EP1144629A2 - Nouveaux pro-polypeptides et sequences correspondantes - Google Patents

Nouveaux pro-polypeptides et sequences correspondantes

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Publication number
EP1144629A2
EP1144629A2 EP99942557A EP99942557A EP1144629A2 EP 1144629 A2 EP1144629 A2 EP 1144629A2 EP 99942557 A EP99942557 A EP 99942557A EP 99942557 A EP99942557 A EP 99942557A EP 1144629 A2 EP1144629 A2 EP 1144629A2
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European Patent Office
Prior art keywords
seq
polypeptide
sequence identity
amino acid
sequence
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EP99942557A
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German (de)
English (en)
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EP1144629A3 (fr
Inventor
Kevin Baker
Audrey Goddard
Austin L. Gurney
Victoria Smith
Colin K. Watanabe
William I. Wood
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Genentech Inc
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Genentech Inc
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Priority claimed from PCT/US1999/020111 external-priority patent/WO2000012708A2/fr
Publication of EP1144629A2 publication Critical patent/EP1144629A2/fr
Publication of EP1144629A3 publication Critical patent/EP1144629A3/fr
Withdrawn legal-status Critical Current

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Definitions

  • the present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.
  • Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms.
  • secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment.
  • Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors.
  • Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins.
  • Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents.
  • Efforts are being undertaken by both industry and proficient to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)].
  • Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms.
  • membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
  • Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
  • the tetraspan family of proteins has grown to include approximately 20 known genes from various species, including drosophila.
  • the tetraspans are also known as the transmembrane 4 (TM4) superfamily and are proposed to have an organizing function in the cell membrane. Their ability to interact with other molecules and function in such diverse activities as cell adhesion, activation and differentiation, point to a role of aggregating large molecular complexes. Skubitz, et al., J. Immunology. 157:3617-3626 (1996).
  • the tetraspan group has also emerged as a set of proteins with prominent functions in Schwann cell biology. Mirsky and Jessen, Curr. Opin. Neurobiol., 6(l):89-96 (1996).
  • Tetraspans also sometimes called tetraspanins
  • Maecker et al., FASEB. 11 :428-442 (1997).
  • members of the tetraspan family are of interest.
  • PRQ1018 Efforts are being undertaken by both industry and proficient to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PRO1018.
  • Retinol dehydrogenase proteins are enzymes which function to recognize holo-cellular retinol-binding protein as a substrate, thereby catalyzing the first step of retinoic acid biogenesis from its substrate.
  • Various retinol dehydrogenase genes have been cloned and characterized, wherein the products of these genes are suggested as potentially being useful for the treatment of retinitis pigmentosa, psoriasis, acne and various cancers (Chai et al., J. Biol. Chem.
  • PRQ1477 Glycosylation is an important mechanism for modulating the physiochemical and biological properties of proteins in a stage- and tissue-specific manner.
  • One of the important enzymes involved in glycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, an enzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2 during the formation of N-linked oligosaccharides.
  • the Saccharomyces cerevisiae alpha 1,2- mannosidase enzyme of is a member of the Class I alpha 1 ,2-mannosidases that are conserved from yeast to mammals.
  • PRQ831 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
  • Protein-proteininter actions include receptor and antigen complexes and signaling mechanisms . As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • IGF insulin like growth factor
  • ALS acid labile subunit of IGF
  • LIG- 1 a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains. Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996).
  • PRQ1194 The nuclear genes PET117 and PET 119 are required for the assembly of active cytochrome c oxidase in S. Cerevisiae, and therefore, are of interest. Also of interest are nucleic acids which have sequence identity with these genes. PET genes are further described in McEwen, et al., Curr. Genet.. 23(1):9-14 (1993). 10. PROl 110
  • the bone marrow plays many important roles in the mammal. One of those roles is to provide a source of various progenitor cells that differentiate into important cells and other components of the blood and immune systems. As such, the function of the myeloid system is of extreme interest.
  • PROl 110 polypeptides having homology to myeloid upregulated protein
  • PRO 1378 a novel secreted protein designated herein as PRO 1378.
  • PRQ1189 There has been much interest in the identification of receptor proteins on stem cells and progenitor cells which may be involved in triggering proliferation or differentiation.
  • a type II transmembrane protein was identified in proliferating progenitor cells in the outer perichondrial rim of the postnatal mandibular condyle proliferation.
  • the investigators concluded that E25 could be a useful marker for chondro-osteogenic differentiation (Deleersnijder, et al. J. Biol. Chem. 271(32): 19475-19482 (1996)).
  • PR01411 a novel secreted protein designated herein as PR01411. 16. PRQ1295
  • PRO 1295 a novel secreted protein designated herein as PRO 1295.
  • Enzymes such as hyaluronidase, sialyltransferase, urokinase-type plasminogenactivator, plasmin, matrix metalloproteinases, and others, play central roles in the catabolism of extracellular matrix molecules. As such, these enzymes and inhibitors thereof, may play roles in metastatic cancer and the treatment thereof. Van Asplatz and du Plessis, Med. Hypotheses. 48(5):443-447 (1997).
  • sialyltransferases are of particular interest.
  • a peptide of interest is the GalNAc alpha 2, 6-sailytransferase as described in Kurosawa, et al., J.
  • sialyltransferases such as this one, and peptides related by sequence identity, are of interest. Sialyltransferases are further described in the literature, see for example, Sjoberg, et al, J. Biol. Chem.. 271(13):7450-7459 (1996), Tsuji, J. Biochem.. 120(1): 1-13 (1996) and Harduin-Lepers, et al., Glvcobiology. 5(8):741-758 (1995).
  • Kang et al. reported the identification a novel cell surface glycoprotein of the lg superfamily (J. Cell biol. (1997) 138(1):203-213).
  • Cell adhesion molecules of the lg superfamily are implicated in a wide variety of biological processes, including cell migration, growth control, and tumorigenesis.
  • the Kang et al. studies suggest that loss of CDO function may play a role in oncogenesis. Accordingly, the identification of additional CDO-like molecules, and more generally, cell adhesion molecules of the lg superfamily, is of interest.
  • Peptidases are enzymatic proteins that function to cleave peptide substrates either in a specific or nonspecific manner. Peptidases are generally involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different peptidase enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized. The mammalian peptidase enzymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • Putative protein-2 (PUT-2) is a homolog of the human disease genes LI CAM, G6PD and P55 (Riboldi Tunnicliffe et al. , Genome Analysis, submitted). As such, there is interest in identifying novel polypeptides and encoding DNA having homology to the PUT-2 protein.
  • PR01248 polypeptides We herein describe the identification and characterization of novel polypeptides having homology to PUT-2 protein, designated herein as PR01248 polypeptides.
  • Dickkopf is a family of secreted proteins having a high degree of homology in the cysteine-rich domains (i.e., 80-90%).
  • Dkk-1 the first discovered member, of this family has potent head-inducgin activity on the Spemann organizer. Glinka et al., Nature 391 (6665): 357-362 (1988).
  • the Spemann organizer of the amphibian embryo can be subdivided into two discrete activities, namely trunk organizer and head organizer.
  • Dkk-1 has been found to be both sufficient and necessary to cause head induction in Xenopus embryos and is further a potent antagonist of Wnt signaling, suggesting that the Dkk genes encode an entire family of Wnt inhibitors.
  • Wnt genes encode a family of secreted glycoproteins that modulate cell fate and behavior in embryos through activation of receptor-mediated signaling pathways.
  • wingless encodes a Wnt-related gene (Rijsewik et al., Cell, 50: 649-657 (1987)) and wg mutations alter the pattern of embryonic ectoderm, neurogenesis, and imaginal disc outgrowth.
  • wg wingless
  • Morata and Lawerence Dev. Biol., 56: 227-240 (1977); Baker, Dev. Biol., 125: 96-108 (1988); Klingensmith and Nusse, Dev. Biol., 166: 396-414 (1994).
  • lin-44 encodes a Wnt homolog which is required for asymmetric cell divisions.
  • Knock-out mutations in mice have shown Wnts to be essential for brain development (McMahon and Bradley, Cell, 62: 1073-1085 (1990); Thomas and Cappechi, Nature, 346: 847-850 (1990)), and the outgrowth of embryonic primordia for kidney (Stark et al., Nature, 372: 679-683 (1994)), tail bud (Takada et al., Genes Dev., 8: 174-189 (1994)), and limb bud.
  • the Wnt/Wg signal transduction pathway plays an important role in the biological development of the organism and has been implicated in several human cancers. This pathway also includes the tumor suppressor gene, APC. Mutations in the APC gene are associated with the development of sporadic and inherited forms of human colorectal cancer. For example, elevated levels of Wnt-2 have been observed in colorectal cancers. Vider, B-Z. et al., Oncogene 12: 153-158 (1996).
  • Immunoglobulins are antibody molecules, the proteins that function both as receptors for antigen on the B-cell membrane and as the secreted products ofthe plasma cell. Like all antibody molecules, immunoglobulins perform two major functions: they bind specifically to an antigen and they participate in a limited number of biological effector functions. Therefore, new members of the lg superfamily and fragments thereof are always of interest. Molecules which act as receptors by various viruses and those which act to regulate immune function are of particular interest. Also of particular interest are those molecules which have homology to known lg family members which act as virus receptors or regulate immune function. Thus, molecules having homology to lg superfamily members and fragments thereof (i.e., heavy and light chain fragments) are of particular interest.
  • novel secreted proteins involved in physiological and metabolic pathways is of interest because of their potential use as pharmaceutical agents.
  • novel polypeptides that are potentially involved in immxme response and inflammation mechanisms.
  • a novel polypeptide has recently been identified that is expressed in mouse B cells in response to IL-4. The gene encoding this polypeptide is referred to as interleukin-four induced gene 1 , or "Figl” (Chu et al. Proc. Natl. Acad. Sci (1997) 94(6): 2507-2512).
  • Long chain fatty acid CoA ligase is an enzymatic protein that functions to ligate together long chain fatty acids, a function that plays important roles in a variety of different physiological processes. Given the importance of this enzymatic protein, efforts are currently being undertaken to identify novel long chain fatty acid CoA ligase homologs. We herein describe the identification and characterization of novel polypeptides having homology to long chain fatty acid CoA ligase, designated herein as PRO 1250 polypeptides.
  • N-acetylglucosaminyltransferase proteins comprise a family of enzymes that provide for a variety of important biological functions in the mammalian organism.
  • 2-N-acetylglucosaminyltransferase I is an enzymatic protein that catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al. , Proc. Natl. Acad. Sci. USA. 88:234-238 (1991).
  • cytokine receptor family includes the interferon receptors, the interleukin-10 receptor and the tissue factor CRFB4 (Spencer et al., J. Exp. Med. 187:571-578 (1998) and Kotenko et al., EMBO J. 16:5894-5903 (1997)).
  • CRF2 class II cytokine receptor family
  • cytokine receptor family-4 proteins designated herein as PRO 1315 polypeptides.
  • Granzyme M is a natural killer cell serine protease.
  • the human gene is 7.5 kilobases, has an exon- intron structure identical to other serine proteases, and is closely linked to the serine protease gene cluster on chromosome 19pl3.3. (Pilat et al., Genomics. 24:445-450 (1994)).
  • Granzyme M has been found in two human natural killer leukemia cell lines, unstimulated human peripheral blood monocytes and untreated purified CD3-
  • Reductases form a large class of enzymatic proteins found in a variety of mammalian tissues and play many important roles for the proper functioning of these tissues. They are antioxidant enzymes that catalyze the conversion of reactive oxygen species to water. Abnormal levels or functioning of reductases have been implicated in several diseases and disorders including strokes, heart attacks, oxidative stress, hypertension and the development of both benign and malignant tumors. For example, malignant prostate epithelium may have lowered expression of such antioxidant enzymes [Baker et al., Prostate 32(4): 229-233 (1997)].
  • International patent application no. WO9622360-A1 describes a prostate specific reductase that is useful for diagnosing and treating prostate cancer and screening new antagonists.
  • Inhibitors of alpha-reductase have been used in the treatment of benign prostatic hyperplasia (Anderson, Drugs Aging (1996) 6(5):388-396). For these reasons, the identification of new members of the reductase family has been of interest for the treatment and diagnosis of cancers and other diseases and disorders.
  • Prolyl 4-hyr oxylase catalyzes the formation of 4-hydroxyproline in collagens .
  • the tetraspan family of proteins also referred to as the "transmembrane 4 (TM4) superfamily" are proposed to have an organizing function in the cell membrane. It is believed that they interact with large molecular complexes and function in such diverse activities as cell adhesion, activation and differentiation (see Maecker et al. FASEB (1997) JT:428-442). Accordingly, the identification of new members of the tetraspan family of proteins is of interest. Efforts are being undertaken by both industry and proficient to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins.
  • Ebnerin is a cell surface protein associated with von Ebner glands in mammals. Efforts are being undertaken by both industry and proficient to identify new, native proteins and specifically those which possess sequence homology to cell surface proteins such as ebnerin or other salivary gland-associated proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. We herein describe the identification of novel polypeptides having significant homology to the von Ebner minor salivary gland-associated protein, designated herein as PR01357 polypeptides.
  • transmembrane protein One type of transmembrane protein that has received attention is implantation-associated uterine protein. Deficiencies or abnormalities of this protein may be a cause of miscarriage. Therefore, the identification and characterization of implantation-associated proteins is of interest.
  • Bone-related sulphatase is an enzymatic protein that has been shown to degrade sulphate groups of proteoglycan sugar chains in bone tissue (Australian Patent Publication No. AU 93/44921-A, March 3, 1994). Because of its specific sulphatase activity, it has been suggested that bone-related sulphatase may find use in the treatment of bone metabolic diseases. As such, there is significant interest in identifymg and characterizing novel polypeptides having sequence similarity to bone-related sulphatase. We herein describe the identification and characterization of novel polypeptides having homology to bone-related sulphatase, designated herein as PR01246 polypeptides.
  • Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)).
  • CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell.
  • CPE-R Clostridium perfringens enterotoxin receptor
  • PRO 1275 a novel secreted protein designated herein as PRO 1275.
  • PRO 1274 a novel secreted protein designated herein as PRO 1274.
  • Chordin protein which has been isolated from Xenopus, is a potent dorsalizing factor that regulates cell-cell interactions in the organizing centers of Xenopus head, trunk and tail development (Sasai et al. , (1994) Cell 79(5):779-790: see also Mullins, (1998) Trends Genet. 14(4): 127-129: and Kessel et al. (1998) ) Trends Genet. 14(5):169-171). It may be used as a component of culture medium for culturing nerve and muscle cells, and may have use in the treatment of neurodegenerative diseases and neural injury (U.S. Pat. No. 5,679,783).
  • the extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery.
  • the major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al. , Proc. Natl. Acad. Sci. USA 90:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143- 9153 (1991)).
  • olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons.
  • olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons.
  • Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation. Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy Sci. 76:3832-3850 (1993), Ogg, et al., Mamm. Genome.
  • butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et al. , supra). Given that butyrophilin plays a role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs.
  • the lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share characteristic conserved sequence motifs.
  • Lipocalins are known to be involved in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis.
  • the lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and as carrier proteins, to act in the general clearance of endogenous and exogenous compounds.
  • novel members of the lipocalin protein family are of interest.
  • PRO1302 CD33 is a cell-surface protein that is a member of the sialoadhesin family of proteins that are capable of mediating sialic-acid dependent binding with distinct specificities for both the type of sialic acid and its linkage to subterminal sugars.
  • CD33 is specifically expressed in early myeloid and some monocyte cell lineages and has been shown to be strongly associated with various myeloid tumors including, for example, acute non-lymphocytic leukemia (ANLL).
  • ANLL acute non-lymphocytic leukemia
  • CD33 has been suggested as a potential target for the treatment of cancers associated with high level expression of the protein.
  • One CD33 homolog (designated CD33L) is described in Takei et al., Cvtogenet. Cell Genet. 78:295-300 (1997).
  • Another study describes the use of CD33 monoclonal antibodies in bone marrow transplantation for acute myeloid leukemia. Robertson, et al., Prog. Clin.
  • Olfactory reception occurs via the interaction of odorants with the chemosensory cilia of the olfactory receptor cells located in the nasal epithelium.
  • the mammalian olfactory system is capable of recognizing and discriminating a large number of different odorant molecules.
  • numerous different odorant binding proteins and their encoding DNA have recently been identified and characterized (Dear etal., Biochemistry 30: 10376-10382 (1991). Pevsner et al., Science 241:336-339 (1988), Buck et al., Cell 65:175-187 (1991) andBreer et al., J. Recept. Res.
  • protease enzymes are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci.. 7(2): 5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem.. 46:313-320 (1998).
  • PR01279 polypeptides having homology to neuropsin protein
  • the immunophilins are a family of proteins that function as receptors for immunosuppressant drugs, such as cyclosporin A, FK506, and rapamycin.
  • the immunophilins occur in two separate classes, (1) the FK506-binding proteins (FKBPs), which bind to FK506 and rapamycin, and (2) the cyclophilins, which bind to cyclosporin A.
  • FKBPs FK506-binding proteins
  • the FK506/FKBP complex functions to inhibit the activity of the serine/threonine protein phosphatase 2B (calcineurin), thereby providmg immunosuppressant activity (Gold, Mol. Neurobiol.
  • FK506 binding protein designated herein as PRO 1304 polypeptides.
  • CD97 a cell surface antigen that is rapidly upregulated upon activation on lymphocytes
  • Leukocytes strongly positive for CD97 are concentrated at sites of inflammation relative to CD97 expression in normal lymphoid tissue.
  • a soluble subunit of CD97, CD97alpha has been found in the body fluids from inflamed tissues (Gray et al. J. Immunol. (1996) 157(12):5438-5447).
  • Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration ofthe physical properties of proteins and enzymes.
  • Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system.
  • Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., J. Neurosci., 7(2):5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem.. 46:313-320 (1998).
  • Other studies have reported that kindling induces neuropsin mRNA in the mouse brain. Okabe, et al., Brain Res. , 728(1): 116-120 (1996).
  • neuropsins and related proteins and agents, including agonists and antagonists are of interest.
  • daintain/AIFl daintain allograft inflammatory factor 1
  • daintain/AIFl may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus (Chen et al. Proc. Natl Acad. Sci. (1997) 94(25): 13879- 13884).
  • AIF-1 has also been implicated in both rat and human allogenic heart transplant rejection (Utans et al. Transplantation (1996) 61(9): 1387-1392), and may play a role in macrophage activation and function (Utans et al. J. Clin. Invest. (1995. 95(6):2954-2962).
  • Protein-protein interactions include receptor and antigen complexes and signalingmechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
  • Leucine-rich proteins are known to be involved in protein-protein interactions.
  • a study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem. Mol. Biol .. 32(2): 141-174 (1997).
  • Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C, et al., Vouv. Rev. Fr. Hematol.
  • slit protein Another protein of particular interest which has been reported to have leucine-rich repeats is the slit protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., WO9210518-A1 by Yale University.
  • the slit protein has been characterized and reported to be secreted by glial cells and involved in the formation of axonal pathways in Drosophila as well as the mediation of extracellular protein interactions. Wharton and Crews, Mech. Dev.. 40(3): 141-154 91993); Rothberg and Artavanis-Tsakonas, J. Mol. Biol.. 227(2):367-370 (1992); Rothberg, et al., Genes Dev.. 4(12A):2169-2187 (1990); and Rothberg, et al., CeJ 55(6): 1047
  • Lysozymes are secretedenzymes that preferentially hydrolyze the [beta] -1 ,4 glucosidic linkages between N-acetylmuramic acid and N-acetylgucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants. It has been found in mammalian secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties. Additional characteristics and possible uses of lysozymes are described in U.S. Pat. No. 5,618,712.
  • glycosylation can determine the fate of a protein, for example, whether it is secreted or not. Also, glycoproteins play many structural and functional roles, particularly as part of the cell membrane. Therefore, glycosylation is of interest. Studies have reported on the growth-related coordinate regulation of the early N- glycosylation genes in yeast. Kukuruzinska and Lennon, Glvcobiologv. 4(4): 437-443 (1994). Moreover, the relationship between protein glycosylation and fatty acylation of glycoproteins was studied in the wild-type and asparagine-linked glycosylation-deficient mutants in yeast. Appukuttan, FEBS Lett.. 255(1): 139-142 (1989).
  • Cytochrome P450 proteins form a large class of monooxygenase enzymes involved in hydroxylation.
  • cytochrome P450 Hydroxylation reactions are important in the synthesis of cholesterol and steroid hormones. Enzymes of the cytochrome P450 family play an important role in the metabolism endogenous compounds such as arachidonic acid. These enzymes are also important in the metabolism of foreign substances such as the elimination of drugs from the body [see, for example, Peterson, Aliment. Pharmacol. Ther.. 9: 1-9 (1995).]. In addition, metabolites generated through the cytochrome P450 pathway may play a role in carcinogenesis, blood pressure regulation and renal function [see, for example, Rahman et al., Am. J. Hypertens.. 10:356-365 (1997)].
  • PRQ1269 Granulocytes the most common type of white blood cell, have the ability to mediate immunologic cytotoxicity against tumor cells and microorganisms. Accordingly, there has been interest in identifying various factors that are produced by these cells because of their potential use as pharmaceutical agents.
  • Patent publication no. W09729765-A1 to Selsted, describes the identification of granulocyte peptide A which was isolated from bovine and murine granulocytes. Several uses for this peptide were identified including, a therapeutic use, use as an agricultural agent, use as a preservative for food, and use as a water treatment agent.
  • Neurexophilin is a protein that was discovered as a neuronal glycoprotein that was copurified with neurexin I alpha during affinity chromatography on immobilized alpha-latrotoxin (Missler et al., J. Neurosci. 18:3630-3638 (1998)).
  • the mammalian brain contains four genes for neurexophilins the products of which share a common structure composed of five domains: (1) an N-terminal signal peptide, (2) a variable N-terminal domain, (3) a highly conserved central domain that is N-glycosylated, (4) a short linker region and (5) a conserved C-terminal domain that is cysteine-rich (Missler et al., supra).
  • These data further demonstrate that the neurexophilins are proteolytically processed after synthesis and bind to alpha-neurexins.
  • the structure and characteristics of neurexophilins indicate that they may function as neuropeptides that may signal via alpha-neurexins. Therefore, there is significant interest in identifying and characterizing novel polypeptides having homology to the neurexophilins.
  • PRO 1327 polypeptides having homology to neurexophilin protein, designated herein as PRO 1327 polypeptides.
  • Cerebellin is a secreted, postsynaptic neuroprotein found throughout the brain. The highest concentrations of this protein have been found in the cerebellum. It has also been detected in the pituitary, spinal cord, and adrenal glands (Satoh etal. J. Endocrinol. (1997) 15491):27-34). The feasibility of using cerebellum as a quantifiable marker for the investigation of the maturation of Purkinje cells of the cerebellum and to chart neurodevelopment has been reported (see Slemmon et al. Proc. Natl. Acad. Sci (1985) 82(20):7145-7148).
  • Cadherins are known as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development.
  • Cadherins are a diverse family of proteins that have been identified in various tissues including nervous tissue (Suzuki et al., Cell Regul.. 2:261- 270 (1991)).
  • Ksp-cadherin is a kidney-specific member of the cadherin multigene family (Thomson et al., Biol. Chem. 270: 17594-17601 (1995)).
  • Cadherins are thought to play an important role in human cancer (Yap, Cancer Invest.. 16:252-261 (1998)).
  • Carboxypeptidases are of interest. Carboxypeptidase E appears to be involved in the biosynthesis of a wide range of peptide hormones. Fricker, Annu. Rev. Physiol.. 50:309-321 (1988). This carboxypeptidase has been associated with obesity. Leiter. J. Endocrinol.. 155(2):211-214 (1997). Carboxypeptidase M has been reported as being a marker of macrophage maturation. Krause, et al., Immunol. Rev.. 161: 119-127 (1998).
  • carboxypeptidases of particular interest which are known in the art include human pancreatic carboxypeptidase 2, carboxypeptidase al and carboxypeptidase B. Therefore, novel members of the carboxypeptidase family are of interest. 68. PRQ1337
  • Thyroxine-binding globulin is synthesized by the liver and secreted into the bloodstream. It is the principal thyroid hormone transport protein in human serum (Refetoff et al. Horm. Res. (1996) 45(3-5): 128-138). High serum levels of TBG have been found to cause hyperthyroxinaemia (Leahy etal. Postgrad Med. J. (1984) 60(703): 324-327). Accordingly, the identification and characterization of TBG proteins is of interest (see Flink et al. Proc. Natl Acad Sci.
  • PRQ1343 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
  • PRO 1343 a novel secreted protein designated herein as PRO 1343.
  • Semaphorins are a large family of transmembrane and secreted proteins, many of which are expressed in the nervous system. Members of the semaphorin family include both ligands and receptors. (Eckhardt et al. , Mol. Cell. Neurosci.. 9: 409-419 (1997)). Studies have revealed a role for semaphorins in embryonic motor and central nervous system axon guidance and synapse formation. (Catalano et al., Mol. Cell. Neurosci.. : 173-182 (1998); Kitsukawa et al., Neuron. .19: 995-1005 (1997); Yu et al., Neuron. 20: 207-220 (1998)).
  • Semaphorins have been shown to induce neuronal growth cone collapse and alter their pathway in vivo. (Shoji et al., Development. 125: 1275-1283 (1998)). Members of the semaphorin family have been shown to be immunologically active, inducing cytokine production in human monocytes. (Comeau et al. , Immunity. 8: 473- 482 (1998)). Semaphorins may also play a role in cancer. Expression of a mouse semaphorin gene is known to correlate with metastatic ability in mouse tumor cell lines. (Christensen et al., Cancer Res.. 58: 1238-1244 (1998)). 72. PRQ1487
  • Fringe is a protein which specifically blocks serrate-mediated activation of notch in the dorsal compartment of the Drosophila wing imaginal disc (see Fleming et al. , Development. 124(15):2973-81 (1997); Wu et al. Science (1996) 273(5273) : 355-358) .
  • Fringe protein is also involved in vertebrate development where a thickening of the apical ectodermal ridge essential for limb bud outgrowth involves an interaction between dorsal cells that express radical fringe and those that do not (see Wolpert, L. Philos Trans R Soc Lond B Biol Sci 1998) 353(1370):871-875: Kengaku et al.
  • fringe protein is of interest for both its role in development as well as its ability to regulate serrate, particularly serrate 's signaling abilities. Also of interest are novel polypeptides which may have a role in development and/or the regulation of serrate-like molecules. Of particular interest are novel polypeptides having homology to fringe protein.
  • PRQ1418 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
  • Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation. Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy Sci. 76:3832-3850 (1993), Ogg, et al., Mamm. Genome.
  • butyrophilin plays a role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs.
  • Members of the butyrophilin family are further described in Tazi-Ahnini, et al., Immunogenetics. 47(l):55-63 (1997); Davey, et al., Gene. 199(l-2):57-62 (1997); and Mather and Jack, J. Dairy Sci.. 76(12):3832-3850 (1993).
  • Proteases are enzymatic proteins which are involved in many biological processes in mammalian and non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that hydrolyzes peptide bonds of ingested proteins. Trypsin-like proteases have been characterized that are cell- surface proteins (see Farley etal.
  • the tetraspanin (or tetraspan) family of proteins has grown to include approximately twenty known genes from various species.
  • the tetraspanins are four transmembrane domain membrane-bound molecules which include for example, CD81, CD82, CD9, CD63, CD37 and CD53.
  • Many of these proteins have a flair for promiscuous associations with other molecules, including lineage-specific proteins, integrins, and other transpanins. In terms of function, they are involved in diverse processes such as cell activation and proliferation, adhesion and motility, differentiation and cancer.
  • Proteases are enzymatic proteins which are involved in many biological processes in mammalian and non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that hydrolyzes peptide bonds of ingested proteins. Trypsin-like proteases have been characterized that are cell- surface proteins (see Farley etal.
  • semaphorins have been identified in the human immune system, where they are believed to play functional roles including B-cell signaling (Hall et al. Proc. Natl. Acad. Sci (1996) 93(21): ! 1780-50).
  • a human semaphorin gene, useful in the diagnosis of nervous system an immune disorders, is disclosed in Japanese Pat. No. J10155490-A, published June 16, 1998. The identification of additional members of the semaphorin family if of interest.
  • Enzymatic proteins that may be implicated in metabolic diseases or disorders are of particular interest.
  • the enzymatic addition of sugars to fat-soluble chemicals is an important process that increases their solubility in water and aids in their excretion.
  • glucuronic acid is the main sugar that is used to prevent the waste products of metabolism and fat-soluble chemicals from reaching toxic levels in the body.
  • the UDP glucuronosyltransferases that carry out this reaction are part of a super family of UDP glycosyltransferases found in animals, plants and bacteria. In the liver, UDP-glucuronosyltransferase conjugates bilirubin.
  • the cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken.
  • cerebellin a hexadecapeptide
  • Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence.
  • the longest clone codes for a protein of 193 amino acids generally termed precerebellin, or a cerebellin precursor.
  • This protein has a significant similarity to the globular region of the B chain of human complement component C lq.
  • the region of .elatedness extends approximately over 145 amino acids located in the carboxyl terminus of both proteins.
  • no collagen-like motifs are present in the amino-terminal regions of precerebellin.
  • cerebellin is not liberated from precerebellin by the classical dibasic amino acid protealytic cleavage mechanism seen in many neuropeptide precursors.
  • the cerebellin precursor has been associated with synaptic physiology. Urade, et al., PNAS. USA. 88(3): 1069-1073 (1991). Cerebellin, its precursor, and related molecules, particularly those having sequence identity with cerebellin, are therefore of interest.
  • Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, and other processes necessary to sustain life.
  • Acyltransferases are enzymes which acylate moieties.
  • acyl-glycerol- phosphate acyltransferases can act on lysophosphatidic acid as a substrate. The lysophosphatidic acid is converted to phophatidic acid and thus plays a role in forming phosphatidylethanolamme found in membranes. See, Brown, et al., Plant Mol. Biol.. 26(l):211-223 (1994).
  • LPAAT l-acyl-sn-glycerol-3-phosphate acyltransferase
  • PRO1490 polypeptides having homology to a l-acyl-sn-glycerol-3-phosphate acyltransferase protein, designated herein as PRO1490 polypeptides.
  • Methyltransferase enzymes catalyze the transfer of methyl groups from a donor molecule to an acceptor molecule. Methyltransferase enzymes play extremely important roles in a number of different biological processes including, for example, in the electron transport chain in the plasma membrane in prokaryotes and in the inner mitochondrial membrane in eukaryotic cells (see , e . g . , Barkovich et al . , J. Biol. Chem. 272 : 9182-9188 (1997), Dibrov et al., J. Biol. Chem. 272:9175-9181 (1997), Lee et al., J. Bacteriol..
  • Methyltransferase enzymes have been shown to be essential for the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin K2), both of which are essential isoprenoid quinone components of the respiratory electron transport chain. Given the obvious importance of the methyltransferase enzymes, there is substantial interest in identifying novel polypeptide homologs of the methyltransferases. We herein describe the identification and characterization of a novel polypeptide having homology to methyltransferase enzymes, designated herein as PR01558 polypeptides.
  • novel growth factors is of particular interest because of the roles they play in inducing cellular growth, proliferation and differentiation in both normal states and abnormal states.
  • the identification of growth factors that are over- or under-expressed in abnormal tissues may lead to the development of diagnostic tools and therapeutic agents.
  • Growth factors have been isolated from hepatoma- derived cell lines. Hepatoma-derived growth factors have been isolated from mouse (Japanese Pat. No. J09313185-A, published December 9, 1997) and human (Japanese Pat. No. J06343470-A, published December 20, 1994) tissues.
  • a hepatoma-derived growth factor isolated from a human hepatoma-derived cell line, has been found to be ubiquitously expressed in several tumor-derived cell lines, as well as in normal tissues (Nakamura et al , J. Biol. Chem (1994) 269(40):25143-9).
  • the growth factor was determined to be a novel heparin-binding protein that is mitogenic for fibroblasts.
  • the neuronal cell body is usually round like any other cell. However, these cells have structures, also referred to as "processes", which grow from them to form synaptic connections. Some of these processes carry information away from the cell body; sometimes over very long distances. These long and thin processes are axons. The axon is a thin, static tube. Other processes carry information either towards the cell body, or both towards and away from the cell body. These shorter and usually thicker processes are called dendrites. Both axons and dendrites are called neurites.
  • a growth cone is the growing tip of a neurite.
  • the growth cone is flattened and highly motile. It is where new material is added and further extension ofthe axon originates. Controlling where the growth cone crawls controls were the axon will be laid down and thus where it will be present.
  • the growth cone has several definable parts.
  • the thin, flattened, veil-like processes that stick out and retract from the leading edge are called lamellipodia.
  • the needle-like processes that stick out and retract from the leading edge are called microspikes or filopodia. These are the structures involved in pushing the leading edge of the growth cone forward.
  • the accurate navigation of growth cones to their appropriate targets requires that they recognize and respond to navigational cues in their immediate environment. Some of these cues encourage extension into certain areas whereas others discourage extension into others.
  • Well characterized molecules that encourage neurite outgrowth in vitro include the extracellular matrix molecule laminin and the neuronal cell surface molecule L1/G4/8D9. These molecules which promote neurite extension are generally widely distributed throughout the body. Laminin immunoreactivity is reasonably widespread in the developing central and peripheral nervous systems. Similarly, L1/G4/8D9 is present on a wide variety of neuronal processes in the developing central nervous system, particularly long projecting axons. It is, therefore, unclear whether the known outgrowth promoting molecules play an important role in self-specific choices growth cones make as they decide between possible routes. Instead, their function is believed to provide a generally permissive environment in which growth cones extend and respond to more specific navigational cues.
  • Collapsins are proteins that function to modulate the activity of molecules which modulate growth cone extension.
  • PR01491 polypeptides we herein describe the identification and characterization of novel polypeptides having homology to a collapsin protein, designated herein as PR01491 polypeptides.
  • signal transduction is crucial to cell processing such as differentiation, motility and division.
  • signal transduction is believed to occur throughout the cell in the form of complex interactions between proteins.
  • protein-protein interactions are often mediated by modular domains within signaling proteins.
  • signal transduction is now modeled as a system in which molecules act in a combination, and the composition of that combination, determines the signal.
  • Src homology domains are two domains found in regions of sequence similarity of proteins involved in signal transduction. Early work on the oncogenic tyrosine kinase Src identified the SH2 domain. Since then, SH2 and SH3 domains have been found in many diverse proteins, making them among the most common type of structural motif. SH2 and SH3 domains are modular in that they fold independently of the protein that contains them, their secondary structure places N- and C- termini close to one another in space, and they appear at variable locations (anywhere from N- to C-terminal) from one protein ot the next (Cohen et al., Cell 80: 237-348, 1995).
  • SH3 domains have a more general function than that which is purported for SH2.
  • SH3 binding proteins have been isolated by screening bacteriophage expression libraries with labeled SH3 domains. The results of these experiments showed that SH3 domains would bind to short proline-rich peptides, in particular the motif PxxP. Based on the level of knowledge present at the time of the preparation of the present patent application, all of the SH3 binding sites identified have the property of being proline rich. Binding of an SH3 domain is independent of covalent modification ofthe binding site, such as phosphorylation as occurs with the SH2 domain. As a result, SH3-ligand interactions are usually constitutive and not inducible, although exceptions do exist.
  • SH3 domains are less likely to act as signal "switches” than as a means of assembling protein complexes via moderate-affinity interactions. Such moderate affinity interactions also imply that the SH3-mediated interactions will be relatively short in duration and remodeled in response to changes in concentration of binding partners.
  • Peptidomimetic ligands based on the sequence of target proteins for SH2 and SH3 domains may represent new lead compounds for the therapy of proliferative diseases that are dependent upon constitutively activated tyrosine kinases (e.g., BCR ABL in chronic myelogenous and acute lymphocytic leukemias or HER-2/Neu in breast and ovarian cancer).
  • constitutively activated tyrosine kinases e.g., BCR ABL in chronic myelogenous and acute lymphocytic leukemias or HER-2/Neu in breast and ovarian cancer.
  • ADAMs Cellular disintegrin and metalloproteinase
  • the ADAMTS-1 gene encodes a new type of ADAM protein with respect to possessing the thrombospondin (TSP) type I motifs, the expression of which is associated with the inflammatory process (Kuno et al., J. Biol. Chem. 273: 13912-13917 (1998), Kuno et al., Genomics 46:466-471 (1997) and Kuno et al., J. Biol. Chem. 272:556-562 (1997)).
  • TSP thrombospondin
  • ADAMTS-1 ADAMTS-1 protein
  • the ADAMTS-1 protein has been suggested as playing a possible role in various inflammatory processes as well as in the development of cancer cachexia (Kuno et al., 1998, supra).
  • PRO 1563 polypeptides novel polypeptides having homology to ADAMTS-1 protein, designated herein as PRO 1563 polypeptides.
  • Chondromodulin proteins are cartilage-generated matrix components that synergistically stimulate the growth and differentiation of chondrocytes (Suzuki, Connect. Tissue Res. 35:303-307 (1996)). More specifically, chondromodulin-I functions to inhibit the proliferation of vascular endothelial cells and tube formation, thereby functioning to stimulate cartilage growth and inhibiting replacing cartilage by bone in an early stage. Chondromodulin-II, while not capable of inhibiting vascularization like chondromodulin-I, also functions to stimulate osteoclast differentiation and cartilage growth. As such, these two polypeptides are essential for the regulation of the formation of cartilage and endochondral bone structures.
  • Clostridium perfringens enterotoxin is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34: 1335-1343 (1996)).
  • CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell.
  • CPE-R Clostridium perfringens enterotoxin receptor
  • Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE-
  • Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.
  • Claudius are integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. Furuse, et al. , J. Cell Biol.. 141(7): 1539-50 (1998).
  • Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo.
  • Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE- R) gene have previously been cloned as described in Katahira, et al. , J. Biol. Chem.. 272(42): 26652-8 (1997). They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.
  • ventral prostate.1 protein (RVP. l) which is transcriptionally induced in the regressing rat prostate after castration. This protein is further described in Peacock, et al., Genomics. 46(3):443-9 (1997).
  • Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo.
  • Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE-R) gene have previously been cloned as described in Katahira, et al., J. Biol. Chem.. 272(42): 26652-8 (1997), and Katahira, etal . J. Cell Biol.. 136(6): 1239-1247 (1997). They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors. Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
  • Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)).
  • CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell.
  • CPE-R Clostridium perfringens enterotoxin receptor
  • Bioactive egg whites are a rich source of protein inhibitors of proteinases belonging to all four mechanistic classes.
  • Ovomucoid and ovoinhibitor are multidomain Kazal-type inhibitors with each domain containing an actual or putative reactive site for a serine proteinase.
  • Cystatin is a cysteine proteinase inhibitor, while ovostatin inhibits proteinases of all four mechanistic classes.
  • New members of protein inhibitors of proteinases are of interest, particularly those having sequence identity with known inhibitors such as ovomucoid.
  • Serine protease inhibitors in general are of interest. Serine proteases such as neuropsin have been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci., 7(2):5088-5097 (1995) and Chen, et al. , J. Histochem. Cvtochem.. 46:313-320 (1998). Another serine protease, the enamel matrix serine proteinase, is associated with the degradation of organic matrix in teeth. Simmer, et al., J. Dent. Res.. 77(2):377-386 (1998), Overall and Limeback, Biochem J.. 256(3): 965-972 (1988), andMoradian-Oldak, Connect. Tissue Res.. 35(l-4):231-238 (1996). Thus, inhibitors of these proteases are of interest in the case that these mechanisms require control.
  • PRO 1508 a novel secreted protein designated herein as PRO 1508.
  • Lysozymes are secreted enzymes that preferentially hydrolyze the [beta] -1,4 glucosidic linkages between N-acetylmuramic acid and N-acetylgucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants. It has been found in mammalian secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties. Additional characteristics and possible uses of lysozymes are described in U.S. Pat. No. 5,618,712.
  • lysozyme C which has been recruited as a digestive enzyme in the stomachs of creatures needing to retrieve nutrients from microorganisms in fermented food.
  • the history of lysozyme C and related proteins are further described in Qasba and Kumar, Crit. Rev. Biochem. Mol. Biol.. 32(4):255-306 (1997); Irwin, EXS, 75:347-361 (1996)
  • Glycosylation is a common and complex form of post-translational protein modification. Although a large and increasing number of unique structures is known to exist, most arise from a series of common synthetic intermediates and differ at their periphery glycosyltransferases, which recognize both the oligosaccharide acceptor and features of the underlying protein.
  • UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase is an enzymatic protein that initiates O-glycosylation of specific serine and threonine amino acids in proteins by adding N-acetylgalactosamine to the hydroxy group of these amino acids.
  • PRQ1755 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PRO 1755.
  • Protein Disulfide Isomerase enhances formation of disulfide bonds in human serum albumin (HSA). Consequently, PDI assists in the formation of the overall structure of human serum albumin. Co- expression of PDI with human serum albumin increases secretion of HSA by reducing the chance of HSA structural instability and destruction by cellular proteases. Co-expression of PDI and HSA improved localization in the endoplasmic reticulum of eukaryotic cells . (Hayano et al . , EP-50941 -A ( 1992)) . PDI and the beta-subunit of human prolyl 4-hydroxylase have been shown to be products of the same gene. (Pihlajaniemi et al.
  • Myelin glycoprotein P0 has been reported on in a number of other studies as well (Blanquet-Grossard, et al., Clin. Genet., 48(6):281-3 (1995), Hayasaka, et al., Nat. Genet., 5(l):31-4 (1993) and Saavedra, et al., J. Mol. Evol., 29(2):149-56 (1989).
  • proteins which may belong to the myelin pO family are of interest.
  • PRO 1760 a novel secreted protein designated herein as PRO 1760.
  • Phospholipase A2 is a protein which hydrolyzes a 2-acyl ester bond of phospholipids, and examples thereof include cytosolic PLA2 and secretory PLA2 which can be clearly distinguished from each other. It has been known that the cytosolic PLA2 (cPLA2) selectively hydrolyzes phospholipids containing arachidonic acid of which 2-position is esterified. Given these important biological activities, there is significant interest in identifying and characterizing novel plypeptides having homology to phospholipase A2 proteins. We herein describe the identification and characterization of novel polypeptides having homology to human phospholipase A2 protein, designated herein as PRO 1561 polypeptides.
  • CSGs Colon specific genes
  • They are useful diagnostic markers for colon cancer and for colon cancer metastasis and can also be used to screen for potential pharmaceutical and diagnostic agents. The identification of new members of the CSG family is of interest.
  • Insulin-like growth factors have both growth-promoting and insulin-like activities.
  • the larger protein is an acid-labile protein of 53K which circulates mostly as a 125 to 150 kD complex thought to be composed of IGF-I or IGF-II, the binding protein itself and an acid-labile non-IGF-binding protein with an approximate molecular mass of 100K kD.
  • the smaller protein has an apparent molecular mass of 28K in the non-reduced form and 34K when reduced.
  • N-acetylglucosaminyltransferase proteins comprise a family of enzymes that provide for a variety of important biological functions in the mammalian organism.
  • UDP-N-acetylglucosamine: alpha-3- D-mannoside beat-l,2-N-acetylglucosarninyltransferase I is an enzymatic protein that catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al., Proc. Natl. Acad. Sci. USA. 88:234-238 (1991).
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape.
  • IGF insulin like growth factor
  • the acid labile subunit of IGF is also of interest in that it increases the half-life of IGF and is part of the IGF complex in vivo.
  • SLIT protein Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neurodegenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., WO9210518-A1 by Yale University.
  • LIG-1 a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains. Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996).
  • Interleukin-10 is a pleiotropic immunosuppressive cytokine that has been implicated as an important regulator of the functions of myeloid and lymphoid cells. It has been demonstrated that IL-10 functions as a potent inhibitor of the activation of the synthesis of various inflammatory cytokines including, for example, IL-1, IL-6, IFN- ⁇ and TNF- ⁇ (Gesser et al., Proc. Natl. Acad. Sci. USA 94: 14620-14625 (1997)).
  • IL-10 has been demonstrated to strongly inhibit several of the accessory activities of macrophages, thereby functioning as a potent suppressor of the effector functions of macrophages, T-cells and NK cells (Kuhn et al., Cell 75:263-274 (1993)). Furthermore, IL-10 has been strongly implicated in the regulation of B-cell, mast cell and thymocyte differentiation. IL-10 was independently identified in two separate lines of experiments.
  • cDNA clones encoding murine IL-10 were identified based upon the expression of cytokine synthesis inhibitory factor (Moore et al., Science 248: 1230-1234 (1990)), wherein the human IL-10 counterpart cDNAs were subsequently identified by cross-hybridization with the murine IL-10 cDNA (Viera et al., Proc. Natl. Acad. Sci. USA 88:1172-1176 (1991)). Additionally, IL-10 was independently identified as a B-cell-derived mediator which functioned to co- stimulate active thymocytes (Suda et al., Cell Immunol. 129:228 (1990)).
  • IL-19 is a 177 amino acid polypeptide having a molecular weight of approximately 20.4 kD (see WO 98/08870, published March 5, 1998). It has been reported that IL-19 is specifically expressed by activated monocytes, wherein increased and/or decreased levels of IL-19 may be associated with one or more physiological disorders that are associated with increased or decreased levels of cytokine production (see WO 98/08870). Specifically, IL-19 is suggested as being capable of inhibiting the synthesis of inflammatory cytokines by cells of the immune system.
  • Uncoupling proteins or "UCPs” believed to play a role in the metabolic process, have been reported in the literature. UCPs were first found and described in the brown fat cells of hibernating animals, such as bears. UCPs were believed to help such hibernators and other cold-weather adapted animals maintain core body temperatures in cold weather by raising their body's resting metabolic rate. Because humans possess relatively small quantities of brown adipose tissue, UCPs were originally thought to play a minor role in human metabolism.
  • UCP1 human uncoupling protein
  • UCP2 Another human UCP, referred to as UCPH or UCP2, has also been described.
  • Fleury et al. teach that the UCP2 protein has 59% amino acid identity to UCP1 , and that UCP2 maps to regions of human chromosome 11 which have been linked to hyperinsulinaemia and obesity. [Fleury et al., supra].
  • UCP2 is expressed in a variety of adult tissues, such as brain and muscle and fat cells. [Gimeno et al., supra, and Fleury et al., supra].
  • Polypeptides such as the human 2-19 protein may function as cytokines.
  • Cytokines are low molecular weight proteins which function to stimulate or inhibit the differentiation, proliferation or function of immune cells. Cytokine proteins often act as intercellular messengers and have multiple physiological effects. Given the physiological importance of immune mechanisms in vivo, efforts are currently being undertaken to identify new, native proteins which are involved in effecting the immune system. We describe herein the identification of a novel polypeptide which has sequence similarity to the human 2-19 protein.
  • Carbonic anhydrase is an enzymatic protein that which aids carbon dioxide transport and release in the mammalian blood system by catalyzing the synthesis (and the dehydration) of carbonic acid from (and to) carbon dioxide and water.
  • the actions of carbonic anhydrase are essential for a variety of important physiological reactions in the mammal.
  • novel polypeptides having homology to carbonic anhydrase there is significant interest in the identification and characterization of novel polypeptides having homology to carbonic anhydrase.
  • novel polypeptides having homology to carbonic anhydrase designated herein as PRO 1335 polypeptides.
  • PRO 1329 a novel secreted protein designated herein as PRO 1329.
  • PRO 1550 a novel secreted protein designated herein as PRO 1550.
  • PRO1560 a novel secreted protein designated herein as PRO 1550.
  • a cDNA clone (DNA 19902- 1669) has been identified that encodes a novel polypeptide believed to be a novel member of the tetraspan family, designated in the present application as "PRO1560.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1560 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1560 polypeptide having the sequence of amino acid residues from 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1560 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 167 and about 775, inclusive, of Figure 1 (SEQ ID NO:3). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203454 (DNA 19902- 1669).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1560 polypeptide having the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1560 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 42 in the sequence of Figure 2 (SEQ ID NO:4).
  • the transmembrane domains have been tentatively identified as at about amino acid positions 19-42, 61-83, 92-114 and 209-230 in the PRO1560 amino acid sequence ( Figure 2, SEQ ID NO:4).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO: 4), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1560 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1560 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 43 through 245 of Figure 2 (SEQ ID NO:4).
  • the invention concerns an isolated PRO1560 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4).
  • the invention concerns an isolated PRO1560 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 43 through 245 of Figure 2 (SEQ ID NO:4).
  • the invention concerns an isolated PRO 1560 polypeptide, comprising the sequence of amino acid residues 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4), or a fragment thereof sufficient to provide a binding site for an anti-PRO1560 antibody.
  • the PRO1560 fragment retains a qualitative biological activity of a native PRO1560 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1560 polypeptide having the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1560 polypeptide.
  • the agonist or antagonist is an anti-PRO1560 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO1560 polypeptide, by contacting the native PRO1560 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PRO1560 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA26846-1393) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0444.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO: 1)
  • the invention concerns an isolated nucleic acid molecule encoding a PR0444 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 656 and about 958, inclusive, of Figure 3 (SEQ ID NO:5).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203406 (DNA26846-1397), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4
  • the invention concerns an isolated nucleic acid molecule having at least about 10 nucleotides, more preferably at least about 20 nucleotides, and most preferably at least about 40 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a
  • PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 16 in the sequence of Figure 4 (SEQ ID NO: 1
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO: 6), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PR0444 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR0444 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 17 to 117 of Figure 4 (SEQ ID NO:6).
  • the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6).
  • the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to 117 of Figure 4 (SEQ ID NO: 6).
  • the invention concerns an isolated PR0444 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or a fragment thereof sufficient to provide a binding site for an anti-PR0444 antibody.
  • the PR0444 fragment retains a qualitative biological activity of a native PR0444 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA56107-1415) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO1018".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1018 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO1018 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO: 8), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO1018 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 129 or about 201 and about 695, inclusive, of Figure 5 (SEQ ID NO:7).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203405 (DNA56107-1415) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203405 (DNA56107-1415).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure62 (SEQ ID NO:8), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1018 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1018 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 6 (SEQ ID NO:8).
  • the transmembrane domains have been tentatively identified as extending from about amino acid position 86 to about amino acid position 103 and from about amino acid position 60 to about amino acid position 75 in the PRO 1018 amino acid sequence ( Figure 6, SEQ ID NO: 8).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1018 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 5 (SEQ ID NO:7).
  • the invention provides isolated PRO1018 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PRO1018 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 189 of Figure 6 (SEQ ID NO:8).
  • the invention concerns an isolated PRO1018 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8).
  • the invention concerns an isolated PRO1018 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8).
  • the invention concerns an isolated PRO1018 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO: 8), or a fragment thereof sufficient to provide a binding site for an anti-PRO1018 antibody.
  • the PRO1018 fragment retains a qualitative biological activity of a native PRO 1018 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1018 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA56406-1704) has been identified, having homology to nucleic acid encoding a retinol dehydrogenase protein that encodes a novel polypeptide, designated in the present application as
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1773 polypeptide.
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1773 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 111 or about 162 and about 1067, inclusive, of Figure 7 (SEQ ID NO:9).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203478 (DNA56406-1704) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in
  • the invention concerns an isolated nucleic acid molecule having at least 525 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01773 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1773 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 8 (SEQ ID NO: 10).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 136 to about amino acid position 152 in the PR01773 amino acid sequence ( Figure 8, SEQ ID NO: 10).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 7 (SEQ ID NO: 9).
  • the invention provides isolated PRO 1773 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01773 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 319 of Figure 8 (SEQ ID NO: 10).
  • the invention concerns an isolated PR01773 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10).
  • the invention concerns an isolated PR01773 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO:10).
  • the invention concerns an isolated PRO 1773 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or a fragment thereof sufficient to provide a binding site for an anti-PR01773 antibody.
  • the PR01773 fragment retains a qualitative biological activity of a native PR01773 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1773 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO: 10), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01773 polypeptide.
  • the agonist or antagonist is an anti-PRO 1773 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01773 polypeptide by contacting the native PR01773 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PRO 1773 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • PRQ1477 A cDNA clone (DNA56529-1647) has been identified, having homology to nucleic acid encoding a mannosidase protein that encodes a novel polypeptide, designated in the present application as "PR01477".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1477 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1477 polypeptide having the sequence of amino acid residues from about 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1477 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 23 and about 2119, inclusive, of Figure 9 (SEQ ID NO: 11).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203293
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 540 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1477 polypeptide having the sequence of amino acid residues from 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01477 polypeptide, with or without and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domains have been tentatively identified as extending from about amino acid position 21 to about amino acid position 40 and from about amino acid position 84 to about amino acid position 105 in the PRO 1477 amino acid sequence ( Figure 10, SEQ ID NO: 12).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1477 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 9 (SEQ ID NO: 11).
  • the invention provides isolated PRO 1477 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01477 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 699 of Figure 10 (SEQ ID NO: 12).
  • the invention concerns an isolated PRO 1477 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12).
  • the invention concerns an isolated PRO 1477 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12).
  • the invention concerns an isolated PRO 1477 polypeptide, comprising the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or a fragment thereof sufficient to provide a binding site for an anti-PR01477 antibody.
  • the PR01477 fragment retains a qualitative biological activity of a native PRO 1477 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1477 polypeptide having the sequence of amino acid residues from about 1 to about 699, inclusive of Figure 10 (SEQ ID NO: 12), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1477 polypeptide.
  • the agonist or antagonist is an anti-PR01477 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1477 polypeptide by contacting the native PRO 1477 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01477 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA56531-1648) has been identified that encodes a novel polypeptide having sequence identity with galactosyltransferase and designated in the present application as "PRO 1478.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01478 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 77 and about 1057, inclusive, of Figure 11 (SEQ ID NO: 16).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203286 (DNA56531-1648), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203286 (DNA56531-1648).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domain (type II) has been tentatively identified as extending from about amino acid position 29 through about amino acid position 49 in the PR01478 amino acid sequence ( Figure 12, SEQ ID NO: 17). Therefore, a peptide including amino acids 50-327, with or without amino acids 1-28, is specifically embodied herein, as well as the nucleic acid encoding such a peptide.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1478 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01478 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 327 of Figure 12 (SEQ ID NO: 17).
  • the invention concerns an isolated PRO 1478 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17).
  • the invention concerns an isolated PRO 1478 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 327 of Figure 12 (SEQ ID NO: 17).
  • the invention concerns an isolated PRO 1478 polypeptide, comprising the sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1478 antibody.
  • the PRO 1478 fragment retains a qualitative biological activity of a native PR01478 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID NO: 17), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1478 polypeptide.
  • the agonist or antagonist is an anti-PR01478 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01478 polypeptide, by contacting the native PR01478 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01478 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA56862-1343) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0831".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO: 22), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR0831 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 40 or about 85 and about 258, inclusive, of Figure 13 (SEQ ID NO:21).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203174 (DNA56862-1343) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203174 (DNA56862-1343).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 470 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO: 22), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 14 (SEQ ID NO:22).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PR0831 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 13 (SEQ ID NO:21).
  • the invention provides isolated PR0831 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR0831 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 73 of Figure 14 (SEQ ID NO:22).
  • the invention concerns an isolated PR0831 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22).
  • the invention concerns an isolated PR0831 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22).
  • the invention concerns an isolated PR0831 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO: 22), or a fragment thereof sufficient to provide a binding site for an anti-PR0831 antibody.
  • the PR0831 fragment retains a qualitative biological activity of a native PR0831 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID NO:22), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA57254-1477) has been identified that encodes a novel polypeptide having sequence identity with leucine rich repeat proteins and designated in the present application as "PROl 113. "
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 113 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROl 113 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 214 and about 2061, inclusive, of Figure 15 (SEQ ID NO:23).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203289 (DNA57254-1477), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203289 (DNA57254-1477).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO: 24), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 113 polypeptide in its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 13 through about amino acid position 40 in the PROl 113 amino acid sequence ( Figure 16, SEQ ID NO:24).
  • Figure 16 SEQ ID NO:24
  • a peptide comprising amino acids 41-616, and optionally 1-12 of SEQ ID NO:24, and the nucleic acids encoding the same.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PROl 113 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1113 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 616 of Figure 16 (SEQ ID NO:24).
  • the invention concerns an isolated PROl 113 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 616, inclusive of Figure 16 (SEQ ID NO:24).
  • the invention concerns an isolated PROl 113 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 616 of Figure 16 (SEQ ID NO:24).
  • the invention concerns an isolated PROl 113 polypeptide, comprising the sequence of amino acid residues 1 to about 616, inclusive of Figure 16 (SEQ ID NO: 24), or a fragment thereof sufficient to provide a binding site for an anti-PROl 113 antibody.
  • the PROl 113 fragment retains a qualitative biological activity of a native PROl 113 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROH 13 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID NO: 24), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PROl 113 polypeptide.
  • the agonist or antagonist is an anti-PROl 113 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PROl 113 polypeptide, by contacting the native PROl 113 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PROl 113 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA57841-1522) has been identified that encodes a novel secreted polypeptide designated in the present application as "PROl 194.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1194 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 194 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROl 194 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 72 and about 251, inclusive, of Figure 17 (SEQ ID NO:28).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203458 (DNA57841-1522), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203458 (DNA57841-1522).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 to about 81, inclusive of Figure 18 (SEQ ID NO: 29), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PROl 194 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1194 polypeptide , which in one embodiment, includes an amino acid sequence comprising residues 22 through 81 of Figure 18 (SEQ ID NO: 29).
  • the invention concerns an isolated PROl 194 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 81 , inclusive of Figure 18 (SEQ ID NO:29).
  • the invention concerns an isolated PROl 194 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 through 81 of Figure 18 (SEQ ID NO:29).
  • the invention concerns an isolated PRO 1194 polypeptide, comprising the sequence of amino acid residues 22 to about 81 , inclusive of Figure 18 (SEQ ID NO: 29), or a fragment thereof sufficient to provide a binding site for an anti-PROl 194 antibody.
  • the PROl 194 fragment retains a qualitative biological activity of a native PRO 1194 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID NO:29), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1194 polypeptide.
  • the agonist or antagonist is an anti-PROl 194 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PROl 194 polypeptide, by contacting the native PROl 194 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PROl 194 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA58727-1474) has been identified, having homology to nucleic acid encoding myeloid upregulated protein that encodes a novel polypeptide, designated in the present application as "PROll lO".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 110 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 110 polypeptide having the sequence of amino acid residues from about 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROlllO polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 131 and about 1096, inclusive, of Figure 19 (SEQ ID NO:30).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203171 (DNA58727-1474) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203171 (DNA58727-1474).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizmg a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROll lO polypeptide having the sequence of amino acid residues from 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROlllO polypeptide, with or without the initiating methionine and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • transmembrane domains have been tentatively identified as extending from about amino acid position 41 to about amino acid position 60, from about amino acid position 66 to about amino acid position 85, from about amino acid position 101 to about amino acid position 120, from about amino acid position 137 to about amino acid position 153, from about amino acid position 171 to about amino acid position 192, from about amino acid position 205 to about amino acid position 226, from about amino acid position 235 to about amino acid position 255, and from about amino acid position 294 to about amino acid position 312 in the PROl l lO amino acid sequence (Figure 20, SEQ ID NO:31).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PROl 110 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 19 (SEQ ID NO:30).
  • the invention provides isolated PROl l lO polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention concerns an isolated PROl 110 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31).
  • the invention concerns an isolated PRO 1110 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31).
  • the invention concerns an isolated PRO 1110 polypeptide, comprising the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or a fragment thereof sufficient to provide a binding site for an anti-PROl 110 antibody.
  • the PROl 110 fragment retains a qualitative biological activity of a native PROll lO polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROlllO polypeptide having the sequence of amino acid residues from about 1 to about 322, inclusive of Figure 20 (SEQ ID NO:31), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PROlllO polypeptide.
  • the agonist or antagonist is an anti-PROl 110 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PROll lO polypeptide by contacting the native PROlllO polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PRO 1110 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA58730-1607) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1378".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1378 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1378 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01378 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1365 and about 2369, inclusive, of Figure 21 (SEQ ID NO:32).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203221 (DNA58730-1607), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203221 (DNA58730-1607).
  • the invention concerns an isolated nucleic acid molecule having at least about 20 nucleotides, preferably at least about 50 nucleotides, and more preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1378 polypeptide having the sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01378 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 15 in the sequence of Figure 22 (SEQ ID NO:33).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1378 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01378 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 to 335 of Figure 22 (SEQ ID NO: 33).
  • the invention concerns an isolated PR01378 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33).
  • the invention concerns an isolated PRO 1378 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 to 335 of Figure 22 (SEQ ID NO:33).
  • the invention concerns an isolated PR01378 polypeptide, comprising the sequence of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1378 antibody.
  • the PRO 1378 fragment retains a qualitative biological activity of a native PR01378 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1378 polypeptide having the sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID NO:33), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA58732-1650) has been identified that encodes a novel polypeptide designated in the present application as "PR01481.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01481 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1481 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1481 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 88 and about 1321, inclusive, of Figure 23 (SEQ ID NO:40).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203290 (DNA58732-1650), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203290 (DNA58732-1650).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01481 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted, truncated or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 24 (SEQ ID NO:41).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 235 through about amino acid position 262 in the PR01481 amino acid sequence ( Figure 24, SEQ ID NO:41).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1481 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1481 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1481 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 334 of Figure 24 (SEQ ID NO:
  • the invention concerns an isolated PR01481 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41).
  • the invention concerns an isolated PR01481 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 through 334 of Figure 24 (SEQ ID NO:41).
  • the invention concerns an isolated PRO 1481 polypeptide, comprising the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or a fragment thereof sufficient to provide a binding site for an anti-PR01481 antibody.
  • the PR01481 fragment retains a qualitative biological activity of a native PRO 1481 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID NO:41), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprismg the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1481 polypeptide.
  • the agonist or antagonist is an anti-PR01481 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1481 polypeptide, by contacting the native PRO 1481 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PRO 1481 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier. 13. PROl 189
  • a cDNA clone (DNA58828-1519) has been identified that encodes a novel polypeptidehaving homology to E25 which is designated in the present application as "PRO 1189.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 189 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PROl 189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROl 189 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 79 and about 867, inclusive, of Figure 25 (SEQ ID NO:42).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203172 (DNA58828-1519), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203172 (DNA58828-1519).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 189 polypeptide with its transmembrane domain deleted or inactivated, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 53 through about amino acid position 75 in the PROl 189 amino acid sequence ( Figure 26, SEQ ID NO:43).
  • the invention concerns an isolated nucleic acid molecule comprismg (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1189 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PROl 189 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PROl 189 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 263 of Figure 26 (SEQ ID NO:43).
  • the invention concerns an isolated PROl 189 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43).
  • the invention concerns an isolated PROl 189 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to 263 of Figure 26 (SEQ ID NO:43).
  • the invention concerns an isolated PRO 1189 polypeptide, comprising the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or a fragment thereof sufficient to provide a binding site for an anti-PROl 189 antibody.
  • the PROl 189 fragment retains a qualitative biological activity of a native PRO 1189 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID NO:43), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PROl 189 polypeptide.
  • the agonist or antagonist is an anti-PROl 189 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1189 polypeptide, by contacting the native PRO 1189 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PRO 1189 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA58852-1637) has been identified that encodes a novel polypeptide, designated in the present application as "PR01415".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 polypeptide.
  • the invention concerns an isolated nucleic acid molecule encoding a PR01415 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 148 or about 223 and about 996, inclusive, of Figure 27 (SEQ ID NO:49).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203271 (DNA58852-1637) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203271 (DNA58852-1637).
  • the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01415 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 28 (SEQ ID NO:50).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 94 to about amino acid position 118 in the PR01415 amino acid sequence ( Figure 28, SEQ ID NO:50).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PR01415 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 27 (SEQ ID NO:49).
  • the invention provides isolated PR01415 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01415 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 283 of Figure 28 (SEQ ID NO:50).
  • the invention concerns an isolated PR01415 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO: 50).
  • the invention concerns an isolated PR01415 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50).
  • the invention concerns an isolated PR01415 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or a fragment thereof sufficient to provide a binding site for an anti-PR01415 antibody.
  • the PR01415 fragment retains a qualitative biological activity of a native PR01415 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1415 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01415 polypeptide.
  • the agonist or antagonist is an anti-PR01415 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01415 polypeptide by contacting the native PR01415 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01415 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA59212-1627) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1411."
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01411 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1411 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01411 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 247 and about 1503, inclusive, of Figure 29 (SEQ ID NO:51).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203245 (DNA59212-1627), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203245 (DNA59212-1627).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO: 52), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PR01411 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1411 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01411 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 through 440 of Figure 30 (SEQ ID NO:52).
  • the invention concerns an isolated PRO 1411 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52).
  • the invention concerns an isolated PRO 1411 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 through 440 of Figure 30 (SEQ ID NO:52).
  • the invention concerns an isolated PRO 1411 polypeptide, comprising the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or a fragment thereof sufficient to provide a binding site for an anti-PR01411 antibody.
  • the PR01411 fragment retains a qualitative biological activity of a native PR01411 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID NO:52), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01411 polypeptide.
  • the agonist or antagonist is an anti-PRO 1411 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01411 polypeptide, by contacting the native PR01411 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01411 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • PRQ1295 A cDNA clone (DNA59218-1559) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1295.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1295 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1295 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01295 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 261 and about 1046, inclusive, of Figure 31 (SEQ ID NO:53).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203287 (DNA59218-1559), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203287 (DNA59218-1559).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1295 polypeptide having the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PR01295 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01295 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 280 of Figure 32 (SEQ ID NO:54).
  • the invention concerns an isolated PRO 1295 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54).
  • the invention concerns an isolated PR01295 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 through 280 of Figure 32 (SEQ ID NO:54).
  • the invention concerns an isolated PRO 1295 polypeptide , comprising the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or a fragment thereof sufficient to provide a binding site for an anti-PR01295 antibody.
  • the PR01295 fragment retains a qualitative biological activity of a native PRO 1295 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1295 polypeptide having the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID NO:54), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01295 polypeptide.
  • the agonist or antagonist is an anti-PR01295 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1295 polypeptide, by contacting the native PRO 1295 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PR01295 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA59219-1613) has been identified that encodes a novel polypeptide having sequence identity with sialytransferases and designated in the present application as "PRO 1359” polypeptides.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1359 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1359 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01359 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 277 and about 1080, inclusive, of Figure 33 (SEQ ID NO:55).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203220 (DNA59219-1613), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203220 (DNA59219-1613).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01359 polypeptide in its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domain (type II) has been tentatively identified as extending from about amino acid position 9 through about amino acid position 31 in the
  • PRO 1359 amino acid sequence ( Figure 34, SEQ ID NO: 56).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1359 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01359 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 through 299 of Figure 34 (SEQ ID NO:56).
  • the invention concerns an isolated PR01359 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56).
  • the invention concerns an isolated PR01359 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 32 through 299 of Figure 34 (SEQ ID NO:56).
  • the invention concerns an isolated PR01359 polypeptide, comprising the sequence of amino acid residues 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or a fragment thereof sufficient to provide a binding site for an anti-PR01359 antibody.
  • the PR01359 fragment retains a qualitative biological activity of a native PRO 1359 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID NO:56), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01359 polypeptide.
  • the agonist or antagonist is an anti-PR01359 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1359 polypeptide, by contacting the native PRO 1359 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PRO 1359 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA59586-1520) has been identified that encodes a novel polypeptide designated in the present application as "PRO1190", and which has homology to CDO protein.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1190 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROl 190 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 340 and about 3684, inclusive, of Figure 35 (SEQ ID NO:58).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203288 (DNA59586-1520), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203288 (DNA59586-1520).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 190 polypeptide, with one or more of its transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domains have been tentatively identified in the PROl 190 amino acid sequence shown in Figure 36 (SEQ ID NO:58) as extending from about amino acid position 16 to about amino acid position 30 and from about amino acid position 854 to about amino acid position 879.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PROl 190 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PROl 190 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 1115 of Figure 36 (SEQ ID NO:58).
  • the invention concerns an isolated PRO 1190 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58).
  • the invention concerns an isolated PROl 190 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to 1115 of Figure 36 (SEQ ID NO:58).
  • the invention concerns an isolated PRO 1190 polypeptide, comprising the sequence of amino acid residues 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or a fragment thereof sufficient to provide a binding site for an anti-PROl 190 antibody.
  • the PROl 190 fragment retains a qualitative biological activity of a native PROl 190 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROl 190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID NO:58), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PROl 190 polypeptide.
  • the agonist or antagonist is an anti-PROl 190 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PROl 190 polypeptide, by contacting the native PROl 190 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PROl 190 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA59817-1703) has been identified, having homology to nucleic acid encoding peptidase enzymes, that encodes a novel polypeptide, designated in the present application as "PR01772".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01772 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01772 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 93 or about 201 and about 1553, inclusive, of Figure 37 (SEQ ID NO:62). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203470 (DNA59817-1703).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO: 63), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 415 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1772 polypeptide having the sequence of amino acid residues from 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PR01772 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 36 in the sequence of Figure 38 (SEQ ID NO:63).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 313 to about amino acid position 331 in the PR01772 amino acid sequence ( Figure 38, SEQ ID NO:63).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 37 (SEQ ID NO: 62).
  • the invention provides isolated PR01772 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01772 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 37 to about 487 of Figure 38 (SEQ ID NO:63).
  • the invention concerns an isolated PR01772 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63).
  • the invention concerns an isolated PR01772 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63).
  • the invention concerns an isolated PRO 1772 polypeptide , comprising the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or a fragment thereof sufficient to provide a binding site for an anti-PR01772 antibody.
  • the PR01772 fragment retains a qualitative biological activity of a native PRO 1772 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID NO:63), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an
  • the invention concerns agonists and antagonists of a native PR01772 polypeptide.
  • the agonist or antagonist is an anti-PRO 1772 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1772 polypeptide by contacting the native PRO 1772 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PR01772 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA60278-1530) has been identified, having homology to nucleic acid encoding PUT- 2, that encodes a novel polypeptide, designated in the present application as "PRO 1248".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01248 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1248 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO: 1).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1248 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 182 and about 670, inclusive, of Figure 39 (SEQ ID NO:67).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203170 (DNA60278-1530) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203170 (DNA60278-1530).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1248 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1248 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 40 (SEQ ID NO: 68).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 90 to about amino acid position 112 in the PR01248 amino acid sequence ( Figure 40, SEQ ID NO:68).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO: 68), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1248 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 39 (SEQ ID NO:67).
  • the invention provides isolated PRO 1248 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01248 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 183 of Figure 40 (SEQ ID NO:68).
  • the invention concerns an isolated PRO 1248 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68).
  • the invention concerns an isolated PRO 1248 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO: 68).
  • the invention concerns an isolated PR01248 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO: 68), or a fragment thereof sufficient to provide a binding site for an anti-PR01248 antibody.
  • the PR01248 fragment retains a qualitative biological activity of a native PRO 1248 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1248 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID NO:68), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1248 polypeptide.
  • the agonist or antagonist is an anti-PR01248 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01248 polypeptide by contacting the native PR01248 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01248 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA60608-1577) has been identified, having homology to Dickkopf that encodes a novel polypeptide, designated in the present application as "PRO 1316. "
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1316 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1316 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 259, inclusive of Figure 42 (SEQ ID NO:70), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01316 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 281 and about 987, inclusive, of Figure 41 (SEQ ID NO:69).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203126 (DNA60608-1577), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203126 (DNA60608-1577).
  • the invention concern an isolated nucleic acid molecule having at least 15 nucleotides which hybridizes under stringent conditions with (a) a DNA molecule having a identity with a region spanning either from residues 1-454 or from residues 1095-3130 of the Figure 41 (SEQ ID NO:69), or (b) the complement of the DNA molecule of (a).
  • an isolated nucleic acid molecule having at least 15 nucleotides having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to: (a) a DNA molecule having a identity with a region spanning either from residues 1-454 or from residues 1095-3130 ofthe Figure 41 (SEQ ID NO: 69), or (b) the complement of the DNA molecule of (a).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1316 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 25 in the sequence of Figure 42 (SEQ ID NO:70).
  • An N-glycosylation site has been identified at position 52 and a fungal Zn(2)-Cys(6) binuclear cluster has been identified at position 99.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 26 to about 259, inclusive of Figure 42 (SEQ ID NO:70), or (b) the complement of the DNA of (a).
  • the invention provides isolated PR01316 polypeptide encoded by any of the isolated nucleic acid sequences herein above defined.
  • the invention provides isolated native sequence PRO 1316 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 to 259 of Figure 42 (SEQ ID NO:70).
  • the invention concerns an isolated PR01316 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ ID NO:70).
  • the invention concerns an isolated PRO 1316 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 26 to 259 of Figure 42 (SEQ ID NO:70).
  • the invention concerns an isolated PRO 1316 polypeptide, comprising the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ ID NO:70), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1316 antibody .
  • the PRO 1316 fragment retains a qualitative biological activity of a native PRO 1316 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1316 polypeptide having the sequence of amino acid residues from about 26 to about 259, inclusive of Figure 42 (SEQ ID NO:70), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of the a native PR01316 polypeptide.
  • the agonist or antagonist is an anti-PR01316 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01316 polypeptide, by contacting the native PR01316 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01316 polypeptide, or an agonist or antagonist as herein above defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA60611-1524) has been identified that encodes a novel secreted polypeptide designated in the present application as "PROl 197.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 197 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROl 197 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PROl 197 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 383 and about 1399, inclusive, of Figure 43 (SEQ ID NO:71).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203175 (DNA60611-1524), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203175 (DNA60611-1524).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO: 1
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PROl 197 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PROl 197 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PROl 197 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 25 through 363 of Figure 44 (SEQ ID NO:72).
  • the invention concerns an isolated PROl 197 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72).
  • the invention concerns an isolated PROl 197 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 through 363 of Figure 44 (SEQ ID NO:72).
  • the invention concerns an isolated PRO 1197 polypeptide , comprising the sequence of amino acid residues 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or a fragment thereof sufficient to provide a binding site for an anti-PROl 197 antibody.
  • the PROl 197 fragment retains a qualitative biological activity of a native PRO 1197 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID NO:72), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PROl 197 polypeptide.
  • the agonist or antagonist is an anti-PROl 197 antibody.
  • a cDNA clone (DNA60618-1557) has been identified, having homology to nucleic acid encoding an immunoglobulin heavy chain variable region protein that encodes a novel polypeptide, designated in the present application as " PRO 1293".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01293 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1293 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1293 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 37 or about 94 and about 1059, inclusive, of Figure 45 (SEQ ID NO:76).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203292
  • nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO: 1
  • the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1293 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1293 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 46 (SEQ ID NO:77).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 237 to about amino acid position 262 in the PR01293 amino acid sequence ( Figure 46, SEQ ID NO:77).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO: 77), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1293 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 45 (SEQ ID NO: 76).
  • the invention provides isolated PRO 1293 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01293 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 341 of Figure 46 (SEQ ID NO:77).
  • the invention concerns an isolated PR01293 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO: 77).
  • the invention concerns an isolated PR01293 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77).
  • the invention concerns an isolated PR01293 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 341 , inclusive of Figure 46 (SEQ ID NO: 77), or a fragment thereof sufficient to provide a binding site for an anti-PR01293 antibody.
  • the PR01293 fragment retains a qualitative biological activity of a native PRO 1293 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1293 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID NO:77), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01293 polypeptide.
  • the agonist or antagonist is an anti-PR01293 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1293 polypeptide by contacting the native PRO 1293 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PR01293 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA60740-1615) has been identified that encodes a novel multi-span transmembrane polypeptide designated in the present application as "PRO1380".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1380 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1380 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 36 and about 1460, inclusive, of Figure 47 (SEQ ID NO:78).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203456 (DNA60740-1615), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203456 (DNA60740-1615).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO: 79), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PRO1380 polypeptide, and its soluble variants (i.e. one or more transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule.
  • Transmembrane domains have been tentatively identified at about the following amino acid positions: 50-74, 105-127, 135-153, 163-183, 228-252,
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1380 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1380 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO1380 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 470 of Figure 48 (SEQ ID NO:79).
  • the invention concerns an isolated PRO1380 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79).
  • the invention concerns an isolated PRO1380 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to 470 of Figure 48 (SEQ ID NO:79).
  • the invention concerns an isolated PRO 1380 polypeptide, comprising the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ ID NO:79), or a fragment thereof sufficient to provide a binding site for an anti-PRO1380 antibody.
  • the PRO1380 fragment retains a qualitative biological activity of a native PRO1380 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID NO: 79), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culmring a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • PRQ1265 A cDNA clone (DNA60764-1533) has been identified that encodes a novel polypeptide having homology to the Figl polypeptide and designated in the present application as "PRO 1265.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1265 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1265 polypeptide having the sequence of amino acid residues from 1 or about about 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01265 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 142 and about 1779, inclusive, of Figure 49 (SEQ ID NO:83). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203452 (DNA60764-1533).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1265 polypeptide having the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01265 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 21 in the sequence of Figure 50 (SEQ ID NO: 1
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1265 polypeptide coding sequence that may find use as hybridization probes.
  • Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1265 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01265 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 22 to 567 of Figure 50 (SEQ ID NO:84).
  • the invention concerns an isolated PR01265 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84).
  • the invention concerns an isolated PRO 1265 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 to 567 of Figure 50 (SEQ ID NO:84).
  • the invention concerns an isolated PRO 1265 polypeptide, comprising the sequence of amino acid residues 22 to about 567, inclusive of Figure 50 (SEQ ID NO:84), or a fragment thereof sufficient to provide a binding site for an anti-PR01265 antibody.
  • the PR01265 fragment retains a qualitative biological activity of a native PR01265 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID NO: 84), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culmring a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA60775-1532) has been identified, having homology to nucleic acid encoding long chain fatty acid CoA ligase that encodes a novel polypeptide, designated in the present application as "PRO1250".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1250 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1250 polypeptide having the sequence of amino acid residues from about 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO1250 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 and about 2290, inclusive, of Figure 51 (SEQ ID NO:85).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203173 (DNA60775-1532) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203173 (DNA60775-1532).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1250 polypeptide having the sequence of amino acid residues from 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1250 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the type II transmembrane domain has been tentatively identified as extending from about amino acid position 61 to about amino acid position 80 in the PRO1250 amino acid sequence ( Figure 52, SEQ ID NO:86).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 51 (SEQ ID NO: 85).
  • the invention provides isolated PRO1250 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PRO1250 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 739 of Figure 52 (SEQ ID NO:86).
  • the invention concerns an isolated PRO 1250 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86).
  • the invention concerns an isolated PRO 1250 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86).
  • the invention concerns an isolated PRO 1250 polypeptide , comprising the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1250 antibody.
  • the PRO 1250 fragment retains a qualitative biological activity of a native PRO 1250 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1250 polypeptide having the sequence of amino acid residues from about 1 to about 739, inclusive of Figure 52 (SEQ ID NO:86), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b) , (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO1250 polypeptide.
  • the agonist or antagonist is an anti-PRO1250 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO1250 polypeptide by contacting the native PRO1250 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PRO1250 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA61185-1646) has been identified, having homology to nucleic acid encoding an N-acetylglucosaminyltransferase that encodes a novel polypeptide, designated in the present application as "PR01475".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01475 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1475 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 130 and about 2109, inclusive, of Figure 53 (SEQ ID NO:87).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203464 (DNA61185-1646) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203464 (DNA61185-1646).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 180 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1475 polypeptide having the sequence of amino acid residues from 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01475 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 38 to about amino acid position 55 in the PR01475 amino acid sequence ( Figure 54, SEQ ID NO:88).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA of (a).
  • Another embodiment is directed to fragments of a PRO 1475 polypeptide coding sequence that may find use as hybridization probes.
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 53 (SEQ ID NO:87).
  • the invention provides isolated PRO 1475 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PRO 1475 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 660 of Figure 54 (SEQ ID NO:88).
  • the invention concerns an isolated PR01475 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO: 88).
  • the invention concerns an isolated PR01475 polypeptide, comprising an amino acid sequence scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88).
  • the invention concerns an isolated PRO 1475 polypeptide, comprising the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or a fragment thereof sufficient to provide a binding site for an anti-PR01475 antibody.
  • the PR01475 fragment retains a qualitative biological activity of a native PR01475 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID NO:88), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01475 polypeptide.
  • the agonist or antagonist is an anti-PR01475 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PR01475 polypeptide by contacting the native PR01475 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PR01475 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier. 28. PRQ1377
  • a cDNA clone (DNA61608- 1606) has been identified that encodes a novel multi-span transmembrane polypeptide designated in the present application as "PRO 1377.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1377 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1377 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01377 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 203 and about 1069, inclusive, of Figure 55 (SEQ ID NO:94).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203239 (DNA61608- 1606), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203239 (DNA61608- 1606).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID NO: 95), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1377 polypeptide having the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID NO: 95), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01377 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and one or more of its transmembrane domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 56 (SEQ ID N0:95).
  • Transmembrane domain has been tentatively identified as extending from about amino acid positions 37-56, 106-122, 211-20, 240-260, and 288-304 in the PRO 1377 amino acid sequence ( Figure 56, SEQ ID NO: 95).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1377 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1377 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 307 of Figure 56 (SEQ ID NO: 95).
  • the invention concerns an isolated PR01377 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95).
  • the invention concerns an isolated PR01377 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 to 307 of Figure 56 (SEQ ID NO:95).
  • the invention concerns an isolated PRO 1377 polypeptide, comprising the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or a fragment thereof sufficient to provide a binding site for an anti-PR01377 antibody.
  • the PR01377 fragment retains a qualitative biological activity of a native PRO 1377 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1377 polypeptide having the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID NO:95), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culmring a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA62808-1582) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1326.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1326 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1326 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 401 , inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01326 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 199 and about 1314, inclusive, of Figure 57 (SEQ ID NO:99).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203358 (DNA62808-1582), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203358 (DNA62808-1582).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 1).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1326 polypeptide having the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01326 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 58 (SEQ ID NO: 100).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1326 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1326 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 to 401 of Figure 58 (SEQ ID NO: 100).
  • the invention concerns an isolated PR01326 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100).
  • the invention concerns an isolated PRO 1326 polypeptide , comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 30 to 401 of Figure 58 (SEQ ID NO: 100).
  • the invention concerns an isolated PRO 1326 polypeptide , comprising the sequence of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or a fragment thereof sufficient to provide a binding site for an anti-PR01326 antibody.
  • the PR01326 fragment retains a qualitative biological activity of a native PR01326 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1326 polypeptide having the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO: 100), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA62809-1531) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO 1249".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01249 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 3 or about 51 and about 3269, inclusive, of Figure 59 (SEQ ID NO: 101).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203237 (DNA62809-1531) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203237 (DNA62809-1531).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1249 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 16 in the sequence of Figure 60 (SEQ ID NO: 102).
  • transmembrane domains have been tentatively identified as extending from about amino acid position 317 to about amino acid position 341, from about amino acid position 451 to about amino acid position 470, from about amino acid position 481 to about amino acid position 500, from about amino acid position 510 to about amino acid position 527, from about amino acid position 538 to about amino acid position 555, from about amino acid position 831 to about amino acid position 850, from about amino acid position 1016 to about amino acid position 1034 and from about amino acid position 1052 to about amino acid position 1070 in the PR01249 amino acid sequence (Figure 60, SEQ ID NO: 102).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 59 (SEQ ID NO: 101).
  • the invention provides isolated PR01249 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01249 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 17 to about 1089 of Figure 60 (SEQ ID NO: 102).
  • the invention concerns an isolated PRO 1249 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102).
  • the invention concerns an isolated PR01249 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102).
  • the invention concerns an isolated PR01249 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or a fragment thereof sufficient to provide a binding site for an anti-PR01249 antibody.
  • the PR01249 fragment retains a qualitative biological activity of a native PRO 1249 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culmring a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • PRQ1315 a DNA molecule encoding a PRO 1249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID NO: 102), or
  • a cDNA clone (DNA62815-1576) has been identified, having homology to nucleic acid encoding cytokine receptor family -4 proteins that encodes a novel polypeptide, designated in the present application as "PR01315" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01315 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1315 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01315 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 121 or about 205 and about 1446, inclusive, of Figure 61 (SEQ ID NO: 103). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203247 (DNA62815-1576).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 1).
  • the invention concerns an isolated nucleic acid molecule having at least 500 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encodmg a PRO 1315 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01315 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 62 (SEQ ID NO: 104).
  • the transmembrane domain has been tentatively identified as extending from about amino acid position 140 to about amino acid position 163 in the PR01315 amino acid sequence ( Figure 62, SEQ ID NO: 104).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 61 (SEQ ID NO: 103).
  • the invention provides isolated PR01315 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01315 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 442 of Figure
  • the invention concerns an isolated PR01315 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104).
  • the invention concerns an isolated PRO 1315 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104).
  • the invention concerns an isolated PRO 1315 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or a fragment thereof sufficient to provide a binding site for an anti-PR01315 antibody.
  • the PR01315 fragment retains a qualitative biological activity of a native PRO 1315 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01315 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID NO: 104), or a fragment thereof sufficient to provide a binding site for an anti-PR01315 antibody.
  • the PR01315 fragment retains a qualitative biological activity of a native PRO 1315 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA
  • the invention concerns agonists and antagonists of a native PR01315 polypeptide.
  • the agonist or antagonist is an anti-PR01315 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1315 polypeptide by contacting the native PRO 1315 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PRO 1315 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA62845-1684)has been identified that encodes a novel polypeptide having homology to Granzyme M and designated in the present application as "PRO 1599.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1599 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1599 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01599 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 and about 917, inclusive, of Figure 63 (SEQ ID NO: 110).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203361 (DNA62845-1684), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203361 (DNA62845-1684).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01599 polypeptide having the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01599 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 64 (SEQ ID NO: 1
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1599 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1599 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 283 of Figure 64 (SEQ ID NO: 111).
  • the invention concerns an isolated PRO 1599 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111).
  • the invention concerns an isolated PR01599 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 283 of Figure 64 (SEQ ID NO:l l l).
  • the invention concerns an isolated PR01599 polypeptide, comprising the sequence of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or a fragment thereof sufficient to provide a binding site for an anti-PR01599 antibody.
  • the PR01599 fragment retains a qualitative biological activity of a native PR01599 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1599 polypeptide having the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID NO: 111), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (n) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (in) recovering the polypeptide from the cell culture
  • the invention concerns agonists and antagonists of a native PR01599 polypeptide
  • the agonist or antagonist is an anti-PRO 1599 antibody
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1599 polypeptide, by contacting the native PRO 1599 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide
  • the invention concerns a composition
  • a composition comprismg a PR01599 polypeptide, or an agonist or antagonist as hereinabove defined, in combmation with a pharmaceutically acceptable carrier
  • a cDN A clone (DNA64842 1632) has been identified that encodes a novel polypeptide having homology to reductase proteins, designated in the present application as "PRO 1430 "
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PRO 1430 polypeptide
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg a PRO 1430 polypeptide having the sequence of ammo acid residues from 1 or about 18 to about 331, inclusive of Figure 66 (SEQ ID NO 116), or (b) the complement of the DNA molecule of (a)
  • the invention concerns an isolated nucleic acid molecule encodmg a PRO 1430 polypeptide comprismg DNA hybridizing to the complement of the nucleic acid between about residues 33 and about 1074, inclusive, of Figure 65 (SEQ ID NO 115) Preferably, hybridization occurs under stringent hybridization and wash conditions
  • the invention concerns an isolated nucleic acid molecule comprismg DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No 203278 (DNA64842-1632), or (b) the complement ofthe DNA molecule of (a)
  • the nucleic acid comprises a DNA encodmg the same mature polypeptide encoded by the human protein cDNA m ATCC Deposit No 203278 (DNA64842-1632)
  • the invention concerns an isolated nucleic acid molecule comprismg (a) DNA encodmg a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues from about 18 to about 331 , mciusive of Figure 66 (SEQ ID NO: 1).
  • the invention concerns an isolated nucleic acid molecule havmg at least about 50 nucleotides, and preferably at least about 100 and produced by hybridizing a test DNA molecule under strmgent conditions with (a) a DNA molecule encoding a PRO 1430 polypeptide having the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID NO 116), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1430 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encodmg nucleic acid molecule
  • the signal peptide has been tentatively identified as extendmg from ammo acid position 1 through about amino acid position 17 in the sequence of Figure 66 (SEQ ID NO 116)
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encodmg a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the ammo acid sequence of residues 18 to about 331 , inclusive of Figure 66 (SEQ ID NO 116), or (b) the complement of the DNA of (a) Another embodiment is directed to fragments of a PRO 1430 polypeptide coding sequence that may find use as hybridization probes Such nucleic acid fragments are
  • the invention provides isolated PRO 1430 polypeptide encoded by any of the isolated nucleic acid sequences heremabove defined
  • the mvention provides isolated native sequence PRO 1430 polypeptide, which in one embodiment, includes an ammo acid sequence comprismg residues 18 to 331 of Figure 66 (SEQ ID NO 116)
  • the mvention concerns an isolated PRO 1430 polypeptide, comprising an ammo acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues 18 to about 331, inclusive of Figure 66 (SEQ ID NO 116)
  • the invention concerns an isolated PRO1430 polypeptide, comprismg an amino acid sequence scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the ammo acid sequence of residues 18 to 331 of Figure 66 (SEQ ID NO 116)
  • the invention concerns an isolated PRO 1430 polypeptide, comprismg the sequence of ammo acid residues 18 to about 331, mciusive of Figure 66 (SEQ ID NO 116), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1430 antibody
  • the PRO 1430 fragment retains a qualitative biological activity of a native PRO 1430 polypeptide
  • the mvention provides a polypeptide produced by (t) hybridizing a test DNA molecule under strmgent conditions with (a) a DNA molecule encodmg a PRO 1430 polypeptide havmg the sequence of ammo acid residues from about 18 to about 331 , inclusive of Figure 66 (SEQ ID NO 116), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 9
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1430 polypeptide, by contacting the native PRO 1430 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition comprising a PRO1430 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA64849-1604) has been identified that encodes a novel polypeptide having sequence identity with P4HA and designated in the present application as "PRO 1374. "
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1374 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1374 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01374 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 78 and about 1652, inclusive, of Figure 67 (SEQ ID NO: 117).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203468 (DNA64849-1604), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203468 (DNA64849-1604).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1374 polypeptide having the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PR01374 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PRO 1374 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 544 of Figure 68 (SEQ ID NO: 118).
  • the invention concerns an isolated PR01374 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118).
  • the invention concerns an isolated PR01374 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 through 544 of Figure 68 (SEQ ID NO: 118).
  • the invention concerns an isolated PR01374 polypeptide, comprising the sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1374 antibody.
  • the PRO 1374 fragment retains a qualitative biological activity of a native PRO 1374 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1374 polypeptide having the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID NO: 118), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (n) culturing a host cell comp ⁇ sing the test DNA molecule under conditions suitable for expression of the polypeptide, and (in) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1374 polypeptide
  • the agomst or antagonist is an ant ⁇ -PR01374 antibody
  • the invention concerns a method of identifying agonists or antagonists of a native PR01374 polypeptide, by contacting the native PR01374 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide
  • the invention concerns a composition
  • a composition comprismg a PRO 1374 polypeptide , or an agonist or antagonist as hereinabove defined, m combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA64863-1573) has been identified that encodes a novel tetraspan polypeptide designated in the present application as "PR01311 "
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PRO 1311 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg a PR01311 polypeptide having the sequence of ammo acid residues from 1 or about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1311 polypeptide comprismg DNA hybridizmg to the complement ofthe nucleic acid between about residues 327 and about 1076, inclusive, of Figure 69 (SEQ ID NO.122).
  • hybridization occurs under strmgent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprismg DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg the same mamre polypeptide encoded by the human protein cDNA m ATCC Deposit No. 203251 (DNA64863-1573), or (b) the complement ofthe DNA molecule of (a).
  • the nucleic acid comprises a DNA encodmg the same mamre polypeptide encoded by the human protem cDNA in ATCC
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01311 polypeptide having the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1311 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 44 in the sequence of Figure 70 (SEQ ID NO: 123).
  • Four transmembrane domains has been tentatively identified as extending from about amino acid 22-42, 57-85, 94-116, and 230-257 in the PR01311 amino acid sequence ( Figure 70, SEQ ID NO: 123).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PRO 1311 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
  • the invention provides isolated native sequence PR01311 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 45 to 294 of Figure 70 (SEQ ID NO: 123).
  • the invention concerns an isolated PR01311 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123).
  • the invention concerns an isolated PR01311 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 45 to 294 of Figure 70 (SEQ ID NO: 123).
  • the invention concerns an isolated PR01311 polypeptide, comprising the sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1311 antibody.
  • the PRO 1311 fragment retains a qualitative biological activity of a native PRO 1311 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01311 polypeptide having the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID NO: 123), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • a cDNA clone (DNA64881-1602) has been identified, having homology to nucleic acid encoding the von Ebner minor salivary gland protein that encodes a novel polypeptide, designated in the present application as "PR01357”.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1357 polypeptide .
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1357 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01357 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 or about 137 and about 1525, inclusive, of Figure 71 (SEQ ID NO: 127). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203240 (DNA64881-1602).
  • the invention concerns an isolated nucleic acid molecule having at least 40 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01357 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PR01357 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extendmg from about amino acid position 1 to about amino acid position 21 in the sequence of Figure 72 (SEQ ID NO: 128).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 71 (SEQ ID NO: 127).
  • the invention provides isolated PR01357 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention provides isolated native sequence PR01357 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 22 to about 484 of Figure 72 (SEQ ID NO: 128).
  • the invention concerns an isolated PR01357 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128).
  • the invention concerns an isolated PR01357 polypeptide, comprising an amino acid sequence scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128).
  • the invention concerns an isolated PRO 1357 polypeptide, comprising the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or a fragment thereof sufficient to provide a binding site for an anti-PR01357 antibody.
  • the PR01357 fragment retains a qualitative biological activity of a native PR01357 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1357 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID NO: 128), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO 1357 polypeptide.
  • the agonist or antagonist is an anti-PR01357 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1357 polypeptide by contacting the native PRO 1357 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the mvention concerns a composition comprising a PRO 1357 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA64883- 1526) has been identified that encodes a novel polypeptide having homology to Implantation-Associated Protein and designated in the present application as "PR01244.”
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01244 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1244 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 335, inclusive of Figure 74 (SEQ ID NO: 130), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01244 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 96 and about 1013, inclusive, of Figure 73 (SEQ ID NO: 129). Preferably, hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No.
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203253 (DNA64883-1526).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues from about 30 to about 335, inclusive of Figure 74 (SEQ ID NO.130), or the complement of the DNA of (a)
  • the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizmg a test DNA molecule under strmgent conditions with (a) a DNA molecule encoding a PRO 1244 polypeptide havmg the sequence of ammo acid residues from about 30 to about 335, inclusive of Figure 74 (SEQ ID NO- 130), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encodmg a PR01244 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionme, and its soluble, l e transmembrane domams deleted or inactivated variants, or is complementary to such encodmg nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from ammo acid position 1 through about ammo acid position 29 m the sequence of Figure 74 (SEQ ID NO.130).
  • the transmembrane domains have been tentatively identified m the PRO 1244 ammo acid sequence at about the following ammo acid regions: 183-205, 217-137, 271-287, and 301-321.
  • the mvention concerns an isolated nucleic acid molecule comprismg (a) DNA encodmg a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the ammo acid sequence of residues 30 to about 335, inclusive of Figure 74 (SEQ ID NO: 130), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides m length, and most preferably from about 20 to about 40 nucleotides in length.
  • the invention provides isolated PR01244 polypeptide encoded by any of the isolated nucleic acid sequences heremabove defined.
  • the invention provides isolated native sequence PR01244 polypeptide, which in one embodiment, includes an ammo acid sequence comprismg residues 30 to 335 of Figure 74 (SEQ ID NO: 130).
  • the invention concerns an isolated PR01244 polypeptide, comprising an ammo acid sequence havmg at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues 30 to about 335, mciusive of Figure 74 (SEQ ID NO: 130).
  • the invention concerns an isolated PRO 1244 polypeptide, comprismg an amino acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 30 to 335 of Figure 74 (SEQ ID NO 130)
  • the invention provides a polypeptide produced by (l) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01244 polypeptide having the sequence of ammo acid residues from about 30 to about 335, inclusive of Figure 74 (SEQ ID NO 130), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (n) culmring a host cell comprismg the test DNA molecule under conditions suitable for expression of the polypeptide, and (in) recovering the polypeptide from the cell culture
  • the invention concerns agonists and antagonists of a native PR01244 polypeptide
  • the agonist or antagonist is an ant ⁇ -PR01244 antibody
  • the mvention concerns a method of identifying agonists or antagonists of a native PRO 1244 polypeptide, by contacting the native PRO 1244 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide
  • the invention concerns a composition
  • a composition comprismg a PRO 1244 polypeptide, or an agomst or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier
  • a cDNA clone (DNA64885-1529) has been identified, havmg homology to nucleic acid encoding bone- related sulphatase that encodes a novel polypeptide, designated m the present application as "PRO 1246"
  • the mvention provides an isolated nucleic acid molecule comprismg DNA encodmg a PRO 1246 polypeptide
  • the isolated nucleic acid comprises DNA havmg at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encodmg a PRO 1246 polypeptide havmg the sequence of ammo acid residues from about 1 or about 16 to about 536, mciusive of Figure 76 (SEQ ID NO 132), or (b) the complement of the DNA molecule of (a)
  • the invention concerns an isolated nucleic acid molecule encodmg a PRO 1246 polypeptide comprismg DNA hybridizing to the complement of the nucleic acid between about nucleotides 119 or about 164 and about 1726, inclusive, of Figure 75 (SEQ ID NO 131)
  • hybridization occurs under strmgent hybridization and wash conditions
  • the invention concerns an isolated nucleic acid molecule comprising DNA havmg at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No 203457 (DNA64885-1529) or (b) the complement of the nucleic acid molecule of (a)
  • the nucleic acid comprises a DNA encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No 203457 (DNA64885-1529)
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1
  • the invention provides an isolated nucleic acid molecule comprismg DNA encodmg a PRO 1246 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule
  • the signal peptide has been tentatively identified as extendmg from about ammo acid position 1 to about ammo acid position 16 in the sequence of Figure 76 (SEQ ID NO: 76).
  • the invention concerns an isolated nucleic acid molecule comprismg (a) DNA encoding a polypeptide scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 16 to about 536, mciusive of Figure 76 (SEQ ID NO.132), or (b) the complement of the DNA of (a)
  • nucleic acid fragments are from about 20 to about 80 nucleotides m length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides m length and most preferably from about 20 to about 40 nucleotides m length and may be derived from the nucleotide sequence shown in Figure 75 (SEQ ID NO: 131).
  • the invention provides isolated PR01246 polypeptide encoded by any of the isolated nucleic acid sequences heremabove identified
  • the invention provides isolated native sequence PRO 1246 polypeptide, which in certain embodiments, mcludes an ammo acid sequence comprismg residues 1 or about 16 to about 536 of Figure 76 (SEQ ID NO 132).
  • the invention concerns an isolated PR01246 polypeptide, comprismg an ammo acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID NO: 132)
  • the invention concerns an isolated PR01246 polypeptide, comprismg an ammo acid sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID NO: 132).
  • the invention concerns an isolated PRO 1246 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID NO: 132), or a fragment thereof sufficient to provide a binding site for an anti-PR01246 antibody.
  • the PR01246 fragment retains a qualitative biological activity of a native PRO 1246 polypeptide.
  • the invention provides a polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1246 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID NO: 132), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprismg the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PR01246 polypeptide.
  • the agonist or antagonist is an anti-PR01246 antibody.
  • the invention concerns a method of identifying agonists or antagonists of a native PRO 1246 polypeptide by contacting the native PRO 1246 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
  • the invention concerns a composition
  • a composition comprising a PR01246 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
  • a cDNA clone (DNA64886-1601) has been identified, having homology to nucleic acid encoding clostridium perfringens enterotoxin receptor, that encodes a novel polypeptide, designated in the present application as " PRO 1356".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1356 polypeptide.
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1356 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 1).
  • the invention concerns an isolated nucleic acid molecule encoding a PRO 1356 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 194 and about 811, inclusive, of Figure 77 (SEQ ID NO: 133).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203241 (DNA64886-1601) or (b) the complement of the nucleic acid molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203241 (DNA64886-1601).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA of (a).
  • the invention concerns an isolated nucleic acid molecule having at least 20 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01356 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO 1356 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
  • the signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 78 (SEQ ID NO: 134).
  • transmembrane domains have been tentatively identified as extending from about amino acid position 82 to about amino acid position 102, from about amino acid position 117 to about amino acid position 140 and from about amino acid position 163 to about amino acid position 182 in the PR01356 amino acid sequence ( Figure 78, SEQ ID NO: 134).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA of (a).
  • nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 77 (SEQ ID NO: 133).
  • the invention provides isolated PR01356 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified
  • the invention provides isolated native sequence PR01356 polypeptide, which in certain embodiments, mcludes an amino acid sequence comprising residues 1 or about 25 to about 230 of Figure 78 (SEQ ID NO 134)
  • the invention concerns an isolated PR01356 polypeptide, comprising an amino acid sequence havmg at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of ammo acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134)
  • the invention concerns an isolated PRO 1356 polypeptide, comprising an ammo acid sequence scormg at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO 134)
  • the invention concerns an isolated PRO 1356 polypeptide, comprising the sequence of ammo acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO 134), or a fragment thereof sufficient to provide a binding site for an ant ⁇ -PR01356 antibody
  • the PR01356 fragment retains a qualitative biological activity of a native PRO 1356 polypeptide
  • the invention provides a polypeptide produced by (1) hybridizmg a test DNA molecule under strmgent conditions with (a) a DNA molecule encoding a PRO 1356 polypeptide havmg the sequence of ammo acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID NO: 134), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (n) culmring a host cell comprismg the test DNA molecule under conditions suitable for expression of the polypeptide, and (in) recovering the polypeptide from the cell culture
  • the invention concerns agonists and antagonists of a native PR01356 polypeptide.
  • the agomst or antagonist is an ant ⁇ -PR01356 antibody.
  • the mvention concerns a method of identifymg agomsts or antagonists of a native PR01356 polypeptide by contactmg the native PR01356 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide
  • the invention concerns a composition
  • a composition comprising a PR01356 polypeptide, or an agonist or antagonist as hereinabove defined, in combmation with a pharmaceutically acceptable carrier
  • a cDNA clone (DNA64888-1542) has been identified that encodes a novel secreted polypeptide designated in the present application as "PRO 1275 "
  • the invention provides an isolated nucleic acid molecule comprismg DNA encoding a PRO 1275 polypeptide
  • the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO 1275 polypeptide having the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or (b) the complement of the DNA molecule of (a).
  • the invention concerns an isolated nucleic acid molecule encoding a PR01275 polypeptide comprising DNA hybridizing to the complement ofthe nucleic acid between about residues 112 and about 393, inclusive, of Figure 79 (SEQ ID NO: 135).
  • hybridization occurs under stringent hybridization and wash conditions.
  • the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mamre polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203249 (DNA64888-1542), or (b) the complement of the DNA molecule of (a).
  • the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203249 (DNA64888-1542).
  • the invention concerns an isolated nucleic acid molecule comprising (a) DNA encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID NO: 136), or the complement of the DNA of (a).

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Abstract

Les protéines membranaires et les molécules de récepteur possèdent différentes applications industrielles ; elles peuvent notamment servir d'agent pharmaceutique et d'agent diagnostique. Les immunoadhésines récepteurs, par exemple, peuvent servir d'agents thérapeutiques afin de bloquer les interactions récepteur-ligand. Les protéines membranaires peuvent également servir à cribler de potentiels inhibiteurs peptidiques ou inhibiteurs de petites molécules de l'interaction récepteur-ligand pertinente. Des recherches sont menées dans les domaines industriel et universitaire afin d'identifier de nouvelles protéines natives de récepteur ou membranaires. Nombre de ces recherches se concentrent sur le criblage des bibliothèques d'ADN recombinant de mammifère afin d'identifier les séquences de codage pour de nouvelles protéines de récepteur ou membranaires. L'invention concerne de nouveaux polypeptides et des molécules d'acide nucléique codant pour ces polypeptides. L'invention concerne également des vecteurs et des cellules hôtes contenant lesdites séquences d'acide nucléique, des molécules de polypeptides chimères contenant les polypeptides selon l'invention fusionnées à des séquences de polypeptides hétérologues, des anticorps qui se lient aux polypeptides selon l'invention ainsi que des méthodes de production de ces polypeptides.
EP99942557A 1998-09-01 1999-09-01 Nouveaux pro-polypeptides et sequences correspondantes Withdrawn EP1144629A3 (fr)

Applications Claiming Priority (221)

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PCT/US1999/020111 WO2000012708A2 (fr) 1998-09-01 1999-09-01 Nouveaux pro-polypeptides et sequences correspondantes
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US9433675B2 (en) 2012-05-23 2016-09-06 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
US9770487B2 (en) 2013-02-20 2017-09-26 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic adenocarcinoma
US10093736B2 (en) 2012-11-13 2018-10-09 Biontech Ag Agents for treatment of claudin expressing cancer diseases
US10137195B2 (en) 2013-03-18 2018-11-27 Ganymed Pharmaceuticals Gmbh Therapy involving antibodies against Claudin 18.2 for treatment of cancer

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9433675B2 (en) 2012-05-23 2016-09-06 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
US10022444B2 (en) 2012-05-23 2018-07-17 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer
US10813996B2 (en) 2012-05-23 2020-10-27 Astellas Pharma Inc. Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer
US12059464B2 (en) 2012-05-23 2024-08-13 Astellas Pharma Inc. Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer
US10093736B2 (en) 2012-11-13 2018-10-09 Biontech Ag Agents for treatment of claudin expressing cancer diseases
US9770487B2 (en) 2013-02-20 2017-09-26 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic adenocarcinoma
US10314890B2 (en) 2013-02-20 2019-06-11 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic cancer
US10946069B2 (en) 2013-02-20 2021-03-16 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic cancer
US11826402B2 (en) 2013-02-20 2023-11-28 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of metastatic pancreatic adenocarcinoma
US10137195B2 (en) 2013-03-18 2018-11-27 Ganymed Pharmaceuticals Gmbh Therapy involving antibodies against Claudin 18.2 for treatment of cancer
US11395852B2 (en) 2013-03-18 2022-07-26 Astellas Pharma Inc. Therapy involving antibodies against Claudin 18.2 for treatment of cancer

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