGCTGGA GATGATCCTCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACT TCAACCAGAGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTG GGATCCCATCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTG TGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTGCAGCGTGGGG TTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAG TTGACTTCAGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATAT TTTTGCTGGCCCCCCTAATTATCCATTTTCTGATGAATATTAACATGGAGGGCATTGCATGAGGTCTG
CCAGAAGGCCCTGCGTGTGGATGGTGACACAGAGGATGGCTCTATGCTGGTGACTGGACACATCGCCT
CTGGTTAAATCTCTCCTGCTTGGCGACTTCAGTAAGCTACAGCTAAGCCCATCGGCCGGAAAAGAAAG:
ACAATAATTTTGTTTTTTCATTTTGAAAAAATTAAATGCTCTCTCCTAAAGATTCTTCACCTAAAAAA
NOV72i, CG59693-08 |SEQ ID NO: 1064 323 aa MW at 36734.9kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGWVLAKSY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72J, CG59693-09 SEQ ID NO: 1065 996 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 9δ5
CACCGCGGCCGCACCATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGT
CCTGGGATTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTGG CAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAGGTTGGACTG GCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTCTACACTTCAAAGCTTTG GTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAAAGGTCACTGAAAAATCTTCAATTGG ATTATGTTGACCTCTACCTTATTCATTTTCCAGTGTCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAA GATGAAAATGGAAAAATACTATTTGACACAGTGGATCTCTGTGCCACGTGGGAGGCCGTGGAGAAGTG TAAAGATGCAGGATTGGCCAAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCC TCAACAAGCCAGGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAG AGAAAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGATCCCA CCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTCCTTTGTGCCTTGG CAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAGCTACAGCGTGGGGTTGTGGTC CTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAACGTGCAGGTGTTTGAATTCCAGTTGACTTC AGAGGAGATGAAAGCCATAGATGGCCTAAACAGAAATGTGCGATATTTGACCCTTGATATTTTTGCTG GCCCCCCTAATTATCCATTTTCTGATGAATATTAGGTCGACGGC
NOV72J, CG59693-09 SEQ ID NO: 1066 323 aa MW at 367δ7.9kD Protein Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSK IADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGK ILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLD FCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKΗKRTPALIALRYQLQRGVVVLAKSY NEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 72B.
Table 72B. Comparison of the NOV72 protein sequences.
NOV72a MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72b MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72C ATMAMDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72d MMVTSCLSWDLAPMRLQRLLP-QVPKSKALEATKLAIEAGFRHI
NOV72e MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72f MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHI NOV72g TMAMDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72h AGTTMGHHHHHHDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72i MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHI
NOV72j MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHI
NOV72a DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72b DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72c DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72d DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72e DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72f DSAHVYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLD
NOV72g DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72h DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72i DSAHVYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLD
NOV72J DSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLD
NOV72a YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72b YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72c YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72d YVDLYLIHFPVSVKPGEEVIPKDESGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72e YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72f YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFN
NOV72g YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
N0V72h YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72i YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFN
NOV72J YVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFN
NOV72a RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72b RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
N0V72c RRQLEMI NKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72d RRQLEMI NKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72e RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72f HRLLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72g RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72h RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72i HRLLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72J RRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVD
NOV72a PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72b PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKRYNEQRIRQNVQVFEFQLT
NOV72C PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72d PNSPVLLEDPVLCALAKKHKRTPALVALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72e PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72f PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72g PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGWVLAKSYNEQRIRQNVQVFEFQLT
NOV72h PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72i PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72J PNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVWLAKSYNEQRIRQNVQVFEFQLT
NOV72a SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72b SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72C SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72d SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72e SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSD
NOV72f SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72g SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSD
NOV72h SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEYLEG NOV72i SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72J SEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
NOV72a (SEQ ID NO 1048)
NOV72b (SEQ ID NO 1050)
NOV72c (SEQ ID NO 1052)
NOV72d (SEQ ID NO 1054)
NOV72e (SEQ ID NO 1056)
NOV72f (SEQ ID NO 1058)
NOV72g (SEQ ID NO 1060)
NOV72h (SEQ ID NO 1062)
NOV72i (SEQ ID NO 1064)
N0V72J (SEQ ID NO 1066)
Further analysis ofthe NOV72a protein yielded the following properties shown in Table
72C.
Table 72C. Protein Sequence Properties NOV72a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 9; pos. chg 2; neg.chg 1 H-region: length 2; peak value -3.30 PSG score: -7.70
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.32 possible cleavage site: between 27 and 28
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: number of TMS(s) .. fixed PERIPHERAL Likelihood = 3.66 (at 253) ALOM score: 3.66 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq
R content : 0 Hyd Moment (75) : 0.10
Hyd Moment (95) : 4.27 G content : 0
D/E content : 2 S/T content: 1 Score: -7.79
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: KKHK (3) at 246 pat4 : KHKR (3) at 247 pat7: none bipartite: none content of basic residues: 13.3% NLS Score : - 0 . 10
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
34.8 %: cytoplasmic
30.4 %: mitochondrial
30.4 %: nuclear
4.3 %: vacuolar
>> prediction for CG59693-01 is cyt (k=23)
A search of the NOV72a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 72D.
Figure imgf000971_0001
In a BLAST search of public sequence databases, the NOV72a protein was found to have homology to the proteins shown in the BLASTP data in Table 72E.
Figure imgf000972_0001
PFam analysis indicates that the NOV72a protein contains the domains shown in the Table 72F.
96δ
Figure imgf000973_0001
Example 73.
The NOV73 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 73A.
Table 73A. NOV73 Sequence Analysis
NOV73a, CG59δ39-02 SEQ ID NO: 1067 4052 bp DNA Sequence ORF Start: ATG at 7δ6 ORF Stop: TAG at 4023
CTTCTGCCTCAGCCTCCCGAGTAGCTGGGATGGGACTACAGATGCACGCCACCACACCTGGCAATTTT
TTTTAGTTTTGTGGAGACAAGGTCCCATGTGAGCCACTGTGCCCCACCTTTTAAAGAAATTACCATAA
GGAAGCAACTGTCTTTAGCAAATAGAAGATCATAAACATCCTTCTGGAGATCTTGAGATGTTGACTGC
GGTTTATAGGGCAATGAAAATCTGCCTACCTGAGTGGGCAATGAGACGGGAGTGCCACCTGTGATCCT
TCCAGGGAGCAATTCTTTCTGGTGCCAGGAGCCCAAAGGAAACTCAGTCAACCAGCTACAGATGGGCT
TGCTCCGAGTTTGTTCTAGAAGTCAGAACTGCCAGCTCTGAAAATAGGTCACAAGTGACAGGCCGTCC
CTGGGCTGCTCACAGGAAGTAGCTGCAAAGGTCAGGGAAAGTTTTTAACGACTATACAGGCCAGTGAA
TGACAGGCTTTGAGGAGCTTCTCTTCTTGGCATCTGAAACAGCATACTTTCTGACTACCGCTGTGTGC
TGTGAGGGGCTGAGGATCCAGACGTGGCTGAGGAAGGTCCCGGCTCATGAGGAGGTGGAAGCCTGGGT
GCTTAAACAGATAATCCAGAGTTTGGATGTGAGGTGGTGAATCACTCTGGCTTCATTTGGTTATACTG
GTCAAGAGTTTGGCTCTGGAGCAACGTGTCTGGGTTTGAATCCTGGCTGTGCTTTTGGTGATCCTCCA
TTGTTTTGAAGCACAAGACCTTTAAACCACTGTAGGTATGGACAAGGAAGAAAGGAAGATCATCAATC
AGGGTCAAGAAGATGAAATGGAGATTTATGGTTACAATTTGAGTCGCTGGAAGCTTGCCATAGTTTCT TTAGGAGTGATTTGCACTGGTGGGTTTCTCCTCCTCCTCCTCTATTGGATGCCTGAGTGGCGGGTGAA AGCGACCTGTGTCAGAGCTGCAATTAAAGACTGTGACGTAGTGCTGCTGAGGACTACTGATGAATTCA AAATGTGGTTTTGTGCAAAAATTCGCGTTCTTTCTTTGGAAACTCACCCAATTTCAAGTCCAAAATCT ATGTCTAATAAGCTTTCAAATGGCCATGCAGTTTGTTTAACTGAGAATCCCACTGGAGAAAATAGGCA CGGGATCAGTAAATATTCACAGGCTGAATCACAACAGATTCGTTATTTCACCCATCATAGTGTAAAAT ATTTCTGGAATGATACCATTCACAATTTTGATTTCTTAAAGGGACTGGATGAAGGTGTTTCTTGTACG TCAATTTATGAAAAGCATAGTGCAGGACTGACAAAGGGGATGCATGCCTACAGAAAACTGCTTTATGG AGTAAATGAAATTGCTGTAAAAGTGCCTTCTGTTTTTAAGCTTCTAATTAAAGAGGTTCTCAACCCAT TTTACATTTTCCAGCTGTTCAGTGTTATACTGTGGAGCACTGATGAATACTATTACTATGCTCTAGCT ATTGTGGTTATGTCCATAGTATCAATCGTAAGCTCACTGTATTCCATTAGAAAGCAATATGTTATGTT GCATGACATGGTGGCAACTCATAGTACTGTAAGAGTTTCAGTTTGTAGAGTAAATGAAGAAATAGAAG AAATCTTTTCTACTGACCTTGTGCCAGGAGATGTCATGGTCATTCCATTAAATGGGACAATAATGCCT TGCGATGCTGTACTTATTAATGGTACCTGCATTGTAAATGAAAGCATGTTAACAGGAGAAAGTGTTCC AGTGACAAAGACTAACTTGCCAAATCCTTCGGTGGATGTGAAAGGAATAGGAGATGAATTATATAATC CAGAAACACATAAACGACATACTTTGTTTTGTGGGACAACTGTTATTCAGACTCGTTTCTACACCGGA GAACTCGTCAAAGCCATAGTTGTTAGAACAGGATTTAGTACTTCCAAAGGACAGCTTGTTCGTTCCAT ATTGTATCCCAAACCAACTGATTTTAAACTCTACAGAGATGCCTACTTGTTTCTACTATGTCTTGTGG CAGTTGCTGGCATTGGGTTTATCTACACTATTATTAATAGCATTTTAAATGAGGTACAAGTTGGGGTC ATAATTATCGAGTCTCTTGATATTATCACAATTACTGTGCCCCCTGCACTTCCTGCTGCAATGACTGC TGGTATTGTGTATGCTCAGAGAAGACTGAAAAAAATCGGTATTTTCTGTATCAGTCCTCAAAGAATAA ATATTTGTGGACAGCTCAATCTTGTTTGCTTTGACAAGACTGGAACTCTAACTGAAGATGGTTTAAAT CTTTGGGGGATTCAACGAGTGGAAAATGCACGGTTTCTTTCACCAGAAGAAAATGTGTGCAATGAGAT GTTGGTAAAATCCCAGTTTGTTGCTTGTATGGCTACTTGTCATTCACTTACAAAAATTGAAGGAGTGC TCTCTGGTGATCCACTTGATCTGAAAATGTTTGAGGCTATTGGATGGATTCTGGAAGAAGCAACTGAA GAAGAAACAGCACTTCATAATCGAATTATGCCCACAGTGGTTCGTCCTCCCAAACAACTGCTTCCTGA ATCTACCCCTGCAGGAAACCAAGAAATGGCTACTTATGAGATAGGAATTGTTCGCCAGTTCCCATTTT CTTCTGCTTTGCAACGTATGAGTGTGGTTGCCAGGGTGCTGGGGGATAGGAAAATGGACGCCTACATG AAAGGAGCGCCCGAGGCCATTGCCGGTCTCTGTAAACCTGAAACAGTTCCTGTCGATTTTCAAAACGT TTTGGAAGACTTCACTAAACAGGGCTTCCGTGTGATTGCTCTTGCACACAGAAAATTGGAGTCAAAAC TGACATGGCATAAAGTACAGAATATTAGCAGGGATGCAATTGAGAACAACATGGATTTTATGGGATTA ATTATAATGCAGAACAAATTAAAGCAAGAAACCCCTGCAGTACTTGAAGATTTGCATAAAGCCAACAT TCGCACCGTCATGGTCACAGGTGACAGTATGTTGACTGCTGTCTCTGTGGCCAGAGATTGTGGAATGA TTCTACCTCAGGATAAAGTGATTATTGCTGAAGCATTACCTCCAAAGGATGGGAAAGTTGCCAAAATA AATTGGCATTATGCAGACTCCCTCACGCAGTGCAGTCATCCATCAGCAATTGACCCAGAGGCTATTCC GGTTAAATTGGTCCATGATAGCTTAGAGGATCTTCAAATGACTCGTTATCATTTTGCAATGAATGGAA AATCATTCTCAGTGATACTGGAGCATTTTCAAGACCTTGTTCCTAAGTTGATGTTGCATGGCACCGTG
TTTGCCCGTATGGCACCTGATCAGAAGACACAGTTGATAGAAGCATTGCAAAATGTTGAGTATTTTGT TGGGATGTGTGGTGATGGCGCAAATGATTGTGGTGCTTTGAAGAGGGCACACGGAGGCATTTCCTTAT CGGAGCTCGAAGCTTCAGTGGCATCTCCCTTTACCTCTAAGACTCCTAGTATTTCCTGTGTGCCAAAC CTTATCAGGGAAGGCCGTGCTGCTTTAATAACTTCCTTCTGTGTGTTTAAATTCATGGCATTGTACAG CATTATCCAGTACTTCAGTGTTACTCTGCTGTATTCTATCTTAAGTAACCTAGGAGACTTCCAGTTTC TCTTCATTGATCTGGCAATCATTTTGGTAGTGGTATTTACAGTGAGTTTAAATCCTGCCTGGAAAGAA CTTGTGGCACAAAGACCACCTTCGGGTCTTATATCTGGGGCCCTTCTCTTCTCCGTTTTGTCTCAGAT TATCATCTGCATTGGATTTCAATCTTTGGGTTTTTTTTGGGTCAAACAGCAACCTTGGTATGAAGTGT GGCATCCAAAATCAGAGGCTTGTAATACAACAGGAAGCGGGTTTTGGAATTCTTCACACGTAGACAAT GAAACCGAACTTGATGAAATAATATACAAAATTATGAAAATACCACAGTGTTTTTTATTTCCAGTTTT CAGTACCTCATAGTGGCAATTGCCTTTTCAAAAGGAAAAC
NOV73a, CG59δ39-02 SEQ ID NO: 106δ 1079 aa MW at 120773.2kD Protein Sequence
MDKEERKIINQGQEDEMEIYGYNLSRWKLAIVSLGVICTGGFLLLLLYWMPE RVKATCVRAAIKDCD WLLRTTDEFKMWFCAKIRVLSLETHPISSPKSMSNKLSNGHAVCLTENPTGENRHGISKYSQAESQQ IRYFTHHSVKYFWNDTIHNFDFLKGLDEGVSCTSIYEKHSAGLTKGMHAYRKLLYGVNEIAVKVPSVF KLLIKEVLNPFYIFQLFSVIL STDEYYYYALAIWMSIVSIVSSLYSIRKQYVMLHDMVATHSTVRV SVCRVNEEIEEIFSTDLVPGDVMVIPLNGTIMPCDAVLINGTCIVNESMLTGESVPVTKTNLPNPSVD VKGIGDELYNPETHKRHTLFCGTTVIQTRFYTGELVKAIWRTGFSTSKGQLVRSILYPKPTDFKLYR DAYLFLLCLVAVAGIGFIYTIINSILNEVQVGVIIIESLDIITITVPPALPAAMTAGIVYAQRRLKKI GIFCISPQRINICGQLNLVCFDKTGTLTEDGLNLWGIQRVENARFLSPEENVCNEMLVKSQFVACMAT CHSLTKIEGVLSGDPLDLKMFEAIGWILEEATEEETALHNRIMPTWRPPKQLLPESTPAGNQEMATY EIGIVRQFPFSSALQRMSWARVLGDRKMDAYMKGAPEAIAGLCKPETVPVDFQNVLEDFTKQGFRVI ALAHRKLESKLTWHKVQNISRDAIENNMDFMGLIIMQNKLKQETPAVLEDLHKANIRTVMVTGDSMLT AVSVARDCGMILPQDKVIIAEALPPKDGKVAKINWHYADSLTQCSHPSAIDPEAIPVKLVHDSLEDLQ MTRYHFAMNGKSFSVILEHFQDLVPKLMLHGTVFARMAPDQKTQLIEALQNVEYFVGMCGDGANDCGA LKRAHGGISLSELEASVASPFTSKTPSISCVPNLIREGRAALITSFCVFKFMALYSIIQYFSVTLLYS ILSNLGDFQFLFIDLAIILVWFTVSLNPA KELVAQRPPSGLISGALLFSVLSQIIICIGFQSLGFF WKQQPWYEVWHPKSEACNTTGSGFWNSSHVDNETELDEIIYKIMKIPQCFLFPVFSTS
NOV73b, CG59839-01 SEQ ID NO: 1069 2649 bp DNA Sequence ORF Start: ATG at 183 ORF Stop: TAG at 2055
CAACTGATTTTAAACTCTACAGAGATGCCTACTTGTTTCTACTATGTCTTGTGGCAGTTGCTGGCATT
GGGTTTATCTACACTATTATTAATAGCATTTTAAATGAGGTACAAGTTGGGGTCATAATTATCGAGTC
TCTTGATATTATCACAATTACTGTGCCCCCTGCACTTCCTGCTGCAATGACTGCTGGTATTGTGTATG
CTCAGAGAAGACTGAAAAAAATCGGTATTTTCTGTATCAGTCCTCAAAGAATAAATATTTGTGGACAG CTCAATCTTGTTTGCTTTGACAAGACTGGAACTCTAACTGAAGATGGTTTAGATCTTTGGGGGATTCA ACGAGTGGAAAATGCACGATTTCTTTCACCAGAAGAAAATGTGTGCAATGAGATGTTGGTAAAATCCC AGTTTGTTGCTTGTATGGCTACTTGTCATTCACTTACAAAAATTGAAGGAGTGCTCTCTGGTGATCCA CTTGATCTGAAAATGTTTGAGGCTATTGGATGGATTCTGGAAGAAGCAACTGAAGAAGAAACAGCACT TCATAATCGAATTATGCCCACAGTGGTTCGTCCTCCCAAACAACTGCTTCCTGAATCTACCCCTGCAG GAAACCAAGAAATGGAGCTGTTTGAACTTCCAGCTACTTATGAGATAGGAATTGTTCGCCAGTTCCCA TTTTCTTCTGCTTTGCAACGTATGAGTGTGGTTGCCAGGGTGCTGGGGGATAGGAAAATGGACGCCTA CATGAAAGGAGCGCCCGAGGCCATTGCCGGTCTCTGTAAACCTGAAACAGTTCCTGTCGATTTTCAAA ACGTTTTGGAAGACTTCACTAAACAGGGCTTCCGTGTGATTGCTCTTGCACACAGAAAATTGGAGTCA AAACTGACATGGCATAAAGTACAGAATATTAGCAGAGATGCAATTGAGAACAACATGGATTTTATGGG ATTAATTATAATGCAGAACAAATTAAAGCAAGAAACCCCTGCAGTACTTGAAGATTTGCATAAAGCCA ACATTCGCACCGTCATGGTCACAGGTGACAGTATGTTGACTGCTGTCTCTGTGGCCAGAGATTGTGGA ATGATTCTACCTCAGGATAAAGTGATTATTGCTGAAGCATTACCTCCAAAGGATGGGAAAGTTGCCAA AATAAATTGGCATTATGCAGACTCCCTCACGCAGTGCAGTCATCCATCAGCAATTGACCCAGAGGCTA TTCCGGTTAAATTGGTCCATGATAGCTTAGAGGATCTTCAAATGACTCGTTATCATTTTGCAATGAAT GGAAAATCATTCTCAGTGATACTGGAGCATTTTCAAGACCTTGTTCCTAAGTTGATGTTGCATGGCAC CGTGTTTGCCCGTATGGCACCTGATCAGAAGACACAGTTGATAGAAGCATTGCAAAATGTTGATTATT TTGTTGGGATGTGTGGTGATGGCGCAAATGATTGTGGTGCTTTGAAGAGGGCACACGGAGGCATTTCC TTATCGGAGCTCGAAGCTTCAGTGGCATCTCCCTTTACCTCTAAGACTCCTAGTATTTCCTGTGTGCC AAACCTTATCAGGGAAGGCCGTGCTGCTTTAATAACTTCCTTCTGTGTGTTTAAATTCATGGCATTGT ACAGCATTATCCAGTACTTCAGTGTTACTCTGCTGTATTCTATCTTAAGTAACCTAGGAGACTTCCAG TTTCTCTTCATTGATCTGGCAATCATTTTGGTAGTGGTATTTACAATGAGTTTAAATCCTGCCTGGAA AGAACTTGTGGCACAAAGACCACCTTCGGGTCTTATATCTGGGGCCCTTCTCTTCTCCGTTTTGTCTC AGATTATCATCTGCATTGGATTTCAATCTTTGGGTTTTTTTTGGGTCAAACAGCAACCTTGGTATGAA GTGTGGCATCCAAAATCAGATGCTTGTAATACAACAGGAAGCGGGTTTTGGAATTCTTCACACGTAGA CAATGAAACCGAACTTGATGAACTAATATACAAAATTATGAAAATACCACAGTGTTTTTTATTTCCAG TTTTCAGTACCTCATAGTGGCAATTGCCTTTTCAAAAGGAAAACCCTTCAGGCAACCTTGCTACAAAA
ATTATTTTTTTGTTTTTTCTGTGATTTTTTTATATATTTTTATATTATTCATCATGTTGTATCCAGTT
GCCTCTGTTGACCAGGTTCTTCAGATAGTGTGTGTACCATATCAGTGGCGTGTAACTATGCTCATCAT
TGTTCTTGTCAATGCCTTTGTGTCTATCACAGTGGAGGAGTCAGTGGATCGGTGGGGAAAATGCTGCT
TACCCTGGGCCCTGGGCTGTAGAAAGAAGACACCAAAGGCAAAGTACATGTATCTGGCGCAGGAGCTC
TTGGTTGATCCAGAATGGCCACCAAAACCTCAGACAACCACAGAAGCTAAAGCTTTAGTTAAGGAGAA
TGGATCATGTCAAATCATCACCATAACATAGCAGTGAATCAGTCTCAGTGGTATTGCTGATAGCAGTA
TTCAGGAATATGTGATTTTAGGAGTTTCTGATCCTGTGTGTCAGAATGGCACTAGTTCAGTTTATGTC
CCTTCTGATATAGTAGCTTATTTGACAGCTTTGCTCTTCCTTAAAATAAAAAAAAAAAAAAAAAA
NOV73b, CG59δ39-01 SEQ ID NO: 1070 624 aa MW at 69590. lkD Protein Sequence
MTAGIVYAQRRLKKIGIFCISPQRINICGQLNLVCFDKTGTLTEDGLDLWGIQRVENARFLSPEENVC NEMLVKSQFVACMATCHSLTKIEGVLSGDPLDLKMFEAIGWILEEATEEETALHNRIMPTWRPPKQL LPESTPAGNQEMELFELPATYEIGIVRQFPFSSALQRMSWARVLGDRKMDAYMKGAPEAIAGLCKPE TVPVDFQNVLEDFTKQGFRVIALAHRKLESKLTWHKVQNISRDAIENNMDFMGLIIMQNKLKQETPAV LEDLHKANIRTVMVTGDSMLTAVSVARDCGMILPQDKVIIAEALPPKDGKVAKIN HYADSLTQCSHP SAIDPEAIPVKLVHDSLEDLQMTRYHFAMNGKSFSVILEHFQDLVPKLMLHGTVFARMAPDQKTQLIE ALQNVDYFVGMCGDGANDCGALKRAHGGISLSELEASVASPFTSKTPSISCVPNLIREGRAALITSFC VFKFMALYSIIQYFSVTLLYSILSNLGDFQFLFIDLAIILVWFTMSLNPAWKELVAQRPPSGLISGA LLFSVLSQIIICIGFQSLGFFWVKQQP YEVWHPKSDACNTTGSGFWNSSHVDNETELDELIYKIMKI PQCFLFPVFSTS
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 73B.
Table 73B. Comparison of the NOV73 protein sequences.
NOV73a MDKEERKIINQGQEDEMEIYGYNLSRWKLAIVSLGVICTGGFLLLLLYWMPE RVKATCV
NOV73b
NOV73a RAAIKDCDWLLRTTDEFKMWFCAKIRVLSLETHPISSPKSMSNKLSNGHAVCLTENPTG
NOV73b
NOV73a ENRHGISKYSQAESQQIRYFTHHSVKYFWNDTIHNFDFLKGLDEGVSCTSIYEKHSAGLT
NOV73b
NOV73a KGMHAYRKLLYGVNEIAVKVPSVFKLLIKEVLNPFYIFQLFSVIL STDEYYYYALAIW
NOV73b
NOV73a MSIVSIVSSLYSIRKQYVMLHDMVATHSTVRVSVCRVNEEIEEIFSTDLVPGDVMVIPLN
NOV73b
NOV73a GTIMPCDAVLINGTCIVNESMLTGESVPVTKTNLPNPSVDVKGIGDELYNPETHKRHTLF
NOV73b
NOV73a CGTTVIQTRFYTGELVKAIWRTGFSTSKGQLVRSILYPKPTDFKLYRDAYLFLLCLVAV
NOV73b NOV73a AGIGFIYTIINSILNEVQVGVIIIESLDIITITVPPALPAAMTAGIVYAQRRLKKIGIFC NOV73b MTAGIVYAQRRLKKIGIFC
NOV73a ISPQRINICGQLNLVCFDKTGTLTEDGLNL GIQRVENARFLSPEENVCNEMLVKSQFVA NOV73b ISPQRINICGQLNLVCFDKTGTLTEDGLDL GIQRVENARFLSPEENVCNEMLVKSQFVA
NOV73a CMATCHSLTKIEGVLSGDPLDLKMFEAIGWILEEATEEETALHNRIMPTWRPPKQLLPE NOV73b CMATCHSLTKIEGVLSGDPLDLKMFEAIG ILEEATEEETALHNRIMPTWRPPKQLLPE
NOV73a STPAGNQ EMATYEIGIVRQFPFSSALQRMSWARVLGDRKMDAYMKGAPEAIAG NOV73b STPAGNQEMELFELPATYEIGIVRQFPFSSALQRMSWARVLGDRKMDAYMKGAPEAIAG
NOV73a LCKPETVPVDFQNVLEDFTKQGFRVIALAHRKLESKLTWHKVQNISRDAIENNMDFMGLI NOV73b LCKPETVPVDFQNVLEDFTKQGFRVIALAHRKLESKLT HKVQNISRDAIENNMDFMGLI
NOV73a IMQNKLKQETPAVLEDLHKANIRTVMVTGDSMLTAVSVARDCGMILPQDKVIIAEALPPK NOV73b IMQNKLKQETPAVLEDLHKANIRTVMVTGDSMLTAVSVARDCGMILPQDKVIIAEALPPK
NOV73a DGKVAKIN HYADSLTQCSHPSAIDPEAIPVKLVHDSLEDLQMTRYHFAMNGKSFSVILE NOV73b DGKVAKINWHYADSLTQCSHPSAIDPEAIPVKLVHDSLEDLQMTRYHFAMNGKSFSVILE
NOV73a HFQDLVPKLMLHGTVFARMAPDQKTQLIEALQNVEYFVGMCGDGANDCGALKRAHGGISL NOV73b HFQDLVPKLMLHGTVFARMAPDQKTQLIEALQNVDYFVGMCGDGANDCGALKRAHGGISL
NOV73a SELEASVASPFTSKTPSISCVPNLIREGRAALITSFCVFKFMALYSIIQYFSVTLLYSIL NOV73b SELEASVASPFTSKTPSISCVPNLIREGRAALITSFCVFKFMALYSIIQYFSVTLLYSIL
NOV73a SNLGDFQFLFIDLAIILVWFTVSLNPAWKELVAQRPPSGLISGALLFSVLSQIIICIGF NOV73b SNLGDFQFLFIDLAIILVWFTMSLNPAWKELVAQRPPSGLISGALLFSVLSQIIICIGF
NOV73a QSLGFF VKQQP YEV HPKSEACNTTGSGF NSSHVDNETELDEIIYKIMKIPQCFLFP NOV73b QSLGFF VKQQP YEV HPKSDACNTTGSGF NSSHVDNETELDELIYKIMKIPQCFLFP
NOV73a VFSTS NOV73b VFSTS
NOV73a (SEQ ID NO: 1068) NOV73b (SEQ ID NO: 1070)
Further analysis ofthe NOV73a protein yielded the following properties shown in Table
73C.
Table 73C. Protein Sequence Properties NOV73a
SignalP analysis: Cleavage site between residues 5δ and 59
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 7; pos. chg 3; neg.chg 3 H-region: length 6; peak value -12.14 PSG score: -16.54
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -4.30 possible cleavage site: between 41 and 42 >>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5:
INTEGRAL Likelihood = -8 .44 T Trraannssimtembrane 31 - 47
INTEGRAL Likelihood = -6 .37 T Trraannssimtembrane 234 - 250
INTEGRAL Likelihood = 0 .32 T Trraannssπmembrane 295 - 311
INTEGRAL Likelihood = -9. .08 T Trraannssimtembrane 410 - 426
INTEGRAL Likelihood = -2, .81 T Trraannssimtembrane 439 - 455
INTEGRAL Likelihood = - 2 . .92 T Trraannssπmembrane 926 - 942
INTEGRAL Likelihood =-11. .15 T Trraannssπmembrane 963 - 979
INTEGRAL Likelihood = -6 .37 T Trraannssπmembrane 996 -1012
PERIPHERAL Likelihood = 1 .11 (at 211)
ALOM score : -11.15 (m:tmber of TMSs: 8)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 38 Charge difference: 4.0 C( 2.0) - N(-2.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.50 Hyd Moment(95): 5.62 G content: 0 D/E content : 2 S/T content : 0 Score: -6.77
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 9.1% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
55.6 %: endoplasmic reticulum
11.1 %: mitochondrial
11.1 %: vacuolar
11.1 %: vesicles of secretory system
11.1 %: Golgi
>> prediction for CG59839-02 is end (k=9)
A search of the NOV73a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 73D.
Figure imgf000979_0001
In a BLAST search of public sequence databases, the NOV73a protein was found to have homology to the proteins shown in the BLASTP data in Table 73E.
Figure imgf000980_0001
PFam analysis indicates that the NOV73a protein contains the domains shown in the Table 73F.
Figure imgf000981_0001
Example 74.
The NOV74 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 74A.
Table 74A. NOV74 Sequence Analysis
NOV74a, CG90866-04 SEQ ID NO: 1071 2937 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 2935
ATGCAGCCCCTGGACTTTAGTTCAGGGGGAAGTGACCCCAACATCAGCCTCTCAGAAAAGATCCGAGA TCAGCTTGTTGTTGGACAGCTGATTCCAGACTGCTATGTAGAACTTGAAAAAATCATTTTATCGGAGC GTAAAAATGTGCCAATTGAATTTCCCGTAATTGACCGGAAACGATTATTACAACTAGTGAGAGAAAAT CAGCTGCAGTTAGATGAAAATGAGCTTCCTCACGCAGTTCACTTTCTAAATGAATCAGGAGTCCTTCT TCATTTTCAAGACCCAGCACTGCAGTTAAGTGACTTGTACTTTGTGGAACCCAAGTGGCTTTGTAAAA TCATGGCACAGGATGTTAGCAGCATTTTTGGCCTTTATATTCGAGACATTTTGACAGTGAAAGTGGAA GGTTGTCCAAAACACCCTAAGGGCATTATTTCGCGTAGAGATGTGGAAAAATTTCTTTCAAAAAAAAG GAAATTTCCAAAGAACTACATGTCACAGTATTTTAAGCTCCTAGAAAAATTCCAGATTGCTTTGCCAA TAGGAGAAGAATATTTGCTGGTTCCAAGCAGTTTGTCTGACCACAGGCCTGTGATAGAGCTTCCCCAT TGTGAGAACTCTGAAATTATCATCCGACTATATGAAATGCCTTATTTTCCAATGGGATTTTGGTCAAG ATTAATCAATCGATTACTTGAGATTTCACCTTACATGCTTTCAGGGAGAGGCTGTATTCTTTTGGGCC AAGTTGTGGACCACATTGATTCTCTCATGGAAGAATGGTTTCCTGGGTTGCTGGAGATTGATATTTGT GGTGAAGGAGAAACTCTGTTGAAGAAATGGGCATTATATAGTTTTAATGATGGTGAAGAACATCAAAA AATCTTACTTGATGACTTGATGAAGAAAGCAGAGGAAGGAGATCTCTTAGTAAATCCAGATCAACCAA GGCTCACCATTCCAATATCTCAGATTGCCCCTGACTTGATTTTGGCTGACCCGCCTAGAAATATTATG TTGAATAATGATGAGTTGGAATTTGAACAAGCTCCAGAGTTTCTCCTAGACTGTTTTGTGTGTATTCA CTTATATCCATCAAGTGACTACATTTCAAGGCACTATATGAGAACCATAAATATTGTACAAACAGGAT TTGCTAAATGTCGGTGGAGAGTAACAGTCCACGGGGCTGATCATGGTGATGGCAGTTTTGGATCAGTT TACCGAGCAGCCTATGAAGGAGAAGAAGTGGCTGTGAAGATTTTTAATAAACATACATCACTCAGGCT GTTAAGACAAGAGCTTGTGGTGCTTTGCCACCTCCACCACCCCAGTTTGATATCTTTGCTGGCAGCTG GGATTCGTCCCCGGATGTTGGTGATGGAGTTAGCCTCCAAGGGTTCCTTGGATCGCCTGCTTCAGCAG GACAAAGCCAGCCTCACTAGAACCCTACAGCACAGGATTGCACTCCACGTAGCTGATGGTTTGAGATA CCTCCACTCAGCCATGATTATATACCGAGACCTGAAACCCCACAATGTGCTGCTTTTCACACTGTATC CCAATGCTGCCATCATTGCAAAGATTGCTGACTACGGCATTGCTCAGTACTGCTGTAGAATGGGGATA AAAACATCAGAGGGCACACCAGGTTTTCGTGCACCTGAAGTTGCCAGAGGAAATGTCATTTATAACCA ACAGGCTGATGTTTATTCATTTGGTTTACTACTCTATGACATTTTGACAACTGGAGGTAGAATAGTAG AGGGTTTGAAGTTTCCAAATGAGTTTGATGAATTAGAAATACAAGGAAAATTACCTGATCCAGTTAAA GAATATGGTTGTGCCCCATGGCCTATGGTTGAGAAATTAATTAAACAGTGTTTGAAAGAAAATCCTCA AGAAAGGCCTACTTCTGCCCAGGTATTCGACATTTTGAATTCAGCTGAATTAGTCTGTCTGACGAGAC GCATTTTATTACCTAAAAACGTAATTGTTGAATGCATGGTTGCTACACATCACAACAGCAGGAATGCA AGCATTTGGCTGGGCTGTGGGCACACCGACAGAGGACAGCTCTCATTTCTTGACTTAAATACTGAAGG ATACACTTCTGAGAGCAAACAAAAAAATTTTCTTTTGGTTGGAACCGCTGATGGCAAGTTAGCAATTT TTGAAGATAAGACTGTTAAGCTTAAAGGAGCTGCTCCTTTGAAGATACTAAATATAGGAAATGTCAGT ACTCCATTGATGTGTTTGAGTGAATCCACAAATTCAACGGAAAGAAATGTAATGTGGGGAGGATGTGG CACAAAGATTTTCTCCTTTTCTAATGATTTCACCATTCAGAAACTCATTGAGACAAGAACAAGCCAAC TGTTTTCTTATGCAGCTTTCAGTGATTCCAACATCATAACAGTGGTGGTAGACACTGCTCTCTATATT GCTAAGCAAAATAGCCCTGTTGTGGAAGTGTGGGATAAGAAAACTGAAAAACTCTGTGGACTAATAGA CTGCGTGCACTTTTTAAGGGAGGTAATGGTAAAAGAAAACAAGGAATCAAAACACAAAATGTCTTATT CTGGGAGAGTGAAAACCCTCTGCCTTCAGAAGAACACTGCTCTTTGGATAGGAACTGGAGGAGGCCAT ATTTTACTCCTGGATCTTTCAACTCGTCGACTTATACGTGTAATTTACAACTTTTGTAATTCGGTCAG AGTCATGATGACAGCACAGCTAGGCAGCCTTAAAAATGTCATGCTGGTATTGGGCTACAACCGGAAAA ATACTGAAGGTACACAAAAGCAGAAAGAGATACAATCTTGCTTGACCGTTTGGGACATCAATCTTCCA CATGAAGTGCAAAATTTAGAAAAACACATTGAAGTGAGAAAAGAATTAGCTGAAAAAATGAGACGAAC ATCTGTTGAGTAA
NOV74a, CG90866-04 SEQ ID NO: 1072 97 aa MW at 111173.δkD Protein Sequence
MQPLDFSSGGSDPNISLSEKIRDQLWGQLIPDCYVELEKIILSERKNVPIEFPVIDRKRLLQLVREN QLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQDVSSIFGLYIRDILTVKVE GCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVIELPH CENSEIIIRLYEMPYFP GF SRLINRLLEISPYMLSGRGCILLGQWDHIDSLMEEWFPGLLEIDIC GEGETLLKK ALYSFNDGEEHQKILLDDL KKAEEGDLLVNPDQPRLTIPISQIAPDLILADPPRNIM LNNDELEFEQAPEFLLDCFVCIHLYPSSDYISRHYMRTINIVQTGFAKCR RVTVHGADHGDGSFGSV YRAAYEGEEVAVKIFNKHTSLRLLRQELWLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQ DKASLTRTLQHRIALHVADGLRYLHSA IIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGI KTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPVK EYGCAPWPMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNVIVECMVATHHNSRNA SIWLGCGHTDRGQLSFLDLNTEGYTSESKQKNFLLVGTADGKLAIFEDKTVKLKGAAPLKILNIGNVS TPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRTSQLFSYAAFSDSNIITVWDTALYI AKQNSP E DKKTEKLCGLIDCVHFLREVMVKENKESKHKMSYSGRVKTLCLQKNTALWIGTGGGH ILLLDLSTRRLIRVIYNFCNSVRVMMTAQLGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLP HEVQNLEKHIEVRKELAEKMRRTSVE
NOV74b, CG90866-03 SEQ ID NO: 1073 J2687 bp DNA Sequence ORF Start: ATG at 108 ORF Stop: TAA at 2658
ACGCAGTTCACTTTCTAAATGAATCAGGAGTCCTTCTTCATTTTCAAGACCCAGCACTGCAGTTAAGT
GACTTGTACTTTGTGGAACCCAAGTGGCTTTGTAAAATCATGGCACAGATTTTGACAGTGAAAGTGGA
AGGTTGTCCAAAACACCCTAAGGGCATTATTTCGCGTAGAGATGTGGAAAAATTTCTTTCAAAAAAAA GGAAATTTCCAAAGAACTACATGTCACAGTATTTTAAGCTCCTAGAAAAATTCCAGATTGCTTTGCCA ATAGGAGAAGAATATTTGCTGGTTCCAAGCAGTTTGTCTGACCACAGGCCTGTGATAGAGCTTCCCCA TTGTGAGAACTCTGAAATTATCATCCGACTATATGAAATGCCTTATTTTCCAATGGGATTTTGGTCAA GATTAATCAATCGATTACTTGAGATTTCACCTTACATGCTTTCAGGGAGAGAACGAGCACTTCGCCCA AACAGAATGTATTGGCGACAAGGCATTTACTTAAATTGGTCTCCTGAAGCTTATTGTCTGGTAGGATC TGAAGTCTTAGACAATCATCCAGAGAGTTTCTTAAAAATTACAGTTCCTTCTTGTAGAAAAGGCTGTA TTCTTTTGGGCCAAGTTGTGGACCACATTGATTCTCTCATGGAAGAATGGTTTCCTGGGTTGCTGGAG ATTGATATTTGTGGTGAAGGAGAAACTCTGTTGAAGAAATGGGCATTATATAGTTTTAATGATGGCGA AGAACATCAAAAAATCTTACTTGATGACTTGATGAAGAAAGCAGAGGAAGGAGATCTCTTAGTAAATC CAGATCAACCAAGGCTCACCATTCCAATATCTCAGATTGCCCCTGACTTGATTTTGGCTGACCTGCCT AGAAATATTATGTTGAATAATGATGAGTTGGAATTTGAACAAGCTCCAGAGTTTCTCCTAGGTGATGG CAGTTTTGGATCAGTTTACCGAGCAGCCTATGAAGGAGAAGAAGTGGCTGTGAAGATTTTTAATAAAC ATACATCACTCAGGCTGTTAAGACAAGAGCTTGTGGTGCTTTGCCACCTCCACCACCCCAGTTTGATA TCTTTGCTGGCAGCTGGGATTCGTCCCCGGATGTTGGTGATGGAGTTAGCCTCCAAGGGTTCCTTGGA TCGCCTGCTTCAGCAGGACAAAGCCAGCCTCACTAGAACCCTACAGCACAGGATTGCACTCCACGTAG CTGATGGTTTGAGATACCTCCACTCAGCCATGATTATATACCGAGACCTGAAACCCCACAATGTGCTG CTTTTCACACTGTATCCCAATGCTGCCATCATTGCAAAGATTGCTGACTACGGCATTGCTCAGTACTG CTGTAGAATGGGGATAAAAACATCAGAGGGCACACCAGGTTTTCGTGCACCTGAAGTTGCCAGAGGAA ATGTCATTTATAACCAACAGGCTGATGTTTATTCATTTGGTTTACTACTCTATGACATTTTGACAACT GGAGGTAGAATAGTAGAGGGTTTGAAGTTTCCAAATGAGTTTGATGAATTAGAAATACAAGGAAAATT ACCTGATCCAGTTAAAGAATATGGTTGTGCCCCATGGCCTATGGTTGAGAAATTAATTAAACAGTGTT TGAAAGAAAATCCTCAAGAAAGGCCTACTTCTGCCCAGGTATTCGACATTTTGAATTCAGCTGAATTA GTCTGTCTGACGAGACGCATTTTATTACCTAAAAACGTAATTGTTGAATGCATGGTTGCTACACATCA CAACAGCAGGAATGCAAGCATTTGGCTGGGCTGTGGGCACACCGACAGAGGACAGCTCTCATTTCTTG ACTTAAATACTGAAGGATACACTTCTGAGGAAGTTGCTGATAGTAGAATATTGTGCTTAGCCTTGGTG CATCTTCCTGTTGAAAAGGAAAGCTGGATTGTGTCTGGGACACAGTCTGGTACTCTCCTGGTCATCAA TACCGAAGATGGGAAAAAGAGACATACCCTAGAAAAGATGACTGATTCTGTCACTTGTTTGTATTGCA ATTCCTTTTCCAAGCAAAGCAAACAAAAAAATTTTCTTTTGGTTGGAACCGCTGATGGCAAGTTAGCA ATTTTTGAAGATAAGACTGTTAAGCTTAAAGGAGCTGCTCCTTTGAAGATACTAAATATAGGAAATGT CAGTACTCCATTGATGTGTTTGAGTGAATCCACAAATTCAACGGAAAGAAATGTAATGTGGGGAGGAT GTGGCACAAAGATTTTCTCCTTTTCTAATGATTTCACCATTCAGAAACTCATTGAGACAAGAACAAGC CAACTGTTTTCTTATGCAGCTTTCAGTGATTCCAACATCATAACAGTGGTGGTAGACACTGCTCTCTA TATTGCTAAGCAAAATAGCCCTGTTGTGGAAGTGTGGGATAAGAAAACTGAAAAACTCTGTGGACTAA TAGACTGCGTGCACTTTTTAAGCCTTAAAAATGTCATGCTGGTATTGGGCTACAACCGGAAAAATACT GAAGGTACACAAAAGCAGAAAGAGATACAATCTTGCTTGACCGTTTGGGACATCAATCTTCCACATGA AGTGCAAAATTTAGAAAAACACATTGAAGTGAGAAAAGAATTAGCTGAAAAAATGAGACGAACATCTG TTGAGTAAGAGAGAAATAGGAATTGTCTTTGGATA
NOV74b, CG90δ66-03 SEQ ID NO: 1074 850 aa MW at 96332.5kD Protein Sequence f4AQILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFILLEKFQIALPIGEEYLLVPSSLS DHRPVIELPHCENSEIIIRLYEMPYFPMGF SRLINRLLEISPYMLSGRERALRPNRMYWRQGIYLN SPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQWDHIDSLMEEWFPGLLEIDICGEGETLLKK WALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFE QAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELWLCHLHHPSLISLLAAGIRPRMLV MELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAK IADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNE FDELEIQGKLPDPVKEYGCAP PMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNV IVECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSG TQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTVKLKGAA PLKILNIGNVSTPLMCLSESTNSTERNVM GGCGTKIFSFSNDFTIQKLIETRTSQLFSYAAFSDSNI ITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLSLKNVMLVLGYNRKNTEGTQKQPEIQSCL TVWDINLPHEVQNLEKHIEVRKELAEKMRRTSVE
NOV74c, CG90866-01 SEQ ID NO: 1075 3052 bp DNA Sequence ORF Start: ATG at 108 ORF Stop: TAA at 2853
ACGCAGTTCACTTTCTAAATGAATCAGGAGTCCTTCTTCATTTTCAAGACCCAGCACTGCAGTTAAGT
GACTTGTACTTTGTGGAACCCAAGTGGCTTTGTAAAATCATGGCACAGATTTTGACAGTGAAAGTGGA
AGGTTGTCCAAAACACCCTAAGGGCATTATTTCGCGTAGAGATGTGGAAAAATTTCTTTCAAAAAAAA GGAAATTTCCAAAGAACTACATGTCACAGTATTTTAAGCTCCTAGAAAAATTCCAGATTGCTTTGCCA ATAGGAGAAGAATATTTGCTGGTTCCAAGCAGTTTGTCTGACCACAGGCCTGTGATAGAGCTTCCCCA TTGTGAGAACTCTGAAATTATCATCCGACTATATGAAATGCCTTATTTTCCAATGGGATTTTGGTCAA GATTAATCAATCGATTACTTGAGATTTCACCTTACATGCTTTCAGGGAGAGAACGAGCACTTCGCCCA AACAGAATGTATTGGCGACAAGGCATTTACTTAAATTGGTCTCCTGAAGCTTATTGTCTGGTAGGATC TGAAGTCTTAGACAATCATCCAGAGAGTTTCTTAAAAATTACAGTTCCTTCTTGTAGAAAAGGCTGTA TTCTTTTGGGCCAAGTTGTGGACCACATTGATTCTCTCATGGAAGAATGGTTTCCTGGGTTGCTGGAG ATTGATATTTGTGGTGAAGGAGAAACTCTGTTGAAGAAATGGGCATTATATAGTTTTAATGATGGCGA AGAACATCAAAAAATCTTACTTGATGACTTGATGAAGAAAGCAGAGGAAGGAGATCTCTTAGTAAATC CAGATCAACCAAGGCTCACCATTCCAATATCTCAGATTGCCCCTGACTTGATTTTGGCTGACCTGCCT AGAAATATTATGTTGAATAATGATGAGTTGGAATTTGAACAAGCTCCAGAGTTTCTCCTAGGTGATGG CAGTTTTGGATCAGTTTACCGAGCAGCCTATGAAGGAGAAGAAGTGGCTGTGAAGATTTTTAATAAAC ATACATCACTCAGGCTGTTAAGACAAGAGCTTGTGGTGCTTTGCCACCTCCACCACCCCAGTTTGATA TCTTTGCTGGCAGCTGGGATTCGTCCCCGGATGTTGGTGATGGAGTTAGCCTCCAAGGGTTCCTTGGA TCGCCTGCTTCAGCAGGACAAAGCCAGCCTCACTAGAACCCTACAGCACAGGATTGCACTCCACGTAG CTGATGGTTTGAGATACCTCCACTCAGCCATGATTATATACCGAGACCTGAAACCCCACAATGTGCTG CTTTTCACACTGTATCCCAATGCTGCCATCATTGCAAAGATTGCTGACTACGGCATTGCTCAGTACTG CTGTAGAATGGGGATAAAAACATCAGAGGGCACACCAGGGTTTCGTGCACCTGAAGTTGCCAGAGGAA ATGTCATTTATAACCAACAGGCTGATGTTTATTCATTTGGTTTACTACTCTATGACATTTTGACAACT GGAGGTAGAATAGTAGAGGGTTTGAAGTTTCCAAATGAGTTTGATGAATTAGAAATACAAGGAAAATT ACCTGATCCAGTTAAAGAATATGGTTGTGCCCCATGGCCTATGGTTGAGAAATTAATTAAACAGTGTT TGAAAGAAAATCCTCAAGAAAGGCCTACTTCTGCCCAGGTATTCTCTCAGGTCTTTGACATTTTGAAT TCAGCTGAATTAGTCTGTCTGACGAGACGCATTTTATTACCTAAAAACGTAATTGTTGAATGCATGGT TGCTACACATCACAACAGCAGGAATGCAAGCATTTGGCTGGGCTGTGGGCACACCGACAGAGGACAGC TCTCATTTCTTGACTTAAATACTGAAGGATACACTTCTGAGGAAGTTGCTGATAGTAGAATATTGTGC TTAGCCTTGGTGCATCTTCCTGTTGAAAAGGAAAGCTGGATTGTGTCTGGGACACAGTCTGGTACTCT CCTGGTCATCAATACCGAAGATGGGAAAAAGAGACATACCCTAGAAAAGATGACTGATTCTGTCACTT GTTTGTATTGCAATTCCTTTTCCAAGCAAAGCAAACAAAAAAATTTTCTTTTGGTTGGAACCGCTGAT GGCAAGTTAGCAATTTTTGAAGATAAGACTGTTAAGCTTAAAGGAGCTGCTCCTTTGAAGATACTAAA TATAGGAAATGTCAGTACTCCATTGATGTGTTTGAGTGAATCCACAAATTCAACGGAAAGAAATGTAA TGTGGGGAGGATGTGGCACAAAGATTTTCTCCTTTTCTAATGATTTCACCATTCAGAAACTCATTGAG ACAAGAACAAGCCAACTGTTTTCTTATGCAGCTTTCAGTGATTCCAACATCATAACAGTGGTGGTAGA CACTGCTCTCTATATTGCTAAGCAAAATAGCCCTGTTGTGGAAGTGTGGGATAAGAAAACTGAAAAAC TCTGTGGACTAATAGACTGCGTGCACTTTTTAAGGTTAGTAAAACCAAATAGAAAAAAATTATCTAAC CTTATGATGTCTTTGGCTTTACATCCTATATGTTTAAAATCAAAGTTAAGATGCAGTTCATCCAAAGG AAGATCCCATATTTTGCTTCGTGTAATTTACAACTTTTGTAATTCGGTCAGAGTCATGATGACAGCAC AGCTAGGCGGAAGCCTTAAAAATGTCATGCTGGTATTGGGCTACAACCGGAAAAATACTGAAGGTACA CAAAAGCAGAAAGAGATACAATCTTGCTTGACCGTTTGGGACATCAATCTTCCACATGAAGTGCAAAA TTTAGAAAAACACATTGAAGTGAGAAAAGAATTAGCTGAAAAAATGAGACGAACATCTGTTGAGTAAG AGAGAAATAGGAATTGTCTTTGGATAGGAAAATTATTCTCTCCTCTTGTAAATATTTATTTTAAAAAT
GTTCACATGGAAAGGGTACTCACATTTTTTGAAATAGCTCGTGTGTATGAAGGAATGTTATTATTTTT lAATTTAAATATATGTAAAAATACTTACCAGTAAATGTGTATTTTAAAGAACTATTTAAAA
NOV74c, CG90866-01 SEQ ID NO: 1076 915 aa MW at l03676.4kD Protein Sequence I
MAQILTV VEGCPKHPKGIISRRDVEKFLSKKRKFPKNY SQYFKLLEKFQIALPIGEEYLLVPSSLS DHRPVIELPHCENSEIIIRLYE PYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYLNW SPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQWDHIDSLMEEWFPGLLEIDICGEGETLLKK WALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFE QAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELWLCHLHHPSLISLLAAGIRPRMLV MELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAK IADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNE FDELEIQGKLPDPVKEYGCAP PMVEKLIKQCLKENPQERPTSAQVFSQVFDILNSAELVCLTRRILL PKNVIVECMVATHHNSRNASI LGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESW IVSGTQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGΪLAIFEDKTVKL KGAAPLKILNIGNVSTPL CLSESTNSTERNVMWGGCGTKIFSFSNDFTIQPLIETRTSQLFSYAAFS DSNIITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCTVHFLRLVKPNRKKLSNLMMSLALHPICLK SKLRCSSSKGRSHILLRVIYNFCNSVRVMMTAQLGGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVW DINLPHEVQNLEKHIEVRKELAEKMRRTSVE
NOV74d, CG90866-02 SEQ ID NO: 1077 3040 bp DNA Sequence ORF Start: ATG at 108 ORF Stop: TAA at 2841
ACGCAGTTCACTTTCTAAATGAATCAGGAGTCCTTCTTCATTTTCAAGACCCAGCACTGCAGTTAAGT
GACTTGTACTTTGTGGAACCCAAGTGGCTTTGTAAAATCATGGCACAGATTTTGACAGTGAAAGTGGA
AGGTTGTCCAAAACACCCTAAGGGCATTATTTCGCGTAGAGATGTGGAAAAATTTCTTTCAAAAAAAA GGAAATTTCCAAAGAACTACATGTCACAGTATTTTAAGCTCCTAGAAAAATTCCAGATTGCTTTGCCA ATAGGAGAAGAATATTTGCTGGTTCCAAGCAGTTTGTCTGACCACAGGCCTGTGATAGAGCTTCCCCA TTGTGAGAACTCTGAAATTATCATCCGACTATATGAAATGCCTTATTTTCCAATGGGATTTTGGTCAA GATTAATCAATCGATTACTTGAGATTTCACCTTACATGCTTTCAGGGAGAGAACGAGCACTTCGCCCA AACAGAATGTATTGGCGACAAGGCATTTACTTAAATTGGTCTCCTGAAGCTTATTGTCTGGTAGGATC TGAAGTCTTAGACAATCATCCAGAGAGTTTCTTAAAAATTACAGTTCCTTCTTGTAGAAAAGGCTGTA TTCTTTTGGGCCAAGTTGTGGACCACATTGATTCTCTCATGGAAGAATGGTTTCCTGGGTTGCTGGAG ATTGATATTTGTGGTGAAGGAGAAACTCTGTTGAAGAAATGGGCATTATATAGTTTTAATGATGGCGA AGAACATCAAAAAATCTTACTTGATGACTTGATGAAGAAAGCAGAGGAAGGAGATCTCTTAGTAAATC CAGATCAACCAAGGCTCACCATTCCAATATCTCAGATTGCCCCTGACTTGATTTTGGCTGACCTGCCT AGAAATATTATGTTGAATAATGATGAGTTGGAATTTGAACAAGCTCCAGAGTTTCTCCTAGGTGATGG CAGTTTTGGATCAGTTTACCGAGCAGCCTATGAAGGAGAAGAAGTGGCTGTGAAGATTTTTAATAAAC ATACATCACTCAGGCTGTTAAGACAAGAGCTTGTGGTGCTTTGCCACCTCCACCACCCCAGTTTGATA TCTTTGCTGGCAGCTGGGATTCGTCCCCGGATGTTGGTGATGGAGTTAGCCTCCAAGGGTTCCTTGGA TCGCCTGCTTCAGCAGGACAAAGCCAGCCTCACTAGAACCCTACAGCACAGGATTGCACTCCACGTAG CTGATGGTTTGAGATACCTCCACTCAGCCATGATTATATACCGAGACCTGAAACCCCACAATGTGCTG CTTTTCACACTGTATCCCAATGCTGCCATCATTGCAAAGATTGCTGACTACGGCATTGCTCAGTACTG CTGTAGAATGGGGATAAAAACATCAGAGGGCACACCAGGGTTTCGTGCACCTGAAGTTGCCAGAGGAA ATGTCATTTATAACCAACAGGCTGATGTTTATTCATTTGGTTTACTACTCTATGACATTTTGACAACT GGAGGTAGAATAGTAGAGGGTTTGAAGTTTCCAAATGAGTTTGATGAATTAGAAATACAAGGAAAATT ACCTGATCCAGTTAAAGAATATGGTTGTGCCCCATGGCCTATGGTTGAAAAATTAATTAAACAGTGTT TGAAAGAAAATCCTCAAGAAAGGCCTACTTCTGCCCAGGTCTTTGACATTTTGAATTCAGCTGAATTA GTCTGTCTGACGAGACGCATTTTATTACCTAAAAACGTAATTGTTGAATGCATGGTTGCTACACATCA CAACAGCAGGAATGCAAGCATTTGGCTGGGCTGTGGGCACACCGACAGAGGACAGCTCTCATTTCTTG ACTTAAATACTGAAGGATACACTTCTGAGGAAGTTGCTGATAGTAGAATATTGTGCTTAGCCTTGGTG CATCTTCCTGTTGAAAAGGAAAGCTGGATTGTGTCTGGGACACAGTCTGGTACTCTCCTGGTCATCAA TACCGAAGATGGGAAAAAGAGACATACCCTAGAAAAGATGACTGATTCTGTCACTTGTTTGTATTGCA ATTCCTTTTCCAAGCAAAGCAAACAAAAAAATTTTCTTTTGGTTGGAACCGCTGATGGCAAGTTAGCA ATTTTTGAAGATAAGACTGTTAAGCTTAAAGGAGCTGCTCCTTTGAAGATACTAAATATAGGAAATGT CAGTACTCCATTGATGTGTTTGAGTGAATCCACAAATTCAACGGAAAGAAATGTAATGTGGGGAGGAT GTGGCACAAAGATTTTCTCCTTTTCTAATGATTTCACCATTCAGAAACTCATTGAGACAAGAACAAGC CAACTGTTTTCTTATGCAGCTTTCAGTGATTCCAACATCATAACAGTGGTGGTAGACACTGCTCTCTA TATTGCTAAGCAAAATAGCCCTGTTGTGGAAGTGTGGGATAAGAAAACTGAAAAACTCTGTGGACTAA TAGACTGCGTGCACTTTTTAAGGTTAGTAAAACCAAATAGAAAAAAATTATCTAACCTTATGATGTCT TTGGCTTTACATCCTATATGTTTAAAATCAAAGTTAAGATGCAGTTCATCCAAAGGAAGATCCCATAT TTTGCTTCGTGTAATTTACAACTTTTGTAATTCGGTCAGAGTCATGATGACAGCACAGCTAGGCGGAA GCCTTAAAAATGTCATGCTGGTATTGGGCTACAACCGGAAAAATACTGAAGGTACACAAAAGCAGAAA GAGATACAATCTTGCTTGACCGTTTGGGACATCAATCTTCCACATGAAGTGCAAAATTTAGAAAAACA CATTGAAGTGAGAAAAGAATTAGCTGAAAAAATGAGACGAACATCTGTTGAGTAAGAGAGAAATAGGA
ATTGTCTTTGGATAGGAAAATTATTCTCTCCTCTTGTAAATATTTATTTTAAAAATGTTCACATGGAA
AGGGTACTCACATTTTTTGAAATAGCTCGTGTGTATGAAGGAATGTTATTATTTTTAATTTAAATATA
TGTAAAAATACTTACCAGTAAATGTGTATTTTAAAGAACTATTTAAAA
NOV74d, CG90866-02 SEQ ID NO: 1078 91 1 aa MW at 103214.9kD Protein Sequence
MAQILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLS DHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYLNW SPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQWDHIDSLMEEWFPGLLEIDICGEGETLLKK WALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFE QAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELWLCHLHHPSLISLLAAGIRPRMLV MELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAK IADYGIAQYCCR GIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNE FDELEIQGKLPDPVKEYGCAP PMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNV IVECMVATHHNSRNASI LGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKES IVSG TQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTVKLKGAA PLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRTSQLFSYAAFSDSNI ITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLRLVKPNRKKLSNLMMSLALHPICLKSKLR CSSSKGRSHILLRVIYNFCNSVRVMTAQLGGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINL PHEVQNLEKHIEVRKELAEKMRRTSVE
NOV74e, CG90866-05 SEQ ID NO: 1079 2955 bp
DNA Sequence lORF Start: ATG at 81 ORF Stop: TAA at 2δ44
GAGTCCTTCTTCATTTTCAAGACCCAGCACTGCAGTTAAGTGACTTGTACTTTGTGGAACCCAAGTGG
CTTTGTAAAATCATGGCACAGATTTTGACAGTGAAAGTGGAAGGTTGTCCAAAACACCCTAAGGGAAT
TATTTCGCGTAGAGATGTGGAAAAATTTCTTTCAAAAAAAAGGAAATTTCCAAAGAACTACATGTCAC AGTATTTTAAGCTCCTAGAAAAATTCCAGATTGCTTTGCCAATAGGAGAAGAATATTTGCTGGTTCCA AGCAGTTTGTCTGACCACAGGCCTGTGATAGAGCTTCCCCATTGTGAGAACTCTGAAATTATCATCCG ACTATATGAAATGCCTTATTTTCCAATGGGATTTTGGTCAAGATTAATCAATCGATTACTTGAGATTT CACCTTACATGCTTTCAGGGAGAGAACGAGCACTTCGCCCAAACAGAATGTATTGGCGACAAGGCATT TACTTAAATTGGTCTCCTGAAGCTTATTGTCTGGTAGGATCTGAAGTCTTAGACAATCATCCAGAGAG TTTCTTAAAAATTACAGTTCCTTCTTGTAGAAAAGGCTGTATTCTTTTGGGCCAAGTTGTGGACCACA TTGATTCTCTCATGGAAGAATGGTTTCCTGGGTTGCTGGAGATTGATATTTGTGGTGAAGGAGAAACT CTGTTGAAGAAATGGGCATTATATAGTTTTAATGATGGTGAAGAACATCAAAAAATCTTACTTGATGA CTTGATGAAGAAAGCAGAGGAAGGAGATCTCTTAGTAAATCCAGATCAACCAAGGCTCACCATTCCAA TATCTCAGATTGCCCCTGACTTGATTTTGGCTGACCTGCCTAGAAATATTATGTTGAATAATGATGAG TTGGAATTTGAACAAGCTCCAGAGTTTCTCCTAGGTGATGGCAGTTTTGGATCAGTTTACCGAGCAGC CTATGAAGGAGAAGAAGTGGCTGTGAAGATTTTTAATAAACATACATCACTCAGGCTGTTAAGACAAG AGCTTGTGGTGCTTTGCCACCTCCACCACCCCAGTTTGATATCTTTGCTGGCAGCTGGGATTCGTCCC CGGATGTTGGTGATGGAGTTAGCCTCCAAGGGTTCCTTGGATCGCCTGCTTCAGCAGGACAAAGCCAG CCTCACTAGAACCCTACAGCACAGGATTGCACTCCACGTAGCTGATGGTTTGAGATACCTCCACTCAG CCATGATTATATACCGAGACCTGAAACCCCACAATGTGCGGCTTTTCACACTGTATCCCAATGCTGCC ATCATTGCAAAGATTGCTGACTACGGCATTGCTCAGTACTGCTGTAGAATGGGGATAAAAACATCAGA GGGCACACCAGGGTTTCGTGCACCTGAAGTTGCCAGAGGAAATGTCATTTATAACCAACAGGCTGATG TTTATTCATTTGGTTTACTACTCTATGACATTTTGACAACTGGAGGTAGAATAGTAGAGGGTTTGAAG TTTCCAAATGAGTTTGATGAATTAGAAATACAAGGAAAATTACCTGATCCAGTTAAAGAATATGGTTG TGCCCCATGGCCTATGGTTGAGAAATTAATTAAACAGTGTTTGAAAGAAAATCCTCAAGAAAGGCCTA CTTCTGCCCAGGTCTTTGACATTTTGAATTCAGCTGAATTAGTCTGTCTGACGAGACGCATTTTATTA CCTAAAAACGTAATTGTTGAATGCATGGTTGCTACACATCACAACAGCAGGAATGCAAGCATTTGGCT GGGCTGTGGGCACACCGACAGAGGACAGCTCTCATTTCTTGACTTAAATACTGAAGGATACACTTCTG AGGAAGTTGCTGATAGTAGAATATTGTGCTTAGCCTTGGTGCATCTTCCTGTTGAAAAGGAAAGCTGG ATTGTGTCTGGGACACAGTCTGGTACTCTCCTGGTCATCAATACCGAAGATGGGAAAAAGAGACATAC CCTAGAAAAGATGACTGATTCTGTCACTTGTTTGTATTGCAATTCCTTTTCCAAGCAAAGCAAACAAA AAAATTTTCTTTTGGTTGGAACCGCTGATGGCAAGTTAGCAATTTTTGAAGATAAGACTGTTAAGCTT AAAGGAGCTGCTCCTTTGAAGATACTAAATATAGGAAATGTCAGTACTCCATTGATGTGTTTGAGTGA ATCCACAAATTCAACGGAAAGAAATGTAATGTGGGGAGGATGTGGCACAAAGATTTTCTCCTTTTCTA ATGATTTCACCATTCAGAAACTCATTGAGACAAGAACAAGCCAACTGTTTTCTTATGCAGCTTTCAGT GATTCCAACATCATAACAGTGGTGGTAGACACTGCTCTCTATATTGCTAAGCAAAATAGCCCTGTTGT GGAAGTGTGGGATAAGAAAACTGAAAAACTCTGTGGGCTAATAGACTGCGTGCACTTTTTAAGGGAGG TAACGGTAAAAGAAAACAAGGAATCAAAACACAAAATGTCTTATTCTGGGAGAGTGAAAACCCTCTGC CTTCAGAAGAACACTGCTCTTTGGATAGGAACTGGAGGAGGCCATATTTTACTCCTGGATCTTTCAAC TCGTCGACTTATACGTGTAATTTACAACTTTTGTAATTCGGTCAGAGTCATGATGACAGCACAGCTAG GAAGCCTTAAAAATGTCATGCTGGTATTGGGCTACAACCGGAAAAATACTGAAGGTACACAAAAGCAG AAAGAGATACAATCTTGCTTGACCGTTTGGGACATCAATCTTCCACATGAAGTGCAAAATTTAGAAAA ACACATTGAAGTGAGAAAAGAATTAGCTGAAAAAATGAGACGAACATCTGTTGAGTAAGAGAGAAATA
GGAATTGTCTTTGGATAGGAAAATTATTCTCTCCTCTTGTAAATATTTATTTTAAAAATGTTCACATG
GAAAGGGTACTCACATTTTTAAGGGCGAATC
NOV74e, CG90866-05 SEQ ID NO: 10δ0 921 aa MW at l04423.0kD Protein Sequence
MAQILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLS DHRPVIELPHCENSEIIIRLYEMPYFPMGF SRLINRLLEISPYMLSGRERALRPNRMYWRQGIYLNW SPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQWDHIDSLMEE FPGLLEIDICGEGETLLKK ALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFE QAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELWLCHLHHPSLISLLAAGIRPRMLV MELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMII RDLKPHNVRLFTLYPNAAIIAK IADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNE FDELEIQGKLPDPVKEYGCAP PMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNV IVECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSG TQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTVKLKGAA PLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRTSQLFSYAAFSDSNI ITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLREVTVKENKESKHKMSYSGRVKTLCLQKN TAL IGTGGGHILLLDLSTRRLIRVIYNFCNSVRVMMTAQLGSLKNVMLVLGYNRKNTEGTQKQKEIQ SCLTV DINLPHEVQNLEKHIEVRKELAEKMRRTSVE
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 74B.
Table 74B. Comparison of the NOV74 protein sequences.
NOV74a MQPLDFSSGGSDPNISLSEKIRDQLWGQLIPDCYVELEKIILSERKNVPIEFPVIDRKR
NOV74b
NOV74c
NOV74d
NOV74e
NOV74a LLQLVRENQLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQDVS
NOV74b MAQ
NOV74c MAQ
NOV74d MAQ
NOV74e MAQ
NOV74a SIFGLYIRDILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIAL
NOV74b ILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIAL
NOV74C ILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIAL
NOV74d ILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIAL
NOV7 e ILTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIAL
9δ2 NOV74a PIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYML
NOV74b PIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYML
NOV74C PIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYML
N0V74d PIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYML
NOV74e PIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGF SRLINRLLEISPYML
NOV74a SG--R GCILLGQV
NOV74b SGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQV
N0V74C SGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQV
NOV74d SGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQV
NOV74e SGRERALRPNRMYWRQGIYLN SPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQV
N0V74a VDHIDSLMEE FPGLLEIDICGEGETLLKK ALYSFNDGEEHQKILLDDLMKKAEEGDLL
NOV74b VDHIDSLMEEWFPGLLEIDICGEGETLLKKWALYSFNDGEEHQKILLDDLMKKAEEGDLL
NOV74C VDHIDSLMEE FPGLLEIDICGEGETLLKK ALYSFNDGEEHQKILLDDLMKKAEEGDLL
NOV74d VDHIDSLMEEWFPGLLEIDICGEGETLLKK ALYSFNDGEEHQKILLDDLMKKAEEGDLL
N0V74e VDHIDSLMEEWFPGLLEIDICGEGETLLKK ALYSFNDGEEHQKILLDDLMKKAEEGDLL
NOV74a VNPDQPRLTIPISQIAPDLILADPPRNIMLNNDELEFEQAPEFLLDCFVCIHLYPSSDYI
NOV74b VNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEQAPEFLL
NOV74C VNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEQAPEFLL
NOV74d VNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEQAPEFLL
NOV74e VNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEQAPEFLL
NOV74a SRHYMRTINIVQTGFAKCRWRVTVHGADHGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRL
NOV74b GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRL
NOV74C GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRL
NOV74d GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRL
NOV74e GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRL
N0V74a LRQELWLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIAL
NOV74b LRQELWLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIAL
NOV74c LRQELWLCHLHHPSLISLLAAGIRPR LVMELASKGSLDRLLQQDKASLTRTLQHRIAL
NOV74d LRQELWLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIAL
NOV74e LRQELWLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIAL
NOV74a HVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTP
NOV74b HVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTP
NOV74c HVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTP
NOV74d HVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTP
NOV74e HVADGLRYLHSAMIIYRDLKPHNVRLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTP
NOV74a GFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPV
NOV74b GFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPV
NOV74C GFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPV
NOV74d GFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPV
NOV74e GFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPV
NOV74a KEYGCAPWPMVEKLIKQCLKENPQERPTSAQVF DILNSAELVCLTRRILLPKNVIV
NOV74b KEYGCAPWPMVEKLIKQCLKENPQERPTSAQVF DILNSAELVCLTRRILLPKNVIV
NOV74C KEYGCAPWPMVEKLIKQCLKENPQERPTSAQVFSQVFDILNSAELVCLTRRILLPKNVIV
NOV74d KEYGCAPWPMVEKLIKQCLKENPQERPTSAQVF DILNSAELVCLTRRILLPKNVIV
NOV74e KEYGCAPWPMVEKLIKQCLKENPQERPTSAQVF DILNSAELVCLTRRILLPKNVIV
NOV74a ECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSE
NOV74b ECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKE NOV74C ECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKE
9δ3 NOV74d ECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKE NOV74e ECMVATHHNSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKE
NOV74a SKQKNFLLVGTADGKL NOV74b SWIVSGTQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKL NOV74C SWIVSGTQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKL NOV74d SWIVSGTQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKL NOV74e SWIVSGTQSGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKL
NOV74a AIFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTI NOV74b AIFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTI NOV74C AIFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTI NOV74d AlFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTI NOV74e AIFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTI
NOV74a QKLIETRTSQLFSYAAFSDSNIITVWDTALYIAKQNSPWEVWDKKTEKLCGLIDCVHF NOV74b QKLIETRTSQLFSYAAFSDSNIITVWDTALYIAKQNSPWEVWDKKTEKLCGLIDCVHF NOV 4C QKLIETRTSQLFSYAAFSDSNIITVWDTALYIAKQNSPWEVWDKKTEKLCGLIDCVHF NOV74d QKLIETRTSQLFSYAAFSDSNIITVWDTALYIAKQNSPWEVWDKKTEKLCGLIDCVHF NOV74e QKLIETRTSQLFSYAAFSDSNIITVWDTALYIAKQNSPWEVWDKKTEKLCGLIDCVHF
NOV74a LREVMVKENKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYNFC NOV74b L s NOV74C LRLVKPNRKKLSNLMMSLA- -LHPICLKSKLRCSSSKGRSHILL RVIYNFC NOV74d LRLVKPNRKKLSNLMMSLA- -LHPICLKSKLRCSSSKGRSHILL RVIYNFC NOV74e LREVTVKENKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYNFC
NOV74a NSVRVMMTAQLG-SLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHI NOV74b LKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHI NOV74C NSVRVMMTAQLGGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHI NOV74d NSVRVMMTAQLGGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHI NOV74e NSVRVMMTAQLG-SLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHI
NOV74a EVRKELAEKMRRTSVE NOV74b EVRKELAEKMRRTSVE NOV74C EVRKELAEKMRRTSVE NOV74d EVRKELAEKMRRTSVE NOV74e EVRKELAEKMRRTSVE
NOV74a (SEQ ID NO 1072) NOV74b (SEQ ID NO 1074) NOV74C (SEQ ID NO 1076) NOV74d (SEQ ID NO 1078) NOV74e (SEQ ID NO 1080)
Further analysis ofthe NOV74a protein yielded the following properties shown in Table
74C.
Table 74C. Protein Sequence Properties NOV74a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 5 ; pos . chg 0; neg . chg 1
9δ4 H-region: length 6; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -11.05 possible cleavage site: between 13 and 14
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 1.96 (at 794) ALOM score: -0.64 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 1.98 Hyd Moment (95): 4.87 G content: 2 D/E content : 2 S/T content : 3 Score: -7.81
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: KKRK (5) at 157 pat7: PVIDRKR (3) at 54 bipartite: RKNVPIEFPVIDRKRLL at 46 content of basic residues: 11.6% NLS Score: 0.59
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none
9δ5 checking 63 PROSITE DNA binding motifs:
Leucine zipper pattern (PS00029) : *** found *** LQLDENELPHAVHFLNESGVLL at 70
Regulator of chromosome condensation (RCC1) signature 2 (PS00626) : *** found ***
IGTGGGHILLL at 878 checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23)
52.2 % cytoplasmic
39.1 % nuclear
8.7 % mitochondrial
>> prediction for CG90866 - 04 is cyt (k=23 )
A search ofthe NOV74a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 74D.
9δ6
Figure imgf000991_0001
In a BLAST search of public sequence databases, the NOV74a protein was found to have homology to the proteins shown in the BLASTP data in Table 74E.
9δ7
Figure imgf000992_0001
PFam analysis indicates that the NOV74a protein contains the domains shown in the Table 74F.
Table 74F. Domain Analysis of NOV74a
Identities/
Pfam Domain NOV74a Match Region Similarities Expect Value for the Matched Region pkinase 394..644 90/302 (30%) 1.4e-33 169/302 (56%)
Example 75.
The NOV75 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 75A.
Table 75A. NOV75 Sequence Analysis
NOV75a, CG91708-02 SEQ ID NO: 1081 1580 bp DNA Sequence ORF Start: ATG at 51 ORF Stop: TGA at 14δ2
CAAGACAGCAAGGCATAGAGACAACATAGAGCTAAGTAAAGCCAGTGGAAATGAAGAGTCTTCCAATC
CTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATTGGATGGAGCTGCAAGGGGTGAGGACAC CAGCATGAACCTTGTTCAGAAATATCTAGAAAACTACTACGACCTCGAAAAAGATGTGAAACAGTTTG TTAGGAGAAAGGACAGTGGTCCTGTTGTTAAAAAAATCCGAGAAATGCAGAAGTTCCTTGGATTGGAG GTGACGGGGAAGCTGGACTCCGACACTCTGGAGGTGATGCGCAAGCCCATGTGTGGAGTTCCTGACGT TGGTCACTTCAGAACCTTTCCTGGCATCCCGAAGTGGAGGAAAACCCACCTTACATACAGGATTGTGA ATTATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCTGTTGAGAAAGCTCTGAAAGTCTGGGAA GAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGAGACTGATATAATGATCTCTTTTGCAGT TAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAAATGTTTTGGCCCATGCCTATGCCCCTG GGCCAGGGATTAATGGAGATGCCCACTTTGATGATGATGAACAATGGACAAAGGATACAACAGGGACC AATTTATTTCTCGTTGCTGCTCATGAAATTGGCCACTCCCTGGGTCTCTTTCACTCAGCCAACACTGA AGCTTTGATGTACCCACTCTATCACTCACTCACAGACCTGACTCGGTTCCGCCTGTCTCAAGATGATA TAAATGGCATTCAGTCCCTCTATGGACCTCCCCCTGACTCCCCTGAGACCCCCCTGGTACCCACGGAA CCTGTCCCTCCAGAACCTGGGACGCCAGCCAACTGTGATCCTGCTTTGTCCTTTGATGCTGTCAGCAC TCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTTGGCGCAAATCCCTCAGGAAGCTTGAAC CTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCTTCAGGCGTGGATGCCGCATATGAAGTT ACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATTCTGGGCCATCAGAGGAAATGAGGTACG AGCTGGATACCCAAGAGGCATCCACACCCTAGGTTTCCCTCCAACCGTGAGGAAAATCGATGCAGCCA TTTCTGATAAGGAAAAGAACAAAACATATTTCTTTGTAGAGGACAAATACTGGAGATTTGATGAGAAG AGAAATTCCATGGAGCCAGGCTTTCCCAAGCAAATAGCTGAAGACTTTCCAGGGATTGACTCAAAGAT TGATGCTGTTTTTGAAGAATTTGGGTTCTTTTATTTCTTTACTGGATCTTCACAGTTGGAGTTTGACC CAAATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGCTGGCTTAATTGTTGAAAGAGATATGTA
GAAGGCACAATATGGGCACTTTAAATGAAGCTAATAATTCTTCACCTAAGTCTCTGTGAATTGAAATG
TTCGTTTTCTCCTGCT
NOV75a, CG91708-02 SEQ ID NO: 1082 477 aa MW at 53982.7kD Protein Sequence
MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLEKDVKQFVRRKDSGPWKKIREMQ KFLGLEVTGKLDSDTLEVMRKPMCGVPDVGHFRTFPGIPKWRKTHLTYRIVNYTPDLPKDAVDSAVEK ALKVWEEVTPLTFSRLYEGETDIMISFAVREHGDFYPFDGPGNVLAHAYAPGPGINGDAHFDDDEQWT KDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPET PLVPTEPVPPEPGTPANCDPALSFDAVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGV DAAYEVTSKDLVFIFKGNQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKY WRFDEKRNSMEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSΞQLEFDPNAKKVTHTLKSNSWLN C
NOV75b, 26275 lδ56 SEQ ID NO: 10δ3 1446 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence
GGATCCACCATGAAGAGTCTTCCAATCCTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATT GGATGGAGCTGCAAGGGGTGAGGACACCAGCATGAACCTTGTTCAGAAATATCTAGAAAACTACTACG ACCTCGAAAAAGATGTGAAACAGTTTGTTAGGAGAAAGGACAGTGGTCCTGTTGTTAAAAAAATCCGA GAAATGCAGAAGTTCCTTGGATTGGAGGTGACGGGGAAGCTGGACTCCGACACTCTGGAGGTGATGCG CAAGCCCAGGTGTGGAGTTCCTGACGTTGGTCACTTCAGAACCTTTCCTGGCATCCCGAAGTGGAGGA AAACCCACCTTACATACAGGATTGTGAATTATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCT GTTGAGAAAGCTCTGAAAGTCTGGGAAGAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGA GGCTGATATAATGATCTCTTTTGCAGTTAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAA ATGTTTTGGCCCATGCCTATGCCCCTGGGCCAGGGATTAATGGAGATGCCCACTTTGATGATGATGAA CAATGGACAAAGGATACAACAGGGACCAATTTATTTCTCGTTGCTGCTCATGAAATTGGCCACTCCCT GGGTCTCTTTCACTCAGCCAACACTGAAGCTTTGATGTACCCACTCTATCACTCACTCACAGACCTGA CTCGGTTCCGCCTGTCTCAAGATGATATAAATGGCATTCAGTCCCTCTATGGACCTCCCCCTGACTCC CCTGAGACCCCCCTGGTACCCACGGAACCTGTCCCTCCAGAACCTGGGACGCCAGCCAACTGTGATCC TGCTTTGTCCTTTGATGCTGTCAGCACTCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTT GGCGCAAATCCCTCAGGAAGCTTGAACCTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCT TCAGGCGTGGATGCCGCATATGAAGTTACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATT CTGGGCCATCAGAGGAAATGAGGTACGAGCTGGATACCCAAGAGGCATCCACACCCTAGGTTTCCCTC CAACCGTGAGGAAAATCGATGCAGCCATTTCTGATAAGGAAAAGAACAAAACATATTTCTTTGTAGAG GACAAATACTGGAGATTTGATGAGAAGAGAAATTCCATGGAGCCAGGCTTTCCCAAGCAAATAGCTGA AGACTTTCCAGGGATTGACTCAAAGATTGATGCTGTTTTTGAAGAATTTGGGTTCTTTTATTTCTTTA CTGGATCTTCACAGTTGGAGTTTGACCCAAATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGC TGGCTTAATTGTCTCGAG
NOV75b, 262751856 SEQ ID NO: 10δ4 482 aa MW at 54465.2kD Protein Sequence
GSTMKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLEKDVKQFVRRKDSGPWKKIR EMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVNYTPDLPKDAVDSA VEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNVLAHAYAPGPGINGDAHFDDDE QWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLYHSLTDLTRFRLSQDDINGIQSLYGPPPDS PETPLVPTEPVPPEPGTPANCDPALSFDAVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLP SGVDAAYEVTSKDLVFIFKGNQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVE DKYWRFDEKRNSMEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNS WLNCLE
NOV75c, CG91708-01 fSEQ ID NO: 1085 |l821 bp
DNA Sequence lORF Start: ATG at 64 ORF Stop: TGA at 1495
ACAAGGAGGCAGGCAAGACAGCAAGGCATAGAGACAACATAGAGCTAAGTAAAGCCAGTGGAAATGAA
GAGTCTTCCAATCCTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATTGGATGGAGCTGCAA GGGGTGAGGACACCAGCATGAACCTTGTTCAGAAATATCTAGAAAACTACTACGACCTCAAAAAAGAT GTGAAACAGTTTGTTAGGAGAAAGGACAGTGGTCCTGTTGTTAAAAAAATCCGAGAAATGCAGAAGTT CCTTGGATTGGAGGTGACGGGGAAGCTGGACTCCGACACTCTGGAGGTGATGCGCAAGCCCAGGTGTG GAGTTCCTGATGTTGGTCACTTCAGAACCTTTCCTGGCATCCCGAAGTGGAGGAAAACCCACCTTACA TACAGGATTGTGAATTATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCTGTTGAGAAAGCTCT GAAAGTCTGGGAAGAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGAGGCTGATATAATGA TCTCTTTTGCAGTTAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAAATGTTTTGGCCCAT GCCTATGCCCCTGGGCCAGGGATTAATGGAGATGCCCACTTTGATGATGATGAACAATGGACAAAGGA TACAACAGGGACCAATTTATTTCTCGTTGCTGCTCATGAAATTGGCCACTCCCTGGGTCTCTTTCACT CAGCCAACACTGAAGCTTTGATGTACCCACTCTATCACTCACTCACAGACCTGACTCGGTTCCGCCTG TCTCAAGATGATATAAATGGCATTCAGTCCCTCTATGGACCTCCCCCTGACTCCCCTGAGACCCCCCT GGTACCCACGGAACCTGTCCCTCCAGAACCTGGGACGCCAGCCAACTGTGATCCTGCTTTGTCCTTTG ATGCTGTCAGCACTCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTTGGCGCAAATCCCTC AGGAAGCTTGAACCTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCTTCAGGCGTGGATGC CGCATATGAAGTTACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATTCTGGGCCATCAGAG GAAATGAGGTACGAGCTGGATACCCAAGAGGCATCCACACCCTAGGTTTCCCTCCAACCGTGAGGAAA ATCGATGCAGCCATTTCTGATAAGGAAAAGAACAAAACATATTTCTTTGTAGAGGACAAATACTGGAG ATTTGATGAGAAGAGAAATTCCATGGAGCCAGGCTTTCCCAAGCAAATAGCTGAAGACTTTCCAGGGA TTGACTCAAAGATTGATGCTGTTTTTGAAGAATTTGGGTTCTTTTATTTCTTTACTGGATCTTCACAG TTGGAGTTTGACCCAAATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGCTGGCTTAATTGTTG AAAGAGATATGTAGAAGGCACAATATGGGCACTTTAAATGAAGCTAATAATTCTTCACCTAAGTCTCT
GTGAATTGAAATGTTCGTTTTCTCCTGCCTGTGCTGTGACTCGAGTCACACTCAAGGGAACTTGAGCG
TGAATCTGTATCTTGCCGGTCATTTTTATGTTATTACAGGGCATTCAAATGGGCTGCTGCTTAGCTTGi
CACCTTGTCACATAGAGTGATCTTTCCCAAGAGAAGGGGAAGCACTCGTGTGCAACAGACAAGTGACTi
GTATCTGTGTAGACTATTTGCTTATTTAATAAAGACGATTTGTCAGTTGTTTT
NO V75c, CG91708-01 SEQ ID NO: 1086 477 aa MW at 53976.7kD Protein Sequence
MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPWKKIREMQ KFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVNYTPDLPKDAVDSAVEK ALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNVLAHAYAPGPGINGDAHFDDDEQWT KDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPET PLVPTEPVPPEPGTPANCDPALSFDAVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGV DAAYEVTSKDLVFIFKGNQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKY WRFDEKRNSMEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLN
NOV75d, CG91708-03 SEQ ID NO: 10δ7 1446 bp
DNA Sequence lORF Start: ATG at 10 ORF Stop: at 1441
GGATCCACCATGAAGAGTCTTCCAATCCTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATT
GGATGGAGCTGCAAGGGGTGAGGACACCAGCATGAACCTTGTTCAGAAATATCTAGAAAACTACTACG
ACCTCGAAAAAGATGTGAAACAGTTTGTTAGGAGAAAGGACAGTGGTCCTGTTGTTAAAAAAATCCGA
GAAATGCAGAAGTTCCTTGGATTGGAGGTGACGGGGAAGCTGGACTCCGACACTCTGGAGGTGATGCG
CAAGCCCAGGTGTGGAGTTCCTGACGTTGGTCACTTCAGAACCTTTCCTGGCATCCCGAAGTGGAGGA
AAACCCACCTTACATACAGGATTGTGAATTATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCT
GTTGAGAAAGCTCTGAAAGTCTGGGAAGAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGA
GGCTGATATAATGATCTCTTTTGCAGTTAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAA
ATGTTTTGGCCCATGCCTATGCCCCTGGGCCAGGGATTAATGGAGATGCCCACTTTGATGATGATGAA
CAATGGACAAAGGATACAACAGGGACCAATTTATTTCTCGTTGCTGCTCATGAAATTGGCCACTCCCT
GGGTCTCTTTCACTCAGCCAACACTGAAGCTTTGATGTACCCACTCTATCACTCACTCACAGACCTGA
CTCGGTTCCGCCTGTCTCAAGATGATATAAATGGCATTCAGTCCCTCTATGGACCTCCCCCTGACTCC
CCTGAGACCCCCCTGGTACCCACGGAACCTGTCCCTCCAGAACCTGGGACGCCAGCCAACTGTGATCC
TGCTTTGTCCTTTGATGCTGTCAGCACTCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTT
GGCGCAAATCCCTCAGGAAGCTTGAACCTGAATTG _CATTTGATCTCTTCATTTTGGCCATCTCTTCCT
Figure imgf000995_0001
TTAGGAGAAAGGACAGTGGTCCTGTTGTTAAAAAAATCCGAGAAATGCAGAAGTTCCTTGGATTGGAG GTGACGGGGAAGCTGGACTCCGACACTCTGGAGGTGATGCGCAAGCCCATGTGTGGAGTTCCTGACGT TGGTCACTTCAGAACCTTTCCTGGCATCCCGAAGTGGAGGAAAACCCACCTTACATACAGGATTGTGA ATTATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCTGTTGAGAAAGCTCTGAAAGTCTGGGAA GAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGAGACTGATATAATGATCTCTTTTGCAGT TAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAAATGTTTTGGCCCATGCCTATGCCCCTG GGCCAGGGATTAATGGAGATGCCCACTTTGATGATGATGAACAATGGACAAAGGATACAACAGGGACC AATTTATTTCTCGTTGCTGCTCATGAAATTGGCCACTCCCTGGGTCTCTTTCACTCAGCCAACACTGA AGCTTTGATGTACCCACTCTATCACTCACTCACAGACCTGACTCGGTTCCGCCTGTCTCAAGATGATA TAAATGGCATTCAGTCCCTCTATGGACCTCCCCCTGACTCCCCTGAGACCCCCCTGGTACCCACGGAA CCTGTCCCTCCAGAACCTGGGACGCCAGCCAACTGTGATCCTGCTTTGTCCTTTGATGCTGTCAGCAC TCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTTGGCGCAAATCCCTCAGGAAGCTTGAAC CTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCTTCAGGCGTGGATGCCGCATATGAAGTT ACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATTCTGGGCCATCAGAGGAAATGAGGTACG AGCTGGATACCCAAGAGGCATCCACACCCTAGGTTTCCCTCCAACCGTGAGGAAAATCGATGCAGCCA TTTCTGATAAGGAAAAGAACAAAACATATTTCTTTGTAGAGGACAAATACTGGAGATTTGATGAGAAG AGAAATTCCATGGAGCCAGGCTTTCCCAAGCAAATAGCTGAAGACTTTCCAGGGATTGACTCAAAGAT TGATGCTGTTTTTGAAGAATTTGGGTTCTTTTATTTCTTTACTGGATCTTCACAGTTGGAGTTTGACC CAAATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGCTGGCTTAATTGTTGAAAGAGATATGTA GAAGGCACAATATGGGCACTTTAAATGAAGCTAATAATTCTTCACCTAAGTCTCTGTGAATTGAAATG
TTCGTTTTCTCCTGCT
NOV75f, SNPl 3380740 of SEQ ID NO: 1092 477 aa MW at 53981.8kD CG9170δ-02, Protein Sequence SNP Pos: 45 SNP Change: Glu to Lys
MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPWKKIREMQ KFLGLEVTGKLDSDTLEVMRKPMCGVPDVGHFRTFPGIPKWRKTHLTYRIVNYTPDLPKDAVDSAVEK ALKVWEEVTPLTFSRLYEGETDIMISFAVREHGDFYPFDGPGNVLAHAYAPGPGINGDAHFDDDEQWT KDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPET PLVPTEPVPPEPGTPANCDPALSFDAVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGV DAAYEVTSKDLVFIFKGNQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKY WRFDEKRNSMEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLN C
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 75B.
Table 75B. Comparison of the NOV75 protein sequences.
NOV75a MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLEKDVKQFVRRKDS
NOV75b GSTMKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLEKDVKQFVRRKDS
NOV75C MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDS
NOV75d MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLEKDVKQFVRRKDS
NOV75e MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDS
NOV75a GPWKKIREMQKFLGLEVTGKLDSDTLEVMRKPMCGVPDVGHFRTFPGIPKWRKTHLTYR
NOV75b GPWKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYR
NOV75C GPWKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYR
NOV75d GPWKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYR
NOV75e GPWKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYR
NOV75a IVNYTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGETDIMISFAVREHGDFYPFDGP
NOV75b IVNYTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGP
NOV75C IVNYTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGP
NOV75d IVNYTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGP
NOV75e IVNYTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGP
NOV75a GNVLAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMY
NOV75b GNVLAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMY
NOV75C GNVLAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMY
_ NOV75d GNVLAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMY NOV75e GNVLAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMY
NOV75a PLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFD NOV75b PLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFD NOV75C PLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFD NOV75 PLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFD NOV75e PLYHSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFD
NOV75a AVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKG NOV75b AVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKG NOV75c AVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKG NOV75d AVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKG NOV75e AVSTLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKG
NOV75a NQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNS NOV75b NQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNS NOV75c NQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNS NOV75d NQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNS NOV75e NQFWAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNS
NOV75a MEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC NOV75b MEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC NOV75C MEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC NOV75 MEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC NOV75e MEPGFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC
NOV75a NOV75b LE NOV75C NOV75d NOV75e
NOV75a (SEQ ID NO 1082) NOV75b (SEQ ID NO 1084) NOV75C (SEQ ID NO 1086) NOV75d (SEQ ID NO 1088) NOV75e (SEQ ID NO 1090)
Further analysis of the NOV75a protein yielded the following properties shown in Table 75C.
Table 75C. Protein Sequence Properties NOV75a
SignalP analysis: Cleavage site between residues lδ and 19
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 2; pos. chg 1; neg.chg 0 H-region: length 18; peak value 10.73 PSG score: 6.33
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 3.45 possible cleavage site: between 17 and 18 >» Seems to have a cleavable signal peptide (1 to 17)
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 18
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 3.87 (at 293) ALOM score: 3.87 (number of TMSs : 0)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 8 Charge difference: -4.0 C(-2.0) - N( 2.0) N >= C: N-terminal side will be inside
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 3.04 Hyd Moment (95): 6.62 G content: 0 D/E content : 1 S/T content : 2 Score: -4.76
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: PWKKIR (3) at 59 pat7: PKWRKTH (5) at 107 bipartite: none content of basic residues: 11.3% NLS Score: 0.22
KDEL: ER retention motif in the C-terminus : none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE riboεomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total : 0 residues
Final Results (k = 9/23) :
33.3 %: extracellular, including cell wall
22.2 %: mitochondrial
22.2 %: endoplasmic reticulum
11.1 %: Golgi
11.1 %: vacuolar
>> prediction for CG91708-02 is exc (k=9)
A search ofthe NOV75a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 75D.
Figure imgf001000_0001
In a BLAST search of public sequence databases, the NOV75a protein was found to have homology to the proteins shown in the BLASTP data in Table 75E.
Figure imgf001001_0001
PFam analysis indicates that the NOV75a protein contains the domains shown in the Table 75F.
Figure imgf001002_0001
Example 76.
The NOV76 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 76A.
Table 76A. NOV76 Sequence Analysis
NOV76a, CG92078-02 SEQ ID NO: 1093 1983 bp DNA Sequence ORF Start: ATG at 6 ORF Stop: TGA at 1836
GCAGCATGAGCCGATCACCCCTCAATCCCAGCCAACTCCGATCAGTGGGCTCCCAGGATGCCCTGGCC
CCCTTGCCTCCACCTGCTCCCCAGAATCCCTCCACCCACTCTTGGGACCCTTTGTGTGGATCTCTGCC TTGGGGCCTCAGCTGTCTTCTGGCTCTGCAGCATGTCTTGGTCATGGCTTCTCTGCTCTGTGTCTCCC ACCTGCTCCTGCTTTGCAGTCTCTCCCCAGGAGGACTCTCTTACTCCCCTTCTCAGCTCCTGGCCTCC AGCTTCTTTTCATGTGGTATGTCTACCATCCTGCAAACTTGGATGGGCAGCAGGCTGCCTCTTGTCCA GGCTCCATCCTTAGAGTTCCTTATCCCTGCTCTGGTGCTGACCAGCCAGAAGCTACCCCGGGCCATCC AGACACCTGGAAACTCCTCCCTCATGCTGCACCTTTGTAGGGGACCTAGCTGCCATGGCCTGGGGCAC TGGAACACTTCTCTCCAGGAGGTGTCCGGGGCAGTGGTAGTATCTGGGCTGCTGCAGGGCATGATGGG GCTGCTGGGGAGTCCCGGCCACGTGTTCCCCCACTGTGGGCCCCTGGTGCTGGCTCCCAGCCTGGTTG TGGCAGGGCTCTCTGCCCACAGGGAGGTAGCCCAGTTCTGCTTCACACACTGGGGGTTGGCCTTGCTG GTTATCCTGCTCATGGTGGTCTGTTCTCAGCACCTGGGCTCCTGCCAGTTTCATGTGTGCCCCTGGAG GCGAGCTTCAACGTCATCAACTCACACTCCTCTCCCTGTCTTCCGGCTCCTTTCGGTGCTGATCCCAG TGGCCTGTGTGTGGATTGTTTCTGCCTTTGTGGGATTCAGTGTTATCCCCCAGGAACTGTCTGCCCCC ACCAAGGCACCATGGATTTGGCTGCCTCACCCAGGTGAGTGGAATTGGCCTTTGCTGACGCCCAGAGC TCTGGCTGCAGGCATCTCCATGGCCTTGGCAGCCTCCACCAGTTCCCTGGGCTGCTATGCCCTGTGTG GCCGGCTGCTGCATTTGCCTCCCCCACCTCCACATGCCTGCAGTCGAGGGCTGAGCCTGGAGGGGCTG GGCAGTGTGCTGGCCGGGCTGCTGGGAAGCCCCATGGGCACTGCATCCAGCTTCCCCAGCGTGGGCAA AGTGGGTCTTATCCAGGCTGGATCTCAGCAAGTGGCTCACTTAGTGGGGCTACTCTGCGTGGGGCTTG GACTCTCCCCCAGGTTGGCTCAGCTCCTCACCACCATCCCACTGCCTGTTGTTGGTGGGGTGCTGGGG GTGACCCAGGCTGTGGTTTTGTCTGCTGGATTCTCCAGCTTCTACCTGGCTGACATAGACTCTGGGCG AAATATCTTCATTGTGGGCTTCTCCATCTTCATGGCCTTGCTGCTGCCAAGATGGTTTCGGGAAGCCC
99δ CAGTCCTGTTCAGCACAGGCTGGAGCCCCTTGGATGTATTACTGCACTCACTGCTGACACAGCCCATC TTCCTGGCTGGACTCTCAGGCTTCCTACTAGAGAACACGATTCCTGGCACACAGCTTGAGCGAGGCCT AGGTCAAGGGCTACCATCTCCTTTCACTGCCCAAGAGGCTCGAATGCCTCAGAAGCCCAGGGAGAAGG CTGCTCAAGTGTACAGACTTCCTTTCCCCATCCAAAACCTCTGTCCCTGCATCCCCCAGCCTCTCCAC TGCCTCTGCCCACTGCCTGAAGACCCTGGGGATGAGGAAGGAGGCTCCTCTGAGCCAGAAGAGATGGC AGACTTGCTGCCTGGCTCAGGGGAGCCATGCCCTGAATCTAGCAGAGAAGGGTTTAGGTCCCAGAAAT GACCAGAACGCCTACTTCTGCCCTGGTTAATTTAGCCCTAACTCTCATCTGCTGGAGAGTCAGCTCCC
AAACTGTTCTTTCTTGTAGGCAGAGGATATGTGTGTGTGTATTACATGGGACTGTCTAGAGGTTCCAT
TTCCCAATAGG
NOV76a, CG9207δ-02 SEQ ID NO: 1094 610 aa MW at 64502.7kD Protein Sequence
MSRSPLNPSQLRSVGSQDALAPLPPPAPQNPSTHSWDPLCGSLPWGLSCLLALQHVLVMASLLCVSHL LLLCSLSPGGLSYSPSQLLASSFFSCGMSTILQTWMGSRLPLVQAPSLEFLIPALVLTSQKLPRAIQT PGNSSLMLHLCRGPSCHGLGHWNTSLQEVSGAVWSGLLQGMMGLLGSPGHVFPHCGPLVLAPSLWA GLSAHREVAQFCFTHWGLALLVILLMWCSQHLGSCQFHVCPWRRASTSSTHTPLPVFRLLSVLIPVA CVWIVSAFVGFSVIPQELSAPTKAPWIWLPHPGEWNWPLLTPRALAAGISMALAASTSSLGCYALCGR LLHLPPPPPHACSRGLSLEGLGSVLAGLLGSPMGTASSFPSVGKVGLIQAGSQQVAHLVGLLCVGLGL SPRLAQLLTTIPLPWGGVLGVTQAWLSAGFSSFYLADIDSGRNIFIVGFSIFMALLLPRWFREAPV LFSTGWSPLDVLLHSLLTQPIFLAGLSGFLLENTIPGTQLERGLGQGLPSPFTAQEARMPQKPREKAA QVYRLPFPIQNLCPCIPQPLHCLCPLPEDPGDEEGGSSEPEEMADLLPGSGEPCPESSREGFRSQK
NOV76b, CG9207δ-01 SEQ ID NO: 1095 2014 bp DNA Sequence ORF Start: ATG at 6 ORF Stop: TAG at 1992
GCAGCATGAGCCGATCACCCCTCAATCCCAGCCAACTCCGATCAGTGGGCTCCCAGGATGCCCTGGCC
CCCTTGCCTCCACCTGCTCCCCAGAATCCCTCCACCCACTCTTGGGACCCTTTGTGTGGATCTCTGCC TTGGGGCCTCAGCTGTCTTCTGGCTCTGCAGCATGTCTTGGTCATGGCTTCTCTGCTCTGTGTCTCCC ACCTGCTCCTGCTTTGCAGTCTCTCCCCAGGAGGACTCTCTTACTCCCCTTCTCAGCTCCTGGCCTCC AGCTTCTTTTCATGTGGTATGTCTACCATCCTGCAAACTTGGATGGGCAGCAGGAGGCTGCCTCTTGT CCAGGCTCCATCCTTAGAGTTCCTTATCCCTGCTCTGGTGCTGACCAGCCAGAAGCTACCCCGGGCCA TCCAGACACCTGGAAACGCCTCCCTCATGCTGCACCTTTGTAGGGGACCTAGCTGCCATGGCCTGGGG CACTGGAACACTTCTCTCCAGGAGGTGGTGGTAGTATCTGGGCTGCTGCAGGGCATGATGGGGCTGCT GGGGAGTCCCGGCCACGTGTTCCCCCACTGTGGGCCCCTGGTGCTGGCTCCCAGCCTGGTTGTGGCAG GGCTCTCTGCCTTTCCCCAAGAGGGAGTTTTGCTCCTGTCACCCAGCCTGGAGTGCAATGGCATGATC TCGGCTCACCACTGGGGAGAAGCCAGCCAGCTCTGCCTCCTGGCCCTGGAGTGCTCACTCCATCCCCT ACCTTTTGGCTTCTGTCTACCCCTGCAAGGCTGGCTCAGAAGGTTCTGGGGGAGGAGTTCTTTTCTCA GTCTCGCCCCTCAGGTGCTGATCCCAGTGGCCTGTGTGTGGATTGTTTCTGCCTTTGTGGGATTCAGT GTTATCCCCCAGGAACTGTCTGCCCCCACCAAGGCACCATGGATTTGGCTGCCTCACCCAGGTGTGTG GAATTGGCCTTTGCTGACGCCCAGAGCTCTGGCTGCAGGCATCTCCATGGCCTTGGCAGCCTCCACCA GTTCCCTGGGCTGCTATGCCCTGTGTGGCCGGCTGCTGCATTTGCCTCCCCCACCTCCACATGCCTGC AGTCGAGGGCTGAGCCTGGAGGGGCTGGGCAGTGTGCTGGCCGGGCTGCTGGGAAGCCCCATGGGCAC TGCATCCAGCTTCCCCAACGTGGGCAAAGTGGGTCTTATCCAGCAGGCTGGATCTCAGCAAGTGGCTC ACTTAGTGGGGCTACTCTGCGTGGGGCTTGGACTCTCCCCCAGGTTGGCTCAGCTCCTCACCACCATC CCACTGCCTGTTGTTGGTGGTGGGGTGCTGGGGGTGACCCAGGCTGTGGTTTTGTCTGCTGGATTCTC CAGCTTCTACCTGGCTGACATAGACTCTGGGCGAAATATCTTCATTGTGGGCTTCTCCATCTTCATGG CCTTGCTGCTGCCAAGATGGTTTCGGGAAGCCCCAGTCCTGTTCAGCACAGGTCACTCACTGCTGATG GAGCCCCTTGGATGTATTACTGCACAGCCCATCTTCCTGGCTGGACTCTCAGGCTTCCTACTAGAGAA CACGATTCGGGGCACACAGCTTGAGCGAGGCCTAGGTCAAGGGCTACCATCTCCTTTCACTGCCCAAG AGGCTCGAATGCCTCAGAAGCCCAGGGAGAAGGCTGCTCAAGTGTACAGACTTCCTTTCCCCATCCAA AACCTCTGTCCCTGCATCCCCCAGCCTCTCCACTGCCTCTGCCCACTGCCTGAAGACCCTGGGGATGA GGAAGGAGGCTCCTCTGAGCAGCAAGAGATGGCAGACTTGCTGCGTGGCTCAGGGGAGCATGCCCTGA ATCTAGCAGAGAAGGGTTTAGGTCCAGAAATGACCAGAACGCGTACTTCTGCCCTGGTTAATTTAGCC CTAACTCTCATCTGCTGGAGAGTCAGCTCCCAAACTGTTCTTTCTTGTAGGCAGAGGATATGTGTGTG TGTATTACATGGGACTGTCTAGAGGTTCCATTTCCCAATAGG
NOV76b, CG9207δ-01 SEQ ID NO: 1096 662 aa MW at 7013δ.5kD Protein Sequence
MSRSPLNPSQLRSVGSQDALAPLPPPAPQNPSTHSWDPLCGSLPWGLSCLLALQHVLVMASLLCVSHL LLLCSLSPGGLSYSPSQLLASSFFSCGMSTILQTWMGSRRLPLVQAPSLEFLIPALVLTSQKLPRAIQ TPGNASLMLHLCRGPSCHGLGHWNTSLQE WSGLLQGMMGLLGSPGHVFPHCGPLVLAPSLWAGL SAFPQEGVLLLSPSLECNGMISAHHWGEASQLCLLALECSLHPLPFGFCLPLQGWLRRFWGRSSFLSL APQVLIPVACVWIVSAFVGFSVIPQELSAPTKAPWIWLPHPGVWNWPLLTPRALAAGISMALAASTSS LGCYALCGRLLHLPPPPPHACSRGLSLEGLGSVLAGLLGSPMGTASSFPNVGKVGLIQQAGSQQVAHL VGLLCVGLGLSPRLAQLLTTIPLPWGGGVLGVTQAWLSAGFSSFYLADIDSGRNIFIVGFSIFMAL LLPRWFREAPVLFSTGHSLLMEPLGCITAQPIFLAGLSGFLLENTIRGTQLERGLGQGLPSPFTAQEA RMPQKPREKAAQVYRLPFPIQNLCPCIPQPLHCLCPLPEDPGDEEGGSSEQQEMADLLRGSGEHALNL AEKGLGPEMTRTRTSALVNLALTLICWRVSSQTVLSCRQRICVCVLHGTV
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 76B.
Table 76B. Comparison of the NO 76 protein sequences.
NOV76a MSRSPLNPSQLRSVGSQDALAPLPPPAPQNPSTHSWDPLCGSLPWGLSCLLALQHVLVMA NOV76b MSRSPLNPSQLRSVGSQDALAPLPPPAPQNPSTHSWDPLCGSLPWGLSCLLALQHVLVMA
NOV76a SLLCVSHLLLLCSLSPGGLSYSPSQLLASSFFSCGMSTILQTWMGSR-LPLVQAPSLEFL NOV76b SLLCVSHLLLLCSLSPGGLSYSPSQLLASSFFSCGMSTILQTWMGSRRLPLVQAPSLEFL
NOV76a IPALVLTSQKLPRAIQTPGNSSLMLHLCRGPSCHGLGHWNTSLQEVSGAVWSGLLQGMM NOV76b IPALVLTSQKLPRAIQTPGNASLMLHLCRGPSCHGLGHWNTSLQEV VWSGLLQGMM
NOV76a GLLGSPGHVFPHCGPLVLAPSLWAGLSAHREVAQFCFT HWGLALLVI NOV76b GLLGSPGHVFPHCGPLVLAPSLWAGLSAFPQEGVLLLSPSLECNGMISAHHWGEASQLC
NOV76a LLMWCSQH LGSCQFHVCPWRRASTSSTHTPLPVFRLLSVLIPVACVWIVSAFVGFS NOV76b LLALECSLHPLPFGFCLPLQGWLRRFWGRSSFLSLAP QVLIPVACVWIVSAFVGFS
NOV76a VIPQELSAPTKAPWIWLPHPGEWNWPLLTPRALAAGISMALAASTSSLGCYALCGRLLHL NOV76b VIPQELSAPTKAPWIWLPHPGVWNWPLLTPRALAAGISMALAASTSSLGCYALCGRLLHL
NOV76a PPPPPHACSRGLSLEGLGSVLAGLLGSPMGTASSFPSVGKVGLIQAG-SQQVAHLVGLLC NOV76b PPPPPHACSRGLSLEGLGSVLAGLLGSPMGTASSFPNVGKVGLIQQAGSQQVAHLVGLLC
NOV76a VGLGLSPRLAQLLTTIPLPWGG-VLGVTQAWLSAGFSSFYLADIDSGRNIFIVGFSIF NOV76b VGLGLSPRLAQLLTTIPLPWGGGVLGVTQAWLSAGFSSFYLADIDSGRNIFIVGFSIF
NOV76a MALLLPRWFREAPVLFSTGWSPLDVLLHSLLTQPIFLAGLSGFLLENTIPGTQLERGLGQ NOV76b MALLLPRWFREAPVLFSTGHSLLMEPLGCITAQPIFLAGLSGFLLENTIRGTQLERGLGQ
NOV76a GLPSPFTAQEARMPQKPREKAAQVYRLPFPIQNLCPCIPQPLHCLCPLPEDPGDEEGGSS NOV76b GLPSPFTAQEARMPQKPREKAAQVYRLPFPIQNLCPCIPQPLHCLCPLPEDPGDEEGGSS
NOV76a EPEEMADLLPGSGEPCPESSREGFRSQK NOV76b EQQEMADLLRGSGEHALNLAEKGLGPEMTRTRTSALVNLALTLICWRVSSQTVLSCRQRI
NOV76a NOV76b CVCVLHGTV
NOV76a (SEQ ID NO: 1094) NOV76b (SEQ ID NO: 1096)
Further analysis ofthe NOV76a protein yielded the following properties shown in Table 76C. Table 76C. Protein Sequence Properties NOV76a
SignalP analysis: Cleavage site between residues 17 and 1 δ
PSORT II analysis:
PSG : a new signal peptide prediction method
N-region : length 3 ; pos . chg 1 ; neg . chg 0 H-region : length 8 ; peak value -1.31 PSG score : -5 .71
GvH : von Heijne ' s method for signal seq . recognition GvH score (threshold : -2 . 1) : -4 . 74 possible cleavage site : between 48 and 49
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 5: 9
INTEGRAL Likelihood -8.60 Transmembrane 56 - 72
INTEGRAL Likelihood 0.16 Transmembrane 110 - 126
INTEGRAL Likelihood -0.11 Transmembrane 167 - 183
INTEGRAL Likelihood -1.70 Transmembrane 192 - 208
INTEGRAL Likelihood -6.90 Transmembrane 216 - 232
INTEGRAL Likelihood -8.23 Transmembrane 265 - 281
INTEGRAL Likelihood -1.97 Transmembrane 421 - 437
INTEGRAL Likelihood -3.24 Transmembrane 454 - 470
INTEGRAL Likelihood 0.21 Transmembrane 491 - 507
PERIPHERAL Likelihood 0.69 (at 394)
ALOM score : -8.60 (number of TMSs: 9)
MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 63 Charge difference: 0.0 C( 0.5) - N( 0.5) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 10.11 Hyd Moment(95): 10.29 G content: 1 D/E content: 1 S/T content: 5 Score: -1.10
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 421 PRL|AQ
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 4.6% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : SRSP none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: Leucine zipper pattern (PS00029) : *** found *** LDVLLHSLLTQPIFLAGLSGFL at 485 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
77.8 %: endoplasmic reticulum
11.1 %: nuclear
11.1 %: mitochondrial
>> prediction for CG92078-02 is end (k=9)
A search ofthe NOV76a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 76D.
Figure imgf001007_0001
In a BLAST search of public sequence databases, the NOV76a protein was found to have homology to the proteins shown in the BLASTP data in Table 76E.
Figure imgf001007_0002
Figure imgf001008_0001
PFam analysis indicates that the NOV76a protein contains the domains shown in the Table 76F.
Figure imgf001008_0002
Example 77.
The NOV77 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 77A.
Figure imgf001008_0003
GAGCTGAAGAAGCGAGCTGGATGGCAAGGCCTGTGCGACAGATAATGCCTGAGGAAATGTTCCTGAGT
CACGCTGAGGAGAGGCTTCACTCAGGAGTTCATGCTGAGATGATCA
NOV77a, CG93669-04 SEQ ID NO: 109δ 489 aa MW at 55700.9kD Protein Sequence
MDDYMVLR IGEGSFGRALLVQHESSNQMFAMKEIRLPKSNTQNSRKEAVLLAKMKHPNIVAFIESFE AEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDILN FTQMCLGVNHIHKKRVLHRDIKSKNIFLTQNG KVKLGDFGSARLLSSPMAFACTYVGTPYYVPPEIWENLPYNNKSDIWSLGCILYELCTLKHPFQANS KNLILKVCQGCISPLPSHYSYELQFLVKQMFKR PSHRPSATTLLSRGIVARLVQKCLPPQIIMEYGE EVLEEIKNSKHNTPRKKSLLKQEEEQDRKGSHTDLESINENLVESALRRVNRKSGNKSVHLRKASSPN LHRRQWEKNVPNTALTALENASILTSSLTAEDDRGGGSVIKYSKNTTRKQ LKETPDTLLNILKNADL SLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTDFEEEDDNPDWVS ELKKRAGWQGLCD
NOV77b, CG93669-01 SEQ ID NO: 1099 2257 bp DNA Sequence ORF Start: ATG at 246 ORF Stop: TAA at 1764
CCGCAAGTCCCTCGCCGCCTTGGGGTCTGGGCGCGCGGTCCGTGGGGGTCAGCAGGGCGAGCGGCTTT
TCCAGGAGAAAGGGCCCTCACGGGTGAGCGGGGCGACTGGGCTCCCCCGCGGTGCAGTTGCCCCGCGC
GACCGGCCCCGGCTTCAACGGATTCTTCTCGCTCGCTGCCCGGAAAGAACCATTTGGGAGAGCCCATG
GTGACTGCGTGAGTGGAGCCCAGCTGTGTGGATGCCCCAGCATGGATGACTACATGGTCCTGAGAATG
ATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCATGAAAGCAGTAATCAGATGTTTGCCAT GAAAGAAATAAGGCTTCCCAAGGTCACTACTAATACACAGAATTCTAGGAAGGAGGCTGTTCTTTTAG CCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAAGCTGAAGGACACTTGTATATT GTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACAGCAGAAAGGAAAGTTATTTCC TGAAGACCAGATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATCACATTCACAAGAAACGTG TGCTACACAGAGATATCAAGTCCCAGAATATCTTCCTCACTCAGAATGGAAAAGTGAAATTGGGAGAC TTTGGATCTGCCCGTCTTCTCTCCAATCCGATGGCATTTGCTTGTACCTATGTGGGAACTCCTTATTA TGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACATCTGGTCCTTGGGTTGCA TCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGGAAAAATCTTATCCTCAAA GTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACTTCAGTTCCTAGTCAAGCA GATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAACGCTTCTCTCTCGAGGCATCGTAGCTC GGCTTGTCCAGAAGTGCTTACCCCCCGAGATCATCATGGAATATGGTGAGGAAGTATTAGAAGAAATA AAAAATTCGAAGCATAACACACCAAGAAAAAAAACAAACCCCAGCAGAATCAGGATAGCTTTGGGAAA TGAAGCAAGCACAGTGCAAGAGGAAGAACAAGATAGAAAGGGTAGCCATACTGATTTGGAAAGCATTA ATGAAAATTTAGTTGAAAGTGCATTGAGAAGAGTAAACAGAGAAGAAAAAGGTAATAAGTCAGTCCAT CTGAGGAAAGCCAGTTCACCAAATCTTCATAGACGACAGTGGGAGAAAAATGTACCCAATACAGCTCT TACAGCTTTGGAAAATGCATCCATACTCACCTCCAGTTTAACAGCAGAGGACGATAGAGGTGGTTCTG TAATAAAGTACAGCAAAAATACTACTCGTAAGCAGTGGCTCAAAGAGACCCCTGACACTTTGTTGAAC ATCCTTAAGAATGCTGATCTCAGCTTGGCTTTTCAAACATACACAATATATAGACCAGGTTCAGAAGG GTTCTTGAAAGGCCCCCTGTCTGAAGAAACAGAAGCATCGGACAGTGTTGATGGAGGTCACGATTCTG TCATTTTGGATCCAGAGCGACTTGAGCCTGGGCTAGATGAGGAGGACACGGACTTTGAGGAGGAAGAT GACAACCCCGACTGGGTGTCAGAGCTGAAGAAGCGAGCTGGATGGCAAGGCCTGTGCGACAGATAATG CCTGAGGAAATGTTCCTGAGTCACGCTGAGGAGAGCCTTCACTCAGGAGTTCATGCTGAGATGATCAT
GAGTTCATGCGACGTATATTTTCCTTTGGAAACAGAATGAAGCAGAGGAAACTCTTAATACTTAAAAT
CGTTCTTGATTAGTATCGTGAGTTTGAAAAGTCTAGAACTCCTGTAAGTTTTTGAACTCAAGGGAGAA
GGTATAGTGGAATGAGTGTGAGCATCGGGCTTTGCAGTCCCATAGAACAGAAATGGGATGCTAGCGTG
CCACTACCTACTTGTGTGATTGTGGGAAATTACTTAACCTCTTCAAGCCCCAATTTCCTCAACCATAA
AATGAAGATAATAATGCCTACCTCAGAGGGATGCTGACCACAGACCTTTATAGCAGCCCGTATGATAT
TATTCACATTATGATATGTGTTTATTATTATGTGACTCTTTTTACATTTCCTAAAGGTTTGAGAATTA lAATATATTTAATT
NOV77b, CG93669-01 SEQ ID NO: 1100 506 aa M at 57681.0kD Protein Sequence
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMKHPNIVAFKES FEAEGHLYIV EYCDGGDLMQKIKQQKGKLFPEDQILNWFTQMCLGVNHIHKKRVLHRDIKSQNIFLT QNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEIWENLPYNNKSDIWSLGCILYELCTLKHPFQA NSWKNLIL?VCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATTLLSRGIVARLVQKCLPPEIIME YGEEVLEEIKNSKHNTPRKKT PSRIRIALGNEASTVQEEEQDRKGSHTDLESINENLVESALRRVNR EEKGNKSVHLRKASSPNLHRRQWEKNVPNTALTALENASILTSSLTAEDDRGGSVIKYSKNTTRKQWL KETPDTLLNILKNADLSLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDE EDTDFEEEDDNPDWVSELKKRAG QGLCDR NOV77c, CG93669-02 SEQ ID NO: 1101 1781 bp DNA Sequence ORF Start: ATG at 246 ORF Stop: TAA at 1713
CCGCAAGTCCCTCGCCGCCTTGGGGTCTGGGCGCGCGGTCCGTGGGGGTCAGCAGGGCGAGCGGCTTT
TCCAGGAGAAAGGGCCCTCACGGGTGAGCGGGGCGACTGGGCTCCCCCGCGGTGCAGTTGCCCCGCGC
GACCGGCCCCGGCTTCAACGGATTCTTCTCGCTCGCTGCCCGGAAAGAACCATTTGGGAGAGCCCATG
GTGACTGCGTGAGTGGAGCCCAGCTGTGTGGATGCCCCAGCATGGATGACTACATGGTCCTGAGAATG
ATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCATGAAAGCAGTAATCAGATGTTTGCCAT GAAAGAAATAAGGCTTCCCAAGGTCACTACTAATACACAGAATTCTAGGAAGGAGGCTGTTCTTTTAG CCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAAGCTGAAGGACACTTGTATATT GTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACAGCAGAAAGGAAAGTTATTTCC TGAAGACCAGATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATCACATTCACAAGAAACGTG TGCTACACAGAGATATCAAGTCCCAGAATATCTTCCTCACTCAGAATGGAAAAGTGAAATTGGGAGAC TTTGGATCTGCCCGTCTTCTCTCCAATCCGATGGCATTTGCTTGTACCTATGTGGGAACTCCTTATTA TGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACATCTGGTCCTTGGGTTGCA TCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGGAAAAATCTTATCCTCAAA GTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACTTCAGTTCCTAGTCAAGCA GATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAACGCTTCTCTCTCGAGGCATCGTAGCTC GGCTTGTCCAGAAGTGCTTACCCCCCGAGATCATCATGGAATATGGTGAGGAAGTATTAGAAGAAATA AAAAATTCGAAGCATAACACACCAAGAAAAAAACAAGAGGAAGAACAAGATAGAAAGGGTAGCCATAC TGATTTGGAAAGCATTAATGAAAATTTAGTTGAAAGTGCATTGAGAAGAGTAAACAGAGAAGAAAAAG GTAATAAGTCAGTCCATCTGAGGAAAGCCAGTTCACCAAATCTTCATAGACGACAGTGGGAGAAAAAT GTACCCAATACAGCTCTTACAGCTTTGGAAAATGCATCCATACTCACCTCCAGTTTAACAGCAGAGGA CGATAGAGGTGGTTCTGTAATAAAGTACAGCAAAAATACTACTCGTAAGCAGTGGCTCAAAGAGACCC CTGACACTTTGTTGAACATCCTTAAGAATGCTGATCTCAGCTTGGCTTTTCAAACATACACAATATAT AGACCAGGTTCAGAAGGGTTCTTGAAAGGCCCCCTGTCTGAAGAAACAGAAGCATCGGACAGTGTTGA TGGAGGTCACGATTCTGTCATTTTGGATCCAGAGCGACTTGAGCCTGGGCTAGATGAGGAGGACACGG ACTTTGAGGAGGAAGATGACAACCCCGACTGGGTGTCAGAGCTGAAGAAGCGAGCTGGATGGCAAGGC CTGTGCGACAGATAATGCCTGAGGAAATGTTCCTGAGTCACGCTGAGGAGAGGCTTCACTCTAGGAGT TCATGCTGAGATG
NOV77c, CG93669-02 SEQ ID NO: 1102 489 aa MW at 55900.0kD Protein Sequence
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMΪCHPNIVAFKES FEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDQIL FTQMCLGV HIHKKRVLHRDIKSQNIFLT QNGKΠOJGDFGSARLLSNPMAFACTYVGTPYYVPPEIWENLPYNNKSDIWSLGCILYELCTLKHPFQA NSWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATTLLSRGIVARLVQKCLPPEIIME YGEEVLEEIKNSKHNTPRKKQEEEQDRKGSHTDLESINE LVESALRRV REEKGNKSVHLRKASSPN LHRRQWEKNVPNTALTALENASILTSSLTAEDDRGGSVIKYSKNTTRKQ LKETPDTLLNILKADLS LAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTDFEEEDDNPD VSE LKKRAG QGLCDR
NOV77d, CG93669-03 SEQ ID NO: 1103 1588 bp DNA Sequence ORF Start: ATG at 246 ORF Stop: TAA at 1521
CCGCAAGTCCCTCGCCGCCTTGGGGTCTGGGCGCGCGGTCCGTGGGGGTCAGCAGGGCGAGCGGCTTT
TCCAGGAGAAAGGGCCCTCACGGGTGAGCGGGGCGACTGGGCTCCCCCGCGGTGCAGTTGCCCCGCGC
GACCGGCCCCGGCTTCAACGGATTCTTCTCGCTCGCTGCCCGGAAAGAACCATTTGGGAGAGCCCATG
GTGACTGCGTGAGTGGAGCCCAGCTGTGTGGATGCCCCAGCATGGATGACTACATGGTCCTGAGAATG
ATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCATGAAAGCAGTAATCAGATGTTTGCCAT GAAAGAAATAAGGCTTCCCAAGGTCACTACTAATACACAGAATTCTAGGAAGGAGGCTGTTCTTTTAG CCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAAGCTGAAGGACACTTGTATATT GTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACAGCAGAAAGGAAAGTTATTTCC TGAAGACCAGATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATCACATTCACAAGAAACGTG TGCTACACAGAGATATCAAGTCCCAGAATATCTTCCTCACTCAGAATGGAAAAGTGAAATTGGGAGAC TTTGGATCTGCCCGTCTCCTCTCCAATCCGATGGCATTTGCTTGTACCTATGTGGGAACTCCTTATTA TGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACATCTGGTCCTTGGGTTGCA TCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGGAAAAATCTTATCCTCAAA GTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACTTCAGTTCCTAGTCAAGCA GATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAGCGCTTCTCTCTCGAGGCATCGTAGCTC GGCTTGTCCAGAAGTGCTTACCCCCCGAGATCATCATGGAATATGGTGAGGAAGTATTAGAAGAAATA AAAAATTCGAAGCATAACACACCAAGAAAAAAACAAGAGGAAGAACAAGATAGAAAGGGTAGCCATAC TGATTTGGAAAGCATTAATGAAAATTTAGTTGAAAGTGCATTGAGAAGAGTAAACAGAGAAGAAAAAG GTAATAAGTCAGTCCATCTGAGGAAAGCCAGTTCACCAAATCTTCATAGACGACAGTGGGAGAAAAAT GTACCCAATACAGCTCTTACAGCTTTGGAAAATGCATCCATACTCACCTCCAGTTTAACAGCAGAGGA CGATAGAGGTTCAGAAGGGTTCTTGAAAGGCCCCCTGTCTGAAGAAACAGAAGCATCGGACAGTGTTG AGGAGGACACGGACTTTGAGGAGGAAGATGACAACCCCGACTGGGTGTCAGAGCTGAAGAAGCGAGCT GGATGGCAAGGCCTGTGCGACAGATAATGCCTGAGGAAATGTACCTGAGTCACGCTGAGGAGAGGCTT CACTCAGGAGTTCATGCTGAGATG
NOV77d, CG93669-03 SEQ ID NO: 1104 425 aa MW at 486δ4.0kD Protein Sequence
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMKHPNIVAFKES FEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDQILN FTQMCLGVNHIHKKRVLHRDIKSQNIFLT QNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEI ENLPY NKSDIWSLGCILYELCTLKHPFQA NSWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATALLSRGIVARLVQKCLPPEIIME YGEEVLEEIKNSKHNTPRKKQEEEQDRKGSHTDLESINENLVESALRRVNREEKGNKSVHLRKASSPN LHRRQWEKNVPNTALTALENASILTSSLTAEDDRGSEGFLKGPLSEETEASDSVEEDTDFEEEDDNPD WVSELKKRAGWQGLCDR
NOV77e, SNPl 3376464 of SEQ ID NO: 1105 1542 bp CG93669-04, DNA Sequence ORF Start: ATG at 1 ORF Stop: at 1468
SNP Pos: 94 SNP Change: A to G
ATGGATGACTACATGGTCCTGAGAATGATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCA TGAAAGCAGTAATCAGATGTTTGCCGTGAAAGAAATAAGGCTTCCCAAGTCTAATACACAGAATTCTA GGAAGGAGGCTGTTCTTTTAGCCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAA GCTGAAGGACACTTGTATATTGTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACA GCAGAAAGGAAAGTTATTTCCTGAAGACATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATC ACATTCACAAGAAACGTGTGCTACACAGAGATATCAAGTCCAAGAATATCTTCCTCACTCAGAATGGA AAAGTGAAATTGGGAGACTTTGGATCTGCCCGTCTTCTCTCCAGTCCGATGGCATTTGCTTGTACCTA TGTGGGAACTCCTTATTATGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACA TCTGGTCCTTGGGTTGCATCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGG AAAAATCTTATCCTCAAAGTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACT TCAGTTCCTAGTCAAGCAGATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAACGCTTCTCT CTCGAGGCATCGTAGCTCGGCTTGTCCAGAAGTGCTTACCCCCCCAGATCATCATGGAATATGGTGAG GAAGTATTAGAAGAAATAAAAAATTCGAAGCATAACACACCAAGAAAAAAATCTCTTTTAAAGCAAGA GGAAGAACAAGATAGAAAGGGTAGCCATACTGATTTGGAAAGCATTAATGAAAATTTAGTTGAAAGTG CATTGAGAAGAGTAAACAGAAAATCAGGTAATAAGTCAGTCCATCTGAGGAAAGCCAGTTCACCAAAT CTTCATAGACGACAGTGGGAGAAAAATGTACCCAATACAGCTCTTACAGCTTTGGAAAATGCATCCAT ACTCACCTCCAGTTTAACAGCAGAGGACGATAGAGGTGGTGGTTCTGTAATAAAGTACAGCAAAAATA CTACTCGTAAGCAGTGGCTCAAAGAGACCCCTGACACTTTGTTGAACATCCTTAAGAATGCTGATCTC AGCTTGGCTTTTCAAACATACACAATATATAGACCAGGTTCAGAAGGGTTCTTGAAAGGCCCCCTGTC TGAAGAAACAGAAGCATCGGACAGTGTTGATGGAGGTCACGATTCTGTCATTTTGGATCCAGAGCGAC TTGAGCCTGGGCTAGATGAGGAGGACACGGACTTTGAGGAGGAAGATGACAACCCCGACTGGGTGTCA GAGCTGAAGAAGCGAGCTGGATGGCAAGGCCTGTGCGACAGATAATGCCTGAGGAAATGTTCCTGAGT
CACGCTGAGGAGAGGCTTCACTCAGGAGTTCATGCTGAGATGATCA
NOV77e, SNPl 3376464 of SEQ ID NO: 1106 489 aa MW at 5566δ.δkD CG93669-04, Protein Sequence SNP Pos: 32 SNP Change: Met to Val
MDDYMVLR IGEGSFGRALLVQHESSNQMFAVKEIRLPKSNTQNSRKEAVLLAKMKHPNIVAFKESFE AEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDILNWFTQMCLGV HIH KRVLHRDIKSKNIFLTQNG KVKLGDFGSARLLSSPMAFACTYVGTPYYVPPEI ENLPY NKSDIWSLGCILYELCTLKHPFQANSW KNLILKVCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATTLLSRGIVARLVQKCLPPQIIMEYGE EVLEEIKNSKHNTPRKKSLLKQEEEQDRKGSHTDLESINENLVESALRRVNRKSGNKSVHLRKASSPN LHRRQWEKNVPNTALTALENASILTSSLTAEDDRGGGSVIKYSKNTTRKQWLKETPDTLLNILKNADL SLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTDFEEEDDNPDWVS ELKKRAG QGLCD
NOV77f, SNPl 3376462 of SEQ ID NO: 1107 1542 bp CG93669-04, DNA Sequence ORF Start: ATG at 1 ORF Stop: at 1468
SNP Pos: 2δ4 SNP Change: A to G
ATGGATGACTACATGGTCCTGAGAATGATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCA TGAAAGCAGTAATCAGATGTTTGCCATGAAAGAAATAAGGCTTCCCAAGTCTAATACACAGAATTCTA GGAAGGAGGCTGTTCTTTTAGCCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAA GCTGAAGGACACTTGTATATTGTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACA GCAGAAAGGAAGGTTATTTCCTGAAGACATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATC ACATTCACAAGAAACGTGTGCTACACAGAGATATCAAGTCCAAGAATATCTTCCTCACTCAGAATGGA AAAGTGAAATTGGGAGACTTTGGATCTGCCCGTCTTCTCTCCAGTCCGATGGCATTTGCTTGTACCTA TGTGGGAACTCCTTATTATGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACA TCTGGTCCTTGGGTTGCATCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGG AAAAATCTTATCCTCAAAGTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACT TCAGTTCCTAGTCAAGCAGATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAACGCTTCTCT CTCGAGGCATCGTAGCTCGGCTTGTCCAGAAGTGCTTACCCCCCCAGATCATCATGGAATATGGTGAG GAAGTATTAGAAGAAATAAAAAATTCGAAGCATAACACACCAAGAAAAAAATCTCTTTTAAAGCAAGA GGAAGAACAAGATAGAAAGGGTAGCCATACTGATTTGGAAAGCATTAATGAAAATTTAGTTGAAAGTG CATTGAGAAGAGTAAACAGAAAATCAGGTAATAAGTCAGTCCATCTGAGGAAAGCCAGTTCACCAAAT CTTCATAGACGACAGTGGGAGAAAAATGTACCCAATACAGCTCTTACAGCTTTGGAAAATGCATCCAT ACTCACCTCCAGTTTAACAGCAGAGGACGATAGAGGTGGTGGTTCTGTAATAAAGTACAGCAAAAATA CTACTCGTAAGCAGTGGCTCAAAGAGACCCCTGACACTTTGTTGAACATCCTTAAGAATGCTGATCTC AGCTTGGCTTTTCAAACATACACAATATATAGACCAGGTTCAGAAGGGTTCTTGAAAGGCCCCCTGTC TGAAGAAACAGAAGCATCGGACAGTGTTGATGGAGGTCACGATTCTGTCATTTTGGATCCAGAGCGAC TTGAGCCTGGGCTAGATGAGGAGGACACGGACTTTGAGGAGGAAGATGACAACCCCGACTGGGTGTCA GAGCTGAAGAAGCGAGCTGGATGGCAAGGCCTGTGCGACAGATAATGCCTGAGGAAATGTTCCTGAGT
CACGCTGAGGAGAGGCTTCACTCAGGAGTTCATGCTGAGATGATCA
NOV77f, SNP13376462 of SEQ ID NO: 110δ 4δ9 aa MW at 5572δ.9kD CG93669-04, Protein Sequence SNP Pos: 95 SNP Change: Lys to Arg
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKSNTQNSRKEAVLLAKMKHPNIVAFKESFE AEGHLYIVMEYCDGGDLMQKIKQQKGRLFPEDILNWFTQMCLGVNHIHKKRVLHRDIKSK IFLTQNG KVKLGDFGSARLLSSPMAFACTYVGTPYYVPPEIWENLPYNNKSDIWSLGCILYELCTLKHPFQANSW KNLILKVCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATTLLSRGIVARLVQKCLPPQIIMEYGE EVLEEIKNSKHNTPRKKSLLKQEEEQDRKGSHTDLESINENLVESALRRVNRKSGNKSVHLRKASSPN LHRRQWEK VPNTALTALENASILTSSLTAEDDRGGGSVIKYSKNTTRKQWLKETPDTLLNILKNADL SLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTDFEEEDDNPDWVS ELKKRAGWQGLCD
NOV77g, SNP133δ2521 of SEQ ID NO: 1109 1542 bp CG93669-04, DNA Sequence ORF Start: ATG at 1 ORF Stop: at 1468
SNP Pos: 1511 SNP Change: G to C
ATGGATGACTACATGGTCCTGAGAATGATTGGGGAGGGCTCCTTCGGCAGAGCTCTTTTGGTTCAGCA TGAAAGCAGTAATCAGATGTTTGCCATGAAAGAAATAAGGCTTCCCAAGTCTAATACACAGAATTCTA GGAAGGAGGCTGTTCTTTTAGCCAAAATGAAACACCCTAATATTGTTGCCTTCAAAGAATCATTTGAA GCTGAAGGACACTTGTATATTGTGATGGAATACTGTGATGGAGGGGATCTAATGCAAAAGATTAAACA GCAGAAAGGAAAGTTATTTCCTGAAGACATACTTAATTGGTTTACCCAAATGTGCCTTGGAGTAAATC ACATTCACAAGAAACGTGTGCTACACAGAGATATCAAGTCCAAGAATATCTTCCTCACTCAGAATGGA AAAGTGAAATTGGGAGACTTTGGATCTGCCCGTCTTCTCTCCAGTCCGATGGCATTTGCTTGTACCTA TGTGGGAACTCCTTATTATGTGCCTCCAGAAATTTGGGAAAACCTGCCTTATAACAATAAAAGTGACA TCTGGTCCTTGGGTTGCATCCTGTATGAACTCTGTACCCTTAAGCATCCATTTCAGGCAAATAGTTGG AAAAATCTTATCCTCAAAGTATGTCAAGGGTGCATCAGTCCACTGCCGTCTCATTACTCCTATGAACT TCAGTTCCTAGTCAAGCAGATGTTTAAAAGGAATCCCTCACATCGCCCCTCGGCTACAACGCTTCTCT CTCGAGGCATCGTAGCTCGGCTTGTCCAGAAGTGCTTACCCCCCCAGATCATCATGGAATATGGTGAG GAAGTATTAGAAGAAATAAAAAATTCGAAGCATAACACACCAAGAAAAAAATCTCTTTTAAAGCAAGA GGAAGAACAAGATAGAAAGGGTAGCCATACTGATTTGGAAAGCATTAATGAAAATTTAGTTGAAAGTG CATTGAGAAGAGTAAACAGAAAATCAGGTAATAAGTCAGTCCATCTGAGGAAAGCCAGTTCACCAAAT CTTCATAGACGACAGTGGGAGAAAAATGTACCCAATACAGCTCTTACAGCTTTGGAAAATGCATCCAT ACTCACCTCCAGTTTAACAGCAGAGGACGATAGAGGTGGTGGTTCTGTAATAAAGTACAGCAAAAATA CTACTCGTAAGCAGTGGCTCAAAGAGACCCCTGACACTTTGTTGAACATCCTTAAGAATGCTGATCTC AGCTTGGCTTTTCAAACATACACAATATATAGACCAGGTTCAGAAGGGTTCTTGAAAGGCCCCCTGTC TGAAGAAACAGAAGCATCGGACAGTGTTGATGGAGGTCACGATTCTGTCATTTTGGATCCAGAGCGAC TTGAGCCTGGGCTAGATGAGGAGGACACGGACTTTGAGGAGGAAGATGACAACCCCGACTGGGTGTCA GAGCTGAAGAAGCGAGCTGGATGGCAAGGCCTGTGCGACAGATAATGCCTGAGGAAATGTTCCTGAGT CACGCTGAGGAGAGCCTTCACTCAGGAGTTCATGCTGAGATGATCA NOV77g, SNP133δ2521 of jSEQ ID NO: 1110 489 aa MW at 55700.9kD CG93669-04, Protein Sequence SNP Change: no change
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKSNTQNSRKEAVLLAKMKHPNIVAFKESFE AEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDILNWFTQMCLGVNHIHKKRVLHRDIKSKNIFLTQNG KVKLGDFGSARLLSSPMAFACTYVGTPYYVPPEI ENLPY NKSDI SLGCILYELCTLKHPFQA SW KNLILKVCQGCISPLPSHYSYELQFLVKQMFKRNPSHRPSATTLLSRGIVARLVQKCLPPQIIMEYGE EVLEEIKNSKH TPRKKSLLKQEEEQDRKGSHTDLESINENLVESALRRVNRKSGNKSVHLRKASSPN LHRRQ EKNVPNTALTALENASILTSSLTAEDDRGGGSVIKYSKNTTRKQWLKETPDTLLNILKNADL SLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTDFEEEDDNPD VS ELKKRAG QGLCD
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 77B.
Table 77B. Comparison of the NOV77 protein sequences.
NOV77a MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKS- -NTQNSRKEAVLLAKMKHP
NOV77b MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMKHP
NOV77C MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMKHP
NOV77d MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKVTTNTQNSRKEAVLLAKMKHP
NOV77a NIVAFKESFEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPED-ILN FTQMCLGVNHIHK
NOV77b NIVAFKESFEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDQILNWFTQMCLGVNHIHK
NOVllc NIVAFKESFEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDQILNWFTQMCLGVNHIHK
NOV77d NIVAFKESFEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDQILNWFTQ CLGVNHIHK
NOV77a IRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLSSPMAFACTYVGTPYYVPPEI ENLPYN
NOV77b KRVLHRDIKSQNIFLTQNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEI ENLPYN
NOV77c KRVLHRDIKSQNIFLTQNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEIWENLPY
NOV77d KRVLHRDIKSQNIFLTQNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEIWENLPYN
NOVlla NKSDIWSLGCILYELCTLKHPFQANSWK LILKVCQGCISPLPSHYSYELQFLVKQMF R
NOV77b NKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKR
NOVllc NKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKR
NOV77d NKSDIWSLGCILYELCTLKΗPFQA SWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKR
NOV77a NPSHRPSATTLLSRGIVARLVQKCLPPQIIMEYGEEVLEEIKNSKHNTPRKKSLLK
NOV77b NPSHRPSATTLLSRGIVARLVQKCLPPEIIMEYGEEVLEEIK SIHNTPRKKTNPSRIRI
NOVllc NPSHRPSATTLLSRGIVARLVQKCLPPEIIMEYGEEVLEEIKNSKHNTPRKKQ
NOV77d NPSHRPSATALLSRGIVARLVQKCLPPEIIMEYGEEVLEEIKNSKHNTPRKKQ
NOV77a QEEEQDRKGSHTDLESINENLVESALRRVNRKS-GNKSVHLRKASSPNLHR
NOV77b ALGNEASTVQEEEQDRKGSHTDLESINENLVESALRRVNREEKGNKSVHLRKASSPNLHR
NOVllc EEEQDRKGSHTDLESINENLVESALRRVNREEKGNKSVHLRKASSPNLHR
NOVlld EEEQDRKGSHTDLESINENLVESALRRVNREEKGNKSVHLRKASSPNLHR
NOV77a RQWEKNVPNTALTALENASILTSSLTAEDDRGGGSVIKYSKNTTRKQWLΪETPDTLLNIL
NOV77b RQWEK VPNTALTALENASILTSSLTAEDDRGG-SVIKYSKNTTRKQWLKETPDTLLNIL
NOVllc RQ EKNVPNTALTALENASILTSSLTAEDDRGG-SVIKYSKNTTRKQWLKETPDTLLNIL
NOVlld RQWEKNVPNTALTALENASILTSSLTAEDDRG
NOV77a KNADLSLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDT
NOV77b K ADLSLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDT
NOVllc KNADLSLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDT
NOV77d SEGFLKGPLSEETEASDSVE EDT N0V77a DFEEEDDNPDWVSELKKRAGWQGLCD-
NOV77b DFEEEDDNPD VSELKKRAGWQGLCDR
NOV77C DFEEEDDNPDWVSELKKRAGWQGLCDR
NOVlld DFEEEDDNPDWVSELKKRAGWQGLCDR
NOVlla (SEQ ID NO 1098)
NOV77b (SEQ ID NO 1100)
NOV77C (SEQ ID NO 1102)
NOV77d (SEQ ID NO 1104)
Further analysis ofthe NOV77a protein yielded the following properties shown in Table
77C.
Table 77C. Protein Sequence Properties NOV77a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 8; pos. chg 1; neg.chg 2 H-region: length 3; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -8.46 possible cleavage site: between 16 and 17
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 4.61 (at 5) ALOM score: 4.61 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.48 Hyd Moment(95): 7.98 G content: 0 D/E content : 2 S/T content : 0 Score: -6.50
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: HKKR (3) at 116 pat4: PRKK (4) at 286 pat7: PRKKSLL (5) at 286 bipartite: none content of basic residues: 13.3% NLS Score: 0.40
KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt 's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
69 .6 % : nuclear
21 .7 % : cytoplasmic 4 .3 % : mitochondrial 4 .3 % : peroxisomal
>> prediction for CG93669-04 is nuc (k=23 )
A search of the NOV77a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 77D.
Figure imgf001016_0001
In a BLAST search of public sequence databases, the NOV77a protein was found to have homology to the proteins shown in the BLASTP data in Table 77E.
Figure imgf001017_0001
PFam analysis indicates that the NOV77a protein contains the domains shown in the Table 77F.
Figure imgf001017_0002
Example 78.
The NOV78 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 78A.
Table 78A. NOV78 Sequence Analysis
NOV78a, CG94235-01 SEQ ID NO: 1111 2856 bp DNA Sequence ORF Start: ATG at 28 JORF Stop: TAG at 1294
GGGCGGCGCGGGGTCTGCGCTGGGGCCATGGCTCCGCCGCGCCGCTTCGTCCTGGAGCTTCCCGACTG CACCCTGGCTCACTTCGCCCTAGGCGCCGACGCCCCCGGCGACGCAGACGCCCCCGACCCCCGCCTGG CGGCGCTGCTGGGGCCCCCGGAGCGCAGCTACTCGCTGTGCGTGCCCGTGACCCCGGACGCCGGCTGC GGGGCCCGGGTCCGGGCGGCGCGGCTGCACCAGCGCCTGCTGCACCAGCTGCGCCGCGGCCCCTTCCA GCGGTGCCAGCTGCTCAGGCTGCTCTGCTACTGCCCGGGCGGCCAGGCCGGCGGCGCACAGCAAGGCT TCCTGCTGCGCGACCCCCTGGATGACCCTGACACCCGGCAAGCGCTGCTCGAGCTGCTGGGCGCCTGT CAGGAGGCACCACGCCCGCACTTGGGCGAGTTCGAGGCCGACCCGCGCGGCCAGCTGTGGCAGCGCCT CTGGGAGGTGCAAGACGGCAGGCGGCTGCAGGTGGGCTGCGCACAGGTCGTGCCCGTCCCGGAGCCCC CGCTGCACCCGGTGGTGCCAGACTTGCCCAGTTCCGTGGTCTTCCCGGACCGGGAAGCCGCCCGGGCC GTTTTGGAGGAGTGTACCTCCTTTATTCCTGAAGCCCGGGCAGTGCTTGACCTGGTCGACCAGTGCCC AAAACAGATCCAGAAAGGAAAGTTCCAGGTTGTTGCCATCGAAGGACTGGATGCCACGGGTGGTAAAA CCACGGTGACCCAGTCAGTGGCAGATTCACTTAAGGCTGTCCTCTTAAAGTCACCACCCTCTTGCATT GGCCAGTGGAGGAAGATCTTTGATGATGAACCAACTATCATTAGAAGAGCTTTTTACTCTTTGGGCAA TTATATTGTGGCCTCCGAAATAGCTAAAGAATCTGCCAAATCTCCTGTGATTGTAGACAGGCACAGCA CGGCCACCTATGCCATAGCCACTGAGGTGAGTGGGGGTCTCCAGCACCTGCCCCCAGCCCATCACCCT GTGTACCAGTGGCCAGAGGACCTGCTCAAACCTGACCTTATCCTGCTGCTCACTGTGAGTCCTGAGGA GAGGTTGCAGAGGCTGCAGGGCCGGGGCATGGAGAAGACCAGGGAAGAAGCAGAACTTGAGGCCAACA GTGTGTTTCGTCAAAAGGTAGAAATGTCCTACCAGCGGATGGAGAATCCTGGCTGCCATGTGGTTGAT GCCAGCCCCTCCAGAGAAAAGGTCCTGCAGACGGTATTAAGCCTAATCCAGAATAGTTTTAGTGAACC GTAGTTACTCTGGCCAGGTGCCACGTCTAACTAGATTAGATGTTGTTTGAAACATCTACATCCACCAT
TTGTTATGCAGTGTTCCCAAATTTCTGTTCTACAAGCATGTTGTGTGGCAGAAAACTGGAGACCAGGC
ATCTTAATTTTACTTCAGCCATCGTACCCTCTTCTGACTGATGGACCCGTCATCACAAAGGTCCCTCT
CATCATGTTCCAGTGAGAGGCCAGCGATTGCTTTCTTCCTGGCATAGTAAACATTTTCTTGGAACATA
TGTTTCACTTAATCACTACCAAATATCTGGAAGACCTGTCTTACTCAGACAGCACCAGGTGTACAGAA
GCAGCAGACAAGATCTTCCAGATCAGCAGGGAGACCCCGGAGCCTCTGCTTCTCCTACACTGGCATGC
TGATGAGATCGTGACATGCCCACATTGGCTTCTTCCACATCTGGTTGCACTCGTCATGATGGGCTCGC jTGCATCTCCCTCAGTCCCAAATTCTAGAGCCAAGTGTTCCTGCAGAGGCTGTCTATGTGTCCTGGCTG
CCCAAGGACACTCCTGCAGAGCCATTTTTGGGTAAGGAACACTTACAAAGAAGGCATTGATCTTGTGT
CTGAGGCTCAGAGCCCTTTTGATAGGCTTCTGAGTCATATATAAAGACATTCAAGCCAAGATGCTCCA lACTGCAAATATACCAACCTTCTCTGAATTATATTTTGCTTATTTATATTTCTTTTCTTTTTTTCTAAA
GTATGGCTCTGAATAGAATGCACATTTTCCATTGAACTGGATGCATTTCATTTAGCCAATCCAGTAAT
TTATTTATATTAATCTATACATAATATGTTTCCTCAGCATAGGAGCTATGATTCATTAATTAAAAGTG
IGAGTCAAAACGCTAAATGCAATGTTTGTTGTGTATTTTCATTACACAAACTTAATTTGTCTTGTTAAA jTAAGTACAGTGGATCTTGGAGTGGGATTTCTTGGTAAATTATCTTGCACTTGAATGTCTCATGATTAC
ATATGAAATCGCTTTGACATATCTTTAGACAGAAAAAAGTAGCTGAGTGAGGGGGAAATTATAGAGCT
GTGTGACTTTAGGGAGTAGGTTGAACCAGGTGATTACCTAAAATTCCTTCCAGTTCAAAGGCAGATAA
ATCTGTAAATTATTTTATCCTATCTACCATTTCTTAAGAAGACATTACTCCAAAATAATTAAATTTAA
IGGCTTTATCAGGTCTGCATATAGAATCTTAAATTCTAATAAAGTTTCATGTTAATGTCATAGGATTTT
TAAAAGAGCTATAGGTAATTTCTATATAATATGTGTATATTAAAATGTAATTGATTTCAGTTGAAAGT
ATTTTAAAGCTGATAAATAGCATTAGGGTTCTTTGCAATGTGGTATCTAGCTGTATTATTGGTTTTAT
TTACTTTAAACATTTTGAAAAGCTTATACTGGCAGCCTAGAAAAACAAACAATTAATGTATCTTTATG:
TCCCTGGCACATGAATAAACTTTGCTGTGGTTTACTAATCTAAAAAAAAAAAAAAAAGGGCGGCCGCTj
NOV78a, CG94235-01 SEQ ID NO: 1112 422 aa MW at 46476.6kD Protein Sequence
MAPPRRFVLELPDCTLAHFALGADAPGDADAPDPRLAALLGPPERSYSLCVPVTPDAGCGARVRAARL HQRLLHQLRRGPFQRCQLLRLLCYCPGGQAGGAQQGFLLRDPLDDPDTRQALLELLGACQEAPRPHLG EFEADPRGQLWQRLWEVQDGRRLQVGCAQWPVPEPPLHPWPDLPSSWFPDREAARAVLEECTSFI PEARAVLDLVDQCPKQIQKGKFQWAIEGLDATGGKTTVTQSVADSLKAVLLKSPPSCIGQWRKIFDD EPTIIRRAFYSLGNYIVASEIAKESAKSPVIVDRHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLL KPDLILLLTVSPEERLQRLQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVL QTVLSLIQNSFSEP
NOV78b, 254647864 SEQ ID NO: 1113 601 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCATCGAAGGACTGGATGCCACGGGTGGTAAAACCACGGTGACCCAGTCAGTGGCAGATT CACTTAAGGCTGTCCTCTTAAAGTCACCACCCTCTTGCATTGGCCAGTGGAGGAAGATCTTTGATGAT GAACCAACTATCATTAGAAGAGCTTTTTACTCTTTGGGCAATTATATTGTGGCCTCCGAAATAGCTAA AGAATCTGCCAAATCTCCTGTGATTGTAGACAGGTACTGGCACAGCACGGCCACCTATGCCATAGCCA CTGAGGTGAGTGGGGGTCTCCAGCACCTGCCCCCAGCCCATCACCCTGTGTACCAGTGGCCAGAGGAC CTGCTCAAACCTGACCTTATCCTGCTGCTCACTGTGAGTCCTGAGGAGAGGTTGCAGAGGCTGCAGGG CCGGGGCATGGAGAAGACCAGGGAAGAAGCAGAACTTGAGGCCAACAGTGTGTTTCGTCAAAAGGTAG AAATGTCCTACCAGCGGATGGAGAATCCTGGCTGCCATGTGGTTGATGCCAGCCCCTCCAGAGAAAAG GTCCTGCAGACGGTATTAAGCCTAATCCAGAATAGTTTTAGTGAACCGGGTACCGGC NOV7δb, 254647864 SEQ ID NO: 1114 1200 aa MW at 22132.8kD Protein Sequence
TGSIEGLDATGGKTTVTQSVADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAK ESAKSPVIVDRYWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQRLQG RGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHVVDASPSREKVLQTVLSLIQNSFSEPGTG
NOV7δc, 254347797 SEQ ID NO: 1115 601 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCATCGAAGGACTGGATGCCACGGGTGGTAAAACCACGGTGACCCAGTCAGTGGCAGATT CACTTAAGGCTGTCCTCTTAAAGTCACCACCCTCTTGCATTGGCCAGTGGAGGAAGATCTTTGATGAT GAACCAACTATCATTAGAAGAGCTTTTTACTCTTTGGGCAATTATATTGTGGCCTCCGAAATAGCTAA AGAATCTGCCAAATCTCCTGTGATTGTAGACAGGTACTGGCACAGCACGGCCACCTATGCCATAGCCA CTGAGGTGAGTGGGGGTCTCCAGCACCTGCCCCCAGCCCATCACCCTGTGTACCAGTGGCCAGAGGAC CTGCTCAAACCTGACCTTATCCTGCTGCTCACTGTGAGTCCTGAGGAGAGGTTGCAGAGGCTGCAGGG CCGGGGCATGGAGAAGACCAGGGAAGAAGCAGAACTTGAGGCCAACAGTGTGTTTCGTCAAAAGGTAG AAATGTCCTACCAGCGGATGGAGAATCCTGGCTGCCATGTGGTTGATGCCAGCCCCTCCAGAGAAAAG GTCCTGCAGACGGTATTAAGCCTAATCCAGAATAGTTTTAGTGAACCGGGTACCGGC
NOV7δc, 254347797 SEQ ID NO: 1116 200 aa MW at 22132.δkD Protein Sequence
TGSIEGLDATGGKTTVTQSVADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAK ESAKSPVIVDRYWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQRLQG RGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNSFSEPGTG
NOV7δd, CG94235-02 SEQ ID NO: 1117 2331 bp DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 769
GTCTGCGCTGGGGCCATGGCTCCGCCGCGCCGCTTCGTCCTGGAGCTTCCTGACTGCACCCTGGCTCA
CTTCGCCCTAGGCGCCGTTTTGGAGGAGTGTACCTCCTTTATTCCTGAAGCCCGGGCAGTGCTTGACC TGGTCGACCAGTGCCCAAAACAGATCCAGAAAGGAAAGTTCCAGGTTGTTGCCATCGAAGGACTGGAT GCCACGGGTAAAACCACGGTGACCCAGTCAGCGGCAGATTCACTTAAGGCTGTCCTCTTAAAGTCACC ACCCTCTTGCATTGGCCAGTGGAGGAAGATCTTTGATGATGAACCAACTATCATTAGAAGAGCTTTTT ACTCTTTGGGCAATTATATTGTGGCCTCCGAAATAGCTAAAGAATCTGCCAAATCTCCTGTGATTGTA GACAGGTACTGGCACAGCACGGCCACCTATGCCATAGCCACTGAGGTGAGTGGGGGTCTCCAGCACCT GCCCCCAGCCCATCACCCTGTGTACCAGTGGCCAGAGGACCTGCTCAAACCTGACCTTATCCTGCTGC TCACTGTGAGTCCTGAGGAGAGGTTGCAGAGGCTGCAGGGCCGGGGCATGGAGAAGACCAGGGAAGAA GCAGAACTTGAGGCCAACAGTGTGTTTCGTCAAAAGGTAGAAATGTCCTACCAGCGGATGGAGAATCC TGGCTGCCATGTGGTTGATGCCAGCCCCTCCAGAGAAAAGGTCCTGCAGACGGTATTAAGCCTAATCC AGAATAGTTTTAGTGAACCGTAGTTACTCTGGCCAGGTGCCACGTCTAACTAGATTAGATGTTGTTTG AAACATCTACATCCACCATTTGTTATGCAGTGTTCCCAAATTTCTGTTCTACAAGCATGTTGTGTGGC AGAAAACTGGAGACCAGGCATCTTAAGTTTACTTCAGCCATCGTACCCTCTTCTGACTGATGGACCCG TCATCACAAAGGTCCCTCTCATCATGTTCCAGTGAGAGGCCAGCGATTGCTTTCTTCCTGGCATAGTA AACATTTTCTTGGAACATATGTTTCACTTAATCACTACCAAATATCTGGAAGACCTGTCTTACTCAGA CAGCACCAGGTGTACAGAAGCAGCAGACAAGATCTTCCAGATCAGCAGGGAGACCCCGGAGCCTCTGC TTCTCCTACACTGGCATGCTGATGAGATCGTGACATGCCCACATTGGCTTCTTCCACATCTGGTTGCA CTCGTCATGATGGGCTCGCTGCATCTCCCTCAGTCCCAAATTCTAGAGCCAAGTGTTCCTGCAGAGGC TGTCTATGTGTCCTGGCTGCCCAAGGACACTCCTGCAGAGCCATTTTTGGGTAAGGAACACTTACAAA GAAGGCATTGATCTTGTGTCTGAGGCTCAGAGCCCTTTTGATAGGCTTCTGAGTCATATATAAAGACA TTCAAGCCAAGATGCTCCAACTGCAAATATACCAACCTTCTCTGAATTATATTTTGCTTATTTATATT TCTTTTCTTTTTTTCTAAAGTATGGCTCTGAATAGAATGCACATTTTCCATTGAACTGGATGCATTTC ATTTAGCCAATCCAGTAATTTATTTATATTAATCTATACATAATATGTTTCCTCAGCATAGGAGCTAT GATTCATTAATTAAAAGTGGAGTCAAAACGCTAAATGCAATGTTTGTTGTGTATTTTCATTACACAAA CTTAATTTGTCTTGTTAAATAAGTACAGTGGATCTTGGAGTGGGATTTCTTGGTAAATTATCTTGCAC TTGAATGTCTCATGATTACATATGAAATCGCTTTGACATATCTTTAGACAGAAAAAAGTAGCTGAGTG AGGGGGAAATTATAGAGCTGTGTGACTTTAGGGAGTAGGTTGAACCAGGTGATTACCTAAAATTCCTT CCAGTTCAAAGGCAGATAAATCTGTAAATTATTTTATCCTATCTACCATTTCTTAAGAAGACATTACT CCAAAATAATTAAATTTAAGGCTTTATCAGGTCTGCATATAGAATCTTAAATTCTAATAAAGTTTCAT GTTAATGTCATAGGATTTTTAAAAGAGCTATAGGTAATTTCTGTATAATATGTGTATATTAAAATGTA ATTGATTTCAGTTGAAAGTATTTTAAAGCTGATAAATAGCATTAGGGTTCTTTGCAATGTGGTATCTA GCTGTATTATTGGTTTTATTTACTTTAAACATTTTGAAAAGCTTATACTGGCAGCCTAGAAAAACAAA CAATTAATGTATCTTTATGTCCCTGGCACATGAATAAACTTTGCTGTGGTTTACTAAAAAAAAAAAAA AAAAAAAAGGGCGGCCGCT NOV78d, CG94235-02 SEQ ID NO: 1118 251 aa MW at 279δ0.8kD Protein Sequence
MAPPRRFVLELPDCTLAHFALGAVLEECTSFIPEARAVLDLVDQCPKQIQKGKFQWAIEGLDATGKT TVTQSAADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAKESAKSPVIVDRYWH STATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQRLQGRGMEKTREEAELEA NSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNSFSEP
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 7δB.
Table 78B. Comparison ofthe NOV78 protein sequences.
NOV78a MAPPRRFVLELPDCTLAHFALGADAPGDADAPDPRLAALLGPPERSYSLCVPVTPDAGCG
NOV78b
NOV78C
NOV78d
NOV78a ARVRAARLHQRLLHQLRRGPFQRCQLLRLLCYCPGGQAGGAQQGFLLRDPLDDPDTRQAL
NOV78b
NOV78c
NOV78d
NOV78a LELLGACQEAPRPHLGEFEADPRGQLWQRLWEVQDGRRLQVGCAQWPVPEPPLHPWPD
NOV78b
NOV78c
NOV78d MAPPRRFVLE
NOV78a LPSSWFPDREAARAVLEECTSFIPEARAVLDLVDQCPKQIQKGKFQWAIEGLDATGGK
NOV78b TGSIEGLDATGGK
NOV78c TGSIEGLDATGGK
NOV78d LPDCTLA- -HFALGAVLEECTSFIPEARAVLDLVDQCPKQIQKGKFQWAIEGLDATG-K
NOV78a TTVTQSVADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAKESAKS
NOV78b TTVTQSVADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAKESAKS
NOV78C TTVTQSVADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAKESAKS
NOV78d TTVTQSAADSLKAVLLKSPPSCIGQWRKIFDDEPTIIRRAFYSLGNYIVASEIAKESAKS
NOV78a PVIVDR--HSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQR
NOV78b PVIVDRYWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQR
NOV78c PVIVDRYWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQR
NOV78d PVIVDRYWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERLQR
NOV78a LQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNS
NOV78b LQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNS
NOV78c LQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNS
NOV78d LQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHWDASPSREKVLQTVLSLIQNS
NOV78a FSEP NOV78b FSEPGTG NOV78C FSEPGTG NOV78d FSEP
NOV78a (SEQ ID NO 1112)
NOV78b (SEQ ID NO 1114)
NOV78c (SEQ ID NO 1116)
NOV78d (SEQ ID NO 1118) Further analysis ofthe NOV7δa protein yielded the following properties shown in Table
7δC.
Table 78C. Protein Sequence Properties NOV78a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 2; neg.chg 1 H-region: length 2; peak value -1.05 PSG score: -5.45
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.20 possible cleavage site: between 22 and 23
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 3.66 (at 7) ALOM score: 3.66 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment (75) : 11.11 Hyd Moment (95): 9.49 G content: 0 D/E content: 2 S/T content: 0 Score: -4.13
Gavel: prediction of cleavage sites for mitochondrial preseq R-3 motif at 48 ERSY | S
NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 10.9% NLS Score: -0.47
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus : APPR none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
47.8 %: cytoplasmic
26.1 %: mitochondrial
17.4 %: nuclear
8.7 %: peroxisomal
>> prediction for CG94235-01 is cyt (k=23)
A search ofthe NOV7δa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7δD.
Figure imgf001023_0001
In a BLAST search of public sequence databases, the NOV78a protein was found to have homology to the proteins shown in the BLASTP data in Table 7δE.
Figure imgf001024_0001
PFam analysis indicates that the NOV78a protein contains the domains shown in the Table 78F.
Figure imgf001024_0002
Example 79.
The NOV79 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 79A.
Table 79A. NOV79 Sequence Analysis
NOV79a, CG95175-01 SEQ ID NO: 1119 3117 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TGA at 3078
CCTCCCCAGTAGCTGGGACTATGGGAGCGTGCCACCATGCCTGGTTAATTTTTGTATTTTTAGTAGAG
ATGGGGTTTCACCATGTTGGCCAGGCTTGTCTTCCCCTCTCCTTAGTTATCCTCCTGGATTCCAAAGC CTCCCAGGCCGAGCTGGGCTGGACTGCACTGCCAAGTAATGGGTGGGAGGAGATCAGCGGCGTGGATG AACACGACCGTCCCATCCGCACGTACCAAGTGTGCAATGTGCTGGAGCCCAACCAGGACAACTGGCTG CAGACTGGCTGGATAAGCCGTGGCCGCGGGCAGCGCATCTTCGTGGAACTGCAGTTCACACTCCGTGA CTGCAGCAGCATCCCTGGCGCCGCGGGTACCTGCAAGGAGACCTTCAACGTCTACTACCTGGAAACTG AGGCCGACCTGGGCCGTGGGCGTCCCCGCCTAGGCGGCAAAATCGACACGATCGCGGCGGACGAGAGC TTCACGCAGGGCGACCTGGGTGAGCGCAAGATGAAGCTGAACACAGAGGTGCGCGAGATCGGACCGCT CAGCCGGCGGGGTTTCCACCTGGCCTTTCAGGACGTGGGCGCATGCGTGGCGCTTGTCTCGGTGCGCG TCTACTACAAGCAGTGCCGCGCCACCGTGCGGGGCCTGGCCACGTTCCCAGCCACCGCAGCCGAGAGC GCCTTCTCCACACTGGTGGAAGTGGCCGGAACGTGCGTGGCGCACTCGGAAGGGGAGCCTGGCAGCCC CCCACGCATGCACTGCGGCGCCGACGGCGAGTGGCTGGTGCCTGTGGGCCGCTGCAGCTGCAGCGCGG GATTCCAGGAGCGTGGTGACTTCTGCGAAGGTATCTGTCCCCCAGGGTTTTACAAGGTGTCCCCGCGG CGGCCCCTCTGCTCACCGTGCCCAGAGCACAGCCGGGCCCTGGAAAACGCCTCCACCTTCTGCGTGTG CCAGGACAGCTATGCGCGCTCACCCACCGACCCGCCCTCGGCTTCCTGCACCCGTCCGCCGTCGGCGC CGCGGGACCTGCAGTACAGCCTGAGCCGCTCGCCGCTGGTGCTGCGACTGCGCTGGCTGCCGCCGGCC GACTCGGGAGGCCGCTCGGACGTCACCTACTCGCTGCTGTGCCTGCGCTGCGGCCGCGAGGGCCCGGC GGGCGCCTGCGAGGGGCCGCGCGTGGCCTTCCTACCGCGCCAGGCAGGGCTGCGGGAGCGAGCCGCCA CGCTGCTGCACCTGCGGCCCGGCGCGCGCTACACCGTGCGCGTGGCCGCGCTCAACGGCGTCTCGGGC CCGGCGGCCGCCGCGGGAACCACCTACGCGCAGGTCACCGTCTCCACCGGGCCCGGGGGTAAGGCCGT CCGCGCCCCCCACCCCGAGGCCACCGCGCCTGCCGCCCCTGCGCCCTCTTGGGGCCGCCCCGTCGGTC CTGCGGGATCAGCGCCCTGGGAGGAGGATGAGATCCGCAGGGACCGAGTGGAACCCCAGAGCGTGTCC CTGTCGTGGCGGGAGCCCATCCCTGCCGGAGCCCCTGGGGCCAATGACACGGAGTACGAGATCCGATA CTACGAGAAGGTGAGTGCGCAGAGTGAGCAGACTTACTCCATGGTGAAGACAGGGGCGCCCACAGTCA CCGTGATTTTCCTCCCAGCTGCCTCAGGGTCCAGGGACCAGAGCCCCGCCATTGTCGTCACCGTAGTG ACCATCTCGGCCCTCCTCGTCCTGGGCTCCGTGATGAGTGTGCTGGCCATTTGGAGGAGGAGGCCCTG CAGCTATGGCAAAGGAGGAGGGGATGCCCATGATGAAGAGGAGCTGTATTTCCACTGTGAGTTGGCTG GGAAAGTCCCAACACGTCGCACATTCCTGGACCCCCAGAGCTGTGGGGACCTGCTGCAGGCTGTGCAT CTGTTCGCCAAGGAACTGGATGCGAAAAGCGTCACGCTGGAGAGGAGCCTTGGAGGAGGCAAGCTGGG CGGGCGGTTTGGGGAGCTGTGCTGTGGCTGCTTGCAGCTCCCCGGTCGCCAGGAGCTGCTCGTAGCCG TGCACATGCTGAGGGACAGCGCCTCCGACTCACAGAGGCTCGGCTTCCTGGCCGAGGCCCTCACGCTG GGCCAGTTTGACCATAGCCACATCGTGCGGCTGGAGGGCGTTGTTACCCGAGGTAGGGGAAGCACCTT GATGATTGTCACCGAGTACATGAGCCATGGGGCCCTGGACGGCTTCCTCAGGCAGCGGCACGAGGGGC AGCTGGTGGCTGGGCAACTGATGGGGTTGCTGCCTGGGCTGGCATCAGCCATGAAGTATCTGTCAGAG ATGGGCTACGTTCACCGGGGCCTGGCAGCTCGCCATGTGCTGGTCAGCAGCGACCTTGTCTGCAAGAT CTCTGGCTTCGGGCGGGGCCCCCGGGACCGATCAGAGGCTGTCTACACCACTATGGTGAGGCTACAGA GTGGCCGGAGCCCAGCGCTATGGGCCGCTCCCGAGACACTTCAGTTTGGCCACTTCAGCTCTGCCAGT GACGTGTGGAGCTTCGGCATCATCATGTGGGAGGTGATGGCCTTTGGGGAGCGGCCTTACTGGGACAT GTCTGGCCAAGACGTGGTGATCAAGGCTGTGGAGGATGGCTTCCGGCTGCCACCCCCCAGGAACTGTC CTAACCTTCTGCACCGACTAATGCTCGACTGCTGGCAGAAGGACCCAGGTGAGCGGCCCAGGTTCTCC CAGATCCACAGCATCCTGAGCAAGATGGTGCAGGACCCAGAGCCCCCCAAGTGTGCCCTGACTACCTG TCCCAGGCCTCTGACCCGCAGGCCTCCCACTCCACTAGCCGACCGTGCCTTCTCCACCTTCCCCTCCT TTGGCTCTGTGGGCGCGTGGCTGGAGGCCCTGGACCTGTGCCGCTACAAGGACAGCTTCGCGGCTGCT GGCTATGGGAGCCTGGAGGCCGTGGCCGAGATGACTAGCCAGGACCTGGTGAGCCTAGGCATCTCTTT GGCTGAACATCGAGAGGCCCTCCTCAGCGGGATCAGCGCCCTGCAGGCACGAGTGCTCCAGCTGCAGG GCCAGGGGGTGCAGGTGTGAGTGGACCCCATTCTTCCAAGGCAGGACTCCGGTGGGG
NO V79a, CG95175-01 SEQ ID NO: 1120 1019 aa MW at l l0412.5kD Protein Sequence
MGACHHAWLIFVFLVEMGFHHVGQACLPLSLVILLDSKASQAELGWTALPSNG EEISGVDEHDRPIR TYQVCNVLEPNQDNWLQTG ISRGRGQRIFVELQFTLRDCSSIPGAAGTCKETFNVYYLETEADLGRG RPRLGGKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRRGFHLAFQDVGACVALVSVRVYYKQCR ATVRGLATFPATAAESAFSTLVEVAGTCVAHSEGEPGSPPRMHCGADGE LVPVGRCSCSAGFQERGD FCEGICPPGFYKVSPRRPLCSPCPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYS LSRSPLVLRLR LPPADSGGRSDVTYSLLCLRCGREGPAGACEGPRVAFLPRQAGLRERAATLLHLRP GARYTVRVAALNGVSGPAAAAGTTYAQVTVSTGPGGKAVRAPHPEATAPAAPAPS GRPVGPAGSAPW EEDEIRRDRVEPQSVSLS REPIPAGAPGANDTEYEIRYYEKVSAQSEQTYSMVKTGAPTVTVIFLPA ASGSRDQSPAIWTWTISALLVLGSVMSVLAIWRRRPCSYGKGGGDAHDEEELYFHCELAGKVPTRR TFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGKLGGRFGELCCGCLQLPGRQELLVAVHMLRDS ASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRGRGSTLMIVTEYMSHGALDGFLRQRHEGQLVAGQL MGLLPGLASAMKYLSE GYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTT VRLQSGRSPAL WAAPETLQFGHFSSASDV SFGIIM EVMAFGERPYWDMSGQDWIKAVEDGFRLPPPRNCPNLLHRL MLDC QKDPGERPRFSQIHSILSKMVQDPEPPKCALTTCPRPLTRRPPTPLADRAFSTFPSFGSVGAW LEALDLCRYKDSFAAAGYGSLEAVAEMTSQDLVSLGISLAEHREALLSGISALQARVLQLQGQGVQV NOV79b, 275697118 SEQ ID NO: 1121 547 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCGTTATCCTCCTGGATTCCAAAGCCTCCCAGGCCGAGCTGGGCTGGACTGCACTGCCAA GTAATGGGTGGGAGGAGATCAGCGGCGTGGATGAACACGACCGTCCCATCCGCACGTACCAAGTGTGC AATGTGCTGGAGCCCAACCAGGACAACTGGCTGCAGACTGGCTGGATAAGCCGTGGCCGCGGGCAGCG CATCTTCGTGGAACTGCAGTTCACACTCCGTGACTGCAGCAGCATCCCTGGCGCCGCGGGTACCTGCA AGGAGACCTTCAACGTCTACTACCTGGAAACTGAGGCCGACCTGGGCCGTGGGCGTCCCCGCCTAGGC GGCAGCCGGCCCCGCAAAATCGACACGATCGCGGCGGACGAGAGCTTCACGCAGGGCGACCTGGGTGA GCGCAAGATGAAGCTGAACACAGAGGTGCGCGAGATCGGACCGCTCAGCCGGCGGGGTTTCCACCTGG CCTTTCAGGACGTGGGCGCATGCGTGGCGCTTGTCTCGGTGCGCGTCTACTACAAGCAGTGCGTCGAC GGC
NOV79b, 2756971 lδ SEQ ID NO: 1122 lδ2 aa MW at 20253.6kD Protein Sequence
TGSVILLDSKASQAELG TALPSNGWEEISGVDEHDRPIRTYQVCNVLEPNQDN LQTGWISRGRGQR IFVELQFTLRDCSSIPGAAGTCKETFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGE RKMKLNTEVREIGPLSRRGFHLAFQDVGACVALVSVRVYYKQCVDG
NOV79c, 275697150 SEQ ID NO: 1123 694 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence
CACCGGATCCCTCGTAGCCGTGCACATGCTGAGGGACAGCGCCTCCGACTCACAGAGGCTCGGCTTCC TGGCCGAGGCCCTCACGCTGGGCCAGTTTGACCATAGCCACATCGTGCGGCTGGAGGGCGTTGTTACC CGAGGAAGCACCTTGATGATTGTCACCGAGTACATGAGCCATGGGGCCCTGGACGGCTTCCTCAGGCG GCACGAGGGGCAGCTGGTGGCTGGGCAACTGATGGGGTTGCTGCCTGGGCTGGCATCAGCCATGAAGT ATCTGTCAGAGATGGGCTACGTTCACCGGGGCCTGGCAGCTCGCCATGTGCTGGTCAGCAGCGACCTT GTCTGCAAGATCTCTGGCTTCGGGCGGGGCCCCCGGGACCGATCAGAGGCTGTCTACACCACTATGAG TGGCCGGAGCCCAGCGCTATGGGCCGCTCCCGAGACACTTCAGTTTGGCCACTTCAGCTCTGCCAGTG ACGTGTGGAGCTTCGGCATCATCATGTGGGAGGTGATGGCCTTTGGGGAGCGGCCTTACTGGGACATG TCTGGCCAAGACGTGATCAAGGCTGTGGAGGATGGCTTCCGGCTGCCACCCCCCAGGAACTGTCCTAA CCTTCTGCACCGACTAATGCTCGACTGCTGGCAGAAGGACCCAGGTGAGCGGCCCAGGTTCTCCCAGA TCCACGTCGACGGC
NOV79c, 275697150 SEQ ID NO: 1124 231 aa MW at 25557.0kD Protein Sequence
TGSLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRGSTLMIVTEYMSHGALDGFLRR HEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARHVLVSSDLVCKISGFGRGPRDRSEAVYTTMS GRSPALWAAPETLQFGHFSSASDV SFGIIM EVMAFGERPYWD SGQDVIKAVEDGFRLPPPRNCPN LLHRLMLDCWQKDPGERPRFSQIHVDG
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table 79B.
Table 79B. Comparison of the NOV79 protein sequences.
NOV79a MGACHHAWLIFVFLVEMGFHHVGQACLPLSLVILLDSKASQAELGWTALPSNGWEEISGV
NOV79b TGSVILLDSKASQAELGWTALPSNGWEEISGV
NOV79C
NOV79a DEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAGTCKE NOV79b DEHDRPIRTYQVCNVLEPNQDNWLQTG ISRGRGQRIFVELQFTLRDCSSIPGAAGTCKE NOV79C
NOV79a TFNVYYLETEADLGRGRPRLGG KIDTIAADESFTQGDLGERKMKLNTEVREIGPLS
NOV79b TFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLS NOV79C
NOV79a RRGFHLAFQDVGACVALVSVRVYYKQCRATVRGLATFPATAAESAFSTLVEVAGTCVAHS N0V79b RRGFHLAFQDVGACVALVSVRVYYKQCVDG- N0V79c
N0V79a EGEPGSPPRMHCGADGEWLVPVGRCSCSAGFQERGDFCEGICPPGFYKVSPRRPLCSPCP
NOV79b
NOV79C
NOV79a EHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYSLSRSPLVLRLRWLPPA
NOV79b
NOV79c
NOV79a DSGGRSDVTYSLLCLRCGREGPAGACEGPRVAFLPRQAGLRERAATLLHLRPGARYTVRV
NOV79b
NOV79C
NOV79a AALNGVSGPAAAAGTTYAQVTVSTGPGGKAVRAPHPEATAPAAPAPSWGRPVGPAGSAPW
NOV79b
NOV79C
NOV79a EEDEIRRDRVEPQSVSLSWREPIPAGAPGANDTEYEIRYYEKVSAQSEQTYSMVKTGAPT
NOV79b
NOV79c
NOV79a VTVIFLPAASGSRDQSPAIVVTVVTISALLVLGSVMSVLAI RRRPCSYGKGGGDAHDEE
NOV79b
NOV79c
NOV79a ELYFHCELAGKVPTRRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGKLGGRFGE
NOV79b
N0V79c
N0V79a LCCGCLQLPGRQELLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRGRG
N0V79b
NOV79C TGSLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRG- -
N0V79a STLMIVTEYMSHGALDGFLRQRHEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARH
NOV79b
N0V79c STLMIVTEYMSHGALDGFLRR-HEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARH
NOV79a VLVSSDLVCKISGFGRGPRDRSEAVYTTMVRLQSGRSPALWAAPETLQFGHFSSASDVWS
NOV79b
NOV79C VLVSSDLVCKISGFGRGPRDRSEAVYTTMS GRSPALWAAPETLQFGHFSSASDVWS
NOV79a FGIIMWEVMAFGERPYWDMSGQDWIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKDPGER
NOV79b
NOV79c FGIIMWEVMAFGERPYWDMSGQ-DVIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKDPGER
NOV79a PRFSQIHSILSKMVQDPEPPKCALTTCPRPLTRRPPTPLADRAFSTFPSFGSVGAWLEAL
NOV79b
NOV79C PRFSQIHVDG
NOV79a DLCRYKDSFAAAGYGSLEAVAEMTSQDLVSLGISLAEHREALLSGISALQARVLQLQGQG
NOV79b
NOV79c
NOV79a VQV
NOV79b --- NOV79c
NOV79a (SEQ ID NO: 1120)
NOV79b (SEQ ID NO: 1122)
NOV79C (SEQ ID NO: 1124)
Further analysis ofthe NOV79a protein yielded the following properties shown in Table 79C.
Table 79C. Protein Sequence Properties NOV79a
SignalP analysis: Cleavage site between residues 43 and 44
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 0; pos . chg 0; neg.chg 0 H-region: length 15; peak value 12.14 PSG score: 7.74
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -2.44 possible cleavage site: between 41 and 42
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al's method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0.5: 3 Number of TMS(s) for threshold 0.5: 1
INTEGRAL Likelihood = -9.08 Transmembrane 555 - 571 PERIPHERAL Likelihood = 0.85 (at 743) ALOM score: -9.08 (number of TMSs: 1)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 562 Charge difference: 3.5 C( 3.5) - N( 0.0) C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide
>>> membrane topology: type lb (cytoplasmic tail 555 to 1019)
MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.60 Hyd Moment (95): 3.84 G content: 1 D/E content: 1 S/T content: 0 Score: -6.09
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: RRRP (4) at 579 pat7: none bipartite: none content of basic residues: 10.1% NLS Score : - 0 . 22
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: too long tail
Dileucine motif in the tail: found LL at 565 LL at 623 LL at 670 LL at 751 LL at 880 LL at 998 checking 63 PROSITE DNA binding motifs: Leucine zipper pattern (PS00029) : found LGGRFGELCCGCLQLPGRQELL at 650 LVSLGISLAEHREALLSGISAL at 984 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 89
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
34.8 %: nuclear
21.7 %: mitochondrial
Figure imgf001030_0001
A search ofthe NOV79a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 79D.
Figure imgf001030_0002
In a BLAST search of public sequence databases, the NOV79a protein was found to have homology to the proteins shown in the BLASTP data in Table 79E.
Figure imgf001031_0001
PFam analysis indicates that the NOV79a protein contains the domains shown in the Table 79F.
Figure imgf001032_0002
Example 80.
The NOV80 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 80A.
Figure imgf001032_0001
CAAGGGTCCTGGTGAAGTCATCCCAGGAGGAAACCACAGTCTGTATTCTTTGAAGGGCTGCTGCACAT TGTTGAATCCATCGACCTTTAACTGCAATGGGATCTCTAATACATTTTGAGGTCAGCCACTTCTCCAG TGGAACTCTGAAGTACAGATGCT
NOVδOa, CG9963δ-01 SEQ ID NO: 1126 665 aa MW at 73δ73.1kD Protein Sequence
MELRSTAAPRAEGYSNVGFQNEENFLENENTSGNNSIRSRAVQSREHTNTKQDEEQVTVEQDSPRNRE HMEDDDEEMQQKGCLERRYDTVCGFCRKHKTTLRHIIWGILLAGYLVMVISACVLNFHRALPLFVITV AAIFFVV DHLMAKYEHRIDEMLSPGRRLLNSH F LK VI SSLVLAVIFWLAFDTAKLGQQQLVSF GGLIMYIVLLFLFSKYPTRVY RPVL GIGLQFLLGLLILRTDPGFIAFDWLGRLVQVLPIWFFSTV SMLYYPGLMQWIIRKVG IMLVTTGSSPIESWASGHIFVGQTESPLLVRPYLPYITKSELHAIMTA GFSTIAGSVLGAYISFGVPSSHLLTASVMSAPASLAAAKLFWPETEKPKITLKNAMKMESGDSGNLLE AATQGASSSISLVANIAVNLIAFLALLSFMNSALSWFGNMFDYPQLSFELICSYIFMPFSFMMGVEWQ DSFMVARLIGYKTFFNEFVAYEHLSK IHLRKEGGPKFVNGVQQYISIRSEIIATYALCGFANIGSLG IVIGGLTSMAPSRKRDIASGAVRALIAGTVACFMTACIAGILSSTPVDINCHHVLENAFNSTFPGNTT KVIACCQSLLSSTVAKGPGEVIPGGNHSLYSLKGCCTLLNPSTFNCNGISNTF
Further analysis of the NOVδOa protein yielded the following properties shown in Table δOB.
Table 80B. Protein Sequence Properties NOV80a
SignalP analysis: No Known Signal Sequence Indicated
PSORT II analysis:
PSG : a new signal peptide prediction method
N- region : length 10 ; pos . chg 2 ; neg . chg 1 H- region : length 1 ; peak value - 3 . 60 PSG score : - 8 . 00
GvH : von Heij ne ' s method for signal seq . recognit ion GvH score ( threshold : - 2 . 1 ) : - 9 . 75 possible cleavage site : between 13 and 14
>>> Seems to have no N-terminal signal peptide
ALOM : Klein et al ' s method for TM region allocation
Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0. 5: 9
INTEGRAL Likelihood -7 96 Transmembrane 107 - 123
INTEGRAL Likelihood -9 08 Transmembrane 128 - 144
INTEGRAL Likelihood -5 84 Transmembrane 175 - 191
INTEGRAL Likelihood -8 97 Transmembrane 201 - 217
INTEGRAL Likelihood -4 51 Transmembrane 228 - 244
INTEGRAL Likelihood -4 35 Transmembrane 259 - 275
INTEGRAL Likelihood -6 58 Transmembrane 418 - 434
INTEGRAL Likelihood -1 59 Transmembrane 534 - 550
INTEGRAL Likelihood -4 94 Transmembrane 569 - 585
PERIPHERAL Likelihood 0 85 (at 454)
ALOM score: -9.08 (number of TMSs: 9)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 114 Charge difference: -3.5 C( 1.5) - N( 5.0) N >= C: N-terminal side will be inside
>>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 4.42 Hyd Moment (95): 1.72 G content: 0 D/E content: 2 S/T content: 2 Score: -5.36
Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found
NUCDISC: discrimination of nuclear localization signals pat4: RKHK (3) at 95 pat7: PSRKRDI (5) at 555 bipartite: none content of basic residues: 7.5% NLS Score: 0.15
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
XXRR-like motif in the N-terminus: ELRS
SKL: peroxisomal targeting signal in the C-terminus: none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt' s method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total 0 residues
Final Results (k = 9/23 ) :
77 8 % : endoplasmic reticulum
11 1 % : vesicles of secretory sy stem
11 1 % : nuclear
>> prediction for CG99638 - Dl is end (k= 9 )
A search ofthe NOVδOa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table δOC.
Figure imgf001035_0001
In a BLAST search of public sequence databases, the NOVδOa protein was found to have homology to the proteins shown in the BLASTP data in Table δOD.
Figure imgf001036_0001
PFam analysis indicates that the NOV80a protein contains the domains shown in the Table 80E.
Figure imgf001036_0002
Example 81.
The NOVδl clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table lA.
Figure imgf001037_0001
Figure imgf001038_0001
A ClustalW comparison ofthe above protein sequences yields the following sequence alignment shown in Table lB.
Table 81 B. Comparison of the NOV81 protein sequences.
NOV79a MGACHHA LIFVFLVEMGFHHVGQACLPLSLVILLDSKASQAELGWTALPSNGWEEISGV
NOV79b TGSVILLDSKASQAELGWTALPSNGWEEISGV
NOV79c
NOV79a DEHDRPIRTYQVCNVLEPNQDN LQTGWISRGRGQRIFVELQFTLRDCSSIPGAAGTCKE
NOV79b DEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAGTCKE
NOV79c
NOV79a TFNVYYLETEADLGRGRPRLGG KIDTIAADESFTQGDLGERKMKLNTEVREIGPLS
NOV79b TFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLS NOVl 9c
NOV79a RRGFHLAFQDVGACVALVSVRVYYKQCRATVRGLATFPATAAESAFSTLVEVAGTCVAHS
NOV79b RRGFHLAFQDVGACVALVSVRVYYKQCVDG
NOV79C
NOV79a EGEPGSPPRMHCGADGE LVPVGRCSCSAGFQERGDFCEGICPPGFYKVSPRRPLCSPCP
NOV79b
NOV79C
NOV79a EHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYSLSRSPLVLRLRWLPPA
NOV79b
NOV79C
NOV79a DSGGRSDVTYSLLCLRCGREGPAGACEGPRVAFLPRQAGLRERAATLLHLRPGARYTVRV
NOV79b
NOV79C
NOV79a AALNGVSGPAAAAGTTYAQVTVSTGPGGKAVRAPHPEATAPAAPAPSWGRPVGPAGSAPW
NOV79b
NOV79C
NOV79a EEDEIRRDRVEPQSVSLS REPIPAGAPGANDTEYEIRYYEKVSAQSEQTYSMVKTGAPT
NOV79b
NOV79C
NOV79a VTVIFLPAASGSRDQSPAIWTWTISALLVLGSVMSVLAIWRRRPCSYGKGGGDAHDEE
NOV79b
NOV79C
NOV79a ELYFHCELAGKVPTRRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGKLGGRFGE
N0V79b
NOV79C
N0V79a LCCGCLQLPGRQELLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRGRG
N0V79b
NOV79C TGSLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGWTRG- -
NOV79a STLMIVTEYMSHGALDGFLRQRHEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARH
NOV79b
N0V79C STLMIVTEYMSHGALDGFLRR-HEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARH
N0V79a VLVSSDLVCKISGFGRGPRDRSEAVYTTMVRLQSGRSPALWAAPETLQFGHFSSASDV S
N0V79b
N0V79C VLVSSDLVCKISGFGRGPRDRSEAVYTTMS GRSPALWAAPETLQFGHFSSASDV S
N0V79a FGIIM EVMAFGERPYWDMSGQDWIKAVEDGFRLPPPRNCPNLLHRLMLDC QKDPGER
N0V79b
N0V79c FGIIM EVMAFGERPYWDMSGQ-DVIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKDPGER
N0V79a PRFSQIHSILSKMVQDPEPPKCALTTCPRPLTRRPPTPLADRAFSTFPSFGSVGA LEAL
N0V79b
N0V79C PRFSQIHVDG
N0V79a DLCRYKDSFAAAGYGSLEAVAEMTSQDLVSLGISLAEHREALLSGISALQARVLQLQGQG
NOV79b
NOV79c NOV79a VQV
NOV79b
NOV79C
NOV81a (SEQ ID NO: 1128)
Further analysis ofthe NOVδl a protein yielded the following properties shown in Table δlC.
Table 81 C. Protein Sequence Properties NOV81a
SignalP analysis: Cleavage site between residues 38 and 39
PSORT II analysis:
PSG: a new signal peptide prediction method
N-region: length 10; pos. chg 0; neg.chg 1 H-region: length 7; peak value 0.00 PSG score: -4.40
GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -4.98 possible cleavage site: between 49 and 50
>>> Seems to have no N-terminal signal peptide
ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1
Tentative number of TMS(s) for the threshold 0 .5: 6
INTEGRAL Likelihood = -7 .11 Transmembrane 22 - 38
INTEGRAL Likelihood = -2 .76 Transmembrane 59 - 75
INTEGRAL Likelihood = -3 .50 Transmembrane 89 - 105
INTEGRAL Likelihood = -2 .28 Transmembrane 140 - 156
INTEGRAL Likelihood =-14 .01 Transmembrane 192 - 208
INTEGRAL Likelihood = -9 .18 Transmembrane 235 - 251
PERIPHERAL Likelihood = 1 .22 (at 110)
ALOM score -14.01 (number of TMSs: 6)
MTOP: Prediction of membrane topology (Hartmann et al . ) Center position for calculation: 29 Charge difference: 3.0 C ( 3.0) - N( 0.0) C > N: C-terminal side will be inside
>>> membrane topology: type 3b
MITDISC: discrimination of mitochondrial targeting seq R content: 4 Hyd Moment(75): 2.17 Hyd Moment(95): 4.19 G content: 3 D/E content: 2 S/T content: 10 Score: -2.58
Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 232 LRT|EE
NUCDISC: discrimination of nuclear localization signals pat4: RRRR (5) at 135 pat7: none bipartite: none content of basic residues: 9.7%
NLS Score: -0.16
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals: none
SKL: peroxisomal targeting signal in the C-terminus : none
PTS2 : 2nd peroxisomal targeting signal: none
VAC: possible vacuolar targeting motif: none
RNA-binding motif: none
Actinin-type actin-binding motif: type 1 : none type 2 : none
NMYR: N-myristoylation pattern : none
Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none
Tyrosines in the tail: none
Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none
NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1
COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues
Final Results (k = 9/23) :
44.4 %: endoplasmic reticulum
22.2 %: vacuolar
11.1 %: Golgi
11.1 %: vesicles of secretory system
11.1 %: mitochondrial
>> prediction for CG99650-01 is end (k=9) A search ofthe NOV81 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several h hommnollnoσnonuss nrrnottpeiiinnss s shhoowwnn i inn T Taahbllee 8 δ1lD.
Figure imgf001042_0001
In a BLAST search of public sequence databases, the NOV81a protein was found to have homology to the proteins shown in the BLASTP data in Table δlE.
103δ
Figure imgf001043_0001
PFam analysis indicates that the NOV l a protein contains the domains shown in the Table δlF.
Figure imgf001043_0002
Example B: Sequencing Methodology and Identification of NOVX Clones
1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., "Gene expression analysis by transcript profiling coupled to a gene database query" Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each ofthe restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing ofthe gene fragment.
2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymoφhisms (SNPs), insertions, deletions and other sequence variations.
3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length ofthe DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.
The laboratory screening was performed using the methods summarized below: cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, CA) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U. S. Patents 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).
Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymoφhisms (SNPs), insertions, deletions and other sequence variations.
Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Coφoration proprietary yeast strains N106' and YULH (U. S. Patents 6,057,101 and 6,083,693).
4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the sequence of the cDNA ofthe invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.
5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case ofthe reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence ofthe target sequence, or by translated homology ofthe exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Coφoration's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.
6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.
The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening puφoses.
Example C. Quantitative expression analysis of clones in various cells and tissues
The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).
RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and lδS ribosomal RNA staining intensity ratio as a guide (2: 1 to 2.5:1 2δs:lδs) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.
First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer's instructions.
In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Coφoration; Catalog No. Iδ064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42°C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using IX TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.
Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration = 250 nM, primer melting temperature (Tm) range = 5 °-60° C, primer optimal Tm = 59° C, maximum primer difference = 2° C, probe does not have 5' G, probe Tm must be 10° C greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, TX, USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5' and 3' ends ofthe probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200nM. PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313δ03) following manufacturer's instructions. Reverse transcription was performed at 48° C for 30 minutes followed by amplification/PCR cycles as follows: 95° C 10 min, then 40 cycles of 95° C for 15 seconds, 60° C for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100. CT values below 28 indicate high expression, CT values between 28 and 32 indicate moderate expression, and CT values between 32 and 35 indicate low expression. CT values above 35 reflect levels of expression that are too low to be reliably measured.
When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using IX TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification was performed as follows: 95° C 10 min, then 40 cycles of 95° C for 15 seconds, 60° C for 1 minute. Results were analyzed and processed as described previously.
Panels 1, 1.1, 1.2, and 1.3D
The plates for Panels 1 , 1.1, 1.2 and 1.3D include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in these panels are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers ofthe following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in these panels are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on these panels are comprised of samples derived from all major organ systems from single adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions ofthe brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose.
In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used: ca. = carcinoma,
* = established from metastasis, met = metastasis, s cell var = small cell variant, non-s = non-sm = non-small, squam = squamous, pi. eff = pi effusion = pleural effusion, glio = glioma, astro = astrocytoma, and neuro = neuroblastoma.
GENERAL_SCREENING_PANEL_V1.4, V1.5, V1.6 AND 1.7
The plates for Panels 1.4, 1.5, 1.6 and 1.7 include 2 control wells (genomic DNA control and chemistry control) and 8δ to 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, 1.6 and 1.7 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers ofthe following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, 1.6 and 1.7 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, 1.6 and 1.7 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions ofthe brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.
Panels 2D, 2.2, 2.3, and 2.4
The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have "matched margins" obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted "NAT" in the results below. The tumor tissue and the "matched margins" are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage ofthe patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated "NAT", for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, CA), Research Genetics, and Invitrogen.
HASS PANEL V 1.0
The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, δl of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, MD) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.
ARDAIS PANEL V 1.0
The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Coφoration. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have "matched margins" obtained from noncancerous lung tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated "NAT", for normal adjacent tissue) in the results below. The tumor tissue and the "matched margins" are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non- malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state ofthe patient.
ARDAIS PROSTATE V 1.0
The plates for ARDAIS prostate 1.0 generally include 2 control wells and 68 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Coφoration. The tissues are derived from human prostate malignancies and in cases where indicated malignant samples have "matched margins" obtained from noncancerous prostate tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated "NAT", for normal adjacent tissue) in the results below. The tumor tissue and the "matched margins" are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). RNA from unmatched malignant and non-malignant prostate samples were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state ofthe patient.
ARDAIS KIDNEY V 1.0
The plates for ARDAIS kidney 1.0 generally include 2 control wells and 44 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Coφoration. The tissues are derived from human prostate malignancies and in cases where indicated malignant samples have "matched margins" obtained from noncancerous prostate tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated "NAT", for normal adjacent tissue) in the results below. The tumor tissue and the "matched margins" are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). RNA from unmatched malignant and non-malignant prostate samples were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.
PANEL 3D AND 3.1 AND 3.2
The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma ofthe tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1., 1.2, 1.3D, 1.4, 1.5, and 1.6 are ofthe most common cell lines used in the scientific literature.
Panels 4D, 4R, and 4.1D
Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, CA) and thymus and kidney (Clontech) was employed. Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, CA). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn's disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, PA).
Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, MD) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5- 10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.
Mononuclear cells were prepared from blood of employees at CuraGen Coφoration, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, MD), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x IO"5 M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 M sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2xl06 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5 x 10"5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1- 7 days for RNA preparation.
Monocytes were isolated from mononuclear cells using CD 14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, UT), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x IO"5 M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), 10 mM Hepes (Gibco) and 10%> AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.
CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CDδ and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CDI 9 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10" M (Gibco), and 10 mM Hepes (Gibco) and plated at 10 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CDδ lymphocytes for 4 days on anti-CD2δ and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CDδ cells were then activated again with plate bound anti-CD3 and anti-CD2δ for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days ofthe second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x IO"5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.
To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 10° cells/ml in DMEM 5%. FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x IO"5 M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,4δ and 72 hours.
To prepare the primary and secondary Thl/Th2 and Trl cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes
5 6
(Poietic Systems, German Town, MD) were cultured at 10 -10 cells/ml in DMEM 5%
FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate
(Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Thl, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Trl . After 4-5 days, the activated Thl , Th2 and Trl lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5%> FCS (Hyclone),
100 μM non essential amino acids (Gibco), 1 M sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml).
Following this, the activated Thl , Th2 and Trl lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Thl, Th2 and Trl lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Thl and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Thl, Th2 and Trl after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD2δ mAbs and 4 days into the second and third expansion cultures in Interleukin 2.
The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5 xlO5 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5 xlO5 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10"5 M (Gibco), and 10 mM Hepes (Gibco). CCDl 106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.
For these cell lines and blood cells, RNA was prepared by lysing approximately IO7 cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Coφoration) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 φm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at -20 degrees C ovemight. The precipitated RNA was spun down at 9,000 φm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37 degrees C for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3 M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at -δO degrees C.
AI_comprehensive panel_vl.O
The plates for AI_comprehensive panel_vl .0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, MD). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.
Joint tissues including synovial fluid, synovium, bone and cartilage were obtained from patients undergoing total knee or hip replacement surgery at the Backus Hospital. Tissue samples were immediately snap frozen in liquid nitrogen to ensure that isolated RNA was of optimal quality and not degraded. Additional samples of osteoarthritis and rheumatoid arthritis joint tissues were obtained from Clinomics. Normal control tissues were supplied by Clinomics and were obtained during autopsy of trauma victims.
Surgical specimens of psoriatic tissues and adjacent matched tissues were provided as total RNA by Clinomics. Two male and two female patients were selected between the ages of 25 and 47. None ofthe patients were taking prescription drugs at the time samples were isolated.
Surgical specimens of diseased colon from patients with ulcerative colitis and Crohns disease and adjacent matched tissues were obtained from Clinomics. Bowel tissue from three female and three male Crohn's patients between the ages of 41-69 were used. Two patients were not on prescription medication while the others were taking dexamethasone, phenobarbital, or tylenol. Ulcerative colitis tissue was from three male and four female patients. Four ofthe patients were taking lebvid and two were on phenobarbital.
Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-lanti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators. In the labels employed to identify tissues in the Al comprehensive panel_vl.O panel, the following abbreviations are used: Al = Autoimmunity Syn = Synovial Normal = No apparent disease Rep22 /Rep20 = individual patients RA = Rheumatoid arthritis Backus = From Backus Hospital OA = Osteoarthritis (SS) (BA) (MF) = Individual patients Adj = Adjacent tissue Match control = adjacent tissues -M = Male -F = Female COPD = Chronic obstructive pulmonary disease
AI.05 chondrosarcoma
The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. ILlbeta). These treatments include: IL-1 β (10 ng/ml), IL-1 β + TNF-α (50 ng/ml), IL-1 β + Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from the ATCC (American Type Culture Collection) and were all cultured under standard recommended conditions. The SW1353 cells were plated at 3 xlO5 cells/ml (in DMEM medium-10 % FBS) in 6-well plates. The treatment was done in triplicate, for 6 and 18 h. The supematants were collected for analysis of MMP 1, 3 and 13 production and for RNA extraction. RNA was prepared from these samples using the standard procedures.
Panels 5D and 51
The plates for Panel 5D and 51 include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.
In the Gestational Diabetes study subjects are young (18 - 40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery ofthe infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<1 cc) ofthe exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:
Patient 2 Diabetic Hispanic, overweight, not on insulin
Patient 7-9 Nondiabetic Caucasian and obese (BMI>30) Patient 10 Diabetic Hispanic, overweight, on insulin Patient 11 Nondiabetic African American and overweight Patient 12 Diabetic Hispanic on insulin Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr 2 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:
Donor 2 and 3 U Mesenchymal Stem cells Undifferentiated Adipose Donor 2 and 3 AM Adipose AdiposeMidway Differentiated
Donor 2 and 3 AD Adipose Adipose Differentiated
Human cell lines were generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells, and adrenal cortical adenoma cells. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. All samples were processed at CuraGen to produce single stranded cDNA.
Panel 51 contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 51.
In the labels employed to identify tissues in the 5D and 51 panels, the following abbreviations are used: GO Adipose = Greater Omentum Adipose SK = Skeletal Muscle UT = Utems PL = Placenta
AD = Adipose Differentiated AM = Adipose Midway Differentiated U = Undifferentiated Stem Cells
Human Metabolic RTQ-PCR Panel
The plates for the Human Metabolic RTQ-PCR Panel include two control wells (genomic DNA control and chemistry control) and 211 cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. This panel is useful for establishing the tissue and cellular expression profiles for genes believed to play a role in the etiology and pathogenesis of obesity and/or diabetes and to confirm differential expression of such genes derived from other methods.
Metabolic tissues were obtained from patients enrolled in the CuraGen Gestational Diabetes study and from autopsy tissues from Type II diabetics and age, sex and race-matched control patients. One or more ofthe following were used to characterize the patients: body mass index [BMI = wt (kg) / ht (m2)], serum glucose, HgbAlc. Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines. RNA from human Pancreatic Islets was also obtained.
In the Gestational Diabetes study, subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective)
Caesarian section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<lcc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted, and then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus), and subcutaneous adipose. Patient descriptions are as follows:
Patient 7 Non-diabetic Caucasian and obese
Patient δ Non-diabetic Caucasian and obese
Patient 12 Diabetic Caucasian with unknown BMI and on insulin
Patient 13 Diabetic Caucasian, overweight, not on insulin
Patient 15 Diabetic Caucasian, obese, not on insulin
Patient 17 Diabetic Caucasian, normal weight, not on insulin
Patient lδ Diabetic Hispanic, obese, not on insulin
Patient 19 Non-diabetic Caucasian and normal weight
Patient 20 Diabetic Caucasian, overweight, and on insulin
Patient 21 Non-diabetic Caucasian and overweight
Patient 22 Diabetic Caucasian, normal weight, on insulin
Patient 23 Non-diabetic Caucasian and overweight
Patient 25 Diabetic Caucasian, normal weight, not on insulin
Patient 26 Diabetic Caucasian, obese, on insulin
Patient 27 Diabetic Caucasian, obese, on insulin
Total RNA was isolated from metabolic tissues of 12 Type II diabetic patients and 12 matched control patients included hypothalamus, liver, pancreas, small intestine, psoas muscle, diaphragm muscle, visceral adipose, and subcutaneous adipose. The diabetics and non-diabetics were matched for age, sex, ethnicity, and BMI where possible.
The panel also contains pancreatic islets from a 22 year old male patient (with a BMI of 35) obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at CuraGen.
Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured at an outside facility. The RNA was extracted at CuraGen according to CuraGen protocols. All samples were then processed at CuraGen to produce single stranded cDNA.
In the labels used to identify tissues in the Human Metabolic panel, the following abbreviations are used:
105δ PI = placenta
Go = greater omentum
Sk = skeletal muscle
Ut = uterus
CC = Caucasian
HI = Hispanic
AA = African American
AS = Asian
Diab = Type II diabetic
Norm = Non-diabetic
Overwt = Overweight; med BMI
Obese = Hi BMI
Low BM = 20-25
Med BM = 26-30
Hi BMI = Greater than 30
M = Male
# = Patient identifier
Vis. = Visceral
SubQ = Subcutaneous
Panel CNSD.01
The plates for Panel CNSD.01 include two control wells and 94 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center. Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at -δ0°C in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.
Disease diagnoses are taken from patient records. The panel contains two brains from each ofthe following diagnoses: Alzheimer's disease, Parkinson's disease,
Huntington's disease, Progressive Supemuclear Palsy, Depression, and "Normal controls". Within each of these brains, the following regions are represented: cingulate gyms, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington's disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington's cases. Likewise Parkinson's disease is characterized by degeneration ofthe substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.
In the labels employed to identify tissues in the CNS panel, the following abbreviations are used: PSP = Progressive supranuclear palsy Sub Nigra = Substantia nigra Glob Palladus= Globus palladus Temp Pole = Temporal pole Cing Gyr = Cingulate gyms BA 4 = Brodman Area 4
Panel CNS_Neurodegeneration_V1.0
The plates for Panel CNS Neurodegeneration Vl .0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at -δO°C in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.
Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer's disease (AD) patients, and eight brains from "Normal controls" who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer's like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0 = no evidence of plaques, 3 = severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages ofthe disease; the occipital cortex is spared in AD and therefore acts as a "control" region within AD patients. Not all brain regions are represented in all cases.
In the labels employed to identify tissues in the CNS Neurodegeneration Vl.O panel, the following abbreviations are used:
AD = Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy
Control = Control brains; patient not demented, showing no neuropathology
Control (Path) = Control brains; pateint not demented but showing sever AD-like pathology
SupTemporal Ctx = Superior Temporal Cortex
Inf Temporal Ctx = Inferior Temporal Cortex
The expression ofthe gene was analyzed after normalization using scaling factor. The scaling factor is calculated from the Grand mean of CT values for a panel and the Well mean which is specific to the tissue. The Grand mean is the average CT value for all wells across all runs. For example, if a panel has 50 samples and has had 100 probe/primer sets mn on it, the grand mean would be the average of these 5000 CT scores. The well mean is tissue-specific. On the above described panel there would be 50 different well means, each taking the average ofthe 100 CT values generated for each sample on the panel from the 100 probe/primer sets.
The asumption is that across a large number of genes, all samples should have the same CT value. If a well is lower than the average across a large number of genes, it is "scaled up" by that difference or the "scaling factor".
Scaling Factor = Grand mean - Well mean The new CT value for the well is:
Scaled CT value = Raw CT + Scaling Factor.
Statistical Analysis of CNS_Neurodegeneration_V1.0 Data All data were analyzed by analysis of covariance (ANCOVA). As a covariate, the average CT value (or number of rounds of PCR until signal from the well was detected) was calculated for 1000 PCR runs on different genes. This number is therefore an estimate of total cDNA quantity and quality for each sample. When RTQ PCR is run for a given gene, CT values are therefore compared to these average values to correct for differences in well loading or original RNA quality. Stats were mn on data from the temporal cortex, as this regions shows sever neurodegeneration in the mid to late stages ofthe disease, and because the largest number of samples were available for this region giving the most statistical power. Covariates for each well corresponding to Temporal Cortex samples are listed below. The well numbers (10-25) are listed under "Order" in the table of CT values given for each gene n. For this analysis, Controls and Control (Path) cases were grouped together as the intention was to find genes associated with dementia as opposed to amyloid deposition.
10 AD1 33.014
11 AD2 32.309
12 AD3 34.195
13 AD4 32.6δ9
14 AD5 Inf 30.829
15 AD5 Sup 31.519
16 AD6 Inf 31.517
17 AD6 Sup 31.415 iδ Conl 34.236
19 Con2 32.352
20 Con3 33.215
21 Con4 33.661
22 Con5 (Path) 31.685
23 Con6 (Path) 32.1δ7
24 Con7 (Path) 34.427
25 Conδ (Path) 32.23δ
Panel CNS_Neurodegeneration_V2.0
The plates for Panel CNS_Neurodegeneration_V2.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at -δO°C in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.
Disease diagnoses are taken from patient records. The panel contains sixteen brains from Alzheimer's disease (AD) patients, and twenty-nine brains from "Normal controls" who showed no evidence of dementia prior to death. The twenty-nine normal control brains are divided into two categories: Fourteen controls with no dementia and no Alzheimer's like pathology (Controls) and fifteen controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0 = no evidence of plaques, 3 = severe AD senile plaque load). Tissue from the temporal cotex (Broddmann Area 21) was selected for all samples from the Harvard Brain Tissue Resource Center; from the two sample from the Human Brain and Spinal Fluid Resource Center (samples 1 and 2) tissue from the inferior and superior temporal cortex was used; each sample on the panel represents a pool of inferior and superior temporal cortex from an individual patient. The temporal cortex was chosen as it shows a loss of neurons in the intermediate stages ofthe disease. Selection of a region which is affected in the early stages of Alzheimer's disease (e.g., hippocampus or entorhinal cortex) could potentially result in the examination of gene expression after vulnerable neurons are lost, and missing genes involved in the actual neurodegeneration process.
In the labels employed to identify tissues in the CNS_Neurodegeneration_V2.0 panel, the following abbreviations are used:
AD = Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy
Control = Control brains; patient not demented, showing no neuropathology
AH3 = Control brains; pateint not demented but showing sever AD-like pathology
Inf & Sup Temp Ctx Pool = Pool of inferior and superior temporal cortex for a given individual
A. CGI 01340-01: PUTATIVE G PROTEIN-COUPLED RECEPTOR 92 Expression of full-length physical clone CGI 01340-01 was assessed using the primer-probe set Gpcr41, described in Table AA. Results ofthe RTQ-PCR mns are shown in Tables AB and AC.
Table AA. Probe Name Gpcr41
Figure imgf001068_0001
Table AB. Panel 1.3D
Figure imgf001068_0002
Figure imgf001069_0001
Table AC. Panel 4D
Figure imgf001069_0002
Figure imgf001070_0001
Figure imgf001071_0001
Panel 1.3D Summary: Gpcr41 Expression ofthe CG101340-01 gene was highest in hippocampus (CT=29.1) and occured at moderate to low levels throughout the brain. This gene encodes a putative GPCR. Several neurotransmitter receptors are GPCRs, including the dopamine receptor family, the serotonin receptor family, the GABAB receptor, muscarinic acetylcholine receptors, and others; thus this GPCR represents novel neurotransmitter receptor. Targeting various neurotransmitter receptors (dopamine, serotonin) has proven to be an effective therapy in psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. Furthermore, the cerebral cortex and hippocampus are regions ofthe brain that are known to be involved in Alzheimer's disease, seizure disorders, and in the normal process of memory formation. Therapeutic modulation of this gene or its protein product is beneficial in the treatment of one or more of these diseases, as is stimulation and/or blockade ofthe receptor coded for by the gene.
This gene was also moderately expressed in a number of other normal tissues including colon, ovary and spleen. Expression of this gene was higher in normal cells than in cancer cell lines and CG 101340-01 expression was downregulated in ovarian and brain cancer cell lines. Expression of this gene or its protein product is useful as a marker to distinguish normal tissue from ovarian or brain tumors.
Among tissues with metabolic or endocrine function, this gene was expressed at low levels in adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, and liver. Therapeutic modulation ofthe activity of this gene or its protein product is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
In addition, expression ofthe CGI 01340-01 gene was upregulated in fetal skeletal muscle and heart when compared to adult tissues. The overexpression of this gene in fetal tissue shows that the protein product enhances skeletal muscle or heart growth and development in the fetus and also acts in a regenerative capacity in the adult. Therapeutic modulation of this gene or its protein product is useful in the treatment of muscular dystrophies or heart disease.
Panel 4D Summary: Gpcr41 Expression ofthe CGI 01340-01 gene was upregulated in several tissues and cell types after activation, including lymphocytes, keratinocytes, basophils, small airway epithelium and T cells. The GPCR encoded by this gene functions in the inflammatory process by promoting leukocyte extravasation or initiating a signaling cascade that results in the release of immunomodulatory products such as cytokines. Antibody or small molecule therapeutics designed against the protein encoded by this gene are useful for the reduction or inhibition of inflammation due to psoriasis, delayed type hypersensitivity, asthma, or emphysema.
B. CG101396-01: GLUTAMATE RECEPTOR DELTA-1
Expression of gene CG 101396-01 was assessed using the primer-probe set Ag4211, described in Table BA. Results ofthe RTQ-PCR mns are shown in Tables BB, BC and BD.
Table BA. Probe Name Ag4211
Figure imgf001072_0001
Figure imgf001072_0002
106δ
Figure imgf001073_0001
Table BC. Panel 4. ID
Figure imgf001073_0002
Figure imgf001074_0001
Table BD. general oncology screening panel_v_2.4
Figure imgf001075_0001
General_screening_panel_vl .4 Summary: Ag4211 Highest expression of the CGI 01396-01 gene was seen in the fetal brain (CT=29). This gene was expressed at moderate levels in all regions ofthe CNS examined. This gene encodes a protein that is homologous to the delta2 glutamate receptor, which is expressed in the cerebellum. This receptor is involved in motor learning and coordination, and synapse plasticity. Based on the prominent expression of this gene product in the CNS, therapeutic modulation of the expression or function of this gene product is useful for the treatment of CNS disorders involving memory deficits, including Alzheimer's disease and aging as well as for motor impairments and learning following stroke-related brain damage.
Among tissues with metabolic function, this gene was expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle and heart. This widespread expression among these tissues shows that this gene product plays a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene contributes to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.
In addition, moderate levels of expression were seen in a cluster of samples derived from ovarian, colon, melanoma and lung cancer cell lines. Thus, expression of this gene is useful as a marker to detect the presence of these cancers. Therapeutic modulation ofthe expression or function of this gene or gene product is effective in the treatment of ovarian, colon, melanoma and lung cancers.
This gene was also expressed at much higher levels in fetal lung tissue (CT=30) when compared to expression in the adult counterpart (CT=35.5). Expression of this gene is useful as a marker to differentiate between the fetal and adult source of this tissue.
Panel 4.1D Summary: Ag4211 Highest expression of this gene was seen in the kidney (CT=30.8). Moderate levels of expression were also seen in the lung and untreated lung microvascular endothelial cells. Low but significant levels of expression were seen in untreated and treated astrocytes and Ramos B cells and activated lung microvascular endothelial cells. Expression in astrocytes was in agreement with the prominent CNS expression seen in Panel 1.4. This expression demonstrates that this gene product is involved in the homeostasis ofthe lung and kidney. Therapeutic modulation ofthe expression of this protein is useful for restoring or maintaining function in these organs during inflammation. general oncology screening panel_v_2.4 Summary: Ag4211 Expression of the CGI 01396-01 gene was detected in a kidney cancer sample (CT=31). Moderate to low expression of this gene was detected in melanoma and prostate cancers. Expression of this gene or its protein product is useful as a marker to detect the presence of these cancers. Therapeutic modulation of the expression or function of this gene product is effective in the treatment of melanoma, kidney and lung cancers.
C. CGI 02348-01: Clr-like proteinase precursor
Expression of gene CGI 02348-01 was assessed using the primer-probe set Ag650, described in Table CA. Results of the RTQ-PCR mns are shown in Table CB. Table CA. Probe Name Ag650
Figure imgf001076_0001
Figure imgf001077_0001
Table CB. Panel 1.1
Figure imgf001077_0002
Figure imgf001078_0001
Panel 1.1 Summary: Ag650 Highest expression of this gene was detected in a lung cancer HOP-62 cell line (CT=22). High levels of expression of this gene were also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, melanoma and brain cancers. Epression of this gene is useful as a marker to detect the presence of these cancers. Therapeutic modulation ofthe expression or function of this gene is effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.
Among tissues with metabolic or endocrine function, this gene was expressed at high levels in pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therapeutic modulation ofthe activity of this gene or its protein product is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
In addition, this gene was expressed at high levels in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
D. CG125860-02: Transmembrane protease, serine 5
Expression of gene CG 125860-02 was assessed using the primer-probe set Agl674, described in Table DA. Results ofthe RTQ-PCR mns are shown in Tables DC,
DD, DE and DF. Table DA. Probe Name Agl674
Figure imgf001079_0001
Table DB. Ardais Prostate 1.0
Figure imgf001079_0002
Figure imgf001080_0001
Table DC. Panel 1.3D
Figure imgf001080_0002
Figure imgf001081_0001
Table DP. Panel 2D
Figure imgf001081_0002
Figure imgf001082_0001
Table DE. Panel 4D
Figure imgf001082_0002
Figure imgf001083_0001
Ardais Prostate 1.0 Summary: Agl674 Expression ofthe CG125860-02 gene was highest in a prostate cancer sample (CT=29.3). This gene was expressed at moderate levels in the majority of samples on this panel, with no apparent disregulation in prostate cancer.
Panel 1.3D Summary: Agl674 Expression of this gene was highest in the hippocampus (CT=29.3). In addition, this gene was expressed at moderate levels in all other regions ofthe central nervous system examined, including amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Expression of this gene or its protein product is useful as a marker for brain tissue. Therapeutic modulation ofthe activity of this gene or its protein product plays a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
Expression ofthe CG125δ60-02 gene was also upregulated in fetal skeletal muscle compared to adult skeletal muscle. The relative overexpression of this gene in fetal tissue demonstrated that the protein product enhances skeletal muscle growth or development in the fetus and also acts in a regenerative capacity in the adult. Therapeutic modulation of this gene or its protein product is useful in the treatment of muscle degenerative diseases, such as muscular dystrophy.
Panel 2D Summary: Agl674 Expression of this gene was highest in a lung cancer sample (CT=29.1) and was significantly downregulated (about 50-fold) in the normal adjacent lung tissue. The CG125δ60-02 gene was also overexpressed in 4 colon cancer samples when compared to the appropriate normal matched colon tissue. Therefore, the CG125δ60-02 gene or protein expression levels are useful as a marker for lung or colon cancer. Gene, protein, antibody or small molecule therapeutics targeting this gene or its protein product are useful in the treatment of lung or colon cancer. Expression of this gene was higher in a number of metastatic tumor samples on this panel, showing that it plays a role in metastasis and is useful as a marker of disease prognosis.
Panel 4D Summary: Agl 674 Expression of this gene was highest in normal kidney (CT=31.δ). This gene was expressed at low but ubiquitous levels in the majority ofthe samples on this panel.
E. CG50235-04: TOLLOID-LIKE 2
Expression of gene CG50235-04 was assessed using the primer-probe set Ag4737, described in Table EA. Results of the RTQ-PCR mns are shown in Tables EB and EC.
10δ0 Table EA. Probe Name Ag4737
Figure imgf001085_0001
Figure imgf001085_0002
Figure imgf001086_0001
Table EC. Panel 4. ID
Figure imgf001086_0002
10δ2
Figure imgf001087_0001
General_screening_panel_vl.4 Summary: Ag4737 Highest expression of this gene was seen in a sample derived from a renal cancer cell line (CT=29.9). This gene showed specific expression restricted to cell lines derived from renal cancer, ovarian cancer and lung cancer. The expression of this gene is useful as marker to detect these cancers. Modulation of this gene, encoded protein and use of small molecule dmgs or antibodies is useful in the treatment of renal, ovarian or lung cancer.
10δ3 This gene was also moderately expressed in several metabolic tissues including adult and fetal heart, pituitary, and skeletal muscle. Thus, this gene is important for the pathogenesis, diagnosis and/or treatment of metabolic diseases, including obesity.
This gene was expressed at low levels in the CNS, except in the spinal cord where expression levels were moderate. Thus, modulation of this gene is useful in treating spinal cord related disorders including spinal cord trauma or spinocerebellar ataxia.
Panel 4.1D Summary: Ag4737 This gene was expressed at moderate levels in TNF-alpha and IL-1 beta treated and resting astrocytes (CTs=32). It was also expressed at a low level in small airway epithelium, and keratinocytes. Expression of this gene was down regulated in both cell types upon treatment with the inflammatory cytokines TNFalpha and IL-1 beta. This gene encodes for a tolloid like 2 protein, a BMP- 1 -related proteinase which was shown to play a role in extracellular matrix biosynthesis (Uzel MI, J Biol Chem 276(25):22537-43). Therefore, modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful to reduce or eliminate the symptoms of inflammatory reactions that occur in multiple sclerosis, and also in chronic obstructive pulmonary disease, asthma, or emphysema, and in inflammatory skin diseases.
F. CG50249-01: VOLTAGE-GATED POTASSIUM CHANNEL PROTEIN KV3.2 (KSHIIIA)
Expression of gene CG50249-01 was assessed using the primer-probe set Ag2503, described in Table FA. Results of the RTQ-PCR mns are shown in Tables FB, FC, FD, FE, FF and FG.
Table FA. Probe Name Ag2503
Figure imgf001088_0001
Table FB. Ardais Breastl.O
Figure imgf001088_0002
Figure imgf001089_0001
10δ5 Table FC. Ardais Panel v.1.0
Figure imgf001090_0001
Table FD. Ardais Prostate 1.0
Figure imgf001090_0002
Figure imgf001091_0001
Table FE. General_screening_panel_vl.4
Figure imgf001091_0002
Figure imgf001092_0001
Table FF. Panel 2D
Figure imgf001092_0002
lOδδ
Figure imgf001093_0001
10δ9 Table FG. Panel 3D
Figure imgf001094_0001
Figure imgf001095_0001
Figure imgf001096_0001
Ardais Breastl.O Summary: Ag2503 Highest expression of this gene was seen in three breast cancer samples (CTs=23.9-25). Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is of use in the treatment of breast cancers.
Ardais Panel v.1.0 Summary: Ag2503 Highest expression of this gene was seen in a lung cancer (369) sample (CT=25). Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is of use in the treatment of lung cancers.
Ardais Prostate 1.0 Summary: Ag2503 Highest expression of this gene was seen in a prostate cancer (BδB) sample (CT=21). This gene showed relatively higher expression in the prostate cancer samples compared to the other samples on this panel. Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is of use in the treatment of prostate cancers.
General_screening_panel_vl.4 Summary: Ag2503 Highest expression of this gene was detected in the thalamus and the cerebral cortex (CTs=25). This gene showed brain preferential expression, with high expression in hippocampus, cortex, amygdala, substantia nigra and thalamus. These regions are susceptible to the neurodegeneration associated with Alzheimer's Disease, Parkinson's disease, Huntington's disease and other pathological neurodegenerative conditions. This gene encodes a protein that is homologous to a potassium channel. Potassium channels play a role in neurodegenerative diseases, including Alzheimer's Disease (Chi X Neurosci Lett 2000 Aug lδ;290(l):9-12; Yu SP Neurobiol Dis 1998 Aug;5(2):81-δ;). Therefore, modulation of this gene or its protein product is useful to reduce the neuronal degeneration in patients with Alzheimer's Disease and other neurodegenerative diseases. Defective potassium channels are known to cause several CNS disorders, including epilepsy and episodic ataxia with myokymia. Therefore, modulation of this gene and/or expressed protein is useful as a treatment for the symptoms produced by ataxia and epilepsy.
Moderate to low expression was also seen in normal prostate and in cell lines derived from breast, lung, and ovarian cancer. Thus, expression of this gene is useful as a diagnostic marker to detect the presence of these cancers. Use of antibodies or small molecule dmg targeting this gene or gene product is useful in the treatment of these cancers.
This gene showed significantly higher levels of expression in the fetal kidney (CTs=30-31) relative to the adult kidney (CTs=35-36). The higher levels of expression in the fetal kidney demonstrate that this gene product is involved in the development of this organ. Modulation of this gene and/or encoded protein is useful in the treatment of kidney related diseases such as lupus erythematus and glomerulonephritis.
Among tissues with metabolic function, the expression of this potassium channel homolog was highest in the pituitary gland. Potassium channels are involved in regulation of secretion in pituitary cells and their modulation by use of small molecule inhibitors or antibodies is important to modulate specific secretory activities in the pituitary.
Panel 2D Summary: Ag2503 The highest level of expression was seen in a breast cancer sample (CTs=25-27). Higher expression of this gene was seen in breast and prostate cancer samples compared to the corresponding normal adjacent tissue. Expression of this gene is useful as a diagnostic marker of these cancers and use of antibodies or small molecule dmg targeting this gene or gene product is useful in the treatment of these cancers.
Panel 3D Summary: Ag2503 The highest level of expression was seen in a lung cancer cell line (NCI-H146) (CTs=30-33.4). Low expression of this gene was observed in normal cerebellum and cell lines derived from lung cancer, and medulloblastoma. The expression of this gene is useful as a diagnostic marker for lung cancer and use of antibodies, protein therapeutics or small molecule dmg is beneficial in the treatment of lung cancer.
G. CG50307-03: Steroid Dehydrogenase
Expression of full-length physical clone CG50307-03 was assessed using the primer-probe sets Ag2248 and Ag2548, described in Tables GA and GB. Results ofthe RTQ-PCR mns are shown in Tables GC, GD, GE, GF and GG.
Table GA. Probe Name Ag224δ
Figure imgf001097_0001
Table GB. Probe Name Ag2548
Figure imgf001098_0001
Table GC. Panel 1.3D
Figure imgf001098_0002
Figure imgf001099_0001
Table GD. Panel 2D
Figure imgf001099_0002
Figure imgf001100_0001
Table GE. Panel 3D
Figure imgf001101_0001
Figure imgf001102_0001
109δ Table GF. Panel 4D
Figure imgf001103_0001
Figure imgf001104_0001
Table GG. Panel 5 Islet
Figure imgf001104_0002
Figure imgf001105_0001
Panel 1.3D Summary: Ag2248/Ag2548 Highest expression of this gene was detected seen in regions ofthe brain (CTs=28-29).
This gene encodes a protein that is homologous to steroid dehydrogenase. Steroid treatment is used in a number of clinical conditions including Alzheimer's disease (estrogen), treatment of symptoms associated with menopause (estrogen), multiple sclerosis (glucocorticoids), and spinal cord injury (methylprednisolone). Treatment with an antagonst of this gene product, or reduction ofthe levels of this gene product is useful for the inhibition of steroid degredation and for lowering the necessary amount given for a therapeutic effect, thus reducing peripheral side effects.
This gene was moderately expressed in a variety of metabolic tissues including pancreas, adrenal, thyroid, pituitary, adult and fetal heart, adult and fetal skeletal muscle, fetal liver, and adipose. This gene product is a small molecule drug target for the treatment of metabolic disease, including obesity and Types 1 and 2 diabetes.
The ubiquitous expression of this gene in this panel also showed that the protein encoded by this gene plays a role in cell survival and proliferation for a majority of cell types. There are significant levels of expression in the lung cancer cell line SHP-77. Expression of this gene is of use as a diagnostic marker for lung cancer. Modulation of the gene product is useful in the treatment of lung cancer
Panel 2D Summary: Ag224δ/Ag254δ The highest level of expression was seen in a breast cancer sample (CTs=27-29). In addition, this gene was overexpressed in ovarian, gastric, breast, uterine, lung and colon cancers relative to the normal adjacent tissues from these patients. The expression of this gene is of use as a diagnostic marker for the presence of these cancers. Therapeutic inhibition ofthe activity of this gene product is effective in the treatment of these cancers.
Panel 3D Summary: Ag254δ This gene was expressed at a low to moderate level in most ofthe cells and tissues used in this panel, with highest expression in the small cell lung cancer cell line DMS-79 (CT=27.79). This ubiquitous expression showed that the gene product plays a role in cell survival and proliferation for a majority of cell types except cell lines derived from tongue squamous cell carcinoma. Panel 4D Summary: Ag2248 This gene encodes a steroid dehydrogenase-like protein and was expressed at moderate levels (CT=28-32) in numerous immune cell types and tissues. Small molecule antagonists that block the function ofthe steroid dehydrogenase-like protein encoded by this gene are useful as therapeutics that reduce or eliminate the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.
Panel 5 Islet Summary: Ag224δ The expression of this novel steroid dehydrogenase-like gene was highest in the liver HepG2 cell line, (CT=32.1). Lower but still significant levels of expression were seen in several placenta samples, uterine smooth muscle, adipose samples, differentiated mesenchymal stem cells, and kidney and skeletal muscle from a diabetic patient. Expression in liver cells and placenta showed that the role of this novel steroid dehydrogenase is similar to the role of other steroid dehydrogenases which are involved in steroid and bile acid metabolism. Very low expression of this gene was also seen in a human pancreatic islet sample. Therefore, small molecule therapeutics against this gene product are effective in disorders in which expression of this gene is dysregulated.
H. CG50315-01: Olfactory Receptor
Expression of full-length physical clone CG50315-01 was assessed using the primer-probe sets Agl665 and Ag2542, described in Tables HA and HB. Results ofthe RTQ-PCR mns are shown in Tables HC, HD, and HE.
Table HA. Probe Name Agl665
Figure imgf001106_0001
Table HB. Probe Name Ag2542
Figure imgf001106_0002
Table HC. PGI 1.0
Figure imgf001107_0001
Table HD. Panel 2D
Figure imgf001107_0002
Figure imgf001108_0001
Figure imgf001109_0001
Table HE. Panel 4D
Figure imgf001109_0002
Figure imgf001110_0001
Figure imgf001111_0001
PGI1.0 Summary: Ag2542 Expression of this gene was highest in a lung fibrosis sample (CT=31). Expression of this gene was also significantly upregulated in another lung fibrosis sample as well as an asthmatic lung sample; more modest overexpression was seen in lung samples from patients with emphysema. Thus, gene or protein levels are useful for the detection of lung diseases such as lung fibrosis, emphysema and asthma. Furthermore, therapeutic modulation ofthe activity of this gene or its protein product is useful in the treatment of lung fibrosis, emphysema or asthma.
Panel 2D Summary: : Agl 665 The expression of this gene was low in the samples on Panel 2D. The highest expression was associated with a sample of normal kidney (CT = 32.9). In addition, there was a cluster of expression associated with normal kidney tissue when compared to malignant kidney tissue. Thus, the loss of expression of this gene was associated with kidney cancer, and as such, therapeutic application ofthe protein or its replacement by gene therapy is of use in the treatment of kidney cancer.
Panel 4D Summary: Agl665/Ag2542 Mmoderate expression of this gene was seen in one IBD colitis sample, with lower expression in a second colitis sample in 3 (of 4 possible) experiments. In addition, low expression was detected in liver cirrhosis (CT = 32.7) and thymus (CT = 35) in 3 (of 4 possible) determinations. The function ofthe GPCR encoded by this gene is important in the disease processes in both inflammatory bowel disease and in liver cirrhosis. Therefore, blocking antibodies or small molecule antagonists targeted to this GPCR are useful as therapeutics in colitis and in cirrhosis.
I. CG50341-01: GPCR
Expression of gene CG50341-01 was assessed using the primer-probe set Agl 201, described in Table IA. Results ofthe RTQ-PCR mns are shown in Tables IB, IC and ID.
Table IA. Probe Name Agl 201
Figure imgf001112_0001
Table IB. Panel 1.3D
Figure imgf001112_0002
Figure imgf001113_0001
Kidney 0.0 0.0 0.0 Adipose 0.0 12.0 0.0
Table IC. Panel 2D
Figure imgf001114_0001
Figure imgf001115_0001
Table ID. Panel 4D
Figure imgf001115_0002
Figure imgf001116_0001
Panel 1.3D Summary: Agl 201 Tissue expression of this was detected at a low level in many tissues. The highest expression was seen in testis. Expression of this gene or its protein product is useful as a marker for male germ cells and has therapeutic applications in fertility disorders as a potential target.
Panel 2D Summary: Agl 201 This gene was overexpressed in tumors derived from tissues responsive to steroid hormones- ovarian, uterine and prostate cancers as shown by panel 2D. It is therefore a marker for cells, especially tumor cells responsive to steroid hormones. Expression of this gene or its protein product are used to differentiate hormone-responsive and non-hormone responsive tumors, that are known to lead to different clinical outcomes. Being a GPCR, the protein is useful to screen candidate therapeutics for molecules able to modulate tumor growth, preferably small molecule therapeutic and human monoclonal antibodies.
Panel 4D Summary: Agl201 The pattern of expression in panel 4 showed that Agl 201 has a potential role in inflammation, since this gene was expressed in activated basophils. Basophils are one ofthe key cell mediators of inflammation during asthma and allergy (Oliver J, Imrnunopharmacology 2000 Jul 25;4δ(3):269-δl). This molecule is important in allowing these cells to extravasate into the site of inflammation and/or in the activation of these cells. Antibody therapeutics to Agl 201 are useful for the inhibition of nasal and lung inflammation due to basophil activation and effectively reduce or eliminate symptoms of asthma, emphysema, and allergic rhinitis.
J. CG50365-01: Carbonate Dehydratase
Expression of gene CG50365-01 was assessed using the primer-probe sets Ag2575 and Ag2644, described in Tables JA and JB. Results ofthe RTQ-PCR mns are shown in Tables JC, JD, JE and JF.
Table JA. Probe Name Ag2575
Figure imgf001117_0001
Table JB. Probe Name Aε2644
Primers] Sequences Length Start SEQ DD
Figure imgf001118_0001
Table JC. Panel 1.3D
Figure imgf001118_0002
Figure imgf001119_0001
Table JP. Panel 2D
Figure imgf001119_0002
Figure imgf001120_0001
Table JE. Panel 3D
Figure imgf001120_0002
Figure imgf001121_0001
Figure imgf001122_0001
Table JF. Panel 4D
Figure imgf001122_0002
Figure imgf001123_0001
Panel 1.3D Summary: Ag2575 The expression ofthe CG50365-01 gene highest in a sample derived from a gastric cancer cell line (NCI-H87)(CTs=31). In addition, there was substantial expression in several colon cancer cell lines, ovarian cancer cell lines and brain cancer cell lines. Thus, the expression of this gene is useful as a marker to distinguish NCI-Hδ7 cells from other samples in the panel. Therapeutic modulation of this gene, through the use of small molecule dmgs, antibodies or protein therapeutics is of benefit in the treatment of colon cancer, brain cancer or ovarian cancer.
In addition, this gene was expressed at low levels in the cerebral cortex. Carbonate dehydratase plays an important role in modulating excitatory synaptic transmission in brain. (Parkkila S. Proc Natl Acad Sci U S A 2001 Feb 13;98(4):1918- 23) Therefore, this molecule is of use in the treatment of schizophrenia, epilepsy, Alzheimer's disease, bipolar disorder, depression, or any clinical condition associated with impaired or altered neurotransmission.
Panel 2D Summary: Ag2644 The expression ofthe CG50365-01 gene was highest in a sample derived from a gastric cancer. In addition there was substantial expression associated with other gastric cancers, when compared to their adjacent normal tissues, as well as expression associated with ovarian cancer, breast cancer, thyroid cancer and colon cancer. This expression conformed with expression in Panel 1.3D. Expression of this is useful as a marker to distinguish this gastric cancer sample from other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule dmgs, antibodies or protein therapeutics is of benefit in the treatment of colon cancer, breast cancer, ovarian cancer, gastric cancer or thyroid cancer.
Panel 3D Summary: Ag2644 The expression ofthe CG50365-01 gene was highest in a sample derived from a lung cancer cell line (DMS-79). In addition there was expression associated with a colon cancer cell line, a gastric cancer cell line and a pancreatic cancer cell line. Thus, the expression of this gene is useful as a marker to distinguish DMS-79 cells from other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule dmgs, antibodies or protein therapeutics is of benefit in the treatment of colon cancer, pancreatic cancer, gastric cancer or lung cancer.
Panel 4D Summary: Ag2644 The CG50365-01 transcript was expressed in lung fibroblasts treated with gamma interferon, NCI-H292 cells regardless of treatment, activated basophil cell line, and gamma interferon treated HUVECs. It was also expressed in normal colon and thymus. The regulation of the transcript expression in fibroblasts and HUVECs showed that the protein encoded by this transcript contributes to the inflammatory changes due to gamma interferon. Therefore, therapies designed with the protein encoded by this transcript are important for the treatment of emphysema, psoriasis, arthritis and IBD.
K. CG50367-01: adaml3
Expression of gene CG50367-01 was assessed using the primer-probe set Ag2425, described in Table KA. Results ofthe RTQ-PCR mns are shown in Tables KB, KC, KD and KE.
Table KA. Probe Name Ag2425
Figure imgf001125_0001
Table KB. Ardais Prostate 1.0
Figure imgf001125_0002
Figure imgf001126_0001
Table KC. Panel 1.3D
Figure imgf001126_0002
Figure imgf001127_0001
Table KD. Panel 2D
Figure imgf001127_0002
Figure imgf001128_0001
Table KE. Panel 4D
Column A - - Rel. Exp.(%) Ag2425, Run 155562267
Tissue Name A Tissue Name A
Secondary Thl act 0.0 HUVEC IL-lbeta 0.0
Figure imgf001129_0001
Figure imgf001130_0001
Ardais Prostate 1.0 Summary: Ag2425 Expression of the CG50367-01 gene was highest in a prostate cancer sample (CT=2δ.3), with expression of this gene slightly downregulated in most ofthe prostate cancer samples.
Panel 1.3D Summary: Ag2425 Highest expression ofthe CG50367-01 gene was seen in fetal skeletal muscle (CT=31.1). This gene was highly expressed in fetal skeletal muscle when compared to expression in adult skeletal muscle (CT=40).Thus expression of this gene is useful as a marker differentiate between fetal and adult skeletal muscle. Furthermore, the higher levels of expression in the fetal source ofthe tissue show that the protein encoded by this gene is involved in the development ofthe skeletal muscle in the fetus. Therapeutic modulation ofthe expression or function of this gene is useful for restoring muscle mass or function to weak or dystrophic muscle in the adult.
This gene was expressed at a very low level in all the cancer cell lines used in this panel. The absence of exprssion of this gene in the cancer cell lines showed that modulation ofthe function ofthe gene product through the use of peptides, polypeptides, chimeric molecules or small molecule dmgs, aree useful in the therapy of cancer.
This gene is a cell-surface metalloprotease expressed at low levels in the hippocampus. It is useful in the treatment of diseases in which the hippocampus is involved, such as Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, or temporal lobe epilepsy.
Panel 2D Summary: Ag2425 The CG50367-01 gene was expressed at low levels in this panel, with highest expression in the colon (CT=32.2). Moderately higher levels of expression were seen in normal breast, uterine and thyroid tissues compared to the adjacent cancers. Expression of this gene is useful as a marker to identify normal tissue from cancerous tissue in these organs. Therapeutic modulation ofthe activity of the product of this gene, through the use of peptides, polypeptides, chimeric molecules or small molecule dmgs, is useful in the therapy of these cancers.
Panel 4D Summary: Ag2425 The CG50367-01 transcript was most highly expressed in dermal fibroblast upon treatment with either 11-4 or IFN gamma (CTs=31- 32) and at lower levels in resting dermal fibroblasts. This transcript was also expressed in lung fibroblasts and normal lung and thymus. This transcript encodes for a ADAM like protein, a member of membrane-anchored glycoproteins that play a role in diverse cellular processes from cell-cell interaction to shedding of cell surface proteases. The expression of this transcript in dermal and lung fibroblasts showed that the protein encoded by this transcript is involved in diseases associated with fibrosis or fϊbroplasia. Modulation of the expression or the function of this molecule is useful for the treatment of psoriasis, chronic obstructive pulmonary diseases and potentially for osteoarthritis and rheumatoid arthritis.
L. CG50718-02 and CG50718-06: GLOMERULAR MESANGIAL CELL RECEPTOR PROTEIN-TYROSINE PHOSPHATASE PRECURSOR,
Expression of gene CG50718-02 and variant CG50718-06 was assessed using the primer-probe sets Agl 555 and Ag2315, described in Tables LA and LB. Results of the RTQ-PCR mns are shown in Tables LC, LD, LE, and LF.
Table LA. Probe Name Agl 555
Figure imgf001131_0001
Table LB. Probe Name Ag2315
Figure imgf001131_0002
Table LC. Panel 1.3D
Column A - Rel. Exp.(%) Agl555, Run 146380268 Column B - Rel. Exp.(%) Agl555, Run 147775028
Tissue Name B Tissue Name B
Figure imgf001132_0001
Figure imgf001133_0001
Table LD. Panel 2D
Figure imgf001133_0002
Figure imgf001134_0001
Table LE. Panel 4D
Figure imgf001135_0001
Figure imgf001136_0001
Table LF. Panel 5D
Figure imgf001136_0002
Figure imgf001137_0001
Panel 1.3D Summary: Agl 555 Highest expression of this gene was seen in the fetal lung (CTs=32). Modulation of this gene is useful in the treatment of lung related diseases.
Low but significant expression was also seen in the thyroid. Biologic cross-talk between the thyroid and adipose tissue is believed to be a component of some forms of obesity. Modulation of this gene and/or encoded protein is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
Panel 2D Summary: Agl 555/2315 Highest expression of this gene was detected in normal kidney tissue (CTs=30.7-32.4). Significant levels of expression of this was also seen in samples derived from normal lung tissue. This gene was preferentially expressed in healthy tissue relative to adjacent cancerous tissue. Modulation of this gene, encoded protein and/or use of small molecule dmgs or antibodies targeting this gene is useful in the treatment of kidney cancer and lung cancer.
Panel 4D Summary: Agl555/Ag2315 This gene was detected at significant levels in the thymus (CT=31.5) and dermal fibroblasts (CT=34). Modulation of this gene, encoded protein and or use of antibodies or small molecule dmg targeting this gene or gene product is useful in maintaining or restoring the normal function to these organs during inflammation.
Panel 5D Summary: Ag2315 This gene showed significant expression in human adipose tissue and in cultured human adipocytes (CT=31-34). Modulation of this gene or gene product is useful in the treatment of obesity.
M. CG50934-03: MASTOCYTOMA PROTEASE PRECURSOR Expression of full-length physical clone CG50934-03 was assessed using the primer-probe set Ag6974, described in Table MA. Results ofthe RTQ-PCR mns are shown in Table MB.
Table MA. Probe Name Ag6974
Figure imgf001138_0001
Figure imgf001138_0002
Figure imgf001139_0001
General_screening_panel_vl.6 Summary: Ag6974 Highest expression of this gene was detected in an ovarian cancer OVCAR-5 cell line (CT=2δ). This gene showed preferential expression in colon cancer tissue and a number of cancer cell lines derived from pancreatic, colon, gastric, lung, breast and ovarian cancers. Expression of this gene is useful as diagnostic marker to detect these cancers and also, modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is useful in the treatment of these cancers.
N. CG51213-01 and CG51213-04: ZINC METALLOENDOPEPTIDASE
Expression of gene CG51213-01 and CG51213-04 was assessed using the primer-probe sets Agδl3, and Ag39δ5, described in Tables NA and NB. Results of the RTQ-PCR mns are shown in Tables NC, ND NE and NF. Please note that the primer- probe set Ag39δ5 is specific for CG51213-04 only.
Table NA. Probe Name Ag l 3
Figure imgf001139_0002
Figure imgf001140_0001
Table NB. Probe Name Ag3985
Figure imgf001140_0002
Table NC. AI_comprehensive panel vl .0
Figure imgf001140_0003
Figure imgf001141_0001
Figure imgf001142_0001
Table ND. General_screening_panel_vl.5
Figure imgf001142_0002
Figure imgf001143_0001
Table NE. Panel 4.1D
Figure imgf001143_0002
Figure imgf001144_0001
Table NF. Panel 5 Islet
Column A - Rel. Exp.(%) Ag813, Run 254387841
Figure imgf001145_0001
AI_comprehensive panel_vl.O Summary: Ag3985/Agδl3 Highest expression of this gene was detected in samples from an osteoarthritic bone sample and synovium
(CTs=30). Significant expression of this gene was detected in samples derived from orthoarthitis bone, cartilage, synovium and synovial fluid samples, from normal lung,
COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is useful for the amelioration of symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, and osteoarthritis.
General_screening_panel_vl.5 Summary: Agδl3 Highest expression of this gene was detected in fetal brain and a brain cancer SNB-75 cell line (CTs=31). In addition, moderate expression of this gene was seen in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene codes for a variant of ADAMTS- 10, a member of Matrix metalloproteinases (MMPs). MMPs are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components ofthe basal lamina, leading to disruption ofthe blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases (Rosenberg GA, 2002, Glia 39(3):279-91, PMID: 12203394). Modulation of this gene, encoded protein and/or use of antibodies of small molecule dmg targeting this gene or gene product is useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia, depression, allergic encephalomyelitis (EAE), allergic neuritis (EAN), and cerebral ischemia.
Moderate to low levels of expression of this gene were also detected in tissues with metabolic/endocrine function including pancreas, adipose, adrenal gland, skeletal muscle, heart, fetal liver and the gastrointestinal tract. Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
This gene was expressed at moderate to low levels in number of cancer cell lines derived from melanoma, ovarian, breast, lung, renal, colon and brain cancers. Modulation of this gene, encoded protein and/or use of antibodies or small molecule dmg targeting this gene or gene product is useful in the treatment of these cancers.
Panel 4.1D Summary: Ag813/Ag3985 Highest expression of this gene was detected in IL-2 treated resting NK cells and lung microvascular endothelial cells (CTs=31-32.δ). Moderate to low levels of expression of this gene were also detected in activated primary polarized T cells, eosinophils, lung microvascular endothelial cells, coronery artery SMC, liver cirrhosis and activated dermal fibroblasts. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of autoimmune and inflammatory diseases including asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.
Panel 5 Islet Summary: Ag l3 Highest expression of this gene was detected in differentiated adipose cells (CT=33.5). Low expression of this gene was seen mainly in adipose and small intestine. Therefore, modulation of this gene and/or encoded protein is useful in the treatment of obesity and diabetes, including Type II diabetes.
O. CG51448-01 and CG51448-05: MYOSIN, LIGHT POLYPEPTD3E KINASE
Expression of gene CG51448-05 was assessed using the primer-probe sets Agl289 and Ag764, described in Tables OA and OB. Results ofthe RTQ-PCR mns are shown in Tables OC, OD and OE.
Table OA. Probe Name Agl2δ9
Figure imgf001147_0001
Table OB. Probe Name Ag764
Figure imgf001147_0002
Table OC. AI_comprehensive panel vl .0
Figure imgf001147_0003
Figure imgf001148_0001
Figure imgf001149_0001
Table OD. Panel 1.3D
Figure imgf001149_0002
Figure imgf001150_0001
Table OE. Panel 4D
Figure imgf001150_0002
Figure imgf001151_0001
Figure imgf001152_0001
AI_comprehensive panel_vl.O Summary: Agl289/Ag764 This gene was moderately expressed in a synovium sample from an osteoarthritis patient. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule dmgs targeting the gene or gene product is useful in the treatment of osteoarthritis.
The gene variant recognized by probe Ag764 was expressed in a Crohn's disease sample. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule dmgs targeting the gene or gene product are useful in the treatment of Crohn's disease.
Panel 1.3D Summary: Agl2δ9 Expression of this gene was highest among normal tissues in skeletal muscle, where it is expressed at roughly 10-fold higher levels than fetal skeletal muscle. Therefore, this gene is useful as a marker to differentiate between adult and fetal skeletal muscle.
This gene was also expressed at low levels in thyroid. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule dmgs targeting the gene or gene product is useful in the treatment of endocrine or metabolically related diseases, such as obesity and diabetes.
Panel 4D Summary: Ag764 This gene was highly expressed in untreated endothelial cells including the microvascular endothelium, human umbilical vein endothelial cells (HUVECS) and lung endothelial cells. This transcript was highly expressed in normal tissue and down regulated in activated endothelium. This gene encodes a protein important for a pathway that is involved in maintaining cellular homeostasis with in a tissue. A protein therapeutic designed with the protein encoded for by this transcript is useful for the reduction or elimination of inflammation in endothelium. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of asthma, allergy, psoriasis and arthritis.
P. CG51752-01 and CG51752-02 and CG51752-03: trypsin family serine protease Tespec PRO-3 Expression of gene CG51752-01, variant CG51752-02 and full-length physical clone CG51752-03 was assessed using the primer-probe sets Agl 541 and Ag346, described in Tables PA and PB. Results ofthe RTQ-PCR rans are shown in Tables PC and PD. Please not that the primer-probe set Agl 541 is specific for CG51752-01 and CG51752-02 only.
Table PA. Probe Name Agl 541
Figure imgf001153_0001
Table PB. Probe Name Ag346
Figure imgf001153_0002
Table PC. Panel 1.3D
Figure imgf001153_0003
Figure imgf001154_0001
Figure imgf001155_0001
Table PD. Panel 2D
Figure imgf001155_0002
Figure imgf001156_0001
Panel 1.3D Summary: Ag346/Agl541 The expression of this gene was only detected in the testis (CT=31). Gene or protein expression levels of this gene are useful as a marker for the detection of testis tissue. Therapeutic modulation ofthe activity of this gene or its protein product is useful for the treatment of male infertility. Panel 2D Summary: Agl 541 Expression of this gene was highest in normal kidney (CT=31-32). This gene was significantly overexpressed in δ/9 normal kidney samples when compared to the adjacent tumor samples. Therefore, the gene or protein expression levels are useful as a marker to distinguish normal kidney from kidney tumors. Therapeutic modulation ofthe activity of this gene or its protein product using protein, antibody or small molecule drags is useful in the treatment of kidney cancer.
Q. CG51914-02: EPHRIN TYPE-A RECEPTOR 7 PRECURSOR
Expression of gene CG51914-02 was assessed using the primer-probe set Ag612, described in Table QA. Results ofthe RTQ-PCR rans are shown in Tables QB, QC and QD.
Table QA. Probe Name Ag612
Figure imgf001157_0001
Figure imgf001157_0002
Figure imgf001158_0001
Table QC. Panel 1.1
Figure imgf001158_0002
Figure imgf001159_0001
Table OD. Panel 4D
Figure imgf001159_0002
Figure imgf001160_0001
CNS_neurodegeneration_vl.O Summary: Ag612 This gene was found to be down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, upregulation of this gene, encoded protein, and/or use of agonists for this receptor is useful in reversing the dementia/memory loss associated with this disease and neuronal death.
Panel 1.1 Summary: Ag612 Highest expression of this gene was detected in a lung cancer NCI-H522 cell line (CT=24). High expression of this gene was also seen in cluster of lung cancer, colon cancer, renal cancer, a liver cancer, two breast cancer and a melanoma cell lines. Levels of expression of this gene are useful as diagnostic markers and modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatments of this cancers.
In addition, high expression of this gene was seen in all the regions ofthe central nervous system (CNS) examined including, amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of CNS disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression and therapeutic modulation of this gene product may be useful in the treatment of these disorders.
Among tissues with metabolic or endocrine function, this gene was expressed at high to moderate levels in pancreas, adrenal gland, pituitary gland, and the gastrointestinal tract. Modulation of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes
Panel 4D Summary: Ag612 Highest expression of this gene was detected in IFN gamma treated NCI-H292 cells (CT=33). Moderate to low expression of this gene was also seen in cytokine treated and untreated NCI-H292 cells, liver cirrhosis and colon tissue samples. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene is useful for the treatment of chronic obstructive pulmonary disease, asthma, allergy, and emphysema, liver cirrhosis, autoimmune and inflammatory disease affecting colon including Crohn's disease and ulcerative colitis.
R. CG51965-01: PROTOCADHERIN FLAMINGO 2 LIKE
Expression of gene CG51965-01 was assessed using the primer-probe sets Agl 989 and Agl 990, described in Tables RA and RB. Results ofthe RTQ- PCR rans are shown in Tables RC, RD, RE and RF.
Table RA. Probe Name Agl9δ9
Figure imgf001161_0001
Table RB. Probe Name Agl 990
Figure imgf001162_0001
Table RC. Al comprehensive panel_vl.O
Figure imgf001162_0002
Figure imgf001163_0001
Table RD. Panel 1.3D
Figure imgf001163_0002
Figure imgf001164_0001
Figure imgf001165_0001
Table RE. Panel 2D
Figure imgf001165_0002
Figure imgf001166_0001
Table RF. Panel 4. ID
Figure imgf001166_0002
Figure imgf001167_0001
Figure imgf001168_0001
AI_comprehensive panel_vl.O Summary: Agl9δ9/Agl990 The highest expression of this gene was detected in an osteoarthritic bone sample (CT=29). The expression of this gene was upregulated in bone, synovium, synovial fluid, and cartilage in patients with rheumatoid arthritis (RA) (CTs = 29-30) compared to normal controls (CTs=32-3δ). In addition, expression of this gene was upregulated in lung samples from patients with asthma compared to normal lung controls (CT values = 29-30 for patients with asthma versus 34-36 for normal controls). Therefore, expression of this gene is useful as a marker to identify samples from patients with rheumatoid arthritis or asthma. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of rheumatoid arthritis or asthma.
Panel 1.3D Summary: Agl989/Agl990 This gene was strongly expressed in most tumor cell lines in this panel, while the expression in most normal tissues was moderate or low. Expression of this gene was up-regulated in a subset of glioma, astrocytoma, pancreatic, colon, kidney, lung, breast and ovarian cancer cell lines. Therefore, expression of this gene is useful in the detection and diagnosis of these types of cancer. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of brain, pancreatic, colon, kidney, lung, breast and ovarian cancer.
Panel 2D Summary: Agl 9δ9/ Agl 990 The highest expression of this gene was detected in a metastatic breast cancer sample (CT=25). For all tumor sites there were several cases where the tumor tissues strongly overexpressed the CG53971-01 gene as compared to the normal adjacent controls, especially for lung, breast and ovarian cancers, indicating a role in tumorgenesis. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of cancers including brain, pancreatic, colon, kidney, lung, breast and ovarian cancers.
Panel 4.1D Summary: Agl9δ9 Expression of this gene was highest in kidney
(CT = 28.2). In addition, this gene was expressed at moderate levels in the lung cell line NCI-H292 and keratinocytes, irrespective of treatment. Expression of this gene was also up-regulated approximately two-fold in activated small airway epithelium, consistent with a potential role for the CG53971-01 gene in asthma and emphysema. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of asthma or emphysema.
S. CG51983-05: A DISINTEGRIN AND METALLOPROTEINASE
7
Expression of gene CG51983-05 was assessed using the primer-probe set Agl 322, described in Table SA. Results ofthe RTQ-PCR rans are shown in Table SB. Table SA. Probe Name Agl 322
Figure imgf001169_0001
Table SB. Panel 1.2
Figure imgf001169_0002
Figure imgf001170_0001
Panel 1.2 Summary: Agl 322 Expression of this gene was highest in testis (CT value = 29). Low expression was also seen in prostate (CT value = 34.6). The gene or encoded protein is useful as a marker for these tissues. This gene encodes a protein with homology to ADAM proteins, which are membrane disintegrin-metalloproteases. The expression of several other ADAM proteins has been shown to be testis-specific and these proteins are thought to play a role in fertilization (Hooft van Huijsduijnen R. (1998) Gene 206: 273-282). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of diseases ofthe prostate and testis, including infertility.
T. CG53390-02: Olfactory Receptor Expression of gene CG53390-02 was assessed using the primer-probe sets Agl5δδ and Ag2015, described in Tables TA and TB. Results ofthe RTQ-PCR rans are shown in Tables TC, TD and TE.
Table TA. Probe Name Agl5δδ
Figure imgf001171_0001
Table TB. Probe Name Ag2015
Figure imgf001171_0002
Table TC. Panel 1.3D
Figure imgf001171_0003
Figure imgf001172_0001
Kidney ] o 0.0! 0.0 Adipose 0.0 0.0 0.0
Table TD. Panel 2D
Figure imgf001173_0001
Figure imgf001174_0001
Table TE. Panel 4D
Figure imgf001174_0002
Figure imgf001175_0001
Panel 1.3D Summary: Agl5δ8/Ag2015 Highest expression was detected in a lung cancer cell line (CTs=29).
Panel 2D Summary: Ag2015 Highest expression was detected in normal liver tissue (CT=33)
Panel 4D Summary: Ag2015 Highest expression was detected in liver cirrhosis (CTs=32-34).
U. CG53530-03: Olfactory Receptor
Expression of full-length physical clone CG53530-03 was assessed using the primer-probe set gl 194 described in Table UA. Results ofthe RTQ-PCR runs are shown in Table UB
Table UA. Probe Name Agl 194
Figure imgf001176_0001
Table UBPanel 1.3D
Figure imgf001176_0002
Figure imgf001177_0001
Panel 1.3D Summary: Agl 194 Expression ofthe CG53530-03 gene was highest in colon (CT=32.4) and was primarily associated with normal tissue. Significant gene expression was also detected in bladder, pancreas, and testis. Expression of this gene was downregulated in colon and pancreatic cancer cell lines when compared to the appropriate normal controls. Therapeutic modulation ofthe activity of this gene or its protein product using nucleic acid, protein, antibody or small molecule drags is useful in the treatment of colon or pancreatic cancer.
Panel 2D Summary: Agl 194 Prominent expression was detected in normal colon and bladder tissues, in agreement with the results in Panel 1.3D. This gene was expressed at higher levels in normal colon and bladder tissues than in malignant colon and bladder tissues. Targeting this gene or its protein product with small molecule, antibody, or protein therapeutics is useful in the treatment of colon and bladder cancers.
V. CG53719-02: Olfactory Receptor
Expression of gene CG53719-02 was assessed using the primer-probe set Ag379, described in Table VA. Results ofthe RTQ-PCR runs are shown in Tables VB and VC. Table VA. Probe Name Ag379
Figure imgf001178_0001
Table VB. Panel 1.3D
Figure imgf001178_0002
Figure imgf001179_0001
Table VC. Panel 4. ID
Figure imgf001179_0002
Figure imgf001180_0001
Panel 1.3D Summary: Ag379 Highest expression of this gene was detected in testis (CTs=32-33). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of disorders ofthe testis, such as infertility.
Panel 4.1D Summary: Ag379 Highest expression of this gene was detected in NCI-H292 cells stimulated by IFN-gamma (CT=34). The gene was also expressed in untreated samples from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The expression ofthe transcript in a mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) showed that this transcript may be important in the proliferation or activation of airway epithelium. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.
W. CG53746-04: ODORANT RECEPTOR S25
Expression of full-length physical clone CG53746-04 was assessed using the primer-probe set Ag2690, described in Table WA. Results ofthe RTQ-PCR runs are shown in Tables WB and WC.
Table WA. Probe Name Ag2690
Figure imgf001181_0001
Table WB. Panel 2D
Figure imgf001181_0002
Figure imgf001182_0001
Figure imgf001183_0001
Table WC. Panel 4D
Figure imgf001183_0002
Figure imgf001184_0001
Panel 2D Summary: Ag2690 Highest expression of this gene was seen in normal lung tissue (CT=30)/. In addition, this gene was overexpressed in normal lung tissue when compared to expression in adjacent malignant tissue. Thus, expression of this gene is useful as a marker of lung cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is usefiil in the treatment of lung cancer.
Panel 4D Summary: Ag2690 Highest expression of this gene was seen in IL-4 treated NCI-H292 cells, a human airway epithelial cell line that produces mucins (CT=28). This gene was also expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line. Mucus overproduction is an important feature of bronchial asthma and chronic obstractive pulmonary disease samples. The transcript was also expressed at lower but still significant levels in small airway epithelium treated with IL-1 beta and TNF-alpha. The expression ofthe transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) showed that this transcript is important in the proliferation or activation of airway epithelium. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product is useful in the treatment of inflammation in lung epithelia in chronic obstractive pulmonary disease, asthma, allergy, and emphysema. X. CG53767-02: Olfactory Receptor
Expression of full-length physical clone CG53767-02 was assessed using the primer-probe sets Ag2687 and Ag440, described in Tables XA and XB. Results of the RTQ-PCR rans are shown in Table XC.
Table XA. Probe Name Ag2687
Figure imgf001185_0001
Table XB. Probe Name Ag440
Table XC. Panel 4D
Figure imgf001185_0003
Figure imgf001186_0001
Panel 4D Summary: Ag26δ7 Highest expression of this gene was seen in IL-4 treated NCI-H292 cells, a human airway epithelial cell line that produces mucins (CT=2δ.δ). The gene was also expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line. Mucus oveφroduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The transcript was
llδ2 also expressed at lower but significant levels in small airway epithelium treated with IL- 1 beta and TNF-alpha. CG53767-02 gene expression in a mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) showed that this gene is important in the proliferation or activation of airway epithelium. Therapeutic modulation ofthe activity of this gene or its protein product using nucleic acid, protein, antibody or small molecule drags is useful in reducing or eliminating the symptoms caused by inflammation in lung epithelia in chronic obstractive pulmonary disease, asthma, allergy, and emphysema.
Y. CG53776-02: Olfactory Receptor
Expression of full-length physical clone CG53776-02 was assessed using the primer-probe set Ag70δl, described in Table YA. Results ofthe RTQ-PCR runs are shown in Table YB.
Table YA. Probe Name Ag7081
Figure imgf001187_0001
Figure imgf001187_0002
ι iδ3
Figure imgf001188_0001
General_screening_panel_vl.6 Summary: Ag7081 Low but significant expression of this gene was detected in fetal lung (CT=34.3). The relative overexpression of this gene in fetal lung showed that the protein enhances lung growth or development in the fetus and also acts in a regenerative capacity in the adult.
Z. CG53803-02: Olfactory Receptor Expression of full-length physical clone CG53803-02 was assessed using the primer-probe set Ag201δ, described in Table ZA. Results ofthe RTQ-PCR runs are shown in Tables ZB and ZC.
Table ZA. Probe Name Ag201δ
Figure imgf001189_0001
Table ZB. Panel 2D
Figure imgf001189_0002
Figure imgf001190_0001
Table ZC. Panel 4D
Figure imgf001190_0002
Figure imgf001191_0001
Panel 2D Summary: Ag201 Significant expression of this gene was seen in a single normal breast sample (CT = 27.6). Expression was down-regulated in the matched adjacent breast tumor tissue (CT = 40). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product is useful in the treatment of breast cancer.
I lδ7 Panel 4D Summary: Ag201δ Significant expression of this gene was detected in a liver cirrhosis sample (CT - 33.7). Epression of this gene was not detected in normal liver in Panel 1.3D, demonstrating that expression of this gene is unique to liver cirrhosis. This gene encodes a GPCR; therefore, antibodies or small molecule therapeutics will reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this GPCR are useful for the diagnosis of liver cirrhosis.
AA. CG53989-04: Mastocytoma Protease Precursor-like.
Expression of gene CG53989-04 was assessed using the primer-probe sets Agl03δ, Agl 590, Agl91δ, Ag2δ99, Ag720, Ag730, Ag443, Ag5δl9, Ag6974 and Agδ406, described in Tables AAA, AAB, AAC, AAD, AAE, AAF, AAG, AAH, AAI and AAJ. Results ofthe RTQ-PCR runs are shown in Tables AAK, AAL, AAM, AAN and AAO.
Table AAA. Probe Name Agl03δ
Figure imgf001192_0001
Table AAB. Probe Name Agl 590
Figure imgf001192_0002
Table AAC. Probe Name Agl 918
Figure imgf001192_0003
Table AAD. Probe Name Ag2899
Figure imgf001193_0001
Table AAE. Probe Name Ag720
Figure imgf001193_0002
Table AAF. Probe Name Ag730
Figure imgf001193_0003
Table AAG. Probe Name Ag443
Figure imgf001193_0004
Table AAH. Probe Name Ag5 l9
Figure imgf001193_0005
Table AAI. Probe Name Ag6974
Figure imgf001193_0006
ι iδ9
Figure imgf001194_0001
Table AAJ. Probe Name Agδ406
Figure imgf001194_0002
Table AAK. Ardais Breastl .0
Figure imgf001194_0003
Figure imgf001195_0001
Table AAL. Panel 1.3D
Figure imgf001195_0002
Figure imgf001196_0001
Figure imgf001197_0001
Table AAM. Panel 2D
Figure imgf001197_0002
Figure imgf001198_0001
Figure imgf001199_0001
Figure imgf001200_0001
Table AAN. Panel 3D
Figure imgf001200_0002
Figure imgf001201_0001
Figure imgf001202_0001
Table AAO. Panel 4D
Figure imgf001202_0002
Figure imgf001203_0001
Figure imgf001204_0001
Ardais Breastl.O Summary: Ag720 Expression of this gene was highest in a breast cancer sample (CT=27.1). Significant CG53989-03 gene expression was detected in 45/64 breast cancer samples but only 1/7 normal breast samples. Gene or protein expression levels are useful for the detection of breast cancer. Therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule drags targeting this gene or gene product is useful in the treatment of breast cancer.
This gene encodes a protein with homology to mastocytoma protease precursor. Mast cell tryptase is a secretory granule associated serine protease with trypsin-like specificity. It is released extracellularly during mast cell degranulation. Mast cells (MC) have been associated with diverse human cancers. The primary function of these cells is to store and release a number of biologically active mediators, including the serine proteases tryptase and chymase. These proteases have been closely related with angiogenesis and tumor invasion, two critical steps during tumor progression. Malignant breast tumors have two to three times more tryptase-containing than chymase-containing mast cells, with the number of mast cells with trptase activity being significantly higher (p<0.02) than in benign lesions. In malignant lesions, tryptase-containing mast cells were concentrated at the tumor edge, i.e. the invasion zone (Kankkunen JP, Harvima IT, Naukkarinen A. Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions. Int J Cancer. 1997 Jul 29; 72(3): 3δ5-δ). Therefore, the protease encoded by this gene plays a role in tumor invasion and metastasis.
General_screening_panel_vl.6 Summary: Ag6974 Highest expression of this gene was detected in a ovarian cancer OVCAR-5 cell line (CT=28). This gene showed preferential expression in colon cancer tissue and a number of cancer cell lines derived from pancreatic, colon, gastric, lung, breast and ovarian cancers. Expression of this gene is useful as diagnostic marker to detect these cancers and also, modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of these cancers.
Panel 1.3D Summary: Agl590/2899 The expression ofthe CG56242-01 gene was assessed in four independent rans using two different probe/primer sets. All ofthe runs show excellent concordance. The expression of this gene was highest in a sample derived from an ovarian cancer cell line (OVCAR-5) (CTs=31-32). There was significant expression associated with a colon cancer cell line, a gastric cancer cell line and pituitary tissue. Therapeutic modulation of this gene, encoded protein and/or use of small molecule or antibodies targeting this gene or gene product is useful in the treatment of ovarian cancer, gastric cancer or colon cancers.
Panel 2D Summary: Ag720/1590/2δ99 The expression of this gene was highest and exclusive to breast cancer samples (CTs=26-2δ). Thus, the expression of this gene is useful as marker for breast cancer. Therapeutic modulation of this gene, encoded protein and/or use of small molecule or antibodies targeting this gene or gene product is useful in the treatment of breast cancer.
Panel 3D Summary: Ag720/2δ99 The expression of this gene was highest in a sample derived from a lung cancer cell line (DMS-79)(CTs=29-31). There was low but significant expression associated with samples derived from an ovarian cancer cell line, a uterine cancer cell line and a pancreatic cancer cell line. The expression of this gene or expressed protein is useful in the detection of lung cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of lung cancer, ovarian cancer, pancreatic cancer or uterine cancer.
Panel 4D Summary: Agl590/Agl918/Ag2δ99 This gene, a tryptase homolog, was expressed at significant levels in IL-9-activated NCI-H292 cells, pulmonary mucoepidermoid cells. Colon, lung, and thymus tissues also showed low levels of expression of this gene. The expression in lung and in the activated NCI-H292 cell line, often used as a model for airway epithelium was consistent with published reports of tryptase in the lung (Walls AF, Bennett AR, Godfrey RC, Holgate ST, Church MK. Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung disease. Clin Sci (Lond) 1991 Aug;δl(2):lδ3-δ). In addition, tryptase has been shown to be up-regulated in lungs affected by disease and specifically in COPD (Grashoff WF, Sont JK, Sterk PJ, Hiemstra PS, de Boer WI, Stolk J, Han J, van Krieken JM. Chronic obstractive pulmonary disease: role of bronchiolar mast cells and macrophages. Am J Pathol 1997 Dec;151(6):17δ5-90). Tryptase has also been implicated in the recruitment of granulocytes and epithelial repair (Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-δ production and intercellular adhesion molecule-1 expression. J Immunol 1996 Jan 1 ; 156(1 ):275-83). Based on these observations, therapeutic modulation of this gene, encoded protein and/use of small molecule or antibodies targeting this gene is useful in the reduction or elimination of symptoms in patients with lung diseases including asthma, allergy, or chronic obstractive pulmonary disease.
AB. CG54212-02: GPCR.
Expression of gene CG54212-02 was assessed using the primer-probe set Ag431, described in Table ABA. Results ofthe RTQ-PCR runs are shown in Tables ABB, ABC and ABD.
Table ABA. Probe Name Ag431
Figure imgf001206_0001
Table ABB. Panel 1
Column A - Rel. Exp.(%) Ag431, Run 98747695
Figure imgf001207_0001
Figure imgf001208_0001
Table ABC. Panel 2D
Figure imgf001208_0002
Figure imgf001209_0001
Table ABD. Panel 4D
Figure imgf001209_0002
Figure imgf001210_0001
Panel 1 Summary: Ag431 Expression of this gene was highest in a melanoma cell line (CT=27.1). Significant expression was also detected in ovarian, lung, and colon cancer cell lines. Modulation of this gene, encoded protein and/or use of small molecule drags or antibodies targeting this gene or gene product is useful in the treatment of melanoma and lung, colon or ovarian cancers.
Among tissues with metabolic function, this gene was expressed in the pituitary and adrenal glands, the hypothalamus, heart and skeletal muscle. Modulation of this gene, encoded protein and or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of metabolic/endocrine diseases such as diabetes and obesity.
This gene was also expressed at moderate levels in all the regions ofthe central nervous system examined including the fetal brain, cerebellum, amygdala, hippocampus, substantia nigra, thalamus, hypothalamus, and spinal cord. This gene codes for a GPCR. , Neurotransmitter receptors belong to GPCR family of proteins. Thus, this protein may represent a novel neurotransmitter receptor. Neurotransmitter receptors that are GPCRs include the dopamine receptor family, the serotonin receptor family, the GABA receptor, and muscarinic acetylcholine receptors. The selected targeting of dopamine and serotonin receptors has proven to be effective in the treatement of psychiatric illnesses such as schizophrenia, bipolar disorder and depression. Furthermore, the cerebral cortex and hippocampus regions ofthe brain are known to play critical roles in Alzheimer's disease, seizure disorders, and in the normal process of memory formation. Therefore, modulation of this gene and/or encoded protein is useful in the treatment of any of these diseases.
Panel 2D Summary: Ag431 Expression of this gene was highest in breast cancer (CT=32.3) and was not detected at significant levels in normal breast tissue. There was significant expression in number of breast cancer samples. Modulation of this gene and encoded protein is useful in the treatment of breast cancer.
Panel 4D Summary: Ag431 This gene was expressed in IFN-gamma- stimulated mucoepidermoid (mucus-producing) NCI-H292 cells, but not in resting NCI- H292 cells, or in IL-4-, IL-9-, or IL-13 -stimulated NCI-H292 cells. The gene was also expressed at low but significant levels at the three-day time point in a two-way mixed lymphocyte reaction with cells from normal human donors. Thus, modulation of this gene, encoded protein and/or use of antibody or small molecule drag targeting this gene or gene product is useful int he treatment of inflammatory diseases such as colitis, chronic obstructive pulmonary disease, asthma, allergy and emphysema.
AC. CG54236-01: Cysteinyl leukotriene receptor 2.
Expression of gene CG54236-01 was assessed using the primer-probe set Ag2695, described in Table ACA. Results ofthe RTQ-PCR runs are shown in Tables ACB, ACC, ACD, ACE and ACF.
Table ACA. Probe Name Ag2695
Figure imgf001211_0001
Figure imgf001212_0001
Table ACB. Al comprehensive panel_vl.O
Figure imgf001212_0002
120δ
Figure imgf001213_0001
Table ACC. CNS_neurodegeneration_vl.O
Figure imgf001213_0002
Figure imgf001214_0001
Table ACD. Panel 1.3D
Figure imgf001214_0002
Figure imgf001215_0001
Table ACE. Panel 2D
Figure imgf001215_0002
Figure imgf001216_0001
Figure imgf001217_0001
Table ACF. Panel 4D
Figure imgf001217_0002
Figure imgf001218_0001
AI_comprehensive panel_vl.O Summary: Ag2695 The highest expression of this gene was detected in synovial fluid cells. Low expression of this gene is also seen in orthoarthritis bone, cartilage, synovium, RA bone, normal lung and a psoriasis sample. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of orthoarthritis, rheumatoid arthritis and psoriasis.
CNS_neurodegeneration_yl.O Summary: Ag2695 This gene was downregulated in the temporal cortex of Alzheimer's disease patients. Up-regulation of this gene or its protein product, or treatment with specific agonists for this protein encoded by this gene is useful in reversing the dementia/memory loss associated with this disease and neuronal death. Panel 1.3D Summary: Ag2695 Highest expression of this gene was seen in adrenal gland and spleen (CTS=317). Significant expression of this gene is seen mainly in the normal tissues including brain, lymphnode, heart, gastrointestinal tract, lung, ovary, placenta and adipose tissue. Expression of this gene was low or undetectable in any ofthe cancer cell lines. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of cancer, metabolic and CNS disorders.
Panel 2D Summary: Ag2695 The expression of this gene was detected in metastatic melanoma (CTs=26-27.δ). High to moderate expression of this gene was also seen in normal and cancer samples from colon, lung, prostate, liver, prostate, thyroid, uterus, breast, ovary and stomach. Expression of this gene is upregulated in ovarian, thyroid and kidney cancers compared to corresponding normal adjacent normal tissues. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of ovarian, thyroid and kidney cancers.
Panel 4D Summary: Ag2695 Highest expression of this gene was seen in resting monocytes (CT=29.6). This gene was expressed by T lymphocytes prepared under a number of conditions at moderate levels and is expressed at significant levels in treated and untreated dendritic cells, LAK cells, PBMC, activated B lymphocytes, activated dermal fibroblasts, liver cirrhosis sample and normal tissues represented by colon, lung, thymus and kidney . Dendritic cells are powerful antigen-presenting cells (APC) whose function is pivotal in the initiation and maintenance of normal immune responses. Autoimmunity and inflammation may also be reduced by suppression of this function. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of autoimmune and inflammatory diseases, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstractive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.
AD. CG54479-05: HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN PRECURSOR.
Expression of gene CG54479-05 was assessed using the primer-probe sets Ag30δ6 and Ag3797, described in Tables ADA and ADB. Results of the RTQ-PCR rans are shown in Tables ADC, ADD, ADE and ADF.
Table ADA. Probe Name Ag30δ6
Figure imgf001220_0001
Table ADB. Probe Name Ag3797
Figure imgf001220_0002
Table ADC. General_screening_panel_vl .4
Figure imgf001220_0003
Table ADD. Panel 1.3D
Figure imgf001221_0002
Figure imgf001222_0001
Table APE. Panel 2.2
Figure imgf001222_0002
Figure imgf001223_0001
Figure imgf001224_0001
Table ADF. Panel 4. ID
Figure imgf001224_0002
Figure imgf001225_0001
General_screening_panel_vl.4 Summary: Ag3797 Highest expression of this gene was detected in liver cancer HepG2 cell line (CT=25.3). High expression of this gene was also seen in fetal and adult liver. Therapeutic modulation of this gene is useful in the treatment of liver related disorders.
Moderate levels of expression of this gene was also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene is useful as a marker to detect these cancers. Therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.
Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therapeutic modulation ofthe activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
In addition, this gene is expressed at moderate levels in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
Panel 1.3D Summary: Ag3086 This gene was highly expressed in both fetal and adult liver tissue (CTs = 26) and liver cancer cell lines (CT = 27). The gene was also expressed at moderate to low levels in most ofthe other tissues in the panel. Therapeutic modulation of this gene is useful in the treatment of liver related disorders.
In tissues involved in the central nervous system, this gene was moderately expressed in the fetal and adult brain, including the adult thalamus, substantia nigra, hippocampus, amygdala and is also expressed at low but significant levels in the cerebellum and cerebral cortex. This expression profile suggests that this gene has functional significance in the CNS. This gene codes for a homolog of hepatocyte growth factor, which has numerous therapeutic applications in the CNS, including prevention of neuronal death in animal models of stroke and ischemia. Hepatocyte growth factor has mitogenic activity and thus has potential application as a protein therapeutic to treat brain pathologies when administered directly to the cortico spinal fluid or systemically when the blood brain barrier is disrupted. Hepatocyte growth factor-like protein is a neurotrophic factor useful in the prevention of motoneuron atrophy upon axotomy. Therefore, this gene, expressed protein and/or use of antibodies or small molecule targeting this gene or gene product is useful as a therapeutic agent in treating stroke and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The potential role of the this gene or its protein product in brain plasticity and regeneration affords utility in treating brain damage and aging related disorders, such as memory impairment that has hippocampal dysfunction as its primary focus.
Panel 2.2 Summary: Ag3086 The expression of this gene was highest in a sample derived from a liver cancer specimen (CT=26) and was expressed at significant levels in a number of samples derived from liver tissue. There was significant expression of this gene associated with normal kidney tissue (CT=27.2) relative to adjacent kidney cancer specimens, therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of kidney cancer.
Panel 4.1D Summary: Ag3797 Highest expression of this gene was detected in kidney (CTs=27.4-29). Moderate levels of expression of this gene was also seen in liver cirrhosis sample. This gene was expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells included members ofthe T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression indicates that this gene is involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.
AE. CG54479-06: Macrophage stimulatory protein.
Expression of gene CG54479-06 was assessed using the primer-probe set Ag6711, described in Table AEA. Results ofthe RTQ-PCR rans are shown in Table AEB.
Table AEA. Probe Name Ag6711
Figure imgf001227_0001
Table AEB. General_screening_panel_vl.6
Figure imgf001227_0002
Figure imgf001228_0001
Figure imgf001229_0001
General_screening_panel_vl.6 Summary: Ag6711 Highest expression of this gene was detected in a liver cancer HepG2 cell line (CT=30.6). Significant expression of this gene was also seen in number of cancer cell lines derived from ovarian, lung, renal, colon and brain cancers. Thus, expression levels of this gene is useful as a marker to detect these cancers. Therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.
Moderate levels of expression of this gene was also seen in fetal and adult liver. Therapeutic modulation of this gene is useful in the treatment of liver related disorders such as obesity, liver cirrhosis and other liver inflammatory diseases.
AF. CG54539-02: Zinc Transporter 1.
Expression of gene CG54539-02 was assessed using the primer-probe set Agl 160, described in Table AFA. Results ofthe RTQ-PCR rans are shown in Tables AFB, AFC and AFD. CG54539-02 represents a full length physical clone.
Table AFA. Probe Name Agl 160
Figure imgf001229_0002
Table AFB. General_screening_panel_vl.4
Figure imgf001229_0003
Figure imgf001230_0002
Table AFC. Panel 2D
Figure imgf001230_0001
Figure imgf001231_0001
Figure imgf001232_0001
Table AFD. Panel 4D
Figure imgf001232_0002
Figure imgf001233_0001
General_screening_panel_vl.4 Summary: Agl 160 Highest expression was detected in spleen (CT=27). This gene was widely expressed in this panel, demonstrating a role for this gene product in cell survival and proliferation. Moderate expression was also seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. Modulation of this gene product is useful in the treatment of these cancers.
Among tissues with metabolic function, this gene was expressed at moderte to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues shows that this gene product plays a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene contributes to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.
This gene was expressed at much higher levels in fetal lung and liver tissue (CTs=27) when compared to expression in the adult counterparts (CTs=30-31). Expression of this gene is useful as a marker to differentiate between the fetal and adult sources of these tissues. The relative overexpression of this gene in fetal lung shows that the protein product enhances lung and liver growth or development in the fetus and also acts in a regenerative capacity in the adult. Therapeutic modulation ofthe protein encoded by this gene is useful in treatment of lung and liver related diseases.
This gene was also expressed at moderate to low in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therapeutic modulation ofthe expression or function of this gene is useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.
Panel 2D Summary: Agl 160 Highest expression of this gene was detected in normal liver (CT=27). This gene was over expressed in gastric, colon, breast and lung cancers samples compared to the normal adjacent tissues. Targeting this gene or its protein product with a small molecule, antibody or protein therapeutic is useful in the treatment of these cancers.
Panel 4D Summary: Agl 160 This gene was upregulated in several normal and activated tissues. This gene was particularly high in activated monocytes and both activated and resting macrophages. Antibodies targeting this gene or gene product is useful to detect monocytes which are differentiating into macrophages. Antagonistic therapeutics to this molecule will inhibit the differentiation process, activation ofthe epithelium or keratinocytes in the skin and block or reduce inflammation in diseases such as asthma, allergy, psoriasis and emphysema.
AG. CG54683-05: GAMMA-AMINOBUTYRIC-ACπ) RECEPTOR RHO-3 SUBUNIT PRECURSOR.
Expression of gene CG54683-05 was assessed using the primer-probe sets Agl 130, Agl 198, Agl 253, Agl 603 and Ag3363, described in Tables AGA, AGB, AGC, AGD and AGE. Results ofthe RTQ-PCR rans are shown in Tables AGF and AGG.
Table AGA. Probe Name Agl 130
Figure imgf001234_0001
Table AGB. Probe Name Agl 198
Figure imgf001235_0001
Table AGC. Probe Name Agl253
Figure imgf001235_0002
Table AGP. Probe Name Agl 603
Figure imgf001235_0003
Table AGE. Probe Name Ag3363
Figure imgf001235_0004
Table AGF. Panel 1.2
Figure imgf001235_0005
Figure imgf001236_0001
Figure imgf001237_0001
Table AGG. Panel 4R
Figure imgf001237_0002
Figure imgf001238_0001
Panel 1.2 Summary: Agl 130/Agl 198 - Significant expression of this gene was seen in testis, a colon cancer and prostate cancer cell line (CTs=33-34). Therefore, modulation of this gene is useful in the treatment of colon and prostate cancers.
Panel 4R Summary: Agl 198 Significant expression of this gene was seen only in the IBD colitis 1 sample (CT=34.2). Modulation of this gene is useful in the treatment of IBD colitis.
AH. CG54692-06: 5-HYDROXYTRYPTAMINE 5A RECEPTOR.
Expression of gene CG54692-06 was assessed using the primer-probe sets Agl 507, Agl 558 and Agl602, described in Tables AHA, AHB and AHC. Results ofthe RTQ-PCR runs are shown in Tables AHD and AHE. Table AHA. Probe Name Agl 507
Figure imgf001239_0001
Table AHB. Probe Name Agl 558
Figure imgf001239_0002
Table AHC. Probe Name Agl 602
Figure imgf001239_0003
Table AHD. Panel 1.2
Figure imgf001239_0004
Figure imgf001240_0001
Table AHE. Panel 2D
Figure imgf001240_0002
Figure imgf001241_0001
Figure imgf001242_0001
Panel 1.2 Summary: Agl 507 Low but significant expression of this gene was detected in ovarian cancer cell lines (CT=32.5). In general, expression of this gene was seen in cancer cell lines rather than in normal tissues, with low but significant expression also detectable in melanoma, breast cancer, lung cancer, and renal cancer cell lines. Thus, expression levels of this gene is useful to detect melanoma, breast, lung, renal and colon cancers. Therapeutic inhibition ofthe this gene or gene product, and/or use of antibodies, small molecule or protein drags, is effective in the treatment ofthe afore mentioned cancers.
Panel 2D Summary: Agl55δ Significant expression of this gene was detected in a gastric cancer tissue sample (CT=347). Thus, expression ofthe gene is useful to distinguish between gastric cancer and normal tissue. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of gastric cancer.
Al. CG55069-01, CG55069-03, CG55069-04, CG55069-09: Ten-m3. Expression of gene CG55069-01, CG55069-03, CG55069-04, and CG55069-09 were assessed using the primer-probe sets Agl479, Ag2674, and Ag2δ20, described in Tables AIA, AIB, and AIC. Results ofthe RTQ-PCR rans are shown in Tables AID, ATE, and AIF. CG55069-04, and CG55069-09 represent a physical clone for EGF domain. Probe-primer set Ag2δ20 is specific for variant CG55069-01.
Table AIA. Probe Name Agl479
Figure imgf001243_0001
Table AIB. Probe Name Ag2674
Figure imgf001243_0002
Table AIC. Probe Name Ag2820
Figure imgf001243_0003
Table AID. Panel 1.3D
Figure imgf001243_0004
Figure imgf001244_0001
Figure imgf001245_0001
Figure imgf001246_0001
Table ATE. Panel 2D
Figure imgf001246_0002
Figure imgf001247_0001
Table AIF. Panel 4D
Column A - Rel. Exp.(%) Agl479, Run 162599612 Column B - Rel. Exp.(%) Ag2674, Run 160645450
Figure imgf001248_0001
Figure imgf001249_0001
Figure imgf001250_0001
This gene codes for TenM3 protein. Ten-M proteins have been shown to be involved in cell migration. This gene was upregulated in a variety of cancers. It was highly expressed in glioma, astrocytoma, lung, renal, ovarian and breast cancer cell lines. It was also expressed at high levels in primary lung, kidney, bladder, ovarian, gastric, melanoma and breast cancer tissues. This EGF repeat domain (CG55069-04 and CG55069-09 variants) of Ten-M3 is known to be involved in dimerization ofthe full length protein in vivo. Treatment of cells expressing Ten-M3 with this purified protein fragment will interfere with the normal function of endogenous Ten-M3 and inhibit cell migration.
Panel 1.3D Summary: Agl479/2674/Ag2820 Highest expression of this gene was seen in the brain and in brain cancer cell lines (CTs=28-31). Thus, inhibitors of this gene or gene product is useful for the treatment of diseases involving neurite outgrowth or organization, such as neurodegenerative diseases.
There was substantial expression in other samples derived from cancer cell lines, such as breast cancer, lung cancer ovarian cancer. Thus, therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of brain cancer, lung cancer, or ovarian cancer.
This gene was also moderately expressed in metabolic tissues including adrenal, thyroid, pituitary, fetal heart, adult and fetal skeletal muscle, and adipose. Thus, this geen product may be an antibody target for the treatment ofany or all diseases in these tissues, including obesity and diabetes.
Panel 2D Summary: Ag2674/2820 The highest expression of this gene is generally associated with kidney cancers. Of particular note is the consistent absence of expression in normal kidney tissue adjacent to malignant kidney. In addition, there is substantial expression associated with ovarian cancer, bladder cancer and lung cancer. Thus, the expression of this gene could be used to distinguish the above listed malignant tissue from other tissues in the panel. Particularly, the expression of this gene could be used to distinguish malignant kidney tissue from normal kidney. Moreover, therapeutic modulation of this gene, through the use of small molecule drags, antibodies or protein therapeutics might be of benefit in the treatment of kidney cancer, ovarian cancer, bladder cancer or lung cancer.
Panel 4D Summary: Agl479/Ag2674/Ag2δ20 The expression of this gene was highest in astrocytes and microvascular dermal endothelial cells (CTs=29-30), with low but significant expression in keratinocytes, and dermal fibroblasts. Expression was not modulated by any treatment, indicating that this protein is important in normal homeostasis. Therefore, modulation of this gene, expressed protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatmen of autoimmune and inflammatory diseases such as asthma, IBD, psoriasis, multiple sclerosis or other inflammatory diseases ofthe CNS.
AJ. CG55343-03: Olfactory Receptor.
Expression of gene CG55343-03 was assessed using the primer-probe sets Agl 592 and Ag457, described in Tables AJA and AJB. Results ofthe RTQ-PCR rans are shown in Tables AJC, AJD, AJE and AJF. CG55343-03 represents the full-length physical clone.
Table AJA. Probe Name Agl 592
Figure imgf001251_0001
Table AJB. Probe Name Ag457
Figure imgf001251_0002
Table AJC. Panel 1.3D
Figure imgf001252_0001
124δ
Figure imgf001253_0001
Table AJD. Panel 2D
Figure imgf001253_0002
Figure imgf001254_0001
Figure imgf001255_0001
Table AJE. Panel 4D
Figure imgf001256_0001
Figure imgf001257_0001
Table AJF. general oncology screening panel_v_2.4
Figure imgf001257_0002
Figure imgf001258_0001
Panel 1.3D Summary: Ag457/Agl592 Expression of this gene, encoding a protein with homology to olfactory receptors, was highest in breast cancer cell line MCF-7 (CTs=32-32.8). In general, this gene was more highly expressed in cancer cell lines relative to normal tissues. Expression of this gene was significantly upregulated in 3/5 breast cancer cell lines, 2/6 ovarian cancer cell lines, and 7/10 lung cancer cell lines. Thus, expression of this gene is useful as a marker for breast, ovarian and lung cancers. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of breast, ovarian and lung cancers.
Panel 2D Summary: Ag457/Agl592 Expression of this gene was upregulated in 6/8 breast cancer samples. Expression of this gene was higher in one ovarian and one bladder cancer sample relative to the normal adjacent tissue. These results are consistent with what was observed on Panel 1.3D. Thus, expression of this gene is useful as a marker for these cancers. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of breast, ovarian and bladder cancers.
Panel 4D Summary: Agl592/Ag457 This gene showed preferential expression in activated basophils (CTs=33.9). Basophils release histamines and other biological modifiers in reponse to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. These cells are a good model for the inflammatory cells that take part in various inflammatory lung and bowel diseases, such as asthma, Crohn's disease, and ulcerative colitis. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful to reduce or eliminate the symptoms of patients suffering from asthma, Crohn's disease, and ulcerative colitis. general oncology screening panel_v_2.4 Summary: Ag457 Moderate levels of expression of this gene was detected in a lung cancer sample (CT=30.8). Low but significant expression of this gene was also seen in a kidney cancer sample. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of lung and kidney cancers.
AK. CG55358-03, CG55358-04: Olfactory Receptor.
Expression of gene CG55358-03 and CG5535δ-04 were assessed using the primer-probe sets Agl 593, Ag455b and Ag455, described in Tables AKA, AKB and AKC. Results ofthe RTQ-PCR runs are shown in Tables AKD, AKE, AKF, AKG and AKH. CG5535δ-03 and CG5535δ-04 represent full-length physical clones.
Table AKA. Probe Name Agl 593
Figure imgf001259_0001
Table AKB. Probe Name Ag455b
Figure imgf001259_0002
Table AKC. Probe Name Ag455
Figure imgf001259_0003
Table AKD. Ardais Breastl .0
Figure imgf001259_0004
Figure imgf001260_0001
Figure imgf001261_0001
Table AKE. Panel 1.3D
Figure imgf001261_0002
Figure imgf001262_0001
Table AKF. Panel 2D
Figure imgf001262_0002
Figure imgf001263_0001
Figure imgf001264_0001
Table AKG. Panel 3D
Figure imgf001264_0002
Figure imgf001265_0001
Figure imgf001266_0001
Table AKH. Panel 4D
Figure imgf001266_0002
Figure imgf001267_0001
Ardais Breastl.O Summary: Agl593/Ag455 Highest expression of this gene is detected in breast cancer 9B6 samples (CTs=25-27). Significant expression of this gene is seen in number of cancer breast cancer samples. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of breast cancer.
Panel 1.3D Summary: Agl593/Ag455b The expression of this gene was detected in a number ofthe cancer cell lines and not in the normal tissues. The highest expression was found in MCF-7 breast cancer cells, which are estrogen receptor positive. Low expression of this gene was also seen in cell lines derived from lung, colon, breast and gastric cancers. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of breast, lung, colon and gastric cancers.
Panel 2D Summary: Agl593/Ag455 Highest expression of this gene was detected in breast cancer samples (CTs=29-30.5). Significant expression of this gene was seen in number of cancer samples derived from breast, ovarian, bladder, colon, and lung cancers. Expression of this gene is useful as marker to detect these cancers and modulation of this gene, encoded protein and or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of breast, ovarian, bladder, colon, and lung cancers.
Panel 3D Summary: Ag455 This gene was expressed widely, but at a low level, across of all ofthe samples in panel 3D. Highest expression was detected in a chronic myelogenous leukemia (megokaryoblast) (CT value = 30), indicating a potential role for the gene in this disease.
Panel 4D Summary: Agl593/Ag455 This gene was highly induced the KU-δl2 basophil cell line and was expressed at lower levels in pokeweed mitogen-activated B cells and PBMC (CTs=31-34). Activated basophils release a number of potent bioresponse modifiers that can damage surrounding tissues. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product will reduce or block inflammation or tissue damage caused by inflammation by blocking activation of basophils and is useful for the treatment of asthma, emphysema, and allergy.
AL. CG55604-04: Olfactory receptor.
Expression of gene CG55604-04 was assessed using the primer-probe set Agl 240, described in Table ALA. Results ofthe RTQ-PCR rans are shown in Tables ALB, ALC, ALD and ALE.
Table ALA. Probe Name Agl 240
Figure imgf001268_0001
Table ALB. AI_comprehensive panel_vl .0
Column A - Rel. Exp.(%) Agl240, Run 306266935
Figure imgf001269_0001
Figure imgf001270_0001
Figure imgf001270_0002
Figure imgf001271_0001
Figure imgf001272_0001
Table ALE. Panel 4D
Figure imgf001272_0002
126δ
Figure imgf001273_0001
Figure imgf001274_0001
AI_comprehensive panel_vl.O Summary: Agl 240 The highest expression of this gene was detected in an ulcerative colitis sample. Moderate levels of expression of this gene were detected in samples derived from normal and orthoarthitis/rheumatoid arthritis bone and adjacent bone, cartilage, synovium and synovial fluid samples, from normal lung, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis (normal matched control and diseased), and psoriasis (normal matched control and diseased). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis.
General screening panel vl.4 Summary: Agl 240 The highest expression of this gene was detected in a colon cancer cell line (CT=31). Significant expression of this gene was seen in pancreas, melanoma, lymph node, spleen, thymus, brain, testis, prostate (both normal and cancer), breast (both normal and cancer), kidney (fetal, and adult normal and cancer). The expression of this gene was upregulated in several ovarian and lung cancer cell lines, and downregulated in stomach and breast cancer cell lines. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of ovarian, lung, stomach and breast cancers.
Panel 1.2 Summary: Agl 240 The highest exoression of this gene was detected in spinal cord. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of disorders and injuries of the spinal cord.
Panel 4D Summary: Agl 240 The highest expression of this gene was seen in the B cell lymphoma Ramos (CT=29). This gene was highly expressed in activated T cells, particularly in activated T cells which have been cultured under conditions which skew their development into Thl , Th2 or Trl cells, but not in resting T cells. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of inflammation resulting from T cell activation and T cell-mediated autoimmune diseases such as arthritis, Crohn's disease, asthma/allergy, diabetes and psoriasis. These therapeutics is also important in preventing organ rejection due to T cell activation.
AM. CG55752-06 and CG55752-07: Glucosidase.
Expression of genes CG55752-06 and CG55752-07 were assessed using the primer-probe set Ag401 , described in Table AMA. Results ofthe RTQ-PCR rans are shown in Tables AMB and AMC.
Table AMA. Probe Name Ag401
Figure imgf001275_0001
Table AMB. Panel 1.3D
Figure imgf001275_0002
Figure imgf001276_0001
Figure imgf001277_0001
Panel 1.3D Summary: Ag401 The highest expression of this gene was detected in skeletal muscle. It was expressed in a variety of metabolic tissues, including pancreas, adipose, adrenal, thyroid, pituitary, adult and fetal heart, adult and fetal skeletal muscle, and adult and fetal liver. This gene encodes an alpha-glucosidase. Alpha-glucosidase inhibitors are cuπently used in the treatment of Type 2 diabetes to decrease glucose absorption from the gut (Raptis SA, Dimitriadis GD. Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers. Exp Clin Endocrinol Diabetes. 2001 ;109 Suppl 2:S265-δ7). Thus, this gene, encoded protein and/or use of small molecule targeting this gene or gene product is useful for the treatment of metabolic diseases, including obesity and Types 1 and 2 diabetes.
This gene was expressed in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders, such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
Panel 5 Islet Summary: Ag401 The highest expression of this gene was detected during adipocyte differention (CT=32). This gene was upregulated during adipocyte differentiation. It was expressed in a variety of metabolic tissues, including adipose, heart, small intestine, kidney, uteras, skeletal muscle. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of obesity and diabetes.
AN. CG55778-03 and CG55778-06: Aldo-Keto Reductase.
Expression of gene CG55778-03 and CG5577δ-06 were assessed using the primer-probe set Ag7193, described in Table ANA. Results ofthe RTQ-PCR rans are shown in Table ANB. CG55778-03 and CG5577δ-06 represent full length physical clones.
Table ANA. Probe Name Ag7193
Figure imgf001278_0001
Table ANB. General_screening_panel_vl7
Figure imgf001278_0002
Figure imgf001279_0001
General_screening_panel_vl.7 Summary: Ag7193 Among tissues with metabolic or endocrine function, this gene was expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
AO. CG55794-03: Novel carboxypeptidase B like protein. Expression of gene CG55794-03 was assessed using the primer-probe sets Ag2622 and Ag3953, described in Tables AOA and AOB. Results of the RTQ-PCR runs are shown in Tables AOC, AOD, AOE and AOF. This gene represents a full-length physical clone.
Table AOA. Probe Name Ag2622
Figure imgf001280_0001
Table AOB. Probe Name Ag3953
Figure imgf001280_0002
Table AOC. Panel 1.3D
Figure imgf001280_0003
Figure imgf001281_0001
Table AOD. Panel 2D
Figure imgf001281_0002
Figure imgf001282_0001
Figure imgf001283_0001
Table AOE. Panel 4D
Figure imgf001283_0002
Figure imgf001284_0001
Table AOF. Panel 5 Islet
Figure imgf001284_0002
12δ0
Figure imgf001285_0001
Panel 1.3D Summary: Ag2622 The highest expression of this gene was detected in the brain and the kidney. There was significantly lower expression in the brain cancer cell lines than normal brain samples. This indicates that downregulation of this gene is important in cell proliferation. Hence this expression profile is useful as a diagnostic marker for brain cancer.
This gene was also expressed at low levels in the CNS. Carboxypeptidase is believed to have a role in the degradation of APP and A-beta, the major component of senile plaques in Alzheimer's disease (Matsumoto A, Itoh K, Matsumoto R. A novel carboxypeptidase B that processes native beta-amyloid precursor protein is present in human hippocampus. Eur J Neurosci 2000 Jan;12(l):227-38). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of Alzheimer's disease.
Panel 2D Summary: Ag2622 This gene was expressed at low levels in the tissues. There was increased expression in normal prostate and kidney compared to the adjacent tumor tissues. There was also increased expression in breast cancer tissues compared to normal breast tissue. Hence, expression of this gene useful as a diagnostic marker in breast, prostate and kidney cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of breast, prostate and kidney cancer.
Panel 4D Summary: Ag 2622 This gene encoding a putative carboxypeptidase, was expressed in the colon (CT=25-27) and down regulated in colon tissue isolated from Crohn's and colitis patients (CTs>31). The carboxypeptidase family of enzymes has been found in the colon and is associated with colon disease (Sommer H, Schweisfurth H, Schulz M. Serum angiotensin-I-converting enzyme and carboxypeptidase N in Crohn's disease and ulcerative colitis. Enzyme 1986;35(4):lδl-δ). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of IBD.
Panel 5 Islet Summary: Ag3953 This gene, a carboxypeptidase Bl homolog, showed moderate expression in small intestine (CT=32.6). Carboxypeptidase Bl is an endocrine tissue-specific protein and is a useful serum marker for acute pancreatitis and dysfunction of pancreatic transplants (Yamamoto, K. K.; Pousette, A.; Chow, P.; Wilson, H.; El Shami, S.; French, C. K. Isolation of a cDNA encoding a human serum marker for acute pancreatitis: identification of pancreas-specific protein as pancreatic procarboxypeptidase B. J. Biol. Chem. 1992 267: 2575-2581 PMID : 1370825). This class of peptidase has been implicated in hormone maturation and/or degradation of secreted peptides such as insulin, GLP-1, and PACAP. PACAP latter has a major role in metabolic processes. Several carboxypeptidases, like CPE or PCI, have been shown to be involved in development of diabetes and obesity. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of diabetes and also, diseases associated with the GI tract and metabolism.
AP. CG55806-04: Factor-IX.
Expression of gene CG55806-04 was assessed using the primer-probe set Ag2613, described in Table APA. Results ofthe RTQ-PCR runs are shown in Tables APB, APC and APD.
Table APA. Probe Name Ag2613
Figure imgf001286_0001
12δ2
Figure imgf001287_0001
Table APB. Panel 1.3D
Figure imgf001287_0002
Figure imgf001288_0001
Table APC. Panel 2.2
Figure imgf001288_0002
12δ4
Figure imgf001289_0001
Table APD. Panel 4D
Figure imgf001289_0002
Figure imgf001290_0001
Panel 1.3D Summary: Ag2613 The highest expression of this gene was found in adult liver. Expression of this gene was also detected in fetal liver and fetal kidney
12δ6 samples on this panel (CTs=27-31). This gene encodes a protein that is homologous to factor IX. The secreted form ofthe protein may be present in the circulatory sysytem and exhibit effects that are unrelated to the site of synthesis. Measurement ofthe expression level of this gene or expressed protein is useful to test liver function. Measurement ofthe expression level of this gene or expressed protein can be used to differentiate between liver derived tissue and other tissues. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are effective in increasing the levels of factor IX in the blood, and useful in the treatment of hemophilia and liver related disease.
Panel 2.2 Summary: Ag2613 Expression of this gene was highest in samples derived from liver (CT=27.9), consistant with the results seen in Panel 1.3D. Therefore, expression of this gene is useful to differentiate between normal sections of liver as compared to tumors that are secordary metastases from other sites (such as melanoma).
Panel 4D Summary: Ag2613 This transcript was highly expressed in cirrhotic liver tissue (CT=27.δ). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of liver cirrhosis.
AQ. CG55828-02: SERINE/THREONINE-PROTEΓN KTNASE PAK
5.
Expression of gene CG5582δ-02 was assessed using the primer-probe set Ag72 l, described in Table AQA. Results ofthe RTQ-PCR runs are shown in Table AQB. Gene CG55828-02 represents full-length physical clone.
Table AOA. Probe Name Ag72 l
Figure imgf001291_0001
Table AQB. General_screening_panel_vl 7
Figure imgf001291_0002
12δ7
Figure imgf001292_0001
General_screening_panel_vl.7 Summary: Ag72δl The highest expression of this gene was detected in fetal brain (CT=25). This gene was expressed in all central nervous system samples on this panel. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of disorders ofthe central nervous system including Alzheimer's disease, Parkinson's disease, trauma, stroke, epilepsy, pain, multiple sclerosis, schizophrenia, bipolar disorder, depression, anxiety, obsessive compulsive disorder, ataxia, autism, drug and alcohol addiction.
AR. CG55988-04: ORGANIC CATION TRANSPORTER OKB1.
Expression of gene CG5598δ-04 was assessed using the primer-probe set Ag63δ9, described in Table ARA. Results ofthe RTQ-PCR rans are shown in Table ARB.
Table ARA. Probe Name Ag6389
Figure imgf001293_0001
Table ARB. General_screening_panel_vl.6
Figure imgf001293_0002
Figure imgf001294_0001
General_screening_panel_vl.6 Summary: Ag6389 Low expression of this gene was detected in testis. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product will be useful in the treatment testis related disorders including fertility and hypogonadism. AS. CG56071-01: MIXED LINEAGE KINASE 2-like.
Expression of gene CG56071-01 was assessed using the primer-probe sets Ag2872 and Ag4847, described in Tables ASA and ASB. Results ofthe RTQ-PCR rans are shown in Tables ASC, ASD, ASE, ASF, ASG, ASH and ASI.
Table ASA. Probe Name Ag2872
Figure imgf001295_0001
Table ASB. Probe Name Ag4847
Figure imgf001295_0002
Table ASC. General_screening_panel_vl .5
Figure imgf001295_0003
Figure imgf001296_0001
Table ASD. Panel 1.3D
Figure imgf001296_0002
Figure imgf001297_0001
Figure imgf001298_0001
Table ASE. Panel 2.2
Figure imgf001298_0002
Figure imgf001299_0001
Table ASF. Panel 2D
Figure imgf001299_0002
Figure imgf001300_0001
Table ASG. Panel 3D
Figure imgf001301_0001
Figure imgf001302_0001
Figure imgf001303_0001
Table ASH. Panel 4. ID
Figure imgf001303_0002
Figure imgf001304_0001
Table ASI. Panel 5 Islet
Figure imgf001304_0002
Figure imgf001305_0001
General_screening_panel_vl.5 Summary: Ag4847 Expression of this gene was highest in the cerebellum (CT = 25.4). This gene was also expressed at more moderate levels in other central nervous system tissues, including amygdala, hippocampus, cerebral cortex, substantia nigra, thalamus and spinal cord (CTs = 27-30). This gene encodes a protein with homology to mixed lineage kinase 2. Mixed lineage kinase 2 is a mammalian protein kinase that activates stress-activated protein kinases/c- jun N-terminal kinases (SAPK/JNKs) through direct phosphorylation of their upstream activator, SEKl/JNKK. MAP kinase signaling pathways are important mediators of cellular responses to a wide variety of stimuli. Signals pass along these pathways via kinase cascades in which three protein kinases are sequentially phosphorylated and activated, initiating a range of cellular programs including cellular proliferation, endocrine, immune and inflammatory responses, and apoptosis. Mixed lineage kinases have been implicated in neuronal apoptosis (Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA.The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol 2001 Jul;21(14):4713-24). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in slowing neuronal apoptosis in the treatment of neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's diseases.
This gene also showed significant expression in cell lines drived from ovarian cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of ovarian cancer. This gene was expressed at low to moderate levels in endocrine and metabolic tissues including adipose, adrenal gland, liver, pancreas, pituitary gland, skeletal muscle and thyroid. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of endocrine/metabolic-related disorders, such as obesity and diabetes.
Panel 1.3D Summary: Ag2872 This gene showed highest expression in samples derived from brain tissue, either normal tissue or cell lines derived from malignant brain tissue. Please see panel General_Screening_Vl .5 for a discussion of this gene in the central nervous system.
There was substantial expression of this gene in a number of cancer cell lines, including ovarian cancer, breast cancer and renal cancer cell lines. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of ovarian, breast or renal cancer.
There was limited expression of this gene in endocrine/metabolic related tissues. Low expression of this gene was seen in adipose, pancreas, reproductive tissues (testes and ovaries) and skeletal muscle. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of different endocrine/metabolic diseases, such as diabetes and obesity.
Panel 2.2 Summary: Ag2872 Expression of this gene was highest in a sample derived from normal kidney tissue adjacent to a kidney cancer (CT = 31.2). In addition, there was substantial expression of this gene in samples derived from a cluster of breast cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of breast cancer.
Panel 2D Summary: Ag2δ72 Expression of this gene was highest in a sample derived from an ovarian cancer (CT = 2δ.4). Thus, expression of this gene can be used to distinguish ovarian cancer tissue from the other tissues in the panel. There was substantial expression of this gene in samples derived from a cluster of breast cancers and well as a small but appreciable difference in expression between a set of colon cancers and their respective normal adjacent tissues. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of breast cancer, ovarian cancer or colon cancer.
Panel 3D Summary: Ag2δ72 This gene showed highest expression in a sample derived from a small cell lung cancer derived cell line (CT = 26.1). There was substantial expression of this gene in two other lung cancer derived cell lines and a pancreatic cancer derived cell line. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of lung cancer.
Panel 4.1D Summary: Ag4δ47 Expression of this gene was highest in kidney (CT = 2δ.3). This gene was also highly expressed in small airway epithelium treated with TNF-a and IL-lb, and to a lower extent in the same non treated tissue and also in the mucoepidermoid cell line H292 upon treatment with the Th2 cytokines IL-4 and 11-9, cytokines that are responsible for increasing mucus production in this cell line. Expression of this gene was up-regulated in bronchial epithelium upon TNF-a and IL-1 treatment. Moderate expression of this gene was also seen in activated B cells. This gene encodes for a mixed lineage kinase 2 (MLK2) like molecule which was reported to activate JNK pathway (Hirai S, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, Fukuyama K, Ohno S. Differential activation of two JNK activators, MKK7 and SEK1, by MKN2δ-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. J Biol Chem 1998 Mar 27;273(13)7406-12). Activation of this pathway has been associated to many inflammatory reactions in many cell types. Il-lb which is produced during airway inflammation, has been shown to regulate JNK pathway, for example (Hallsworth MP, Moir LM, Lai D, Hirst SJ. Inhibitors of mitogen-activated protein kinases differentially regulate eosinophil-activating cytokine release from human airway smooth muscle. Am J Respir Crit Care Med 2001 Aug 15;164(4):688-97 ). The role of 11-4 and IL-13 in airway remodeling appears also to use JNK pathway (Hashimoto S, Gon Y, Takeshita I, Maraoka S, Horie T. IL-4 and IL-13 induce myofibroblastic phenotype of human lung fibroblasts through c-Jun NH2 -terminal kinase-dependent pathway. J Allergy Clin Immunol 2001 Jun;107(6):1001-δ). Finally, JNK is required for the production of metalloproteinases (Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001 Jul; 108(1 ):73-81), molecules that play an important role in inflammatory disesease such as rheumatoid arthritis, asthma, and inflammatory bowel disease (IBD). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of inflammatory diseseas such as in chronic obstractive pulmonary disease, asthma, emphysema and also rheumatoid arthritis/osteoarthritis, IBD and psoriasis.
Panel 5 Islet Summary: Ag2δ72 This gene was expressed at low to moderate levels in pancreatic islet cells and placenta in panel 51. Please refer to General_screening_panel_vl.5 for a synopsis ofthe the potential function of this MLK2-like gene in endocrine and metabolic disorders.
AT. CG56142-01 and CG56142-04: Prostasin.
Expression of gene CG56142-01 and CG56142-04 were assessed using the primer-probe sets Ag2δδδ and Ag4095, respectively, described in Table ATA and ATB. Results ofthe RTQ-PCR rans are shown in Tables ATC, ATD, ATE, ATF, ATG and ATH.
Table ATA. Probe Name Ag2δδδ
Figure imgf001308_0001
Table ATB. Probe Name Ag4095
Figure imgf001308_0002
Table ATC. General_screening_panel_vl.4
Figure imgf001308_0003
Figure imgf001309_0001
Figure imgf001310_0001
Figure imgf001311_0001
Table ATE. Panel 2D
Figure imgf001311_0002
Figure imgf001312_0001
Table ATF. Panel 3D
Figure imgf001312_0002
Figure imgf001313_0001
Figure imgf001314_0001
Table ATG. Panel 4. ID
Figure imgf001314_0002
Figure imgf001315_0001
Figure imgf001316_0001
General_screening_panel_vl.4 Summary: Ag4095 The expression of this gene was highest and almost exclusive to a sample derived from a colon cancer tissue (CT=27). Low to moderate levels of expression of this gene was also detected in two ovarian, two colon and a brain cancer cell lines. Expression levels of this gene is useful as marker to detect colon, ovarian, and brain cancers. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drags targeting this gene or gene product is useful in the treatment of colon ovarian, and brain cancers.
General screening panel vl.5 Summary: Ag28δδ Significant expression of the CG56142-01 gene was limited to cancer cell lines, with highest expression in a colon cancer cell line (CT=27.9). This gene encodes a putative prostasin, which has been identified as a potential marker of epithelial ovarian cancer. Based on the expression in these panels, expression of this gene will be used as a marker for colon cancer. Therapeutic modulation this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of colon cancer.
Panel 2D Summary: Ag2δδδ The expression ofthe CG56142-01 gene appears to be highest and almost exclusive to a sample derived from a colon cancer (CT=30). Therapeutic modulation this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product is useful in the treatment of colon cancer.
Panel 3D Summary: Ag2δδδ The expression ofthe CG56142-01 gene was highest and almost exclusive to a sample derived from a gastric cancer cell line (CT=34.1). Thus, the expression of this gene is useful as marker for gastric cancer. Moreover, therapeutic modulation of this gene, throguh the use of small molecule drags, antibodies or protein therapeutics might be beneficial in the treatment of gastric cancer.
Panel 4.1D Summary: Ag4095 This gene, which encodes a prostasin homolog, was expressed almost exclusively in resting neutrophils (CTs=31). This expression was down regulated in neutrophils activated by TNF-alpha and LPS. Modulation of this gene, encoded protein and/or use of agonist to activated this gene or gene product is useful to reduce activation of these inflammatory cells and eliminate the symptoms in patients with Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstractive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis, AIDS or other immunodeficiencies. general oncology screening panel_v_2.4 Summary: Ag4095 Expression of this gene was highest in a prostate adenocarcinoma sample (CT = 33). Expression of this gene was upregulated in 2/4 colon cancer samples compared to normal adjacent tissue. Therefore, expression of this gene is useful as a marker for colon cancer. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drags targeting this gene or gene product are beneficial in the treatment of colon cancer.
AV. CG56144-01: 7 transmembrane receptor.
Expression of gene CG56144-01 was assessed using the primer-probe sets Agl221, Agl221b and Agl60δ, described in Tables AVA, AVB and AVC. Results of the RTQ-PCR runs are shown in Tables AVD, AVE, AVF and AVG.
Table AVA. Probe Name Agl 221
Figure imgf001317_0001
Figure imgf001318_0001
Table AVB. Probe Name Agl 22 lb
Figure imgf001318_0002
Table AVC. Probe Name Agl 608
Figure imgf001318_0003
Table AVD. AI_comprehensive panel_vl .0
Figure imgf001318_0004
Figure imgf001319_0001
Table AVE. Panel 1.3D
Figure imgf001320_0001
Figure imgf001321_0001
Table AVF. Panel 2D
Figure imgf001321_0002
Figure imgf001322_0001
Table AVG. Panel 4D
Figure imgf001322_0002
Figure imgf001323_0001
Figure imgf001324_0001
Figure imgf001325_0001
AI_comprehensive panel_vl.O Summary: Agl 22 lb Highest expression of this gene was detected in synovial fluid from a rheumatoid arthritis (RA) patient (CT=33). This gene showed preferential expression in rheumatoid arthritis bone, cartilage, synovium and synovial fluid samples. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of rheumatoid arthritis.
Panel 1.3D Summary: Agl221b/Agl60δ The expression of this gene was seen predominantly in one gastric cancer cell line derived from a metastasis (CTs=30-32). This expression profile indicates that this gene plays a role in liver cancer metastasis to gastric. Significant expression was also seen in bone marrow and spleen indicating that this gene is also important in the hematopoietic system. Modulation of this gene, encoded protein and or use of antibodies or small molecule drug are useful in treatment of gastric cancer, and disorders related to hematopoietic system.
Panel 2D Summary: Agl221b Highest expression of this gene was detected in normal lung (CTs=31). Expression of this gene was downregulated in the lung cancers. Upregulation of this gene and/or use of agonist is useful in the treatment of lung cancers.
Significant expression of this gene was also seen in breast cancer, thyroid cancer, gastric cancer, ovarian cancer and renal cell carcinoma. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of breast cancer, thyroid cancer, gastric cancer, ovarian cancer and renal cell carcinoma.
Panel 4D Summary: Agl221b/Agl60δ Highest expression of this gene was detected in resting monocytes and LPS activated macrophages (CTs=28-33). The expression of this gene in resting monocytes indicated that this gene encoded a differentation antigen. Signalling through this molecule will stimulate activation. This gene was down regulated during activation of monocytes, but upregulated in activated macrophages indicating a role in antigen presentation. Significant expression of this gene was also detected in resting and activated LAK cells, two way MLR, resting eosinophils, activated PBMC and liver cirrhosis samples. Modulation of this gene, encoded protein and/or use of antibodies or small molecule targeting this gene or gene product will help reduce or eliminate inflammatory and autoimmune diseases such as asthma/allergy, emphysema, psoriasis, arthritis, IBD Colitis, liver ciπhosis.
AW. CG56146-01, CG56146-02 and CG56146-03: 7 transmembrane receptor.
Expression of gene CG56146-01, CG56146-02 and CG56146-03 were assessed using the primer-probe sets Agl 175 and Agl201, described in Tables AWA and AWB. Results ofthe RTQ-PCR rans are shown in Tables AWC, AWD, AWE and AWF. CG56146-02 and CG56146-03 represent full-length physical clones.
Table AWA. Probe Name Agl 175
Figure imgf001326_0001
Table AWB. Probe Name Agl201
Figure imgf001326_0002
Table AWC. AI_comprehensive panel_vl.O
Figure imgf001326_0003
Figure imgf001327_0001
Figure imgf001328_0001
Table AWD. Panel 1.3D
Figure imgf001328_0002
Figure imgf001329_0001
Figure imgf001330_0001
Table AWE. Panel 2D
Figure imgf001330_0002
Figure imgf001331_0001
Table AWF. Panel 4D
Figure imgf001331_0002
Figure imgf001332_0001
Figure imgf001333_0001
AI_comprehensive panel_vl.O Summary: Agl l75/Agl201 Highest expression of this gene was detected in orthoarthritis bone and matched control psoriasis sample (CTs=32-33.5). Significant expression of this gene was also seen in psoriasis and asthma samples. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of orthoarthritis, asthma and psoriasis.
Panel 1.3D Summary: Agl201 This gene showed significant expression mainly in testis (CTs=33-34). Modulation of this gene and encoded protein is useful in the treatment of testis related disorders such as fertility and hypogonadism.
Panel 2D Summary: Agl 201 Highest expression of this gene was detected in prostate cancer sample (CTs=32). This gene was over-expressed in tumors derived from tissues responsive to steroid hormones- ovarian, uterine and prostate cancers. Expression level of this gene is useful as a marker to detect tumor cells responsive to steroid hormones and to differentiate hormone-responsive and non-hormone responsive tumors that are known to lead to different clinical outcomes. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of ovarian, uterine and prostate cancers.
Panel 4D Summary: Agl 201 This gene showed low expression in activated basophils (CTs=32-33). Basophils are one of the key cell mediators of inflammation during asthma and allergy (Oliver JM, Kepley CL, Ortega E, Wilson BS, 2000, Immunologically mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human Fcvar epsilonRl signaling pathway. Immunopharmacology 48(3):269-δl). This expression indicated that this gene has a potential role in inflammation and helps the basophils to extravasate into the site of inflammation and/or in the activation of these cells. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful to inhibit nasal and lung inflammation caused by basophil activation and effectively reduce or eliminate symptoms of asthma, emphysema, and allergic rhinitis.
AX. CG56258-02: sodium/calcium exchanger.
Expression of gene CG56258-02 was assessed using the primer-probe sets Ag2903, Ag5035 and Ag6163, described in Tables AXA, AXB and AXC. Results ofthe RTQ-PCR rans are shown in Tables AXD, AXE, AXF, AXG, AXH, AXI and AXJ.
Table AXA. Probe Name Ag2903
Figure imgf001334_0001
Table AXB. Probe Name Ag5035
Figure imgf001334_0002
Table AXC. Probe Name Ag6163
Figure imgf001334_0003
Figure imgf001335_0001
Figure imgf001336_0001
Table AXE. Cellular OA/RA
Figure imgf001336_0002
Figure imgf001337_0001
Table AXF. PGI 1.0
Figure imgf001337_0002
Figure imgf001338_0001
Table AXG. Panel 1.3D
Figure imgf001338_0002
Figure imgf001339_0001
Table AXH. Panel 2D
Figure imgf001339_0002
Figure imgf001340_0001
Table AXI. Panel 4. ID
Figure imgf001340_0002
Figure imgf001341_0001
Table AXJ. Panel 5 Islet
Figure imgf001342_0001
Figure imgf001343_0001
AI_comprehensive panel_vl.0 Summary: Ag2903/Ag5035 The highest expression of this gene was detected in an OA bone sample. Expression ofthe CG5625δ-01 gene was highly associated with synovium and bone samples from patients with osteoarthritis when compared to expression in the control samples. Therapeutic modulation of this gene, expressed protein and or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of osteoarthritis.
Cellular OA/RA Summary: Ag2903 Moderate expression of this gene was detected in chondrosarcoma cell line (SWl 353) and synoviocyte cell line (CTs=31-32). Significant expression of this gene was also detected in cells treated with IL-1 -beta, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases which participate in the destruction of cartilage observed in Osteoarthritis (OA). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the prevention or treatment ofthe degeneration of cartilage observed in OA.
PGI1.0 Summary: Ag2903 The highest expression level of this gene was detected in a lung fibrosis sample (CT=26). It was upregulated in lung fibrosis and several emphysema samples. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung fibrosis and emphysema.
Panel 1.3D Summary: Ag2903 Expression of this gene was highest in fetal skeletal muscle (CT=26.δ). Significant levels of expression are also seen in adult skeletal muscle and fetal heart. This gene encodes a putative sodium/calcium exchanger. Altered levels of intracellular calcium have been implicated in many diseases, including type 2 diabetes. Based on its expression profile and homology to a calcium transport protein, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of type 2 diabetes.
Moderate to low levels of expression were seen in all regions ofthe CNS examined. Inhibition of calcium uptake has been shown to decrease neuronal death in response to cerebral ischemia. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of stroke by decreasing the total infarct volume.
Panel 2D Summary: Ag2903 The expression ofthe CG5625δ-01 gene was consistent with the profile seen in Panel 1.3D. Expression was highest and most prominent in a normal muscle sample (CT=2δ.7). Please see Panel 1.3D for discussion of this gene in metabolic disease.
Panel 4.1D Summary: Ag5035 Expression ofthe CG5625δ-02 gene was restricted to TNF-alpha and IL-1 beta treated lung and dermal microvasculature (CTs=33-34). Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruitment of effector inflammatory cells. The expression of this gene in dermal microvascular endothelial cells indicated that this protein product is involved in inflammatory responses to skin disorders, including psoriasis. Expression in lung microvascular endothelial cells indicated that the protein encoded by this gene is involved in lung disorders including asthma, allergies, chronic obstractive pulmonary disease, and emphysema. Therapeutic modulation of this gene, expressed protein and or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of psoriasis, asthma, allergies, chronic obstractive pulmonary disease, and emphysema.
Panel 5 Islet Summary: Ag2903/Ag5035 The expression of this gene in this panel was consistent with the profile seen in Panel 1.3D. Expression was highest and most prominent in sampels derived from skeletal muscle (CTs=29-33). Please see Panel 1.3D for discussion of this gene in metabolic disease.
AY. CG56258-04: SCL8A3 splice form B-like.
Expression of gene CG56258-04 was assessed using the primer-probe sets Ag5035 and Ag6142, described in Tables AYA and AYB. Results of the RTQ-PCR runs are shown in Tables AYC, AYD, AYE and AYF.
Table AYA. Probe Name Ag5035
Figure imgf001344_0001
Table AYB. Probe Name Ag6142
Figure imgf001345_0001
Figure imgf001345_0002
Figure imgf001346_0001
Table AYD. General_screening_panel_vl.5
Figure imgf001346_0002
Figure imgf001347_0001
Figure imgf001348_0001
Figure imgf001349_0001
Table AYE. Panel 4. ID
Figure imgf001349_0002
Figure imgf001350_0001
Table AYF. Panel 5 Islet
Figure imgf001350_0002
Figure imgf001351_0001
AI_comprehensive panel_vl.O Summary: Ag5035/ Ag6142 The highest expression of this gene was detected in an OA bone sample. Expression ofthe The expression of this gene was highly associated with synovium and bone samples from patients with osteoarthritis when compared to expression in the control samples. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of osteoarthritis.
General_screening_panel_vl.5 Summary: Ag5035/Ag6142 This gene showed highly brain preferential expression (CTs=30-31). Inhibition of calcium uptake has been shown to decrease neuronal death in response to cerebral ischemia. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of stroke by decreasing the total infarct volume.
Moderate levels of expression were seen in fetal and adult skeletal muscle (CTs=30-31). This gene encodes a putative sodium/calcium exchanger. Altered levels of intracellular calcium have been implicated in many diseases, including type 2 diabetes. Based on its expression profile and homology to a calcium transport protein, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of type 2 diabetes.
Panel 4.1D Summary: Ag5035 Expression of this gene was restricted to TNFalpha and IL-1 beta treated lung and dermal microvasculature (CTs=33-34). Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruitment of effector inflammatory cells. The expression of this gene in dermal microvascular endothelial cells indicated that this protein product may be involved in inflammatory responses to skin disorders, including psoriasis. Expression in lung microvascular endothelial cells indicated that the protein encoded by this transcript may also be involved in lung disorders including asthma, allergies, chronic obstractive pulmonary disease, and emphysema. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of psoriasis, asthma, allergies, chronic obstructive pulmonary disease, and emphysema.
Panel 5 Islet Summary: Ag5035 Expression of this gene was highest and most prominent in sampels derived from skeletal muscle (CTs=29-33). Please see Panel 1.5 for discussion of this gene in metabolic disease.
AZ. CG56262-01: Ca-binding transporter.
Expression of gene CG56262-01 was assessed using the primer-probe sets Ag2δ96 and Ag2920, described in Tables AZA and AZB. Results ofthe RTQ-PCR rans are shown in Tables AZC, AZD, AZE, AZF and AZG.
Table AZA. Probe Name Ag2δ96
Start
Primers Sequences Length SEQ ΓD Position No
Forward 5 ' -gtcagcttctcttgctttgaga-3 ' 22 900 1344
TET-5 ' - cactgtcaggcactcgccaatgt -3 '
Probe TAMRA 23 932 1345
Reverse 5 ' -ctgtatttctggaagcattcca-3 ' 22 964 1346
Table AZB. Probe Name Ag2920
Figure imgf001352_0001
134δ
Figure imgf001353_0001
Table AZD. Panel 1.3D
Figure imgf001353_0002
Figure imgf001354_0001
Table AZE. Panel 4D
Figure imgf001355_0001
Figure imgf001356_0001
Table AZF. Panel 5 Islet
Figure imgf001356_0002
Figure imgf001357_0001
Figure imgf001357_0002
CNS_neurodegeneration_vl.O Summary: Ag2δ96/Ag2920 This gene was found to be down-regulated in the temporal cortex of Alzheimer's disease patients. Upregulation of this gene or its protein product, or treatment with specific agonists for this receptor is of use in reversing the dementia, memory loss and neuronal death associated with this disease.
Panel 1.3D Summary: Ag2δ96/Ag2920 Highest expression of this gene was detected in the cerebral cortex (CTs=26). High expression of this gene was seen predominantly in all the regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene encodes a Ca binding transporter. Ca++ is critical for synaptic vesicle release (Kovacs I, Neurochem Int 199δ Nov;33(5):399-405). Targeting this gene with a small molecule drag, protein therapeutic or antibody is useful for the treatment of diseases resulting from altered/inappropriate synaptic transmission such as epilepsy, schizophrenia, bipolar disorder, depression, and mania.
This gene also had moderate levels of expression adult and fetal heart, skeletal muscle and liver, and adipose. This gene product is homologous to a mitochondrial calcium-dependent transporter. Since intracellular calcium homeostasis is critically important for energy metabolism and signal transduction, modulation of this gene or gene product is useful as a therapeutic for metabolic and endocrine diseases.
Moderate expression was also seen in almost all the cancer cell lines on this panel. This shows that expression of this gene product is required for cell growth and proliferaton in almost all cell types.
Panel 4D Summary: Ag2δ96/Ag2920 Moderate to low expression of this gene was detected across a wide range of cells on this panel including epithelium, fibroblasts, and endothelial cells. Lower but still significant levels of expression were also seen in monocytes/macrophages, T and B cells, which all play an importan role in both innate and adaptive immunity. Expression of this gene was highest in the B cell lymphoma cell line, and the NCI H292 mucoepidermoid cell line (CTs=26.4-27). Inhibition ofthe function ofthe protein encoded by this transcript with a small molecule drag, protein therapeutic, or antibody is useful for the reduction ofthe symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, COPD, emphysema, psoriasis, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.
Panel 5 Islet Summary: Ag2δ96 This gene showed widespread expression in this panel with highest expression seen in uterus from a non-diabetic patient (CT=28.8). Significant expression of this gene was seen in adipose, skeletal muscle, uteras, kidney, small intestine and a liver cancer cell line, which is in agreement with expression seen in panel 1.3D. general oncology screening panel_v_2.4 Summary: Ag2896/Ag2920 Highest expression of this gene was detected in a kidney cancer sample (CTs=27). Prominent expression of this gene was also seen in melanoma and prostate cancer samples. This gene was overexpressed in lung cancer samples when compared to expression in matched normal adjacent tissue. Expression of this gene or its protein product is useful as a marker of lung cancers. Targeting this gene or its protein product with a small molecule drug, protein therapeutic, or antibody is useful in the treatment of these cancers.
BA. CG56398-01: Na/glucose cotransporter.
Expression of gene CG56398-01 was assessed using the primer-probe set Ag2925, described in Table BAA. Results of he RTQ-PCR rans are shown in Tables BAB, BAC, BAD and BAE.
Table BAA. Probe Name Ag2925
Figure imgf001359_0001
Table BAB. CNS_neurodegeneration_vl.O
Figure imgf001359_0002
Figure imgf001360_0001
Table BAC. Panel 1.3D
Figure imgf001360_0002
Figure imgf001361_0001
Table BAD. Panel 2D
Figure imgf001361_0002
Figure imgf001362_0001
Table BAE. Panel 4D
Figure imgf001362_0002
Figure imgf001363_0001
Figure imgf001364_0001
CNS_neurodegeneration_vl.O Summary: Ag2925 This gene was found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful for decreasing neuronal death and as a treatment for this disease.
Panel 1.3D Summary: Ag2925 Expression of this gene was brain-specific. Highest expression was detected in the hippocampus (CT=28) a region that degenerates in Alzheimer's disease. Expression of this gene or its protein product is useful for distinguishing brain tissue from non-neural tissue. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of neurodegenerative diseases.
Panel 2D Summary: Ag2925 This gene was most highly expressed in a normal kidney sample (CT= 2δ.95). Expression of this gene was lost in the adjacent cancer samples. The loss of expression of this gene or its protein product is useful as a marker for kidney cancer. This gene was also expressed at low levels in breast and bladder cancer samples and was absent or extremely low in normal adjacent tissue. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of breast and bladder cancer and as a diagnostic marker for the presence of these cancers.
Panel 4D Summary: Ag2925 Expression of this transcript was almost exclusively restricted to colon and thymus, with highest expression in normal colon (CT=29). This gene was expressed at much lower levels in IBD colon. The protein encoded by this transcript is involved in normal tissue/cellular functions in the kidney and colon. Loss-of-expression of this protein is useful as a diagnostic marker for lupus or IBD.
BB. CG56645-03 and CG56645-04: Sodium glucose cotransporter.
Expression of genes CG56645-03 and CG56645-04 were assessed using the primer-probe sets Ag2966 and Ag6497, described in Tables BBA and BBB. Results of the RTQ-PCR runs are shown in Tables BBC, BBD and BBE. Table BBA. Probe Name Ag2966
Figure imgf001365_0001
Table BBB. Probe Name Ag6497
Figure imgf001365_0002
Table BBC. Panel 1.3D
Figure imgf001365_0003
Figure imgf001366_0001
Table BBD. Panel 2D
Figure imgf001366_0002
Figure imgf001367_0001
Table BBE. Panel 4D
Column A ■ - Rel. Exp.(%) Ag2966, Run 160660646
Tissue Name A Tissue Name
Secondary Thl act 0.0 HUVEC IL-lbeta 1 0 A.3
Secondary Th2 act 0.0 HUVEC IFN gamma 0.9
Figure imgf001368_0001
Figure imgf001369_0001
Panel 1.3D Summary: Ag2966 Expression of this gene, a sodium-glucose cotransporter homolog, was limited to the kidney (CTs=29). This restricted expression was in agreement with published data, where secondary active transport of glucose in the kidney is mediated by sodium glucose cotransporter. (Bissonnette P. J Physiol 1999 Oct 15;520 Pt 2:359-71). Expression of this gene or its protein product is useful as a marker of kidney tissue. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of diseases that affect the kidney, including diabetes.
Panel 2D Summary: Ag2966 Expression of this gene was predominantly limited to the kidney. The expression was downregulated in kidney cancer samples. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of diseases that affect the kidney, including kidney cancer.
Panel 4D Summary: Ag2966 Expression of this gene was predominantly found in normal tissue from thymus, lung, colon and kidney. This expression profile indicates that the protein product is involved in glucose transport and normal homeostasis in these tissues. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful for maintaining or restoring normal function to these organs during inflammation.
BC. CG56667-01: GPCR.
Expression of gene CG56667-01 was assessed using the primer-probe set Ag2973, described in Table BCA. Results ofthe RTQ-PCR rans are shown in Table BCB.
Table BCA. Probe Name Ag2973
Figure imgf001369_0002
Figure imgf001370_0001
Table BCB. Panel 4D
Figure imgf001370_0002
Figure imgf001371_0001
Panel 4D Summary: Ag2973 Significant expression of the CG56667-01 gene was detected in a liver cirrhosis sample (CT = 32.7). Expression of this gene was not detected in normal liver in Panel 1.3D, suggesting that its expression is unique to liver cirrhosis. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of fibrosis that occurs in liver ciπhosis. Expression of this gene or expressed protein is useful in the diagnosis of liver cirrhosis.
BD. CG56868-01: ADAM7.
Expression of gene CG5686δ-01 was assessed using the primer-probe sets Agl 322, Agl 322b, Ag2071 and Ag209δ, described in Tables BDA, BDB, BDC and BDD. Results of the RTQ-PCR rans are shown in Table BDE.
Table BDA. Probe Name Agl 322
Figure imgf001371_0002
Table BDB. Probe Name Agl 322b
Figure imgf001372_0001
Table BDC. Probe Name Ag2071
Figure imgf001372_0002
Table BDD. Probe Name Ag2098
Figure imgf001372_0003
Table BDE. Panel 1.2
Figure imgf001372_0004
Figure imgf001373_0001
Panel 1.2 Summary: Agl 322 Expression of this gene was highest in testis (CT value = 29). Low expression was also seen in prostate (CT value = 34.6). The gene or encoded protein is useful as a marker for these tissues. This gene encodes a protein with homology to ADAM proteins, which are membrane disintegrin-metalloproteases. The expression of several other ADAM proteins has been shown to be testis-specific and these proteins are thought to play a role in fertilization (Hooft van Huijsduijnen R. (1998) ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha. Gene 206: 273-282). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of diseases ofthe prostate and testis, including infertility.
BE. CG56870-01: NDR3.
Expression of genes CG56870-01 and CG56δ70-06 was assessed using the primer-probe set Ag2075, described in Table BEA. Results ofthe RTQ-PCR runs are shown in Tables BEB, BEC, BED and BEE.
Table BEA. Probe Name Ag2075
Figure imgf001374_0001
Table BEB. Panel 1.3D
Figure imgf001374_0002
Figure imgf001375_0001
Table BEC. Panel 2.2
Figure imgf001375_0002
Figure imgf001376_0001
Table BED. Panel 3D
Figure imgf001377_0001
Figure imgf001378_0001
Table BEE. Panel 4D
Figure imgf001378_0002
Figure imgf001379_0001
Figure imgf001380_0001
Panel 1.3D Summary: Ag2075 Highest expression of the CG56870-01 and CG56δ70-06 genes was detected in the cerebral cortex (CT=24.2). Thus expression of this gene is useful in distinguishing this sample from other samples in the panel. Significant expression of this gene is observed throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG56δ70-01 and CG56δ70-06 genes encode an Ndr3 homolog which is a putative member of Ndr family. This family consists of proteins from different gene families: Ndrl/RTP/Drgl/NDRGl, Ndr2, andNdr3 (PFAM: IPR004142). NDRG1 is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lorn. Recently, NDRG4, another memember of Ndr family, was shown to be expressed in neurons of the brain and spinal cord. Its expression was markedly decreased in the brain of Alzheimer's disease patient (Zhou RH, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T. (2001) Characterization ofthe human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Genomics 73(l):δ6-97). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
This gene also showed moderate levels of expression in adipose, adrenal, thyroid, liver, heart, thyroid and skeletal muscle. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of metabolic and endocrine disease, including Types 1 and 2 diabetes and obesity. In addition, there was significant expression in other samples derived from breast cancer cell lines, lung cancer cell lines, renal cancer cell lines and colon cancer cell lines. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of breast, lung, renal or colon cancer.
Panel 2.2 Summary: Ag2075 Highest expression ofthe CG56δ70-01 and CG56δ70-06 genes was detected in breast cancer sample (CT=29.δ9). Expression of this gene is useful as a marker for breast cancer. There was significant expression in other samples derived from breast cancers, kidney cancers and colon cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of breast, kidney or colon cancer.
Panel 3D Summary: Ag2075 The expression of this gene was highest in a sample derived from a lung cancer cell line (DMS-79)(CT=26.4). There was significant expression in other samples derived from pancreatic cancer cell lines, lung cancer cell lines, brain cancer cell lines and cervical cancer cell lines. Expression of this gene is useful as a marker for pancreatic, lung, brain and cervical cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of pancreatic, lung, brain or cervical cancer.
Panel 4D Summary: Ag2075 Expression of the CG56δ70-01 and CG56δ70-06 genes was ubiquitous througout this panel, with highest expression in samples derived from ionomycin treated Ramos (B cell) cells (CT=26.1). Expression was also detected in PWM treated PBMC cells and PWM treated B lymphocytes. Therapeutic modulation of these gene, expressed proteins and/or use of antibodies or small molecule drags targeting the genes or gene products are useful in the treatment of autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression ofthe disease process, such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstractive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.
BF. CG57109-01 and CG57109-05: doublecortin/CAMkinase.
Expression of genes CG57109-01 and CG57109-05 was assessed using the primer-probe sets Agl 137, Agl 150, Agl δ60, Ag3112 and Ag42δl , described in Tables BFA, BFB, BFC, BFD and BFE. Results ofthe RTQ-PCR runs are shown in Tables BFF, BFG, BFH, BFI, BFJ, BFK, BFL and BFM. CG57109-05 represents a full-length physical clone ofthe CG57109-01 gene. Table BFA. Probe Name Agl 137
Figure imgf001382_0001
Table BFB. Probe Name Agl 150
Figure imgf001382_0002
Table BFC. Probe Name Agl δ60
Figure imgf001382_0003
Table BFD. Probe Name Ag3112
Figure imgf001382_0004
Table BFE. Probe Name Ag4281
Figure imgf001382_0005
Table BFF. AI.05 chondrosarcoma
Figure imgf001383_0001
Table BFG. Al comprehensive panel vl .0
Figure imgf001383_0002
Figure imgf001384_0001
Table BFH. General_screening_panel_vl.4
Figure imgf001384_0002
Figure imgf001385_0001
Table BFI. PGI1.0
Figure imgf001385_0002
Figure imgf001386_0001
Table BFK. Panel 3D
Figure imgf001386_0002
Figure imgf001387_0001
Figure imgf001388_0001
Table BFM. Panel 4D
Figure imgf001388_0002
13δ4
Figure imgf001389_0001
Figure imgf001390_0001
AI.05 chondrosarcoma Summary: Agl 860 Highest expression was detected in IL-1/TNF-a treated chondrosarcoma cells (SWl 353 cell lines). Expression of this gene was up-regulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases, which participate in the destraction of cartilage observed in Osteoarthritis (OA). Therapeutic modulation of these genes, expressed proteins and/or use of antibodies or small molecule drags targeting the genes or gene products are useful in the treatment of the degeneration of cartilage observed in OA.
AI_comprehensive panel_vl.O Summary: Agl 860 Highest expression in this panel was seen in synovium from an OA patient (CT=337). Overall, the CG57109-01 and CG57109-05 genes were expressed in OA tissue but not in normal joint tissue and were expressed in pulmonary tissue from patients with atopic asthma but not in normal lung tissue. Therapeutic modulation of these genes, expressed proteins and/or use of antibodies or small molecule drags targeting the genes or gene products are useful in the treatment of inflammatory diseases including OA and asthma.
General_screening_panel_vl.4 Summary: Ag4281 Highest expression of the
CG57109-01 and CG57109-05 genes was detected in the fetal brain (CT=29.5). Overall, expression of this gene was highly brain-specific in this panel, with moderate levels of expression in the amygdala, hippocampus, thalamus and spinal cord and low but significant levels in the cerebral cortex and the substantia nigra. CG57109-01 and
CG57109-05 encode a novel doublecortin/CAM kinase like protein. Other members of this family have been implicated in the calcium-signaling pathway that controls neuronal migration in the developing brain. In addition, CAM kinase has been shown to play a crucial role in hippocampal Long Term Potentiation (LTP) from studies in transgenic and knock-out mice, and may also play a role in memory formation in the mature nervous system as well as the developing brain. CAM kinases have also been shown to phosporylate tau, an integral component ofthe neurofibrillary tangles seen in
Alzheimer's, in a manner which shifts tau electrophorytic motility to that seen in the AD brain. Furthermore, tau from AD brains shows aberrent phosphorylation. Therapeutic modulation of these gene, expressed protein and/or use of antibodies or small molecule drugs targeting the genes or gene products are useful in the treatment of learning and memory deficits that are a result of aging or neurodegenerative disease and also in the treatment of neurologic disorders themselves, including Alzheimer's disease.
Moderate to low levels of expression were also seen in a variety of samples from normal tissues, including testis, fetal and adult heart and skeletal muscle and fetal lung.
Expression was much higher in fetal lung (CT=32.3) when compared to expression in the adult counterpart (CT=40). Expression of this gene is useful for distinguishing between the fetal and adult source of this tissue.
PGI1.0 Summary: Ag3112 Highest expression was detected in a colon sample from an ulcerative colitis patient (CT=307). Strong expression was observed in a cluster of colon samples derived from ulcerative colitis patients and in fϊbrotic lung samples. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of inflammatory conditions ofthe colon and lung.
Panel 3D Summary: Ag3112 Expression was restricted to a sample derived from a lung cancer cell line (CT=32.6). Expression of this gene or expressed protein could be used to detect the presence of lung cancer. Therapeutic modulation of these genes, expressed proteins and/or use of antibodies or small molecule drags targeting the genes or gene products are useful in the treatment of lung cancer.
Panel 4D Summary: Agl δ60 This transcript was highly expressed in activated dermal fibroblasts, endothelial cells, and astrocytes after treatment with IL-1 or TNFalpha, with highest expression in TNF alpha and IL-1 beta treated HPAECs (CT=30.9). The proteins encoded by the CG57109-01 and CG57109-05 genes have homology to protein kinase and may be involved in leukocyte extravasation from the peripheral blood into tissues (Borbiev T, Am J Physiol Lung Cell Mol Physiol 2001 May;280(5):L983-90). Therapeutic modulation of these genes, expressed proteins and/or use of antibodies or small molecule drags targeting the genes or gene products are useful in the treatment of inflammation due to asthma, allergy, emphysema, osteoarthritis, colitis, psoriasis, or delayed type hypersensitivity. Agonistic therapies are useful for directing leukocyte traffic into tumors or sites of infection.
Ag3112 Highest expression ofthe transcript was seen in IL-1 beta treated dermal fibroblasts (CT=30.4). Expression was in agreement with the profile seen with Aglδ60, except no expression was seen in astrocytes.
BG. CG57399-04: PHOSPHOLIPASE ADRAB-B PRECURSOR. Expression of gene CG57399-04 was assessed using the primer-probe set Ag3952, described in Table BGA. Results ofthe RTQ-PCR rans are shown in Tables BGB and BGC. CG57399-04 represents a full-length physical clone ofthe CG57399-02 gene.
Table BGA. Probe Name Ag3952
Figure imgf001392_0001
Table BGB. General_screening_panel_vl.4
Figure imgf001392_0002
Figure imgf001393_0001
Table BGC. Panel 5 Islet
Figure imgf001393_0002
Figure imgf001394_0001
General_screening_panel_vl.4 Summary: Ag3952 Highest expression of this gene was seen in the adrenal gland (CT=29). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of Addi son's disease and other adrenalopathies. This gene showed significant expression in adipose, heart, skeletal muscle, pituitary, thyroid, and pancreas. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of endocrine or metabolic disease, including Types 1 and 2 diabetes, obesity and pancreatitis.
Expression of this gene was detected in samples derived from colon, gastric, lung and breast cancers. Expression of this gene is useful for detecting the presence of these cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of colon, gastric, lung and breast cancers.
Low but significant levels of expression were seen for all regions ofthe CNS examined. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of CNS disorders such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, schizophrenia and multiple sclerosis.
Panel 5 Islet Summary: Ag3952 Highest expression was detected in small intestine (CT=32.5). Low but significant expression was also detected in adipose.
BH. CG57562-02: cation-transporting ATPase. Expression of gene CG57562-02 was assessed using the primer-probe sets Agl 179, Ag32δ7 and Ag6477, described in Tables BHA, BHB and BHC. Results ofthe RTQ-PCR rans are shown in Tables BHD, BHE and BHF.
Table BHA. Probe Name Agl 179
Figure imgf001395_0001
Table BHB. Probe Name Ag32δ7
Figure imgf001395_0002
Table BHC. Probe Name Ag6477
Figure imgf001395_0003
Table BHD. General_screening_panel_vl.4
Figure imgf001395_0004
Figure imgf001396_0001
Table BHE. Panel 4D
Figure imgf001396_0002
Figure imgf001397_0001
Figure imgf001398_0001
Figure imgf001398_0002
Figure imgf001399_0001
General_screening_panel_vl.4 Summary: Ag3287 - This gene showed moderate to high expression in all samples on this panel, with the highest level of expression in breast cancer cell line BT 549 (CT=25.0). The widespread expression of this gene indicates that the gene product may be involved in cell differentiation and growth.
This gene was widely expressed among tissues with metabolic function, including adipose, adult and fetal skeletal muscle and heart, the pancreas, fetal liver, and the adrenal, thyroid, and pituitary glands. This expression profile indicates that this gene product is involved in metabolic function. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of metabolic disorders, such as obesity and diabetes.
This gene showed widespread expression of this gene in the brain. This indicates that the protein encoded by this gene is important for normal neurological function. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.
Panel 4D Summary: Agl 179/Ag3287 This gene was expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members ofthe T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression indicates that this gene product may be involved in homeostatic processes for these and other cell types and tissues.
This pattern is in agreement with the expression profile in General_screening_panel_vl .5 and also indicates a role for the gene product in cell survival and proliferation.
Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis. general oncology screening panel_v_2.4 Summary: Ag3287 Highest expression was detected in a colon cancer sample (CT=26.4), with prominent expression seen in squamous cell carcinoma and melanoma samples. This gene was overexpressed in colon and lung cancers when compared to expression in the normal adjacent tissues. Expression of this gene is useful as a marker of colon and lung cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of colon and lung cancers.
Bl. CG57758-03: RENAL SODIUM DICARBOXYLATE COTRANSPORTER.
Expression of gene CG57758-03 was assessed using the primer-probe sets Ag3326 and Ag3692, described in Tables BIA and BIB. Results ofthe RTQ-PCR rans are shown in Tables BIC, BID and BIE. CG5775δ-03 represents a full-length physical clone ofthe CG57758-01 gene.
Table BIA. Probe Name Ag3326
Figure imgf001400_0001
Table BIB. Probe Name Ag3692
Figure imgf001400_0002
Figure imgf001400_0003
Figure imgf001401_0001
Figure imgf001402_0001
Table BID. Panel 4. ID
Figure imgf001402_0002
139δ
Figure imgf001403_0001
General_screening_panel_vl.4 Summary: This gene was highly expressed in fetal liver (CT=26.5-27.0) and moderately expressed in adult liver and liver cancer cell line HepG2. This result agrees with the results seen in Panel 5 (expression in HepG2). These results are in agreement with published data that show a novel sodium dicarboxylate transporter in brain, choroid plexus kidney, intestine and liver (Chen XZ, Shayakul C, Berger UV, Tian W, Hediger MA. Characterization of a rat Na+- dicarboxylate cotransporter. J Biol Chem 199δ Aug 14;273(33):20972-δl; Pajor AM, Gangula R, Yao X. Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain. Am J Physiol Cell Physiol 2001 May;280(5):C1215-23). Expression of this gene is useful as a marker for liver derived tissue.
This gene was expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, and cerebral cortex. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
Low but significant levels of expression were also seen in the adrenal gland. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of metabolic disorders ofthe adrenal gland, including adrenoleukodystrophy and congenital adrenal hyperplasia.
Panel 4.1D Summary: Ag3692 Significant expression of this gene was seen only in kidney and a liver cirrhosis sample (CTs=34.0). These results confirm that this gene was expressed in liver derived samples. The presence in the kidney was also in agreement with published results. Please see Panel 1.4. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of kidney inflammation.
BJ. CG58504-01: ADAMTS12.
Expression of gene CG58504-01 was assessed using the primer-probe set Ag2475, described in Table BJA. Results ofthe RTQ-PCR rans are shown in Tables BJB, BJC, BJD, BJE and BJF.
Table BJA. Probe Name Ag2475
Figure imgf001404_0001
Table BJB. HASS Panel vl .0
Figure imgf001404_0002
Figure imgf001405_0001
Table BJC. Panel 1.3D
Figure imgf001405_0002
Figure imgf001406_0001
Table BJD. Panel 2D
Figure imgf001407_0001
Figure imgf001408_0001
Table BJF. Panel 4D
Figure imgf001408_0002
HASS Panel vl.O Summary: Ag2475 This gene was expressed in glioma samples and primary astrocytes in culture (highest expression CT=27.δ) indicating a role in cell growth. Expression of this gene in Uδ7-MG (a mixed glial/astrocytoma cell line) was repressed by reducing the oxygen content ofthe environment. Seram starvation of these cells induces expression. This effect was not observed in T24 (bladder cancer) cells and thus may reflect tissue specific regulation of this gene.
Panel 1.3D Summary: Ag2475 Highest expression ofthe CG5δ504-01 gene was seen in fetal skeletal muscle (CT=2δ.4). This expression was significantly higher than expression seen in the corresponding adult tissue (CT=36.9). In addition, the relative overexpression of this gene in fetal skeletal muscle indicates that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in restoring muscle mass or function in the treatment of muscle related diseases.
Low levels of expression were also seen in other metabolic tissues, including adipose and fetal heart, indicating a potential role for this gene in obesity and/or diabetes.
Moderate levels of expression were also seen in cell lines derived from brain cancer, breast cancer, renal cancer, lung cancer, colon cancer and melanoma. Since cell lines and fetal tissues are, on the whole, more proliferative than normal tissues, this expression profile indicates that this gene might be involved in cell proliferation. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of cancer or other diseases that involve cell proliferation. Furthermore, therapeutic targeting of this gene product with a monoclonal antibody is anticipated to limit or block the extent of tumor cell migration and invasion and tumor metastasis, particularly in brain cancer, breast cancer, renal cancer, lung cancer, colon cancer and melanoma. Expression of this gene or expressed protein is useful in the diagnosis and detection of these cancers.
Panel 2D Summary: Ag2475 Highest expression ofthe CG58504-01 gene was seen in a lung cancer (CT=28.3). This gene encodes a putative member ofthe ADAMS family. The ADAMS family of proteins has multiple domains associated with function; A fibronectin domain involved cell/extracellular matrix interaction, a thrombospondin domain involved in angiogenesis and a metalloproteinase domain involved in matrix degredation. This multi-domain structure has implications for this molecule in several tumorigenic processes, including invasion and metastasis and proliferation and cell survival. Thus, the metalloproteinase domain might play a role in cell invasion and metastasis, the fibronectin domain may play a role in cell adhesion or survival and the thrombospondin domain might play a role in angiogenesis. ADAM 12-S cleaves insulinlike growth factor binding protein-3 (IGFBP-3). IGFBP-3 enhances the p53-dependent apoptotic response of colorectal cells to DNA damage. IGF-BP3 is inversely, associated with risk for colorectal cancer. Expression of IGFBP-3 induces growth inhibition and differentiation ofthe human colon carcinoma cell line, Caco-2. All these data indicate that the protein encoded by CG5δ504-01 acts by cleaving and inactivating IGFBP-3 limiting its anti-tumor activity. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of those cancer types, like colon, lung, kidney, bladder ovarian and gastric tumors where the gene is overexpressed in the tumor compared to the normal adjacent tissue.
Panel 4D Summary: Ag2475 Highest expression ofthe CG5δ504-01 gene was seen in resting coronary artery smooth muscle cells (CT=27.3). Moderate to low levels of expression were seen in resting astrocytes and TNFalpha + IL-lbeta treated astrocytes and coronary artery smooth muscle cells, TNF alpha and IL-4 treated dermal fibroblasts, and lung. Lower levels of expression were seen in treated and untreated lung fibroblasts. This expression indicates that this gene is a marker of smooth muscle. In addition, expression in fibroblasts and astrocytes indicates that this gene product may be involved in inflammatory conditions that involve these cells. This gene encodes a putative ADAMTS molecule which has been implicated in extracellular proteolysis and may play a critical role in the tissue degradation seen in arthritis and other inflammatory conditions (Kuno K. : J Biol Chem 1997 Jan 3;272(l):556-62). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of pathological and inflammatory lung and skin disorders that include chronic obstractive pulmonary disease, asthma, allergy, psoriasis and emphysema.
BK. CG59309-01: ACYL-COENZYME A THIOESTER HYDROLASE.
Expression of gene CG59309-01 was assessed using the primer-probe set Ag3540, described in Table BKA. Results ofthe RTQ-PCR rans are shown in Tables BKB, BKC, BKD and BKE.
Table BKA. Probe Name Ag3540
Figure imgf001411_0001
Table BKB. General_screening_panel_vl .4
Column A - Rel. Exp.(%) Ag3540, Run 217049291
Tissue Name A Tissue Name
Adipose 1.3 Renal ca. TK-10 1 1 o A.i
Figure imgf001412_0001
Figure imgf001413_0001
Table BKC. Panel 4D
Figure imgf001413_0002
Figure imgf001414_0001
Table BKD. Panel 5 Islet
Figure imgf001414_0002
Figure imgf001415_0001
Figure imgf001415_0002
General_screening_panel_vl.4 Summary: Ag3540 This gene was most highly expressed in a breast cancer cell line (CT=27.1). Expression of this gene is useful as a marker to detect the presence of breast cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of breast cancer.
Among metabolic tissues, this gene, an acyl coA thioesterase homolog, had a low level of expression in adipose, adult and fetal liver, adrenal, thyroid and pancreas. Acyl CoA thioesterases have multiple roles in lipid homeostasis (Hunt MC, Alexson SE. The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Prog Lipid Res. 2002 Mar;41(2):99-130; Hunt MC, Nousiainen SE, Huttunen MK, Orii KE, Svensson LT, Alexson SE. Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism. J Biol Chem. 1999 Nov 26;274(4δ):34317-26). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of endocrine and metabolic disease, including Types 1 and 2 diabetes and obesity.
In addition, this gene was expressed in all CNS regions examined. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of neurologic disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, stroke, schizophrenia and multiple sclerosis.
Panel 4D Summary: Ag3540 Highest expression of the CG59309-01 gene was seen in the thymus and colon (CTs=31.5). Significant levels of expression were also seen in a cluster of treated and untreated samples derived from the NCI-H292 mucoepidermoid cell line. Expression of this gene is useful as a marker for thymus and colon tissue. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in regulating T cell development in the thymus or in the treatment of T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis. Small molecule or antibody therapeutics designed against this protein disrupts T cell development in the thymus and functions as an immunosuppresant for tissue transplants.
Panel 5 Islet Summary: Ag3540 This gene had moderate expression in skeletal muscle (highest expression CT=30.5). Acyl CoA thioesterases function in peroxisomal fatty acid oxidation (Hunt MC, Solaas K, Kase BF, Alexson SE. Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. J Biol Chem. 2002 Jan 11 ;277(2): 1128-38). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in increasing fatty acid oxidation in muscle, and in the treatment of Type 2 diabetes and obesity. general oncology screening panel_y_2.4 Summary: Ag3540 Prominent expression was detected in a kidney cancer sample (CT=31.δ). Expression of this gene is useful as a marker of this cancer. Targeting this gene or gene product with small molecule, antibody, or protein therapeutics is useful in the treatment of kidney cancer.
BL. CG59490-01: S562_F7.
Expression of gene CG59490-01 was assessed using the primer-probe sets Agl038, Agl590, Agl91 δ, Ag2δ99, Ag720, Ag730 and Ag443, described in Tables BLA, BLB, BLC, BLD, BLE, BLF and BLG. Results ofthe RTQ-PCR runs are shown in Tables BLH, BLI, BLJ, BLK and BLL.
Table BLA. Probe Name Agl03δ
Figure imgf001417_0001
Table BLB. Probe Name Agl 590
Figure imgf001417_0002
Table BLC. Probe Name Agl 918
Figure imgf001417_0003
Table BLD. Probe Name Ag2899
Primers Sequences Length Start SEQ ED
Figure imgf001418_0001
Table BLE. Probe Name Ag720
Figure imgf001418_0002
Table BLF. Probe Name Ag730
Figure imgf001418_0003
Table BLG. Probe Name Ag443
Figure imgf001418_0004
Table BLH. Ardais Breastl.O
Figure imgf001418_0005
Figure imgf001419_0001
Table BLI. Panel 1.3D
Figure imgf001419_0002
Figure imgf001420_0002
Figure imgf001420_0001
Figure imgf001421_0001
Figure imgf001422_0001
Table BLJ. Panel 2D
Figure imgf001422_0002
Figure imgf001423_0001
Figure imgf001424_0001
Table BLK. Panel 3D
Figure imgf001424_0002
Figure imgf001425_0001
Figure imgf001426_0001
Table BLL. Panel 4D
Figure imgf001426_0002
Figure imgf001427_0001
Figure imgf001428_0001
Figure imgf001429_0001
Ardais Breastl.O Summary: Ag720 Expression of this gene was highest in a breast cancer sample (CT=27.1). Significant expression of this gene was detected in 45/64 breast cancer samples but only 1/7 normal breast samples. Gene or protein expression levels are useful for the detection of breast cancer. Therapeutic modulation of the activity of this gene or its protein product using nucleic acid, protein, antibody or small molecule drugs are useful in the treatment of breast cancer.
This gene encodes a protein with homology to mastocytoma protease precursor. Mast cell tryptase is a secretory granule associated serine protease with trypsin-like specificity. It is released extracellularly during mast cell degranulation. Mast cells (MC) have been associated with diverse human cancers. The primary function of these cells is to store and release a number of biologically active mediators, including the serine proteases tryptase and chymase. These proteases have been closely related with angiogenesis and tumor invasion, two critical steps during tumor progression. Malignant breast tumors have two to three times more tryptase-containing than chymase-containing mast cells, with the number of mast cells with trptase activity being significantly higher (p<0.02) than in benign lesions. In malignant lesions, tryptase-containing mast cells were concentrated at the tumor edge, i.e. the invasion zone (Kankkunen JP, Harvima IT, Naukkarinen A. Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions. Int J Cancer. 1997 Jul 29; 72(3): 3δ5-8). It is therefore likely that this protein has a role in tumor invasion and metastasis.
Panel 1.3D Summary: Agl 590/2899 The expression of this gene was assessed in four independent runs using two different probe/primer sets. All ofthe runs show excellent concordance. The expression of this gene appears to be highest in a sample derived from an ovarian cancer cell line (OVCAR-5) (CTs=31-32). In addition, there appears to be substantial expression associated with a colon cancer cell line, a gastric cancer cell line and pituitary tissue. Thus, the expression of this gene could be used to distinguish OVCAR-5 cells from the other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, protein therapeutics or antibodies might be of benefit in the treatment of ovarian cancer, gastric cancer or colon cancer
Panel 2D Summary: Ag720/1590/2899 The expression of this gene was assessed in five independent runs in panel 2D using three different primer/probe paris. There is excellent concordance of between these runs. The expression of this gene was highest and exclusive to breast cancer samples (CTs=26-28). Thus, the expression of this gene could be used to distinguish breast cancer samples from other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, protein therapeutics or antibodies might be of benefit in the treatment of breast cancer.
Panel 3D Summary: Ag720/2δ99 The expression of this gene was highest and almost exclusive to a sample derived from a lung cancer cell line (DMS-79)(CTs=29- 31). In addition, there was low but substantial expression associated with samples derived from an ovarian cancer cell line, a uterine cancer cell line and a pancreatic cancer cell line. The expression of this gene or expressed protein is useful in the detection of lung cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung cancer, ovarian cancer, pancreatic cancer or uterine cancer.
Panel 4D Summary: Agl590/Agl91δ/Ag2δ99 This gene, a tryptase homolog, was expressed at significant levels in IL-9-activated NCI-H292 cells, pulmonary mucoepidermoid cells. Colon, lung, and thymus tissues also showed low levels of expression of this gene. The expression in lung and in the activated NCI-H292 cell line - often used as a model for airway epithelium - is consistent with published reports of tryptase in the lung (Walls AF, Bennett AR, Godfrey RC, Holgate ST, Church MK. Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung disease. Clin Sci (Lond) 1991 Aug;δl(2):lδ3-δ). In addition, tryptase has been shown to be up-regulated in lungs affected by disease and specifically in COPD (Grashoff WF, Sont JK, Sterk PJ, Hiemstra PS, de Boer WI, Stolk J, Han J, van Krieken JM. Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages. Am J Pathol 1997 Dec;151(6):17δ5-90). Tryptase has also been implicated in the recruitment of granulocytes and epithelial repair (Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-δ production and intercellular adhesion molecule- 1 expression. J Immunol 1996 Jan l;156(l):275-δ3). Based On these observations, small molecule antagonists or antagonist antibodies are useful in the reduction or elimination of symptoms in patients with lung diseases including asthma, allergy, or chronic obstructive pulmonary disease.
BM. CG59693-01 and CG59693-03: 20 alpha-hydroxysteroid dehydrogenase. Expression of genes CG59693-01 and CG59693-03 was assessed using the primer-probe set Ag3562, described in Table BMA. Results ofthe RTQ-PCR runs are shown in Tables BMB, BMC, BMD, BME, BMF, BMG, BMH and BMI. CG59693-03 represents a full-length physical clone ofthe CG59693-01 gene.
Table BMA. Probe Name Ag3562
Figure imgf001431_0001
Table BMB. Ardais Panel v.1.0
Figure imgf001431_0002
Table BMC. CNS_neurodegeneration_vl .0
Figure imgf001431_0003
Figure imgf001432_0001
Figure imgf001432_0002
Figure imgf001433_0001
Table BME. HASS Panel vl .0
Figure imgf001433_0002
Figure imgf001434_0001
Table BMF. Oncology_cell_line_screening_panel_v3.1
Figure imgf001434_0002
Figure imgf001435_0001
Figure imgf001436_0001
Table BMG. Panel 2D
Figure imgf001436_0002
Figure imgf001437_0001
Table BMH. Panel 4. ID
Figure imgf001438_0001
Figure imgf001439_0001
Table BMI. Panel 5 Islet
Figure imgf001439_0002
Figure imgf001440_0001
Ardais Panel v.1.0 Summary: Ag3562 Highest expression of this gene was seen in lung cancer (CT=19.1). In addition, this gene was more highly expressed in three lung cancer samples than in the corresponding normal adjacent tissue. Thus, expression of this gene is useful as a marker of this cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung cancer.
CNS_neurodegeneration_vl.O Summary: Ag3562 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene was found to be upregulated in the temporal cortex of Alzheimer's disease patients when analyzed by ANCOVA, (p = 0.002). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in prevention or slowing the progression of Alzheimer's disease.
General_screening_panel_vl.4 Summary: Ag3562 Highest expression of this gene was detected in lung cancer A549 cell line (CT=20.01). High expression of this gene was also seen in cluster of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene is useful as a marker to detect the presence of these cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.
Among tissues with metabolic or endocrine function, this gene was expressed at moderate to high levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
In addition, this gene was expressed at high levels in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
HASS Panel vl.O Summary: Ag3562. The expression of this gene was not increased by oxygen deprivation, acidic or a serum starved environment in the breast , bladder, pancreatic and prostate cell line in this panel.
However expression was increased in a glioblastoma/ astrocytoma cell line when these cells are subjected to an acidic environment (Maximum expression Uδ7-MG FI 1 ; CT=23.96) which indicates that expression may also be upregulated in the acidic regions of brain cancers. Moderate to low expression was also shown in 2 of 5 glioma and 2 of 4 medulloblastoma tissue samples in this panel. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of brain cancer.
Oncology_cell_line_screeningjpanel_v3.1 Summary: Ag3562 Highest expression of this gene was detected in lung carcinoid sample (CT=217). High to moderate levels of expression of this gene was also seen in number of cancer samples including tongue, breast, prostate, melanoma, bone marrow, bladder, pancreatic, renal, lymphoma, ovarian, cervical, uterine, gastric, lung and brain cancer. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of cancers, including tongue, breast, prostate, melanoma, bone marrow, bladder, pancreatic, renal, lymphoma, ovarian, cervical, uterine, gastric, lung and brain cancer.
Panel 2D Summary: Ag3562 Highest expression of this gene was detected in lung cancer (CT=23.5). High expression of this gene was seen in number of lung cancer samples. Expression of this gene was higher in cancer sample as compared to corresponding adjacent control samples. Therefore, expression of this gene is useful as marker to detect the presence of lung cancer. Therapeutic modulation of this gene, expressed protein and or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung cancer.
High to moderate levels of expression of this gene was also seen in number of cancer samples including colon, gastric, ovarian, liver, breast, thyroid, kidney, and prostate cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of these cancers.
Panel 4.1D Summary: Ag3562 Highest expression of this gene was detected in IL-4 treated dermal fibroblasts (CT=25.2). This gene was expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression indicates that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_vl .5 and also indicates a role for the gene product in cell survival and proliferation. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.
Panel 5 Islet Summary: Ag3562 Highest expression of this gene was detected in islet cells (Bayer patient 1) (CT=25.3). High to moderate levels of expression of this gene were also seen in adipose, skeletal muscle, placenta, uterus, liver, heart, small intestine and kidney. Therefore, therapeutic modulation ofthe activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
BN. CG59839-02: CATION-TRANSPORTING ATPASE.
Expression of gene CG59839-02 was assessed using the primer-probe sets Agl417, Ag3604 and Ag3956, described in Tables BNA, BNB and BNC. Results ofthe RTQ-PCR runs are shown in Tables BND, BNE and BNF.
Table BNA. Probe Name Ag 1417
Figure imgf001442_0001
Table BNB. Probe Name Ag3604
Figure imgf001443_0001
Table BNC. Probe Name Ag3956
Figure imgf001443_0002
Figure imgf001443_0003
Figure imgf001444_0001
Table BNE. Panel 4. ID
Figure imgf001444_0002
Figure imgf001445_0001
Figure imgf001446_0001
Figure imgf001446_0002
General_screening_panel_yl.4 Summary: Ag3604/Ag3956 Highest expression of this gene was seen in a breast cancer cell line (CTs=24-25). High levels of expression were also seen in all the cell lines on this panel. Significant levels of expression were seen in the fetal tissue samples. Expression in fetal liver and lung (CTs=27) was significantly higher than in the adult liver and lung (CTs=31.5). Furthermore, this expression profile indicates a role for this gene product in cell growth and proliferation.
Among tissues with metabolic function, this gene was expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues indicates that this gene product plays a role in normal neuroendocrine and metabolic tissues. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.
This gene was also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.
The CG94δ20-02 gene codes for a cation-transporting ATPase A, P type. A P- type cation transporting ATPase has been implicated in Menkes disease, a disorder of copper transport characterized by progressive neurological degeneration and death in early childhood (Harrison MD, Dameron CT. (1999) Molecular mechanisms of copper metabolism and the role of the Menkes disease protein. J Biochem Mol Toxicol 1999;13(2):93-106). Thus, the CG94δ20-02 gene product may play a role in this disease. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of Menkes disease.
Panel 4.1D Summary: Ag3604/Ag3956 Highest expression ofthe CG94δ20-02 gene was seen in LPS stimulated monocytes (CTs=25-26). The protein encoded by this gene may therefore be involved in the activation of monocytes in their function as antigen-presenting cells. This indicates that therapeutics that block the function of this membrane protein are useful as anti-inflammatory therapeutics for the treatment of autoimmune and inflammatory diseases. Antibodies or small molecule therapeutics that stimulate the function of this protein may be useful therapeutics for the treatment of immunosupressed individuals.
This gene was expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members ofthe T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression indicates that this gene product is involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_vl .4 and also indicates a role for the gene product in cell survival and proliferation. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis. general oncology screening panel_v_2.4 Summary: Ag3604 Highest expression was detected in a lung cancer sample, with prominent expression seen in prostate and melanoma cancer samples. This gene was more highly expressed in lung, kidney, and colon cancers than in the normal adjacent tissues. Expression of this gene is useful as a marker of these cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung, colon, kidney, melanoma and prostate cancers.
BO. CG90866-03 and CG90866-04: Serine/threonine-protein kinase.
Expression of genes CG90δ66-03 and CG90δ66-04 was assessed using the primer-probe sets AglOδδ, Ag941 and Ag3771, described in Tables BOA, BOB and BOC. Results ofthe RTQ-PCR runs are shown in Tables BOD, BOE, BOF and BOG.
Table BOA. Probe Name AglOδδ
Figure imgf001448_0001
Table BOB. Probe Name Ag941
Figure imgf001449_0001
Table BOC. Probe Name Ag3771
Figure imgf001449_0002
Table BOD. AJ comprehensive panel vl .0
Figure imgf001449_0003
Figure imgf001450_0001
Table BOE. General_screening_panel_vl .4
Figure imgf001450_0002
Figure imgf001451_0001
Table BOF. Panel 4. ID
Figure imgf001451_0002
Figure imgf001452_0001
144δ
Figure imgf001453_0001
Figure imgf001453_0002
Figure imgf001454_0001
AI_comprehensive panel_vl.O Summary: Ag3771 Highest expression of this gene was detected in a bone sample from a rheumatoid arthritis patient (CT=26). Prominent expression was detected in a cluster of rheumatoid arthritis samples, including samples from bone, synovium, and cartilage. Targeting this gene or gene product with small molecule, antibody, or protein therapeutics is useful in the treatment of rheumatoid arthritis.
General_screening_panel_vl.4 Summary: Ag3771 Highest expression of this gene was detected in fetal lung sample (CT=27.5). The expression of this gene is much higher in fetal (27-31) as compared to adult lung and liver (CT=32-3 ). Therefore, expression of this gene can be used to distinguish these fetal from adult tissues. In addition, the relative overexpression of this gene in these fetal tissues indicates that the protein product enhances growth or development of these tissues in the fetus and thus may also act in a regenerative capacity in the adult. Therapeutic modulation of this gene, expressed protein and or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of lung and liver related diseases.
Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.
In addition, this gene was expressed at moderate levels in all regions ofthe central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.
Panel 4.1D Summary: Ag3771 Highest expression of this gene was detected in resting neutropils (CT=27.3). In addition, this gene was expressed in TNFalpha + LPS treated neutrophils. Therefore, the gene product may reduce activation of these inflammatory cells and be useful as a protein therapeutic to reduce or eliminate the symptoms in patients with Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in increasing the immune response in patients with AIDS or other immunodeficiencies.
In addition, expression of this gene was down-regulated in cytokine stimulated LAK cells and LPS-treated monocytes. Therefore, expression of this gene is useful for distinguishing these stimulated versus resting cells.
In addition, low to moderate expression of this gene was also seen in B cells, dendritic cells, endothelial cells, fibroblasts and normal tissues represented by kidney, thymus, lung, and colon. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of cancer, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis, microbial and viral infections. general oncology screening panel_v_2.4 Summary: Ag941/Ag3771 Highest expression of this gene was detected in a kidney cancer sample (CTs=27). Prominent expression was also seen in prostate and melanoma cancer samples. This gene was overexpressed in the kidney cancer samples when compared to expression in the normal adjacent tissue. Expression of this gene is useful as a marker of kidney cancer. Therapeutic modulation of this gene, expressed protein and or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of kidney, melanoma and prostate cancers.
BP. CG91708-02: Stromelysin-1.
Expression of gene CG91708-02 was assessed using the primer-probe set Ag3395, described in Table BPA. Results ofthe RTQ-PCR runs are shown in Tables BPB, BPC, BPD, BPE, BPF, BPG, BPH, BPI and BPJ. CG9170δ-02 represents a full- length physical clone ofthe CG9170δ-01 gene.
Table BPA. Probe Name Ag3395
Figure imgf001455_0001
Figure imgf001456_0001
Table BPB. AI.05 chondrosarcoma
Figure imgf001456_0002
Table BPC. Al comprehensive panel_vl .0
Figure imgf001456_0003
Figure imgf001457_0001
Table BPD. Ardais Panel v.1.0
Figure imgf001457_0002
Table BPE. Ardais Prostate 1.0
Figure imgf001458_0001
Figure imgf001459_0001
Figure imgf001460_0001
Table BPG. Panel 2D
Figure imgf001460_0002
Figure imgf001461_0001
Table BPH. Panel 3D
Figure imgf001461_0002
Figure imgf001462_0001
Table BPI. Panel 4D
Figure imgf001463_0002
Figure imgf001464_0001
Table BPJ. Panel 5 Islet
Figure imgf001465_0001
AI.05 chondrosarcoma Summary: Ag3395 Highest expression of this gene was detected in IL-1 and TNF alpha treated chondrosarcoma cell line (SW1353) (CT=18.δ). Expression of this gene was upregulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases. This gene codes for matrix metalloproteinase 3 (MMP3), which is capable of degrading proteoglycan, fibronectin, laminin, and type IV collagen. MMPs are known to participate in the destruction of cartilage observed in Osteoarthritis (OA). Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the prevention of the degeneration of cartilage observed in OA.
Al comprehensive panel_vl.O Summary: Ag3395 This gene was expressed in orthoarthritis (OA) tissues but not in control tissue. This gene encodes MMP3 protein, which has been shown to be present in OA joint (Bluteau G, Conrozier T, Mathieu P, Vignon E, Herbage D, Mallein-Gerin F. Matrix metalloproteinase- 1, -3, -13 and aggrecanase-1 and -2 are differentially expressed in experimental osteoarthritis. Biochim Biophys Acta 2001 May 3; 1526(2): 147-5 δ) tissue and may contribute to the pathology of this disease. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of OA.
Ardais Panel v.1.0 Summary: Ag3395 Highest expression of this gene was detected in a normal adjacent lung (375) sample (CT=247). Significant expression of this gene was seen in normal and cancer samples from lung. This gene shows upregulated expression in 4/6 cancer samples relative to corresponding normal adjacent samples. Therefore, modulation of this, expressed protein, and/or use of antibodies or small molecule drug targeting this gene or gene product will be of use to treat lung cancer.
Ardais Prostate 1.0 Summary: Ag3395 Highest expression of this gene was detected in prostate cancer (D4F) sample (CT=27). Significant expression of this gene was seen in normal and cancer samples from prostate. The expression of this gene was relatively higher in number of prostate cancer samples. Therefore, modulation of this, expressed protein, and/or use of antibodies or small molecule drag targeting this gene or gene product will be of use to treat prostate cancer.
General_screening_panel_vl.4 Summary: Ag3395 The expression of this gene was highest in a sample derived a brain cancer cell line (U87-MG) (CTs=22-24). Significant expression of this gene was also seen in brain cancer cell lines, colon cancer cell lines and melanoma cell lines. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product is useful in the treatment of brain or colon cancer or melanoma.
Among tissues with metabolic function, this gene was expressed at low levels in pancreas, adipose, and fetal skeletal muscle. This expression indicates that this gene product plays a role in normal neuroendocrine and metabolic and that disregulated expression of this gene will contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.
This gene was also expressed at low but significant levels in the hippocampus, a structure critical for learning and memory. The hippocampus-preferential expression of this gene indicate that it plays a role in learning and memory processes. Modulation of this gene is useful in treatment of CNS disorders involving memory deficits, including Alzheimer's disease and aging.
Panel 2D Summary: Ag3395 Highest expression of this gene was detected in a sample derived from a colon cancer (CT=26.8). Significant expression was also seen in gastric cancer, bladder cancer, breast cancer, lung cancer and colon cancer. Expression levels of this gene is useful as marker to detect these cancers. Therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule drag targeting this gene or gene product is useful in the treatment of gastric, bladder, breast, lung or colon cancers.
Panel 3D Summary: Ag3395 The expression of this gene was highest in a sample derived from a brain cancer cell line (SF-295) (CTs=24-26). Significant levels of expression of this gene was also seen in cell lines derived from brain, lung, ovarian, cervical, pancreatic, vulval, and bone cancers. Therapeutic modulation of this gene, encoded protein and/or use of antibodies or small molecule drugs is useful in the treatment of brain lung, ovarian, cervical, pancreatic, vulval, and bone cancers.
Panel 4D Summary: Ag3395 The expression level of this gene was upregulated in lung and dermal fibroblasts after treatment with IL-1 beta and or TNF alpha (CTs=21.5-22.5). High expression of this gene was also seen in activated small airway and bronchial epithelium, activated naive T cells (CD45RA CD4 lymphocyte), activated asatrocytes, resting and activated coronary artery SMC cells. This expression profile indicates that the stromolysin protein encoded by this gene may facilitate tissue destruction, remodeling and participate in cell ell interactions that prevent the resolution ofthe inflammatory response. Modulation of this gene, encoded protein and/or use of antibodies or small molecule drug targeting this gene or gene product will help to reduce or eliminate inflammation in the skin and lung resulting from psoriasis, allergy, asthma, emphysema, promote wound healing and prevent delayed type hypersensitivity type reactions.
Panel 5 Islet Summary: Ag3395 Highest expression of this gene was detected in islet cells (bayer patient 1) (CT=27.9). Significant expression of this gene was also seen in adipose, skeletal muscle and uteras. Modulation of this gene or expressed protein is useful in the treatment of metabolic disorders, including type II diabetes and obesity.
BQ. CG94235-01: thymidylate kinase.
Expression of gene CG94235-01 was assessed using the primer-probe sets Agl9δ0 and Ag3909, described in Tables BQA and BQB. Results ofthe RTQ-PCR runs are shown in Tables BQC, BQD, BQE, BQF, BQG, BQH, BQI and BQJ.
Table BOA. Probe Name Agl 980
Figure imgf001468_0001
Table BOB. Probe Name Ag3909
Figure imgf001468_0002
Table BQC. AI.05 chondrosarcoma
Figure imgf001468_0003
Table BQD. Al comprehensive panel_vl .0
Figure imgf001468_0004
Figure imgf001469_0001
Figure imgf001470_0001
Table BQE. General_screening_panel_vl.4
Figure imgf001470_0002
Figure imgf001471_0001
Table BOF. Panel 1.3D
Figure imgf001471_0002
Figure imgf001472_0001
146δ Table BOG. Panel 2D
Figure imgf001473_0001
Figure imgf001474_0001
Table BOH. Panel 4. ID
Figure imgf001474_0002
Figure imgf001475_0001
Table BOJ. Panel 5 Islet
Figure imgf001475_0002
Figure imgf001476_0001
AI.05 chondrosarcoma Summary: Agl9δ0 Highest expression of this gene was detected in the IL-1 beta/TNF-a treated chondrosarcoma cell line (SW1353). Expression of this gene was up-regulated upon IL-1 treatment, a potent activator of pro- inflammatory cytokines and matrix metalloproteinases, which participate in the destruction of cartilage observed in Osteoarthritis (OA). Modulation ofthe expression of this transcript in chondrocytes by either small molecules, antibody, or protein therapeutics is useful for preventing the degeneration of cartilage observed in OA.
AI_comprehensive panel_vl.0 Summary: Agl9δ0 Highest expression was detected in normal tissue adjacent to psoriasis (CTs=30.5-31.2). Expression of this gene was induced in bone tissue, synovial fluid, synovial fluid cells and synovium from arthritis patients (rheumatoid-RA and osteoarthritis-OA), while the expression of this transcript in these samples from normal patients was much lower. Other tissues including skin and lung also expressed this transcript. However, a consistent expression in diseased tissue, as compared to adjacent tissue or normal lung, is not apparent. This may be due to contamination with activated monocytes which highly express this transcript (see panel 4. ID) Modulation ofthe expression of this transcript in chondrocytes by either small molecules, antibody, or protein therapeutics is useful for treating rheumatoid arthritis and preventing the degeneration of cartilage observed in OA. General_screening_panel_vl.4 Summary: Ag3909 Highest expression ofthe CG94235-01 gene was detected in a gastric cancer cell line (CTs=23.6-24.4). Thus, expression of this gene is useful as a marker of gastric cancer. This gene encodes a putative thymidylate kinase, a DNA synthesis enzyme necessary for cell growth. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of gastric cancer.
Among tissues with metabolic function, this gene was expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. The widespread expression among these tissues indicates that this gene product may play a role in normal neuroendocrine and metabolic disorders. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.
In addition, this gene was expressed at much higher levels in fetal lung, liver and skeletal muscle tissue (CTs=2δ-30) when compared to expression in the adult counterpart (CTs=32.5-35). Thus, expression of this gene is useful for distinguishing between the fetal and adult source of these tissues.
This gene was also expressed at moderate to low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.
Panel 1.3D Summary: Agl9δ0 Highest expression of the CG94235-01 gene in this panel was seen in a gastric cancer cell line (CT=26). Overall, expression was in reasonable agreement with the results in Panel 1.4. Moderate to low levels of expression were seen in metabolic tissues including adipose, adult and fetal liver, skeletal muscle, heart, pituitary, thyroid, adrenal and pituitary. Moderate to low levels of expression were seen in all CNS regions examined.
In addition, higher levels of expression were seen in fetal liver (CT=30.2) when compared to expression in adult liver (CT=337). Thus, expression of this gene is useful for distinguishing between the adult and fetal sources of this tissue. Panel 2D Summary: Agl980 Highest expression ofthe CG94235-01 gene was seen in normal bladder (CT=27.3). In addition, higher levels of expression were seen in ovarian, bladder and lung cancers when compared to expression in normal adjacent tissue. Thus, expression of this gene is useful as a marker of these cancers. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of ovarian, bladder and lung cancers.
Panel 4.1D Summary: Ag3909 Highest expression of the CG94235-01 gene was seen in LPS treated monocytes (CT=25.4). Prominent levels of expression were also seen in LPS activated macrophages and dendritic cells. This transcript encodes a protein that may be important in the normal regulation of cytokines. Inappropriate regulation of the protein encoded by this gene may result in the enhanced and uncontrolled expression of inflammatory cytokines. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of osteoarthritis and rheumatoid arthritis.
Panel 5 Islet Summary: Ag3909 Highest expression ofthe CG94235-01 gene was seen in islet cells (CT=33.4). Low but significant levels of expression were seen in other metabolic tissues, including adipose, placenta and skeletal muscle. Please see Panel 1.4 for discussion of this gene in metabolic disease.
BR. CG95175-01: EPHRIN TYPE-A RECEPTOR 7 PRECURSOR.
Expression of gene CG95175-01 was assessed using the primer-probe sets Ag3992 and Ag612, described in Tables BRA and BRB. Results ofthe RTQ-PCR runs are shown in Tables BRC, BRD, BRE and BRF.
Table BRA. Probe Name Ag3992
Figure imgf001478_0001
Table BRB. Probe Name Ag612
Figure imgf001478_0002
Figure imgf001479_0001
Table BRC. CNS_neurodegeneration_vl.O
Figure imgf001479_0002
Table BRE. Panel 1.3D
Figure imgf001479_0003
Figure imgf001480_0001
Table BRF. Panel 4D
Column A - Rel. Exp.(%) Ag612, Run 145645058
Figure imgf001481_0001
Figure imgf001482_0001
CNS_neurodegeneration_vl.0 Summary: Ag612 This gene was found to be down-regulated in the temporal cortex of Alzheimer's disease patients. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of dementia/memory loss associated with this disease and neuronal death.
Panel 1.3D Summary: Ag612 Highest expression ofthe CG95175-01 gene was detected in testis (CT=29). In addition, high expression of this gene was also detected in all the region ofthe central nervous system examined, and in a cluster of lung cancer, colon cancer, renal cancer, a liver cancer, breast cancer, ovarian cancer and an astrocytoma cell lines, pancreas, pituitary gland, and the gastrointestinal tract. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of diseases ofthe central nervous system including Alzheimer's disease.
Panel 4D Summary: Ag612 Highest expression of this gene was detected in IFN gama treated NCI-H292 cells (CT=33). Moderate to low expression of this gene was also seen in cytokine treated and untreated NCI-H292 cells, liver cirrhosis and colon tissue samples. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of chronic obstractive pulmonary disease, asthma, allergy, and emphysema, liver cirrhosis, autoimmune and inflammatory disease affecting colon including Crohn's disease and ulcerative colitis.
BS. CG99638-01: SODIUM/NUCLEOSIDE COTRANSPORTER 1. Expression of gene CG9963δ-01 was assessed using the primer-probe set Agl 521, described in Table BSA. Results ofthe RTQ-PCR runs are shown in Tables BSB, BSC and BSD.
Table BSA. Probe Name Agl 521
Figure imgf001483_0001
Table BSB. Panel 1.3D
Figure imgf001483_0002
Figure imgf001484_0001
Table BSC. Panel 2.2
Figure imgf001484_0002
14δ0
Figure imgf001485_0001
Table BSD. Panel 4D
Figure imgf001485_0002
Figure imgf001486_0001
Figure imgf001487_0001
Panel 1.3D Summary: Agl 521 Highest expression of this gene was detected in the bone marrow (CT=30.5). Moderate to low expression was also detected in other normal tissues, including pancreas, adipose, bladder and trachea. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drags targeting the gene or gene product are useful in the treatment of diseases ofthe bone marrow, pancreas, adipose, bladder and trachea.
Panel 2.2 Summary: Agl 521 Prominent expression was detected in the breast (CT=33), but not in malignant breast samples. Expression of this gene or its protein product was useful as a marker of this tissue, pancreas, adipose, bladder and trachea breast cancer.
Panel 4D Summary: AG1521 Highest expression was detected in resting macrophages (CT=27). Prominent expression was also detected in a cluster of treated and untreated dendritic cells. The protein encoded by this gene was down regulated in macrophages after LPS stimulation. This gene product responds to inflammatory stimuli and becomes down regulated after 12-24hr exposure. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of inflammation in diseases such as asthma, IBD, psoriasis, arthritis and allergy. Agonistic (ligand-like) therapeutics designed with this protein product are useful for stimulating the immune response and improving the efficacy of vaccines and antiviral or antibacterial treatments. Therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in immune modulation, organ/bone marrow transplantation, and the treatment of diseases where antigen presentation, a function of mature dendritic cells, plays an important role such as asthma, rheumatoid arthritis, IBD, and psoriasis.
TRA 1801057vl Example D: CG55806-04, NOV47a
Coagulation Factor IX is one ofthe many proteins involved in the cascade of reactions leading to blood coagulation. This protein exists as a zymogen which is processed by either factor Vila or factor Xla to yield the activated version, IXa which then binds with factor Villa to convert factor X to its active form (factor Xa). Factor IXa exists as a complex of a disulfide-linked heavy and light chain with removal ofthe activation peptide. The heavy chain contains a serine protease domain which is used to activate factor X. The enzymatic activity of IXa by itself is very low, but the catalytic efficiency is increased by about 7 orders of magnitude higher when bound to factor vπia.
The light chain contains a γ-carboxyglutamic acid (Gla) domain followed by two EGF domains. The EGF1 domain binds Ca++ and has been shown, along with a small portion ofthe serine protease domain, to interact with factor Villa (Mathur, A. and Bajaj, S.P., 1999, J. Biol. Chem., 274, 18477-1 δ4δ6). The Gla domain is essential for interaction with phospholipid vesicles which help to increase the catalytic efficiency of the serine protease domain of factor IXa (Freedman, S.J., Blostein, M.D., Baleja, J.D., Jacobs, M., Furie, B.C., and Furie, B., 1996, J. Biol. Chem., 271, 16227-16236). A series of experiments have shown that the EGF2 domain is essential for factor IXa binding to surface of activated platelets (Wong, M.Y., Gurr, J.A., and Walsh, P.N., 1999, Biochemistry, 38, 8948-8960). This platelet binding is essential for efficient catalysis to activate factor X.
Figure Dl shows the alignment of CG55806-02 (wild type factor IX), the splice variant CG55δ06-04 and the sequence ofthe porcine factor IXa denoted as IPFX. Figure D2 shows the structure of porcine factor IXa (IPFX) (Brandstetter, H., Bauer, M., Huber, R., Lollar, P., and Bode, W., 1995, Proc. Natl. Acad. Sci. USA, 92, 9796- 9800). The deleted portion of CG55806-04 corresponds to the EGF2 domain. Since EGF2 domain has been shown to be essential for platelet binding, the CG55δ06-04 splice variant may prevent blood clotting.
14δ4 Example E: CG59693-01, NOV72A Knockdown Cell Validation:
Knockdown Oligonucleotides. All oligonucleotides were mixed-backbone oligonucleotides containing modified phosphorothioate segments at 5' and 3' ends and 2'-O-methyl RNA oligoribonucleotide segments located in the middle synthesized by Midland, Inc.. All oligonucleotides were desalted and gel purified. The purity ofthe oligonucleotides was confirmed by Mass spectroscopy. The antisense oligonucleotide sequences for CG59693-01 used were: ASI - 5' GATATTTCGAATCCATTTCTGG 3" (SEQ ID NO: 1477)
AS2 - 5' CATCATTCAGCTTCACACAC 3' (SEQ ID NO:147δ) AS3 - 5' GAACCTCTGCAGGCGCATAG 3' (SEQ ID NO: 1479) AS4 - 5' CACTGGAAAATGAATAAGGTA 3' (SEQ ID NO:14δO) AS5 - 5' CCATGTTAATATTCATCAGA 3' (SEQ ID NO:1481) Al 7-mer targeted to human immunodeficiency virus was used as a scramble control (5' GAGCTCCCAGGCTCAGA 3'). (SEQ ID NO:1482)
Oligonucleotide Transfection. Ten thousand cells were seeded in each well of the 96 well plate in complete medium 24 h before transfection to reach 50% confluency on the day of transfection. Oligonucleotides were diluted with Optimen to 400 nM, and mixed with Oligofectamine (Invitrogen) according to manufacturer's instructions. Cells were first washed with serum-free medium. The oligo and liposome mixture was then added to cells. After 4 h incubation period, serum was added back to cells. Readout assays were performed 24 and 48 h after transfection.
Cell Proliferation Assay. CELLTITER 96® AQueous Non-Radioactive Cell
Porliferation Assay (MTS) Kit from PROMEGA was used to determine the number of viable cells in the proliferation assay. Briefly, 20 μl of combined MTS/PMS solution were diluted with 100 μl complete medium and added to each well ofthe 96 well plate. After 1 h incubation at 37°C, the absorbance at 490 nm was recorded using an ELISA plate reader. Chemosensitivity Analysis. MCF-7 cells were transfected with 400 nM CG59693-01 knockdown oligonucleotides. Four hours after transfection, different chemotherapeutic agents were added to the cells at indicated concentration. Drug- treated cells were collected 2 days after and analyzed by MTS assay.
Knockdown Results.
Transfection with antisense oligonucleotides had minimal inhibitory effect (about 10-20%) on NCI-H460 cell proliferation when compared with the results of untransfected (UC), liposome (LC) and scrambled oligonucleotide transfected (SC) controls, as shown in Figure E 1.
The antisense oligonucleotides transfected cells and control cells were then treated with different chemotherapeutic agents that are used clinically for NSCLC. In the control cells, the chemoagents resulted in less than 40% inhibitory effect on cell growth at indicated concentrations, as shown in Figures E2-E9. However, up to 90% of growth inhibition was observed in CG59693-01 antisense oligonucleotide transfected cells treated with different chemotherapeutic agents, as shown in Figures E2-E9. Therefore, knockdown of CG59693-01 expression sensitized NCI-H460 cells to chemotherapeutic agents, such as paclitaxel, gemcitabine, etoposide, daunorubicin and cisplatin.
Role(s) of CG59693-01 in Tumorgenesis: Some lung tumors, especially non- small cell lung tumors, are known to be especially detrimental to health. Such characteristic is strongly associated with the ability of these tumors to have acquired resistance to chemotherapy. As shown above, CG59693-01 gene is over expressed in that subset of lung tumors (see differential expression data, also referred to as RTQ PCR data or as TAQMAN data; see also Hsu et al., Cancer Res 2001 Mar 15;61(6):2727-31, Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer). Additionally, over expression of this gene has been linked to chemotherapy resistance in human ovarian carcinoma (Deng H B, Parekh H K, Chow K, Simpkins H., J Biol Chem 2002 Feb 12; [epub ahead of print], Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells). The antisense experiments showed that decreasing activity ofthe enzyme encoded by the CG59693-01 gene reduces the level of drug resistance. This reduction should correlate with an improved clinical outcome in patients treated with chemotherapy.
Impact of therapeutic targeting of CG59693-01: Therapeutic targeting ofthe enzymatic activity ofthe protein encoded by CG59693-01 with a small molecule inhibitor is anticipated to reduce or eliminate resistance to chemotherapy in lung cancers, especially non-small cell lung tumors. Additionally, targeting ofthe enzymatic activity ofthe CG59693-01 protein with a small molecule inhibitor may be effective in reduction of resistance to chemotherapy in other types of cancers.
OTHER EMBODIMENTS
Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope ofthe appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge ofthe embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope ofthe following claims. The claims presented are representative ofthe inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.

Claims

CLAIMSWhat is claimed is:
1. An isolated polypeptide comprising the mature form of an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566.
5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.
6. A composition comprising the polypeptide of claim 1 and a carrier.
7. A kit comprising, in one or more containers, the composition of claim 6.
8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1.
9. A method for determining the presence or amount ofthe polypeptide of claim 1 in a sample, the method comprising:
(a) providing said sample;
(b) introducing said sample to an antibody that binds immunospecifϊcally to the polypeptide; and
(c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.
10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression ofthe polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression ofthe polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression ofthe polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression ofthe polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.
11. A method of identifying an agent that binds to the polypeptide of claim 1 , the method comprising:
(a) introducing said polypeptide to said agent; and
(b) determining whether said agent binds to said polypeptide.
12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.
13. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions ofthe polypeptide of claim 1, the method comprising:
(a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide;
(b) contacting the cell with a composition comprising a candidate substance; and
(c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence ofthe substance is not observed when the cell is contacted with a composition in the absence ofthe substance, the substance is identified as a potential therapeutic agent.
14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising:
(a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1;
(b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and
(c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator of activity or of latency or of predisposition to, a pathology associated with the polypeptide of claim 1.
15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.
16. A method for modulating the activity ofthe polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity ofthe polypeptide.
17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.
18. The method of claim 17, wherein the subject is a human.
19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 566 or a biologically active fragment thereof.
20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ DD NO:2n-l, wherein n is an integer between 1 and 566.
21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring.
22. A nucleic acid molecule, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566.
23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO:2n, wherein n is an integer between 1 and 566.
24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n-l, wherein n is an integer between 1 and 566.
25. The nucleic acid molecule of claim 20, wherein said nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 566, or a complement of said nucleotide sequence.
26. A vector comprising the nucleic acid molecule of claim 20.
27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.
28. A cell comprising the vector of claim 26.
29. An antibody that immunospecifically binds to the polypeptide of claim 1.
30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.
31. The antibody of claim 29, wherein the antibody is a humanized antibody.
32. A method for determining the presence or amount ofthe nucleic acid molecule of claim 20 in a sample, the method comprising: (a) providing said sample;
(b) introducing said sample to a probe that binds to said nucleic acid molecule; and
(c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount ofthe nucleic acid molecule in said sample.
33. The method of claim 32 wherein presence or amount ofthe nucleic acid molecule is used as a marker for cell or tissue type.
34. The method of claim 33 wherein the cell or tissue type is cancerous.
35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression ofthe nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression ofthe nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression ofthe nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of expression ofthe nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression ofthe polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566.
37. The method of claim 36 wherein the cell is a bacterial cell.
38. The method of claim 36 wherein the cell is an insect cell.
39. The method of claim 36 wherein the cell is a yeast cell.
40. The method of claim 36 wherein the cell is a mammalian cell.
41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression ofthe polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 566.
42. The method of claim 41 wherein the cell is a bacterial cell.
43. The method of claim 41 wherein the cell is an insect cell.
44. The method of claim 41 wherein the cell is a yeast cell.
45. The method of claim 41 wherein the cell is a mammalian cell.
PCT/US2003/017573 2002-06-04 2003-06-04 Novel proteins and nucleic acids encoding same Ceased WO2003102159A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP03817179A EP1590480A2 (en) 2002-06-04 2003-06-04 Novel proteins and nucleic acids encoding same
CA002488539A CA2488539A1 (en) 2002-06-04 2003-06-04 Novel proteins and nucleic acids encoding same
AU2003256263A AU2003256263A1 (en) 2002-06-04 2003-06-04 Novel proteins and nucleic acids encoding same

Applications Claiming Priority (116)

Application Number Priority Date Filing Date Title
US38575502P 2002-06-04 2002-06-04
US38549002P 2002-06-04 2002-06-04
US38561502P 2002-06-04 2002-06-04
US60/385,755 2002-06-04
US60/385,615 2002-06-04
US60/385,490 2002-06-04
US38604102P 2002-06-05 2002-06-05
US60/386,041 2002-06-05
US38646502P 2002-06-06 2002-06-06
US38645902P 2002-06-06 2002-06-06
US38686402P 2002-06-06 2002-06-06
US38635502P 2002-06-06 2002-06-06
US38635702P 2002-06-06 2002-06-06
US38644702P 2002-06-06 2002-06-06
US60/386,355 2002-06-06
US60/386,864 2002-06-06
US60/386,357 2002-06-06
US60/386,465 2002-06-06
US60/386,459 2002-06-06
US60/386,447 2002-06-06
US38708302P 2002-06-07 2002-06-07
US38707802P 2002-06-07 2002-06-07
US38708102P 2002-06-07 2002-06-07
US38676902P 2002-06-07 2002-06-07
US38670102P 2002-06-07 2002-06-07
US38693102P 2002-06-07 2002-06-07
US60/386,931 2002-06-07
US60/386,796 2002-06-07
US60/387,081 2002-06-07
US60/387,078 2002-06-07
US60/386,701 2002-06-07
US60/387,083 2002-06-07
US38754002P 2002-06-10 2002-06-10
US38786602P 2002-06-10 2002-06-10
US38742902P 2002-06-10 2002-06-10
US60/387,540 2002-06-10
US60/387,429 2002-06-10
US60/387,866 2002-06-10
US38766802P 2002-06-11 2002-06-11
US38769602P 2002-06-11 2002-06-11
US38785902P 2002-06-11 2002-06-11
US38761002P 2002-06-11 2002-06-11
US38760602P 2002-06-11 2002-06-11
US38765902P 2002-06-11 2002-06-11
US60/387,610 2002-06-11
US60/387,859 2002-06-11
US60/387,668 2002-06-11
US60/387,696 2002-06-11
US60/387,606 2002-06-11
US60/387,659 2002-06-11
US38809602P 2002-06-12 2002-06-12
US38843202P 2002-06-12 2002-06-12
US38847902P 2002-06-12 2002-06-12
US38793402P 2002-06-12 2002-06-12
US38802202P 2002-06-12 2002-06-12
US38796002P 2002-06-12 2002-06-12
US60/388,022 2002-06-12
US60/387,934 2002-06-12
US60/388,096 2002-06-12
US60/388,432 2002-06-12
US60/388,479 2002-06-12
US60/387,960 2002-06-12
US38912302P 2002-06-13 2002-06-13
US60/389,123 2002-06-13
US38914602P 2002-06-14 2002-06-14
US38912002P 2002-06-14 2002-06-14
US60/389,146 2002-06-14
US60/389,120 2002-06-14
US38974202P 2002-06-17 2002-06-17
US60/389,742 2002-06-17
US38988402P 2002-06-18 2002-06-18
US38960402P 2002-06-18 2002-06-18
US60/389,884 2002-06-18
US60/389,604 2002-06-18
US39020902P 2002-06-19 2002-06-19
US39000602P 2002-06-19 2002-06-19
US39014402P 2002-06-19 2002-06-19
US60/390,144 2002-06-19
US60/390,006 2002-06-19
US60/390,209 2002-06-19
US39172602P 2002-06-25 2002-06-25
US60/391,726 2002-06-25
US40162802P 2002-08-06 2002-08-06
US60/401,628 2002-08-06
US40226802P 2002-08-09 2002-08-09
US60/402,268 2002-08-09
US40282202P 2002-08-12 2002-08-12
US60/402,822 2002-08-12
US40345802P 2002-08-13 2002-08-13
US60/403,458 2002-08-13
US40361702P 2002-08-15 2002-08-15
US40373202P 2002-08-15 2002-08-15
US60/403,732 2002-08-15
US60/403,617 2002-08-15
US40618202P 2002-08-26 2002-08-26
US60/406,182 2002-08-26
US41008502P 2002-09-12 2002-09-12
US60/410,085 2002-09-12
US41050502P 2002-09-13 2002-09-13
US60/410,505 2002-09-13
US41295502P 2002-09-23 2002-09-23
US60/412,955 2002-09-23
US41519502P 2002-09-30 2002-09-30
US60/415,195 2002-09-30
US42071802P 2002-10-23 2002-10-23
US42062702P 2002-10-23 2002-10-23
US60/420,627 2002-10-23
US60/420,718 2002-10-23
US42085202P 2002-10-24 2002-10-24
US60/420,852 2002-10-24
US42275002P 2002-10-31 2002-10-31
US60/422,750 2002-10-31
US42309502P 2002-11-01 2002-11-01
US60/423,095 2002-11-01
US42374802P 2002-11-05 2002-11-05
US60/423,748 2002-11-05

Publications (2)

Publication Number Publication Date
WO2003102159A2 true WO2003102159A2 (en) 2003-12-11
WO2003102159A3 WO2003102159A3 (en) 2005-08-11

Family

ID=34831606

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/017573 Ceased WO2003102159A2 (en) 2002-06-04 2003-06-04 Novel proteins and nucleic acids encoding same

Country Status (1)

Country Link
WO (1) WO2003102159A2 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006003427A1 (en) * 2004-07-05 2006-01-12 Celltech R & D Limited A protein involved in carcinoma
EP2433959A3 (en) * 2005-09-12 2012-06-27 Ganymed Pharmaceuticals AG Identification of tumor-associated antigens for diagnosis and therapy
US8961980B2 (en) 2007-03-14 2015-02-24 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
US9216218B2 (en) 2010-03-23 2015-12-22 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
AU2013206613B2 (en) * 2005-09-12 2017-03-02 Biontech Ag Identification of tumor-associated antigens for diagnosis and therapy
CN112194944A (en) * 2020-10-10 2021-01-08 张万林 Preparation process of acrylic coating
CN115518161A (en) * 2022-11-02 2022-12-27 天津医科大学总医院 Application of ZIP1 as a therapeutic target for epilepsy

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20010080882A (en) * 1998-10-13 2001-08-25 리처드 피. 버군 쥬니어 Non-Endogenous, Constitutively Activated Human G Protein-Coupled Receptors

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006003427A1 (en) * 2004-07-05 2006-01-12 Celltech R & D Limited A protein involved in carcinoma
US9919036B2 (en) 2005-09-12 2018-03-20 Ganymed Pharmaceuticals Ag Identification of tumor-associated antigens for diagnosis and therapy
AU2013206613B2 (en) * 2005-09-12 2017-03-02 Biontech Ag Identification of tumor-associated antigens for diagnosis and therapy
US20140017254A1 (en) * 2005-09-12 2014-01-16 Ugur Sahin Identification of Tumor-Associated Antigens for Diagnosis and Therapy
EP2433959A3 (en) * 2005-09-12 2012-06-27 Ganymed Pharmaceuticals AG Identification of tumor-associated antigens for diagnosis and therapy
US8975375B2 (en) 2005-09-12 2015-03-10 Ganymed Pharmaceuticals Ag Identification of tumor-associated antigens for diagnosis and therapy
EP2433958A3 (en) * 2005-09-12 2012-07-04 Ganymed Pharmaceuticals AG Identification of tumor-associated antigens for diagnosis and therapy
US9475867B2 (en) 2007-03-14 2016-10-25 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
US8961980B2 (en) 2007-03-14 2015-02-24 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
US10125196B2 (en) 2007-03-14 2018-11-13 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
US9216218B2 (en) 2010-03-23 2015-12-22 Ganymed Pharmaceuticals Ag Monoclonal antibodies for treatment of cancer
US10596256B2 (en) 2010-03-23 2020-03-24 TRON—Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz gemeinnützige GmbH Monoclonal anti-GT 468 antibodies for treatment of cancer
CN112194944A (en) * 2020-10-10 2021-01-08 张万林 Preparation process of acrylic coating
CN115518161A (en) * 2022-11-02 2022-12-27 天津医科大学总医院 Application of ZIP1 as a therapeutic target for epilepsy
CN115518161B (en) * 2022-11-02 2023-11-10 天津医科大学总医院 ZIP1 as a therapeutic target for epilepsy

Also Published As

Publication number Publication date
WO2003102159A3 (en) 2005-08-11

Similar Documents

Publication Publication Date Title
WO2003029423A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
WO2003083046A2 (en) Novel proteins and nucleic acids encoding same
US20030219823A1 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
WO2002099062A2 (en) Novel antibodies that bind to antigenic polypeptides, nucleic acids encoding the antigens, and methods of use
US20040038223A1 (en) Novel proteins and nucleic acids encoding same
WO2003102159A2 (en) Novel proteins and nucleic acids encoding same
US20040014053A1 (en) Novel proteins and nucleic acids encoding same
WO2003064628A2 (en) Novel proteins and nucleic acids encoding same
EP1549671A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
EP1576146A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
EP1572922A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20060084054A1 (en) Novel proteins and nucleic acids encoding same
US20040023241A1 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
WO2003023002A2 (en) Novel human proteins, polynucleotides encoding them and methods of using the same
US20030229016A1 (en) Novel human proteins, polynucleotides encoding them and methods of using the same
EP1401470A2 (en) Novel antibodies that bind to antigenic polypeptides, nucleic acids encoding the antigens, and methods of use
WO2004089282A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
EP1576168A2 (en) Therapeutic polypeptides nucleic acids encoding same and methods of use
WO2003064589A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
EP1590480A2 (en) Novel proteins and nucleic acids encoding same
WO2003050245A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20040002453A1 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
EP1581618A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20040058347A1 (en) Novel proteins and nucleic acids encoding same
WO2003066881A2 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 2003256263

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2488539

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2003817179

Country of ref document: EP

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWP Wipo information: published in national office

Ref document number: 2003817179

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP