CN100432103C - Peptides effective in the treatment of tumors and other diseases requiring the removal or destruction of cells - Google Patents

Abstract

The present invention relates to peptides, compositions, and methods of treating conditions requiring removal or destruction of harmful or unwanted cells in a patient using proteins (and peptides derived from the amino acid sequences of such proteins), the amino acid sequence of which includes at least one amino acid sequence derived from neural thread proteins and other related molecules.

Description

Peptides effective in the treatment of tumors and other diseases requiring the removal or destruction of cells

This application claims priority to Provisional Application Serial No. 60/306,161, filed July 19, 2001, entitled "Proteins and Peptides Effective in Treating Tumors and Other Diseases Requiring Removal or Destruction of Cells," filed July 19, 2001 Priority to Provisional Patent Application Serial No. 60/306,150 entitled "Peptides Effective in the Treatment of Tumors and Other Diseases Requiring Priority of Provisional Patent Application Serial No. 60/331,477, "Peptides for Diseases that Remove or Destroy Cells", which are hereby incorporated by reference in their entirety.

field of invention

The present invention relates to methods of treating diseases requiring removal or destruction of cellular components, such as benign or malignant tumors, with proteins and peptide compounds containing amino acid sequences corresponding to, similar to, or homologous to parts of the amino acid sequence of neurofilament proteins . Such methods include, but are not limited to, intramuscular, oral, intravenous, intrathecal, intratumoral, intranasal, topical, transdermal, etc. administration of the compound, or the compound alone or coupled to a carrier.

Background of the invention

Many medical treatments and procedures involve the removal or destruction of unwanted or unwanted tissue. Examples of this important treatment include surgery to remove cancerous growths, chemotherapy to destroy metastatic tumors, and reduction of glandular (eg, prostate) hyperplasia. Other examples include removal of unwanted facial hair, warts, subcutaneous tissue, lymphatic tissue, or fatty tissue.

Effective agents are needed to disrupt to facilitate removal or inhibit further growth of harmful or unwanted cells and tissues, primarily locally acting with minimal or no systemic toxicity. Neurofilament proteins and related molecules are agents of the type described in pending U.S. Patent Application Serial No. 10/092,934, filed March 8, 2002, entitled "Methods of Treating Tumors and Related Diseases with Neurofilament Proteins" One, the content of its publication is incorporated herein by reference in its entirety. Peptides containing amino acid sequences corresponding to partial amino acid sequences of neurofilament proteins, AD7c-NTP are also such reagents. These peptides are described in co-pending U.S. Patent Application Serial No. 10/153,334, entitled "Peptides Effective in Treating Tumors and Other Diseases Requiring Removal or Destruction of Cells," filed May 24, 2002, the entire disclosure of which is published Incorporated herein by reference.

Cancer is an abnormality in the regulatory mechanisms within a cell that results in uncontrolled cell growth and reproduction. Normal cells make up tissues, and when these cells lose their ability to function as specific, controlled, and cooperative units (dedifferentiation), this defect leads to disorder in cell populations. When it does, a tumor forms.

A benign overgrowth of tissue is an abnormal condition in which cells need to be removed from the body. Benign tumors are cell proliferations that do not metastasize throughout the body but can cause disease symptoms. If such tumors are located in hard-to-reach areas of an organ, such as the brain, they can be fatal. Benign tumors are present in many organs, including lung, brain, skin, pituitary gland, thyroid, adrenal cortex and adrenal medulla, ovary, uterus, testes, connective tissue, muscle, intestine, ear, nose, throat, tonsils, mouth, Liver, gallbladder, pancreas, prostate, heart and other organs.

Surgery is usually the first step in cancer treatment. The purpose of surgery is different. Sometimes surgery is used to remove as much of the apparent tumor as possible, or at least to "debulk" it (removing the main tumor mass thereby reducing the need for other methods of treatment). Depending on the type and location of the cancer, surgery may also provide some symptom relief for the patient. For example, if most of the enlarged brain tumor is surgically removed, intracranial pressure will decrease and the patient's symptoms will improve.

Not all tumors can be removed surgically. Some tumors may be in parts of the body that prevent them from being completely removed. Examples of these tumors are tumors in the brainstem (the part of the brain that controls breathing) or tumors that grow in and around major blood vessels. In these cases, surgery is limited due to the high risks associated with tumor resection.

In some cases, the tumor mass cannot be surgically removed because it is not needed. One example is Hodgkin lymphoma, a cancer of the lymph nodes that responds well to a combination of chemotherapy and radiation therapy. In Hodgkin lymphoma, surgery is rarely needed to achieve a cure, and surgery is almost always used to confirm the diagnosis.

Chemotherapy is a common form of cancer treatment that involves the use of drugs (usually given by mouth or injection) that specifically attack rapidly dividing cells throughout the body, such as those found in tumors. This allows chemotherapy to be used in the treatment of metastatic cancer and tumors that have a high chance of spreading through the blood and lymphatic system but have not yet significantly spread beyond the primary tumor site. Chemotherapy may also be used to improve local tumor response to surgery and radiation. For example, some cancers of the head and neck.

Unfortunately, other cells in the body that normally divide rapidly, such as the lining of the stomach and hair, are also affected by chemotherapy. For this reason, many chemotherapeutic agents can cause adverse side effects such as nausea, vomiting, anemia, hair loss, or other symptoms. These side effects are temporary, and current medications can help reduce many of these side effects. As our knowledge continues to grow, scholars have designed newer chemotherapeutic agents that are better at killing cancer cells and have fewer side effects for patients.

Chemotherapy drugs can be given to patients in a variety of ways. Some are pills, and some are given intravenously or by injection into another site. For injectable chemotherapy drugs, patients have to go to a doctor's office or hospital for treatment. Other chemotherapeutic agents require continuous infusion into the bloodstream 24 hours a day. For these types of chemotherapy drugs, a minor surgery is performed to implant a small pump into the patient. Give slowly with a pump. In many cases, a permanent infusion port must be placed in the patient's vein to eliminate the need for repeated needle sticks.

Radiation therapy is another common weapon in the fight against cancer. Radiation kills cancer by damaging the DNA inside tumor cells. Radiation therapy can be delivered in different ways. The most common method involves directing radiation beams at the patient in a highly precise manner, concentrating the radiation on the tumor. To do this, the patient has to lie on the table and the light beam moves around him/her. This procedure can last for a few minutes, but can be done daily for several weeks (depending on the tumor type) to achieve the specific total prescribed radiation dose.

Another method of radiation, called brachytherapy, is sometimes used and involves the use of radioactive pellets ("radiation boxes") or wires that are implanted in the tumor area of the body. Implants can be temporary or permanent. With permanent implants, the radiation in the radiation box "decays" over days or weeks so that the patient is not radioactive. For temporary implants, the total radiation dose is usually delivered over several days, during which time the patient must be hospitalized. With both types of brachytherapy, it is generally necessary to deliver radiation precisely to the tumor area to achieve local control of the cancer (as opposed to systemic treatments such as chemotherapy).

Some highly selected patients may resort to bone marrow transplantation. This treatment is usually done because patients have significantly aggressive cancer or because their cancer has returned after conventional therapy. A bone marrow transplant is a complex procedure. There are many types and they differ in their likelihood of causing side effects and healing. Most transplants are performed at specialized medical centers, and in many cases transplants are considered research.

There are a number of other treatments, although most are still being explored in clinical trials, that have not become standard of care. Examples include immunotherapy, monoclonal antibodies, anti-angiogenic factors, and gene therapy.

Immunotherapy: A variety of techniques are designed to boost the patient's own immune system to fight cancer, unlike radiation therapy or chemotherapy. Usually for this purpose, scholars inject patients with special vaccines. Monoclonal Antibody: An antibody designed to attack cancer cells (and not normal cells), taking advantage of differences in antigenicity or/or other characteristics between cancer and non-cancer cells. Antibodies can be administered to a patient alone, or conjugated to various cytotoxic compounds or in a radioactive form so that the antibodies are preferentially targeted to cancerous cells, thereby delivering the toxic or radioactive agent to the desired cells.

Anti-angiogenic factors: As cancer cells divide rapidly and tumors grow, they may quickly outgrow their blood supply. To compensate for this, some tumors secrete substances that help induce the growth of blood vessels around them, providing cancer cells with vascularly delivered nutrients. Experimental treatments have been designed to stop blood vessels from growing into tumors.

Gene Therapy: Cancer is the product of a series of mutations that eventually lead to the development of cancer cells and their excessive proliferation. Treating cancer may involve introducing genes that control or stop cancer growth into cancer cells, turning on programmed cell (death) mechanisms of cells to destroy cancer cells, enhancing immune recognition of cells, or expressing prodrugs that can be converted into toxic metabolites or inhibiting Cytokines for tumor growth.

Benign tumors and malformations can also be treated by a variety of methods, including surgery, radiation therapy, drug therapy, heat and electrical cautery, cryotherapy, and others. Although benign tumors do not metastasize, they can grow large and recur. Surgical eradication of benign tumors usually has difficulties and surgical side effects, and some benign tumors require repeated operations, such as pituitary adenomas, meningiomas, and benign prostatic hyperplasia.

Still other disorders contain unwanted cellular components that require selective removal. For example, heart disease and stroke are generally caused by atherosclerosis, which is the proliferative damage of fibrofat and smooth muscle components, resulting in distortion of vessel walls, narrowing of vessel lumen, constriction of blood flow, susceptibility to focal thrombosis and eventually lead to obstruction and infarction. Various methods of treating atherosclerosis include: bypass grafting; artificial grafting; angioplasty with recanalization, curettage, radiation, laser, or other blockage removal; drug therapy to inhibit atherosclerosis through lipid reduction ; anticoagulant therapy; and systemic therapy with diet, exercise, and lifestyle. There remains a need for a method of removing atherosclerotic lesions without risk and side effects.

Other examples of unwanted cellular abundance that require selective removal include virus-induced growths such as warts. Another example is hypertrophic inflammatory masses and hypertrophic scars or keloids seen in inflammatory situations. Other examples are found in cosmetic procedures such as the removal of unwanted hair such as facial hair, or areas of shriveled unwanted tissue in the skin and connective tissue of the face or extremities for cosmetic purposes.

Other examples are known to those of ordinary skill in the art. In all or most of these instances, there is a need for therapeutics that remove or destroy unwanted cellular components without the risks and side effects of conventional therapies, and for more precise methods of removing unwanted cellular components.

Neurofilament proteins (NTPs) are a recently identified family of brain proteins. One of the members of this family, AD7c-NTP, is a membrane-bound phosphoprotein with 41kD function and nerve sprouting (de la Monte et al., J.Clin.Invest., 100:3093-3104 (1997); de la Monte et al., Alz.Rep ., 2:327-332 (1999); de la Monte SM and Wands JR, Journal of Alzheimer's Disease, 3:345-353 (2001)). The gene encoding AD7c-NTP and the predicted protein sequence of AD7c-NTP have been identified and reported (de la Monte et al., J. Clin. Invest., 100:3093-3104 (1997)). In addition to the 41 kD species, other classes of neurofilament proteins (about 26 kD, about 21 kD, about 17 kD, and about 15 kD) have also been identified and associated with neuroectodermal, astrocytoma, and glioblastoma as well as hypoxia, hypoxia, and Associated with damage caused by blood or cerebral infarction (Xu et al., Cancer Research, 53: 3823-3829 (1993); de la Monte et al., J. Neuropathol. Exp. Neurol., 55 (10): 1038-50 (1996) , de la Monte et al., J.Neurol.Sci., 138(1-2):26-35(1996); de la Monte et al., J.Neurol.Sci., 135(2):118-25(1996) ; de la Monte et al., J. Clin. Invest., 100:3093-3104 (1997); de la Monte et al., Alz. Rep., 2:327-332 (1999)).

Classes of neurofilament proteins have been described and claimed, see U.S. Patent Nos. 5,948,634; Methods for detecting neurological disease or dysfunction". The disclosures of these patents are expressly incorporated herein by reference in their entirety. As described therein, NTPs are upregulated and produced during cell death. Therefore, it has been reported that dead and dying neuronal cells result from overproduction of NTP, and thus its presence indicates neuronal cell death and the onset of Alzheimer's disease (AD).

Other classes of neurofilament proteins have been identified as other products of the AD7c-NTP gene (a 112 amino acid protein as described in NCBI Entrez-Protein Database Accession #XP_032307 PID g15928971) or similar to neurofilament proteins ( A 106 amino acid protein as described in NCBI Entrez-Protein Database Accession #AAH14951 PID g15928971, another 106 amino acid protein described in NCBI Entrez-Protein Database Accession #XP_039102 PID g18599339 and described in NCBI Entrez - A 61 amino acid protein with Protein Data Bank accession #AAH02534 PID g12803421).

Neurofilament proteins associated with AD and NTP are upregulated in cell death in AD. AD7c-NTP mRNA is upregulated in AD brains compared to controls; AD7c-NTP protein levels in brain and CSF are higher in AD than in controls; AD7c-NTP immunoreactivity is found in senile plaques, Neurofibrillary tangles (NFT), degenerated neurons, neuropil threads, and dystrophic neurite outgrowth (Ozturk et al., Proc. Natl. Acad. Sci. USA, 86:419-423 (1989); de la Monte et al., J.Clin.Invest., 86(3):1004-13(1990); de la Monte et al., J.Neurol.Sci., 113(2):152-64(1992); de la Monte etc., Ann.Neurol., 32(6):733-42(1992); de la Monte et al., J.Neuropathol.Exp.Neurol., 55(10):1038-50(1996), de la Monte et al., J.Neurol.Sci., 138(1-2):26-35(1996); de la Monte et al., J.Neurol.Sci., 135(2):118-25(1996); de la Monte et al., J. Clin. Invest., 100:3093-3104 (1997); de la Monte et al., Alz. Rep., 2:327-332 (1999)). NTP localizes intracellularly, in the fine processing of the neuropil, or extracellularly in AD and Down syndrome brains. de la Monte et al., Ann. Neurol., 32(6):733-42 (1992).

All find AD7c-NTP protein level to increase in AD patient's CSF and urine (de la Monte and Wands, Front Biosci 7:989-96 (2002); de la Monte and Wands, Journal of Alzheimer's Disease, 3:345 -353 (2001); Munzar et al., Alzheimer's Reports 4:61-65 (2001); Kahle et al., Neurology 54:1498-1504 (2000); Munzar et al., Alzheimer's Reports 3:155-159 (2000); de la Monte et al., Alzheimer's Reports 2:327-332 (1999); and de la Monte et al., J Clin Invest 100:3093-3104 (1997).

NTP overexpression has also been linked to the cell death process in Alzheimer's disease (de la Monte and Wands, J. Neuropathol Exp. Neurol., 60:195-207 (2001); de la Monte and Wands, CellMol Life Sci 58:844-49 (2001). AD7c-NTP was also identified in Down syndrome brain tissue (Wands et al., International Patent Publication No. WO 90/06993; de la Monte et al., J Neurol Sci 135:118-25 (1996); de la Monte et al., Alz.Rep., 2:327-332 (1999)).There is some evidence that overexpression of NTP may also be associated with normal tension glaucoma (Golubnitschaja-Labudova et al., Curr Eye Res 21:867 -76(2000)).

NTP has been shown to be active in glioma and neuroblastoma cell cultures in vitro, in normal rodent muscle tissue, subcutaneous connective tissue, and dermis in vivo, and in a variety of tumors of different human and nonhuman origins (including breast cancer, An effective agent that induces dead cell death in skin cancer and papilloma, colon cancer, glioma and other tumors in rodent models). See pending US Patent Application Serial No. 10/092,934, filed March 8, 2002; entitled "Methods of Treating Tumors and Related Diseases Using Neurofilament Proteins."

Included in this description is the description of the relevant art above, and any and all publications described herein, including any and all US patents, are hereby incorporated by reference in their entirety. The above description of the related art is not in any way an admission that any of the documents described herein, including pending US patent applications, are prior art to the present invention.

* * * * *

There remains a need in the art for new, less toxic methods of treating unwanted cellular components. The present invention fulfills these needs.

Summary of the invention

(局部序列比对基本检索工具)找到这些蛋白质。参见Altschul，Stephen F.，Thomas L.Madden，Alejandro A.

Jinghui Zhang，ZhengZhang，Webb Miller和David J.Lipman(1997)，“缺口BLAST和PSI-BLAST：新一代蛋白质数据库检索程序(Gapped BLAST and PSI-BLAST：a new generation of proteindatabase search programs)”，Nucleic Acids Res.25：3389-3402。Part of the present invention includes the discovery by the inventors that the peptide sequences contained in AD7c-NTP, and variants or homologues thereof, including those found in other proteins of organisms such as humans and other mammals, are effective in destroying or removing harmful cells or Effective preparation of unwanted cells,. Once such a peptide sequence has been discovered, one of ordinary skill in the art can do so by utilizing widely available public or commercial protein databases, such as the National Center Biotechnology Information's Protein database, and search programs such as

(local sequence alignment basic search tool) to find these proteins. See Altschul, Stephen F., Thomas L. Madden, Alejandro A.

Jinghui Zhang, ZhengZhang, Webb Miller and David J. Lipman (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs (Gapped BLAST and PSI-BLAST: a new generation of protein database search programs)", Nucleic Acids Res. 25: 3389-3402.

One of ordinary skill in the art can then screen these proteins using the assays described herein to determine their efficacy as agents to destroy or remove unwanted or harmful cells. Upon discovery of one or more such effective agents, one of ordinary skill in the art can then determine those agents comprising the compounds described herein or in the patent application entitled "Effective Treatment of Tumors and Others Needing to Remove or Peptides for diseases that destroy cells" are homologous or similar to the AD7c-NTP peptide sequences described in co-pending U.S. Patent Application Serial No. 10/153,334, these preparations can be synthesized by methods known to those skilled in the art, and the synthesized The effectiveness of an agent as an agent that destroys or removes unwanted or harmful cells. In addition, one of ordinary skill in the art can also discover the amino acid sequence of such proteins to determine the same as described herein and in the article entitled "Effective Treatment of Tumors and Other Diseases Requiring Removal or Destruction of Cells" and filed on May 24, 2002. The peptide sequence of AD7c-NTP described in US Patent Application Serial No. 10/153,334 is not similar or not homologous, and homologous or similar to other peptide sequences. These newly synthesized sequences can then be tested for their efficacy as agents to destroy or remove unwanted or harmful cells.

The present invention relates to peptides, compositions and methods for treating unwanted cell proliferation, such as benign or malignant tumors, glandular (eg, prostate) hyperplasia, unwanted facial hair, warts, and unwanted adipose tissue. This method involves administering to a mammal in need thereof a therapeutically effective amount of a related protein, a related peptide known to be an effective agent capable of causing cell death, or an NTP peptide. "Related protein", "related peptide" and "NTP peptide" are defined as follows.

The peptide of the present invention has at least one amino acid sequence corresponding to a part of the amino acid sequence of neurofilament protein. The composition of the present invention includes this peptide and a pharmaceutically acceptable carrier. The peptides or proteins of the invention ("cell death peptides") can be administered alone or conjugated to a carrier or antibody. Administration of the cell death peptide can be by intramuscular, oral, intravenous, intraperitoneal, intracerebral (intraparenchymal), intracerebroventricular, intratumoral, intralesional, intradermal, intrathecal, intranasal, intraocular, intraarterial, topical , transdermally, by aerosol, infusion, bolus injection, implant device, sustained release system, etc., either alone or in combination with a carrier. In addition, the cell death peptide can be expressed in vivo by administering a gene expressing the peptide, by administering a vaccine capable of inducing expression of the peptide in vivo in cells, bacteria or viruses into which the gene has been introduced, or by causing genetic modification, etc. to produce the peptide.

In addition, the cell death peptides can be used in conjunction with other therapies to treat benign or malignant tumors and other unwanted or deleterious cell growth. The foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the claims of the invention. From the detailed description of the present invention, those skilled in the art can easily understand other objects, advantages and novel features of the present invention.

Brief description of the drawings

Figure 1: Shows the complete amino acid sequence and nucleotide sequence of the AD7c-NTP gene and the AD7c-NTP protein product of the gene (sequences 120 and 121 obtained from U.S. Patent Nos. 5,830,670, 5,948,634 and 5,948,888; de la Monte et al., J.Clin. Invest., 100:3093-3104 (1997); NCBI Entrez-Protein Bank accession number #AAC08737; PID g3002527) [SEQ ID NO.1].

Figure 2: Shows the complete amino acid sequence of the 122 amino acid neurofilament protein (Sequence 40 obtained from US Patent Nos. 5,830,670, 5,948,634, and 5,948,888; NCBI Entrez-Protein Database Accession #AAE25447 PID g10048540) [SEQ ID NO.2] (“NTP-122”).

Figure 3: Shows the complete amino acid sequence of the 112 amino acid neurofilament protein (NCBI Entrez-Protein Database Accession #XP_032307 PID g15928971) [SEQ ID NO.3] ("NTP-112").

Figure 4: Shows the complete amino acid sequence of the 106 amino acid neurofilament-like protein (NCBIEntrez-Protein Database Accession #AAH14951 PID g15928971) [SEQ ID NO. 4] ("NTP-106A").

Figure 5: Shows the complete amino acid sequence of the 106 amino acid neurofilament-like protein (NCBIEntrez-Protein Database Accession #XP_039102 PID g18599339) [SEQ ID NO.5] ("NTP-106B").

Figure 6: Shows the complete amino acid sequence of the 98 amino acid neurofilament protein (Sequence 30 obtained from US Patent Nos. 5,830,670, 5,948,634, and 5,948,888; NCBI Entrez-Protein Database Accession #AAE25445, PID g10048538) [SEQ ID NO.6 ]("NTP-98").

Figure 7: Shows the complete amino acid sequence of the 75 amino acid neurofilament protein (Sequence 48 obtained from US Patent Nos. 5,830,670, 5,948,634, and 5,948,888; NCBI Entrez-Protein Database Accession #AAE25448, PID g10048541) [SEQ ID NO.7 ]("NTP-75").

Figure 8: Shows the complete amino acid sequence of the 68 amino acid neurofilament protein (Sequence 36 obtained from US Patent Nos. 5,830,670, 5,948,634, and 5,948,888; NCBI Entrez-Protein Database Accession #AAE25446, PID g10048539) [SEQ ID NO.8 ]("NTP-66").

Figure 9: Shows the complete amino acid sequence of the 61 amino acid neurofilament-like protein (NCBI Entrez-Protein Database Accession #AAH02534, PID g12803421) [SEQ ID NO.9] ("NTP-61").

Detailed Description of the Preferred Embodiment

Unless otherwise stated, terms and phrases used herein are defined as follows.

The term "AD7c-NTP" refers to an approximately 41 kD protein and gene and nucleic acid sequence encoding it, described by de la Monte et al., J. Clin. Invest., 100:3093-104 (1997), U.S. Pat. Nos. 5,948,634; 5,948,888 and 5,830,670 Sequences 120 and 121 of and GenBank #AF010144, the nucleic acid and amino acid sequences of which are shown in FIG. 1 . The term "AD7c-NTP" also includes biologically active fragments, variants, derivatives, homologues and mimetics of AD7c-NTP.

The term "NTP" or "neurofilament protein" refers to neurofilament proteins and related molecules (including pancreatic filaments) and nucleic acid sequences encoding these proteins, and includes, but is not limited to, the following proteins and amino acid sequences encoding these proteins Nucleic acid sequence:

(a) AD7c-NTP;

(b) Neurofilament proteins of the ˜42, ˜26, ˜21, ˜17, ˜14, and ˜8 kD species described in U.S. Pat. Nos. 5,948,634; .Neurol., 55(10):1038-50(1996), de la Monte et al., J.Neurol.Sci., 138(1-2):26-35(1996); de la Monte et al., J.Neurol.Sci., 138(1-2):26-35(1996); .Sci., 135(2):118-25(1996); de la Monte et al., J.Clin.Invest., 100:3093-3104(1997); de la Monte et al., Alz.Rep., 2:327 -332(1999);

(c) The protein specifically recognized by mAb #2 is deposited with the American Type Culture Collection, Manassas, Va., accession number HB-12546, or the protein specifically recognized by mAb #5 is deposited with the American Type Culture Collection Institute, Manassas, Va., accession number HB-12545;

(d) a protein encoded by the AD7c-NTP gene;

(e) 122 amino acid neurofilament protein, described in sequence 40 of U.S. Patent Nos. 5,830,670, 5,948,634 and 5,948,888, and listed in NCBI Entrez-Protein Accession #AAE25447, PID g10048540, the amino acid sequence of which is shown in Figure 2 ( "NTP-122");

(f) 122 amino acid neurofilament protein listed in NCBI Entrez-Protein Accession #XP_032307, PID g14725132, the amino acid sequence of which is shown in Figure 3 ("NTP-112");

(g) the 106 amino acid neurofilament protein listed in NCBI Entrez-Protein Accession No. #AAH14951 PID g15928971, the amino acid sequence of which is shown in Figure 4 ("NTP-106A");

(h) 106 amino acid neurofilament protein listed in NCBI Entrez-Protein Accession #XP_039102 PID g18599399, the amino acid sequence of which is shown in Figure 5 ("NTP-106B");

(i) 98 amino acid neurofilament protein, described in sequence 30 of US Patent Nos. 5,830,670, 5,948,634 and 5,948,88 and listed in NCBI Entrez-Protein Accession #AAE25445, PIDg10048538, the amino acid sequence of which is shown in Figure 6 ("NTP-98");

(j) 75 amino acid neurofilament protein described in sequence 48 of US Patent Nos. 5,830,670, 5,948,634 and 5,948,888 and listed in NCBI Entrez-Protein Accession #AAE25448, PIDg10048541, the amino acid sequence of which is shown in Figure 7 (“ NTP-75');

(k) 68 amino acid neurofilament protein described in sequence 36 of U.S. Patent Nos. 5,830,670, 5,948,634 and 5,948,888 and listed in NCBI Entrez-Protein Accession #AAE25446, PIDg10048539, the amino acid sequence of which is shown in Figure 8 (“ NTP-68');

(l) the 61 amino acid neurolike protein listed in NCBI Entrez-Protein Accession No. #AAH02534, PID g12803421, the amino acid sequence of which is shown in Figure 9 ("NTP-61");

(m) pancreatic filament protein;

(n) neuropancreatic filament protein (nPTP) described in U.S. Patent No. 6,071,705;

(o) Proteins specifically recognized by antibodies produced by hybridomas HB 9934, HB 9935, and HB 9936 deposited with the American Type Culture Collection.

The peptides referred to by the term "NTP peptide" include amino acid sequences corresponding to at least a portion of the amino acid sequence of NTP or NTP fragments, and unless otherwise stated, also include homologues, derivatives, variants, fusion proteins and peptidomimetics of these peptides things. The term "NTP peptide" also includes, but is not limited to, the peptides specifically listed in US Patent Application Serial No. 10/092,934 and 10/153334. The term "NTP peptide" preferably includes, but is not limited to, the following amino acid sequences of NTP:

a) NTP peptide #1 [SEQ ID NO.10], AD7c-NTP p239-243

SSWDY

Ser-Ser-Trp-Asp-Tyr

b) NTP peptide #2 [SEQ ID NO.11], AD7c-NTP p31-39

PASASPVAG

Pro-Ala-Ser-Ala-Ser-Pro-Val-Ala-Gly

c) NTP peptide #3 [SEQ ID NO.12], AD7c-NTP p14-24

GAISA HRN LRL

Gly-Ala-Ile-Ser-Ala-His-Arg-Asn-Leu-Arg-Leu

d) NTP peptide #4 [SEQ ID NO.13], AD7c-NTP p53-58

FFLVEM

Phe-Phe-Leu-Val-Glu-Met

e) NTP peptide #5 [SEQ ID NO.14], AD7c-NTP p208-216

SVTQAGVQW

Ser-Val-Thr-Gln-Ala-Gly-Val-Gln-Trp

f) NTP peptide #6 [SEQ ID NO.15], NTP-122p106-122

IDQQVLSRIKLEIKRCL

Ile-Asp-Gln-Gln-Val-Leu-Ser-Arg-Ile-Lys-Leu-Glu-Ile-Lys-Arg-Cys-Leu

g) NTP peptide #7 [SEQ ID NO.16], NTP-122p111-119

LSRIKLEIK

Leu-Ser-Arg-Ile-Lys-Leu-Glu-Ile-Lys

Homologues, derivatives, variants, fragments, fusion proteins and peptidomimetics of these specifically listed NTP peptides are also included.

The term "related protein" refers to a protein that contains one or more amino acid sequences that are identical, very similar or homologous to one or more NTP peptides.

The expression "related peptide" refers to a peptide consisting of an amino acid sequence corresponding to at least a part of the amino acid sequence of said related protein, and includes homologues, variants, fusion proteins, anti-D peptides and peptidomimetics of such peptides . The expression "related peptide" also preferably includes (but is not limited to) the following amino acid sequences of said related protein:

(a) Related peptide #1 [SEQ ID NO.17], transient receptor potential channel 6, delta variant (NCBI accession number CAC01686, PID g9716913), p356-377

GDHGRPNLSRLKLAIKYEVKKM

Gly-Asp-His-Gly-Arg-Pro-Asn-Leu-Ser-Arg-Leu-Lys-Leu-Ala-Ile-Lys-Tyr-Glu-Val-Lys-Lys-Met

(b) Related peptide #2 [SEQ ID NO.18], putative calcium channel (NCBI Accession No. NP_065122, PIDg9966865), p345-360

QQSIAVKFLAVFGVSI

Gln-Gln-Ser-Ile-Ala-Val-Lys-Phe-Leu-Ala-Val-Phe-Gly-Val-Ser-Ile

(c) Related peptide #3 [SEQ ID NO.19], trp-related protein 4 truncated gamma variant (NCBI accession number AF063825_1, PID g6665596), p337-357

GLLFPVFSVCYLIAPKSPLGL

Gly-Leu-Leu-Phe-Pro-Val-Phe-Ser-Val-Cys-Tyr-Leu-Ile-Ala-Pro-Lys-Ser-Pro-Leu-Gly-Leu

Homologues, derivatives, variants, fragments, fusion proteins and peptidomimetics of these specifically listed related peptides are also included.

The expression "cell death peptide" refers to related proteins or related peptides which have been shown to be effective agents in causing cell death.

The term "fragment" refers to a protein or polypeptide consisting of a contiguous subsequence of the amino acid sequence of an NTP protein, NTP peptide, related protein or related peptide, including naturally occurring fragments such as splice variants and fragments naturally occurring in vivo due to proteolytic activity . Such fragments may be truncated at the amino-terminus, carboxy-terminus, and/or in the middle (eg, by natural splicing). Such fragments can be prepared with or without an amino-terminal methionine. The term "fragment" includes fragments of the same NTP protein or NTP peptide, or related proteins or peptides, which may be the same or different, share or have no contiguous amino acid sequence, joined together directly or via a linker.

The term "variant" refers to a protein or polypeptide in which one or more amino acid substitutions, deletions and/or insertions exist compared to the amino acid sequence of an NTP protein, NTP peptide, related protein or related peptide, including naturally occurring NTP proteins, Allelic variants or alternative splice variants of NTP peptides, related proteins or related peptides. The term "variant" includes the substitution of one or more amino acids in a peptide sequence with similar or homologous or dissimilar amino acids. Amino acids can be grouped on many levels into similar or homologous amino acids (Gunnar von Heijne, Sequence Analysis in Molecular Biology, pp. 123-39 Academic Press, New York, NY 1987.) Preferred variants The variants include alanine substitutions at one or more amino acid positions. Other preferred substitutions include conservative substitutions that have little or no effect on the overall net charge, polarity or hydrophobicity of the protein. Conservative substitutions are listed in Table 2 below.

Table 2

conservative amino acid substitutions

Alkaline: Arginine

Lysine

Histidine

Acidity: Glutamic acid

Aspartic Acid

Uncharged polarity: Glutamine

Asparagine

Serine

Threonine

Tyrosine

Non-polar: Phenylalanine

Tryptophan

Cysteine

Glycine

Alanine

Valine

Proline

          Methionine

Leucine

Isoleucine

Table 3 lists another scheme of amino acid substitution:

table 3

original residue substitution

Alanine Glycine; Serine

Arginine Lysine

Asparagine Glutamine; Histidine

Aspartic Acid Glutamic Acid

cysteine serine

glutamine asparagine

glutamic acid aspartic acid

Glycine Alanine; Proline

Histidine Asparagine; Glutamine

Isoleucine Leucine; Valine

Leucine Isoleucine; Valine

Lysine Arginine; Glutamine; Glutamic Acid

Methionine Leucine; Tyrosine; Isoleucine

Phenylalanine Methionine; Leucine; Tyrosine

Serine Threonine

Threonine Serine

Tryptophan Tyrosine

Tyrosine Tryptophan; Phenylalanine

Valine Isoleucine; Leucine

Other variants may consist of less conservative amino acid substitutions, such as residues selected that differ more significantly in their contribution to maintaining (a) the structure of the polypeptide backbone, such as sheet or helical configuration, in the region of the substitution, (b) Charge or hydrophobicity of the target site molecule, (c) side chain size. Substitutions expected to generally have a more pronounced effect on function are (a) substitution or deletion or insertion of glycine and/or proline by another amino acid; (b) substitution of a hydrophilic residue such as seryl or threonyl ( or by) a hydrophobic residue such as leucyl, isoleucyl, phenylalanyl, valyl or alanyl; (c) a cysteine residue substituted for (or by) any other residue; (d) a residue with a positive charge such as lysyl, arginyl, or histidyl is substituted for (or replaced by) a residue with a negative charge such as glutamyl or aspartyl; or (e) a residue with a large Residues with side chains such as phenylalanine are substituted for (or are replaced by) residues without such side chains such as glycine. Other variants include residues designed to create new glycosylation and/or phosphorylation sites, or designed to delete existing glycosylation and/or phosphorylation sites. Variants include at least one amino acid substitution at a glycosylation site, a proteolytic cleavage site, and/or a cysteine residue. Variants also include NTP proteins, NTP peptides, related proteins or related peptides having other amino acid residues before or after the NTP protein, NTP peptide, related protein or related peptide amino acid sequence on the linker peptide. For example, cysteine residues can be added to the amino and carboxyl termini of the related peptides to cyclize the related peptides by forming disulfide bonds. The term "variant" also includes polypeptides having the amino acid sequence of a related protein or related peptide flanked by at least 1 and up to 25 or more additional amino acids at the 3' or 5' end of the related protein or related peptide .

The term "derivative" refers to chemically modified proteins or polypeptides which have been chemically modified by natural processes such as processing and other post-translational modifications, and which may also be chemically modified by the addition of one or more molecules of polyethylene glycol, sugars, phosphates And/or other such molecules, wherein such molecules are not molecules that naturally bind to wild-type NTP proteins or peptides. Derivatives include salts. Such chemical modifications are described in basic texts and more detailed monographs as well as in the extensive research literature and are well known to those skilled in the art. It will be appreciated that the same type of modification may be present at some positions in a given protein or polypeptide to the same or to varying degrees. Likewise, a given protein or polypeptide may contain many types of modifications. These modifications can occur anywhere in the protein or polypeptide, including the peptide backbone, amino acid side chains, and amino or carboxyl termini. These modifications include, for example, acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavins, covalent attachment of heme moieties, covalent attachment of nucleotides or nucleotide derivatives, lipid Or covalent binding of lipid derivatives, covalent binding of phosphatidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyrogens Amino acid, formylation, γ-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, epinylation Racemization, glycosylation, lipid binding, sulfation, γ-carboxylation of glutamic acid residues, hydroxylation and ADP-ribosylation, selenoylation, transfer RNA-mediated incorporation of amino acids into proteins , such as arginylation and ubiquitination. See, e.g., Proteins-Structure And Molecular Properties, 2nd ed., T.E. Creighton, W.H. Freeman and Company, New York (1993) and Wold, F., "Post-translational protein modifications: perspectives and perspectives "(Posttranslational Protein Modifcation: Perspective and Prospects), "Posttranslational Convalent Modification of Proteins", pp. 1-12, edited by B.C. Johnson, Academic Press, New York (1983); Seifter et al., Meth. Enzymol. 182: 626-646 (1990) and Rattan et al., "Protein Synthesis: Posttranslational Modifcation and Aging," Ann. N. Y. Acad. Sci. 663: 48-62 (1992). The term "derivative" includes chemical modifications that result in a protein or polypeptide becoming branched or circular with or without branching. Circular, branched and branched circular proteins or polypeptides may result from post-translational natural processes and may also be produced entirely synthetically.

The term "homologue" refers to a protein that is at least 60% identical to the amino acid sequence of an NTP protein, NTP peptide, related protein or related peptide as determined by standard methods commonly used to compare the similarity of amino acid positions of two polypeptides. The degree of similarity or identity between two proteins can be calculated using known methods, including but not limited to those described in: Computational Molecular Biology, ed. Lesk, A.M., Oxford University Press , New York, 1988; "Biocomputing: Informatics and Genome Projects", edited by Smith, D.W., Academic Press, New York, 1993; "Computer Analysis of Sequence Data" (Computer Analysis of Sequence Data) , Part I, Griffin, A.M. and Griffin, H.G. eds., Humana Press, New Jersey, 1994); Sequence analysis in Molecular Biology, von Heinje, G., Academic Press, New York, 1987) ; Sequence analysis Primery, edited by Gribskov, M. and Devereux, J., M Stockton Press, New York, 1991; Carillo H. and Lipman, D., SIAM, J. Applied Math., 48: 1073 (1988). Preferred methods of determining identity are designed to give the largest match between the sequences tested. Methods for determining identity and similarity are codified in publicly available computer programs.

Preferred computer program methods for determining identity and similarity between two sequences include, but are not limited to, the GCG package (Devereux, J. et al., Nucleic Acids Research, 12(1):387 (1984)), BLASTP, BLASTN and FASTA, Atschul, S.F. et al., J. Molec. Biol., 215:403-410 (1990). The BLASTX program is publicly available from NCBI and other sources (BLAST Handbook, Altschul, S. et al., NCBI NLM NIH Bethesda, Md. 20894; Altschul, S. et al., J. Mol. Biol., 215:403-410 (1990). For example, computer algorithms such as GAP (Genetics Computer Group, University of Wisconsin, Madison, Wis.) are used to align and compare the sequence identity percentages of two proteins or polypeptides to be determined to best match their respective amino acids ("matching range ” determined by an algorithm).

Gap opening penalty (gap opening penalty) (calculated as 3x times the average diagonal; "average diagonal" is the diagonal average of the comparison matrix used; "diagonal" is given to each preferred amino acid by the specific comparison matrix score or value) and a gap extension penalty (usually 1/10 times the gap opening penalty) and a comparison matrix such as PAM250 or BLOSUM 62 can be used in conjunction with this algorithm. This algorithm can also use standard comparison matrices (PAM250 comparison matrix see Dayhoff et al., "Protein Sequence and Structure Atlas" (Atlas of Protein Sequence and Structure), Vol. 5, Supplement 3 [1978]; BLOSUM62 comparison matrix see Henikoff et al. USA, 89:10915-10919 [1992]). The algorithm is then used to calculate percent identity. A homologue typically has one or more amino acid substitutions, deletions and/or insertions compared to the NTP protein, NTP peptide, related protein or related peptide.

The term "peptidomimetic" or "mimetic" refers to biologically active compounds that mimic the biological activity of a peptide or protein but are no longer chemically peptides, i.e. they no longer contain any peptide bonds (i.e. amide bonds between amino acids) . The term peptidomimetics is used herein in a broader sense to include molecules that are no longer fully peptides in nature such as pseudopeptides, hemipeptides and peptoids. Examples of peptidomimetics in this broad sense (in which a portion of a peptide is replaced by a structure lacking a peptide bond) are described below. Whether wholly or partially non-peptidic, the peptidomimetics of the present invention provide a spatial arrangement of reactive chemical constituents by which the peptidomimetic closely resembles the three-dimensional nature of active groups in NTP peptide-related proteins or related peptides. arrangement. Due to this similar active site geometry, the effect of the peptidomimetic on biological systems is similar to the biological activity of NTP peptides, related proteins or related peptides.

Peptidomimetics of the invention are preferably substantially similar in three-dimensional shape and biological activity to the NTP peptides, related proteins or related peptides described herein. Examples of methods known in the art for structurally modifying peptides to produce peptidomimetics include inversion of backbone chiral centers to create D-amino acid residue structures, particularly at the N-terminus, for increased stability to protease degradation and Activity was not adversely affected. An example is described in the paper "Triatic D-alanine ¹ -peptide T binding", Smith CS et al., Drug Development Res., 15, pp. 371-379 (1988). The second approach is to alter the cyclic structures required for stability, such as N to C interchain imides and lactams (Ede et al., eds. Smith and Rivier, Peptides: Chemistry and Biology). and Biology), Escom, Leiden, 1991, pp. 268-270). See, for example, conformationally constrained thymopentin-like compounds as disclosed in US Patent No. 4,457,489 (1985), Goldstein, G. et al., the contents of which are incorporated herein by reference in their entirety. A third approach is to replace peptide bonds in related proteins or related peptides with pseudopeptide bonds that are resistant to proteolysis.

It has been reported that some pseudo-peptide bonds generally do not affect the structure and biological activity of the peptide. An example of this approach is the substitution of retro-inverso pseudopeptide bonds ("Biologically active retroinverso analogue of thymopentin") (Biologically active retroinverso analogue of thymopentin), Sisto A et al., Rivier, J.E. and Marshall, G.R. eds. , "Peptides, Chemistry, Structure and Biology" (Peptides, Chemistry, Structure and Biology), Escom, Leiden, 1990, pp. 722-773) and Dalpozzo et al. (1993), Int. J. Peptide Protein Res., 41: 561-566, incorporated herein by reference). Depending on this modification, the amino acid sequence of the peptide may be identical to that of the NTP peptides, related proteins or related peptides described above, except that one or more peptide bonds are replaced by retro-inverted pseudo-peptide bonds. Preferably most of the N-terminal peptide bonds are substituted, since such substitutions will render the N-terminus proteolytically resistant to exopeptidases. Other chemical groups of similar structure can also be used to replace the chemical groups of amino acids for modification. Another suitable pseudopeptide bond known to increase stability against enzymatic cleavage with little or no loss of biological activity is the reduced isostere (isostere) pseudopeptide bond (Couder et al. (1993), Int. J . Peptide Protein Res., 41:181-184, fully incorporated herein by reference).

Thus, the amino acid sequences of these peptides may be identical to the sequences of NTP peptides, related proteins, or related peptides, except that one or more peptide bonds are replaced by isostere pseudo-peptide bonds. The term "amino acid sequence" as used herein preferably refers to a sequence of at least 2 amino acids, preferably at least 4, more preferably at least 5. Preferably a majority of the N-terminal peptide bonds are substituted, as such substitutions render the N-terminus proteolytically resistant to exopeptidases. Synthesis of peptides with one or more reduced isosteric pseudopeptide bonds is known in the art (Couder et al., cited above). Another example involves the introduction of ketomethylene or methylsulfide bonds in place of peptide bonds.

Peptidomimetic derivatives of NTP peptides, related proteins, or related peptides represent another class of peptidomimetics that retain important structural determinants of biological activity but remove the peptide bond, thereby conferring resistance to proteolysis (Simon et al. , 1992, Proc. Natl. Acad. Sci. USA, 89:9367-9371, fully incorporated herein by reference). Peptoids are oligomers of N-substituted glycines. A number of N-alkyl groups have been reported, each corresponding to the side chain of a natural amino acid (Simon et al., 1992, cited above). Some or all of the amino acids of an NTP peptide, related protein, or related peptide may be substituted with an N-substituted glycine corresponding to the amino acid being substituted.

The term "peptide mimetic" or "mimetic" also includes trans-D peptide and enantiomers as defined below.

The term "inverse-D peptide" refers to a biologically active protein or peptide consisting of D-amino acids arranged in reverse order compared to the L-amino acid sequence of an NTP peptide, related protein or related peptide. Thus, the carboxy-terminal residue of the L-amino acid NTP peptide, related protein or related peptide becomes the amino-terminal of the D-amino acid peptide. For example, NTP _peptide , SSWDY becomes TdDdWdSdSd, where _{Dd , Sd , Wd and Yd} are D-amino acids corresponding to L-amino acids D, S, W _and Y, respectively.

The term "enantiomer" refers to a biologically active protein or peptide in which one or more L-amino acid residues in the amino acid sequence of an NTP peptide, related protein or related peptide are replaced by the corresponding D-amino acid residues.

Amino acids and amino acid residues described herein may be referred to by reference to the publicly accepted one-letter or three-letter codes provided in the table below.

Table 1

Amino Acids One-letter Three-letter

Alanine A Ala

Arginine R R Arg

Asparagine N Asn

Aspartic Acid D Asp

Cysteine C Cys

Glutamine Q Gln

Glutamic Acid E Glu

Glycine G Gly

Histidine H H His

Isoleucine I Ile

Leucine L L Leu

Lysine K Lys

Methionine M M Met

Phenylalanine F Phe

Proline P Pro

Serine S Ser

Threonine T T Thr

Tryptophan W Trp

Tyrosine Y Tyr

Valine V V Val

The present invention relates to a composition comprising a cell death peptide as defined above in the present invention. Preferred cell death peptides are similar or homologous to NTP peptides. However, the use of cell death peptides based on parts or fragments of related proteins is also within the scope of the invention. For example, the AD7c-NTP peptide sequence and similar variants and homologues are also found in a number of human and non-human proteins ("related proteins"). In particular, the AD7c-NTP gene contains Alu-type sequences that are very similar to those also found in other genes in human and other primate genomes.

Thus, it is understood that some, if not all, related proteins will also prove to be effective agents in causing cell death, since they contain peptide sequences homologous or very similar to the AD7c-NTP peptide ("related peptides"). Likewise, one of ordinary skill in the art can synthesize specific related peptides based on the amino acid sequence of any protein of interest that are potent agents of cell death and test their efficacy as agents of cell death.

Other peptide sequences derived from related proteins that have been found to be potent agents of cell death are also potent agents of cell death. One of ordinary skill in the art can, without undue experimentation, synthesize fragments of effectively related proteins spanning the entire amino acid sequence of the protein in order to identify other useful peptide sequences.

Some related proteins include the following proteins known to contain amino acids that are identical, very similar, or homologous to the NTP peptide sequence.

protein sequence amino acid sequence of protein

Identification No. No.

(PID)

g10121865 20 MEVSPLQPVNENMQVN KIKKNEDAKKRLSVER IYQKKTQLEHILLRPD

        TYIGSVELVTQQMWVY DEDVGINYREVTFVPG LYKIFDEILVNAADNK

QRDPKMSCIRVTIDPE NNLISIWNNGKGIPVV EHKVEKMYVPALIFGQ

LLTSSNYDDDEKKVTG GRNGYGAKLCNIFSTK FTVETASREYKKMFKQ

TWMDNMGRAGEMELKP FNGEDYTCITFQPDLS KFKMQSLDKDIVALMV

RRAYDIAGSTKDVKVF LNGNKLPVKGFRSYVD MYLKDKLDETGNSLKV

IHEQVNHRWEVCLTMS EKGFQQISFVNSIATS KGGRHVDYVADQIVTK

LVDVVKKKNKGGVAVK AHQRELCNGAILAHCN LRLMGSSSPASASRV

AGIAGGCHHTQLIFVF LVETGFHHVGQAGLER LTSGDPASASQSSGI

TDVKVKNHWMIFVNAL IENPTFDSQTKENMTL QPKSFGSTCQLSEKFI

              KAAIGCGIVESILNWV KFKAQVQLNKKCSAVK HNRIKGIPKLDANDA

GGRNSTECTLILTEGD SAKTLAVSGLGVVGRD KYGVFPLRGKILNVRE

ASHKQ

g10257409 21 MTGDKGPQRLSGSSYG SISSPTSPTSPGPQQA PPRETYLSEKIPIPDT

KPGTFSLRKLWAFTGP GFLMSIAFLDPGNIES DLQAGAVAGFKLLWVL

LWATVLGLLCQRLAAR LGVVTGKDLGEVCHLY YPKSESRSVAQSGVQW

CDVSSLQPLPPRCPAP SSG

g10433567 22 MMLSVQENVHRCICKH YAPPTAPPHLFFETESH SVTQAGVQWCDLGSLQ

PSPPGFKQFSCLSLSR SWDYRRVPLCLANFIV FLVETGFCRVGQAGLK

        LLTSSDLPASACQSAG DYRHEPLRLALTLCHF ISRTCTSVDFYICRDL

ERIPHGH

g10434441 23 MISAHRNLHLPGSSNS PASAFLSSWDYRHVPP CPANVVFLVEMGFLHV

GQAGLELPTSDDPPTL ASQSAGITGVSHRTWQ EFASLTVSQAVLRMLV

WGPQFENHCSKLLMAS EGDSSLVFFLYPLSNL N

g10436387 24 MQGSHSAVQAGVWWCH HDSLQPWPPGLRRSSC LSLQSLWDYRSLALSL

RLACNGTTSAHCDLCL LSSSSPASASQVAGI TGEKTAEPHKAHAAQG

            ERHLSSHMSPDENMTE KFCPGPRASFHLRILA ASRHLVKRLLNEYTVT

VLRDKSYLRNN

g10437485 25 MKNYYYFLGQGLTLSP RLECSSTISAHCNLHL LGSSNSPVAASSPVAGT

TGTCHHDWLIFVFLVE TGFHHIGQTGLEFLTS GDPPTLASKSAGITGV

SHCAWPTFLLNDMRHS FNKNLVIIFYVPAIS

g10441986 26 MRRELLAGILLRITFN FFLFFFLPFPLVVFFI YFYFYFFLEMESHYVA

QAGLELLGSSNPPASA SLVAGTLSVHHCACFE SFTKRKKKLKKAFRFI

QCLLLGLLKVRPLQHQ GVNSCDCERGYFQGIF MQAAPWEGT

g10945428 27 MSKTLKKKKHWLSKVQ ECAVSWAGPPGDFGAE IRGGAERGEFPYLGRL

REEPGGGTCCIVSGKA PNPSDVLLEVNGTPVS GLTNRDTLAVIRHFRE

            PIRLKTVKPGKVINKD LRHYLSLQFQKGSIDH KLQQVIRDNLYLRTIP

CTTRAPRDGEVPGVDY NFISVEQFKALEESGA LLESGTYDGNFYGTPK

PPAEPSPFQPDPVDQV LFDNEFDAESQRKRTT SVSKMERMDSSLPEEE

                  EDEDKGAINGSGNAEN RERHSESSDWMKTVPS YNQTNSSMDFRNYMMR

DETLEPLPKNWEMAYT DTGMIYFIDHNTKTTT WLDPRLCKKAKAPEDC

              EDGELPYGWEKIEDPQ YGTYYVDFTLVAQAGV QWHDLGSLQPPPPGFN

          HLNQKTQFENPVEEAK RKKQLGQVEIGSSKPD MEKSHFTRDPSQLKGV

LVRASLKKSTMGFGFT IIGGDRPDEFLQVKNV LKDGPAAQDGKIAPGD

VIVDINGNCVFGHTHA DVVQMFQLVPVNQYVN LTLCRGYPLPDDSEDP

VVDIVAATPVINGQSL TKGETCMNPQDFKPGA MVLEQNGKSGHTSTGD

GLNGPSDASEQRVSMA SSGSSQPELVTIPLIK GPKGFGFAIADSPTGQ

KVKMILDSQWCQGLQK EDIIKEIYHQNVQNLT HLQVVEVLKQFPVGAD

VPLLILRGGPPSTTKT AKMKTDKKENAGSLEA INEPIPQPMPFPSII

RSGSPKLDPSEVYLKS KTLYEDKPPNTKDLDV FLRKQESGFGFRVLGG

DGPDQSIYIGAIIPLG AAEKDGRLRAADELMC IDGIPVKGKSHKQVLD

LMTTAARNGHVLLTVR RKIFYGEKQPEDDSSQ AFISTQNGSPRLNRAE

VPARPAPQEPYDVVLQ RKENEGFGFVILTSKN KPPPGVIPHKIGRVIE

GSPADRCGKLKVGDHI SAVNGQSIVELSHANI VQLIKDAGVTVTLTVI

AEEEHHGPPSGTNSAR QSPALQHRPMGQSQAN HIPGDRSALEGEIGKD

VSTSYRHSWSDHKHLA QPDTAVISVVGSRHNQ NLGCYPVELERGPRGF

GFSLRGGKEYNMGLFI LRLAEDGPAIKDGRIH VGDQIVEINGEPTQGI

                        THTRAIELIQAGGNKV LLLLRPGTGLIPDHGL APSGLCSYVKPEQH

g1117849 28 MADDQGCIEEQGVEDS ANEDSVDAKPDRSSFV PSLFSKKKKNVTMRSI

KTTRDRVPTYQYNMNF EKLGKCIIINNKNFDK VTGMGVRNGTDKDAEA

            LFKCFRSLGFDVIVYN DCSCAKMQDLLKKASE EDHTNAACFACILLSH

GEENMESCSVTQAGVQ RRDLGRLQPPPPRLAE GPSLMMASRPTRGPSM

TQMLILDTRSQWKLTS SSPIPRFQAITRGGAQ EEAPGLCKPSAPSWRS

TEKTWKSCRSSPG

g11493409 29 MGLSIASHFGLLIKKV ERNILFFFRRSLALCQ AGVQWRYLSQLTAASA

SWVQAILCLSLPSSWD YRHMPPRPANFCILSR DGISPCWPGWRSSLDL

VIRPPRPPKVLRLQA

g11493483 30 MQIIFFFFLRWSFTL VAQAGVQWRDLSSPQP PPPRFKRFSCLSPPSS

WDYRHAPPHPANFVFL VETGFLRVGQAGLELL TSGDPASASQSAGIT

GVSHHTQPDANNFLRK LFQKLF

g12654881 31 MGHPRAIQPSVFFSPY DVHFLLYPIRCPYLKI GRFHIKLKGLHFLFSF

        LFFFFETQSHSVTRLE CSGTISAHCNLCLPGS SNSPASASQVAGTTGT

CHHAQLIFVFLAEMGF HHIGQDGLDLNLVIHP PRSPKALGLQA

g12803929 32 MPNHYSFCFCFCFCFR RSLALSPRLECSGAIL AHGKLHLPGSRHSPAS

ASPVAGTKGARHHARL IFLYF

g13359183 33 LFTNSPFSLLSPAQWL CFGTHLGHVQSVSHLQ WEGSVQESLRSVRNSR

CALPMLSAPCSLSLHF LLFSLSSPFFFFEIRVL LYRQAGVQWCYLGSLQ

          PLPPGFKQFSCLSYPS SWDYRRPPPRQANFCI FSTDGVSPCWPRWSLS

LDLMIRPPQPPEVLGL QV

g13375624 34 MGRLVLLWGAAVFLLG GWMALGQGGAEGVQIQ IIYFNLETVQVTWNAS

KYSRTNLTFHYRFNGD EAYDQCTNYLLQEGHT SGCLLDAEQRDDILYF

SIRNGTHPVFTASRWM VYYLKPSSPKHVRFSW HQDAVTVTCSDLSYGD

LLYEVQYRSPFDTEWQ TQSRSVTQAGVQWCDL CLLQPSPPRFKRFSCL

SLPSSWDYRHPPPRLA NFCIISRDGVSPCWPG WSRTCDLR

g13376528 35 MEFLKVARRNKREQLE QIQKELSVLEEDIKRV EEMSGLYSPVSEDSTV

PQFEAPSPSHSSIIDS TEYSQPPGFSGSSQAG VQWRYLGSLQPPPPRY

KRFSCLTLPSSWDYRR LPPHLTKKQPWYNSTL ASRRKRLTAHFEDLEQ

CYFSTRMSRISDDSRT ASQLDEFQECLSKFTR YNSVRPLATLSYASDL

YNGSSIVSSIEFDRDC DYFAIAGVTKKIKVYE YDTVIQDAVDIHYPEN

          EMTCNSKISCISWSSY HKNLLASSDYEGTVIL WDGFTGQRSKVYQEHE

KRCWSVDFNLMDPKLL ASGSDDAKVKLWSTNL DNSVASIEAKANVCCV

KFSPSSRYHLAFGCAD HCVHYYDLRNTKQPIM VFKGHRKAVSYAKFVS

GEEIVSASTDSQLKLW NVGKPYCLRSFKGHIN EKNFVGLASNGDYIAC

            GSENNSLYLYYKGLSK TLLTFKFDTVKSVLDK DRKEDDTNEFVSAVCW

RALPDGESNVLIAANS QGTIKVLEV

g13376550 36 MGSYFVARAGCKLLGL KGTSHFSLPKCRNCRR EPLPGLFFFLFFVFFFL

          RRSLALSPRLECSGAI VAHCKLGLPGSLHSPA SASQVAGTIGTCHNTR

IIFCILVETGFHRVSQ DGVDLLTL

g13430856 37 MDCGSVGGQRTQRLPG RQRLLFLPVGLSGRPG GSETSARRCPSALSDG

LGALRPRAPAARGGVS RASPLLLLLLLVPSPRL AAAAPRRQLGDWERSR

LGYAAPPAGRSGAWRC SPGVAAAAGALPQYHG PAPALVSCRRELSLSA

GSLQLERKRRDFTSSG SRKLYFDTHALVCLLE DNESHSFIQAGVQWHS

LGLLQPPPPGFKRSSH LILLSSWDYRHAPPHL DNFSVFLLETGFHHVG

QAGLKLLTSSDPPPTLA S

g13431835 38 MSPATTGTFLLTVYSI FSKVHSDRNVYPSAGV LFVHVLEREYFKGEFP

PYPKPGEISNDPITFN TNLMGYPDRPGWLRYI QRTPYSDGVLYGSPTA

ENVGKPTIIEITAYNR RTFETARHNLIINIMS AEDFPLPYQAEFFIKN

MNVEEMLASEVLGDFL GAVKNVWQPERLNAIN ITSALDRGGRVPLPIN

            DLKEGVYVMVGADVPF SSCLREVENPQNQLRC SQEMEPVITCDKKFRT

QFYIDWCKISLVDKTK QVSTYQEVIRGEGILP DGGEYKPPSDSLKSRD

YYTDFLILAVPSAVA LVLFLILAYIMCCRRE GVEKRNMQTPDIQLVH

            HSAIQKSTKELRDMSK NREIAWPLSTLPVFHP VTGEIIPPLHTDNYDS

TNMPLMQTQQWSFAPV AQAGVQWRDLGSLQPP PPRNLPHQTQIPQQQT

TGKWYP

g13435153 39 MLGLRKAAAISLLLRN VGLQLATLLMSQKKLG FCGNFLFLNLAIIQTK

ISSSFFFFLRQSLTLS PRLECNGAISAHCHLR LPDSSNSPASASQVTG

ITGSHHHAWLIFVFLV ETGFCHVGQDGLELLT SGDPASASQSAGITG

MSHHTWPTDLFFKTVL PARLGLWDSSV

g13489079 40 MHAVPRGFGKKVRVGV QSCPSPFSGQACPQPS SVFWSLLKNLPFLEHL

ELIGSNFSSAMPRNEP AIRNSLPPCSRAQSVG DSEVAAIGQLAFLRHL

TLAQLPSVLTGSGLVN IGPQCQQLRSLSLANL GMMGKVVYMPALSDML

KHCKRLRDLRLEQPYF SANAQFFQALSQCPSL QRLCLVSRSGTLQPDA

VLAFMARCLQVVMCHL FTGESLATCKSLQQSL LRRWGEVTGRRPQLFT

          ELREEPSARTSRATGR RQPCLPDSGVVCCPCG RPLAVSGIILVGVSPS

LVVKTTCVYRVLFKNL DYASIFFLVCLFETES HSVVQAGVQWRDLSSL

QPLLSGLQPQPPEQLE NELEIGFSYCFVI

g13489081 41 MEEDEFIGEKTFQRYC AEFIKHSQQIGDSWEW RPSKDCSDGYMCKIHF

QIKNGSVMSHLGASTH GQTCLPMEVKSCSVTQ AGVQLRDLSSLQPPPS

GFKQFSCLSLPSNWDY RGSPLHLANFLYF

g13540498 42 MTTCEFEFIFLKEQVT RICNIAPLKAYFSVHK MGKILKKLSNFSFLTH

RQSLTLSPRLECSGAI SAHCNLHLLGSSNSAA SASRVAGTTGACHHAQ

LIFVFLVETGFHHVGQ DGLGLLTS

g13543287 43 MSCNPSFGGIGKGHLM REVDALDGLCSRICDQ SGVHYKVLNRRKGPAV

WGLRAQIDRKLYKQNM QKEILNTPLLTVQEGAVEDLILTEPEPEHTGK

CRVSGVVLVDGSTVYA ESVILTTGTFLRGMIV IGLETHPAGRLGDQPS

IGLAQTLEKLGFVVGR LKTGTPPRIAKESINF SILNKHIPDNPSIPFS

FTNETVWIKPEDQLPC YLTHTNPRVDEIVLKN LHLNSHVKETTRGPRY

CPSIESKVLRFPNRLH QVWLEPEGMDSDLIYP QGLSMTLPAELQEKMI

TCIRGLEKAKVIQPDG VLLLLPRMECNGAISA HHNLPLPGYGVQYDYL

DPRQITPSLETHLVQR LFFAGQINGTTGYEEA AAQGVIAGINASLRVS

RKPPFVVSRTEGYIGV LIDDLTTLGTSEPYRM FTSRVEFRLSLRPDNA

DSRLTLRGYKDAGCVS QQRYERACWMKSSLEE GISVLKSIEFLSSKWK

KLIPEASISTRSLPV RALDVLKYEEVDMDSL AKAVPEPLKKYTKCRE

LAERLKIEATYESVLF HQLQEIKGVQQDEALQ LPKDLDYLTIRDVSLS

HEVREKLHFSRPQTIG AASRIPGVTPAAIINL LRFVKTTQRRQSAMNE

SSKTDQYLCDADRLQE REL

g13569856 44 MPFLYDISSCWTSFCF LFFSPLDGVLLCFPGW NAVARSQLTATSASQV

QAILLVSASGVAGIIG TCHHAQPIFVFLVEMG FHHVGQACLKLLNSGD

                              PPASASQSAGITGMSH HARPFFFFSF

g13591868 45 MSEAENEFINWVATAA IEANCSQCWLCVELPE AAGNGLPWRIVPANIS

EWICQYQWEWDNTWFC FDFLSQSVSLSPRLEC SGTILAQCNLCLLGSS

DSPASASQVAGIIGAC RHAWLIFCIFSRDGVS PYCPG

g13591870 46 MALFLDKMGSLQKGNY SSQSGMIPGSWQHKMK LQLILKSSKAYYVLSD

AAMSLQKYGRALRYIK LALQSHDTYCCLCTNM LSEVLLFLSQYLTLCG

              DIQLMLAQNANNRAAH LEEFHYQTKEDQEILH SLHRESSCQGVPQAWT

TWFTVGLCSLAHAYLS IQKRGRNIRVLIFALY LFIYFLRRSFALVAQA

GVQWCNLGSLKPPPPG FKQFSCLSLPSSWNYR HAPPCPASPPWPPKVL

                GLQV

g1362993 47 RSLTLWPSLEYSGTIS AHCNLRLPGSSDSRAS ASRAAGITGVSHCARP

            CMLFDPEFDLLAGVQL LPFEPPTGKALSRKD

g13631907 48 MEFRKLRGMETRPPAN TARLQPPRDLRSSSPR KQLSESSDDDYDDVDI

          PTPAEDTPPPLPPKPK FRSPSDEGPGSMGDDG QLSPGVLVRCASGPPP

NSPRPGPPPSTSSPHL TAHSEPSLWNPPSREL DKPPLLPPKKEKMKRK

GCALLVKLFNGCPLRI HSTAAWTHPSTKDQHL LLGAEEGIFILNRNDQ

          EATLEMLFPSRTTWVY SINNVLMSLSGKTPHL YSHSILGLLERKETRA

GNPIAHISPHRLLARK NMVSTKIQDTKGCRAC CVAEGASSGGPFLCGA

          LETSVVLLQWYQPMNK FLLVRQVLFPLPTPLS VFALLTGPGSELPAVC

IGVSPRPPGKSVLFHT VRFGALSCWLGEMSTE HRGPVQVTQVEEDMVM

VLMDGSVKLVTPEGSP VRGLRTPEIPMTEAVE AVAMVGGQLQAFWKHG

VQVWALGSDQLLQELR DPTLTFRLLGSPRLEC SGTISPHCNLLLPGSS

NSPASASRVAGITGL

g13644612 49 MSMVLGGPFSKGHTAS DEYFQIFHNISFFETE SCSVAQAGVQWCNLGS

LQALPPRFTPFSCLSL PSSWDYRHPPPCPDNV FVFSVETGLHCVSQDG

LNLLTL

g13646055 50 MDCGSVGGQRTQRLPG RQRLLFLPVGLSGRPG GSETSARRCLSALSDG

LGALRPRAPAARGGVS RASPLLLLLLLVPSPRL AAAAPRRQLGDWERSR

LGYAAPPAGRSSAWRC SPGVAAAAGALPQYHG PAPALVSCRRELSLSA

GSLQLERKRRDFTSSG SRKLYFDTHALVCLLE DNESHSFIQAGVQWHS

LGLLQPPPPGFKRSSH LILLSSWDYRHAPPHL DNFSVFLLETGFHHVG

QAGLKLLTSSDPPPTLA S

g13646423 51 MNFFFKTEFLSVTQAG MQWHNFSSLQPLPPGF KQFSCLSLLSSWDYRH

TPPCPANFCIFSRGGV SPCWSGWSRTPDFMIH PPRPPKVLRLQK

g13648611 52 MPLAAYCYLRVVGKGS YGEVTLVKHRRDGKQY VIKKLNLRNASSRERR

AAEQEAQLLSQLKHPN IVTYKESWEGGDGLLY IVMGFCEGGDLYRKLK

EQKGQLLPENQVVEWF VQIAMALQYLHEKHIL HRDLKTQNVFLTRTNI

IKVGDLGIARVLENHC DMASTLIGTPYYMSPE LFSNKPYNYKSDVWAL

GCCVYEMATLKHAFNA KDMNSLVYRIIEGKLP PMPRDYSPELAELIRT

        MLSKRPEEPSVRSIL RQPYIKRQISFFLEAT KIKTSKNNIKNGDSQS

KPFATVVSGEAESNHE VIHPQPLSSEGSQTYI MGEGKCLSQEKPRASG

          LLKSPASLKAHTCKQD LSNTTELATISSVNID ILPAKGRDSVSDGFVQ

ENQPRYLDASNELGGI CSISQVEEEMLQDNTK SSAQPENLIPMWSSDI

VTGEKNEPVKPLQPLI KEQKPKDQSLALSPKL ECSGTILAHSNLRLLG

SSDSPASASSRVAGITG VCHHAQDQVAGECIIE KQGRIHPDLQPHNSGS

EPSLSRQRRQKRREQT EHRGEKRQVRRDLFAF QESPPRFLPSPHPIVGK

VDVTSTQKEAENQRRV VTGSVSSSSRSSEMSSS KDRPLSARERRRLKQS

QEEMSSSGPSVRKASL SVAGPGKPQEEDQPLP ARRLSSDCSVTQERKQ

IHCLSEDELSSSSTSST DKSDGDYGEGKGQTNE INALVQLMTQTLKLDS

KESCEDVPVANPVSEF KLHRKYRDTLILHGKV AEEAEEIHFKELPSAI

MPGSEKIRRLVEVLRT DVIRGLGVQLLEQVYD LLEEEDEFDREVRLRE

HMGEKYTTYSVKARQL KFFEENMNF

g13651342 53 MFISFGRLIFSFFLTW SLSLSPRLECSGTILA HCNPTSQVQAILPASA

          SRVAGITGMHHHTCLI FVLLVKMGFCHVGHAG LELVT

g13652010 54 MESGQPSLSFYFLFIY FFEIGSHFVTQAGVQW HNLDSLQLSLASAPQV

AGTTGACHHARLIFGV FCRDWVLPC

g13653409 55 MLLVDADQPEPMRSGA RELALFLTPEPGAEAK EVEETIEGMLLRLEEF

CSLADLIRSDTSQILE ENIPVLKAKLTEMRGI YAKVDRLEAFVKMVGH

HVAFLEADVLQAERDH GAFPQALRRWLGSAGL PSFRNVECSGTIPARC

NLRLPGSSSPASASQ VAGIPEVTCTGARDVR AAHTV

g13699916 56 MSRGNENRLTHRQTV LREKGRRLANRGPAYM FNDHSTSLSIEEERFL

DAAEYGNIPVVRKMLE ECLSLNVNCVDYMGQN ALQLAVANEHLEITEL

          LLKKENLSRVGDALLL AISKGYVRIVEAILNH PAFAEGKRLATSPSQS

          ELQQDDFYAYDEDGTR FSHDVTPIILAAHCQE YEIVHTLLRKGARIER

PHDYFCKCTECSQKQK HDSFSHSRSRINAYKG LASPAYLSLSSEDPVM

                                                         

AILNGDAETRQPGDLA RPNLSRLKLAIKYEVK KFVAHPNCQQQLLSIW

YENLSGLRQQTMAVKF LVVLAVAIGLPFLALI YWCAPCSKMGKILRGP

FMKFVAHAASFTIFLG LLVMNAADRFEGTKLL PNETSTDNARQLFRMK

TSCFSWMEMLIISWVI GMIWAECKEIWTQGPK EYLFELWNMLDFGMLA

IFAASFIARFMAFWHA SKAQSIIDANDTLKDL TKVTLGDNVKYYNLAR

IKWDPTDPQIISEGLY AIAVVLSFSRIAYILP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYIGAK QNEAFTTVEESFKTLF

          WAIFGLSEVKSVVINY NHKFIENIGYVLYGVY NVTMVIVLLNMLIAMI

NSSFQEIEDDADVEWK FARAKLWFSYFEEGRT LPVPFNLVPSPKSLLY

LLLKFKKWMSELIQGH KKGFQEDAEMNKRNEE KKFGILGSHEDLSKFS

LDRNQLAHNKQSSTRS SEDFHLNSFSNPPRQY QKIMKRLIKRYVLQAQ

IDKESDEVNEGELKEI KQDISSLRYELLEEKS QNTEDLAELIRKLGER

LSLESKQEESRR

g13702149 57 MSRGNENRLTHRQTV LREKGRRLANRGPAYM FNDHSTSLSIEEERFL

DAAEYGNIPVVRKMLE ECLSLNVNCVDYMGQN ALQLAVANEHLEITEL

          LLKKENLSRVGDALLL AISKGYVRIVEAILNH PAFAEGKRLATSPSQS

          ELQQDDFYAYDEDGTR FSHDVTPIILAAHCQE YEIVHTLLRKGARIER

PHDYFCKCTECSQKQK HDSFSHSRSRINAYKG LASPAYLSLSSEDPVM

                                                         

AILNGDAETRQPGDLA RPNLSRLKLAIKYEVK KFVAHPNCQQQLLSIW

YENLSGLRQQTMAVKF LVVLAVAIGLPFLALI YWCAPCSKMGKILRGP

FMKFVAHAASFTIFLG LLVMNAADRFEGTKLL PNETSTDNARQLFRMK

TSCFSWMEMLIISWVI GMIWAECKEIWTQGPK EYLFELWNMLDFGMLA

IFAASFIARFMAFWHA SKAQSIIDANDTLKDL TKVTLGDNVKYYNLAR

IKWDPTDPQIISEGLY AIAVVLSFSRIAYILP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYIGAK QNEAFTTVEESFKTLF

          WAIFGLSEVRSVVINY NHKFIENIGYVLYGVY NVTMVIVLLNMLIAMI

NSSFQEIERNEEKKFG ILGSHEDLSKFSLDRN QLAHNKQSSTRSSEDF

          HLNSFSNPPRQYQKIM KRLIKRYVLQAQIDKE SDEVNEGELKEIKQDI

SSLRYELLEEKSQNTE DLAELIRRLGERLSLE SKQEESRR

g14043238 58 MESRSVAQAGVQWPDL GSLQPLPPRFKRFFCL SLQSSWDYRHAPPPRPA

NFVFLVETGFCHVSQA GLELLTSSDPPPRPPK VLR

g14192931 59 MISVHCNLCLPGSSDP PASASQVAGITGVRHC MASGAVLNKVRRHQCS

GDLEVRGSHGSLGEAP WGKSVPGRGTASRKGP GAGVIGNSKEASTGRA

QWSAPVIPATQEAKAG GLLEPRSLISAWATYQ DLISINKLKEKRG

g14198309 60 MTRSLFKGNFWSADIL STIGYDNIIQHLNNGR KNCKEFEDFLKERAAI

EERYGKDLLNLSRKKP CGQSEINTLKRALEVF KQQVDNVAQCHIQLAQ

        SLREEARKMEEFREKQ KLQRKKMESHSVTQAG AQWHDLGSLQALPPGF

MPFSCLSLPSSWNYRL PPPPRLAEPRNQDHGV A

g14249973 61 MESHSVTQAGVQWRDL GSLQPLPPGFKQFSHL SLPSSWDYRRVPPYLG

NFCIFSGEGVSPCWPG WS

g16226025 62 MGSLSTANVEFCLDVF KELNSNNIGDNIFFSS LSLLYALSMVLLGARG

ETAEQLEKVLHFSHTV DSLKPGFKDSPKCSQA GRIHSEFGVEFSQINQ

PDSNCTLSIANRLYGT KTMAFHQQYLSCSEKW YQARLQTVDFEQSTEE

TRKTINAWVENKTNGK VANLFGKSTIDPSSVM VLVNTIYFKGQRQNKF

QVRETVKSPFQLSEGK NVTVEMMYQIGTFKLA FVKEPQMQVLELPYVN

          NKLSMIILLPVGIANL KQIEKQLNSGTFHEWT SSSNMMEREVEVHLPR

FKLEIKYELNSLLKPL GVTDLFNQVKADLSGM SPTKGLYLSKAIHKSY

LDVSEEGTEAAAATGD SIAVKSLPMRAQFKAN HPFLFFIRHTHTNTIL

FCGKLASP

g16517174 63 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEFVAQP NCQQLLASRWYDEFPG WRRRHWAVKMVTCFII

GLLFPVFSVCYLIAPK SPLGLFIRKPFIKFIC HTASYLTFLFLLLLAS

QHIDRSDLNRQGPPPT IVEWMILPWVLGFIWG EIKQMWDGGLQDYIHD

WWNLMDFVMNSLYLAT ISLKIVAFVKYSALNP RESWDMWHPTLVAEAL

            FAIANIFSSLRLISLF TANSHLGPLQISLGRM LLDILKFLFIYCLVLL

AFANGLNQLYFYYEET KGLTCKGIRCEKQNNA FSTLFETLQSLFWSIF

              GLINLYVTNVKAQHEF TEFVGATMFGTYNVIS LVVLLNMLIAMMNNSY

QLIADHADIEWKFART KLWMSYFEEGGTLPTP FNVIPSPKSLWYLIKW

IWTHLCKKKMRRKPES FGTIGVRTQHRRAADN LRRHHQYQEVMRNLVK

RYVAAMIRDAKTEEGL TEENFKELKQDISSFR FEVLGLLRGSKLSTIQ

SANASKESSSNSADSDE KSDSEGNSKDKKKNFS LFDLTTLIHPRSAAIA

SERHNISNNGSALVVQE PPREKQRKVNFVTDIK NFGLFHRRSKQNAAEQ

NANQIFSVSEEVARQQ AAGPLERNIQLESRGL ASRGDLSIPGLSEQCV

          LYDHRERNTDTLGLQV GKRVCPFKSEKVVVED TVPIIPKEKHAKEEDS

SIDYDLNLPDTVTHED YVTTRL

g16517176 64 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEASYGE KLNRCGMADFRTTSMI GGI

g16758330 65 MSQSPGFVTRRGGSPK AAPGAGARRNESQDYL LMDELGDDGYPQLQQP

PYGYYPSFRGNENRLT HRRQTVLREKGRRLAN RGPAYMFNDHSTSLSI

                EEERFLDAAEYGNIPV VRKMLEECLSLNVNCV DYMGQNALQLAVANEH

          LEITELLLKKENLSRV GDALLLAISKGYVRIV EAILNHPAFAEGKRLA

            TSPSQSELQQDDFYAY DEDGTRFSHDVTPIIL AAHCQEYEIVHTLLRK

GARIERPHDYFCKCTE CSQKQKHDSFSHSRSR INAYKGLASPAYLSLS

SEDPVMTALELSNELA VLANIEKEFKNDYRKL SMQCKDFVVGLLDLCR

       NTEEVEAILNGDAETR QPGDLARPNLSRLKLA IKYEVKKFVAHPNCQQ

QLLSIWYENLSGLRQQ TMAVKFLVVLAVAIGL PFLALIYWCAPCSKMG

KILRGPFMKFVAHAAS FTIFLGLLVMNAADRF EGTKLLPNETSTDNAR

QLFRMKTSCFSWMEML IISWVIGMIWAECKEI WTQGPKEYLFELWNML

                                                             

YYNLARIKWDPTDPQI ISEGLYAIAVVLSFSR IAYILPANESFGPLQI

        SLGRTVKDIFKFMVIF IMVFVAFMIGMFNLYS YYIGAKQNEAFTTVEE

SFKTLFWAIFGLSEVK SVVINYNHKFIENIGY VLYGVYNVTMVIVLLN

MLIAMINSSFQEIEDD ADVEWKFARAKLWFSY FEEGRTLPVPFNLVPS

PKSLLYLLLLKFKKWMS ELIQGHKKGFQEDAEM NKRNEEKKFGILGSHE

            DLSKFSLDRNQLAHNK QSSTRSSEDFHLNSFS NPPRQYQKIMKRLIKR

YVLQAQIDKESDEVNE GELKEIKQDISSLRYE LLEEKSQNTEDLAELI

RKLGERLSLESKQEES RR

g1710216 66 MGHPRAIQPSVFFSPY DVHFLLYPIRCPYLKI GRFHIKLKGLHFLFSF

        LFFFFETQSHSVTRLE CSGTISAHCNLCLPGS SNSPASASRVAGTAGT

              CRRAQLIFVFLAEMGF HHVGRDGLDLNLVIHP PRSPKALGLQA

g17978303 67 MGSLSTANVEFCLDVF KELNSNNIGDNIFFSS LSLLYALSMVLLGARG

ETAEQLEKVLHFSHTV DSLKPGFKDSPKCSQA GRIHSEFGVEFSQINQ

PDSNCTLSIANRLYGT KTMAFHQQYLSCSEKW YQARLQTVDFEQSTEE

TRKMINAWVENKTNGK VANLFGKSTIDPSSVM VLVNTIYFKGQRQNKF

QVRETVKSPFQLSEGK NVTVEMMYQIGTFKLA FVKEPQMQVLELPYVN

          NKLSMIILLPVGIANL KQIEKQLNSGTFHEWT SSSNMMEREVEVHLPR

FKLEIKYELNSLLKPL GVTDLFNQVKADLSGM SPTKGLYLSKAIHKSY

LDVSEEGTEAAAATGD SIAVKSLPMRAQFKAN HPFLFFIRHTHTNTIL

FCGKLASP

g18376629 68 MLRNSTFKNMQRRHTT LREKGRRQAIRGPAYM FNEKGTSLTPEEERFL

DSAEYGNIPVVRKMLE ESKTLNFNCVDYMGQN ALQLAVGNEHLEVTEL

        LLKKENLARVGDALPL AISKGYVRIVEAILNH PAFAQGQRLTLSPLEQ

ELRDDDFYAYDEDGTR FSHDITPIILAAHCQE YEIVHILLLKGARIER

PHDYFCKCNECTEKQR KDSFSHSRSRMNAYKG LASAAYLSLSSEDPVL

            TALELSNELARLANIE TEFKNDYRKLSMQCKD FVVGVLDLCRDTEEVE

AILNGDVNFQVWSDHH RPSLSRIKLAIKYEVK KFVAHPNCQQQLLTMW

YENLSGLR(QQSIAVKF LAVFGVSI)GLPFLAIA YWIAPCSKLGRTLRSP

                              FMKFVAHAVSFTIFLG LLVVNASDRFEGVKTL PNETFTDYPKQIFRVK

              TTQFSWTEMLIMKWVL GMIWSECKEIWEEGPR EYVLHLWNLLDFGMLS

IFVASFTARFMAFLKA TEAQLYVDQHVQDDTL HNVSLPPEVAYFTYAR

DKWWPSDPQIISEGLY AIAVVLSFSRIAYILP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYRGAK YNPAFTTVEESFKTLF

                                                                                             

NNSYQEIEEDADVEWK FARAKLWLSYFDEGRT LPAPFNLVPSPKSFYY

LIMRIKMCLIKLCKSK AKSCENDLEMGMLNSK FKKTRYQAGMRNSENL

            TANNTLSKPTRYQKIM KRLIKRYVLKAQVDRE NDEVNEGELKEIKQDI

SSLRYELLEEKSQATG ELADLIQQLSEKFGKN LNKDHLRVNKGKDI

g1843388 69 MKVRLLRQLSAAAKVK APSGLQGPPQAHQFIS LLLEEYGALCQAARSI

STFLGTLENEHLKKFQ VTWELHNKHLFENLVF SEPLLQSNLPALVSQI

RLGTTHDTCSEDTYS TLLQRYQRSEEELRRV AEEWLECQKRIDAYVD

EQMTMKTKQRMLTEDW ELFKQRRFIEEQLTNK KAVTGENNFTDTMRHV

            LSSRLSMPDCPNCNYR RRCACDDCSLSHILTC GIMDPPVTDDIHIHQL

            PLQVDPAPDYLAERSP PSVSSASSGSGSSSPI TIQQHPRLILTDSGSA

PTFCSDDEDVAPLSAK FADIYPLSNYDDTEVV ANMNGIHSELNGGGEN

MALKDESPQISSTSSS SSEADDEEADGESSGE PPGAPKEDGVLGSRSP

          RTEESKADSPPPSYPT QQAEQAPNTCECHVCK QEASGLTPSAMTAGAL

                    PPGHQFLSPEKPTHPA LHLYPHIHGHVPLHTV PHLPRPLIHPTLYATP

          PFTHSKALPPAPVQNH TNKHQVFNASLQDHIY PSCFGNTPEWNSSKFI

SLWGSEVMNDKNWNPG TFLPDTISGSEILGPT LSETRPEALPPPSSNE

        TPAVSDSKEKKNAAKK KCLYNFQDAFMEANKV VMATSSATSSVSCTAT

TVQSSNSQFRVSSKRP PSVGDVFHGISKEDHR HSAPAAPRNSPTGLAP

LPALSPAALSPAALSP ASTPHLANLAAPSFPK TATTTPGFVDTRKSFC

PAPLPPATDGSISAPP SVCSDPDCEGHRCENG VYDPQQDDGDESADED

SCSEHSSSTSTSTNQK EGKYCDCCYCEFFGHG GPPAAPTSRNYAEMRE

KLRLRLTKRKEEQPKK MDQISERESVVDHRRV EDLLQFINSSETKPVS

          STRAAKRARHKQRKLE EKARLEAEARAREHLH LQEEQRRREEEEEDEEE

EEDRFKEEFQRLQELQ KLRAVKKKKKERPSKD CPKLDMLTRNFQAATE

SVPNSGNIHNGSLEQT EEPETSSHSPSRHMNH SEPRPGLGADGDAADP

VDTRDSKFLLPKEVNG KQHEPLSFFFDIMQHH KEGNGKQKLRQTSKAS

SEPARRPTEPPKATEG QSKPRAQTESKAKVVD LMSITEQKREERKVNS

NNNNKKQLNHIKDEKS NPTPMEPTSPGEHQQN SKLVLAESPQPKGKNK

KNKKKKGDRVNNSIDG VSLLLPSLGYNGAILA HCNLRLPGSSDCAASA

SQVVGITDDVFLPKDI DLDSVDMDETEREVEY FKRFCLDSARQTRQRL

SINWSNFSLKKATFAAH

g20140144 70 MGSLSTANVEFCLDVF KELNSNNIGDNIFFSS LSLLYALSMVLLGARG

ETAEQLEKVLHFSHTV DSLKPGFKDSPKCSQA GRIHSEFGVEFSQINQ

PDSNCTLSIANRLYGT KTMAFHQQYLSCSEKW YQARLQTVDFEQSTEE

TRKMINAWVENKTNGK VANLFGKSTIDPSSVM VLVNIIYFKGQRQNKF

QVRETVKSPFQLSEGK NVTVEMMYQIGTFKLA FVKEPQMQVLELPYVN

          NKLSMIILLPVGIANL KQIEKQLNSGTFHEWT SSSNMMEREVEVHLPR

FKLEIKYELNSLLKPL GVTDLFNQVKADLSGM SPTKGLYLSKAIHKSY

LDVSEEGTEAAAATGD SIAVKSLPMRAQFKAN HPFLFFIRHTHTNTIL

FCGKLASP

g20476660 71 MMAALYPSTDLSGASS SSLPSSPSSSSSPNEVM ALKDVREVKEENTLNE

KLFLLACDKGDYYMVKKILEENSSGDLNINCVDVLGRNAVTITIENEN

LDILQLLLDYGCQSAD ALLVAIDSEVVGAVDI LLNHRPKRSSRPTIVK

LMERIQNPEYSTTMDV APVILAAHRNNYEILT MLLKQDVSLPKPHAVG

CECTLCSAKNKKDSLR HSRFRLDIYRCLASPA LIMLTEEDPILRAFEL

SADLKELSLVEVEFRN DYEELARQCKMFAKDL LAQARNSRELEVILNH

            TSSDEPLDKRGLLEER MNLSRLKLAIKYNQKE FVSQSNCQQFLNTVWF

GQMSGYRRKPTCKKIM TVLTVGIFWPVLSLCY LIAPKSQFGRIIHTPF

MKFIIHGASYFTFLLL LNLYSLVYNEDKKNTM GPALERIDYLLILWII

GMIWSDIKRLWYEGLE DFLEESRNQLSFVMNS LYLATFALKVVAHNKF

HDFADRKDWDAFHPTL VAEGLFAFANVLSYLR LFFMYTTSSILGPLQI

SMGQMLQDFGKFLGMF LLVLFSFTIGLTQLYD KGYTSKEQKDCVGIFC

EQQSNDTFHSFIGTCF ALFWYIFSLAHVAIFV TRFSYGEELQSFVGAV

            IVGTYNVVVVIVLTKL LVAMLHKSFQLIANHE DKEWKFARAKLWLSYF

                                                                           

RNLKQKRDENYQKVWC CLVHRYLTSMRQKMQS TDQATVENLNELRQDL

SKFRNEIRDLLGFRTS KYAMFYPRN

g20546044 72 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEFVAQP NCQQLLASRWYDEFPG WRRRHWAVKMVTCFII

GLLFPVFSVCYLIAPK SPLGLFIRKPFIKFIC HTASYLTFLFLLLLAS

QHIDRSDLNRQGPPPT IVEWMILPWVLGFIWG EIKQMWDGGLQDYIHD

WWNLMDFVMNSLYLAT ISLKIVAFVKYSALNP RESWDMWHPTLVAEAL

            FAIANIFSSLRLISLF TANSHLGPLQISLGRM LLDILKFLFIYCLVLL

AFANGLNQLYFYYEET KGLTCKGIRCEKQNNA FSTLFETLQSLFWSIF

              GLINLYVTNVKAQHEF TEFVGATMFGTYNVIS LVVLLNMLIAMMNNSY

QLIADHADIEWKFART KLWMSYFEEGGTLPTP FNVIPSPKSLWYLIKW

IWTHLCKKKMRRKPES FGTIGVRTQHRRAADN LRRHHQYQVIMRNLVK

RYVAAMIRDAKTEEGL TEENFKELKQDISSFR FEVLGLLRGSKLSTIQ

SANASKESSSNSADSDE KSDSEGNSKDKKKNFS LFDLTTLIHPRSAAIA

SERHNISNNGSALVVQE PPREKQRKVNFVTDIK NFGLFHRRSKQNAAEQ

NANQIFSVSEEVARQQ AAGPLERNIQLESRGL ASRGDLSIPGLSEQCV

LVDHRERNTDTLGLQV GKRVCPFKSEKVVVED TVPIIPKEKHAKEEDS

SIDYDLNLPDTVTHED YVTTRL

g20881287 73 MSQSPRFVTRRGGSLK AAPGAGTRRNESQDYL LMDELGDDGYPQLPLP

PYGYYPSFRGNENRLT HRRQTILREKGRRLAN RGPAYMFNDHSTSLSI

              EEERFLDAAEYGNIPV VRKMLEECHSLNVNCV DYMGQNALQLAVANEH

          LEITELLLKKENLSRV GDALLLAISKGYVRIV EAILNHPAFAEGKRLA

            TSPSQSELQQDDFYAY DEDGTRFSHDVTPIIL AAHCQEYEIVHTLLRK

GARIERPHDYFCKCTE CSQKQKHDSFSHSRSR INAYKGLASPAYLSLS

SEDPVMTALELSNELA VLANIEKEFKNDYRKL SMQCKDFVVGLLDLCR

        NTEEVEAILNGDAETR QPGDFGRPNLSRLKLA IKYEVKKFVAHPNCQQ

QLLSIWYENLSGLRQQ TMAVKFLVVLAVAIGL PFLALIYWCAPCSKMG

KILRGPFMKFVAHAAS FTIFLGLLVMNAADRF EGTKLLPNETSTDNAR

QLFRMKTSCFSWMEML IISWVIGMIWAECKEI WTQGPKEYLFELWNML

                                                             

YYNLARIKWDPTDPQI ISEGLYAIAVVLSFSR IAYILPANESFGPLQI

        SLGRTVKDIFKFMVIF IMVFVAFMIGMFNLYS YYIGAKQNEAFTTVEE

SFKTLFWAIFGLSEVK SVVINYNHKFIENIGY VLYGVYNVTMVIVLLN

MLIAMINSSFQEIEDD ADVEWKFARAKLWFSY FEEGRTLPVPFNLVPS

PKSLLYLLLLKFKKWMC ELIQGQKQGFQEDAEM NKRNEEKKFGISGSHE

            DLSKFSLDKNQLAHNK QSSTRSSEDYHLNSFS NPPRQYQKIMKRLIKR

YVLQAQIDKESDEVNE GELKEIKQDISSLRYE LLEEKSQNTEDLAELI

RKLGERLSLEPKLEES RR

g2105420 74 PSGLPLLPVLFALGGL LLLSNASCVGGVLWQR RLRRLAEALNFPPHLH

            PGRSEEDRVRNEYEES QWTGERDTQSSTVSTT EAEPYYRSLRDFSPQL

PPTQEEVSYSRGFTGE DEDMAFPGHLYDEVER TYPPSGAWGPLYDEVQ

MGPWDLHWPEDTYQDP RGIYDQVAGDLDTLEP DSLFELRGHLVWGFN

HVSQAGLKLLASSDPP ASASQSAEITESHSVV QVGVQWRYFGSLHPLP

          PGSRDSLASASRIAGI TAPWEAEVSRSPQGTQ DSPVTRSGPPSRGWQS

LSFDGGAFHLKGTGEL TRALLVLRLCAWPPLV THGLLLQAWSRRLLGS

RLSGAFLRASVYGQFV AGETAEEVKGCVQQLR TLSLRPLLAVPTEEEP

                DSAAKRMRLHHVGQAG LELLTPAASGSVAQAG VQWRQSSDRGGGNQAA

ASRSSLQEAAFSPPC GRLQLPAQPASRHGAR GRGSMKAKSLTSRHLL

ASQGQETIIKTKVRIP ALWKAEPGQHSKTPSQ QNKSQYVTTLWEADVG

RSLENLQVSCLNAEQN QHLRASLSRLHRVTPP AGTSTSGPPSAACIGW

            HSRLHRVAQYARAQHV RLLVDAEYTSLNPALS LLVAALAVRWNSPGEG

GPWVWNTYQACLKDTF ERLGRDAEAAHRAGLA FGVKLVRGAYLDKERA

            VAQLHGMEDPTQPDYE ATSELNRASPFSYSRC LELMLTHVARHGPMCH

            LMVASHNEESVRQATK RMWELGIPLDGTVCFG QLLGMCDHVSLALGQA

GYVVYKSIPYGSLEEV IPYLIRRAQENRSVLQ GARREQELLSQELWRR

LLPGCRRIPH

g2119643 75 SCSVTLAGVQWRDLGL LQPLPPKFKRFSCLSF PSSWDYR

g2119644 76 EMEFNCESCSVTLAGV QWRDLGLLQPLPPKFK RFSCLSFPSSWDYR

g2136328 77 MCPGIPGPRAEAAVGT THPFSSPGAWLGSGSG SGPVGAPPPSPGLPPS

            WAAMMAALYPSTDLSG ASSSSLPSSSPSSSSPN EVMALKDVREVKEENT

LNEKLFLLACDKGDYY MVKKILEENSSGDLNI NCVDVLGRNAVTITIE

NENLDILQLLLDYGCQ KLMERIQNPEYSTTMD VAPVILAAHRNNYEIL

TMLLKQDVSLPKPHAV GCECTLCSAKNKKDSL RHSRFRLDIYRCLASP

ALIMLTEEDPILRAFE LSADLKELSLVEVEFR NDYEELARQCKMFAKD

LLAQARNSRELEVILN HTSSDEPLDKRGLLEE RMNLSRLKLAIKYNQK

EFVSQSNCQQFLNTVW FGQMSGYRRKPTCKKI MTVLTVGIFWPVLSLC

YLIAPKSQFGRIIHTP FMKFIIHGASYFTFLL LLNLYSLVYNEDKKNT

MGPALERIDYLLILWI IGMIWSDIKRLWYEGL EDFLEESRNQLSFVMN

SLYLATFALKVVAHNK FHDFADRKDWDAFHPT LVAEGLFAFANVLSYL

RLFFMYTTSSILGPLQ ISMGQMLQDFGKFLGM FLLVLFSFTIGLTQLY

DKGYTSKEQKDCVGIF CEQQSNDTFHSFIGTC FALFWYIFSLAHVAIF

VTRFSYGEELQSFVGA VIVGTYNVVVVIVLTK LLVAMLHKSFQLIANH

                                                                               

SHTSKGKVKRQNSLKE WRNLKQKRDENYQKVM CCLVHRYLTSMRQKMQ

STDQATVENLNELRQD LSKFRNEIRDLLGFRT SKYAMFYPRN

g3766191 78 MSRGNENRLTHRQTI LREKGRRLANRGPAYM FNDHSTSLSIEEERFL

DAAEYGNIPVVRKMLE ECHSLNVNCVDYMGQD ALQLAVANEHLEITEL

          LLKKENLSRVGDALLL AISKGYVRIVEAILNH PAFAEGKRLATSPSQS

          ELQQDDFYAYDEDGTR FSHDVTPIILAAHCQE YEIVHTLLRKGARIER

PHDYFCKCTECSQKQK HDSFSHSRSRINAYKG LASPAYLSLSSEDPVM

                                                         

AILNGDAETRQPGDFG RPNLSRLKLAIKYEVK KFVAHPNCQQQLLSIW

YENLSGLRQQTMAVKF LVVLAVAIGLPFLALI YWCAPCSKMGKILRGP

FMKFVAHAASFTIFLG LLVMNAADRFEGTKLL PNETSTDNARQLFRMK

TSCFSWMEMLIISWVI GMIWAECKEIWTQGPK EYLFELWNMLDFGMLA

IFAASFIARFMAFWHA SKAQSIIDANDTLKDL TKVTLGDNVKYYNLAR

IKWDPTDPQIISEGLY AIAVVLSFSRIAYILP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYIGAK QNEAFTTVEESFKTLF

          WAIFGLSEVKSVVINY NHKFIENIGYVLYGVY NVTMVIVLLNMLIAMI

NSSFQEIEDDADVEWK FARAKLWFSYFEEGRT LPVPFNLVPSPKSLLY

LLLKFKKWMCELIQGQ KQGFQEDAEMNKRNEE KKFGISGSHEDLSKFS

LDKNQLAHNKQSSTRS SEDYHLNSFSNPPRQY QKIMKRLIKRYVLQAQ

IDKESDEVNEGELKEI KQDISSLRYELLEEKS QNTEDLAELIRKLGER

LSLEPKLEESRR

g403460 79 DRLSLLSPRLECNGMI LAHCKLRLPGFKRFSC LSLPSSWDYRHVPPRQ

VHFVFSVETGFHRAGQ AGLELLTSSVPPTSAF PKCWDYRRDDQAWPTL

                SSFRGLNKFAFLPKFF AHPISQFQRVECNVGC PILLAMKYLAYSSLPG

ADTMLYFYFYEQEASL AVCNICRQKFHWVLYQ ISHLYRGVIVDNFLLH

PDGRFTWTIFFLSWVK QNSLYDFFFGTESRSV ALLPRLECSGAMSTLH

                            TVLRPAYSHIYHPDVK EKTHFLGNVFNKRKLQ KKILKTPNPLCALHSA

PSPSLPPFLRCTGRLP FYLGLDFLFVAGALM FLPVSFLNPHTLTWPP

                  QCCTRSDCNPLRGQRE ISALSHSLPTGLSMPL

g4200234 80 MAALYACTKCHQRFPF EALSQGQQLCKECRIA HPVVKCTYCRTEYQQE

RLECNGTISAHCNLHL PGSSSPASSSRVAGI TGIKTNTICKKCAQNV

                   QLYGTPKPCQYCNIIA AFIGNKCQRCTNSEKK YGPPYSCEQCKQQCAF

DRKDDRKKVDGKLLCW LCTLSYKRVLQKTKEQ RKHLSSSSRAGHQEKE

QYSRLSGGGHYNSQKT LSTSSIQNEIPKKKSK FESITTNGDSFSPDLA

LDSPGTDHFVIIAQLK EEVATLKKMLHQKDQM ILEKEKKITELKADFQ

YQESQMRAKMNQMEKT HKEVTEQLQAKNRELL KQAAALSKSKKSEKSG

AITSP

g4200238 81 MAALYACTKCHQRFPF EALSQGQQLCKECRIA HPVVKCTYCRTEYQQE

RLECNGTISAHCNLHL PGSSSPASSSRVAGI TGIKTNTICKKCAQNV

                   QLYGTPKPCQYCNIIA AFIGNKCQRCTNSEKK YGPPYSCEQCKQQCAF

DRKDDRKKVDGKLLCW LCTLSYKRVLQKTKEQ RKHLSSSSRAGHQEKE

QYSRLSGGGHYNSFSP DLALDSPGTDHFVIIA QLKEEVATLKKMLHQK

DQMILEKEKKITELKA DFQYQESQMRAKMNQM EKTHKEVTEQLQAKNR

        ELLKQAAALSKSKKSE KSGAITSP

g423149 82 FFFFFFETESCSVAEA GVQWCDLGSLKSPPPG SSDSPASASRVAGITG

MHHHTQLIFVFLVETG SHMQLSDSTLVITTAQ NAKITARAPRDLFFFF

              FFFF

g4336401 83 LPLLPRMECRGMISAH CNLCRSGSSSPASAS RVAGITGTCHHAQLSF

PFFLFMRW

g4336402 84 LPLLPRMECRGMISAH CNLCRSGSSSPASAS RVAGITGTCHHAQL

g4379098 85 MDIEDEENMSSSSTDV KENRNLDNVSPKDGST PGPGEGSQLSNGGGGG

          PGRKRPLEEGSNGHSK YRLKKRRKTPGPVLPK NALMQLNEIKPGLQYT

LLSQTGPVHAPLFVMS VEVNGQVFEGSGPTKK KAKLHAAEKALRSFVQ

          FPNASEAHLAMGRTLS VNTDFTSDQADFPDTL FNGFETPDKAEPPFYV

GSNGDDSFSSSGDLSL SASPVPASLAQPPLPV LPPFPPPSGKNPVMIL

NELRPGLKYDFLSESG ESHAKSFVMSVVVDGQ FFEGSGRNKKLAKARA

AQSALAAIFNLHLDQT PSRQPIPSEGLQLHLP QVLADAVSRLVLGKFG

DLTNDNFSSPHARRKVL AGVVMTTGTDVKDAKV ISVSTGTKCINGEYMS

                  DRGLALNDCHAEIISR RSLLRFLYTQLELYLN NKDDQKRSIFQKSERG

            GFRLKENVQFHLYIST SPCGDARIFSPHEPIL EGSRSYTQAGVQWCNH

GSLQPRPPGLLSDPST STFQGAGTTEPADRHP NRKARGQLRTKIESGE

GTIPVRSNASIQTWDG VLQGERLLTMSCSDKI ARWNVVGIQGSLLSIF

        VEPIYFSSIILGSLYH GDHLSRAMYQRISNIE DLPPLYTLNKPLLSGI

SNAEARQPGKAPNFSV NWTVGDSAIEVINATT GKDELGRASRLCKHAL

YCRWXaAACARQGSLPLT TLQDYQAQRVP

g4504601 86 MLLSQNAFIVRSLNLV LMVYISLVFGISYDSP DYTDESCTFKISLRNF

RSILSWELKNHSIVPT HYTLLYTIMSKPEDLK VVKNCANTRSFCDLT

DEWRSTHEAYVTVLEG FSGNTTLFSCSHNFWL AIDMSFEPPEFEIVGF

TNHINVMVKFPSIVEE ELQFDLSLVIEEQSEG IVKKHKPEIKGNMSGN

FTYIIDKLIPNTNYCV SVYLEHSDEQAVIKSP LKCTLLPPGQESESAE

SAKIGGIITVFLIALV LTSTIVTLKWIGYICL RNSLPKVLRQGLTKGW

NAVAIHRCSHNALQSE TPELKQSSCLSFPSSW DYKRASLCPSD

g4507277 87 MPLAAYCYLRVVGKGS YGEVTLVKHRRDGKQY VIKKLNLRNASSRERR

AAEQEAQLLSQLKHPN IVTYKESWEGGDGLLY IVMGFCEGGDLYRKLK

EQKGQLLPENQVVEWF VQIAMALQYLHEKHIL HRDLKTQNVFLTRTNI

IKVGDLGIARVLENHC DMASTLIGTPYYMSPE LFSNKPYNYKSDVWAL

GCCVYEMATLKHAFNA KDMNSLVYRIIEGKLP AMPRDYSPELAELIRT

        MLSKRPEERPSYRSIL RQPYIKRQISFFLEAT KIKTSKNNIKNGDSQS

KPFATVVSGEAESNHE VIHPQPLSSEGSQTYI MGEGKCLSQEKPRASG

          LLKSPASLKAHTCKQD LSNTTELATISSVNID ILPAKGRDSVSDGFVQ

ENQPRYLDASNELGGI CSISQVEEEMLQDNTK SSAQPENLIPMWSSDI

VTGEKNEPVKPLQPLI KEQKPKDQSLALSPKL ECSGTILAHSNLRLLG

SSDSPASASSRVAGITG VCHHAQDQVAGECIIE KQGRIHPDLQPHNSGS

EPSLSRQRRQKRREQT EHRGEKRQVRRDLFAF QESPPRFLPSPHPIVGK

VDVTSTQKEAENQRRV VTGSVSSSSRSSEMSSS KDRPLSARERRRLKQS

QEEMSSSGPSVRKASL SVAGPGKPQEEDQPLP ARRLSSDCSVTQERKQ

IHCLSEDELSSSSTSST DKSDGDYGEGKGQTNE INALVQLMTQTLKLDS

KESCEDVPVANPVSEF KLHRKYRDTLILHGKV AEEAEEIHFKELPSAI

MPGSEKIRRLVEVLRT DVIRGLGVQLLEQVYD LLEEEDEFDREVRLRE

HMGEKYTTYSVKARQL KFFEENMNF

g4507685 88 MMAALYPSTDLSGASS SSLPSSPSSSSSPNEVM ALKDVREVKEENTLNE

KLFLLACDKGDYYMVKKILEENSSGDLNINCVDVLGRNAVTITIENEN

            LDILQLLLDYGCQKLM ERIQNPEYSTTMDVAP VILAAHRNNYEILTML

LKQDVSLPKPHAVGCE CTLCSAKNKKDSLRHS RFRLDIYRCLASPALI

        MLTEEDPILRAFELSA DLKELSLVEVEFRNDY EELARQCKMFAKDLLA

QARNSRELEVILNHTS SDEPLDKRGLLEERMN LSRLKLAIKYNQKEFV

SQSNCQQFLNTVWFGQ MSGYRRKPTCKKIMTV LTVGIFWPVLSLCYLI

APKSQFGRIIHTPFMK FIIHGASYFTFLLLLN LYSLVYNEDKKNTMGP

                ALERIDYLLILWIIGM IWSDIKRLWYEGLEDF LEESRNQLSFVMNSLY

LATFALKVVAHNKFHD FADRKDWDAFHPTLVA EGLFAFANVLSYLRLF

                    FMYTTSSILGPLQISM GQMLQDFGKFLGMFLL VLFSFTIGLTQLYDKG

YTSKEQKDCVGIFCEQ QSNDTFHSFIGTCFAL FWYIFSLAHVAIFVTR

                                                                                             

EWKFARAKLWLSYFDD KCTLPPPFNIIPSPKT ICYMISSSLSKWICSHT

            SKGKVKRQNSLKEWRN LKQKRDENYQKVMCCL VHRYLTSMRQKMQSTD

QATVENLNELRQDLSK FRNEIRDLLGFRTSKY AMFYPRN

g4507687 89 MEGSPSLRRMTVMREK GRRQAVRGPAFMFNDR GTSLTAEEERFLDAAE

YGNIPVVRKMLEESKT LNVNCVDYMGQNALQL AVGNEHLEVTELLLKK

ENLARIGDALLLAISK GYVRIVEAILNHPGFA ASKRLTLSPCEQELQD

DDFYAYDEDGTRFSPD ITPIILAAHCQKYEVV HMLLMKGARIERPHDY

FCKCGDCMEKQRHDSF SHSRSRINAYKGLASP AYLSLSSEDPVLTALE

          LSNELAKLANIEKEFK NDYRKLSMQCKDFVVG VLDLCRDSEEVEAILN

GDLESAEPLEVHRHKA SLSRVKLAIKYEVKKF VAHPNCQQQLLTIWYE

NLSGLREQTIAIKCLV VLVVALGLPFLAIGYW IAPCSRLGKILRSPFM

KFVAHAASFIIFLGLL VFNASDRFEGITTLPN ITVTDYPKQIFRVKTT

QFTWTEMLIMVWVLGM MWSECKELWLEGPREY ILQLWNVLDFGMLSIF

                                                                         

WLPSDPQIISEGLYAI AVVLSFSRIAYILPAN ESFGPLQISLGRTVKD

IFKFMVLFIMVFFFAFM IGMFILYSYYLGAKVN AAFTTVEESFKTLFWS

IFGLSEVTSVVLKYDH KFIENIGYVLYGIYNV TMVVVLLNMLIAMINS

SYQEIEEDDSDVEWKFA RSKLWLSYFDDGKTLP PPFSLVPSPKSFVYFI

          MRIVNFPKCRRRRLQK DIEMGMGNSKSRLNLF TQSNSRVFESHSFNSI

LNQPTRYQQIMKRLIK RYVLKAQVDKENDEVN EGELKEIKQDISSLRY

          ELLEDKSQATEELAIL IHKLSEKLNPSMLRCE

g4885373 90 MSETVPPAPAASAAPE KPLAGKKAKKPAKAAA ASKKKPAGPSVSELIV

QAASSSKERGGVSLAA LKKALAAAGYDVEKNN SRIKLGIKSLVSKGTL

VQTKGTGASGSFKLNK KASSVETKPGASKVAT KTKATGASKKLKKATG

ASKKSVKTPKKAKKPA ATRKSSKNPKKPKTVK PKKVAKSPAKAKAVKP

KAAKARYTKPKTAKPK KAAPKKK

g5730102 91 MSQSPAFGPRRGSSPR GAAGAAARRNESQDYL LMDSELGEDGCPQAPL

PCYGYYPCFRGSDNRL AHRRQTVLREKGRRLA NRGPAYMFSDRSTSLS

            IEEERFLDAAEYGNIP VVRKMLEECHSLNVNC VDYMGQNALQLAVANE

HLEITELLLKKENLSR VGDALLLAISKGYVRI VEAILSHPAFAEGKRL

ATSPSQSELQQDDFYA YDEDGTRFSHDVTPII LAAHCQEYEIVHTLLR

KGARIERPHDYFCKCN DCNQKQKHDSFSHSRS RINAYKGLASPAYLSL

SSEDPVMTALELSNEL AVLANIEKEFKNDYKK LSMQCKDFVVGLLDLC

        RNTEEVEAILNGDVET LQSGDHGRPNLSRLKL AIKYEVKKFVAHPNCQ

QQLLSIWYENLSGLRQ QTMAVKFLVVLAVAIG LPFLALIYWFAPCSKM

GKIMRGPFMKFVAHAA SFTIFLGLLVMNAADR FEGTKLLPNETSTDNA

KQLFRMKTSCFSWMEM LIISWVIGMIWAECKE IWTQGPKEYLFELWNM

LDFGMLAIFAASFIAR FMAFWHASKAQSIIDA NDTLKDLTKVTLGDNV

KYYNLARIKWDPSDPQ IISEGLYAIAVVLSFS RIAYILPANESFGPLQ

ISLGRTVKDIFKFMVI FIMVFVAFMIGMFNLY SYYIGAKQNEAFTTVE

ESFKTLFWAIFGLSEV KSVVINYNHKFIENIG YVLYGVYNVTMVIVLL

NMLIAMINSSFQEIED DADVEWKFARAKLWFS YFEEGRTLPVPFNLVP

         SPKSLFYLLLKLKKWI SELFQGHKKGFQEDAE MNKINEEKKLGILGSH

EDLSKLSLDKKQVGHN KQPSIRSSEDFHLNSF NNPPRQYQKIMKRLIK

RYVLQAQIDKESDEVN EGELKEIKQDISSLRY ELLEEKSQNTEDLAEL

IRELGEKLSMEPNQEE TNR

g5802234 93 SRDPPASASQVTGIR

g6005868 94 MASLSRALRVAAAHPR QSPTRGMGPCNLSSAA GPTAEKSVPYQRTLKE

GQGTSVVAQGPSRPLP STANVVVIGGGSLGCQ TLYHLAKLGMSGAVLL

ERERLTSGTTWHTAGL LWQLRPSDVEVELLAH TRRVVSRELEEETGLH

TGWIQNGGLFIASNRQ RLDEYKRLMSLGKAYG VESHVLSPAETKTLYP

                  LMNVDDLYGTLYVPHD GTMDPAGTCTTTLARAA SARGAQVIENCPVTGI

RVWTDDFGVRRVAGVE TQHGSIQTPCVVNCAG VWASAVGRMAGVKVPL

VAMHHAYVVTERIEGI QSFTLLPTLEYSGTVS AHCNLRLPGSSNSRAS

ASHVAGIKCARHHTRL IFFCILVETEFHHVAK AGLELLSSGNPPISDF

QSARITGVSHHA

g604969 95 LLWVLLWATVLGLLCQ RLAARLGVVTGKDLGE VCHLYYPKSESRSVAQ

SGVQWCDVSSLQPLPP RCPAPSSG

g6650810 96 METESGSVAQAGVQWH NLGSLQPPPSRLKQLS YLSLPSSWDYRCTPPH

PANFLYFNRDGISPCC PGWSPTPKLTQSTHLG LSKC

g6665594 97 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEFVAQP NCQQLLASRWYDEFPG WRRRHWAVKMVTCFII

GLLFPVFSVCYLIAPK SPLGLFIRKPFIKFIC HTASYLTFLFLLLLAS

QHIDRSDLNRQGPPPT IVEWMILPWVLGFIWG EIKQMWDGGLQDYIHD

WWNLMDFVMNSLYLAT ISLKIVAFVKYSALNP RESWDMWHPTLVAEAL

            FAIANIFSSLRLISLF TANSHLGPLQISLGRM LLDILKFLFIYCLVLL

AFANGLNQLYFYYEET KGLTCKGIRCEKQNNA FSTLFETLQSLFWSIF

              GLINLYVTNVKAQHEF TEFVGATMFGTYNVIS LVVLLNMLIAMMNNSY

QLIADHADIEWKFART KLWMSYFEEGGTLPTP FNVIPSPKSLWYLIKW

IWTHLCKKKMRRKPES FGTIGRRAADNLRRHH QYQEVMRNLVKRYVAA

MIRDAKTEEVARQQAA GPLERNIQLESRGLAS RGDLSIPGLSEQCVLV

DHRERNTDTLGLQVGK RVCPFKSEKVVVEDTV PIIPKEKHAKEEDSSI

DYDLNLPDTVTHEDYV TTRL

g6665596 98 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEFVAQP NCQQLLASRWYDEFPG WRRRHWAVKMVTCFII

GLLFPVFSVCYLIAPK SPLGLFIRKPFIKFIC HTASYLTFLFLLLLAS

QHIDRSDLNRQGPPPT IVEWMILPWVLGFIWG EIKQMWDGGLQDYIHD

WWNLMDFVMNSLYLAT ISLKIVAFVKYSALNP RESWDMWHPTLVAEAL

            FAIANIFSSLRLISLF TANSHLGPLQISLGRM LLDILKFLFIYCLVLL

AFANGLNQLYFYYEET KGLTCKGIRCEKQNNA FSTLFETLQSLFWSIF

              GLINLYVTNVKAQHEF TEFVGATMFGTYNVIS LVVLLNMLIAMMNNSY

QLIARRAADNLRRHHQ YQEVMRNLVKRYVAAM IRDAKTEEGLTEENFK

ELKQDISSFRFEVLGL LRGSKLSTIQSANASK ESSNSADSDEKSDSEE

EVARQQAAGPLERNIQ LESRGLASRGDLSIPG LSEQCVLVDHRERNTD

          TLGLQVGKRVCPFKSE KVVVEDTVPIIPKEKH AKEEDSSIDYDLNLPD

TVTHEDYVTTRL

g6690167 99 MRTKSEREIHLCVLGF FXFFFETGSRSVAQAG VQRHSHGSLQPRPPGL

IQFSHLSSLPSSWDYRH APPHLVNFL

g6690252 100 RFFFFFFEESRSFAQ AGVQWRYLGSLQPPPP GFTRFSCLSLLSSWDY

RRPPPRPANFLYF

g7243280 101 ELSFPLLSLDFGAHQG LGSADMGDMKTPDFDD LLAAFDIPDIDANEAI

          HSGPEENEGPGGPGKP EPGVGSESEDTAAASA GDGPGVPAQASDHGLP

PPDISVVSVIVKNTVC PEQSEALAGGSAGDGA QAAGVTKEGPVGPHRM

QNGFGSPEPSLPGTPH SPAPPSGGTWKEKGME GKTPLDLFAHFGPEPG

DHSDPLPPSAPSPTR GALTPPPFPSSFELAQ ENGPGMQPPVSSPPLG

                ALKQESCSPHHPQVLA QQGSGSSPKATDIPAS ASPPPVAGVPFFKQSP

GHQSPLASPKVPVCQP LKEEDDDEGPVDKSSP GSPQSPSSGAEAADED

SNDSPASSSSRPLKVR IKTIKTSCGNITRTVT QVPSDPDPPALAEGA

FLAEASLLKLSPATPT SEGPKVVSVQLGDGTR LKGTVLPVATIQNAST

AMLMAASVARKAVVLP GGTATSPKMIAKNVLG LVPQALPKADGRAGLG

TGGQKVNGASVVMVQP SKTATGPSTGGGTVIS RTQSSLVEAFNKILNS

KNLLPAYRPNLSPPAE AGLALPPTGYRCLECG DAFSLEKSLARHYDRR

SMRIEVTCNHCARRLV FFNKCSLLLHAREHKD KGLVMQCSHLVMRPVA

LDQMVGQPDITPLLPV AVPPVSGPLALPALGK GEGAITSSAITTVAAE

             APVLPLSTEPPAAPAT SAYTCFRCLECKEQCR DKAGMAAHFQQLGPPA

          PGATSNVCPTCPMMLP NRCSFSAHQRMHKNRP PHVCPECGGNFLQANF

QTHLREACLHVSRRVG YRCPSCSVVFGGVNSI KSHIQTSHCEVFHKCP

ICPMAFKSGPSAHAHL YSQHPSFQTQQAKLIY KCAMCDTVFTHKPLLS

SHFDQHLLPQRVSVFK CPSCPLLFAQKRTMLE HLKNTHQSGRLEETAG

KGAGGALLTPKTEPEE LAVSQGGAAPATEESS SSSEEEEVPSSPEPPR

PAKRPRRELGSKGLKG GGGGPGGWTCGLCHSW FPERDEYVAHMKKEHG

KSVKKFPCRLCERSFC SAPSLRRHVRVNHEGI KRVYPCRYCTEGKRTF

SSRLILEKHVQVRHGL QLGAQSPGRGTTLARG SSARAQGPGRKRRQSS

DSCSEPDSTTPPAKS PRGGPGSGGHGPLRYR SSSSTEQSLMMGLRVE

DGAQQCLDCGLCFASP GSLSRHRFISHKKRRG VGKASALGLGDGEEEA

        PPSRSDPDGGDSPLPA SGGPLTCKVCGKSCDS PLNLKTHFRTHGMAFI

RARQGAVGDN

g7305597 102 MSQSPRFVTRRGGSLK AAPGAGTRRNESQDYL LMDELGDDGYPQLPLP

PYGYYPSFRGNENRLT HRRQTILREKGRRLAN RGPAYMFNDHSTSLSI

              EEERFLDAVEYGNIPV VWKMLEECHSLNVNCV DYMGQNALQLAVANEH

          LEITELLLKKENLSRV GDALLLAISKGYVRIV EAILNHPSFAEGKRLA

            TSPSQSELQQDDFYAY DEDGTRFSHDVTPIIL AAHCQEYEIVHTLLRK

GARIERPHDYFCKCTE CSQKQKHDSFSHSRSR INAYKGLASPAYLSLS

SEDPVMTALELSNELA VLANIEKEFKNDYRKL SMQCKDFVVGLLDLCR

        NTEEVEAILNGDAETR QPGDFGRPNLSRLKLA IKDEVKKFVAHPNCQQ

QLLSIWYENLSGLRQQ TMAVKFLVVLAVAIGL PFLALIYWCAPCSKMG

KILPRPFMKFVAHAAS FTIFLGLLVMNAADRF EGTKLLPNETSTDNAR

QLFRMKTSCFSWMEML IISWVIGMIWAECKEI WTQGPKEYLFELWNML

                                                             

YYNLARIKWDPTDPQI ISEGLYAIAVVLSFSR IAYILPANESFGPLQI

        SLGRTVKDIFKFMVIF IMVFVAFMIGMFNLYS YYIGAKQNEAFTTVEE

SFKTLFWAIFGLSEVK SVVINYNHKFIENIGY VLYGVYNVTMVIVLLN

MLIAMINSSFQEIEDD ADVEWKFARAKLWFSY FEEGRTLPVPFNLYPS

PKSLLYLLLLKFKKWMC ELIQGQKQGFQEDAEM NKRNEEKKFGISGSHE

            DLSKFSLDKNQLAHNK QSSTRSSEDYHLNSFS NPPRQYQKIMKRLIKR

YVLQAQIDKESDEVNE GELKEIKQDISSLRYE LLEEKSQNSEDLAELI

RKLGERLSLEPKLEES RR

g7512448 103 GFLPATKNLLNEKNHG VLHTSVVLLTEMCERS PDMLAHFRENEKLVPQ

LVRILKNLIMSGYSPG HDVSGISDPFLQVRIL RLLRILGRNDDDSSEA

MNDILAQVATNTETSK NVGNAILYETVLTIMD IKSESGLRVLAINILG

RFLLNNDKNIRYVALT SLLKTVQTDHNAVQRH RSTIVDCLKDLDVSIK

RRAMELSFALVNGNNI RGMMKELLYFLDSCEP EFKADCASGIFLAAEK

YAPSKRWHIDTIMRVL TTAGSYVRDDAVPNLI QLITNSVEMHAYTVQR

                LYKAILGDYSQQPLVQ VAAWCIGEYGDLLVSG QCEEEEPIQVTEDEVL

DILESVLISNMSTSVT RGYALTAIMKLSTRFT CTVNRIKKVVSIYGSS

IDVELQRRAVEYNALF KKYDHMRSALLERMPV MEKVTTNGPTEIVQTN

GETEPAPLETKPPPSG PQPTSQANDLLDLLGG NDITPVIPTAPTSKPS

SAGGELLDLLGDINLT GSHSVSQAGVQWDYLG SLQPLPPAFR

g7522630 104 MWPNGSSLGPCFRPTN ITLEERRLIASPWFAA SFCVVGLASNLLALSV

LAGARQGGSHTRSSFL TFLCGLVLTDFLGLLV TGTIVVSQHAALFEWH

AVDPGCRLCRFMGVVM IFFGLSPLLLGAAMAS ERYLGITRPFSRPAVA

SQRRAWATVGLVWAAA LALGLLPLLGVGRYTV QYPGSWCFLTLGAESG

                                                                                 

VEMMAQLLGIMVVASV CWLPLLVFIAQTVLRN PPAMSPAGQLSRTTEK

      ELLIYLRVATWNQILD PWVYILFRRAVLRRLQ PRLSTRPRRSLTLWPS

                                                                                       

DLLAGVQLLPFEPPTG KALSRKD

g7669477 105 MDIEDEENMSSSSTDV KENRNLDNVSPKDGST PGPGEGSQLSNGGGGG

          PGRKRPLEEGSNGHSK YRLKKRRKTPGPVLPK NALMQLNEIKPGLQYT

LLSQTGPVHAPLFVMS VEVNGQVFEGSGPTKK KAKLHAAEKALRSFVQ

          FPNASEAHLAMGRTLS VNTDFTSDQADFPDTL FNGFETPDKAEPPFYV

GSNGDDSFSSSGDLSL SASPVPASLAQPPLPV LPPFPPPSGKNPVMIL

NELRPGLKYDFLSESG ESHAKSFVMSVVVDGQ FFEGSGRNKKLAKARA

AQSALAAIFNLHLDQT PSRQPIPSEGLQLHLP QVLADAVSRLVLGKFG

DLTNDNFSSPHARRKVL AGVVMTTGTDVKDAKV ISVSTGTKCINGEYMS

                  DRGLALNDCHAEIISR RSLLRFLYTQLELYLN NKDDQKRSIFQKSERG

            GFRLKENVQFHLYIST SPCGDARIFSPHEPIL EGSRSYTQAGVQWCNH

GSLQPRPPGLLSDPST STFQGAGTTEPADRHP NRKARGQLRTKIESGE

GTIPVRSNASIQTWDG VLQGERLLTMSCSDKI ARWNVVGIQGSLLSIF

        VEPIYFSSIILGSLYH GDHLSRAMYQRISNIE DLPPLYTLNKPLLSGI

SNAEARQPGKAPNFSV NWTVGDSAIEVINATT GKDELGRASRLCKHAL

YCRWMRVHGKVPSHLL RSKITKPNVYHESKLA AKEYQAAKARLFTAFI

                                             

g7669479 106 MDIEDEENMSSSSTDV KENRNLDNVSPKDGST PGPGEGSQLSNGGGGG

          PGRKRPLEEGSNGHSK YRLKKRRKTPGPVLPK NALMQLNEIKPGLQYT

LLSQTGPVHAPLFVMS VEVNGQVFEGSGPTKK KAKLHAAEKALRSFVQ

          FPNASEAHLAMGRTLS VNTDFTSDQADFPDTL FNGFETPDKAEPPFYV

GSNGDDSFSSSGDLSL SASPVPASLAQPPLPV LPPFPPPSGKNPVMIL

NELRPGLKYDFLSESG ESHAKSFVMSVVVDGQ FFEGSGRNKKLAKARA

AQSALAAIFNLHLDQT PSRQPIPSEGLQLHLP QVLADAVSRLVLGKFG

DLTNDNFSSPHARRKVL AGVVMTTGTDVKDAKV ISVSTGTKCINGEYMS

                  DRGLALNDCHAEIISR RSLLRFLYTQLELYLN NKDDQKRSIFQKSERG

            GFRLKENVQFHLYIST SPCGDARIFSPHEPIL EGSRSYTQAGVQWCNH

GSLQPRPPGLLSDPST STFQGAGTTEPADRHP NRKARGQLRTKIESGE

GTIPVRSNASIQTWDG VLQGERLLTMSCSDKI ARWNVVGIQGSLLSIF

        VEPIYFSSIILGSLYH GDHLSRAMYQRISNIE DLPPLYTLNKPLLSGI

SNAEARQPGKAPNFSV NWTVGDSAIEVINATT GKDELGRASRLCKHAL

YCRWMRVHGKVPSHLL RSKITKPNVYHESKLA AKEYQAAKVH

g7770147 107 MEVLLFLFIFETESCS VIRLECSGSLQPPPPR FKQFSCLSLPSSWDYR

          CPPPCPINFCIFGTDR VSPCWPGWSRSR

g7706747 108 MAQFYYKRNVNAPYRD RIPLRIVRAESELSPS EKAYLNAVEKGDYASV

KKSLEEAEIYFKININ CIDPLGRTALLIAIEN ENLELIELLLSFNVYV

GDALLHAIRKEVVGAV ELLLNHKKPSGEKQVP PILLDKQFSEFPDIT

            PIILAAHTNNYEIIKL LVQKGVSVPRPHEVRC NCVECVSSSSDVDSLRH

SRSRLNIYKALASPSL IALSSEDPFLTAFQLS WELQELSKVENEFKSE

YEELSRQCKQFAKDLL DQTRSSRELEIILNYR DDNSLIEEQSGNDLAR

LKLAIKYRQKEFVAQP NCQQLLASRWYDEFPG WRRRHWAVKMVTCFII

GLLFPVFSVCYLIAPK SPLGLFIRKPFIKFIC HTASYLTFLFLLLLAS

QHIDRSDLNRQGPPPT IVEWMILPWVLGFIWG EIKQMWDGGLQDYIHD

WWNLMDFVMNSLYLAT ISLKIVAFVKYSALNP RESWDMWHPTLVAEAL

            FAIANIFSSLRLISLF TANSHLGPLQISLGRM LLDILKFLFIYCLVLL

AFANGLNQLYFYYEET KGLTCKGIRCEKQNNA FSTLFETLQSLFWSIF

              GLINLYVTNVKAQHEF TEFVGATMFGTYNVIS LVVLLNMLIAMMNNSY

QLIADHADIEWKFART KLWMSYFEEGGTLPTP FNVIPSPKSLWYLIKW

IWTHLCKKKMRRKPES FGTIGRRAADNLRRHH QYQEVMRNLVKRYVAA

MIRDAKTEEGLTEENF KELKQDISSFRFEVLG LLRGSKLSTIQSANAS

KESSNSADSDEKSDSE GNSKDKKKNFSLFDLT TLIHPRSAAIASERHN

          ISNGSALVVQEPPREK QRKVNFVTDIKNFGLF HRRSKQNAAEQNANQI

FSVSEEVARQQAAGPL ERNIQLESRGLASRGD LSIPGLSEQCVLVDHR

ERNTDTLGLQVGKRVC PFKSEKVVVEDTVPII PKEKHAKEEDSSIDYD

LNLPDTVTHEDYVTTR L

g8922960 109 MESYSVTQAGVQWHEL CSLQPSPPRFREMCIE QDGRVHLTVVYFGKEE

        INEVKGVLENTSKAAN FRNFTFIQLNGEFSRG KGLDVGARFWKGSNVL

          LFFCDVDIYFTSEFLN TCRLNTQPGKKVFYPV LFSQYNPGIIYGHHDA

VPPLEQQLVIKKETGF WRDFGFGMTCQYRSDF INIGGFDLDIKGWGGE

                    DVHLYRKYLHSNLIVV RTPVRGLFHLWHEKRC MDELTPEQYKMCMQSK

AMNEASHGQLGMLVFR HEIEAHLRKQKQKTSS KKT

g8923251 110 MDITLVRKELQELQNL YKQNSTHTAQQAELIQ QLQVLNMDTQKVLRNQ

EDVHTAESISYQKLYN ELHICFETTKSNEAML RQSVTNLQDQLLQKEQ

ENAKLKEKLQESQGAP LPLPQESDPDYSAQVP HRPSLSSLETLMVSQK

SEIEYLQEKLKIANEK LSENISANKGFSRKSI MTSAEGKHKEPPVKRS

RSLSPKSSFTDSEELQ KLRKAERKIENLEKAL QLKSQENDELRDAHEK

RKERLQMLQTNYRAVK EQLKQWEEGSGMTEIR KIKRADPQQLRQEDSD

AVWNELAYFKRENQEL MIQKMNLEEELDELKV HISIDKAAIQELNRCV

AERREEQLFRSGEDDE VKRSTPEKNGKEMLEQ TLQKVIELENRLKSFE

KRSRKLKEGNKKLMKE NDFLKSLLKQQQEDTE TREKELEQIIKGSKDV

EKENTELQVKISELET EVTSLRRQVAEANALR NENEELINPMEKSHQS

ADRAKSEMATMKVRSG RYDCKTTMTKVKFKAA KKNCSVGRHHTVLNHS

IKVMSNVFENLSKDGW EDVSESSSSEAQTSQ TLGTIIVETSQKISPT

                                                               

QKKNCKMQKSSHTAVP TRVNREKYKNITAQKS SSNIILLRERIISLQQ

QNSVLQNAKKTAELSV KEYKEVNEKLLHQQQV SDQRFQTSRQTIKKLN

LDLAGLRKEKEDLLKK LESSSEITSLAEENSQ VTFPRIQVTSLSPSRS

MDLEMKQLQYKLKNAT NELTKQSSNVKTLKFE LLAKEEHIKEMHEKIS

RMERDITMKRHLIEDL KFRQKVNLESNKSFSE MLQNLDKKVKTLTEEC

SNKKVSIDSLKQRLNV AVKEKSQYEQMYQKSK EELEKKDLKLTLLVSR

ISETESAMAEIETAAS KQLQELALQSEQVLEG AQKTLLLANEKVEEFT

          TFVKALAKELQNDVHV VRRQIRELKKMKKNRD ACKTSTHKAQTLAASI

LNISRSDLEILDTED QVEIEKTKIDAENDKE WMLYIQKLLEGQSLTL

SPRLKCNGAIMAHQNL RLPDSSSSASAS

g8923273 111 MKVVPEKNAVRILWGR ERGARAMGAQRLLQEL VEDKTRWMKWEGKRVE

        LPDSPRSTFLLAFSPD RTLLASTHVNHNIYIT EVKTGKCVHSLIGHRR

TPWCVTFHPTISGLIA SGCLDGEVRIWDLHGG SESWFTDSNNAIASLA

FHPTAQLLLIATANEI HFWDRSRREPFAVVKT ASEMERVRLVRFDPLG

            HYLLTAIVNPSNQQGD DEPEIPIDGTELSHYR QRALLQSQPVRRTPLL

HNFLHMLSSRSSGIQT EPFHPPEQASSTQQDQ GLLNRPSAFSTVQSST

AGNTLRNLSLGPTRRS LGGPLSSHSPRYHREI APGLTGSEWTRTVLSL

NSRSEAESMPPPRTSA SSVSLLSVLRQQEGGS QASVYTSATEGRGFPA

SGLATESDGGNGSSQN NSGSIRHELQCDLRRF FLEYDRLQELDQSLSG

EAPQTQQAQEMLNNNI ESERPGPSHQPTPHSS ENNSNLSRGHLNRCRA

CHNLLTFNNDTLRWER TTPNYSSGEASSSWQV PSSFESVPSSGSQLPP

          LERTEGQTPSSSRLEL SSSASPQEERTVGVAF NQETGHWERIYTQSSR

SGTVSQEALHQDMPEE SSEEDSLRRRSLALSP RLEYSGAILAHCKLRL

          PGSCHSPASASQVAGT TGAHHHARLIFAFLVE MEFHHVSQAGLELLTS

GDLPTSASQVLGLQA

g8923360 112 MVHSPRSLVANPSQVL FFLSFLFFFFLRQSFA LVAQAGVQWRNLGSLQ

                  PPPPGFKQFSCLSLLS SWDYRHAPPCPAYFVF LVDMGFPHVGQTGLEL

LTSGDPASASQSAGI TGGSHRAQPTSSNPYG IVFFFLPVKTFSGMSQ

EAGDCRET

g8923452 113 MPTATGLTLLTSASSA ISDPGGEVSAPWGGLR TWTQPLRCWERLLPPP

GDPRTVAENTQQDECG LPGSCPARPLSRKPEC GREGILPCCSSSAWPE

GSFRPFQMNLFSFLSFFFFLFFFFLRWSLTLSPRLECSSAISAHCNLRL

          PGSSNSPALASQVAGI TGICHHARQIFVFLVE TGFCHVGQAGLELLIS

GDSPASAFQSAGIIGV SHRARPGSVFLARSEE SLYLRPGQQSQEVKV

g8923454 114 MLLVDADQPEPMRSGA RELALFLTPEPGAEAK EVEETIEGMLLRLEEF

CSLADLIRSDTSQILE ENIPVLKAKLTEMRGI YAKVDRLEAFVKMVGH

HVAFLEADVLQAERDH GAFPQALRRWLGSAGL PSFRNVECSGTIPARC

NLRLPGSSSPASASQ VAGITEVTCTGARDVR AAHTV

g8923691 115 MSVYSGKVLLQTTPPH VIGQLDKLIREVSTLD GVLEVRNEHFWTLGFG

SLAGSVHVRIRRDANE QMVLAHVTNRLYTLVS TLTVQIFKDDWIRPAL

LSGPVAANVLNFSDHH VIPMPLLKGTDGLNPY VHFLWKINFFLFFDME

SLSVAQAGVQWHDLGS LQPHLPGSSSNSACLSL PSSWDYRHAPPHLPNF

CIISKDGVLPCWPCWS

g8924071 116 MESRSVAQTGVHWHNL SSLQPLPPRFKQFSCL SLRSSWDYTHLPPCLA

NFFVFLVETAFRHVGQ AGLKLLTSGDQPTSAS QSAGITGISHRTQPVG

RFLITDSIFLFVTDLL KFSISS

g8924204 117 MSKVLGGPFSKGHTAS DKYFQIFHNISFFETE SCSVAQAGVQWCNLGS

LQALPPRFTPFSCLSL PSSWDYRHPPPCPDNV FVFSVETGFHCVSQDG

LNLLTL

g8980667 118 MAQGTLIRVTPEQPTH AVCVLGTLTQLDISSS APEDCTSFSINASPGV

VVDIAHSPPAKKKSTG SSTWPLDPGVEVTLTM KAASGSTGDQKVQISY

YGPKTPVKALLYLTA VDGVSPCHPGWSAMHD LAHCNLRLQVQAILCF

SVPSSWTTGACHHAWL IFVFLVEMEFHHVGQA GLELLTSGDLPASGSQ

SARITGMNHCARPSIF LILKYL

g9716913 119 MSQSPAFGPRRGSSPR GAAGAAARRNESQDYL LMDSELGEDGCPQAPL

PCYGYYPCFRGSDNRL AHRRQTVLREKGRRLA NRGPAYMFSDRSTSLS

            IEEERFLDAAEYGNIP VVRKMLEECHSLNVNC VDYMGQNALQLAVANE

HLEITELLLKKENLSR VGDALLLAISKGYVRI VEAILSHPAFAEGKRL

ATSPSQSELQQDDFYA YDEDGTRFSHDVTPII LAAHCQEYEIVHTLLR

KGARIERPHDYFCKCN DCNQKQKHDSFSHSRS RINAYKGLASPAYLSL

SSEDPVMTALELSNEL AVLANIEKEFKNDYKK LSMQCKDFVVGLLDLR

          RNTEEVEAILNGDVET LQSGDHGRPNLSRLKL AIKYEVKKMGKIMRGP

                                FMKFVAHAASFTIFLG LLVMNAADRFEGTKLL PNETSTDNAKQLFRMK

TSCFSWMEMLIISWVI GMIWAECKEIWTQGPK EYLFELWNMLDFGMLA

IFAASFIARFMAFWHA SKAQSIIDANDTLKDL TKVTLGDNVKYYNLAR

IKWDPSDPQIISEGLY AIAVVLSFSRIAYTLP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYIGAK QNEAFTTVEESFKTLF

          WAIFGLSEVKSVVINY NHKFIENIGYVLYGVY NVTMVIVLLNMLIAMI

NSSFQEIEDDADVEWK FARAKLWFSYFEEGRT LPVPFNLVPSPKSLFY

LLLKLKKWISELFQGH KKGFQEDAEMNKINEE KKLGILGSHEDLSKLS

LDKKQVGHNKQPSIRS SEDFHLNSFNNPPRQY QKIMKRLIKRYVLQAQ

IDKESDEVNEGELKEI KQDISSLRYELLEEKS QNTEDLAELIRELGEK

LSMEPNQEETNR

g9966865 120 MLRNSTFKNMQRRHTT LREKGRRQAIRGPAYM FNEKGTSLTPEEERFL

DSAEYGNIPVVRKMLE ESKTLNFNCVDYMGQN ALQLAVGNEHLEVTEL

          LLKKENLARVGDALLL AISKGYVRIVEAILNH PAFAQGQRLTLSPLEQ

ELRDDDFYAYDEDGTR FSHDITPIILAAHCQE YEIVHILLLKGARIER

PHDYFCKCNECTEKQR KDSFSHSRSRMNAYKG LASAAYLSLSSEDPVL

            TALELSNELARLANIE TEFKNDYRKLSMQCKD FVVGVLDLCRDTEEVE

AILNGDVNFQVWSDHH RPSLSRIKLAIKYEVK KFVAHPNCQQQLLTMW

YENLSGLR(QQSIAVKF LAVFGVSI)GLPFLAIA YWIAPCSKLGRTLRSP

                              FMKFVAHAVSFTIFLG LLVVNASDRFEGVKTL PNETFTDYPKQIFRVK

              TTQFSWTEMLIMKWVL GMIWSECKEIWEEGPR EYVLHLWNLLDFGMLS

IFVASFTARFMAFLKA TEAQLYVDQHVQDDTL HNVSLPPEVAYFTYAR

DKWWPSDPQIISEGLY AIAVVLSFSRIAYILP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYRGAK YNPAFTTVEESFKTLF

                                                                                             

NNSYQEIEEDADVEWK FARAKLWLSYFDEGRT LPAPFNLVPSPKSFYY

LIMRIKMCLIKLCKSK AKSCENDLEMGMLNSK FKKTRYQAGMRNSENL

            TANNTLSKPTRYQKIM KRLIKRYVLKAQVDRE NDEVNEGELKEIKQDI

SSLRYELLEEKSQATG ELADLIQQLSEKFGKN LNKDHLRVNKGKDI

g9967846 121 MDDGCPQLPLPPHGYY PSLRGTDNRLTHRRQT VLREKGRRLANRGPAY

                                                                

NALQLAVANEHLEITE LLLKKENLSRVGDALL LAISKGYVRIVEAILS

HPAFAEGKRLATSPSQ SELQQDDFYAYDEDGT RFSHDVTPIILAAHCQ

EYEIVHTLLRKGARIE RPHDYFCKCSECNQKQ KHDSFSHSRSRINAYK

          GLASPAYLSLSSEDPV MTALELSNELAVLANI EKEFKNDYKKLSMQCK

DFVVGLLDLCRNTEEV EAILNGDVETCQSGDQ GRPNLSRLKLAIKYEV

KKFVAHPNCQQQLLSI WYENLSGLRQQTMAVK FLVVLGVAIGLPFLAL

IYWCAPCSKMGKIMRG PFMKFVAHAASFTIFL GLLVMNAADRFEGTKL

RPNETSTDNAKQLFRM KTSCFSWMEMLIISWV IGMIWAECKEIWAQGP

                                                     

LTKVTLGEDVKYYNLA RIKWDPSDPQIISEGL YAIAVVLSFSRIAYIL

PANESFGPLQISLGRT VKDIFKFMVIFIMVFVAFMIGMFNLYSYYIGA

KQNEAFTTVEESFKTL FWAIFGLSEVKSVVIN YNHKFIENIGYVLYGV

YNVTMVIVLLNMLIAM INSSFQEIEDDADVEW KFARAKLWFSYFEEGR

TLPPFNLVPSPKSLL YLLLKFKKWGFELFQG HKKAFQEDAEMNKRNE

EKKFGILGSHEDLSKL SVDKKQLGQNKQSSIR SSEDFHLNSFNNPPRQ

YQKIMKRLIKRYVLQA QIDKESDEVNEGELKE IKQDISSLRYELLEEK

SQNTEDLAELIRKLGE KLSSEPKQEEINR

g9967886 122 MFNDHSTTLSIEEERF LDAAEYGNIPVVRKML EECLSLNVNCVDYMGQ

NALQLAVANEHLEITE LLLKKENLSRVGDALL LAISKGYVRIVEAILS

HPAFAEGKRLATSLSQ SELQQDDFYAYDEDGT RFSHDVTPIILAAHCQ

EYEIVHTLLRKGARIE RPHDYFCKCSECNQKQ KHDSFSHSRSRINAYK

          GLASPAYLSLSSEDPV MTALELSNELAVLANI EKEFKNDYKKLSMQCK

DFVVGLLDLCRNTEEV EAILNGDIETCQPGDQ GRPNLSRLKLAIKYEV

KKFVAHPNCQQQLLSI WYENLSGLRQQTMAVK FLVVLGVAIGLPFLAL

IYWCAPCSKMGKIMRG PFMKFVAHAASFTIFL GLLVMNAADRFEGTKL

RPNETSTDNAKQLFRM KTSCFSWMEMLIISWV IGMVWAECKEIWAQGP

                                                     

LTKVTLGEDVKYYNLA RIKWDPSDPQIISEGL YAIAVVLSFSRIAYIL

PANESFGPLQISLGRT VKDIFKFMVIFIMVFVAFMIGMFNLYSHYIGA

KQNEAFTTYVISDVLT MEIAD

g9967888 123 MDDGCPQLPLPPHGYY PSLRGTDNRLTHRRQT VLREKGRRLANRGPAY

                                                                

NALQLAVANEHLEITE LLLKKENLSRVGDALL LAISKGYVRIVEAILS

HPAFAEGKRLATSPSQ SELQQDDFYAYDEDGT RFSHDVTPIILAAHCQ

EYEIVHTLLRKGARIE RPHDYFCECSECNQKQ KHDSFSHSRSRINAYK

          GLASPAYLSLSSEDPV MTALELSNELAVLANI EKEFKNDYKKLSMQCK

DFVVGLLDLCRNTEEV EAILNGDVETCQPGDQ GRPNLSRLKLAIKYEV

KKFVAHPNCQQQLLSI WYENLSGLRQQTMAVK FLVVLGVAIGLPFLAL

IYWCAPCSKMGKIMRG PFMKFVAHAASFTIFL GLLVMNAADRFEGTKL

RPNETSTDNAKQLFRM KTSCFSWMEMLIISWV IARIKWDPSDPQIISE

GLYAIAVVLSFSRIAY ILPANESFGPLQISLG RTVKDIFKFMVIFIMV

FVAFMIGMFHLYSYYI GAKQNEAFTTVEESFK TLFWAIFGLSEVKSVV

INYNHKFIENIGYVLY GVYNVTMVIVLLNMLI AMINSSFQEIEDDADV

EWKFARAKLWFSYFEE GRTLPVPFNLVPSPKS LLYLLLKFKKWGFELF

QGHKKAFQEDAEMNKR NEEKKFGILGSHEDLS KLSVDKKQLGQNKQSS

IRSSEDFHLNSFNNPP RQYQKIMKRLIKRYVL QAQIDKESDEVNEGEL

KEIKQDISSLRYELLE EKSQNTEDLAELIRKL GEKLSSEPKQEEINR

g9716913 124 MSQSPAFGPRRGSSPR GAAGAAARRNESQDYL LMDSELGEDGCPQAPL

PCYGYYPCFRGSDNRL AHRRQTVLREKGRRLA NRGPAYMFSDRSTSLS

            IEEERFLDAAEYGNIP VVRKMLEECHSLNVNC VDYMGQNALQLAVANE

HLEITELLLKKENLSR VGDALLLAISKGYVRI VEAILSHPAFAEGKRL

ATSPSQSELQQDDFYA YDEDGTRFSHDVTPII LAAHCQEYEIVHTLLR

KGARIERPHDYFCKCN DCNQKQKHDSFSHSRS RINAYKGLASPAYLSL

SSEDPVMTALELSNEL AVLANIEKEFKNDYKK LSMQCKDFVVGLLDLR

          RNTEEVEAILNGDVET LQSGDHGRPNLSRLKL AIKYEVKKMGKIMRGP

                                FMKFVAHAASFTIFLG LLVMNAADRFEGTKLL PNETSTDNAKQLFRMK

TSCFSWMEMLIISWVI GMIWAECKEIWTQGPK EYLFELWNMLDFGMLA

IFAASFIARFMAFWHA SKAQSIIDANDTLKDL TKVTLGDNVKYYNLAR

IKWDPSDPQIISEGLY AIAVVLSFSRIAYTLP ANESFGPLQISLGRTV

KDIFKFMVIFIMVFVA FMIGMFNLYSYYIGAK QNEAFTTVEESFKTLF

          WAIFGLSEVKSVVINY NHKFIENIGYVLYGVY NVTMVIVLLNMLIAMI

NSSFQEIEDDADVEWK FARAKLWFSYFEEGRT LPVPFNLVPSPKSLFY

LLLKLKKWISELFQGH KKGFQEDAEMNKINEE KKLGILGSHEDLSKLS

LDKKQVGHNKQPSIRS SEDFHLNSFNNPPRQY QKIMKRLIKRYVLQAQ

IDKESDEVNEGELKEI KQDISSLRYELLEEKS QNTEDLAELIRELGEK

LSMEPNQEETNR

The NTP peptides, related proteins, related peptides and fragments thereof, variants, derivatives, homologues and mimetics of the present invention can be prepared by methods known to those skilled in the art, such as recombinant DNA techniques, protein synthesis and isolation of naturally occurring NTP peptides, related proteins, related peptides and fragments, variants, derivatives and homologues thereof.

NTP peptides, related proteins, or related peptides can be prepared by well-known methods of recombinant DNA technology, such as those listed in Sambrook et al., (Molecular Cloning: A Laboratory Manual), Cold Spring Harbor Laboratory Press, Cold Spring Harbor , N.Y. [1989]) and/or the methods of Ausubel et al., eds., "Current Protocols in Molecular Biology", GreenPublishers Inc. and Wiley and Sons, N.Y. [1994].

Genes or cDNAs encoding NTP peptides, related proteins or related peptides can be obtained, for example, by screening genomic or cDNA libraries or by PCR amplification. Probes or primers for screening libraries can be generated based on sequence information of other known genes or gene fragments from the same or related gene families, such as conserved motifs found in other related proteins. In addition, having identified a gene encoding an NTP peptide, related protein or related peptide from an organism, all or a portion of this gene can be used as a probe to identify homologous genes in other organisms. Such probes or primers can be used to screen cDNA libraries from various tissue sources that are believed to express NTP peptides, related proteins, or related peptide genes. Usually, high stringency conditions can be used to minimize the number of false positives obtained by screening.

Another method for preparing genes encoding NTP peptides, related proteins or related peptides is chemical synthesis using methods well known to those skilled in the art, such as Engels et al. (Angew. Chem. Intl. Ed., 28:716-734 [1989 ]) described method. These methods include, inter alia, the phosphotriester, phosphoramidite, H-phosphonate methods for nucleic acid synthesis. A preferred method of such chemical synthesis is polymer-supported synthesis using standard phosphoramidite chemistry. Typically, the DNA encoding an NTP peptide, related protein or related peptide is several hundred nucleotides in length. Nucleic acids of greater than about 100 nucleotides can be synthesized into several fragments using these methods. These fragments can then be linked together to form full length NTP peptides, related proteins or related peptides. Typically, the DNA segment encoding the amino terminus of this protein has an ATG encoding methionine. This methionine may or may not be present in the mature form of the related protein, related peptide or NTP peptide, depending on whether the protein produced in the host cell is designed to be secreted by the cell.

Genes, cDNAs or fragments thereof encoding related proteins, related peptides or NTP peptides can be inserted into suitable expression or amplification vectors using standard ligation techniques. Vectors are generally selected to be functional in the particular host cell used (ie, the vector is compatible with the host cell machinery such that genes therein can be amplified and/or expressed). Genes, cDNAs or fragments thereof encoding related proteins, related peptides or NTP peptides can be amplified/expressed in prokaryotic, yeast, insect (baculovirus system) and/or eukaryotic host cells. The choice of host cell depends in part on whether the protein of interest, peptide of interest or NTP peptide is glycosylated and/or phosphorylated. If so, yeast, insect or mammalian host cells are preferred.

In general, vectors for use in any host cell contain a 5' flanking sequence (also referred to as a "promoter") and other regulatory elements such as enhancers, origins of replication elements, transcription termination elements, donor and acceptor splice-site-containing Complete intron sequences, signal peptide sequences, ribosome binding site elements, polyadenylation sequences, polylinker regions for insertion of nucleic acid encoding the polypeptide to be expressed, and optional marker elements. Each of these elements is discussed below. Optionally, the vector may comprise a tail sequence, an oligonucleotide molecule located at the 5' or 3' end of the coding sequence of the related protein, related peptide or NTP peptide; the oligonucleotide molecule encodes a polyhistidine (e.g. 6 histidines) or other markers such as FLAG, HA (influenza hemagglutinin) or myc in the presence of commercially available antibodies. This tail is often fused to the polypeptide when it is expressed, and can be used as a tool for affinity purification of related proteins, related peptides or NTP peptides from host cells. Affinity purification can be accomplished, for example, by column chromatography using an antibody raised against the tail as the affinity matrix. Optionally, the tail can then be removed from the purified related protein, related peptide or NTP peptide by certain peptidases in various ways.

One skilled in the art can fuse the human immunoglobulin hinge region and Fc region to the N- or C-terminus of the related protein, related peptide or NTP peptide. The Fc fusion protein can then be purified using a protein A affinity column. Fc is known to exhibit a long pharmacokinetic half-life in vivo and it was found that proteins fused to Fc exhibited a half-life in vivo that was significantly greater than that of the unfused protein. Also, fused Fc regions allow dimerization/multimerization of some molecules to exploit their biological activity.

The 5' flanking sequence can be homologous (i.e. from the same species and/or strain as the host cell), heterologous (i.e. from a different species or quality than the host cell), hybrid (i.e. the 5' flanking sequence from more than one source combination), synthetic, or can be a natural related protein, related peptide or NTP peptide gene 5' flanking sequence. Likewise, the source of the 5' flanking sequence can be a unicellular prokaryotic or eukaryotic organism, any vertebrate or invertebrate, or any plant, so long as the 5' flanking sequence is functional and can be activated by the host cell machinery.

The 5' flanking sequences used in the vectors of the present invention can be obtained by a number of methods well known in the art. Typically, the 5' flanking sequences used herein have been previously identified by mapping and/or restriction enzyme digestion, in addition to the gene flanking sequences of related proteins, related peptides or NTP peptides, and thus can be obtained from the appropriate restriction endonuclease. isolated from tissue sources. In some cases, the full nucleotide sequence of this 5' flanking sequence may be known. Here, the 5' flanking sequence can be synthesized by the above nucleic acid synthesis or cloning method.

When all or only part of the 5' flanking sequence is known, it can be obtained by PCR and/or by screening a genomic library with suitable oligonucleotides and/or 5' flanking sequence fragments from the same or another species.

柱或其它本领域技术人员已知的方法来分离。选择适当酶以达到此目的对此领域的一般技术人员是不难懂得的。When the 5' flanking sequence is not known, the DNA fragment containing the 5' flanking sequence can be isolated from a larger fragment of DNA which may comprise, for example, a coding sequence or even an additional gene. Isolation can be accomplished by restriction enzyme digestion, using one or more carefully selected enzymes to isolate the appropriate DNA fragments. After digestion, desired fragments can be purified by agarose gel,

column or other methods known to those skilled in the art. Selection of an appropriate enzyme for this purpose will be readily apparent to those of ordinary skill in the art.

The origin of the replication element is usually part of a commercially available prokaryotic expression vector that facilitates amplification of the vector in the host cell. In some cases, vector amplification to a certain copy number is important for optimal expression of related proteins, related peptides or NTP peptides. If the selected vector does not contain an origin of replication, the origin can be chemically synthesized based on the known sequence and ligated into the vector. The transcription termination element is generally located at the 3' end of the NTP protein or NTP/peptide coding sequence, and its function is to terminate the transcription of the related protein, related peptide or NTP peptide. Typically, the transcription termination element in prokaryotic cells is a G-c rich fragment followed by a poly-T sequence. Although this element can be cloned from a library or purchased commercially as part of a vector, it can be readily synthesized using the nucleic acid synthesis methods described above.

Selectable marker gene elements encode proteins necessary for host cell survival and growth in selective media. A typical selectable marker gene element encodes a protein that (a) confers resistance to an antibiotic or other toxin, such as ampicillin, tetracycline or kanamycin, in a prokaryotic host cell, (b) compensates for an auxotrophic deficiency in the cell; or ( c) Provide key nutrients that complex media do not have. Preferred selectable markers are the kanamycin resistance gene, ampicillin resistance gene and tetracycline resistance gene.

The ribosome binding element, commonly referred to as the SD sequence (prokaryotes) or the Kozak sequence (eukaryotes), is generally required for the initiation of mRNA translation. This element is usually located at the 3' end of the promoter and the 5' end of the coding sequence of the related protein, related peptide or NTP peptide to be synthesized. The SD sequences vary but are generally polypurines (ie, have high A-G content). Many SD sequences have been identified, and those skilled in the art can easily use the above method to synthesize various SD sequences and use them in prokaryotic vectors.

When the related protein, related peptide or NTP peptide is required to be secreted from the host cell, a signal sequence can be used to guide the related protein, related peptide or NTP peptide to be secreted outside the host cell, and the carboxy-terminal part of the protein can be deleted to prevent membrane anchoring. Usually, the signal sequence is located in the coding region of the related protein/related peptide/NTP peptide gene or cDNA, or linked to the 5' end of the related protein/related peptide/NTP peptide gene coding region. A number of signal sequences have been identified and any one that is functional in the host cell of choice can be used in conjunction with the relevant protein/peptide/NTP peptide gene or cDNA. Therefore, the signal sequence may be homologous or heterologous to the related protein/related peptide/NTP peptide gene or cDNA, and may be homologous or heterologous to the related protein/related peptide/NTP peptide gene or cDNA. Alternatively, this signal sequence can be chemically synthesized by the method described above. In most cases, secretion of the polypeptide by the host cell through the presence of a signal peptide will result in the removal of the amino-terminal methionine from the polypeptide.

In many cases, transcription of a related protein/related peptide/NTP peptide gene or cDNA can be increased by the presence of one or more introns in the vector; when the related protein, related peptide or NTP peptide is produced in a eukaryotic host cell This is especially true when a mammalian host cell is born. The intron used may be naturally occurring in the related protein/related peptide/NTP peptide gene, especially when the used gene is a full-length genomic sequence or a fragment thereof. When the intron is not naturally occurring in the gene (as is the case with most cDNAs), the intron can be obtained from another source. Since this intron must be transcriptionally efficient, the relative position of its flanking sequences and related protein/related peptide/NTP peptide genes is often important. Likewise, when the related protein/related peptide/NTP peptide gene inserted into the expression vector is a cDNA molecule, the preferred position of the intron is the 3' end of the transcription initiation site and the 5' end of the poly A transcription termination sequence. For related proteins/related peptides/NTP peptide cDNAs, the intron or introns are preferably located on one side or the other (ie 5' or 3') of the cDNA so as not to interrupt the coding sequence. Any intron of any origin may be used in the practice of the present invention, including viral, prokaryotic and eukaryotic (plant or animal) organisms, as long as the intron is compatible with the host cell into which it is inserted. Also included herein are synthetic introns. Optionally, more than one intron may be used in the vector.

When the above-mentioned one or more elements do not exist in the vector to be used, they can be obtained separately and ligated into the vector. The methods used to obtain the individual elements are well known to those skilled in the art and comparable to those described above (ie synthetic DNA, library screening, etc.).

Final vectors useful in practicing the invention can be constructed from starting vectors, such as commercially available vectors. Such vectors may or may not contain some of the elements contained in complete vectors. If the desired element is not present in the starting vector, each element can be individually ligated into the vector by cutting the vector with an appropriate restriction enzyme so that the end of the element to be ligated and the end of the vector are suitable for ligation. In some cases, it may be necessary to "butt" the ends to be joined together in order to obtain a satisfactory connection. Blunt ends are obtained by first filling in "sticky ends" with Klenow DNA polymerase or T4 DNA polymerase when all four nucleotides are present. This procedure is well known in the art and is described, eg, in Sambrook et al., supra. Alternatively, two or more elements to be inserted into the vector may first be ligated together (if they are located adjacent to each other) and subsequently ligated into the vector.

Another way to construct the vector is to perform all ligation of the various elements simultaneously in one reaction mixture. Here, many meaningless and non-functional vectors will be generated due to improper ligation or insertion of elements. Functional vectors can however be identified and selected by restriction enzyme digestion.

Preferred vectors for practicing the invention are those compatible with bacterial, insect and mammalian host cells. Such vectors include pCRII, pCR3, and pcDNA3.1 (Invitrogen Company, San Diego, Calif.), pBSII (Stratagene Company, La Jolla, Calif.), pET15b (Novagen, Madison, Wis.), PGEX (Pharmacia Biotech, Piscataway , N.J.), pEGFP-N2 (Clontech, Palo Alto, Calif.), pETL (BlueBacII; Invitrogen) and pFastBacDual (Gibco/BRL, Grand Island, N.Y.).

After vector construction and insertion of nucleic acid molecules encoding full-length or truncated related proteins, related peptides or NTP peptides into appropriate sites of the vector, the complete vector can be inserted into a suitable host cell for amplification and/or polypeptide Express. The host cell may be a prokaryotic host cell (such as E. coli) or a eukaryotic host cell (such as a yeast cell, an insect cell or a vertebrate cell). When host cells are cultured under suitable conditions, related proteins, related peptides or NTP peptides can be synthesized and subsequently harvested from the culture medium (if the host cells secrete them into the culture medium) or directly from the host cell that produced them (if it is not secretion) collection.

After collection, related proteins, related peptides or NTP peptides can be purified by methods such as molecular sieve chromatography and affinity chromatography. The choice of host cell to produce the protein of interest, peptide of interest or NTP peptide depends in part on whether the protein of interest, peptide of interest or NTP peptide is glycosylated or phosphorylated (with eukaryotic host cells being preferred), and whether the host cell is capable of folding the protein into its Natural tertiary structure (such as the correct orientation of disulfide bridges, etc.), so as to prepare biologically active proteins through biologically active related proteins, related peptides or NTP peptides. Following synthesis, the related protein, related peptide or NTP peptide can be folded using appropriate chemical conditions discussed below. Suitable cells or cell lines for use in the present invention include mammalian cells, such as Chinese hamster ovary cells (CHO), human embryonic kidney (HEK) 293 or 293T cells, or 3T3 cells. Methods for selection of suitable mammalian host cells and transformation, cultivation, amplification, screening and product generation and purification are known to those skilled in the art. Other suitable mammalian cell lines include the monkey COS-1 and COS-7 cell lines and the CV-1 cell line. More exemplary mammalian host cells include primate and rodent cell lines, including transformed cell lines. Normal diploid cells, in vitro cultured cell lines derived from primary tissues, and primary explants are also suitable. Candidate cells may be genetically deficient in a selected gene or may contain a dominant effect of the selected gene. Other suitable mammalian cell lines include, but are not limited to, mouse neuroblastoma N2A cells, HeLa cells, mouse L-929 cells, 3T3 lines derived from Swiss, Balb-c or NIH mice, BHK or HaK hamsters cell line.

Also useful as host cells suitable for the present invention are bacterial cells. For example, various strains of E. coli (such as HB101, DH5α, DH10, and MC1061) are well-known host cells in the field of biotechnology. Various strains of Bacillus subtilis (B.subtilis), Pseudomonas spp., other Bacillus spp., Streptomyces spp., etc. can be used in this method. Many strains of yeast cells known to those skilled in the art can also serve as host cells for expressing the polypeptides of the present invention.

In addition, insect cell systems can be used in the methods of the present invention if desired. Such systems have been described, for example, by Kitts et al. (Biotechniques, 14:810-817 [1993]), Lucklow (Curr. Opin. Biotechnol., 4:564-572 [1993]) and Lucklow et al. (J. Virol., 67:4566-4579 [1993]). Preferred insect cells are Sf-9 and Hi5 (Invitrogen, Carlsbad, Calif.).

Insertion (also referred to as transformation or transfection) of the vector into the host cell of choice can be accomplished using methods such as calcium chloride, electroporation, microinjection, lipofection, or DEAE-dextran methods. The chosen method exploits, in part, the capabilities of the type of host cell used. These methods and other suitable methods are well known to those skilled in the art and are listed, eg, see Sambrook et al., supra.

Host cells containing this vector (ie, transformed or transfected) can be cultured using standard media well known to those skilled in the art. This medium usually contains all the nutrients necessary for cell growth and survival. Suitable media for culturing E. coli cells are, for example, Luria Broth (LB) and/or Terrific Broth (TB). Suitable media for culturing eukaryotic cells are RPMI1640, MEM, DMEM, all supplemented with serum and/or growth factors required for culturing a particular cell line. A suitable medium for growing insects is Grace's medium supplemented with the necessary yeasttolate, lactalbumin hydrolyzate and/or fetal bovine serum. Typically, the culture medium is supplemented with antibiotics or other compounds intended only to selectively grow transformed cells. The compound used will be determined by the selectable marker element present on the plasmid transforming the host cell. For example, when the selectable marker element is kanamycin resistance, the compound added to the medium is kanamycin.

The amount of related protein, related peptide or NTP peptide produced in the host cell can be estimated by standard methods known in the art. Such methods include, but are not limited to, Western blot analysis, SDS-polyacrylamide gel electrophoresis, native gel electrophoresis, HPLC separation, mass spectrometry, immunoprecipitation, and/or activity assays such as DNA binding gel shift assays.

If the related protein, related peptide or NTP peptide is designed to be secreted from the host cell, most of the related protein, related peptide or NTP peptide can be found in the cell culture medium. Proteins prepared in this way generally do not have an amino-terminal methionine because it is removed upon cell secretion. However, if the related protein, related peptide or NTP peptide is not secreted from the host cell, it will be present in the cytoplasm and/or nucleus (eukaryotic host cells) or cytosol (Gram-negative bacterial host cells), and may have amino groups terminal methionine.

For related proteins, related peptides or NTP peptides located in the cytoplasm and/or nucleus of host cells, the host cells are usually mechanically disrupted or detergents are used to release intracellular components into a buffer solution. The related protein, related peptide or NTP peptide can then be isolated from the solution.

Purification of related proteins, related peptides or NTP peptides from solution can be accomplished using a variety of techniques. If the synthesized protein contains palladium such as 6 histidines (NTP protein/hexa His) or other small peptides such as FLAG (Sigma-Aldritch, St. Louis, MI) or contains calmodulin-binding at its carboxyl or amino terminus Peptide (Stratagene, LaJolla, CA), which can be purified in a one-step process by passing a solution through an affinity column in which the column matrix has high affinity for the tail or directly for the protein (i.e., specifically recognizes the protein of interest or monoclonal antibody to the peptide). For example, polyhistidine specifically binds nickel, zinc, and cobalt with high affinity; therefore, use a nickel-based affinity resin (as used in Qiagen's QIAexpress system or Invitrogen's Xpress System) or a cobalt-based affinity resin. Immobilized metal ion affinity chromatography on an affinity resin (as used in BD Biosciences-CLONTECH's Talon system) can be used to purify NTP-related proteins/polyhistidine. (See eg, Ausubel et al., eds., A New Laboratory Manual for Molecular Biology, Section 10.11.8, John Wiley & Sons, New York [1993]).

When a related protein, related peptide or NTP peptide is prepared without a tail attached and antibodies thereto cannot be obtained, other well-known purification methods can be used. Such methods include, but are not limited to, ion exchange chromatography, hydroxyapatite chromatography, hydrophobic interaction chromatography, molecular sieve chromatography, HPLC, native gel electrophoresis combined with gel elution, and preparative isoelectric focusing (Isoprime machine/ Technology, Hoefer Scientific). In some cases one or more techniques can be combined to increase purity.

If the protein of interest, peptide of interest or NTP peptide is expected to be found primarily intracellularly, intracellular material (including inclusion bodies of Gram-negative bacteria) in the host cell can be extracted using standard techniques known to those skilled in the art. For example, host cells can be lysed after centrifugation by a French press, homogenization, and/or sonication to release periplasmic/cytoplasmic components. If related proteins, related peptides or NTP peptides form inclusion bodies in the cytosol, these inclusion bodies are often bound to the inner and/or outer cell membranes and are therefore mainly found in the pellet after centrifugation. Then extreme pH in the presence of reducing agents such as dithiothreitol at basic pH or tricarboxyethylphosphine at acidic pH or treatment with chaotropic agents such as detergents, guanidine, guanidine derivatives, urea or urea derivatives This precipitate releases, ruptures and dissolves the inclusion body. The related proteins, related peptides or NTP peptides which are in soluble form can then be analyzed by gel electrophoresis, immunoprecipitation and the like. If it is desired to isolate related proteins, related peptides or NTP peptides, this can be accomplished by standard methods, such as those outlined below and in Marston et al. (Meth. Enz., 182:264-275 [1990]).

In some cases, related proteins, related peptides or NTP peptides may not be biologically active in isolation. Various methods of refolding or converting the polypeptide into its tertiary structure and creating disulfide bonds can be used to restore its biological activity. These methods involve exposing the solubilized polypeptide to a pH, usually above 7, and the presence of a specific concentration of a chaotropic agent. The choice of chaotrope is very similar to that used for inclusion body solubilization, but is usually at a lower concentration and is not necessarily the same chaotrope used for solubilization. In most cases, the refolding/oxidation solution also contains a reducing agent or a reducing agent plus its oxidized form in a specific ratio to generate a specific redox potential for disulfide shuffling to form cysteine bridges in the protein. Some commonly used redox couples include cysteine/cystamine, glutathione (GSH)/dithiobis GSH (dithiobis GSH), copper chloride, dithiothreitol (DTT)/dithiane DTT, 2-Mercaptoethanol (bME)/dithio-b(ME). In many cases, co-solvents are required to increase the efficiency of refolding, and more commonly used reagents for this purpose include glycerol, polyethylene glycols of different molecular weights, and arginine.

If the host cells do not form inclusion bodies of related proteins, related peptides or NTP peptides to a significant extent, and the related proteins, related peptides or NTP peptides are mainly found in the supernatant after centrifugation of the cell homogenate, the related proteins, related peptides or NTP peptides can be used as follows Methods Separated from the supernatant.

Where partial or complete isolation of related proteins, related peptides or NTP peptides is preferred, purification can be accomplished using standard methods well known to those skilled in the art. Such methods include, but are not limited to, electrophoretic separation followed by electroelution, various types of chromatography (immunoaffinity, molecular sieves, and/or ion exchange), and/or high pressure liquid chromatography. In some cases it is preferred to use more than one of these methods for complete purification.

In addition to preparing and purifying related proteins, related peptides or NTP peptides using recombinant DNA techniques, related proteins, related peptides or NTP peptides and their fragments, variants, homologues and derivatives can be prepared by chemical synthesis (e.g. solid-phase peptide Synthesis), using techniques known in the art as described in Merrifield et al., (J.Am.Chem.Soc., 85:2149 [1963]), Houghten et al. (Proc.Natl.Acad.Sci.USA, 85:5132[ 1985]), Stewart and Young (Solid Phase Peptide Synthesis, Pierce Chemical Co., Rockford, III. [1984]). These polypeptides can be synthesized with or without a methionine at the amino terminus. Chemically synthesized related proteins, related peptides or NTP peptides can be oxidized to form disulfide bridges by methods outlined in the references. Related proteins, related peptides or NTP peptides are expected to have biological activity equivalent to those of related proteins, related peptides or NTP peptides recombinantly produced or purified from natural sources and thus may be used interchangeably with recombinant or native related proteins, related peptides or NTP peptides .

Chemically Modified Related Proteins, Related Peptides or NTP Peptides Compositions comprising related proteins, related peptides or NTP peptides linked to a polymer are within the scope of the invention. The selected polymer is generally soluble in water so that the protein it binds will not precipitate in an aqueous environment, such as a physiological environment. The selected polymer is usually modified to have a reactive group such as an active ester for acylation or an aldehyde for alkylation, which allows control of the degree of polymerization as provided by the present method. The polymers can be of any molecular weight and can be branched or unbranched. The scope of related protein/related peptide/NTP peptide polymers includes mixtures of polymers.

In some cases, it is desirable to produce nucleic acid and/or amino acid variants of naturally occurring related proteins, related peptides or NTP peptides. Nucleic acid variants can be produced by site-directed mutagenesis, PCR amplification, or other suitable methods in which primers have the desired point mutations (see Sambrook et al., supra, and Ausubel et al., supra for descriptions of mutagenesis techniques). Such variants can also be prepared using the chemical synthesis described by Engels et al., supra. Other methods known to those skilled in the art may also be used.

Preferred nucleic acid variants are those containing codon-preferential nucleotide substitutions in the host cell used to produce the related protein, related peptide or NTP peptide. This "codon optimization" can be determined by a computer algorithm that incorporates codon frequency tables such as "Ecohigh.Cod" as codon preferences for highly expressed bacterial genes, as provided by the University of Wisconsin package version 9.0, Genetics Computer Group, Madison, Wis. Other useful codon frequency tables include "Celegans_high.cod", "Celegans_low.cod", "Drosophila_high.cod", "Human_high.cod", "Maize_high.cod", and "Yeast_high.cod". Other preferred variants are those that encode the conservative amino acid changes described above compared to wild type (e.g., wherein the charge or polarity of the side chain of a naturally occurring amino acid is not significantly altered by substitution with a different amino acid), and/or are designed to produce Variants with new glycosylation and/or phosphorylation sites, or variants designed to delete existing glycosylation and/or phosphorylation sites.

Related proteins, related peptides, NTP peptides, fragments, homologues, variants, derivatives and salts thereof can be produced using conventional peptide synthesis techniques known to those of ordinary skill in the art. These techniques include chemical coupling methods (see Wunch, E: "Methods in Organic Chemistry", Vol. 15, Band 1+2, Synthese von Peptiden, thimeVerlag, Stuttgart (1974) and Barrany, G.; Marrifield, R.B.: " "(The Peptides), edited by E.Gross, J.Meienhofer, Vol. 2, Chapter 1, pp. 1-284, Academic Press (1980)), enzyme coupling method (see Widmer, F.Johansen, J.T., Carlsverg Res.Commun., Vol. 44, pp. 37-46 (1979) and Kullmann, W.: "Enzymatic Peptide Synthesis", CRC Press Inc. Boca Raton, Fla. (1987) and Widmer, F ., Johansen, J.T., "Synthetic Peptides in Biology and Medicines", edited by Alitalo, K., Partanen, P., Vatieri, A., pp. 79-86, Elsevier, Amsterdam (1985) ), or a combination of chemical and enzymatic methods, if this has process design and economic advantages. Using the guidelines provided herein, one skilled in the art can alter the peptide sequence of a related protein, related peptide or NTP peptide to produce a homologue having the same or similar biological activity as the original or native related protein, related peptide or NTP peptide.

There are advantages to using a mimetic of a given protein of interest, peptide of interest or NTP peptide rather than the protein itself. In general, peptidomimetics are more bioavailable, have a longer duration of action, and are less expensive to produce than the proteins and peptides.

Therefore, the above-mentioned related proteins, related peptides and NTP peptides can be used to develop small chemical compounds with similar biological activities and thus similar therapeutic effects. Peptide mimetics of related proteins, related peptides and NTP peptides can be developed using combinatorial chemistry techniques and other techniques known in the art (see, e.g., Proceedings of the 20th European Peptide Symposium) , G. Jung, E. Bayer, eds., pp. 289-336, and references therein).

Examples of methods for structurally modifying peptides known in the art to generate peptidomimetics include inversion of backbone chiral centers to create D-amino acid residue structures, particularly at the N-terminus, resulting in increased stability to protease degradation and to Activity was not adversely affected. An example is given in the paper "Tritiated D-alanine ¹ -peptide T binding", Smith CS et al., Drug Development Res., 15, pp. 371-379 (1988).

The second approach is to alter the cyclic structures required for stability, such as imides and lactams between N to C chains (Ede et al., Smith and Rivier eds., Peptides: Chemistry and Biology, Escom, Leiden , 1991, pp. 268-270). See, for example, conformationally constrained thymopentin-like compounds as disclosed in US Patent No. 4,457,489 (1985), Goldstein, G. et al., the contents of which are incorporated herein by reference in their entirety.

A third approach is to replace peptide bonds in related proteins, related peptides, or NTP peptides with pseudo-peptide bonds that confer proteolytic resistance. It has been reported that some pseudo-peptide bonds generally do not affect the structure and biological activity of the peptide. An example of this approach is the substitution of retro-anti-pseudopeptide bonds ("Biologically active retro-inverso homologues of thymopentin", Sisto A et al., Rivier, J.E. and Marshall, G.R. eds., "Peptides, Chemistry, Structure, and Biology Peptide Protein Res., 41:561-566, incorporated herein by reference). According to this modification, the amino acid sequence of this peptide may be identical to the sequence of the above-mentioned related protein, related peptide and NTP peptide, except that one or more peptide bonds are replaced by reverse reverse pseudo-peptide bonds. Preferably most of the N-terminal peptide bonds are substituted, since such substitutions will confer resistance to the action of exopeptidases on the N-terminal hydrolyzed protein.

The synthesis of peptides with one or more reduced retro-inverso pseudopeptide bonds is known in the art (Sisto (1990) and Dalpozzo et al., (1993), supra). Peptide bonds can thus be replaced by non-peptide bonds to allow the peptidomimetic to obtain a structure similar to the original peptide and thus similar biological activity. Other chemical groups of similar structure can also be used to replace the chemical groups of amino acids for further modification. Another suitable pseudopeptide bond known to increase stability to enzymatic cleavage with little or no loss of biological activity is the reduced isosteric pseudopeptide bond (Couder et al. (1993), Int. J. Peptide Protein Res. ., 41:181-184, fully incorporated herein by reference). Thus, the amino acid sequences of these peptides may be identical to related proteins, related peptides, or NTP peptide sequences except that one or more peptide bonds are replaced by isosteric pseudo-peptide bonds. Preferably most of the N-terminal peptide bonds are substituted, since such substitutions will confer resistance to the action of exopeptidases on the N-terminal hydrolyzed protein. The synthesis of peptides with one or more reduced isosteric pseudopeptide bonds is known in the art (Couder et al. 1993, supra). Other examples include the introduction of ketomethylene or methylsulfide bonds in place of peptide bonds.

Peptidomimetic derivatives of related proteins, related peptides, and NTP peptides represent another class of peptidomimetics, peptidomimetics that retain important structural determinants of biological activity but remove the peptide bond, conferring resistance to proteolysis (Simon USA, 89:9367-9371, incorporated herein by reference in its entirety). Peptoids are oligomers of N-substituted glycines. Several N-alkyl groups have been reported, each corresponding to the side chain of a natural amino acid (Simon et al., 1992, supra). Some or all of the amino acids of the protein of interest, peptide of interest, or NTP peptide are substituted with N-substituted glycines corresponding to the amino acids replaced.

The development of peptidomimetics can be assisted by determination of the tertiary structure of the original related protein, related peptide or NTP peptide by NMR spectroscopy, crystallography and/or computer-aided molecular modeling. These techniques can aid in the development of new compositions with higher potency and/or higher bioavailability and/or higher stability than the original peptide (Dean (1994), BioEssays, 16:683-687; Cohen and Shatzmiller (1993 ), J.Mol.Graph., 11:166-173; Wiley and Rich (1993), Med.Res.Rev., 13:327-384; Moore (1994), Trends Pharmacol.Sci., 15:124- 129; Hruby (1993), Biopolymers., 33:1073-1082; Bugg et al. (1993) Sci. Am., 269:92-98, incorporated herein by reference in its entirety).

Once a potential peptidomimetic compound has been identified, it can be synthesized and analyzed to assess its activity using the methods outlined in the examples below. Peptidomimetic compounds obtained by the above methods are included within the scope of the present invention, which compounds have the biological activity of related proteins, related peptides or NTP peptides and similar three-dimensional structures. Those skilled in the art will readily understand that the peptidomimetic can be produced from any related protein, related peptide or NTP peptide carrying one or more of the above modifications. It will also be appreciated that, in addition to their use as therapeutic compounds, the peptidomimetics of the present invention can be further used to develop even stronger non-peptidic compounds.

Many institutions today are capable of synthesizing related proteins, related peptides and NTP peptides described herein. For example, with the sequence of an NTP peptide, these institutions can synthesize the peptide and provide corresponding documentation for the synthesized peptide and certify the identity of the peptide.

The invention also includes assays using related proteins, related peptides and NTP peptides and their corresponding nucleic acid molecules for the qualitative or quantitative determination of related proteins, related peptides, NTP peptides, related proteins/related peptides/NTPs in mammalian tissue or body fluid samples Presence of peptide DNA or corresponding RNA. Related proteins, related peptides, NTP peptides and their corresponding nucleic acid molecules can be used in the preparation of these assays regardless of whether the related protein, related peptide or NTP peptide or the encoded related protein, related peptide or NTP peptide exhibits biological activity. Nucleic acid sequences of related proteins, related peptides or NTP peptides may be useful sources of hybridization probes to qualitatively or quantitatively determine the presence of related protein, related peptides or NTP peptide DNA or corresponding RNA in mammalian tissue or body fluid samples.

Related proteins, related peptides or NTP peptides that are not biologically active themselves can be used to prepare antibodies that recognize and/or bind related proteins, related peptides or NTP peptides. Such antibodies can be prepared by standard methods. Thus, antibodies reactive with related proteins, related peptides or NTP peptides, as well as short chain antibody fragments and other reactive fragments of such antibodies are also within the scope of the invention. Antibodies can be polyclonal, monoclonal, recombinant, chimeric, single chain and/or bispecific. Typically, antibodies or fragments thereof are of human origin or "humanized", ie, prepared so that an immune response to the antibody is prevented or minimized when administered to a patient. Preferred antibodies are human antibodies, polyclonal or monoclonal. Antibody fragments can be any fragments that can react with related proteins, related peptides or NTP peptides of the present invention, such as F _ab , F _ab' and the like. The present invention also provides a hybridoma by presenting a related protein, a related peptide or an NTP peptide as an antigen source to a selected mammal, and then using known techniques to combine cells of the mammal (such as spleen cells) with some cancer cells Fusion to generate immortalized cell lines. The present invention also includes methods of producing such cell lines and producing antibodies against all or a portion of related proteins, related peptides or NTP peptides.

Such antibodies can further be used for in vivo and in vitro diagnostic or research purposes, such as in labeled form to detect the presence of related proteins, related peptides or NTP peptides in body fluid or cell samples.

The present invention also includes the use of one or more related proteins, related peptides or NTP peptides as calibration standards in assays to qualitatively or quantitatively determine related proteins, related peptides, NTP peptides, related proteins/ Presence of DNA or corresponding RNA of the relevant peptide/NTP peptide.

The present invention relates to new methods of treating diseases requiring removal of cells, such as benign or malignant tumors, hyperplasia of glands (eg, prostate), unwanted facial hair, warts, and unwanted fatty tissue. This method involves administering to a mammal in need thereof a therapeutically effective amount of a related protein, related peptide or NTP peptide.

Such diseases may be, for example, lung, breast, stomach, pancreas, prostate, bladder, bone, ovary, skin, kidney, sinus, colon, intestine, stomach, rectum, esophagus, blood, brain and its covering, spinal cord and its covering Tumors, muscles, connective tissue, adrenals, parathyroid, thyroid, uterus, testes, pituitary, genitals, liver, gallbladder, eyes, ears, nose, throat, tonsils, mouth, lymph nodes and lymphatic system and other organs.

As used herein, the term "malignancy" includes all forms of human carcinomas, sarcomas and melanomas, which occur in poorly differentiated, moderately differentiated, and highly differentiated forms.

The present invention satisfies the needs of treatment in the art, and can remove benign tumors with less risk and fewer adverse surgical side effects. There is a particular need for methods of removing benign tumors in areas of surgical risk, such as deep sites within the body (eg, brain, heart, lungs, and others).

Methods of treating diseases in which cells must be removed can be used in conjunction with conventional methods of treating these diseases, such as surgical resection, chemotherapy, and radiation therapy. Related proteins, related peptides or NTP peptides can be administered before, during or after these conventional treatments.

The disease to be treated may also be selected from the group consisting of lung, breast, stomach, pancreas, prostate, bladder, bone, ovary, skin, kidney, sinus, colon, intestine, stomach, rectum, esophagus, blood, brain and its covering, spinal cord and its coverings, muscles, connective tissue, adrenal, parathyroid, thyroid, uterus, testes, pituitary, genitals, liver, gallbladder, eyes, ears, nose, throat, tonsils, mouth, lymph nodes and tissue hyperplasia of the lymphatic system, Hypertrophy or overgrowth.

Other diseases that can be treated by the method of the present invention are selected from the group consisting of lung, breast, stomach, pancreas, prostate, bladder, bone, ovary, skin, kidney, sinus, colon, intestine, stomach, rectum, esophagus, blood, brain and its covering , spinal cord and its covering, muscles, connective tissue, adrenal gland, parathyroid gland, thyroid gland, uterus, testes, pituitary gland, genitals, liver, gallbladder, eyes, ear, nose, throat, tonsils, mouth, lymph nodes, and lymphatic system , tissues altered by bacteria or parasites.

The disease to be treated may also be selected from the group consisting of lung, breast, stomach, pancreas, prostate, bladder, bone, ovary, skin, kidney, sinus, colon, intestine, stomach, rectum, esophagus, blood, brain and its covering, spinal cord and its coverings, muscles, connective tissue, adrenal, parathyroid, thyroid, uterus, testes, pituitary, genitals, liver, gallbladder, eyes, ears, nose, throat, tonsils, mouth, lymph nodes and tissue malformations of the lymphatic system or chaos.

Specifically, the disease to be treated may be tonsil hypertrophy, benign prostatic hyperplasia, psoriasis, eczema, skin disease or hemorrhoids. The disease to be treated may be a vascular disease such as atherosclerosis or arteriosclerosis, or a vascular disease such as varicose veins. The disease to be treated may also be a cosmetic modification of tissues such as skin, eye, ear, nose, throat, mouth, muscle, connective tissue, hair or breast tissue.

Therapeutic compositions of related proteins, related peptides and/or NTP peptides are within the scope of the present invention. Such compositions may include a therapeutically effective amount of the related protein, related peptide or NTP peptide in admixture with a pharmaceutically acceptable carrier. The carrier substance can be water for injection, and other substances commonly used for administration to mammals are preferably added to the solution. Usually, related proteins, related peptides or NTP peptides used for treatment are administered in the form of a composition, which includes purified related proteins, related peptides or NTP peptides, plus one or more physiologically acceptable carriers, excipient or diluent. Neutral buffered saline or saline mixed with serum albumin are examples of suitable carriers. Preferably this product is lyophilized with a suitable excipient such as sucrose. Other standard carriers, diluents and excipients can be included if desired. The composition includes a suitable buffer in the pH range known to those of ordinary skill in the art, including Tris buffer at pH 7.0-8.5, or acetic acid buffer at pH 4.0-5.5, which buffer may also include sorbitol or its suitable substitute.

Antibodies, antibody fragments, antibody-like molecules conjugated or linked or conjugated to related proteins, related peptides or NTP peptides targeting unwanted cellular components or to specific tumor markers such as cell receptors, signal peptides or overexpressed Molecules with high affinity for enzymes are also within the scope of the invention. These antibodies, antibody fragments, antibody-like molecules or molecules with high affinity for specific tumor markers can be used to conjugate the related proteins, related peptides or NTP peptides to specific cells or target tissues. For example, tumors with specific surface antigens or expressing antigens can be targeted by these antibodies, antibody fragments, antibody-like binding molecules, and thus tumor cells can be killed by related proteins, related peptides or NTP peptides. The advantages of this approach using antibody targeting are lower doses, increased likelihood of binding and uptake by target cells, and increased efficiency in targeting and treating metastatic and microtumor tumors.

The present invention also includes the use of said related proteins, related peptides and NTP peptides coupled or linked or bound to proteins or other molecules to form compositions by tumor-specific or site-specific enzymes or proteases or by target Antibody conjugates directed to tumors or other unwanted cells, when lysed at or near the tumor or other unwanted cells, release associated proteins, associated peptides or NTP peptides at or near the tumor or other unwanted cells.

The present invention also includes the use of said related proteins, related peptides and NTP peptides coupled or linked or bound to proteins or other molecules to form compositions, after exposure of the tissue to be treated to light (such as laser therapy or other photodynamic or Photoactivation therapy), other forms of electromagnetic radiation, the composition can release related proteins, related peptides or NTP peptides or some biologically active fragments of related proteins, related peptides or NTP peptides. Radiation, x-ray or gamma radiation, localized heating, alpha or beta radiation, ultrasound emissions or other localized energy sources.

Related proteins, related peptides or NTP peptides may be used alone, together or in combination with other pharmaceutical compositions, such as appropriate cytokines, growth factors, antibiotics, apoptosis inducers, anti-inflammatory drugs and/or chemotherapeutic agents for the indications to be treated.

The invention also includes compositions of said proteins, related peptides or NTP peptides using dendrimers, fullerenes and other synthetic molecules, polymers and macromolecules, the related proteins, related peptides or NTPs in the compositions Peptides and/or their corresponding DNA molecules are coupled, bound or encapsulated in the aforementioned molecules, polymers or macromolecules either by themselves or with other kinds of molecules such as tumor-specific markers. For example, U.S. Patent No. 5,714,166 "Bioactive and/or Targeted Dendrimer Conjugates" provides methods for making and utilizing targeted dendrimer conjugates including At least one dendrimer and target indicator and at least one bioactive agent coupled thereto.

The present invention also includes therapeutic compositions of said related proteins, related peptides or NTP peptides and/or genes and drug delivery vehicles, such as lipid emulsions, micellar polymers, polymer microspheres, electroactive polymers , hydrogels and liposomes.

It is also within the scope of the invention to employ related proteins, related peptides or NTP peptides or related genes or gene equivalents that can be transported to unwanted cells. Intratumoral overexpression of such related proteins, related peptides or NTP peptides can be used to induce cell death in the tumor and thus reduce the tumor cell population. The use of genes or gene equivalents capable of transporting said related proteins, related peptides or NTP peptides for the treatment of unwanted cellular components has the advantages of requiring fewer doses, passaging through the cell progeny of the target cell molecule, and necessarily reducing the number of treatments , Overall treatment reduction. The present invention also includes the transfer of a gene encoding a fusion protein containing related proteins, related peptides or NTP peptides to unwanted cells or adjacent cells thereof, after expressing the gene and producing and/or secreting the fusion protein, the fusion protein is protected by natural Cleavage by an enzyme or protease or a prodrug can release the associated protein, associated peptide or NTP peptide into unwanted cells or proximity.

Application of cloned recombinant related protein-, related peptide- or NTP peptide-antibody conjugate; cloned recombinant related protein, related peptide, or NTP peptide-antibody fragment conjugate; cloned recombinant related protein-, related peptide- Or NTP peptide-antibody-like protein conjugates are also included within the scope of the present invention. Said related proteins, related peptides or NTP peptides of clones that bind to targeting conjugates such as antibodies, antibody fragments, antibody-like molecules, or molecules with high affinity for cancer-specific receptors or other tumor markers The advantage is that this molecule combines the advantages of targeting described above with the advantages of conjugated molecules that can be manufactured and standardized for production of clones.

Solid dosage forms for oral administration include, but are not limited to, capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is preferably admixed with at least one of: (a) one or more inert excipients (or carriers), such as sodium citrate or dicalcium phosphate; (b) a filler or bulking agents, such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; (c) binders, such as carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (d ) humectants, such as glycerin; (e) disintegrants, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, some complex silicates and sodium carbonate; (f) solution retarders, such as paraffin; (g) absorption accelerators, such as quaternary ammonium compounds; (h) wetting agents, such as acetyl alcohol and glycerol monostearate; (i) absorbents, such as china clay and bentonite; (j) lubricants, such as talc , Calcium Stearate, Magnesium Stearate, Polyethylene Glycol Solid, Sodium Lauroyl Sulfate and mixtures thereof. In the case of capsules, tablets, pills, the dosage form may also include buffering agents.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. Liquid dosage forms may contain, in addition to the active compound, inert diluents such as water or other solvents, solubilizers, and emulsifiers commonly used in the art. Examples of emulsifiers are ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethylformamide, oils such as cottonseed oil, peanut oil , corn germ oil, olive oil, castor oil and sesame oil, glycerin, tetrahydrofurfuryl alcohol, polyethylene glycol, fatty acid esters of sorbitan or a mixture of these substances, etc.

Besides such inert diluents, the compositions can also include coadjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

Actual dosage levels of the active ingredients in the compositions of this invention may be varied to obtain a therapeutically effective amount of the related protein, related peptide or NTP peptide to obtain the desired therapeutic response to the particular composition and method of administration. The selection of dosage level will therefore depend upon the desired therapeutic effect, the route of administration, the duration of treatment desired, and other factors.

Effective amounts for mammals, including humans, can be administered based on body surface area. The correlation between doses (on a mg/ ^M2 basis of body surface) for animals of different sizes and species and humans is described in EJ Freireich et al., Cancer Chemother. Rep., 50(4):219 (1966). Body surface area can be determined approximately from the individual's height and weight (see, eg, Scientific Tables, Geigy Pharmaceuticals, Ardsley, NY, pp. 537-538 (1970)).

The total daily dose of the related protein, related peptide or NTP peptide administered to the host may be a single dose or divided doses. Dosage unit compositions contain fractional amounts which are used to make up the daily dose. It is to be understood, however, that the specific dosage level for any particular patient will depend on a variety of factors, including body weight, general health, sex, diet, time and route of administration, potency of the drug administered, ratio of absorption and excretion, combination Other medications and the severity of the specific condition being treated.

Methods of administering a related protein, related peptide or NTP peptide composition of the invention include, but are not limited to, intramuscular, oral, intravenous, intraperitoneal, intracerebral (intraparenchymal), intraventricular, intratumoral, intralesional, cutaneous Intrathecal, intranasal, intraocular, intraarterial, topical, transdermal, by aerosol, infusion, push injection, implanted device, sustained release system, etc.

Another method of administering the related protein, related peptide or NTP peptide composition of the present invention is transdermal or transdermal route. An example of such an embodiment is the use of a patch. Specifically, patches can be prepared with fine suspensions of related proteins, related peptides, or NTP peptides, such as dimethyl sulfoxide (DMSO) or a mixture of DMSO and cottonseed oil, which are brought into contact with the skin of a tumor-bearing mammal, leaving the skin capsule (pouch) internal tumor localization site. Other media or mixtures thereof containing other solvents and solid supports will work equally well. The patch may contain the protein-related, peptide-related or NTP peptide compound in solution or suspension. The patch can then be applied to the patient's skin, for example by inserting it into the patient's skin pocket, which can be formed by folding the skin and holding it together with stitches, clips, or other holding means. It should be ensured that the capsule is in continuous contact with the skin without disturbing the mammal. Instead of using a skin pouch, any device that ensures a securely placed patch in contact with the skin can be used. For example, adhesive bandages can be used to keep the patch on the skin.

The related protein, related peptide or NTP peptide can be administered in a sustained release formulation or preparation. Suitable examples of sustained release formulations include semipermeable polymer matrices in the form of shaped substances, such as films or microcapsules. Sustained-release matrices include polyesters, hydrogels, polylactide (US 3,773,919, EP 58,481), copolymers of L-glutamic acid and gamma ethyl-L-glutamine (Sidman et al., Biopolymers, 22:547 -556 [1983]), poly(2-hydroxyethyl-methacrylate) (Langer et al., J.Biomed.Mater.Res., 15:167-277 [1981] and Langer et al., Chem.Tech., 12:98-105 [1982]), polyethylene acetate (Langer et al., supra) or poly-D(-)-3-hydroxybutyrate (EP 133,988). Sustained release compositions also include liposomes, which can be prepared by one of several methods known in the art (e.g. Eppstein et al., Proc. Natl. Acad. Sci. USA, 82:3688-3692 [1985]; EP 36,676; EP 88,046 and EP 143,949).

Another method of administering the related protein, related peptide or NTP peptide of the present invention is to directly or indirectly infuse the related protein, related peptide or NTP peptide into the tumor or other tissues to be treated. An example of such an embodiment is the direct injection of a related protein, related peptide or NTP peptide into the tumor or other tissue to be treated. The treatment may be a single injection, multiple injections over a period of time, or a series of injections over hours, days, or months, with regression or destruction of the tumor or other tissue being treated being monitored by biopsy, photography, or other tissue growth methods to monitor. Can be injected into the tumor or other tissue to be treated or through an incision to reach a tumor or tissue in the body through a device inserted into a hole such as the nose, mouth, ear, vagina, rectum, or urethra, such injection can be combined with imaging or optical Systems such as ultrasound or fiber optic microscopy are performed in conjunction to determine where injection sites are inappropriate. Another example of such an embodiment would be the use of a device that allows constant delivery of related proteins, related peptides or NTP peptides to the tissue.

Yet another method of administering the related proteins, related peptides or NTP peptides of the present invention is in combination with surgery or similar methods for physical resection, ablation or killing or destroying tumors or other tissue or cellular components that need to be removed or destroyed , wherein a related protein, related peptide or NTP peptide of the invention is administered to the immediate surrounding area of a tumor or other tissue to be removed to destroy or prevent the growth of tumor cells, or without removing or destroying other cellular components.

Another method of administering a related protein, related peptide or NTP peptide of the invention is to implant the device into the tumor or other tissue to be treated. An example of such an embodiment is the implantation of sheets containing related proteins, related peptides or NTP peptides into tumors or other tissues to be treated. The flakes are ready to release therapeutic doses of related proteins, related peptides or NTP peptides into the tissue. In addition, the composition can be applied topically by implanting a membrane, sponge or other suitable substance onto the affected area, on which the relevant protein, related peptide or NTP peptide is adsorbed. When using an implantable device, which can be implanted into any suitable tissue or organ, the delivery of the relevant protein, related peptide or NTP peptide can be directly through the device, either by bolus injection or by continuous administration or continuous infusion via catheter .

Another method of administration is to introduce one or more copies of a related protein-, related peptide- or NTP peptide-encoding gene into target cells, and if necessary, induce the replication of this gene to start intracellular production of the related protein, related peptide or NTP peptide. One approach that can be used in gene therapy is the use of related protein-, related peptide- or NTP peptide-encoding genes (genomes encoding related proteins, related peptides or NTP peptides (or fragments, variants, homologues or derivatives thereof) DNA, cDNA and/or synthetic DNA), the gene can hereby be operably linked to a constitutive or inducible promoter to form a "gene therapy DNA construct". As long as the promoter is active in the cell or tissue type into which the construct is inserted, it may be homologous or heterologous to the endogenous related protein-, related peptide- or NTP peptide-encoding gene. Other components of the gene therapy DNA construct may optionally include, if desired, DNA molecules designed for site-specific integration (e.g., endogenous flanking sequences for homologous recombination), tissue-specific promoters, enhancing DNA molecules that provide selectivity over parental cells, DNA molecules used to identify markers of transformed cells, negative selection systems, cell-specific binders (e.g. for cell targeting), cell-specific internalization factors , transcription factors that increase expression of the vector, and factors that enable production of the vector.

Methods for delivering genes into cells or tissues in vivo or ex vivo, including (but not limited to) direct injection of naked DNA, ballistic methods, liposome-mediated transport, receptor-mediated transport (ligand-DNA complexes) , electroporation, and calcium phosphate precipitation, see U.S. Patent No. 4,970,154, WO 96/40958, U.S. Patent No. 5,679,559, U.S. Patent No. 5,676,954, and U.S. Patent No. 5,593,875, the disclosures of which are incorporated herein by reference in their entirety.

Related protein-, related peptide- or NTP peptide-encoding genes can be delivered by implantation into cells of the patient which have been genetically engineered ex vivo using the methods described herein to express and secrete the desired Said related proteins, related peptides or NTP peptides or fragments, variants, homologues or derivatives thereof. Such cells may be animal or human, and may be obtained from the patient's own tissue or another human or non-human source. Optionally such cells may be immortal cells or may be stem cells. However, to reduce the chance of an immune response, it is preferred to encapsulate such cells to prevent infiltration into surrounding tissue. The encapsulating substance is generally a biocompatible semipermeable polymeric seal or membrane that enables release of the protein product but prevents destruction of the patient's immune system cells or other deleterious agents of the surrounding tissue. Methods for membrane-encapsulated cells are familiar to those skilled in the art, and encapsulated cells can be prepared and implanted into patients without undue experimentation. See, eg, US Patent Nos. 4,892,538; 5,001,472 and 5,106,627, the disclosures of which are incorporated herein by reference in their entirety. A system for encapsulating living cells is described in PCTWO 91/10425. Techniques for preparing various other sustained or controlled delivery modes are known to those skilled in the art, such as liposomal vehicles, bioerodible particles or beads, and are described, for example, in U.S. Patent No. 5,653,975, the disclosure of which is in its entirety Incorporated herein by reference. The encapsulated or unencapsulated cells can be implanted into the appropriate body tissue or organ of the patient.

* * * * *

The following examples are provided to illustrate the invention. It should be understood, however, that the invention is not to be limited to the specific conditions and details described in these examples. Throughout this specification, any and all publicly available documents are incorporated by reference, including US patents.

In particular, the present invention expressly includes by reference the examples set forth in co-pending U.S. Patent Application Serial No. 10/092,934: "Methods of Treating Tumors and Related Diseases Using Neurofilament Proteins," which shows the full AD7c- NTP proteins are expressed in glioma and neuroblastoma cell cultures in vitro and in normal rodent muscle tissue, subcutaneous connective tissue, and dermis in vivo, as well as in a variety of tumors of different human and non-human origins (including breast cancer, skin cancer and papilloma, colon cancer, glioma, and other tumors in rodent models) that cause cell death. The present invention also expressly includes by reference the examples of co-pending U.S. Patent Application Serial No. 10/153,334, which show that NTP peptides cause cell death in normal rodent muscle tissue, subcutaneous connective tissue, dermis, and other tissues in vivo Effective formulation.

Example 1

The purpose of this example was to determine the effect of NTP peptide #6 on injection site tissue.

Male Sprague-Dawley rats (body weight range 300 grams) were anesthetized with ether and administered NTP peptide #6 by intraprostatic instillation after surgical exposure of the prostate. Injections included 300 μl NTP peptide #6, 1 mg/mL PBS pH 7.4 (1.0 mg/kg) (n=8), controls with only PBS injections (n=6), and no injection controls (n=2). Animals were euthanized after 72 hours. Prostates were dissected, fixed in 10% buffered formalin for 24 hours, embedded in paraffin, sectioned and stained with H&E. The intact prostate from each animal was embedded and sectioned. All stained sections were histologically examined and measured. At least 4 tissue sections were detected for each prostate, and the diameters of two sections perpendicular to each other (90°) were measured for each tissue section (a total of 8 or more measurements were made for each prostate). Using the average diameter of these measurements for each prostate, according to the formula

$V=\frac{4}{3}{\left(\frac{\mathrm{D.}}{2}\right)}^3$ Estimate volume.

Results: Rats injected with NTP Peptide #6 had an estimated mean reduction in prostate volume of 45% compared to controls (PBS only injected controls and uninjected controls had no appreciable change). Treated rat prostates showed extensive loss, flattening, and atrophy of the glandular epithelium. NTP Peptide #6 in PBS (pH 7.4) typically instilled at 1.0 mg/kg into the rat prostate resulted in an estimated greater than 40% reduction in prostate volume at 72 hours compared to untreated or PBS-treated controls.

Example 2

The purpose of this example was to determine the effect of NTP peptide #7 on injection site tissue.

Give intradermal and subcutaneous injection to 4 normal rats, each injecting four different points, when injecting limb skeletal muscles, injecting two different points each, infusing 0.1-1mg/ml from a plastic syringe through a stainless steel 26-gauge needle Concentration of 100-400ml of saline with NTP peptide #7.

Animals were observed for 24 hours and euthanized after 24 hours. Each infiltration lesion was excised, fixed in 10% formalin, embedded in paraffin, stained and examined by standard histopathological methods.

Controls received saline injections only.

Results: Acute tissue necrosis occurred at the injection site after injection of NTP peptide #7. Necrosis was evident in the muscle tissue, subcutaneous connective tissue, and dermis at the site of NTP peptide #7 injection. Necrosis was associated with the injected area and did not appear to spread very far from the injected site.

Away from mild areas of inflammation, controls showed no necrosis or cell loss. Controls showed little or no muscle changes. Control injections had mild to minimal acute inflammation at the injection site and focal microbleeds caused by the needle.

Example 3

The purpose of this example was to determine the effect of related peptide #1 on injection site tissue.

Peptide #1 was injected cutaneously and subcutaneously into rats as in Example 2 above.

Animals were observed for 24 hours and were euthanized at 24 hours. Tissues were excised, fixed in 10% formalin, embedded in paraffin, stained and examined by standard histopathological methods.

The control is the same as in Example 2.

Results: Injection-related peptide #1 produced cell death and tissue necrosis at the injection site. Similar to Example 2 above, cell death occurred in the muscle tissue, subcutaneous connective tissue, and dermis injected with the related peptide #1.

Away from areas of mild inflammation, the controls showed very little necrosis or cell loss. Control injections had mild to minimal acute inflammation at the injection site with occasional needle-induced focal microbleeds.

Example 4

The purpose of this example was to determine the effect of related peptide #2 on injection site tissue.

Male Sprague-Dawley rats (body weight range 300 g) were anesthetized with ether and given the relevant peptide #2 by intra-prostatic instillation after surgical exposure of the prostate. Injections included 300 μl of related peptide #2, 1 mg/mL PBS pH 7.4 (1.0 mg/kg) (n=8), controls injected with PBS only (n=6), and uninjected controls (n=2). Animals were euthanized after 72 hours. Prostates were dissected, fixed in 10% buffered formalin for 24 hours, embedded in paraffin, sectioned and stained with H&E. The intact prostate from each animal was embedded and sectioned. All stained sections were histologically examined and measured. At least 4 tissue sections were detected for each prostate, and the diameters of two sections perpendicular to each other (90°) of each tissue section were measured (a total of 8 or more measurements were made for each prostate). Using the average diameter of these measurements for each prostate, according to the formula

$V=\frac{4}{3}{\left(\frac{\mathrm{D.}}{2}\right)}^3$ Estimate volume.

The control is the same as in Example 1.

Results: As shown in Example 1 above, injection of the relevant peptide #2 at 72 hours caused significant cell loss and atrophy in the prostate. Controls showed minimal or no changes, including mild focal inflammation caused by the needle.

Example 5

The purpose of this example was to determine the effect of related peptide #3 on injection site tissue.

Related peptide #3 was injected in the prostate of normal rats as in Examples 1 and 4. Animals were euthanized 72 hours later and the prostate was examined as in Examples 1 and 4 above.

Results: Significant cell loss and atrophy were noted at 72 hours compared to controls, which had only minimal changes.

* * * * *

The invention has been described with reference to particularly preferred embodiments and examples. However, those skilled in the art will understand that various changes can be made to the present invention without departing from the spirit and or scope of the present invention.

sequence listing

<110> NYMOX CORPORATION

<120> Peptides effective in treating tumors and other diseases requiring removal or destruction of cells

<130>10107-44

<140>PCT/CA02/01106

<141>2002-07-19

<150> US 60/306,161

<151>2001-07-19

<150>US 60/306,150

<151>2001-07-19

<150>US 60/331,477

<151>2001-11-16

<160>125

<170>PatentIn Ver.2.1

<210>1

<211>375

<212>PRT

<213> Homo sapiens

<400>1

Met Glu Phe Ser Leu Leu Leu Pro Arg Leu Glu Cys Asn Gly Ala Ile

1 5 10 15

Ser Ala His Arg Asn Leu Arg Leu Pro Gly Ser Ser Asp Ser Pro Ala

20 25 30

Ser Ala Ser Pro Val Ala Gly Ile Thr Gly Met Cys Thr His Ala Arg

35 40 45

Leu Ile Leu Tyr Phe Phe Leu Val Glu Met Glu Phe Leu His Val Gly

50 55 60

Gln Ala Gly Leu Glu Leu Pro Thr Ser Asp Asp Pro Ser Val Ser Ala

65 70 75 80

Ser Gln Ser Ala Arg Tyr Arg Thr Gly His His Ala Arg Leu Cys Leu

85 90 95

Ala Asn Phe Cys Gly Arg Asn Arg Val Ser Leu Met Cys Pro Ser Trp

100 105 110

Ser Pro Glu Leu Lys Gln Ser Thr Cys Leu Ser Leu Pro Lys Cys Trp

115 120 125

Asp Tyr Arg Arg Ala Ala Val Pro Gly Leu Phe Ile Leu Phe Phe Leu

130 135 140

Arg His Arg Cys Pro Thr Leu Thr Gln Asp Glu Val Gln Trp Cys Asp

145 150 155 160

His Ser Ser Leu Gln Pro Ser Thr Pro Glu Ile Lys His Pro Pro Ala

165 170 175

Ser Ala Ser Gln Val Ala Gly Thr Lys Asp Met His His Tyr Thr Trp

180 185 190

Leu Ile Phe Ile Phe Ile Phe Asn Phe Leu Arg Gln Ser Leu Asn Ser

195 200 205

Val Thr Gln Ala Gly Val Gln Trp Arg Asn Leu Gly Ser Leu Gln Pro

210 215 220

Leu Pro Pro Gly Phe Lys Leu Phe Ser Cys Pro Ser Leu Leu Ser Ser

225 230 235 240

Trp Asp Tyr Arg Arg Pro Pro Arg Leu Ala Asn Phe Phe Val Phe Leu

245 250 255

Val Glu Met Gly Phe Thr Met Phe Ala Arg Leu Ile Leu Ile Ser Gly

260 265 270

Pro Cys Asp Leu Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile Thr Gly

275 280 285

Val Ser His His Ala Arg Leu Ile Phe Asn Phe Cys Leu Phe Glu Met

290 295 300

Glu Ser His Ser Val Thr Gln Ala Gly Val Gln Trp Pro Asn Leu Gly

305 310 315 320

Ser Leu Gln Pro Leu Pro Pro Gly Leu Lys Arg Phe Ser Cys Leu Ser

325 330 335

Leu Pro Ser Ser Trp Asp Tyr Gly His Leu Pro Pro His Pro Ala Asn

340 345 350

Phe Cys Ile Phe Ile Arg Gly Gly Val Ser Pro Tyr Leu Ser Gly Trp

355 360 365

Ser Gln Thr Pro Asp Leu Arg

370 375

<210>2

<211>122

<212>PRT

<213> unknown creature

<220>

<223> Description of unknown organism: Unknown NTP peptide

<400>2

Met Met Val Cys Trp Asn Arg Phe Gly Lys Trp Val Tyr Phe Ile Ser

1 5 10 15

Ala Ile Phe Asn Phe Gly Pro Arg Tyr Leu Tyr His Gly Val Pro Phe

20 25 30

Tyr Phe Leu Ile Leu Val Arg Ile Ile Ser Phe Leu Ile Gly Asp Met

35 40 45

Glu Asp Val Leu Leu Asn Cys Thr Leu Leu Lys Arg Ser Ser Arg Phe

50 55 60

Arg Phe Trp Gly Ala Leu Val Cys Ser Met Asp Ser Cys Arg Phe Ser

65 70 75 80

Arg Val Ala Val Thr Tyr Arg Phe Ile Thr Leu Leu Asn Ile Pro Ser

85 90 95

Pro Ala Val Trp Met Ala Arg Asn Thr Ile Asp Gln Gln Val Leu Ser

100 105 110

Arg Ile Lys Leu Glu Ile Lys Arg Cys Leu

115 120

<210>3

<211>112

<212>PRT

<213> Homo sapiens

<400>3

Met Ala Gln Ser Arg Leu Thr Ala Thr Ser Ala Ser Arg Val Gln Ala

1 5 10 15

Ile Leu Leu Ser Gln Pro Pro Lys Gln Leu Gly Leu Arg Ala Pro Ala

20 25 30

Asn Thr Pro Leu Ile Phe Val Phe Ser Leu Glu Ala Gly Phe His His

35 40 45

Ile Cys Gln Ala Gly Leu Lys Leu Leu Thr Ser Gly Asp Pro Pro Ala

50 55 60

Ser Ala Phe Gln Ser Ala Gly Ile Thr Gly Val Ser His Leu Thr Gln

65 70 75 80

Pro Ala Asn Leu Asp Lys Lys Ile Cys Ser Asn Gly Gly Ser Cys Tyr

85 90 95

Val Ala Gln Ala Gly Leu Lys Leu Leu Ala Ser Cys Asn Pro Ser Lys

100 105 110

<210>4

<211>106

<212>PRT

<213> Homo sapiens

<400>4

Met Trp Thr Leu Lys Ser Ser Leu Val Leu Leu Leu Leu Cys Leu Thr Cys

1 5 10 15

Ser Tyr Ala Phe Met Phe Ser Ser Leu Arg Gln Lys Thr Ser Glu Pro

20 25 30

Gln Gly Lys Val Pro Cys Gly Glu His Phe Arg Ile Arg Gln Asn Leu

35 40 45

Pro Glu His Thr Gln Gly Trp Leu Gly Ser Lys Trp Leu Trp Leu Leu

50 55 60

Phe Ala Val Val Pro Phe Val Ile Leu Lys Cys Gln Arg Asp Ser Glu

65 70 75 80

Lys Asn Lys Val Arg Met Ala Pro Phe Phe Leu His His Ile Asp Ser

85 90 95

Ile Ser Gly Val Ser Gly Lys Arg Met Phe

100 105

<210>5

<211>106

<212>PRT

<213> Homo sapiens

<400>5

Met Phe Phe Val Leu Tyr Arg Phe Cys Phe Cys Phe Phe Glu Thr Glu

1 5 10 15

Ser His Ser Leu Thr Gln Ala Gly Val Gln Trp Cys Glu Leu Gly Ser

20 25 30

Pro Gln Pro Leu Pro Ser Gly Phe Lys Arg Phe Ser Cys Leu Ser Leu

35 40 45

Leu Ser Ser Trp Asp Tyr Ser His Glu Pro Pro His Pro Val Ile Cys

50 55 60

Ser Phe Leu Met Glu Lys Cys Leu Ile Leu Tyr Lys Pro Asn Gly Asp

65 70 75 80

Thr Ile Gly Pro Ile Leu Val Gln Gln Gly Lys Arg Gln Lys Leu Tyr

85 90 95

Ile Ser Ala Asp Leu Val His Leu Ile Ala

100 105

<210>6

<211>98

<212>PRT

<213> Artificial sequence

<220>

<223> Description of artificial sequence: Unknown NTP peptide

<400>6

Glu Ala Tyr Tyr Thr Met Leu His Leu Pro Thr Thr Asn Arg Pro Lys

1 5 10 15

Ile Ala His Cys Ile Leu Phe Asn Gln Pro His Ser Pro Arg Ser Asn

20 25 30

Ser His Ser His Pro Asn Pro Leu Lys Leu His Arg Arg Ser His Ser

35 40 45

His Asn Arg Pro Arg Ala Tyr Ile Leu Ile Thr Ile Leu Pro Ser Lys

50 55 60

Leu Lys Leu Arg Thr His Ser Gln Ser His His Asn Pro Leu Ser Arg

65 70 75 80

Thr Ser Asn Ser Thr Pro Thr Asn Ser Phe Leu Met Thr Ser Ser Lys

85 90 95

Pro Arg

<210>7

<211>75

<212>PRT

<213> Artificial sequence

<220>

<223> Description of artificial sequence: Unknown NTP peptide

<400>7

Ser Ser Ser Leu Gly Leu Pro Lys Cys Trp Asp Tyr Arg His Glu Leu

1 5 10 15

Leu Ser Leu Ala Leu Met Ile Asn Phe Arg Val Met Ala Cys Thr Phe

20 25 30

Lys Gln His Ile Glu Leu Arg Gln Lys Ile Ser Ile Val Pro Arg Lys

35 40 45

Leu Cys Cys Met Gly Pro Val Cys Pro Val Lys Ile Ala Leu Leu Thr

50 55 60

Ile Asn Gly His Cys Thr Trp Leu Pro Ala Ser

65 70 75

<210>8

<211>68

<212>PRT

<213> Artificial sequence

<220>

<223> Description of artificial sequence: Unknown NTP peptide

<400>8

Met Phe Val Phe Cys Leu Ile Leu Asn Arg Glu Lys Ile Lys Gly Gly

1 5 10 15

Asn Ser Ser Phe Phe Leu Leu Ser Phe Phe Phe Ser Phe Gln Asn Cys

20 25 30

Cys Gln Cys Phe Gln Cys Arg Thr Thr Glu Gly Tyr Ala Val Glu Cys

35 40 45

Phe Tyr Cys Leu Val Asp Lys Ala Ala Phe Glu Cys Trp Trp Phe Tyr

50 55 60

Ser Phe Asp Thr

65

<210>9

<211>61

<212>PRT

<213> Homo sapiens

<400>9

Met Glu Pro His Thr Val Ala Gln Ala Gly Val Pro Gln His Asp Leu

1 5 10 15

Gly Ser Leu Gln Ser Leu Leu Pro Arg Phe Lys Arg Phe Ser Cys Leu

20 25 30

Ile Leu Pro Lys Ile Trp Asp Tyr Arg Asn Met Asn Thr Ala Leu Ile

35 40 45

Lys Arg Asn Arg Tyr Thr Pro Glu Thr Gly Arg Lys Ser

50 55 60

<210>10

<211>5

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>10

Ser Ser Trp Asp Tyr

1 5

<210>11

<211>9

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>11

Pro Ala Ser Ala Ser Pro Val Ala Gly

1 5

<210>12

<211>11

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>12

Gly Ala Ile Ser Ala His Arg Asn Leu Arg Leu

1 5 5 10

<210>13

<211>6

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>13

Phe Phe Leu Val Glu Met

1 5

<210>14

<211>9

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>14

Ser Val Thr Gln Ala Gly Val Gln Trp

1 5

<210>15

<211>17

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>15

Ile Asp Gln Gln Val Leu Ser Arg Ile Lys Leu Glu Ile Lys Arg Cys

1 5 10 15

Leu

<210>16

<211>9

<212>PRT

<213> Artificial sequence

<220>

<223> Description of Artificial Sequences: Synthetic Peptides

<400>16

Leu Ser Arg Ile Lys Leu Glu Ile Lys

1 5

<210>17

<211>22

<212>PRT

<213> Homo sapiens

<400>17

Gly Asp His Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys

1 5 10 15

Tyr Glu Val Lys Lys Met

20

<210>18

<211>16

<212>PRT

<213> Homo sapiens

<400>18

Gln Gln Ser Ile Ala Val Lys Phe Leu Ala Val Phe Gly Val Ser Ile

1 5 10 15

<210>19

<211>21

<212>PRT

<213> Homo sapiens

<400>19

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

1 5 10 15

Ser Pro Leu Gly Leu

20

<210>20

<211>581

<212>PRT

<213> Homo sapiens

<400>20

Met Glu Val Ser Pro Leu Gln Pro Val Asn Glu Asn Met Gln Val Asn

1 5 10 15

Lys Ile Lys Lys Asn Glu Asp Ala Lys Lys Arg Leu Ser Val Glu Arg

20 25 30

I1e Tyr Gln Lys Lys Thr Gln Leu Glu His Ile Leu Leu Arg Pro Asp

35 40 45

Thr Tyr Ile Gly Ser Val Glu Leu Val Thr Gln Gln Met Trp Val Tyr

50 55 60

Asp Glu Asp Val Gly Ile Asn Tyr Arg Glu Val Thr Phe Val Pro Gly

65 70 75 80

Leu Tyr Lys Ile Phe Asp Glu Ile Leu Val Asn Ala Ala Asp Asn Lys

85 90 95

Gln Arg Asp Pro Lys Met Ser Cys Ile Arg Val Thr Ile Asp Pro Glu

100 105 110

Asn Asn Leu Ile Ser Ile Trp Asn Asn Gly Lys Gly Ile Pro Val Val

115 120 125

Glu His Lys Val Glu Lys Met Tyr Val Pro Ala Leu Ile Phe Gly Gln

130 135 140

Leu Leu Thr Ser Ser Ser Asn Tyr Asp Asp Asp Glu Lys Lys Val Thr Gly

145 150 155 160

Gly Arg Asn Gly Tyr Gly Ala Lys Leu Cys Asn Ile Phe Ser Thr Lys

165 170 175

Phe Thr Val Glu Thr Ala Ser Arg Glu Tyr Lys Lys Met Phe Lys Gln

180 185 190

Thr Trp Met Asp Asn Met Gly Arg Ala Gly Glu Met Glu Leu Lys Pro

195 200 205

Phe Asn Gly Glu Asp Tyr Thr Cys Ile Thr Phe Gln Pro Asp Leu Ser

210 215 220

Lys Phe Lys Met Gln Ser Leu Asp Lys Asp Ile Val Ala Leu Met Val

225 230 235 240

Arg Arg Ala Tyr Asp Ile Ala Gly Ser Thr Lys Asp Val Lys Val Phe

245 250 255

Leu Asn Gly Asn Lys Leu Pro Val Lys Gly Phe Arg Ser Tyr Val Asp

260 265 270

Met Tyr Leu Lys Asp Lys Leu Asp Glu Thr Gly Asn Ser Leu Lys Val

275 280 285

Ile His Glu Gln Val Asn His Arg Trp Glu Val Cys Leu Thr Met Ser

290 295 300

Glu Lys Gly Phe Gln Gln Ile Ser Phe Val Asn Ser Ile Ala Thr Ser

305 310 315 320

Lys Gly Gly Arg His Val Asp Tyr Val Ala Asp Gln Ile Val Thr Lys

325 330 335

Leu Val Asp Val Val Lys Lys Lys Asn Lys Gly Gly Val Ala Val Lys

340 345 350

Ala His Gln Arg Glu Leu Cys Asn Gly Ala Ile Leu Ala His Cys Asn

355 360 365

Leu Arg Leu Met Gly Ser Ser Asp Ser Pro Ala Ser Ala Ser Arg Val

370 375 380

Ala Gly Ile Ala Gly Gly Cys His His Thr Gln Leu Ile Phe Val Phe

385 390 395 400

Leu Val Glu Thr Gly Phe His His Val Gly Gln Ala Gly Leu Glu Arg

405 410 415

Leu Thr Ser Gly Asp Pro Pro Ala Ser Ala Ser Gln Ser Ser Gly Ile

420 425 430

Thr Asp Val Lys Val Lys Asn His Met Trp Ile Phe Val Asn Ala Leu

435 440 445

Ile Glu Asn Pro Thr Phe Asp Ser Gln Thr Lys Glu Asn Met Thr Leu

450 455 460

Gln Pro Lys Ser Phe Gly Ser Thr Cys Gln Leu Ser Glu Lys Phe Ile

465 470 475 480

Lys Ala Ala Ile Gly Cys Gly Ile Val Glu Ser Ile Leu Asn Trp Val

485 490 495

Lys Phe Lys Ala Gln Val Gln Leu Asn Lys Lys Cys Ser Ala Val Lys

500 505 510

His Asn Arg Ile Lys Gly Ile Pro Lys Leu Asp Asp Ala Asn Asp Ala

515 520 525

Gly Gly Arg Asn Ser Thr Glu Cys Thr Leu Ile Leu Thr Glu Gly Asp

530 535 540

Ser Ala Lys Thr Leu Ala Val Ser Gly Leu Gly Val Val Gly Arg Asp

545 550 555 560

Lys Tyr Gly Val Phe Pro Leu Arg Gly Lys Ile Leu Asn Val Arg Glu

565 570 575

Ala Ser His Lys Gln

580

<210>21

<211>163

<212>PRT

<213> Homo sapiens

<400>21

Met Thr Gly Asp Lys Gly Pro Gln Arg Leu Ser Gly Ser Ser Tyr Gly

1 5 10 15

Ser Ile Ser Ser Pro Thr Ser Pro Thr Ser Pro Gly Pro Gln Gln Ala

20 25 30

Pro Pro Arg Glu Thr Tyr Leu Ser Glu Lys Ile Pro Ile Pro Asp Thr

35 40 45

Lys Pro Gly Thr Phe Ser Leu Arg Lys Leu Trp Ala Phe Thr Gly Pro

50 55 60

Gly Phe Leu Met Ser Ile Ala Phe Leu Asp Pro Gly Asn Ile Glu Ser

65 70 75 80

Asp Leu Gln Ala Gly Ala Val Ala Gly Phe Lys Leu Leu Trp Val Leu

85 90 95

Leu Trp Ala Thr Val Leu Gly Leu Leu Cys Gln Arg Leu Ala Ala Arg

100 105 110

Leu Gly Val Val Thr Gly Lys Asp Leu Gly Glu Val Cys His Leu Tyr

115 120 125

Tyr Pro Lys Ser Glu Ser Arg Ser Val Ala Gln Ser Gly Val Gln Trp

130 135 140

Cys Asp Val Ser Ser Leu Gln Pro Leu Pro Pro Arg Cys Pro Ala Pro

145 150 155 160

Ser Ser Gly

<210>22

<211>151

<212>PRT

<213> Homo sapiens

<400>22

Met Met Leu Ser Val Gln Glu Asn Val His Arg Cys Ile Cys Lys His

1 5 10 15

Tyr Ala Pro Pro Thr Ala Pro His Leu Phe Phe Glu Thr Glu Ser His

20 25 30

Ser Val Thr Gln Ala Gly Val Gln Trp Cys Asp Leu Gly Ser Leu Gln

35 40 45

Pro Ser Pro Pro Gly Phe Lys Gln Phe Ser Cys Leu Ser Leu Ser Arg

50 55 60

Ser Trp Asp Tyr Arg Arg Val Pro Leu Cys Leu Ala Asn Phe Ile Val

65 70 75 80

Phe Leu Val Glu Thr Gly Phe Cys Arg Val Gly Gln Ala Gly Leu Lys

85 90 95

Leu Leu Thr Ser Ser Asp Leu Pro Ala Ser Ala Cys Gln Ser Ala Gly

100 105 110

Asp Tyr Arg His Glu Pro Leu Arg Leu Ala Leu Thr Leu Cys His Phe

115 120 125

Ile Ser Arg Thr Cys Thr Ser Val Asp Phe Tyr Ile Cys Arg Asp Leu

130 135 140

Glu Arg Ile Pro His Gly His

145 150

<210>23

<211>129

<212>PRT

<213> Homo sapiens

<400>23

Met Ile Ser Ala His Arg Asn Leu His Leu Pro Gly Ser Ser Asn Ser

1 5 10 15

Pro Ala Ser Ala Phe Leu Ser Ser Trp Asp Tyr Arg His Val Pro Pro

20 25 30

Cys Pro Ala Asn Val Val Phe Leu Val Glu Met Gly Phe Leu His Val

35 40 45

Gly Gln Ala Gly Leu Glu Leu Pro Thr Ser Asp Asp Pro Pro Thr Leu

50 55 60

Ala Ser Gln Ser Ala Gly Ile Thr Gly Val Ser His Arg Thr Trp Gln

65 70 75 80

Glu Phe Ala Ser Leu Thr Val Ser Gln Ala Val Leu Arg Met Leu Val

85 90 95

Trp Gly Pro Gln Phe Glu Asn His Cys Ser Lys Leu Leu Met Ala Ser

100 105 110

Glu Gly Asp Ser Ser Leu Val Phe Phe Leu Tyr Pro Leu Ser Asn Leu

115 120 125

Asn

<210>24

<211>155

<212>PRT

<213> Homo sapiens

<400>24

Met Gln Gly Ser His Ser Ala Val Gln Ala Gly Val Trp Trp Cys His

1 5 10 15

His Asp Ser Leu Gln Pro Trp Pro Pro Gly Leu Arg Arg Ser Ser Cys

20 25 30

Leu Ser Leu Gln Ser Leu Trp Asp Tyr Arg Ser Leu Ala Leu Ser Leu

35 40 45

Arg Leu Ala Cys Asn Gly Thr Thr Ser Ala His Cys Asp Leu Cys Leu

50 55 60

Leu Ser Ser Ser Asp Ser Pro Ala Ser Ala Ser Gln Val Ala Gly Ile

65 70 75 80

Thr Gly Glu Lys Thr Ala Glu Pro His Lys Ala His Ala Ala Gln Gly

85 90 95

Glu Arg His Leu Ser Ser His Met Ser Pro Asp Glu Asn Met Thr Glu

100 105 110

Lys Phe Cys Pro Gly Pro Arg Ala Ser Phe His Leu Arg Ile Leu Ala

115 120 125

Ala Ser Arg His Leu Val Lys Arg Leu Leu Asn Glu Tyr Thr Val Thr

130 135 140

Val Leu Arg Asp Lys Ser Tyr Leu Arg Asn Asn

145 150 155

<210>25

<211>127

<212>PRT

<213> Homo sapiens

<400>25

Met Lys Asn Tyr Tyr Tyr Phe Leu Gly Gln Gly Leu Thr Leu Ser Pro

1 5 10 15

Arg Leu Glu Cys Ser Ser Thr Ile Ser Ala His Cys Asn Leu His Leu

20 25 30

Leu Gly Ser Ser Asn Ser Pro Val Ala Ala Ser Pro Val Ala Gly Thr

35 40 45

Thr Gly Thr Cys His His Asp Trp Leu Ile Phe Val Phe Leu Val Glu

50 55 60

Thr Gly Phe His His Ile Gly Gln Thr Gly Leu Glu Phe Leu Thr Ser

65 70 75 80

Gly Asp Pro Pro Thr Leu Ala Ser Lys Ser Ala Gly Ile Thr Gly Val

85 90 95

Ser His Cys Ala Trp Pro Thr Phe Leu Leu Asn Asp Met Arg His Ser

100 105 110

Phe Asn Lys Asn Leu Val Ile Ile Phe Tyr Val Pro Ala Ile Ser

115 120 125

<210>26

<211>137

<212>PRT

<213> Homo sapiens

<400>26

Met Arg Arg Glu Leu Leu Ala Gly Ile Leu Leu Arg Ile Thr Phe Asn

1 5 10 15

Phe Phe Leu Phe Phe Phe Leu Pro Phe Pro Leu Val Val Phe Phe Ile

20 25 30

Tyr Phe Tyr Phe Tyr Phe Phe Leu Glu Met Glu Ser His Tyr Val Ala

35 40 45

Gln Ala Gly Leu Glu Leu Leu Gly Ser Ser Asn Pro Pro Ala Ser Ala

50 55 60

Ser Leu Val Ala Gly Thr Leu Ser Val His His Cys Ala Cys Phe Glu

65 70 75 80

Ser Phe Thr Lys Arg Lys Lys Lys Leu Lys Lys Ala Phe Arg Phe Ile

85 90 95

Gln Cys Leu Leu Leu Gly Leu Leu Lys Val Arg Pro Leu Gln His Gln

100 105 110

Gly Val Asn Ser Cys Asp Cys Glu Arg Gly Tyr Phe Gln Gly Ile Phe

115 120 125

Met Gln Ala Ala Pro Trp Glu Gly Thr

130 135

<210>27

<211>1150

<212>PRT

<213> Homo sapiens

<400>27

Met Ser Lys Thr Leu Lys Lys Lys Lys His Trp Leu Ser Lys Val Gln

1 5 10 15

Glu Cys Ala Val Ser Trp Ala Gly Pro Pro Gly Asp Phe Gly Ala Glu

20 25 30

Ile Arg Gly Gly Ala Glu Arg Gly Glu Phe Pro Tyr Leu Gly Arg Leu

35 40 45

Arg Glu Glu Pro Gly Gly Gly Thr Cys Cys Ile Val Ser Gly Lys Ala

50 55 60

Pro Asn Pro Ser Asp Val Leu Leu Glu Val Asn Gly Thr Pro Val Ser

65 70 75 80

Gly Leu Thr Asn Arg Asp Thr Leu Ala Val Ile Arg His Phe Arg Glu

85 90 95

Pro Ile Arg Leu Lys Thr Val Lys Pro Gly Lys Val Ile Asn Lys Asp

100 105 110

Leu Arg His Tyr Leu Ser Leu Gln Phe Gln Lys Gly Ser Ile Asp His

115 120 125

Lys Leu Gln Gln Val Ile Arg Asp Asn Leu Tyr Leu Arg Thr Ile Pro

130 135 140

Cys Thr Thr Arg Ala Pro Arg Asp Gly Glu Val Pro Gly Val Asp Tyr

145 150 155 160

Asn Phe Ile Ser Val Glu Gln Phe Lys Ala Leu Glu Glu Ser Gly Ala

165 170 175

Leu Leu Glu Ser Gly Thr Tyr Asp Gly Asn Phe Tyr Gly Thr Pro Lys

180 185 190

Pro Pro Ala Glu Pro Ser Pro Phe Gln Pro Asp Pro Val Asp Gln Val

195 200 205

Leu Phe Asp Asn Glu Phe Asp Ala Glu Ser Gln Arg Lys Arg Thr Thr

210 215 220

Ser Val Ser Lys Met Glu Arg Met Asp Ser Ser Leu Pro Glu Glu Glu Glu

225 230 235 240

Glu Asp Glu Asp Lys Gly Ala Ile Asn Gly Ser Gly Asn Ala Glu Asn

245 250 255

Arg Glu Arg His Ser Glu Ser Ser Asp Trp Met Lys Thr Val Pro Ser

260 265 270

Tyr Asn Gln Thr Asn Ser Ser Met Asp Phe Arg Asn Tyr Met Met Arg

275 280 285

Asp Glu Thr Leu Glu Pro Leu Pro Lys Asn Trp Glu Met Ala Tyr Thr

290 295 300

Asp Thr Gly Met Ile Tyr Phe Ile Asp His Asn Thr Lys Thr Thr Thr

305 310 315 320

Trp Leu Asp Pro Arg Leu Cys Lys Lys Ala Lys Ala Pro Glu Asp Cys

325 330 335

Glu Asp Gly Glu Leu Pro Tyr Gly Trp Glu Lys Ile Glu Asp Pro Gln

340 345 350

Tyr Gly Thr Tyr Tyr Val Asp Phe Thr Leu Val Ala Gln Ala Gly Val

355 360 365

Gln Trp His Asp Leu Gly Ser Leu Gln Pro Pro Pro Pro Gly Phe Asn

370 375 380

His Leu Asn Gln Lys Thr Gln Phe Glu Asn Pro Val Glu Glu Ala Lys

385 390 395 400

Arg Lys Lys Gln Leu Gly Gln Val Glu Ile Gly Ser Ser Lys Pro Asp

405 410 415

Met Glu Lys Ser His Phe Thr Arg Asp Pro Ser Gln Leu Lys Gly Val

420 425 430

Leu Val Arg Ala Ser Leu Lys Lys Ser Thr Met Gly Phe Gly Phe Thr

435 440 445

Ile Ile Gly Gly Asp Arg Pro Asp Glu Phe Leu Gln Val Lys Asn Val

450 455 460

Leu Lys Asp Gly Pro Ala Ala Gln Asp Gly Lys Ile Ala Pro Gly Asp

465 470 475 480

Val Ile Val Asp Ile Asn Gly Asn Cys Val Phe Gly His Thr His Ala

485 490 495

Asp Val Val Gln Met Phe Gln Leu Val Pro Val Asn Gln Tyr Val Asn

500 505 510

Leu Thr Leu Cys Arg Gly Tyr Pro Leu Pro Asp Asp Ser Glu Asp Pro

515 520 525

Val Val Asp Ile Val Ala Ala Thr Pro Val Ile Asn Gly Gln Ser Leu

530 535 540

Thr Lys Gly Glu Thr Cys Met Asn Pro Gln Asp Phe Lys Pro Gly Ala

545 550 555 560

Met Val Leu Glu Gln Asn Gly Lys Ser Gly His Thr Ser Thr Gly Asp

565 570 575

Gly Leu Asn Gly Pro Ser Asp Ala Ser Glu Gln Arg Val Ser Met Ala

580 585 590

Ser Ser Gly Ser Ser Gln Pro Glu Leu Val Thr Ile Pro Leu Ile Lys

595 600 605

Gly Pro Lys Gly Phe Gly Phe Ala Ile Ala Asp Ser Pro Thr Gly Gln

610 615 620

Lys Val Lys Met Ile Leu Asp Ser Gln Trp Cys Gln Gly Leu Gln Lys

625 630 635 640

Glu Asp Ile Ile Lys Glu Ile Tyr His Gln Asn Val Gln Asn Leu Thr

645 650 655

His Leu Gln Val Val Glu Val Leu Lys Gln Phe Pro Val Gly Ala Asp

660 665 670

Val Pro Leu Leu Ile Leu Arg Gly Gly Pro Pro Ser Thr Thr Lys Thr

675 680 685

Ala Lys Met Lys Thr Asp Lys Lys Glu Asn Ala Gly Ser Leu Glu Ala

690 695 700

Ile Asn Glu Pro Ile Pro Gln Pro Met Pro Phe Pro Pro Ser Ile Ile

705 710 715 720

Arg Ser Gly Ser Pro Lys Leu Asp Pro Ser Glu Val Tyr Leu Lys Ser

725 730 735

Lys Thr Leu Tyr Glu Asp Lys Pro Pro Asn Thr Lys Asp Leu Asp Val

740 745 750

Phe Leu Arg Lys Gln Glu Ser Gly Phe Gly Phe Arg Val Leu Gly Gly

755 760 765

Asp Gly Pro Asp Gln Ser Ile Tyr Ile Gly Ala Ile Ile Pro Leu Gly

770 775 780

Ala Ala Glu Lys Asp Gly Arg Leu Arg Ala Ala Asp Glu Leu Met Cys

785 790 795 800

Ile Asp Gly Ile Pro Val Lys Gly Lys Ser His Lys Gln Val Leu Asp

805 810 815

Leu Met Thr Thr Ala Ala Arg Asn Gly His Val Leu Leu Thr Val Arg

820 825 830

Arg Lys Ile Phe Tyr Gly Glu Lys Gln Pro Glu Asp Asp Ser Ser Gln

835 840 845

Ala Phe Ile Ser Thr Gln Asn Gly Ser Pro Arg Leu Asn Arg Ala Glu

850 855 860

Val Pro Ala Arg Pro Ala Pro Gln Glu Pro Tyr Asp Val Val Leu Gln

865 870 875 880

Arg Lys Glu Asn Glu Gly Phe Gly Phe Val Ile Leu Thr Ser Lys Asn

885 890 895

Lys Pro Pro Pro Gly Val Ile Pro His Lys Ile Gly Arg Val Ile Glu

900 905 910

Gly Ser Pro Ala Asp Arg Cys Gly Lys Leu Lys Val Gly Asp His Ile

915 920 925

Ser Ala Val Asn Gly Gln Ser Ile Val Glu Leu Ser His Ala Asn Ile

930 935 940

Val Gln Leu Ile Lys Asp Ala Gly Val Thr Val Thr Leu Thr Val Ile

945 950 955 960

Ala Glu Glu Glu His His Gly Pro Pro Ser Gly Thr Asn Ser Ala Arg

965 970 975

Gln Ser Pro Ala Leu Gln His Arg Pro Met Gly Gln Ser Gln Ala Asn

980 985 990

His Ile Pro Gly Asp Arg Ser Ala Leu Glu Gly Glu Ile Gly Lys Asp

995 1000 1005

Val Ser Thr Ser Tyr Arg His Ser Trp Ser Asp His Lys His Leu Ala

1010 1015 1020

Gln Pro Asp Thr Ala Val Ile Ser Val Val Gly Ser Arg His Asn Gln

1025 1030 1035 1040

Asn Leu Gly Cys Tyr Pro Val Glu Leu Glu Arg Gly Pro Arg Gly Phe

                                                                                           

Gly Phe Ser Leu Arg Gly Gly Lys Glu Tyr Asn Met Gly Leu Phe Ile

1060 1065 1070

Leu Arg Leu Ala Glu Asp Gly Pro Ala Ile Lys Asp Gly Arg Ile His

1075 1080 1085

Val Gly Asp Gln Ile Val Glu Ile Asn Gly Glu Pro Thr Gln Gly Ile

1090 1095 1100

Thr His Thr Arg Ala Ile Glu Leu Ile Gln Ala Gly Gly Asn Lys Val

1105 1110 1115 1120

Leu Leu Leu Leu Arg Pro Gly Thr Gly Leu Ile Pro Asp His Gly Leu

                                                                                                         

Ala Pro Ser Gly Leu Cys Ser Tyr Val Lys Pro Glu Gln His

1140 1145 1150

<210>28

<211>253

<212>PRT

<213> Homo sapiens

<400>28

Met Ala Asp Asp Gln Gly Cys Ile Glu Glu Gln Gly Val Glu Asp Ser

1 5 10 15

Ala Asn Glu Asp Ser Val Asp Ala Lys Pro Asp Arg Ser Ser Phe Val

20 25 30

Pro Ser Leu Phe Ser Lys Lys Lys Lys Asn Val Thr Met Arg Ser Ile

35 40 45

Lys Thr Thr Arg Asp Arg Val Pro Thr Tyr Gln Tyr Asn Met Asn Phe

50 55 60

Glu Lys Leu Gly Lys Cys Ile Ile Ile Asn Asn Lys Asn Phe Asp Lys

65 70 75 80

Val Thr Gly Met Gly Val Arg Asn Gly Thr Asp Lys Asp Ala Glu Ala

85 90 95

Leu Phe Lys Cys Phe Arg Ser Leu Gly Phe Asp Val Ile Val Tyr Asn

100 105 110

Asp Cys Ser Cys Ala Lys Met Gln Asp Leu Leu Lys Lys Ala Ser Glu

115 120 125

Glu Asp His Thr Asn Ala Ala Cys Phe Ala Cys Ile Leu Leu Ser His

130 135 140

Gly Glu Glu Asn Met Glu Ser Cys Ser Val Thr Gln Ala Gly Val Gln

145 150 155 160

Arg Arg Asp Leu Gly Arg Leu Gln Pro Pro Pro Pro Arg Leu Ala Glu

165 170 175

Gly Pro Ser Leu Met Met Ala Ser Arg Pro Thr Arg Gly Pro Ser Met

180 185 190

Thr Gln Met Leu Ile Leu Asp Thr Arg Ser Gln Trp Lys Leu Thr Ser

195 200 205

Ser Ser Pro Ile Pro Arg Phe Gln Ala Ile Thr Arg Gly Gly Ala Gln

210 215 220

Glu Glu Ala Pro Gly Leu Cys Lys Pro Ser Ala Pro Ser Trp Arg Ser

225 230 235 240

Thr Glu Lys Thr Trp Lys Ser Cys Arg Ser Ser Pro Gly

245 250

<210>29

<211>111

<212>PRT

<213> Homo sapiens

<400>29

Met Gly Leu Ser Ile Ala Ser His Phe Gly Leu Leu Ile Lys Lys Val

1 5 10 15

Glu Arg Asn Ile Leu Phe Phe Phe Arg Arg Ser Leu Ala Leu Cys Gln

20 25 30

Ala Gly Val Gln Trp Arg Tyr Leu Ser Gln Leu Thr Ala Ala Ser Ala

35 40 45

Ser Trp Val Gln Ala Ile Leu Cys Leu Ser Leu Pro Ser Ser Trp Asp

50 55 60

Tyr Arg His Met Pro Pro Arg Pro Ala Asn Phe Cys Ile Leu Ser Arg

65 70 75 80

Asp Gly Ile Ser Pro Cys Trp Pro Gly Trp Ser Arg Ser Leu Asp Leu

85 90 95

Val Ile Arg Pro Pro Arg Pro Pro Lys Val Leu Arg Leu Gln Ala

100 105 110

<210>30

<211>118

<212>PRT

<213> Homo sapiens

<400>30

Met Gln Ile Ile Phe Phe Phe Leu Phe Leu Arg Trp Ser Phe Thr Leu

1 5 10 15

Val Ala Gln Ala Gly Val Gln Trp Arg Asp Leu Ser Ser Pro Gln Pro

20 25 30

Pro Pro Pro Arg Phe Lys Arg Phe Ser Cys Leu Ser Pro Pro Ser Ser

35 40 45

Trp Asp Tyr Arg His Ala Pro Pro His Pro Ala Asn Phe Val Phe Leu

50 55 60

Val Glu Thr Gly Phe Leu Arg Val Gly Gln Ala Gly Leu Glu Leu Leu

65 70 75 80

Thr Ser Gly Asp Pro Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile Thr

85 90 95

Gly Val Ser His His Thr Gln Pro Asp Ala Asn Asn Phe Leu Arg Lys

100 105 110

Leu Phe Gln Lys Leu Phe

115

<210>31

<211>139

<212>PRT

<213> Homo sapiens

<400>31

Met Gly His Pro Arg Ala Ile Gln Pro Ser Val Phe Phe Ser Pro Tyr

1 5 10 15

Asp Val His Phe Leu Leu Tyr Pro Ile Arg Cys Pro Tyr Leu Lys Ile

20 25 30

Gly Arg Phe His Ile Lys Leu Lys Gly Leu His Phe Leu Phe Ser Phe

35 40 45

Leu Phe Phe Phe Phe Glu Thr Gln Ser His Ser Val Thr Arg Leu Glu

50 55 60

Cys Ser Gly Thr Ile Ser Ala His Cys Asn Leu Cys Leu Pro Gly Ser

65 70 75 80

Ser Asn Ser Pro Ala Ser Ala Ser Gln Val Ala Gly Thr Thr Gly Thr

85 90 95

Cys His His Ala Gln Leu Ile Phe Val Phe Leu Ala Glu Met Gly Phe

100 105 110

His His Ile Gly Gln Asp Gly Leu Asp Leu Asn Leu Val Ile His Pro

115 120 125

Pro Arg Ser Pro Lys Ala Leu Gly Leu Gln Ala

130 135

<210>32

<211>69

<212>PRT

<213> Homo sapiens

<400>32

Met Pro Asn His Tyr Ser Phe Cys Phe Cys Phe Cys Phe Cys Phe Arg

1 5 10 15

Arg Ser Leu Ala Leu Ser Pro Arg Leu Glu Cys Ser Gly Ala Ile Leu

20 25 30

Ala His Gly Lys Leu His Leu Pro Gly Ser Arg His Ser Pro Ala Ser

35 40 45

Ala Ser Pro Val Ala Gly Thr Lys Gly Ala Arg His His Ala Arg Leu

50 55 60

Ile Phe Leu Tyr Phe

65

<210>33

<211>162

<212>PRT

<213> Homo sapiens

<400>33

Leu Phe Thr Asn Ser Pro Phe Ser Leu Leu Ser Pro Ala Gln Trp Leu

1 5 10 15

Cys Phe Gly Thr His Leu Gly His Val Gln Ser Val Ser His Leu Gln

20 25 30

Trp Glu Gly Ser Val Gln Glu Ser Leu Arg Ser Val Arg Asn Ser Arg

35 40 45

Cys Ala Leu Pro Met Leu Ser Ala Pro Cys Ser Leu Ser Leu His Phe

50 55 60

Leu Leu Phe Ser Leu Ser Pro Phe Phe Phe Phe Glu Ile Arg Val Leu

65 70 75 80

Leu Tyr Arg Gln Ala Gly Val Gln Trp Cys Tyr Leu Gly Ser Leu Gln

85 90 95

Pro Leu Pro Pro Gly Phe Lys Gln Phe Ser Cys Leu Ser Tyr Pro Ser

100 105 110

Ser Trp Asp Tyr Arg Arg Pro Pro Pro Arg Gln Ala Asn Phe Cys Ile

115 120 125

Phe Ser Thr Asp Gly Val Ser Pro Cys Trp Pro Arg Trp Ser Leu Ser

130 135 140

Leu Asp Leu Met Ile Arg Pro Pro Gln Pro Pro Glu Val Leu Gly Leu

145 150 155 160

Gln Val

<210>34

<211>232

<212>PRT

<213> Homo sapiens

<400>34

Met Gly Arg Leu Val Leu Leu Trp Gly Ala Ala Val Phe Leu Leu Gly

1 5 10 15

Gly Trp Met Ala Leu Gly Gln Gly Gly Ala Glu Gly Val Gln Ile Gln

20 25 30

Ile Ile Tyr Phe Asn Leu Glu Thr Val Gln Val Thr Trp Asn Ala Ser

35 40 45

Lys Tyr Ser Arg Thr Asn Leu Thr Phe His Tyr Arg Phe Asn Gly Asp

50 55 60

Glu Ala Tyr Asp Gln Cys Thr Asn Tyr Leu Leu Gln Glu Gly His Thr

65 70 75 80

Ser Gly Cys Leu Leu Asp Ala Glu Gln Arg Asp Asp Ile Leu Tyr Phe

85 90 95

Ser Ile Arg Asn Gly Thr His Pro Val Phe Thr Ala Ser Arg Trp Met

100 105 110

Val Tyr Tyr Leu Lys Pro Ser Ser Pro Lys His Val Arg Phe Ser Trp

115 120 125

His Gln Asp Ala Val Thr Val Thr Cys Ser Asp Leu Ser Tyr Gly Asp

130 135 140

Leu Leu Tyr Glu Val Gln Tyr Arg Ser Pro Phe Asp Thr Glu Trp Gln

145 150 155 160

Thr Gln Ser Arg Ser Val Thr Gln Ala Gly Val Gln Trp Cys Asp Leu

165 170 175

Cys Leu Leu Gln Pro Ser Pro Pro Arg Phe Lys Arg Phe Ser Cys Leu

180 185 190

Ser Leu Pro Ser Ser Trp Asp Tyr Arg His Pro Pro Pro Arg Leu Ala

195 200 205

Asn Phe Cys Ile Ile Ser Arg Asp Gly Val Ser Pro Cys Trp Pro Gly

210 215 220

Trp Ser Arg Thr Cys Asp Leu Arg

225 230

<210>35

<211>506

<212>PRT

<213> Homo sapiens

<400>35

Met Glu Phe Leu Lys Val Ala Arg Arg Asn Lys Arg Glu Gln Leu Glu

1 5 10 15

Gln Ile Gln Lys Glu Leu Ser Val Leu Glu Glu Asp Ile Lys Arg Val

20 25 30

Glu Glu Met Ser Gly Leu Tyr Ser Pro Val Ser Glu Asp Ser Thr Val

35 40 45

Pro Gln Phe Glu Ala Pro Ser Pro Ser His Ser Ser Ile Ile Asp Ser

50 55 60

Thr Glu Tyr Ser Gln Pro Pro Gly Phe Ser Gly Ser Ser Gln Ala Gly

65 70 75 80

Val Gln Trp Arg Tyr Leu Gly Ser Leu Gln Pro Pro Pro Pro Pro Arg Tyr

85 90 95

Lys Arg Phe Ser Cys Leu Thr Leu Pro Ser Ser Trp Asp Tyr Arg Arg

100 105 110

Leu Pro Pro His Leu Thr Lys Lys Gln Pro Trp Tyr Asn Ser Thr Leu

115 120 125

Ala Ser Arg Arg Lys Arg Leu Thr Ala His Phe Glu Asp Leu Glu Gln

130 135 140

Cys Tyr Phe Ser Thr Arg Met Ser Arg Ile Ser Asp Asp Ser Arg Thr

145 150 155 160

Ala Ser Gln Leu Asp Glu Phe Gln Glu Cys Leu Ser Lys Phe Thr Arg

165 170 175

Tyr Asn Ser Val Arg Pro Leu Ala Thr Leu Ser Tyr Ala Ser Asp Leu

180 185 190

Tyr Asn Gly Ser Ser Ile Val Ser Ser Ile Glu Phe Asp Arg Asp Cys

195 200 205

Asp Tyr Phe Ala Ile Ala Gly Val Thr Lys Lys Ile Lys Val Tyr Glu

210 215 220

Tyr Asp Thr Val Ile Gln Asp Ala Val Asp Ile His Tyr Pro Glu Asn

225 230 235 240

Glu Met Thr Cys Asn Ser Lys Ile Ser Cys Ile Ser Trp Ser Ser Tyr

245 250 255

His Lys Asn Leu Leu Ala Ser Ser Asp Tyr Glu Gly Thr Val Ile Leu

260 265 270

Trp Asp Gly Phe Thr Gly Gln Arg Ser Lys Val Tyr Gln Glu His Glu

275 280 285

Lys Arg Cys Trp Ser Val Asp Phe Asn Leu Met Asp Pro Lys Leu Leu

290 295 300

Ala Ser Gly Ser Asp Asp Ala Lys Val Lys Leu Trp Ser Thr Asn Leu

305 310 315 320

Asp Asn Ser Val Ala Ser Ile Glu Ala Lys Ala Asn Val Cys Cys Val

325 330 335

Lys Phe Ser Pro Ser Ser Ser Arg Tyr His Leu Ala Phe Gly Cys Ala Asp

340 345 350

His Cys Val His Tyr Tyr Asp Leu Arg Asn Thr Lys Gln Pro Ile Met

355 360 365

Val Phe Lys Gly His Arg Lys Ala Val Ser Tyr Ala Lys Phe Val Ser

370 375 380

Gly Glu Glu Ile Val Ser Ala Ser Thr Asp Ser Gln Leu Lys Leu Trp

385 390 395 400

Asn Val Gly Lys Pro Tyr Cys Leu Arg Ser Phe Lys Gly His Ile Asn

405 410 415

Glu Lys Asn Phe Val Gly Leu Ala Ser Asn Gly Asp Tyr Ile Ala Cys

420 425 430

Gly Ser Glu Asn Asn Ser Leu Tyr Leu Tyr Tyr Lys Gly Leu Ser Lys

435 440 445

Thr Leu Leu Thr Phe Lys Phe Asp Thr Val Lys Ser Val Leu Asp Lys

450 455 460

Asp Arg Lys Glu Asp Asp Thr Asn Glu Phe Val Ser Ala Val Cys Trp

465 470 475 480

Arg Ala Leu Pro Asp Gly Glu Ser Asn Val Leu Ile Ala Ala Asn Ser

485 490 495

Gln Gly Thr Ile Lys Val Leu Glu Leu Val

500 505

<210>36

<211>120

<212>PRT

<213> Homo sapiens

<400>36

Met Gly Ser Tyr Phe Val Ala Arg Ala Gly Cys Lys Leu Leu Gly Leu

1 5 10 15

Lys Gly Thr Ser His Phe Ser Leu Pro Lys Cys Arg Asn Cys Arg Arg

20 25 30

Glu Pro Leu Pro Gly Leu Phe Phe Leu Phe Phe Val Phe Phe Phe Leu

35 40 45

Arg Arg Ser Leu Ala Leu Ser Pro Arg Leu Glu Cys Ser Gly Ala Ile

50 55 60

Val Ala His Cys Lys Leu Gly Leu Pro Gly Ser Leu His Ser Pro Ala

65 70 75 80

Ser Ala Ser Gln Val Ala Gly Thr Ile Gly Thr Cys His Asn Thr Arg

85 90 95

Ile Ile Phe Cys Ile Leu Val Glu Thr Gly Phe His Arg Val Ser Gln

100 105 110

Asp Gly Val Asp Leu Leu Thr Leu

115 120

<210>37

<211>257

<212>PRT

<213> Homo sapiens

<400>37

Met Asp Cys Gly Ser Val Gly Gly Gln Arg Thr Gln Arg Leu Pro Gly

1 5 10 15

Arg Gln Arg Leu Leu Phe Leu Pro Val Gly Leu Ser Gly Arg Pro Gly

20 25 30

Gly Ser Glu Thr Ser Ala Arg Arg Cys Pro Ser Ala Leu Ser Asp Gly

35 40 45

Leu Gly Ala Leu Arg Pro Arg Ala Pro Ala Ala Arg Gly Gly Val Ser

50 55 60

Arg Ala Ser Pro Leu Leu Leu Leu Leu Leu Val Pro Ser Pro Arg Leu

65 70 75 80

Ala Ala Ala Ala Pro Arg Arg Gln Leu Gly Asp Trp Glu Arg Ser Arg

85 90 95

Leu Gly Tyr Ala Ala Pro Pro Ala Gly Arg Ser Gly Ala Trp Arg Cys

100 105 110

Ser Pro Gly Val Ala Ala Ala Ala Gly Ala Leu Pro Gln Tyr His Gly

115 120 125

Pro Ala Pro Ala Leu Val Ser Cys Arg Arg Glu Leu Ser Leu Ser Ala

130 135 140

Gly Ser Leu Gln Leu Glu Arg Lys Arg Arg Asp Phe Thr Ser Ser Gly

145 150 155 160

Ser Arg Lys Leu Tyr Phe Asp Thr His Ala Leu Val Cys Leu Leu Glu

165 170 175

Asp Asn Glu Ser His Ser Phe Ile Gln Ala Gly Val Gln Trp His Ser

180 185 190

Leu Gly Leu Leu Gln Pro Pro Pro Pro Gly Phe Lys Arg Ser Ser His

195 200 205

Leu Ile Leu Leu Ser Ser Trp Asp Tyr Arg His Ala Pro Pro His Leu

210 215 220

Asp Asn Phe Ser Val Phe Leu Leu Glu Thr Gly Phe His His Val Gly

225 230 235 240

Gln Ala Gly Leu Lys Leu Leu Thr Ser Ser Asp Pro Pro Thr Leu Ala

245 250 255

Ser

<210>38

<211>438

<212>PRT

<213> Homo sapiens

<400>38

Met Ser Pro Ala Thr Thr Gly Thr Phe Leu Leu Thr Val Tyr Ser Ile

1 5 10 15

Phe Ser Lys Val His Ser Asp Arg Asn Val Tyr Pro Ser Ala Gly Val

20 25 30

Leu Phe Val His Val Leu Glu Arg Glu Tyr Phe Lys Gly Glu Phe Pro

35 40 45

Pro Tyr Pro Lys Pro Gly Glu Ile Ser Asn Asp Pro Ile Thr Phe Asn

50 55 60

Thr Asn Leu Met Gly Tyr Pro Asp Arg Pro Gly Trp Leu Arg Tyr Ile

65 70 75 80

Gln Arg Thr Pro Tyr Ser Asp Gly Val Leu Tyr Gly Ser Pro Thr Ala

85 90 95

Glu Asn Val Gly Lys Pro Thr Ile Ile Glu Ile Thr Ala Tyr Asn Arg

100 105 110

Arg Thr Phe Glu Thr Ala Arg His Asn Leu Ile Ile Asn Ile Met Ser

115 120 125

Ala Glu Asp Phe Pro Leu Pro Tyr Gln Ala Glu Phe Phe Ile Lys Asn

130 135 140

Met Asn Val Glu Glu Met Leu Ala Ser Glu Val Leu Gly Asp Phe Leu

145 150 155 160

Gly Ala Val Lys Asn Val Trp Gln Pro Glu Arg Leu Asn Ala Ile Asn

165 170 175

Ile Thr Ser Ala Leu Asp Arg Gly Gly Arg Val Pro Leu Pro Ile Asn

180 185 190

Asp Leu Lys Glu Gly Val Tyr Val Met Val Gly Ala Asp Val Pro Phe

195 200 205

Ser Ser Cys Leu Arg Glu Val Glu Asn Pro Gln Asn Gln Leu Arg Cys

210 215 220

Ser Gln Glu Met Glu Pro Val Ile Thr Cys Asp Lys Lys Phe Arg Thr

225 230 235 240

Gln Phe Tyr Ile Asp Trp Cys Lys Ile Ser Leu Val Asp Lys Thr Lys

245 250 255

Gln Val Ser Thr Tyr Gln Glu Val Ile Arg Gly Glu Gly Ile Leu Pro

260 265 270

Asp Gly Gly Glu Tyr Lys Pro Pro Ser Asp Ser Leu Lys Ser Arg Asp

275 280 285

Tyr Tyr Thr Asp Phe Leu Ile Thr Leu Ala Val Pro Ser Ala Val Ala

290 295 300

Leu Val Leu Phe Leu Ile Leu Ala Tyr Ile Met Cys Cys Arg Arg Glu

305 310 315 320

Gly Val Glu Lys Arg Asn Met Gln Thr Pro Asp Ile Gln Leu Val His

325 330 335

His Ser Ala Ile Gln Lys Ser Thr Lys Glu Leu Arg Asp Met Ser Lys

340 345 350

Asn Arg Glu Ile Ala Trp Pro Leu Ser Thr Leu Pro Val Phe His Pro

355 360 365

Val Thr Gly Glu Ile Ile Pro Pro Leu His Thr Asp Asn Tyr Asp Ser

370 375 380

Thr Asn Met Pro Leu Met Gln Thr Gln Gln Trp Ser Phe Ala Pro Val

385 390 395 400

Ala Gln Ala Gly Val Gln Trp Arg Asp Leu Gly Ser Leu Gln Pro Pro

405 410 415

Pro Pro Arg Asn Leu Pro His Gln Thr Gln Ile Pro Gln Gln Gln Thr

420 425 430

Thr Gly Lys Trp Tyr Pro

435

<210>39

<211>171

<212>PRT

<213> Homo sapiens

<400>39

Met Leu Gly Leu Arg Lys Ala Ala Ala Ile Ser Leu Leu Leu Arg Asn

1 5 10 15

Val Gly Leu Gln Leu Ala Thr Leu Leu Met Ser Gln Lys Lys Leu Gly

20 25 30

Phe Cys Gly Asn Phe Leu Phe Leu Asn Leu Ala Ile Ile Gln Thr Lys

35 40 45

Ile Ser Ser Ser Phe Phe Phe Phe Leu Arg Gln Ser Leu Thr Leu Ser

50 55 60

Pro Arg Leu Glu Cys Asn Gly Ala Ile Ser Ala His Cys His Leu Arg

65 70 75 80

Leu Pro Asp Ser Ser Asn Ser Pro Ala Ser Ala Ser Gln Val Thr Gly

85 90 95

Ile Thr Gly Ser His His His His Ala Trp Leu Ile Phe Val Phe Leu Val

100 105 110

Glu Thr Gly Phe Cys His Val Gly Gln Asp Gly Leu Glu Leu Leu Thr

115 120 125

Ser Gly Asp Pro Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile Thr Gly

130 135 140

Met Ser His His Thr Trp Pro Thr Asp Leu Phe Phe Lys Thr Val Leu

145 150 155 160

Pro Ala Arg Leu Gly Leu Trp Asp Ser Ser Val

165 170

<210>40

<211>365

<212>PRT

<213> Homo sapiens

<400>40

Met His Ala Val Pro Arg Gly Phe Gly Lys Lys Val Arg Val Gly Val

1 5 10 15

Gln Ser Cys Pro Ser Pro Phe Ser Gly Gln Ala Cys Pro Gln Pro Ser

20 25 30

Ser Val Phe Trp Ser Leu Leu Lys Asn Leu Pro Phe Leu Glu His Leu

35 40 45

Glu Leu Ile Gly Ser Asn Phe Ser Ser Ala Met Pro Arg Asn Glu Pro

50 55 60

Ala Ile Arg Asn Ser Leu Pro Pro Cys Ser Arg Ala Gln Ser Val Gly

65 70 75 80

Asp Ser Glu Val Ala Ala Ile Gly Gln Leu Ala Phe Leu Arg His Leu

85 90 95

Thr Leu Ala Gln Leu Pro Ser Val Leu Thr Gly Ser Gly Leu Val Asn

100 105 110

Ile Gly Pro Gln Cys Gln Gln Leu Arg Ser Leu Ser Leu Ala Asn Leu

115 120 125

Gly Met Met Gly Lys Val Val Tyr Met Pro Ala Leu Ser Asp Met Leu

130 135 140

Lys His Cys Lys Arg Leu Arg Asp Leu Arg Leu Glu Gln Pro Tyr Phe

145 150 155 160

Ser Ala Asn Ala Gln Phe Phe Gln Ala Leu Ser Gln Cys Pro Ser Leu

165 170 175

Gln Arg Leu Cys Leu Val Ser Arg Ser Gly Thr Leu Gln Pro Asp Ala

180 185 190

Val Leu Ala Phe Met Ala Arg Cys Leu Gln Val Val Met Cys His Leu

195 200 205

Phe Thr Gly Glu Ser Leu Ala Thr Cys Lys Ser Leu Gln Gln Ser Leu

210 215 220

Leu Arg Arg Trp Gly Glu Val Thr Gly Arg Arg Pro Gln Leu Phe Thr

225 230 235 240

Glu Leu Arg Glu Glu Pro Ser Ala Arg Thr Ser Arg Ala Thr Gly Arg

245 250 255

Arg Gln Pro Cys Leu Pro Asp Ser Gly Val Val Cys Cys Pro Cys Gly

260 265 270

Arg Pro Leu Ala Val Ser Gly Ile Ile Leu Val Gly Val Ser Pro Ser

275 280 285

Leu Val Val Lys Thr Thr Cys Val Tyr Arg Val Leu Phe Lys Asn Leu

290 295 300

Asp Tyr Ala Ser Ile Phe Phe Leu Val Cys Leu Phe Glu Thr Glu Ser

305 310 315 320

His Ser Val Val Gln Ala Gly Val Gln Trp Arg Asp Leu Ser Ser Leu

325 330 335

Gln Pro Leu Leu Ser Gly Leu Gln Pro Gln Pro Pro Glu Gln Leu Glu

340 345 350

Asn Glu Leu Glu Ile Gly Phe Ser Tyr Cys Phe Val Ile

355 360 365

<210>41

<211>125

<212>PRT

<213> Homo sapiens

<400>41

Met Glu Glu Asp Glu Phe Ile Gly Glu Lys Thr Phe Gln Arg Tyr Cys

1 5 10 15

Ala Glu Phe Ile Lys His Ser Gln Gln Ile Gly Asp Ser Trp Glu Trp

20 25 30

Arg Pro Ser Lys Asp Cys Ser Asp Gly Tyr Met Cys Lys Ile His Phe

35 40 45

Gln Ile Lys Asn Gly Ser Val Met Ser His Leu Gly Ala Ser Thr His

50 55 60

Gly Gln Thr Cys Leu Pro Met Glu Val Lys Ser Cys Ser Val Thr Gln

65 70 75 80

Ala Gly Val Gln Leu Arg Asp Leu Ser Ser Leu Gln Pro Pro Pro Ser

85 90 95

Gly Phe Lys Gln Phe Ser Cys Leu Ser Leu Pro Ser Asn Trp Asp Tyr

100 105 110

Arg Gly Ser Pro Leu His Leu Ala Asn Phe Leu Tyr Phe

115 120 125

<210>42

<211>120

<212>PRT

<213> Homo sapiens

<400>42

Met Thr Thr Cys Glu Phe Glu Phe Ile Phe Leu Lys Glu Gln Val Thr

1 5 10 15

Arg Ile Cys Asn Ile Ala Pro Leu Lys Ala Tyr Phe Ser Val His Lys

20 25 30

Met Gly Lys Ile Leu Lys Lys Leu Ser Asn Phe Ser Phe Leu Thr His

35 40 45

Arg Gln Ser Leu Thr Leu Ser Pro Arg Leu Glu Cys Ser Gly Ala Ile

50 55 60

Ser Ala His Cys Asn Leu His Leu Leu Gly Ser Ser Asn Ser Ala Ala

65 70 75 80

Ser Ala Ser Arg Val Ala Gly Thr Thr Gly Ala Cys His His His Ala Gln

85 90 95

Leu Ile Phe Val Phe Leu Val Glu Thr Gly Phe His His Val Gly Gln

100 105 110

Asp Gly Leu Gly Leu Leu Thr Ser

115 120

<210>43

<211>643

<212>PRT

<213> Homo sapiens

<400>43

Met Ser Cys Asn Pro Ser Phe Gly Gly Ile Gly Lys Gly His Leu Met

1 5 10 15

Arg Glu Val Asp Ala Leu Asp Gly Leu Cys Ser Arg Ile Cys Asp Gln

20 25 30

Ser Gly Val His Tyr Lys Val Leu Asn Arg Arg Lys Gly Pro Ala Val

35 40 45

Trp Gly Leu Arg Ala Gln Ile Asp Arg Lys Leu Tyr Lys Gln Asn Met

50 55 60

Gln Lys Glu Ile Leu Asn Thr Pro Leu Leu Thr Val Gln Glu Gly Ala

65 70 75 80

Val Glu Asp Leu Ile Leu Thr Glu Pro Glu Pro Glu His Thr Gly Lys

85 90 95

Cys Arg Val Ser Gly Val Val Leu Val Asp Gly Ser Thr Val Tyr Ala

100 105 110

Glu Ser Val Ile Leu Thr Thr Gly Thr Phe Leu Arg Gly Met Ile Val

115 120 125

Ile Gly Leu Glu Thr His Pro Ala Gly Arg Leu Gly Asp Gln Pro Ser

130 135 140

Ile Gly Leu Ala Gln Thr Leu Glu Lys Leu Gly Phe Val Val Gly Arg

145 150 155 160

Leu Lys Thr Gly Thr Pro Pro Arg Ile Ala Lys Glu Ser Ile Asn Phe

165 170 175

Ser Ile Leu Asn Lys His Ile Pro Asp Asn Pro Ser Ile Pro Phe Ser

180 185 190

Phe Thr Asn Glu Thr Val Trp Ile Lys Pro Glu Asp Gln Leu Pro Cys

195 200 205

Tyr Leu Thr His Thr Asn Pro Arg Val Asp Glu Ile Val Leu Lys Asn

210 215 220

Leu His Leu Asn Ser His Val Lys Glu Thr Thr Arg Gly Pro Arg Tyr

225 230 235 240

Cys Pro Ser Ile Glu Ser Lys Val Leu Arg Phe Pro Asn Arg Leu His

245 250 255

Gln Val Trp Leu Glu Pro Glu Gly Met Asp Ser Asp Leu Ile Tyr Pro

260 265 270

Gln Gly Leu Ser Met Thr Leu Pro Ala Glu Leu Gln Glu Lys Met Ile

275 280 285

Thr Cys Ile Arg Gly Leu Glu Lys Ala Lys Val Ile Gln Pro Asp Gly

290 295 300

Val Leu Leu Leu Leu Pro Arg Met Glu Cys Asn Gly Ala Ile Ser Ala

305 310 315 320

His His Asn Leu Pro Leu Pro Gly Tyr Gly Val Gln Tyr Asp Tyr Leu

325 330 335

Asp Pro Arg Gln Ile Thr Pro Ser Leu Glu Thr His Leu Val Gln Arg

340 345 350

Leu Phe Phe Ala Gly Gln Ile Asn Gly Thr Thr Gly Tyr Glu Glu Ala

355 360 365

Ala Ala Gln Gly Val Ile Ala Gly Ile Asn Ala Ser Leu Arg Val Ser

370 375 380

Arg Lys Pro Pro Phe Val Val Ser Arg Thr Glu Gly Tyr Ile Gly Val

385 390 395 400

Leu Ile Asp Asp Leu Thr Thr Leu Gly Thr Ser Glu Pro Tyr Arg Met

405 410 415

Phe Thr Ser Arg Val Glu Phe Arg Leu Ser Leu Arg Pro Asp Asn Ala

420 425 430

Asp Ser Arg Leu Thr Leu Arg Gly Tyr Lys Asp Ala Gly Cys Val Ser

435 440 445

Gln Gln Arg Tyr Glu Arg Ala Cys Trp Met Lys Ser Ser Leu Glu Glu

450 455 460

Gly Ile Ser Val Leu Lys Ser Ile Glu Phe Leu Ser Ser Lys Trp Lys

465 470 475 480

Lys Leu Ile Pro Glu Ala Ser Ile Ser Thr Ser Arg Ser Leu Pro Val

485 490 495

Arg Ala Leu Asp Val Leu Lys Tyr Glu Glu Val Asp Met Asp Ser Leu

500 505 510

Ala Lys Ala Val Pro Glu Pro Leu Lys Lys Tyr Thr Lys Cys Arg Glu

515 520 525

Leu Ala Glu Arg Leu Lys Ile Glu Ala Thr Tyr Glu Ser Val Leu Phe

530 535 540

His Gln Leu Gln Glu Ile Lys Gly Val Gln Gln Asp Glu Ala Leu Gln

545 550 555 560

Leu Pro Lys Asp Leu Asp Tyr Leu Thr Ile Arg Asp Val Ser Leu Ser

565 570 575

His Glu Val Arg Glu Lys Leu His Phe Ser Arg Pro Gln Thr Ile Gly

580 585 590

Ala Ala Ser Arg Ile Pro Gly Val Thr Pro Ala Ala Ile Ile Asn Leu

595 600 605

Leu Arg Phe Val Lys Thr Thr Gln Arg Arg Gln Ser Ala Met Asn Glu

610 615 620

Ser Ser Lys Thr Asp Gln Tyr Leu Cys Asp Ala Asp Arg Leu Gln Glu

625 630 635 640

Arg Glu Leu

<210>44

<211>123

<212>PRT

<213> Homo sapiens

<400>44

Met Pro Phe Leu Tyr Asp Ile Ser Ser Cys Trp Thr Ser Phe Cys Phe

1 5 10 15

Leu Phe Phe Ser Pro Leu Asp Gly Val Leu Leu Cys Phe Pro Gly Trp

20 25 30

Asn Ala Val Ala Arg Ser Gln Leu Thr Ala Thr Ser Ala Ser Gln Val

35 40 45

Gln Ala Ile Leu Leu Val Ser Ala Ser Gly Val Ala Gly Ile Ile Gly

50 55 60

Thr Cys His His Ala Gln Pro Ile Phe Val Phe Leu Val Glu Met Gly

65 70 75 80

Phe His His Val Gly Gln Ala Cys Leu Lys Leu Leu Asn Ser Gly Asp

85 90 95

Pro Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile Thr Gly Met Ser His

100 105 110

His Ala Arg Pro Phe Phe Phe Phe Phe Ser Phe

115 120

<210>45

<211>133

<212>PRT

<213> Homo sapiens

<400>45

Met Ser Glu Ala Glu Asn Glu Phe Ile Asn Trp Val Ala Thr Ala Ala

1 5 10 15

Ile Glu Ala Asn Cys Ser Gln Cys Trp Leu Cys Val Glu Leu Pro Glu

20 25 30

Ala Ala Gly Asn Gly Leu Pro Trp Arg Ile Val Pro Ala Asn Ile Ser

35 40 45

Glu Trp Ile Cys Gln Tyr Gln Trp Glu Trp Asp Asn Thr Trp Phe Cys

50 55 60

Phe Asp Phe Leu Ser Gln Ser Val Ser Leu Ser Pro Arg Leu Glu Cys

65 70 75 80

Ser Gly Thr Ile Leu Ala Gln Cys Asn Leu Cys Leu Leu Gly Ser Ser

85 90 95

Asp Ser Pro Ala Ser Ala Ser Gln Val Ala Gly Ile Ile Gly Ala Cys

100 105 110

Arg His Ala Trp Leu Ile Phe Cys Ile Phe Ser Arg Asp Gly Val Ser

115 120 125

Pro Tyr Cys Pro Gly

130

<210>46

<211>244

<212>PRT

<213> Homo sapiens

<400>46

Met Ala Leu Phe Leu Asp Lys Met Gly Ser Leu Gln Lys Gly Asn Tyr

1 5 10 15

Ser Ser Gln Ser Gly Met Ile Pro Gly Ser Trp Gln His Lys Met Lys

20 25 30

Leu Gln Leu Ile Leu Lys Ser Ser Lys Ala Tyr Tyr Val Leu Ser Asp

35 40 45

Ala Ala Met Ser Leu Gln Lys Tyr Gly Arg Ala Leu Arg Tyr Ile Lys

50 55 60

Leu Ala Leu Gln Ser His Asp Thr Tyr Cys Cys Leu Cys Thr Asn Met

65 70 75 80

Leu Ser Glu Val Leu Leu Phe Leu Ser Gln Tyr Leu Thr Leu Cys Gly

85 90 95

Asp Ile Gln Leu Met Leu Ala Gln Asn Ala Asn Asn Arg Ala Ala His

100 105 110

Leu Glu Glu Phe His Tyr Gln Thr Lys Glu Asp Gln Glu Ile Leu His

115 120 125

Ser Leu His Arg Glu Ser Ser Cys Gln Gly Val Pro Gln Ala Trp Thr

130 135 140

Thr Trp Phe Thr Val Gly Leu Cys Ser Leu Ala His Ala Tyr Leu Ser

145 150 155 160

Ile Gln Lys Arg Gly Arg Asn Ile Arg Val Leu Ile Phe Ala Leu Tyr

165 170 175

Leu Phe Ile Tyr Phe Leu Arg Arg Ser Phe Ala Leu Val Ala Gln Ala

180 185 190

Gly Val Gln Trp Cys Asn Leu Gly Ser Leu Lys Pro Pro Pro Pro Gly

195 200 205

Phe Lys Gln Phe Ser Cys Leu Ser Leu Pro Ser Ser Trp Asn Tyr Arg

210 215 220

His Ala Pro Pro Cys Pro Ala Ser Pro Pro Trp Pro Pro Lys Val Leu

225 230 235 240

Gly Leu Gln Val

<210>47

<211>79

<212>PRT

<213> Homo sapiens

<400>47

Arg Ser Leu Thr Leu Trp Pro Ser Leu Glu Tyr Ser Gly Thr Ile Ser

1 5 10 15

Ala His Cys Asn Leu Arg Leu Pro Gly Ser Ser Asp Ser Arg Ala Ser

20 25 30

Ala Ser Arg Ala Ala Gly Ile Thr Gly Val Ser His Cys Ala Arg Pro

35 40 45

Cys Met Leu Phe Asp Pro Glu Phe Asp Leu Leu Ala Gly Val Gln Leu

50 55 60

Leu Pro Phe Glu Pro Pro Thr Gly Lys Ala Leu Ser Arg Lys Asp

65 70 75

<210>48

<211>495

<212>PRT

<213> Homo sapiens

<400>48

Met Glu Phe Arg Lys Leu Arg Gly Met Glu Thr Arg Pro Pro Ala Asn

1 5 10 15

Thr Ala Arg Leu Gln Pro Pro Arg Asp Leu Arg Ser Ser Ser Pro Arg

20 25 30

Lys Gln Leu Ser Glu Ser Ser Asp Asp Asp Tyr Asp Asp Val Asp Ile

35 40 45

Pro Thr Pro Ala Glu Asp Thr Pro Pro Pro Leu Pro Pro Lys Pro Lys

50 55 60

Phe Arg Ser Pro Ser Asp Glu Gly Pro Gly Ser Met Gly Asp Asp Gly

65 70 75 80

Gln Leu Ser Pro Gly Val Leu Val Arg Cys Ala Ser Gly Pro Pro Pro Pro

85 90 95

Asn Ser Pro Arg Pro Gly Pro Pro Pro Ser Thr Ser Ser Pro His Leu

100 105 110

Thr Ala His Ser Glu Pro Ser Leu Trp Asn Pro Pro Ser Arg Glu Leu

115 120 125

Asp Lys Pro Pro Leu Leu Pro Pro Lys Lys Glu Lys Met Lys Arg Lys

130 135 140

Gly Cys Ala Leu Leu Val Lys Leu Phe Asn Gly Cys Pro Leu Arg Ile

145 150 155 160

His Ser Thr Ala Ala Trp Thr His Pro Ser Thr Lys Asp Gln His Leu

165 170 175

Leu Leu Gly Ala Glu Glu Gly Ile Phe Ile Leu Asn Arg Asn Asp Gln

180 185 190

Glu Ala Thr Leu Glu Met Leu Phe Pro Ser Arg Thr Thr Trp Val Tyr

195 200 205

Ser Ile Asn Asn Val Leu Met Ser Leu Ser Gly Lys Thr Pro His Leu

210 215 220

Tyr Ser His Ser Ile Leu Gly Leu Leu Glu Arg Lys Glu Thr Arg Ala

225 230 235 240

Gly Asn Pro Ile Ala His Ile Ser Pro His Arg Leu Leu Ala Arg Lys

245 250 255

Asn Met Val Ser Thr Lys Ile Gln Asp Thr Lys Gly Cys Arg Ala Cys

260 265 270

Cys Val Ala Glu Gly Ala Ser Ser Gly Gly Pro Phe Leu Cys Gly Ala

275 280 285

Leu Glu Thr Ser Val Val Leu Leu Gln Trp Tyr Gln Pro Met Asn Lys

290 295 300

Phe Leu Leu Val Arg Gln Val Leu Phe Pro Leu Pro Thr Pro Leu Ser

305 310 315 320

Val Phe Ala Leu Leu Thr Gly Pro Gly Ser Glu Leu Pro Ala Val Cys

325 330 335

Ile Gly Val Ser Pro Gly Arg Pro Gly Lys Ser Val Leu Phe His Thr

340 345 350

Val Arg Phe Gly Ala Leu Ser Cys Trp Leu Gly Glu Met Ser Thr Glu

355 360 365

His Arg Gly Pro Val Gln Val Thr Gln Val Glu Glu Asp Met Val Met

370 375 380

Val Leu Met Asp Gly Ser Val Lys Leu Val Thr Pro Glu Gly Ser Pro

385 390 395 400

Val Arg Gly Leu Arg Thr Pro Glu Ile Pro Met Thr Glu Ala Val Glu

405 410 415

Ala Val Ala Met Val Gly Gly Gln Leu Gln Ala Phe Trp Lys His Gly

420 425 430

Val Gln Val Trp Ala Leu Gly Ser Asp Gln Leu Leu Gln Glu Leu Arg

435 440 445

Asp Pro Thr Leu Thr Phe Arg Leu Leu Gly Ser Pro Arg Leu Glu Cys

450 455 460

Ser Gly Thr Ile Ser Pro His Cys Asn Leu Leu Leu Pro Gly Ser Ser

465 470 475 480

Asn Ser Pro Ala Ser Ala Ser Arg Val Ala Gly Ile Thr Gly Leu

485 490 495

<210>49

<211>102

<212>PRT

<213> Homo sapiens

<400>49

Met Ser Met Val Leu Gly Gly Pro Phe Ser Lys Gly His Thr Ala Ser

1 5 10 15

Asp Glu Tyr Phe Gln Ile Phe His Asn Ile Ser Phe Phe Glu Thr Glu

20 25 30

Ser Cys Ser Val Ala Gln Ala Gly Val Gln Trp Cys Asn Leu Gly Ser

35 40 45

Leu Gln Ala Leu Pro Pro Arg Phe Thr Pro Phe Ser Cys Leu Ser Leu

50 55 60

Pro Ser Ser Trp Asp Tyr Arg His Pro Pro Pro Cys Pro Asp Asn Val

65 70 75 80

Phe Val Phe Ser Val Glu Thr Gly Leu His Cys Val Ser Gln Asp Gly

85 90 95

Leu Asn Leu Leu Thr Leu

100

<210>50

<211>257

<212>PRT

<213> Homo sapiens

<400>50

Met Asp Cys Gly Ser Val Gly Gly Gln Arg Thr Gln Arg Leu Pro Gly

1 5 101 5

Arg Gln Arg Leu Leu Phe Leu Pro Val Gly Leu Ser Gly Arg Pro Gly

20 25 30

Gly Ser Glu Thr Ser Ala Arg Arg Cys Leu Ser Ala Leu Ser Asp Gly

35 40 45

Leu Gly Ala Leu Arg Pro Arg Ala Pro Ala Ala Arg Gly Gly Val Ser

50 55 60

Arg Ala Ser Pro Leu Leu Leu Leu Leu Leu Val Pro Ser Pro Arg Leu

65 70 75 80

Ala Ala Ala Ala Pro Arg Arg Gln Leu Gly Asp Trp Glu Arg Ser Arg

85 90 95

Leu Gly Tyr Ala Ala Pro Pro Ala Gly Arg Ser Ser Ala Trp Arg Cys

100 105 110

Ser Pro Gly Val Ala Ala Ala Ala Gly Ala Leu Pro Gln Tyr His Gly

115 120 125

Pro Ala Pro Ala Leu Val Ser Cys Arg Arg Glu Leu Ser Leu Ser Ala

130 135 140

Gly Ser Leu Gln Leu Glu Arg Lys Arg Arg Asp Phe Thr Ser Ser Gly

145 150 155 160

Ser Arg Lys Leu Tyr Phe Asp Thr His Ala Leu Val Cys Leu Leu Glu

165 170 175

Asp Asn Glu Ser His Ser Phe Ile Gln Ala Gly Val Gln Trp His Ser

180 185 190

Leu Gly Leu Leu Gln Pro Pro Pro Pro Gly Phe Lys Arg Ser Ser His

195 200 205

Leu Ile Leu Leu Ser Ser Trp Asp Tyr Arg His Ala Pro Pro His Leu

210 215 220

Asp Asn Phe Ser Val Phe Leu Leu Glu Thr Gly Phe His His Val Gly

225 230 235 240

Gln Ala Gly Leu Lys Leu Leu Thr Ser Ser Asp Pro Pro Thr Leu Ala

245 250 255

Ser

<210>51

<211>92

<212>PRT

<213> Homo sapiens

<400>51

Met Asn Phe Phe Phe Lys Thr Glu Phe Leu Ser Val Thr Gln Ala Gly

1 5 10 15

Met Gln Trp His Asn Phe Ser Ser Leu Gln Pro Leu Pro Pro Gly Phe

20 25 30

Lys Gln Phe Ser Cys Leu Ser Leu Leu Ser Ser Trp Asp Tyr Arg His

35 40 45

Thr Pro Pro Cys Pro Ala Asn Phe Cys Ile Phe Ser Arg Gly Gly Val

50 55 60

Ser Pro Cys Trp Ser Gly Trp Ser Arg Thr Pro Asp Phe Met Ile His

65 70 75 80

Pro Pro Arg Pro Pro Lys Val Leu Arg Leu Gln Lys

85 90

<210>52

<211>841

<212>PRT

<213> Homo sapiens

<400>52

Met Pro Leu Ala Ala Tyr Cys Tyr Leu Arg Val Val Gly Lys Gly Ser

1 5 10 15

Tyr Gly Glu Val Thr Leu Val Lys His Arg Arg Asp Gly Lys Gln Tyr

20 25 30

Val Ile Lys Lys Leu Asn Leu Arg Asn Ala Ser Ser Arg Glu Arg Arg

35 40 45

Ala Ala Glu Gln Glu Ala Gln Leu Leu Ser Gln Leu Lys His Pro Asn

50 55 60

Ile Val Thr Tyr Lys Glu Ser Trp Glu Gly Gly Asp Gly Leu Leu Tyr

65 70 75 80

Ile Val Met Gly Phe Cys Glu Gly Gly Asp Leu Tyr Arg Lys Leu Lys

85 90 95

Glu Gln Lys Gly Gln Leu Leu Pro Glu Asn Gln Val Val Glu Trp Phe

100 105 110

Val Gln Ile Ala Met Ala Leu Gln Tyr Leu His Glu Lys His Ile Leu

115 120 125

His Arg Asp Leu Lys Thr Gln Asn Val Phe Leu Thr Arg Thr Asn Ile

130 135 140

Ile Lys Val Gly Asp Leu Gly Ile Ala Arg Val Leu Glu Asn His Cys

145 150 155 160

Asp Met Ala Ser Thr Leu Ile Gly Thr Pro Tyr Tyr Met Ser Pro Glu

165 170 175

Leu Phe Ser Asn Lys Pro Tyr Asn Tyr Lys Ser Asp Val Trp Ala Leu

180 185 190

Gly Cys Cys Val Tyr Glu Met Ala Thr Leu Lys His Ala Phe Asn Ala

195 200 205

Lys Asp Met Asn Ser Leu Val Tyr Arg Ile Ile Glu Gly Lys Leu Pro

210 215 220

Pro Met Pro Arg Asp Tyr Ser Pro Glu Leu Ala Glu Leu Ile Arg Thr

225 230 235 240

Met Leu Ser Lys Arg Pro Glu Glu Arg Pro Ser Val Arg Ser Ile Leu

245 250 255

Arg Gln Pro Tyr Ile Lys Arg Gln Ile Ser Phe Phe Leu Glu Ala Thr

260 265 270

Lys Ile Lys Thr Ser Lys Asn Asn Ile Lys Asn Gly Asp Ser Gln Ser

275 280 285

Lys Pro Phe Ala Thr Val Val Ser Gly Glu Ala Glu Ser Asn His Glu

290 295 300

Val Ile His Pro Gln Pro Leu Ser Ser Glu Gly Ser Gln Thr Tyr Ile

305 310 315 320

Met Gly Glu Gly Lys Cys Leu Ser Gln Glu Lys Pro Arg Ala Ser Gly

325 330 335

Leu Leu Lys Ser Pro Ala Ser Leu Lys Ala His Thr Cys Lys Gln Asp

340 345 350

Leu Ser Asn Thr Thr Glu Leu Ala Thr Ile Ser Ser Val Asn Ile Asp

355 360 365

Ile Leu Pro Ala Lys Gly Arg Asp Ser Val Ser Asp Gly Phe Val Gln

370 375 380

Glu Asn Gln Pro Arg Tyr Leu Asp Ala Ser Asn Glu Leu Gly Gly Ile

385 390 395 400

Cys Ser Ile Ser Gln Val Glu Glu Glu Met Leu Gln Asp Asn Thr Lys

405 410 415

Ser Ser Ala Gln Pro Glu Asn Leu Ile Pro Met Trp Ser Ser Asp Ile

420 425 430

Val Thr Gly Glu Lys Asn Glu Pro Val Lys Pro Leu Gln Pro Leu Ile

435 440 445

Lys Glu Gln Lys Pro Lys Asp Gln Ser Leu Ala Leu Ser Pro Lys Leu

450 455 460

Glu Cys Ser Gly Thr Ile Leu Ala His Ser Asn Leu Arg Leu Leu Gly

465 470 475 480

Ser Ser Asp Ser Pro Ala Ser Ala Ser Arg Val Ala Gly Ile Thr Gly

485 490 495

Val Cys His His Ala Gln Asp Gln Val Ala Gly Glu Cys Ile Ile Glu

500 505 510

Lys Gln Gly Arg Ile His Pro Asp Leu Gln Pro His Asn Ser Gly Ser

515 520 525

Glu Pro Ser Leu Ser Arg Gln Arg Arg Gln Lys Arg Arg Glu Gln Thr

530 535 540

Glu His Arg Gly Glu Lys Arg Gln Val Arg Arg Asp Leu Phe Ala Phe

545 550 555 560

Gln Glu Ser Pro Pro Arg Phe Leu Pro Ser His Pro Ile Val Gly Lys

565 570 575

Val Asp Val Thr Ser Thr Gln Lys Glu Ala Glu Asn Gln Arg Arg Val

580 585 590

Val Thr Gly Ser Val Ser Ser Ser Ser Arg Ser Ser Glu Met Ser Ser Ser

595 600 605

Lys Asp Arg Pro Leu Ser Ala Arg Glu Arg Arg Arg Leu Lys Gln Ser

610 615 620

Gln Glu Glu Met Ser Ser Ser Ser Gly Pro Ser Val Arg Lys Ala Ser Leu

625 630 635 640

Ser Val Ala Gly Pro Gly Lys Pro Gln Glu Glu Asp Gln Pro Leu Pro

645 650 655

Ala Arg Arg Leu Ser Ser Asp Cys Ser Val Thr Gln Glu Arg Lys Gln

660 665 670

Ile His Cys Leu Ser Glu Asp Glu Leu Ser Ser Ser Thr Ser Ser Ser Thr

675 680 685

Asp Lys Ser Asp Gly Asp Tyr Gly Glu Gly Lys Gly Gln Thr Asn Glu

690 695 700

Ile Asn Ala Leu Val Gln Leu Met Thr Gln Thr Leu Lys Leu Asp Ser

705 710 715 720

Lys Glu Ser Cys Glu Asp Val Pro Val Ala Asn Pro Val Ser Glu Phe

725 730 735

Lys Leu His Arg Lys Tyr Arg Asp Thr Leu Ile Leu His Gly Lys Val

740 745 750

Ala Glu Glu Ala Glu Glu Ile His Phe Lys Glu Leu Pro Ser Ala Ile

755 760 765

Met Pro Gly Ser Glu Lys Ile Arg Arg Leu Val Glu Val Leu Arg Thr

770 775 780

Asp Val Ile Arg Gly Leu Gly Val Gln Leu Leu Glu Gln Val Tyr Asp

785 790 795 800

Leu Leu Glu Glu Glu Asp Glu Phe Asp Arg Glu Val Arg Leu Arg Glu

805 810 815

His Met Gly Glu Lys Tyr Thr Thr Tyr Ser Val Lys Ala Arg Gln Leu

820 825 830

Lys Phe Phe Glu Glu Asn Met Asn Phe

835 840

<210>53

<211>85

<212>PRT

<213> Homo sapiens

<400>53

Met Phe Ile Ser Phe Gly Arg Leu Ile Phe Ser Phe Phe Leu Thr Trp

1 5 10 15

Ser Leu Ser Leu Ser Pro Arg Leu Glu Cys Ser Gly Thr Ile Leu Ala

20 25 30

His Cys Asn Pro Thr Ser Gln Val Gln Ala Ile Leu Pro Ala Ser Ala

35 40 45

Ser Arg Val Ala Gly Ile Thr Gly Met His His His Thr Cys Leu Ile

50 55 60

Phe Val Leu Leu Val Lys Met Gly Phe Cys His Val Gly His Ala Gly

65 70 75 80

Leu Glu Leu Val Thr

85

<210>54

<211>73

<212>PRT

<213> Homo sapiens

<400>54

Met Glu Ser Gly Gln Pro Ser Leu Ser Phe Tyr Phe Leu Phe Ile Tyr

1 5 10 15

Phe Phe Glu Ile Gly Ser His Phe Val Thr Gln Ala Gly Val Gln Trp

20 25 30

His Asn Leu Asp Ser Leu Gln Leu Ser Leu Ala Ser Ala Pro Gln Val

35 40 45

Ala Gly Thr Thr Gly Ala Cys His His His Ala Arg Leu Ile Phe Gly Val

50 55 60

Phe Cys Arg Asp Trp Val Leu Pro Cys

65 70

<210>55

<211>181

<212>PRT

<213> Homo sapiens

<400>55

Met Leu Leu Val Asp Ala Asp Gln Pro Glu Pro Met Arg Ser Gly Ala

1 5 10 15

Arg Glu Leu Ala Leu Phe Leu Thr Pro Glu Pro Gly Ala Glu Ala Lys

20 25 30

Glu Val Glu Glu Thr Ile Glu Gly Met Leu Leu Arg Leu Glu Glu Phe

35 40 45

Cys Ser Leu Ala Asp Leu Ile Arg Ser Asp Thr Ser Gln Ile Leu Glu

50 55 60

Glu Asn Ile Pro Val Leu Lys Ala Lys Leu Thr Glu Met Arg Gly Ile

65 70 75 80

Tyr Ala Lys Val Asp Arg Leu Glu Ala Phe Val Lys Met Val Gly His

85 90 95

His Val Ala Phe Leu Glu Ala Asp Val Leu Gln Ala Glu Arg Asp His

100 105 110

Gly Ala Phe Pro Gln Ala Leu Arg Arg Trp Leu Gly Ser Ala Gly Leu

115 120 125

Pro Ser Phe Arg Asn Val Glu Cys Ser Gly Thr Ile Pro Ala Arg Cys

130 135 140

Asn Leu Arg Leu Pro Gly Ser Ser Asp Ser Pro Ala Ser Ala Ser Gln

145 150 155 160

Val Ala Gly Ile Pro Glu Val Thr Cys Thr Gly Ala Arg Asp Val Arg

165 170 175

Ala Ala His Thr Val

                           

<210>56

<211>876

<212>PRT

<213> Rat (Rattus norvegicus)

<400>56

Met Ser Arg Gly Asn Glu Asn Arg Leu Thr His Arg Arg Gln Thr Val

1 5 10 15

Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn Arg Gly Pro Ala Tyr Met

20 25 30

Phe Asn Asp His Ser Thr Ser Leu Ser Ile Glu Glu Glu Arg Phe Leu

35 40 45

Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu

50 55 60

Glu Cys Leu Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln Asn

65 70 75 80

Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu Leu

85 90 95

Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu Leu

100 105 110

Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His

115 120 125

Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Pro Ser Gln Ser

130 135 140

Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg

145 150 155 160

Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln Glu

165 170 175

Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu Arg

180 185 190

Pro His Asp Tyr Phe Cys Lys Cys Thr Glu Cys Ser Gln Lys Gln Lys

195 200 205

His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys Gly

210 215 220

Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val Met

225 230 235 240

Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile Glu

245 250 255

Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp

260 265 270

Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val Glu

275 280 285

Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg Gln Pro Gly Asp Leu Ala

290 295 300

Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val Lys

305 310 315 320

Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile Trp

325 330 335

Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys Phe

340 345 350

Leu Val Val Leu Ala Val Ala Ile Gly Leu Pro Phe Leu Ala Leu Ile

355 360 365

Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Leu Arg Gly Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu Leu

405 410 415

Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg Gln Leu Phe Arg Met Lys

420 425 430

Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val Ile

435 440 445

Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Thr Gln Gly Pro Lys

450 455 460

Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu Ala

465 470 475 480

Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His Ala

485 490 495

Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp Leu

500 505 510

Thr Lys Val Thr Leu Gly Asp Asn Val Lys Tyr Tyr Asn Leu Ala Arg

515 520 525

Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala Lys

595 600 605

Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val Ile Asn Tyr

625 630 635 640

Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu Gly Arg Thr

690 695 700

Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Leu Leu Tyr

705 710 715 720

Leu Leu Leu Lys Phe Lys Lys Trp Met Ser Glu Leu Ile Gln Gly His

725 730 735

Lys Lys Gly Phe Gln Glu Asp Ala Glu Met Asn Lys Arg Asn Glu Glu

740 745 750

Lys Lys Phe Gly Ile Leu Gly Ser His Glu Asp Leu Ser Lys Phe Ser

755 760 765

Leu Asp Arg Asn Gln Leu Ala His Asn Lys Gln Ser Ser Thr Arg Ser

770 775 780

Ser Glu Asp Phe His Leu Asn Ser Phe Ser Asn Pro Pro Arg Gln Tyr

785 790 795 800

Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala Gln

805 810 815

Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile

820 825 830

Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser

835 840 845

Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Lys Leu Gly Glu Arg

850 855 860

Leu Ser Leu Glu Ser Lys Gln Glu Glu Ser Arg Arg

865 870 875

<210>57

<211>808

<212>PRT

<213> Rat (Rattus norvegicus)

<400>57

Met Ser Arg Gly Asn Glu Asn Arg Leu Thr His Arg Arg Gln Thr Val

1 5 10 15

Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn Arg Gly Pro Ala Tyr Met

20 25 30

Phe Asn Asp His Ser Thr Ser Leu Ser Ile Glu Glu Glu Arg Phe Leu

35 40 45

Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu

50 55 60

Glu Cys Leu Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln Asn

65 70 75 80

Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu Leu

85 90 95

Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu Leu

100 105 110

Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His

115 120 125

Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Pro Ser Gln Ser

130 135 140

Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg

145 150 155 160

Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln Glu

165 170 175

Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu Arg

180 185 190

Pro His Asp Tyr Phe Cys Lys Cys Thr Glu Cys Ser Gln Lys Gln Lys

195 200 205

His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys Gly

210 215 220

Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val Met

225 230 235 240

Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile Glu

245 250 255

Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp

260 265 270

Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val Glu

275 280 285

Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg Gln Pro Gly Asp Leu Ala

290 295 300

Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val Lys

305 310 315 320

Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile Trp

325 330 335

Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys Phe

340 345 350

Leu Val Val Leu Ala Val Ala Ile Gly Leu Pro Phe Leu Ala Leu Ile

355 360 365

Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Leu Arg Gly Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu Leu

405 410 415

Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg Gln Leu Phe Arg Met Lys

420 425 430

Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val Ile

435 440 445

Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Thr Gln Gly Pro Lys

450 455 460

Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu Ala

465 470 475 480

Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His Ala

485 490 495

Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp Leu

500 505 510

Thr Lys Val Thr Leu Gly Asp Asn Val Lys Tyr Tyr Asn Leu Ala Arg

515 520 525

Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala Lys

595 600 605

Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

6l0 615 620

Trp Ala Ile Phe Gly Leu Ser Glu Val Arg Ser Val Val Ile Asn Tyr

625 630 635 640

Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Ser Ser Phe Gln Glu Ile Glu Arg Asn Glu Glu Lys Lys Phe Gly

675 680 685

Ile Leu Gly Ser His Glu Asp Leu Ser Lys Phe Ser Leu Asp Arg Asn

690 695 700

Gln Leu Ala His Asn Lys Gln Ser Ser Thr Arg Ser Ser Glu Asp Phe

705 710 715 720

His Leu Asn Ser Phe Ser Asn Pro Pro Arg Gln Tyr Gln Lys Ile Met

725 730 735

Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala Gln Ile Asp Lys Glu

740 745 750

Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile

755 760 765

Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser Gln Asn Thr Glu

770 775 780

Asp Leu Ala Glu Leu Ile Arg Arg Leu Gly Glu Arg Leu Ser Leu Glu

785 790 795 800

Ser Lys Gln Glu Glu Ser Arg Arg

805

<210>58

<211>83

<212>PRT

<213> Homo sapiens

<400>58

Met Glu Ser Arg Ser Val Ala Gln Ala Gly Val Gln Trp Pro Asp Leu

1 5 10 15

Gly Ser Leu Gln Pro Leu Pro Pro Arg Phe Lys Arg Phe Phe Cys Leu

20 25 30

Ser Leu Gln Ser Ser Trp Asp Tyr Arg His Ala Pro Pro Arg Pro Ala

35 40 45

Asn Phe Val Phe Leu Val Glu Thr Gly Phe Cys His Val Ser Gln Ala

50 55 60

Gly Leu Glu Leu Leu Thr Ser Ser Asp Pro Pro Pro Arg Pro Pro Lys

65 70 75 80

Val Leu Arg

<210>59

<211>141

<212>PRT

<213> Homo sapiens

<400>59

Met Ile Ser Val His Cys Asn Leu Cys Leu Pro Gly Ser Ser Asp Pro

1 5 10 15

Pro Ala Ser Ala Ser Gln Val Ala Gly Ile Thr Gly Val Arg His Cys

20 25 30

Met Ala Ser Gly Ala Val Leu Asn Lys Val Arg Arg His Gln Cys Ser

35 40 45

Gly Asp Leu Glu Val Arg Gly Ser His Gly Ser Leu Gly Glu Ala Pro

50 55 60

Trp Gly Lys Ser Val Pro Gly Arg Gly Thr Ala Ser Arg Lys Gly Pro

65 70 75 80

Gly Ala Gly Val Ile Gly Asn Ser Lys Glu Ala Ser Thr Gly Arg Ala

85 90 95

Gln Trp Ser Ala Pro Val Ile Pro Ala Thr Gln Glu Ala Lys Ala Gly

100 105 110

Gly Leu Leu Glu Pro Arg Ser Leu Ile Ser Ala Trp Ala Thr Tyr Gln

115 120 125

Asp Leu Ile Ser Ile Asn Lys Leu Lys Glu Lys Arg Gly

130 135 140

<210>60

<211>177

<212>PRT

<213> Homo sapiens

<400>60

Met Thr Arg Ser Leu Phe Lys Gly Asn Phe Trp Ser Ala Asp Ile Leu

1 5 10 15

Ser Thr Ile Gly Tyr Asp Asn Ile Ile Gln His Leu Asn Asn Gly Arg

20 25 30

Lys Asn Cys Lys Glu Phe Glu Asp Phe Leu Lys Glu Arg Ala Ala Ile

35 40 45

Glu Glu Arg Tyr Gly Lys Asp Leu Leu Asn Leu Ser Arg Lys Lys Pro

50 55 60

Cys Gly Gln Ser Glu Ile Asn Thr Leu Lys Arg Ala Leu Glu Val Phe

65 70 75 80

Lys Gln Gln Val Asp Asn Val Ala Gln Cys His Ile Gln Leu Ala Gln

85 90 95

Ser Leu Arg Glu Glu Ala Arg Lys Met Glu Glu Phe Arg Glu Lys Gln

100 105 110

Lys Leu Gln Arg Lys Lys Met Glu Ser His Ser Val Thr Gln Ala Gly

115 120 125

Ala Gln Trp His Asp Leu Gly Ser Leu Gln Ala Leu Pro Pro Gly Phe

130 135 140

Met Pro Phe Ser Cys Leu Ser Leu Pro Ser Ser Trp Asn Tyr Arg Leu

145 150 155 160

Pro Pro Pro Pro Arg Leu Ala Glu Pro Arg Asn Gln Asp His Gly Val

165 170 175

Ala

<210>61

<211>66

<212>PRT

<213> Homo sapiens

<400>61

Met Glu Ser His Ser Val Thr Gln Ala Gly Val Gln Trp Arg Asp Leu

1 5 10 15

Gly Ser Leu Gln Pro Leu Pro Pro Gly Phe Lys Gln Phe Ser His Leu

20 25 30

Ser Leu Pro Ser Ser Trp Asp Tyr Arg Arg Val Pro Pro Tyr Leu Gly

35 40 45

Asn Phe Cys Ile Phe Ser Gly Glu Gly Val Ser Pro Cys Trp Pro Gly

50 55 60

Trp Ser

65

<210>62

<211>392

<212>PRT

<213> Homo sapiens

<400>62

Met Gly Ser Leu Ser Thr Ala Asn Val Glu Phe Cys Leu Asp Val Phe

1 5 10 15

Lys Glu Leu Asn Ser Asn Asn Ile Gly Asp Asn Ile Phe Phe Ser Ser

20 25 30

Leu Ser Leu Leu Tyr Ala Leu Ser Met Val Leu Leu Gly Ala Arg Gly

35 40 45

Glu Thr Ala Glu Gln Leu Glu Lys Val Leu His Phe Ser His Thr Val

50 55 60

Asp Ser Leu Lys Pro Gly Phe Lys Asp Ser Pro Lys Cys Ser Gln Ala

65 70 75 80

Gly Arg Ile His Ser Glu Phe Gly Val Glu Phe Ser Gln Ile Asn Gln

85 90 95

Pro Asp Ser Asn Cys Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Thr

100 105 110

Lys Thr Met Ala Phe His Gln Gln Tyr Leu Ser Cys Ser Glu Lys Trp

115 120 125

Tyr Gln Ala Arg Leu Gln Thr Val Asp Phe Glu Gln Ser Thr Glu Glu

130 135 140

Thr Arg Lys Thr Ile Asn Ala Trp Val Glu Asn Lys Thr Asn Gly Lys

145 150 155 160

Val Ala Asn Leu Phe Gly Lys Ser Thr Ile Asp Pro Ser Ser Val Met

165 170 175

Val Leu Val Asn Thr Ile Tyr Phe Lys Gly Gln Arg Gln Asn Lys Phe

180 185 190

Gln Val Arg Glu Thr Val Lys Ser Pro Phe Gln Leu Ser Glu Gly Lys

195 200 205

Asn Val Thr Val Glu Met Met Tyr Gln Ile Gly Thr Phe Lys Leu Ala

210 215 220

Phe Val Lys Glu Pro Gln Met Gln Val Leu Glu Leu Pro Tyr Val Asn

225 230 235 240

Asn Lys Leu Ser Met Ile Ile Leu Leu Pro Val Gly Ile Ala Asn Leu

245 250 255

Lys Gln Ile Glu Lys Gln Leu Asn Ser Gly Thr Phe His Glu Trp Thr

260 265 270

Ser Ser Ser Asn Met Met Glu Arg Glu Val Glu Val His Leu Pro Arg

275 280 285

Phe Lys Leu Glu Ile Lys Tyr Glu Leu Asn Ser Leu Leu Lys Pro Leu

290 295 300

Gly Val Thr Asp Leu Phe Asn Gln Val Lys Ala Asp Leu Ser Gly Met

305 310 315 320

Ser Pro Thr Lys Gly Leu Tyr Leu Ser Lys Ala Ile His Lys Ser Tyr

325 330 335

Leu Asp Val Ser Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Gly Asp

340 345 350

Ser Ile Ala Val Lys Ser Leu Pro Met Arg Ala Gln Phe Lys Ala Asn

355 360 365

His Pro Phe Leu Phe Phe Ile Arg His Thr His Thr Asn Thr Ile Leu

370 375 380

Phe Cys Gly Lys Leu Ala Ser Pro

385 390

<210>63

<211>982

<212>PRT

<213> Homo sapiens

<400>63

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Val Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Phe Val Ala Gln Pro

290 295 300

Asn Cys Gln Gln Leu Leu Ala Ser Arg Trp Tyr Asp Glu Phe Pro Gly

305 310 315 320

Trp Arg Arg Arg His Trp Ala Val Lys Met Val Thr Cys Phe Ile Ile

325 330 335

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

340 345 350

Ser Pro Leu Gly Leu Phe Ile Arg Lys Pro Phe Ile Lys Phe Ile Cys

355 360 365

His Thr Ala Ser Tyr Leu Thr Phe Leu Phe Leu Leu Leu Leu Ala Ser

370 375 380

Gln His Ile Asp Arg Ser Asp Leu Asn Arg Gln Gly Pro Pro Pro Thr

385 390 395 400

Ile Val Glu Trp Met Ile Leu Pro Trp Val Leu Gly Phe Ile Trp Gly

405 410 415

Glu Ile Lys Gln Met Trp Asp Gly Gly Leu Gln Asp Tyr Ile His Asp

420 425 430

Trp Trp Asn Leu Met Asp Phe Val Met Asn Ser Leu Tyr Leu Ala Thr

435 440 445

Ile Ser Leu Lys Ile Val Ala Phe Val Lys Tyr Ser Ala Leu Asn Pro

450 455 460

Arg Glu Ser Trp Asp Met Trp His Pro Thr Leu Val Ala Glu Ala Leu

465 470 475 480

Phe Ala Ile Ala Asn Ile Phe Ser Ser Leu Arg Leu Ile Ser Leu Phe

485 490 495

Thr Ala Asn Ser His Leu Gly Pro Leu Gln Ile Ser Leu Gly Arg Met

500 505 510

Leu Leu Asp Ile Leu Lys Phe Leu Phe Ile Tyr Cys Leu Val Leu Leu

515 520 525

Ala Phe Ala Asn Gly Leu Asn Gln Leu Tyr Phe Tyr Tyr Glu Glu Thr

530 535 540

Lys Gly Leu Thr Cys Lys Gly Ile Arg Cys Glu Lys Gln Asn Asn Ala

545 550 555 560

Phe Ser Thr Leu Phe Glu Thr Leu Gln Ser Leu Phe Trp Ser Ile Phe

565 570 575

Gly Leu Ile Asn Leu Tyr Val Thr Asn Val Lys Ala Gln His Glu Phe

580 585 590

Thr Glu Phe Val Gly Ala Thr Met Phe Gly Thr Tyr Asn Val Ile Ser

595 600 605

Leu Val Val Leu Leu Asn Met Leu Ile Ala Met Met Asn Asn Ser Tyr

610 615 620

Gln Leu Ile Ala Asp His Ala Asp Ile Glu Trp Lys Phe Ala Arg Thr

625 630 635 640

Lys Leu Trp Met Ser Tyr Phe Glu Glu Gly Gly Thr Leu Pro Thr Pro

645 650 655

Phe Asn Val Ile Pro Ser Pro Lys Ser Leu Trp Tyr Leu Ile Lys Trp

660 665 670

Ile Trp Thr His Leu Cys Lys Lys Lys Met Arg Arg Lys Pro Glu Ser

675 680 685

Phe Gly Thr Ile Gly Val Arg Thr Gln His Arg Arg Ala Ala Asp Asn

690 695 700

Leu Arg Arg His His Gln Tyr Gln Glu Val Met Arg Asn Leu Val Lys

705 710 715 720

Arg Tyr Val Ala Ala Met Ile Arg Asp Ala Lys Thr Glu Glu Gly Leu

725 730 735

Thr Glu Glu Asn Phe Lys Glu Leu Lys Gln Asp Ile Ser Ser Phe Arg

740 745 750

Phe Glu Val Leu Gly Leu Leu Arg Gly Ser Lys Leu Ser Thr Ile Gln

755 760 765

Ser Ala Asn Ala Ser Lys Glu Ser Ser Ser Asn Ser Ala Asp Ser Asp Glu

770 775 780

Lys Ser Asp Ser Glu Gly Asn Ser Lys Asp Lys Lys Lys Asn Phe Ser

785 790 795 800

Leu Phe Asp Leu Thr Thr Leu Ile His Pro Arg Ser Ala Ala Ile Ala

805 810 815

Ser Glu Arg His Asn Ile Ser Asn Gly Ser Ala Leu Val Val Gln Glu

820 825 830

Pro Pro Arg Glu Lys Gln Arg Lys Val Asn Phe Val Thr Asp Ile Lys

835 840 845

Asn Phe Gly Leu Phe His Arg Arg Ser Lys Gln Asn Ala Ala Glu Gln

850 855 860

Asn Ala Asn Gln Ile Phe Ser Val Ser Glu Glu Val Ala Arg Gln Gln

865 870 875 880

Ala Ala Gly Pro Leu Glu Arg Asn Ile Gln Leu Glu Ser Arg Gly Leu

885 890 895

Ala Ser Arg Gly Asp Leu Ser Ile Pro Gly Leu Ser Glu Gln Cys Val

900 905 910

Leu Val Asp His Arg Glu Arg Asn Thr Asp Thr Leu Gly Leu Gln Val

915 920 925

Gly Lys Arg Val Cys Pro Phe Lys Ser Glu Lys Val Val Val Glu Asp

930 935 940

Thr Val Pro Ile Ile Pro Lys Glu Lys His Ala Lys Glu Glu Asp Ser

945 950 955 960

Ser Ile Asp Tyr Asp Leu Asn Leu Pro Asp Thr Val Thr His Glu Asp

965 970 975

Tyr Val Thr Thr Arg Leu

980

<210>64

<211>323

<212>PRT

<213> Homo sapiens

<400>64

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Mal Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Ala Ser Tyr Gly Glu

290 295 300

Lys Leu Asn Arg Cys Gly Met Ala Asp Phe Arg Thr Thr Ser Met Ile

305 310 315 320

Gly Gly Ile

<210>65

<211>930

<212>PRT

<213> Rat (Rattus norvegicus)

<400>65

Met Ser Gln Ser Pro Gly Phe Val Thr Arg Arg Gly Gly Ser Pro Lys

1 5 10 15

Ala Ala Pro Gly Ala Gly Ala Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Glu Leu Gly Asp Asp Gly Tyr Pro Gln Leu Gln Gln Pro

35 40 45

Pro Tyr Gly Tyr Tyr Pro Ser Phe Arg Gly Asn Glu Asn Arg Leu Thr

50 55 60

His Arg Arg Gln Thr Val Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn

65 70 75 80

Arg Gly Pro Ala Tyr Met Phe Asn Asp His Ser Thr Ser Leu Ser Ile

85 90 95

Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val

100 105 110

Val Arg Lys Met Leu Glu Glu Cys Leu Ser Leu Asn Val Asn Cys Val

115 120 125

Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His

130 135 140

Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val

145 150 155 160

Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val

165 170 175

Glu Ala Ile Leu Asn His Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala

180 185 190

Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr

195 200 205

Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu

210 215 220

Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys

225 230 235 240

Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Thr Glu

245 250 255

Cys Ser Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser Arg

260 265 270

Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser

275 280 285

Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala

290 295 300

Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu

305 310 315 320

Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg

325 330 335

Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg

340 345 350

Gln Pro Gly Asp Leu Ala Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala

355 360 365

Ile Lys Tyr Glu Val Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln

370 375 380

Gln Leu Leu Ser Ile Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln

385 390 395 400

Thr Met Ala Val Lys Phe Leu Val Val Leu Ala Val Ala Ile Gly Leu

405 410 415

Pro Phe Leu Ala Leu Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly

420 425 430

Lys Ile Leu Arg Gly Pro Phe Met Lys Phe Val Ala His Ala Ala Ser

435 440 445

Phe Thr Ile Phe Leu Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe

450 455 450

Glu Gly Thr Lys Leu Leu Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg

465 470 475 480

Gln Leu Phe Arg Met Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu

485 490 495

Ile Ile Ser Trp Val Ile Gly Met Ile Trp Ala Glu Cys Lys Glu Ile

500 505 510

Trp Thr Gln Gly Pro Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu

515 520 525

Asp Phe Gly Met Leu Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe

530 535 540

Met Ala Phe Trp His Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn

545 550 555 560

Asp Thr Leu Lys Asp Leu Thr Lys Val Thr Leu Gly Asp Asn Val Lys

565 570 575

Tyr Tyr Asn Leu Ala Arg Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile

580 585 590

Ile Ser Glu Gly Leu Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg

595 600 605

Ile Ala Tyr Ile Leu Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile

610 615 620

Ser Leu Gly Arg Thr Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe

625 630 635 640

Ile Met Val Phe Val Ala Phe Met Ile Gly Met Phe Asn Leu Tyr Ser

645 650 655

Tyr Tyr Ile Gly Ala Lys Gln Asn Glu Ala Phe Thr Thr Val Glu Glu

660 665 670

Ser Phe Lys Thr Leu Phe Trp Ala Ile Phe Gly Leu Ser Glu Val Lys

675 680 685

Ser Val Val Ile Asn Tyr Asn His Lys Phe Ile Glu Asn Ile Gly Tyr

690 695 700

Val Leu Tyr Gly Val Tyr Asn Val Thr Met Val Ile Val Leu Leu Asn

705 710 715 720

Met Leu Ile Ala Met Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp

725 730 735

Ala Asp Val Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr

740 745 750

Phe Glu Glu Gly Arg Thr Leu Pro Val Pro Phe Asn Leu Val Pro Ser

755 760 765

Pro Lys Ser Leu Leu Tyr Leu Leu Leu Lys Phe Lys Lys Trp Met Ser

770 775 780

Glu Leu Ile Gln Gly His Lys Lys Gly Phe Gln Glu Asp Ala Glu Met

785 790 795 800

Asn Lys Arg Asn Glu Glu Lys Lys Phe Gly Ile Leu Gly Ser His Glu

805 810 815

Asp Leu Ser Lys Phe Ser Leu Asp Arg Asn Gln Leu Ala His Asn Lys

820 825 830

Gln Ser Ser Thr Arg Ser Ser Glu Asp Phe His Leu Asn Ser Phe Ser

835 840 845

Asn Pro Pro Arg Gln Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys Arg

850 855 860

Tyr Val Leu Gln Ala Gln Ile Asp Lys Glu Ser Asp Glu Val Asn Glu

865 870 875 880

Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu

885 890 895

Leu Leu Glu Glu Lys Ser Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile

900 905 910

Arg Lys Leu Gly Glu Arg Leu Ser Leu Glu Ser Lys Gln Glu Glu Ser

915 920 925

Arg Arg

930

<210>66

<211>139

<212>PRT

<213> Homo sapiens

<400>66

Met Gly His Pro Arg Ala Ile Gln Pro Ser Val Phe Phe Ser Pro Tyr

1 5 10 15

Asp Val His Phe Leu Leu Tyr Pro Ile Arg Cys Pro Tyr Leu Lys Ile

20 25 30

Gly Arg Phe His Ile Lys Leu Lys Gly Leu His Phe Leu Phe Ser Phe

35 40 45

Leu Phe Phe Phe Phe Glu Thr Gln Ser His Ser Val Thr Arg Leu Glu

50 55 60

Cys Ser Gly Thr Ile Ser Ala His Cys Asn Leu Cys Leu Pro Gly Ser

65 70 75 80

Ser Asn Ser Pro Ala Ser Ala Ser Arg Val Ala Gly Thr Ala Gly Thr

85 90 95

Cys Arg Arg Ala Gln Leu Ile Phe Val Phe Leu Ala Glu Met Gly Phe

100 105 110

His His Val Gly Arg Asp Gly Leu Asp Leu Asn Leu Val Ile His Pro

115 120 125

Pro Arg Ser Pro Lys Ala Leu Gly Leu Gln Ala

130 135

<210>67

<21l>392

<212>PRT

<213> Homo sapiens

<400>67

Met Gly Ser Leu Ser Thr Ala Asn Val Glu Phe Cys Leu Asp Val Phe

1 5 10 15

Lys Glu Leu Asn Ser Asn Asn Ils Gly Asp Asn Ile Phe Phe Ser Ser

20 25 30

Leu Ser Leu Leu Tyr Ala Leu Ser Met Val Leu Leu Gly Ala Arg Gly

35 40 45

Glu Thr Ala Glu Gln Leu Glu Lys Val Leu His Phe Ser His Thr Val

50 55 60

Asp Ser Leu Lys Pro Gly Phe Lys Asp Ser Pro Lys Cys Ser Gln Ala

65 70 75 80

Gly Arg Ile His Ser Glu Phe Gly Val Glu Phe Ser Gln Ile Asn Gln

85 90 95

Pro Asp Ser Asn Cys Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Thr

100 105 110

Lys Thr Met Ala Phe His Gln Gln Tyr Leu Ser Cys Ser Glu Lys Trp

115 120 125

Tyr Gln Ala Arg Leu Gln Thr Val Asp Phe Glu Gln Ser Thr Glu Glu

130 135 140

Thr Arg Lys Met Ile Asn Ala Trp Val Glu Asn Lys Thr Asn Gly Lys

145 150 155 160

Val Ala Asn Leu Phe Gly Lys Ser Thr Ile Asp Pro Ser Ser Val Met

165 170 175

Val Leu Val Asn Thr Ile Tyr Phe Lys Gly Gln Arg Gln Asn Lys Phe

180 185 190

Gln Val Arg Glu Thr Val Lys Ser Pro Phe Gln Leu Ser Glu Gly Lys

195 200 205

Asn Val Thr Val Glu Met Met Tyr Gln Ile Gly Thr Phe Lys Leu Ala

210 215 220

Phe Val Lys Glu Pro Gln Met Gln Val Leu Glu Leu Pro Tyr Val Asn

225 230 235 240

Asn Lys Leu Ser Met Ile Ile Leu Leu Pro Val Gly Ile Ala Asn Leu

245 250 255

Lys Gln Ile Glu Lys Gln Leu Asn Ser Gly Thr Phe His Glu Trp Thr

260 265 270

Ser Ser Ser Asn Met Met Glu Arg Glu Val Glu Val His Leu Pro Arg

275 280 285

Phe Lys Leu Glu Ile Lys Tyr Glu Leu Asn Ser Leu Leu Lys Pro Leu

290 295 300

Gly Val Thr Asp Leu Phe Asn Gln Val Lys Ala Asp Leu Ser Gly Met

305 310 315 320

Ser Pro Thr Lys Gly Leu Tyr Leu Ser Lys Ala Ile His Lys Ser Tyr

325 330 335

Leu Asp Val Ser Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Gly Asp

340 345 350

Ser Ile Ala Val Lys Ser Leu Pro Met Arg Ala Gln Phe Lys Ala Asn

355 360 365

His Pro Phe Leu Phe Phe Ile Arg His Thr His Thr Asn Thr Ile Leu

370 375 380

Phe Cys Gly Lys Leu Ala Ser Pro

385 390

<210>68

<211>862

<212>PRT

<213> Homo sapiens

<400>68

Met Leu Arg Asn Ser Thr Phe Lys Asn Met Gln Arg Arg His Thr Thr

1 5 10 15

Leu Arg Glu Lys Gly Arg Arg Gln Ala Ile Arg Gly Pro Ala Tyr Met

20 25 30

Phe Asn Glu Lys Gly Thr Ser Leu Thr Pro Glu Glu Glu Arg Phe Leu

35 40 45

Asp Ser Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu

50 55 60

Glu Ser Lys Thr Leu Asn Phe Asn Cys Val Asp Tyr Met Gly Gln Asn

65 70 75 80

Ala Leu Gln Leu Ala Val Gly Asn Glu His Leu Glu Val Thr Glu Leu

85 90 95

Leu Leu Lys Lys Glu Asn Leu Ala Arg Val Gly Asp Ala Leu Pro Leu

100 105 110

Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His

115 120 125

Pro Ala Phe Ala Gln Gly Gln Arg Leu Thr Leu Ser Pro Leu Glu Gln

130 135 140

Glu Leu Arg Asp Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg

145 150 155 160

Phe Ser His Asp Ile Thr Pro Ile Ile Leu Ala Ala His Cys Gln Glu

165 170 175

Tyr Glu Ile Val His Ile Leu Leu Leu Lys Gly Ala Arg Ile Glu Arg

180 185 190

Pro His Asp Tyr Phe Cys Lys Cys Asn Glu Cys Thr Glu Lys Gln Arg

195 200 205

Lys Asp Ser Phe Ser His Ser Arg Ser Arg Met Asn Ala Tyr Lys Gly

2l0 215 220

Leu Ala Ser Ala Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val Leu

225 230 235 240

Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Arg Leu Ala Asn Ile Glu

245 250 255

Thr Glu Phe Lys Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp

260 265 270

Phe Val Val Gly Val Leu Asp Leu Cys Arg Asp Thr Glu Glu Val Glu

275 280 285

Ala Ile Leu Asn Gly Asp Val Asn Phe Gln Val Trp Ser Asp His His

290 295 300

Arg Pro Ser Leu Ser Arg Ile Lys Leu Ala Ile Lys Tyr Glu Val Lys

305 310 315 320

Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Thr Met Trp

325 330 335

Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Ser Ile Ala Val Lys Phe

340 345 350

Leu Ala Val Phe Gly Val Ser Ile Gly Leu Pro Phe Leu Ala Ile Ala

355 360 365

Tyr Trp Ile Ala Pro Cys Ser Lys Leu Gly Arg Thr Leu Arg Ser Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Val Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Val Asn Ala Ser Asp Arg Phe Glu Gly Val Lys Thr Leu

405 410 415

Pro Asn Glu Thr Phe Thr Asp Tyr Pro Lys Gln Ile Phe Arg Val Lys

420 425 430

Thr Thr Gln Phe Ser Trp Thr Glu Met Leu Ile Met Lys Trp Val Leu

435 440 445

Gly Met Ile Trp Ser Glu Cys Lys Glu Ile Trp Glu Glu Gly Pro Arg

450 455 460

Glu Tyr Val Leu His Leu Trp Asn Leu Leu Asp Phe Gly Met Leu Ser

465 470 475 480

Ile Phe Val Ala Ser Phe Thr Ala Arg Phe Met Ala Phe Leu Lys Ala

485 490 495

Thr Glu Ala Gln Leu Tyr Val Asp Gln His Val Gln Asp Asp Thr Leu

500 505 510

His Asn Val Ser Leu Pro Pro Glu Val Ala Tyr Phe Thr Tyr Ala Arg

515 520 525

Asp Lys Trp Trp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Arg Gly Ala Lys

595 600 605

Tyr Asn Pro Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ser Ile Phe Gly Leu Ser Glu Val Ile Ser Val Val Leu Lys Tyr

625 630 635 640

Asp His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Val Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Asn Ser Tyr Gln Glu Ile Glu Glu Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Leu Ser Tyr Phe Asp Glu Gly Arg Thr

690 695 700

Leu Pro Ala Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Phe Tyr Tyr

705 710 715 720

Leu Ile Met Arg Ile Lys Met Cys Leu Ile Lys Leu Cys Lys Ser Lys

725 730 735

Ala Lys Ser Cys Glu Asn Asp Leu Glu Met Gly Met Leu Asn Ser Lys

740 745 750

Phe Lys Lys Thr Arg Tyr Gln Ala Gly Met Arg Asn Ser Glu Asn Leu

755 760 765

Thr Ala Asn Asn Thr Leu Ser Lys Pro Thr Arg Tyr Gln Lys Ile Met

770 775 780

Lys Arg Leu Ile Lys Arg Tyr Val Leu Lys Ala Gln Val Asp Arg Glu

785 790 795 800

Asn Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile

805 810 815

Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser Gln Ala Thr Gly

820 825 830

Glu Leu Ala Asp Leu Ile Gln Gln Leu Ser Glu Lys Phe Gly Lys Asn

835 840 845

Leu Asn Lys Asp His Leu Arg Val Asn Lys Gly Lys Asp Ile

850 855 860

<210>69

<211>1265

<212>PRT

<213> Homo sapiens

<400>69

Met Lys Val Arg Leu Leu Arg Gln Leu Ser Ala Ala Ala Lys Val Lys

1 5 10 15

Ala Pro Ser Gly Leu Gln Gly Pro Pro Gln Ala His Gln Phe Ile Ser

20 25 30

Leu Leu Leu Glu Glu Tyr Gly Ala Leu Cys Gln Ala Ala Arg Ser Ile

35 40 45

Ser Thr Phe Leu Gly Thr Leu Glu Asn Glu His Leu Lys Lys Phe Gln

50 55 60

Val Thr Trp Glu Leu His Asn Lys His Leu Phe Glu Asn Leu Val Phe

65 70 75 80

Ser Glu Pro Leu Leu Gln Ser Asn Leu Pro Ala Leu Val Ser Gln Ile

85 90 95

Arg Leu Gly Thr Thr Thr His Asp Thr Cys Ser Glu Asp Thr Tyr Ser

100 105 110

Thr Leu Leu Gln Arg Tyr Gln Arg Ser Glu Glu Glu Leu Arg Arg Val

115 120 125

Ala Glu Glu Trp Leu Glu Cys Gln Lys Arg Ile Asp Ala Tyr Val Asp

130 135 140

Glu Gln Met Thr Met Lys Thr Lys Gln Arg Met Leu Thr Glu Asp Trp

145 150 155 160

Glu Leu Phe Lys Gln Arg Arg Phe Ile Glu Glu Gln Leu Thr Asn Lys

165 170 175

Lys Ala Val Thr Gly Glu Asn Asn Phe Thr Asp Thr Met Arg His Val

180 185 190

Leu Ser Ser Arg Leu Ser Met Pro Asp Cys Pro Asn Cys Asn Tyr Arg

195 200 205

Arg Arg Cys Ala Cys Asp Asp Cys Ser Leu Ser His Ile Leu Thr Cys

210 215 220

Gly Ile Met Asp Pro Pro Val Thr Asp Asp Ile His Ile His Gln Leu

225 230 235 240

Pro Leu Gln Val Asp Pro Ala Pro Asp Tyr Leu Ala Glu Arg Ser Pro

245 250 255

Pro Ser Val Ser Ser Ala Ser Ser Ser Gly Ser Gly Ser Ser Ser Pro Ile

260 265 270

Thr Ile Gln Gln His Pro Arg Leu Ile Leu Thr Asp Ser Gly Ser Ala

275 280 285

Pro Thr Phe Cys Ser Asp Asp Glu Asp Val Ala Pro Leu Ser Ala Lys

290 295 300

Phe Ala Asp Ile Tyr Pro Leu Ser Asn Tyr Asp Asp Thr Glu Val Val

305 310 315 320

Ala Asn Met Asn Gly Ile His Ser Glu Leu Asn Gly Gly Gly Glu Asn

325 330 335

Met Ala Leu Lys Asp Glu Ser Pro Gln Ile Ser Ser Thr Ser Ser Ser

340 345 350

Ser Ser Glu Ala Asp Asp Glu Glu Ala Asp Gly Glu Ser Ser Gly Glu

355 360 365

Pro Pro Gly Ala Pro Lys Glu Asp Gly Val Leu Gly Ser Arg Ser Pro

370 375 380

Arg Thr Glu Glu Ser Lys Ala Asp Ser Pro Pro Pro Ser Tyr Pro Thr

385 390 395 400

Gln Gln Ala Glu Gln Ala Pro Asn Thr Cys Glu Cys His Val Cys Lys

405 410 415

Gln Glu Ala Ser Gly Leu Thr Pro Ser Ala Met Thr Ala Gly Ala Leu

420 425 430

Pro Pro Gly His Gln Phe Leu Ser Pro Glu Lys Pro Thr His Pro Ala

435 440 445

Leu His Leu Tyr Pro His Ile His Gly His Val Pro Leu His Thr Val

450 455 460

Pro His Leu Pro Arg Pro Leu Ile His Pro Thr Leu Tyr Ala Thr Pro

465 470 475 480

Pro Phe Thr His Ser Lys Ala Leu Pro Pro Ala Pro Val Gln Asn His

485 490 495

Thr Asn Lys His Gln Val Phe Asn Ala Ser Leu Gln Asp His Ile Tyr

500 505 510

Pro Ser Cys Phe Gly Asn Thr Pro Glu Trp Asn Ser Ser Lys Phe Ile

515 520 525

Ser Leu Trp Gly Ser Glu Val Met Asn Asp Lys Asn Trp Asn Pro Gly

530 535 540

Thr Phe Leu Pro Asp Thr Ile Ser Gly Ser Glu Ile Leu Gly Pro Thr

545 550 555 560

Leu Ser Glu Thr Arg Pro Glu Ala Leu Pro Pro Pro Ser Ser Asn Glu

565 570 575

Thr Pro Ala Val Ser Asp Ser Lys Glu Lys Lys Asn Ala Ala Lys Lys

580 585 590

Lys Cys Leu Tyr Asn Phe Gln Asp Ala Phe Met Glu Ala Asn Lys Val

595 600 605

Val Met Ala Thr Ser Ser Ala Thr Ser Ser Val Ser Cys Thr Ala Thr

6l0 615 620

Thr Val Gln Ser Ser Asn Ser Gln Phe Arg Val Ser Ser Lys Arg Pro

625 630 635 640

Pro Ser Val Gly Asp Val Phe His Gly Ile Ser Lys Glu Asp His Arg

645 650 655

His Ser Ala Pro Ala Ala Pro Arg Asn Ser Pro Thr Gly Leu Ala Pro

660 665 670

Leu Pro Ala Leu Ser Pro Ala Ala Leu Ser Pro Ala Ala Leu Ser Pro

675 680 685

Ala Ser Thr Pro His Leu Ala Ash Leu Ala Ala Pro Ser Phe Pro Lys

690 695 700

Thr Ala Thr Thr Thr Pro Gly Phe Val Asp Thr Arg Lys Ser Phe Cys

705 710 715 720

Pro Ala Pro Leu Pro Pro Ala Thr Asp Gly Ser Ile Ser Ala Pro Pro

725 730 735

Ser Val Cys Ser Asp Pro Asp Cys Glu Gly His Arg Cys Glu Asn Gly

740 745 750

Val Tyr Asp Pro Gln Gln Asp Asp Gly Asp Glu Ser Ala Asp Glu Asp

755 760 765

Ser Cys Ser Glu His Ser Ser Ser Ser Thr Ser Thr Ser Thr Asn Gln Lys

770 775 780

Glu Gly Lys Tyr Cys Asp Cys Cys Tyr Cys Glu Phe Phe Gly His Gly

785 790 795 800

Gly Pro Pro Ala Ala Pro Thr Ser Arg Asn Tyr Ala Glu Met Arg Glu

805 810 815

Lys Leu Arg Leu Arg Leu Thr Lys Arg Lys Glu Glu Gln Pro Lys Lys

820 825 830

Met Asp Gln Ile Ser Glu Arg Glu Ser Val Val Asp His Arg Arg Val

835 840 845

Glu Asp Leu Leu Gln Phe Ile Asn Ser Ser Glu Thr Lys Pro Val Ser

850 855 860

Ser Thr Arg Ala Ala Lys Arg Ala Arg His Lys Gln Arg Lys Leu Glu

865 870 875 880

Glu Lys Ala Arg Leu Glu Ala Glu Ala Arg Ala Arg Glu His Leu His

885 890 895

Leu Gln Glu Glu Gln Arg Arg Arg Glu Glu Glu Glu Asp Glu Glu Glu Glu

900 905 910

Glu Glu Asp Arg Phe Lys Glu Glu Phe Gln Arg Leu Gln Glu Leu Gln

915 920 925

Lys Leu Arg Ala Val Lys Lys Lys Lys Lys Glu Arg Pro Ser Lys Asp

930 935 940

Cys Pro Lys Leu Asp Met Leu Thr Arg Asn Phe Gln Ala Ala Thr Glu

945 950 955 960

Ser Val Pro Asn Ser Gly Asn Ile His Asn Gly Ser Leu Glu Gln Thr

965 970 975

Glu Glu Pro Glu Thr Ser Ser His Ser Ser Pro Ser Arg His Met Asn His

980 985 990

Ser Glu Pro Arg Pro Gly Leu Gly Ala Asp Gly Asp Ala Ala Asp Pro

995 1000 1005

Val Asp Thr Arg Asp Ser Lys Phe Leu Leu Pro Lys Glu Val Asn Gly

1010 1015 1020

Lys Gln His Glu Pro Leu Ser Phe Phe Phe Asp Ile Met Gln His His

1025 1030 1035 1040

Lys Glu Gly Asn Gly Lys Gln Lys Leu Arg Gln Thr Ser Lys Ala Ser

                                                                                           

Ser Glu Pro Ala Arg Arg Pro Thr Glu Pro Pro Lys Ala Thr Glu Gly

1060 1065 1070

Gln Ser Lys Pro Arg Ala Gln Thr Glu Ser Lys Ala Lys Val Val Asp

1075 1080 1085

Leu Met Ser Ile Thr Glu Gln Lys Arg Glu Glu Arg Lys Val Asn Ser

1090 1095 1100

Asn Asn Asn Asn Lys Lys Gln Leu Asn His Ile Lys Asp Glu Lys Ser

1105 1110 1115 1120

Asn Pro Thr Pro Met Glu Pro Thr Ser Pro Gly Glu His Gln Gln Asn

                                                                                                         

Ser Lys Leu Val Leu Ala Glu Ser Pro Gln Pro Lys Gly Lys Asn Lys

1140 1145 1150

Lys Asn Lys Lys Lys Lys Gly Asp Arg Val Asn Asn Ser Ile Asp Gly

1155 1160 1165

Val Ser Leu Leu Leu Pro Ser Leu Gly Tyr Asn Gly Ala Ile Leu Ala

1170 1175 1180

His Cys Asn Leu Arg Leu Pro Gly Ser Ser Asp Cys Ala Ala Ser Ala

1185 1190 1195 1200

Ser Gln Val Val Gly Ile Thr Asp Asp Val Phe Leu Pro Lys Asp Ile

                                                                                                   

Asp Leu Asp Ser Val Asp Met Asp Glu Thr Glu Arg Glu Val Glu Tyr

1220 1225 1230

Phe Lys Arg Phe Cys Leu Asp Ser Ala Arg Gln Thr Arg Gln Arg Leu

1235 1240 1245

Ser Ile Asn Trp Ser Asn Phe Ser Leu Lys Lys Ala Thr Phe Ala Ala

1250 1255 1260

His

1265

<210>70

<211>392

<212>PRT

<213> Homo sapiens

<400>70

Met Gly Ser Leu Ser Thr Ala Asn Val Glu Phe Cys Leu Asp Val Phe

1 5 10 15

Lys Glu Leu Asn Ser Asn Asn Ile Gly Asp Asn Ile Phe Phe Ser Ser

20 25 30

Leu Ser Leu Leu Tyr Ala Leu Ser Met Val Leu Leu Gly Ala Arg Gly

35 40 45

Glu Thr Ala Glu Gln Leu Glu Lys Val Leu His Phe Ser His Thr Val

50 55 60

Asp Ser Leu Lys Pro Gly Phe Lys Asp Ser Pro Lys Cys Ser Gln Ala

65 70 75 80

Gly Arg Ile His Ser Glu Phe Gly Val Glu Phe Ser Gln Ile Asn Gln

85 90 95

Pro Asp Ser Asn Cys Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Thr

100 105 110

Lys Thr Met Ala Phe His Gln Gln Tyr Leu Ser Cys Ser Glu Lys Trp

115 120 125

Tyr Gln Ala Arg Leu Gln Thr Val Asp Phe Glu Gln Ser Thr Glu Glu

130 135 140

Thr Arg Lys Met Ile Asn Ala Trp Val Glu Asn Lys Thr Asn Gly Lys

145 150 155 160

Val Ala Asn Leu Phe Gly Lys Ser Thr Ile Asp Pro Ser Ser Val Met

165 170 175

Val Leu Val Asn Ile Ile Tyr Phe Lys Gly Gln Arg Gln Asn Lys Phe

180 185 190

Gln Val Arg Glu Thr Val Lys Ser Pro Phe Gln Leu Ser Glu Gly Lys

195 200 205

Asn Val Thr Val Glu Met Met Tyr Gln Ile Gly Thr Phe Lys Leu Ala

210 215 220

Phe Val Lys Glu Pro Gln Met Gln Val Leu Glu Leu Pro Tyr Val Asn

225 230 235 240

Asn Lys Leu Ser Met Ile Ile Leu Leu Pro Val Gly Ile Ala Asn Leu

245 250 255

Lys Gln Ile Glu Lys Gln Leu Asn Ser Gly Thr Phe His Glu Trp Thr

260 265 270

Ser Ser Ser Asn Met Met Glu Arg Glu Val Glu Val His Leu Pro Arg

275 280 285

Phe Lys Leu Glu Ile Lys Tyr Glu Leu Asn Ser Leu Leu Lys Pro Leu

290 295 300

Gly Val Thr Asp Leu Phe Asn Gln Val Lys Ala Asp Leu Ser Gly Met

305 310 315 320

Ser Pro Thr Lys Gly Leu Tyr Leu Ser Lys Ala Ile His Lys Ser Tyr

325 330 335

Leu Asp Val Ser Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Gly Asp

340 345 350

Ser Ile Ala Val Lys Ser Leu Pro Met Arg Ala Gln Phe Lys Ala Asn

355 360 365

His Pro Phe Leu Phe Phe Ile Arg His Thr His Thr Asn Thr Ile Leu

370 375 380

Phe Cys Gly Lys Leu Ala Ser Pro

385 390

<210>71

<211>793

<212>PRT

<213> Homo sapiens

<400>71

Met Met Ala Ala Leu Tyr Pro Ser Thr Asp Leu Ser Gly Ala Ser Ser

1 5 10 15

Ser Ser Leu Pro Ser Ser Ser Pro Ser Ser Ser Ser Ser Pro Asn Glu Val Met

20 25 30

Ala Leu Lys Asp Val Arg Glu Val Lys Glu Glu Asn Thr Leu Asn Glu

35 40 45

Lys Leu Phe Leu Leu Ala Cys Asp Lys Gly Asp Tyr Tyr Met Val Lys

50 55 60

Lys Ile Leu Glu Glu Asn Ser Ser Gly Asp Leu Asn Ile Asn Cys Val

65 70 75 80

Asp Val Leu Gly Arg Asn Ala Val Thr Ile Thr Ile Glu Asn Glu Asn

85 90 95

Leu Asp Ile Leu Gln Leu Leu Leu Asp Tyr Gly Cys Gln Ser Ala Asp

100 105 110

Ala Leu Leu Val Ala Ile Asp Ser Glu Val Val Gly Ala Val Asp Ile

115 120 125

Leu Leu Asn His Arg Pro Lys Arg Ser Ser Arg Pro Thr Ile Val Lys

130 135 140

Leu Met Glu Arg Ile Gln Asn Pro Glu Tyr Ser Thr Thr Met Asp Val

145 150 155 160

Ala Pro Val Ile Leu Ala Ala His Arg Asn Asn Tyr Glu Ile Leu Thr

165 170 175

Met Leu Leu Lys Gln Asp Val Ser Leu Pro Lys Pro His Ala Val Gly

180 185 190

Cys Glu Cys Thr Leu Cys Ser Ala Lys Asn Lys Lys Asp Ser Leu Arg

195 200 205

His Ser Arg Phe Arg Leu Asp Ile Tyr Arg Cys Leu Ala Ser Pro Ala

2l0 215 220

Leu Ile Met Leu Thr Glu Glu Asp Pro Ile Leu Arg Ala Phe Glu Leu

225 230 235 240

Ser Ala Asp Leu Lys Glu Leu Ser Leu Val Glu Val Glu Phe Arg Asn

245 250 255

Asp Tyr Glu Glu Leu Ala Arg Gln Cys Lys Met Phe Ala Lys Asp Leu

260 265 270

Leu Ala Gln Ala Arg Asn Ser Arg Glu Leu Glu Val Ile Leu Asn His

275 280 285

Thr Ser Ser Asp Glu Pro Leu Asp Lys Arg Gly Leu Leu Glu Glu Arg

290 295 300

Met Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Asn Gln Lys Glu

305 310 315 320

Phe Val Ser Gln Ser Asn Cys Gln Gln Phe Leu Asn Thr Val Trp Phe

325 330 335

Gly Gln Met Ser Gly Tyr Arg Arg Lys Pro Thr Cys Lys Lys Ile Met

340 345 350

Thr Val Leu Thr Val Gly Ile Phe Trp Pro Val Leu Ser Leu Cys Tyr

355 360 365

Leu Ile Ala Pro Lys Ser Gln Phe Gly Arg Ile Ile His Thr Pro Phe

370 375 380

Met Lys Phe Ile Ile His Gly Ala Ser Tyr Phe Thr Phe Leu Leu Leu

385 390 395 400

Leu Asn Leu Tyr Ser Leu Val Tyr Asn Glu Asp Lys Lys Asn Thr Met

405 410 415

Gly Pro Ala Leu Glu Arg Ile Asp Tyr Leu Leu Ile Leu Trp Ile Ile

420 425 430

Gly Met Ile Trp Ser Asp Ile Lys Arg Leu Trp Tyr Glu Gly Leu Glu

435 440 445

Asp Phe Leu Glu Glu Ser Arg Asn Gln Leu Ser Phe Val Met Asn Ser

450 455 460

Leu Tyr Leu Ala Thr Phe Ala Leu Lys Val Val Ala His Asn Lys Phe

465 470 475 480

His Asp Phe Ala Asp Arg Lys Asp Trp Asp Ala Phe His Pro Thr Leu

485 490 495

Val Ala Glu Gly Leu Phe Ala Phe Ala Asn Val Leu Ser Tyr Leu Arg

500 505 510

Leu Phe Phe Met Tyr Thr Thr Ser Ser Ser Ile Leu Gly Pro Leu Gln Ile

515 520 525

Ser Met Gly Gln Met Leu Gln Asp Phe Gly Lys Phe Leu Gly Met Phe

530 535 540

Leu Leu Val Leu Phe Ser Phe Thr Ile Gly Leu Thr Gln Leu Tyr Asp

545 550 555 560

Lys Gly Tyr Thr Ser Lys Glu Gln Lys Asp Cys Val Gly Ile Phe Cys

565 570 575

Glu Gln Gln Ser Asn Asp Thr Phe His Ser Phe Ile Gly Thr Cys Phe

580 585 590

Ala Leu Phe Trp Tyr Ile Phe Ser Leu Ala His Val Ala Ile Phe Val

595 600 605

Thr Arg Phe Ser Tyr Gly Glu Glu Leu Gln Ser Phe Val Gly Ala Val

610 615 620

Ile Val Gly Thr Tyr Asn Val Val Val Val Ile Val Leu Thr Lys Leu

625 630 635 640

Leu Val Ala Met Leu His Lys Ser Phe Gln Leu Ile Ala Asn His Glu

645 650 655

Asp Lys Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Leu Ser Tyr Phe

660 665 670

Asp Asp Lys Cys Thr Leu Pro Pro Pro Phe Asn Ile Ile Pro Ser Pro

675 680 685

Lys Thr Ile Cys Tyr Met Ile Ser Ser Leu Ser Lys Trp Ile Cys Ser

690 695 700

His Thr Ser Lys Gly Lys Val Lys Arg Gln Asn Ser Leu Lys Glu Trp

705 710 715 720

Arg Asn Leu Lys Gln Lys Arg Asp Glu Asn Tyr Gln Lys Val Met Cys

725 730 735

Cys Leu Val His Arg Tyr Leu Thr Ser Met Arg Gln Lys Met Gln Ser

740 745 750

Thr Asp Gln Ala Thr Val Glu Asn Leu Asn Glu Leu Arg Gln Asp Leu

755 760 765

Ser Lys Phe Arg Asn Glu Ile Arg Asp Leu Leu Gly Phe Arg Thr Ser

770 775 780

Lys Tyr Ala Met Phe Tyr Pro Arg Asn

785 790

<210>72

<211>982

<212>PRT

<213> Homo sapiens

<400>72

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Val Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Phe Val Ala Gln Pro

290 295 300

Asn Cys Gln Gln Leu Leu Ala Ser Arg Trp Tyr Asp Glu Phe Pro Gly

305 310 315 320

Trp Arg Arg Arg His Trp Ala Val Lys Met Val Thr Cys Phe Ile Ile

325 330 335

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

340 345 350

Ser Pro Leu Gly Leu Phe Ile Arg Lys Pro Phe Ile Lys Phe Ile Cys

355 360 365

His Thr Ala Ser Tyr Leu Thr Phe Leu Phe Leu Leu Leu Leu Ala Ser

370 375 380

Gln His Ile Asp Arg Ser Asp Leu Asn Arg Gln Gly Pro Pro Pro Thr

385 390 395 400

Ile Val Glu Trp Met Ile Leu Pro Trp Val Leu Gly Phe Ile Trp Gly

405 410 415

Glu Ile Lys Gln Met Trp Asp Gly Gly Leu Gln Asp Tyr Ile His Asp

420 425 430

Trp Trp Asn Leu Met Asp Phe Val Met Asn Ser Leu Tyr Leu Ala Thr

435 440 445

Ile Ser Leu Lys Ile Val Ala Phe Val Lys Tyr Ser Ala Leu Asn Pro

450 455 460

Arg Glu Ser Trp Asp Met Trp His Pro Thr Leu Val Ala Glu Ala Leu

465 470 475 480

Phe Ala Ile Ala Asn Ile Phe Ser Ser Leu Arg Leu Ile Ser Leu Phe

485 490 495

Thr Ala Asn Ser His Leu Gly Pro Leu Gln Ile Ser Leu Gly Arg Met

500 505 510

Leu Leu Asp Ile Leu Lys Phe Leu Phe Ile Tyr Cys Leu Val Leu Leu

515 520 525

Ala Phe Ala Asn Gly Leu Asn Gln Leu Tyr Phe Tyr Tyr Glu Glu Thr

530 535 540

Lys Gly Leu Thr Cys Lys Gly Ile Arg Cys Glu Lys Gln Asn Asn Ala

545 550 555 560

Phe Ser Thr Leu Phe Glu Thr Leu Gln Ser Leu Phe Trp Ser Ile Phe

565 570 575

Gly Leu Ile Asn Leu Tyr Val Thr Asn Val Lys Ala Gln His Glu Phe

580 585 590

Thr Glu Phe Val Gly Ala Thr Met Phe Gly Thr Tyr Asn Val Ile Ser

595 600 605

Leu Val Val Leu Leu Asn Met Leu Ile Ala Met Met Asn Asn Ser Tyr

610 615 620

Gln Leu Ile Ala Asp His Ala Asp Ile Glu Trp Lys Phe Ala Arg Thr

625 630 635 640

Lys Leu Trp Met Ser Tyr Phe Glu Glu Gly Gly Thr Leu Pro Thr Pro

645 650 655

Phe Asn Val Ile Pro Ser Pro Lys Ser Leu Trp Tyr Leu Ile Lys Trp

660 665 670

Ile Trp Thr His Leu Cys Lys Lys Lys Met Arg Arg Lys Pro Glu Ser

675 680 685

Phe Gly Thr Ile Gly Val Arg Thr Gln His Arg Arg Ala Ala Asp Asn

690 695 700

Leu Arg Arg His His Gln Tyr Gln Val Ile Met Arg Asn Leu Val Lys

705 710 715 720

Arg Tyr Val Ala Ala Met Ile Arg Asp Ala Lys Thr Glu Glu Gly Leu

725 730 735

Thr Glu Glu Asn Phe Lys Glu Leu Lys Gln Asp Ile Ser Ser Phe Arg

740 745 750

Phe Glu Val Leu Gly Leu Leu Arg Gly Ser Lys Leu Ser Thr Ile Gln

755 760 755

Ser Ala Asn Ala Ser Lys Glu Ser Ser Ser Asn Ser Ala Asp Ser Asp Glu

770 775 780

Lys Ser Asp Ser Glu Gly Asn Ser Lys Asp Lys Lys Lys Asn Phe Ser

785 790 795 800

Leu Phe Asp Leu Thr Thr Leu Ile His Pro Arg Ser Ala Ala Ile Ala

805 810 815

Ser Glu Arg His Asn Ile Ser Asn Gly Ser Ala Leu Mal Val Gln Glu

820 825 830

Pro Pro Arg Glu Lys Gln Arg Lys Val Asn Phe Val Thr Asp Ile Lys

835 840 845

Asn Phe Gly Leu Phe His Arg Arg Ser Lys Gln Asn Ala Ala Glu Gln

850 855 860

Asn Ala Asn Gln Ile Phe Ser Val Ser Glu Glu Val Ala Arg Gln Gln

865 870 875 880

Ala Ala Gly Pro Leu Glu Arg Asn Ile Gln Leu Glu Ser Arg Gly Leu

885 890 895

Ala Ser Arg Gly Asp Leu Ser Ile Pro Gly Leu Ser Glu Gln Cys Val

900 905 910

Leu Val Asp His Arg Glu Arg Asn Thr Asp Thr Leu Gly Leu Gln Val

915 920 925

Gly Lys Arg Val Cys Pro Phe Lys Ser Glu Lys Val Val Val Glu Asp

930 935 940

Thr Val Pro Ile Ile Pro Lys Glu Lys His Ala Lys Glu Glu Asp Ser

945 950 955 960

Ser Ile Asp Tyr Asp Leu Asn Leu Pro Asp Thr Val Thr His Glu Asp

965 970 975

Tyr Val Thr Thr Arg Leu

980

<210>73

<211>930

<212>PRT

<213> Mus musculus (Mus musculus)

<400>73

Met Ser Gln Ser Pro Arg Phe Val Thr Arg Arg Gly Gly Ser Leu Lys

1 5 10 15

Ala Ala Pro Gly Ala Gly Thr Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Glu Leu Gly Asp Asp Gly Tyr Pro Gln Leu Pro Leu Pro

35 40 45

Pro Tyr Gly Tyr Tyr Pro Ser Phe Arg Gly Asn Glu Asn Arg Leu Thr

50 55 60

His Arg Arg Gln Thr Ile Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn

65 70 75 80

Arg Gly Pro Ala Tyr Met Phe Asn Asp His Ser Thr Ser Leu Ser Ile

85 90 95

Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val

100 105 110

Val Arg Lys Met Leu Glu Glu Cys His Ser Leu Asn Val Asn Cys Val

115 120 125

Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His

130 135 140

Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val

145 150 155 160

Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val

165 170 175

Glu Ala Ile Leu Asn His Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala

180 185 190

Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr

195 200 205

Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu

210 215 220

Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys

225 230 235 240

Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Thr Glu

245 250 255

Cys Ser Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser Arg

260 265 270

Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser

275 280 285

Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala

290 295 300

Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu

305 310 315 320

Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg

325 330 335

Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg

340 345 350

Gln Pro Gly Asp Phe Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala

355 360 365

Ile Lys Tyr Glu Val Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln

370 375 380

Gln Leu Leu Ser Ile Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln

385 390 395 400

Thr Met Ala Val Lys Phe Leu Val Val Leu Ala Val Ala Ile Gly Leu

405 410 415

Pro Phe Leu Ala Leu Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly

420 425 430

Lys Ile Leu Arg Gly Pro Phe Met Lys Phe Val Ala His Ala Ala Ser

435 440 445

Phe Thr Ile Phe Leu Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe

450 455 460

Glu Gly Thr Lys Leu Leu Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg

465 470 475 480

Gln Leu Phe Arg Met Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu

485 490 495

Ile Ile Ser Trp Val Ile Gly Met Ile Trp Ala Glu Cys Lys Glu Ile

500 505 510

Trp Thr Gln Gly Pro Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu

515 520 525

Asp Phe Gly Met Leu Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe

530 535 540

Met Ala Phe Trp His Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn

545 550 555 560

Asp Thr Leu Lys Asp Leu Thr Lys Val Thr Leu Gly Asp Asn Val Lys

565 570 575

Tyr Tyr Asn Leu Ala Arg Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile

580 585 590

Ile Ser Glu Gly Leu Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg

595 600 605

Ile Ala Tyr Ile Leu Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile

610 615 620

Ser Leu Gly Arg Thr Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe

625 630 635 640

Ile Met Val Phe Val Ala Phe Met Ile Gly Met Phe Asn Leu Tyr Ser

645 650 655

Tyr Tyr Ile Gly Ala Lys Gln Asn Glu Ala Phe Thr Thr Val Glu Glu

660 665 670

Ser Phe Lys Thr Leu Phe Trp Ala Ile Phe Gly Leu Ser Glu Val Lys

675 680 685

Ser Val Val Ile Asn Tyr Asn His Lys Phe Ile Glu Asn Ile Gly Tyr

690 695 700

Val Leu Tyr Gly Val Tyr Asn Val Thr Met Val Ile Val Leu Leu Asn

705 710 715 720

Met Leu Ile Ala Met Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp

725 730 735

Ala Asp Val Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr

740 745 750

Phe Glu Glu Gly Arg Thr Leu Pro Val Pro Phe Asn Leu Val Pro Ser

755 760 765

Pro Lys Ser Leu Leu Tyr Leu Leu Leu Lys Phe Lys Lys Trp Met Cys

770 775 780

Glu Leu Ile Gln Gly Gln Lys Gln Gly Phe Gln Glu Asp Ala Glu Met

785 790 795 800

Asn Lys Arg Asn Glu Glu Lys Lys Phe Gly Ile Ser Gly Ser His Glu

805 810 815

Asp Leu Ser Lys Phe Ser Leu Asp Lys Asn Gln Leu Ala His Asn Lys

820 825 830

Gln Ser Ser Thr Arg Ser Ser Glu Asp Tyr His Leu Asn Ser Phe Ser

835 840 845

Asn Pro Pro Arg Gln Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys Arg

850 855 860

Tyr Val Leu Gln Ala Gln Ile Asp Lys Glu Ser Asp Glu Val Asn Glu

865 870 875 880

Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu

885 890 895

Leu Leu Glu Glu Lys Ser Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile

900 905 910

Arg Lys Leu Gly Glu Arg Leu Ser Leu Glu Pro Lys Leu Glu Glu Ser

915 920 925

Arg Arg

930

<210>74

<211>826

<212>PRT

<213> Homo sapiens

<400>74

Pro Ser Gly Leu Pro Leu Leu Pro Val Leu Phe Ala Leu Gly Gly Leu

1 5 10 15

Leu Leu Leu Ser Asn Ala Ser Cys Val Gly Gly Val Leu Trp Gln Arg

20 25 30

Arg Leu Arg Arg Leu Ala Glu Ala Leu Asn Phe Pro Pro His Leu His

35 40 45

Pro Gly Arg Ser Glu Glu Asp Arg Val Arg Asn Glu Tyr Glu Glu Ser

50 55 60

Gln Trp Thr Gly Glu Arg Asp Thr Gln Ser Ser Thr Val Ser Thr Thr

65 70 75 80

Glu Ala Glu Pro Tyr Tyr Arg Ser Leu Arg Asp Phe Ser Pro Gln Leu

85 90 95

Pro Pro Thr Gln Glu Glu Val Ser Tyr Ser Arg Gly Phe Thr Gly Glu

100 105 110

Asp Glu Asp Met Ala Phe Pro Gly His Leu Tyr Asp Glu Val Glu Arg

115 120 125

Thr Tyr Pro Pro Ser Gly Ala Trp Gly Pro Leu Tyr Asp Glu Val Gln

130 135 140

Met Gly Pro Trp Asp Leu His Trp Pro Glu Asp Thr Tyr Gln Asp Pro

145 150 155 160

Arg Gly Ile Tyr Asp Gln Val Ala Gly Asp Leu Asp Thr Leu Glu Pro

165 170 175

Asp Ser Leu Pro Phe Glu Leu Arg Gly His Leu Val Trp Gly Phe Asn

180 185 190

His Val Ser Gln Ala Gly Leu Lys Leu Leu Ala Ser Ser Asp Pro Pro

195 200 205

Ala Ser Ala Ser Gln Ser Ala Glu Ile Thr Glu Ser His Ser Val Val

210 215 220

Gln Val Gly Val Gln Trp Arg Tyr Phe Gly Ser Leu His Pro Leu Pro

225 230 235 240

Pro Gly Ser Arg Asp Ser Leu Ala Ser Ala Ser Arg Ile Ala Gly Ile

245 250 255

Thr Ala Pro Trp Glu Ala Glu Val Ser Arg Ser Pro Gln Gly Thr Gln

260 265 270

Asp Ser Pro Val Thr Arg Ser Gly Pro Pro Ser Arg Gly Trp Gln Ser

275 280 285

Leu Ser Phe Asp Gly Gly Ala Phe His Leu Lys Gly Thr Gly Glu Leu

290 295 300

Thr Arg Ala Leu Leu Val Leu Arg Leu Cys Ala Trp Pro Pro Leu Val

305 310 315 320

Thr His Gly Leu Leu Leu Gln Ala Trp Ser Arg Arg Leu Leu Gly Ser

325 330 335

Arg Leu Ser Gly Ala Phe Leu Arg Ala Ser Val Tyr Gly Gln Phe Val

340 345 350

Ala Gly Glu Thr Ala Glu Glu Val Lys Gly Cys Val Gln Gln Leu Arg

355 360 365

Thr Leu Ser Leu Arg Pro Leu Leu Ala Val Pro Thr Glu Glu Glu Glu Pro

370 375 380

Asp Ser Ala Ala Lys Arg Met Arg Leu His His Val Gly Gln Ala Gly

385 390 395 400

Leu Glu Leu Leu Thr Pro Ala Ala Ser Gly Ser Val Ala Gln Ala Gly

405 410 415

Val Gln Trp Arg Gln Ser Ser Asp Arg Gly Gly Gly Asn Gln Ala Ala

420 425 430

Ala Ser Arg Ser Ser Leu Leu Gln Glu Ala Ala Phe Ser Pro Pro Cys

435 440 445

Gly Arg Leu Gln Leu Pro Ala Gln Pro Ala Ser Arg His Gly Ala Arg

450 455 460

Gly Arg Gly Ser Met Lys Ala Lys Ser Leu Thr Ser Arg His Leu Leu

465 470 475 480

Ala Ser Gln Gly Gln Glu Thr Ile Ile Lys Thr Lys Val Arg Ile Pro

485 490 495

Ala Leu Trp Lys Ala Glu Pro Gly Gln His Ser Lys Thr Pro Ser Gln

500 505 510

Gln Asn Lys Ser Gln Tyr Val Thr Thr Leu Trp Glu Ala Asp Val Gly

515 520 525

Arg Ser Leu Glu Asn Leu Gln Val Ser Cys Leu Asn Ala Glu Gln Asn

530 535 540

Gln His Leu Arg Ala Ser Leu Ser Arg Leu His Arg Val Thr Pro Pro

545 550 555 560

Ala Gly Thr Ser Ser Thr Ser Gly Pro Pro Ser Ala Ala Cys Ile Gly Trp

565 570 575

His Ser Arg Leu His Arg Val Ala Gln Tyr Ala Arg Ala Gln His Val

580 585 590

Arg Leu Leu Val Asp Ala Glu Tyr Thr Ser Leu Asn Pro Ala Leu Ser

595 600 605

Leu Leu Val Ala Ala Leu Ala Val Arg Trp Asn Ser Pro Gly Glu Gly

610 615 620

Gly Pro Trp Val Trp Asn Thr Tyr Gln Ala Cys Leu Lys Asp Thr Phe

625 630 635 640

Glu Arg Leu Gly Arg Asp Ala Glu Ala Ala His Arg Ala Gly Leu Ala

645 650 655

Phe Gly Val Lys Leu Val Arg Gly Ala Tyr Leu Asp Lys Glu Arg Ala

660 665 670

Val Ala Gln Leu His Gly Met Glu Asp Pro Thr Gln Pro Asp Tyr Glu

675 680 685

Ala Thr Ser Glu Leu Asn Arg Ala Ser Pro Phe Ser Tyr Ser Arg Cys

690 695 700

Leu Glu Leu Met Leu Thr His Val Ala Arg His Gly Pro Met Cys His

705 710 715 720

Leu Met Val Ala Ser His Asn Glu Glu Ser Val Arg Gln Ala Thr Lys

725 730 735

Arg Met Trp Glu Leu Gly Ile Pro Leu Asp Gly Thr Val Cys Phe Gly

740 745 750

Gln Leu Leu Gly Met Cys Asp His Val Ser Leu Ala Leu Gly Gln Ala

755 760 765

Gly Tyr Val Val Tyr Lys Ser Ile Pro Tyr Gly Ser Leu Glu Glu Val

770 775 780

Ile Pro Tyr Leu Ile Arg Arg Ala Gln Glu Asn Arg Ser Val Leu Gln

785 790 795 800

Gly Ala Arg Arg Glu Gln Glu Leu Leu Ser Gln Glu Leu Trp Arg Arg

805 810 815

Leu Leu Pro Gly Cys Arg Arg Ile Pro His

820 825

<210>75

<211>39

<212>PRT

<213> Homo sapiens

<400>75

Ser Cys Ser Val Thr Leu Ala Gly Val Gln Trp Arg Asp Leu Gly Leu

1 5 10 15

Leu Gln Pro Leu Pro Pro Lys Phe Lys Arg Phe Ser Cys Leu Ser Phe

20 25 30

Pro Ser Ser Trp Asp Tyr Arg

35

<210>76

<211>46

<212>PRT

<213> Homo sapiens

<400>76

Glu Met Glu Phe Asn Cys Glu Ser Cys Ser Val Thr Leu Ala Gly Val

1 5 10 15

Gln Trp Arg Asp Leu Gly Leu Leu Gln Pro Leu Pro Pro Lys Phe Lys

20 25 30

Arg Phe Ser Cys Leu Ser Phe Pro Ser Ser Trp Asp Tyr Arg

35 40 45

<210>77

<211>810

<212>PRT

<213> Homo sapiens

<400>77

Met Cys Pro Gly Ile Pro Gly Pro Arg Ala Glu Ala Ala Val Gly Thr

1 5 10 15

Thr His Pro Phe Ser Ser Pro Gly Ala Trp Leu Gly Ser Gly Ser Gly

20 25 30

Ser Gly Pro Val Gly Ala Pro Pro Pro Pro Ser Pro Gly Leu Pro Pro Ser

35 40 45

Trp Ala Ala Met Met Ala Ala Leu Tyr Pro Ser Thr Asp Leu Ser Gly

50 55 60

Ala Ser Ser Ser Ser Ser Leu Pro Ser Ser Pro Ser Ser Ser Ser Pro Asn

65 70 75 80

Glu Val Met Ala Leu Lys Asp Val Arg Glu Val Lys Glu Glu Asn Thr

85 90 95

Leu Asn Glu Lys Leu Phe Leu Leu Ala Cys Asp Lys Gly Asp Tyr Tyr

100 105 110

Met Val Lys Lys Ile Leu Glu Glu Asn Ser Ser Gly Asp Leu Asn Ile

115 120 125

Asn Cys Val Asp Val Leu Gly Arg Asn Ala Val Thr Ile Thr Ile Glu

130 135 140

Asn Glu Asn Leu Asp Ile Leu Gln Leu Leu Leu Asp Tyr Gly Cys Gln

145 150 155 160

Lys Leu Met Glu Arg Ile Gln Asn Pro Glu Tyr Ser Thr Thr Met Asp

165 170 175

Val Ala Pro Val Ile Leu Ala Ala His Arg Asn Asn Tyr Glu Ile Leu

180 185 190

Thr Met Leu Leu Lys Gln Asp Val Ser Leu Pro Lys Pro His Ala Val

195 200 205

Gly Cys Glu Cys Thr Leu Cys Ser Ala Lys Asn Lys Lys Asp Ser Leu

210 215 220

Arg His Ser Arg Phe Arg Leu Asp Ile Tyr Arg Cys Leu Ala Ser Pro

225 230 235 240

Ala Leu Ile Met Leu Thr Glu Glu Asp Pro Ile Leu Arg Ala Phe Glu

245 250 255

Leu Ser Ala Asp Leu Lys Glu Leu Ser Leu Val Glu Val Glu Phe Arg

260 265 270

Asn Asp Tyr Glu Glu Leu Ala Arg Gln Cys Lys Met Phe Ala Lys Asp

275 280 285

Leu Leu Ala Gln Ala Arg Asn Ser Arg Glu Leu Glu Val Ile Leu Asn

290 295 300

His Thr Ser Ser Asp Glu Pro Leu Asp Lys Arg Gly Leu Leu Glu Glu

305 310 315 320

Arg Met Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Asn Gln Lys

325 330 335

Glu Phe Val Ser Gln Ser Asn Cys Gln Gln Phe Leu Asn Thr Val Trp

340 345 350

Phe Gly Gln Met Ser Gly Tyr Arg Arg Lys Pro Thr Cys Lys Lys Ile

355 360 365

Met Thr Val Leu Thr Val Gly Ile Phe Trp Pro Val Leu Ser Leu Cys

370 375 380

Tyr Leu Ile Ala Pro Lys Ser Gln Phe Gly Arg Ile Ile His Thr Pro

385 390 395 400

Phe Met Lys Phe Ile Ile His Gly Ala Ser Tyr Phe Thr Phe Leu Leu

405 410 415

Leu Leu Asn Leu Tyr Ser Leu Val Tyr Asn Glu Asp Lys Lys Asn Thr

420 425 430

Met Gly Pro Ala Leu Glu Arg Ile Asp Tyr Leu Leu Ile Leu Trp Ile

435 440 445

Ile Gly Met Ile Trp Ser Asp Ile Lys Arg Leu Trp Tyr Glu Gly Leu

450 455 460

Glu Asp Phe Leu Glu Glu Ser Arg Asn Gln Leu Ser Phe Val Met Asn

465 470 475 480

Ser Leu Tyr Leu Ala Thr Phe Ala Leu Lys Val Val Ala His Asn Lys

485 490 495

Phe His Asp Phe Ala Asp Arg Lys Asp Trp Asp Ala Phe His Pro Thr

500 505 510

Leu Val Ala Glu Gly Leu Phe Ala Phe Ala Asn Val Leu Ser Tyr Leu

515 520 525

Arg Leu Phe Phe Met Tyr Thr Thr Ser Ser Ser Ile Leu Gly Pro Leu Gln

530 535 540

Ile Ser Met Gly Gln Met Leu Gln Asp Phe Gly Lys Phe Leu Gly Met

545 550 555 560

Phe Leu Leu Val Leu Phe Ser Phe Thr Ile Gly Leu Thr Gln Leu Tyr

565 570 575

Asp Lys Gly Tyr Thr Ser Lys Glu Gln Lys Asp Cys Val Gly Ile Phe

580 585 590

Cys Glu Gln Gln Ser Asn Asp Thr Phe His Ser Phe Ile Gly Thr Cys

595 600 605

Phe Ala Leu Phe Trp Tyr Ile Phe Ser Leu Ala His Val Ala Ile Phe

610 615 620

Val Thr Arg Phe Ser Tyr Gly Glu Glu Leu Gln Ser Phe Val Gly Ala

625 630 635 640

Val Ile Val Gly Thr Tyr Asn Val Val Val Val Ile Val Leu Thr Lys

645 650 655

Leu Leu Val Ala Met Leu His Lys Ser Phe Gln Leu Ile Ala Asn His

660 665 670

Glu Asp Lys Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Leu Ser Tyr

675 680 685

Phe Asp Asp Lys Cys Thr Leu Pro Pro Pro Phe Asn Ile Ile Pro Ser

690 695 700

Pro Lys Thr Ile Cys Tyr Met Ile Ser Ser Leu Ser Lys Trp Ile Cys

705 710 715 720

Ser His Thr Ser Lys Gly Lys Val Lys Arg Gln Asn Ser Leu Lys Glu

725 730 735

Trp Arg Asn Leu Lys Gln Lys Arg Asp Glu Asn Tyr Gln Lys Val Met

740 745 750

Cys Cys Leu Val His Arg Tyr Leu Thr Ser Met Arg Gln Lys Met Gln

755 760 765

Ser Thr Asp Gln Ala Thr Val Glu Asn Leu Asn Glu Leu Arg Gln Asp

770 775 780

Leu Ser Lys Phe Arg Asn Glu Ile Arg Asp Leu Leu Gly Phe Arg Thr

785 790 795 800

Ser Lys Tyr Ala Met Phe Tyr Pro Arg Asn

805 810

<210>78

<211>876

<212>PRT

<213> Mus musculus (Mus musculus)

<400>78

Met Ser Arg Gly Asn Glu Asn Arg Leu Thr His Arg Arg Gln Thr Ile

1 5 10 15

Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn Arg Gly Pro Ala Tyr Met

20 25 30

Phe Asn Asp His Ser Thr Ser Leu Ser Ile Glu Glu Glu Arg Phe Leu

35 40 45

Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu

50 55 60

Glu Cys His Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln Asp

65 70 75 80

Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu Leu

85 90 95

Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu Leu

100 105 110

Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His

115 120 125

Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Pro Ser Gln Ser

130 135 140

Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg

145 150 155 160

Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln Glu

165 170 175

Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu Arg

180 185 190

Pro His Asp Tyr Phe Cys Lys Cys Thr Glu Cys Ser Gln Lys Gln Lys

195 200 205

His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys Gly

210 215 220

Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val Met

225 230 235 240

Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile Glu

245 250 255

Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp

260 265 270

Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val Glu

275 280 285

Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg Gln Pro Gly Asp Phe Gly

290 295 300

Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val Lys

305 310 315 320

Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile Trp

325 330 335

Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys Phe

340 345 350

Leu Val Val Leu Ala Val Ala Ile Gly Leu Pro Phe Leu Ala Leu Ile

355 360 365

Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Leu Arg Gly Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu Leu

405 410 415

Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg Gln Leu Phe Arg Met Lys

420 425 430

Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val Ile

435 440 445

Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Thr Gln Gly Pro Lys

450 455 460

Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu Ala

465 470 475 480

Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His Ala

485 490 495

Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp Leu

500 505 510

Thr Lys Val Thr Leu Gly Asp Asn Val Lys Tyr Tyr Asn Leu Ala Arg

515 520 525

Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala Lys

595 600 605

Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val Ile Asn Tyr

625 630 635 640

Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu Gly Arg Thr

690 695 700

Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Leu Leu Tyr

705 710 715 720

Leu Leu Leu Lys Phe Lys Lys Trp Met Cys Glu Leu Ile Gln Gly Gln

725 730 735

Lys Gln Gly Phe Gln Glu Asp Ala Glu Met Asn Lys Arg Asn Glu Glu

740 745 750

Lys Lys Phe Gly Ile Ser Gly Ser His Glu Asp Leu Ser Lys Phe Ser

755 760 765

Leu Asp Lys Asn Gln Leu Ala His Asn Lys Gln Ser Ser Thr Arg Ser

770 775 780

Ser Glu Asp Tyr His Leu Asn Ser Phe Ser Asn Pro Pro Arg Gln Tyr

785 790 795 800

Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala Gln

805 810 815

Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile

820 825 830

Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser

835 840 845

Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Lys Leu Gly Glu Arg

850 855 860

Leu Ser Leu Glu Pro Lys Leu Glu Glu Ser Arg Arg

865 870 875

<210>79

<211>368

<212>PRT

<213> Homo sapiens

<400>79

Asp Arg Leu Ser Leu Leu Ser Pro Arg Leu Glu Cys Asn Gly Met Ile

1 5 10 15

Leu Ala His Cys Lys Leu Arg Leu Pro Gly Phe Lys Arg Phe Ser Cys

20 25 30

Leu Ser Leu Pro Ser Ser Trp Asp Tyr Arg His Val Pro Pro Arg Gln

35 40 45

Val His Phe Val Phe Ser Val Glu Thr Gly Phe His Arg Ala Gly Gln

50 55 60

Ala Gly Leu Glu Leu Leu Thr Ser Ser Val Pro Pro Thr Ser Ala Phe

65 70 75 80

Pro Lys Cys Trp Asp Tyr Arg Arg Asp Asp Gln Ala Trp Pro Thr Leu

85 90 95

Ser Ser Phe Arg Gly Leu Asn Lys Phe Ala Phe Leu Pro Lys Phe Phe

100 105 110

Ala His Pro Ile Ser Gln Phe Gln Arg Val Glu Cys Asn Val Gly Cys

115 120 125

Pro Ile Leu Leu Ala Met Lys Tyr Leu Ala Tyr Ser Ser Leu Pro Gly

130 135 140

Ala Asp Thr Met Leu Tyr Phe Tyr Phe Tyr Glu Gln Glu Ala Ser Leu

145 150 155 160

Ala Val Cys Asn Ile Cys Arg Gln Lys Phe His Trp Val Leu Tyr Gln

165 170 175

Ile Ser His Leu Tyr Arg Gly Val Ile Val Asp Asn Phe Leu Leu His

180 185 190

Pro Asp Gly Arg Phe Thr Trp Thr Ile Phe Phe Leu Ser Trp Val Lys

195 200 205

Gln Asn Ser Leu Val Asp Phe Phe Phe Gly Thr Glu Ser Arg Ser Val

210 215 220

Ala Leu Leu Pro Arg Leu Glu Cys Ser Gly Ala Met Ser Thr Leu His

225 230 235 240

Thr Val Leu Arg Pro Ala Tyr Ser His Ile Tyr His Pro Asp Val Lys

245 250 255

Glu Lys Thr His Phe Leu Gly Asn Val Phe Asn Lys Arg Lys Leu Gln

260 265 270

Lys Lys Ile Leu Lys Thr Pro Asn Pro Leu Cys Ala Leu His Ser Ala

275 280 285

Pro Ser Pro Ser Leu Pro Pro Phe Leu Arg Cys Thr Gly Arg Leu Pro

290 295 300

Phe Tyr Leu Gly Leu Asp Asp Phe Leu Phe Val Ala Gly Ala Leu Met

305 310 315 320

Phe Leu Pro Val Ser Phe Leu Asn Pro His Thr Leu Thr Trp Pro Pro

325 330 335

Gln Cys Cys Thr Arg Ser Asp Cys Asn Pro Leu Arg Gly Gln Arg Glu

340 345 350

Ile Ser Ala Leu Ser His Ser Ser Leu Pro Thr Gly Leu Ser Met Pro Leu

355 360 365

<210>80

<211>341

<212>PRT

<213> Homo sapiens

<400>80

Met Ala Ala Leu Tyr Ala Cys Thr Lys Cys His Gln Arg Phe Pro Phe

1 5 10 15

Glu Ala Leu Ser Gln Gly Gln Gln Leu Cys Lys Glu Cys Arg Ile Ala

20 25 30

His Pro Val Val Lys Cys Thr Tyr Cys Arg Thr Glu Tyr Gln Gln Glu

35 40 45

Arg Leu Glu Cys Asn Gly Thr Ile Ser Ala His Cys Asn Leu His Leu

50 55 60

Pro Gly Ser Ser Asp Ser Pro Ala Ser Ser Ser Arg Val Ala Gly Ile

65 70 75 80

Thr Gly Ile Lys Thr Asn Thr Ile Cys Lys Lys Cys Ala Gln Asn Val

85 90 95

Gln Leu Tyr Gly Thr Pro Lys Pro Cys Gln Tyr Cys Asn Ile Ile Ala

100 105 110

Ala Phe Ile Gly Asn Lys Cys Gln Arg Cys Thr Asn Ser Glu Lys Lys

115 120 125

Tyr Gly Pro Pro Tyr Ser Cys Glu Gln Cys Lys Gln Gln Cys Ala Phe

130 135 140

Asp Arg Lys Asp Asp Arg Lys Lys Val Asp Gly Lys Leu Leu Cys Trp

145 150 155 160

Leu Cys Thr Leu Ser Tyr Lys Arg Val Leu Gln Lys Thr Lys Glu Gln

165 170 175

Arg Lys His Leu Ser Ser Ser Ser Ser Arg Ala Gly His Gln Glu Lys Glu

180 185 190

Gln Tyr Ser Arg Leu Ser Gly Gly Gly His Tyr Asn Ser Gln Lys Thr

195 200 205

Leu Ser Thr Ser Ser Ser Ile Gln Asn Glu Ile Pro Lys Lys Lys Ser Lys

210 215 220

Phe Glu Ser Ile Thr Thr Asn Gly Asp Ser Phe Ser Pro Asp Leu Ala

225 230 235 240

Leu Asp Ser Pro Gly Thr Asp His Phe Val Ile Ile Ala Gln Leu Lys

245 250 255

Glu Glu Val Ala Thr Leu Lys Lys Met Leu His Gln Lys Asp Gln Met

260 265 270

Ile Leu Glu Lys Glu Lys Lys Ile Thr Glu Leu Lys Ala Asp Phe Gln

275 280 285

Tyr Gln Glu Ser Gln Met Arg Ala Lys Met Asn Gln Met Glu Lys Thr

290 295 300

His Lys Glu Val Thr Glu Gln Leu Gln Ala Lys Asn Arg Glu Leu Leu

305 310 315 320

Lys Gln Ala Ala Ala Leu Ser Lys Ser Lys Lys Ser Glu Lys Ser Gly

325 330 335

Ala Ile Thr Ser Pro

340

<210>81

<211>312

<212>PRT

<213> Homo sapiens

<400>81

Met Ala Ala Leu Tyr Ala Cys Thr Lys Cys His Gln Arg Phe Pro Phe

1 5 10 15

Glu Ala Leu Ser Gln Gly Gln Gln Leu Cys Lys Glu Cys Arg Ile Ala

20 25 30

His Pro Val Val Lys Cys Thr Tyr Cys Arg Thr Glu Tyr Gln Gln Glu

35 40 45

Arg Leu Glu Cys Asn Gly Thr Ile Ser Ala His Cys Asn Leu His Leu

50 55 60

Pro Gly Ser Ser Asp Ser Pro Ala Ser Ser Ser Arg Val Ala Gly Ile

65 70 75 80

Thr Gly Ile Lys Thr Asn Thr Ile Cys Lys Lys Cys Ala Gln Asn Val

85 90 95

Gln Leu Tyr Gly Thr Pro Lys Pro Cys Gln Tyr Cys Asn Ile Ile Ala

100 105 110

Ala Phe Ile Gly Asn Lys Cys Gln Arg Cys Thr Asn Ser Glu Lys Lys

115 120 125

Tyr Gly Pro Pro Tyr Ser Cys Glu Gln Cys Lys Gln Gln Cys Ala Phe

130 135 140

Asp Arg Lys Asp Asp Arg Lys Lys Val Asp Gly Lys Leu Leu Cys Trp

145 150 155 160

Leu Cys Thr Leu Ser Tyr Lys Arg Val Leu Gln Lys Thr Lys Glu Gln

165 170 175

Arg Lys His Leu Ser Ser Ser Ser Ser Arg Ala Gly His Gln Glu Lys Glu

180 185 190

Gln Tyr Ser Arg Leu Ser Gly Gly Gly His Tyr Asn Ser Phe Ser Pro

195 200 205

Asp Leu Ala Leu Asp Ser Pro Gly Thr Asp His Phe Val Ile Ile Ala

210 215 220

Gln Leu Lys Glu Glu Val Ala Thr Leu Lys Lys Met Leu His Gln Lys

225 230 235 240

Asp Gln Met Ile Leu Glu Lys Glu Lys Lys Ile Thr Glu Leu Lys Ala

245 250 255

Asp Phe Gln Tyr Gln Glu Ser Gln Met Arg Ala Lys Met Asn Gln Met

260 265 270

Glu Lys Thr His Lys Glu Val Thr Glu Gln Leu Gln Ala Lys Asn Arg

275 280 285

Glu Leu Leu Lys Gln Ala Ala Ala Leu Ser Lys Ser Lys Lys Ser Glu

290 295 300

Lys Ser Gly Ala Ile Thr Ser Pro

305 310

<210>82

<211>100

<212>PRT

<213> Homo sapiens

<400>82

Phe Phe Phe Phe Phe Phe Glu Thr Glu Ser Cys Ser Val Ala Glu Ala

1 5 10 15

Gly Val Gln Trp Cys Asp Leu Gly Ser Leu Lys Ser Pro Pro Pro Gly

20 25 30

Ser Ser Asp Ser Pro Ala Ser Ala Ser Arg Val Ala Gly Ile Thr Gly

35 40 45

Met His His His Thr Gln Leu Ile Phe Val Phe Leu Val Glu Thr Gly

50 55 60

Ser His Met Gln Leu Ser Asp Ser Thr Leu Val Ile Thr Thr Ala Gln

65 70 75 80

Asn Ala Lys Ile Thr Ala Arg Ala Pro Arg Asp Leu Phe Phe Phe Phe

85 90 95

Phe Phe Phe Phe

100

<210>83

<211>56

<212>PRT

<213> Homo sapiens

<400>83

Leu Pro Leu Leu Pro Arg Met Glu Cys Arg Gly Met Ile Ser Ala His

1 5 10 15

Cys Asn Leu Cys Arg Ser Gly Ser Ser Asp Ser Pro Ala Ser Ala Ser

20 25 30

Arg Val Ala Gly Ile Thr Gly Thr Cys His His Ala Gln Leu Ser Phe

35 40 45

Pro Phe Phe Leu Phe Met Arg Trp

50 55

<210>84

<211>46

<212>PRT

<213> Homo sapiens

<400>84

Leu Pro Leu Leu Pro Arg Met Glu Cys Arg Gly Met Ile Ser Ala His

1 5 10 15

Cys Asn Leu Cys Arg Ser Gly Ser Ser Asp Ser Pro Ala Ser Ala Ser

20 25 30

Arg Val Ala Gly Ile Thr Gly Thr Cys His His Ala Gln Leu

35 40 45

<210>85

<211>699

<212>PRT

<213> Homo sapiens

<220>

<221>MOD_RES

<222>(677)

<223> variable amino acid

<400>85

Met Asp Ile Glu Asp Glu Glu Asn Met Ser Ser Ser Ser Thr Asp Val

1 5 10 15

Lys Glu Asn Arg Asn Leu Asp Asn Val Ser Pro Lys Asp Gly Ser Thr

20 25 30

Pro Gly Pro Gly Glu Gly Ser Gln Leu Ser Asn Gly Gly Gly Gly Gly

35 40 45

Pro Gly Arg Lys Arg Pro Leu Glu Glu Gly Ser Asn Gly His Ser Lys

50 55 60

Tyr Arg Leu Lys Lys Arg Arg Lys Thr Pro Gly Pro Val Leu Pro Lys

65 70 75 80

Asn Ala Leu Met Gln Leu Asn Glu Ile Lys Pro Gly Leu Gln Tyr Thr

85 90 95

Leu Leu Ser Gln Thr Gly Pro Val His Ala Pro Leu Phe Val Met Ser

100 105 110

Val Glu Val Asn Gly Gly Gln Val Phe Glu Gly Ser Gly Pro Thr Lys Lys

115 120 125

Lys Ala Lys Leu His Ala Ala Glu Lys Ala Leu Arg Ser Phe Val Gln

130 135 140

Phe Pro Asn Ala Ser Glu Ala His Leu Ala Met Gly Arg Thr Leu Ser

145 150 155 160

Val Asn Thr Asp Phe Thr Ser Asp Gln Ala Asp Phe Pro Asp Thr Leu

165 170 175

Phe Asn Gly Phe Glu Thr Pro Asp Lys Ala Glu Pro Pro Phe Tyr Val

180 185 190

Gly Ser Asn Gly Asp Asp Ser Phe Ser Ser Ser Ser Gly Asp Leu Ser Leu

195 200 205

Ser Ala Ser Pro Val Pro Ala Ser Leu Ala Gln Pro Pro Leu Pro Val

210 215 220

Leu Pro Pro Phe Pro Pro Pro Ser Gly Lys Asn Pro Val Met Ile Leu

225 230 235 240

Asn Glu Leu Arg Pro Gly Leu Lys Tyr Asp Phe Leu Ser Glu Ser Gly

245 250 255

Glu Ser His Ala Lys Ser Phe Val Met Ser Val Val Val Asp Gly Gln

260 265 270

Phe Phe Glu Gly Ser Gly Arg Asn Lys Lys Leu Ala Lys Ala Arg Ala

275 280 285

Ala Gln Ser Ala Ala Leu Ala Ala Ile Phe Asn Leu His Leu Asp Gln Thr

290 295 300

Pro Ser Arg Gln Pro Ile Pro Ser Glu Gly Leu Gln Leu His Leu Pro

305 310 315 320

Gln Val Leu Ala Asp Ala Val Ser Arg Leu Val Leu Gly Lys Phe Gly

325 330 335

Asp Leu Thr Asp Asn Phe Ser Ser Pro His Ala Arg Arg Lys Val Leu

340 345 350

Ala Gly Val Val Met Thr Thr Gly Thr Asp Val Lys Asp Ala Lys Val

355 360 365

Ile Ser Val Ser Thr Gly Thr Lys Cys Ile Asn Gly Glu Tyr Met Ser

370 375 380

Asp Arg Gly Leu Ala Leu Asn Asp Cys His Ala Glu Ile Ile Ser Arg

385 390 395 400

Arg Ser Leu Leu Arg Phe Leu Tyr Thr Gln Leu Glu Leu Tyr Leu Asn

405 410 415

Asn Lys Asp Asp Gln Lys Arg Ser Ile Phe Gln Lys Ser Glu Arg Gly

420 425 430

Gly Phe Arg Leu Lys Glu Asn Val Gln Phe His Leu Tyr Ile Ser Thr

435 440 445

Ser Pro Cys Gly Asp Ala Arg Ile Phe Ser Pro His Glu Pro Ile Leu

450 455 460

Glu Gly Ser Arg Ser Tyr Thr Gln Ala Gly Val Gln Trp Cys Asn His

465 470 475 480

Gly Ser Leu Gln Pro Arg Pro Pro Gly Leu Leu Ser Asp Pro Ser Thr

485 490 495

Ser Thr Phe Gln Gly Ala Gly Thr Thr Glu Pro Ala Asp Arg His Pro

500 505 510

Asn Arg Lys Ala Arg Gly Gln Leu Arg Thr Lys Ile Glu Ser Gly Glu

515 520 525

Gly Thr Ile Pro Val Arg Ser Asn Ala Ser Ile Gln Thr Trp Asp Gly

530 535 540

Val Leu Gln Gly Glu Arg Leu Leu Thr Met Ser Cys Ser Asp Lys Ile

545 550 555 560

Ala Arg Trp Asn Val Val Gly Ile Gln Gly Ser Leu Leu Ser Ile Phe

565 570 575

Val Glu Pro Ile Tyr Phe Ser Ser Ile Ile Leu Gly Ser Leu Tyr His

580 585 590

Gly Asp His Leu Ser Arg Ala Met Tyr Gln Arg Ile Ser Asn Ile Glu

595 600 605

Asp Leu Pro Pro Leu Tyr Thr Leu Asn Lys Pro Leu Leu Ser Gly Ile

610 615 620

Ser Asn Ala Glu Ala Arg Gln Pro Gly Lys Ala Pro Asn Phe Ser Val

625 630 635 640

Asn Trp Thr Val Gly Asp Ser Ala Ile Glu Val Ile Asn Ala Thr Thr

645 650 655

Gly Lys Asp Glu Leu Gly Arg Ala Ser Arg Leu Cys Lys His Ala Leu

660 665 670

Tyr Cys Arg Trp Xaa Ala Cys Ala Arg Gln Gly Ser Leu Pro Leu Thr

675 680 685

Thr Leu Gln Asp Tyr Gln Ala Gln Arg Val Pro

690 695

<210>86

<21l>331

<212>PRT

<213> Homo sapiens

<400>86

Met Leu Leu Ser Gln Asn Ala Phe Ile Val Arg Ser Leu Asn Leu Val

1 5 10 15

Leu Met Val Tyr Ile Ser Leu Val Phe Gly Ile Ser Tyr Asp Ser Pro

20 25 30

Asp Tyr Thr Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe

35 40 45

Arg Ser Ile Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr

50 55 60

His Tyr Thr Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys

65 70 75 80

Val Val Lys Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr

85 90 95

Asp Glu Trp Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly

100 105 110

Phe Ser Gly Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu

115 120 125

Ala Ile Asp Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe

130 135 140

Thr Asn His Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu

145 150 155 160

Glu Leu Gln Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly

165 170 175

Ile Val Lys Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn

180 185 190

Phe Thr Tyr Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val

195 200 205

Ser Val Tyr Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro

210 215 220

Leu Lys Cys Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu

225 230 235 240

Ser Ala Lys Ile Gly Gly Ile Ile Thr Val Phe Leu Ile Ala Leu Val

245 250 255

Leu Thr Ser Thr Ile Val Thr Leu Lys Trp Ile Gly Tyr Ile Cys Leu

260 265 270

Arg Asn Ser Leu Pro Lys Val Leu Arg Gln Gly Leu Thr Lys Gly Trp

275 280 285

Asn Ala Val Ala Ile His Arg Cys Ser His Asn Ala Leu Gln Ser Glu

290 295 300

Thr Pro Glu Leu Lys Gln Ser Ser Cys Leu Ser Phe Pro Ser Ser Trp

305 310 315 320

Asp Tyr Lys Arg Ala Ser Leu Cys Pro Ser Asp

325 330

<210>87

<211>841

<212>PRT

<213> Homo sapiens

<400>87

Met Pro Leu Ala Ala Tyr Cys Tyr Leu Arg Val Val Gly Lys Gly Ser

1 5 10 15

Tyr Gly Glu Val Thr Leu Val Lys His Arg Arg Asp Gly Lys Gln Tyr

20 25 30

Val Ile Lys Lys Leu Asn Leu Arg Asn Ala Ser Ser Arg Glu Arg Arg

35 40 45

Ala Ala Glu Gln Glu Ala Gln Leu Leu Ser Gln Leu Lys His Pro Asn

50 55 60

Ile Val Thr Tyr Lys Glu Ser Trp Glu Gly Gly Asp Gly Leu Leu Tyr

65 70 75 80

Ile Val Met Gly Phe Cys Glu Gly Gly Asp Leu Tyr Arg Lys Leu Lys

85 90 95

Glu Gln Lys Gly Gln Leu Leu Pro Glu Asn Gln Val Val Glu Trp Phe

100 105 110

Val Gln Ile Ala Met Ala Leu Gln Tyr Leu His Glu Lys His Ile Leu

115 120 125

His Arg Asp Leu Lys Thr Gln Asn Val Phe Leu Thr Arg Thr Asn Ile

130 135 140

Ile Lys Val Gly Asp Leu Gly Ile Ala Arg Val Leu Glu Asn His Cys

145 150 155 160

Asp Met Ala Ser Thr Leu Ile Gly Thr Pro Tyr Tyr Met Ser Pro Glu

165 170 175

Leu Phe Ser Asn Lys Pro Tyr Asn Tyr Lys Ser Asp Val Trp Ala Leu

180 185 190

Gly Cys Cys Val Tyr Glu Met Ala Thr Leu Lys His Ala Phe Asn Ala

195 200 205

Lys Asp Met Asn Ser Leu Val Tyr Arg Ile Ile Glu Gly Lys Leu Pro

210 215 220

Ala Met Pro Arg Asp Tyr Ser Pro Glu Leu Ala Glu Leu Ile Arg Thr

225 230 235 240

Met Leu Ser Lys Arg Pro Glu Glu Arg Pro Ser Val Arg Ser Ile Leu

245 250 255

Arg Gln Pro Tyr Ile Lys Arg Gln Ile Ser Phe Phe Leu Glu Ala Thr

260 265 270

Lys Ile Lys Thr Ser Lys Asn Asn Ile Lys Asn Gly Asp Ser Gln Ser

275 280 285

Lys Pro Phe Ala Thr Val Val Ser Gly Glu Ala Glu Ser Asn His Glu

290 295 300

Val Ile His Pro Gln Pro Leu Ser Ser Glu Gly Ser Gln Thr Tyr Ile

305 310 315 320

Met Gly Glu Gly Lys Cys Leu Ser Gln Glu Lys Pro Arg Ala Ser Gly

325 330 335

Leu Leu Lys Ser Pro Ala Ser Leu Lys Ala His Thr Cys Lys Gln Asp

340 345 350

Leu Ser Asn Thr Thr Glu Leu Ala Thr Ile Ser Ser Val Asn Ile Asp

355 360 365

Ile Leu Pro Ala Lys Gly Arg Asp Ser Val Ser Asp Gly Phe Val Gln

370 375 380

Glu Asn Gln Pro Arg Tyr Leu Asp Ala Ser Asn Glu Leu Gly Gly Ile

385 390 395 400

Cys Ser Ile Ser Gln Val Glu Glu Glu Met Leu Gln Asp Asn Thr Lys

405 410 415

Ser Ser Ala Gln Pro Glu Asn Leu Ile Pro Met Trp Ser Ser Asp Ile

420 425 430

Val Thr Gly Glu Lys Asn Glu Pro Val Lys Pro Leu Gln Pro Leu Ile

435 440 445

Lys Glu Gln Lys Pro Lys Asp Gln Ser Leu Ala Leu Ser Pro Lys Leu

450 455 460

Glu Cys Ser Gly Thr Ile Leu Ala His Ser Asn Leu Arg Leu Leu Gly

465 470 475 480

Ser Ser Asp Ser Pro Ala Ser Ala Ser Arg Val Ala Gly Ile Thr Gly

485 490 495

Val Cys His His Ala Gln Asp Gln Val Ala Gly Glu Cys Ile Ile Glu

500 505 510

Lys Gln Gly Arg Ile His Pro Asp Leu Gln Pro His Asn Ser Gly Ser

515 520 525

Glu Pro Ser Leu Ser Arg Gln Arg Arg Gln Lys Arg Arg Glu Gln Thr

530 535 540

Glu His Arg Gly Glu Lys Arg Gln Val Arg Arg Asp Leu Phe Ala Phe

545 550 555 560

Gln Glu Ser Pro Pro Arg Phe Leu Pro Ser His Pro Ile Val Gly Lys

565 570 575

Val Asp Val Thr Ser Thr Gln Lys Glu Ala Glu Asn Gln Arg Arg Val

580 585 590

Val Thr Gly Ser Val Ser Ser Ser Ser Arg Ser Ser Glu Met Ser Ser Ser

595 600 605

Lys Asp Arg Pro Leu Ser Ala Arg Glu Arg Arg Arg Leu Lys Gln Ser

610 615 620

Gln Glu Glu Met Ser Ser Ser Ser Gly Pro Ser Val Arg Lys Ala Ser Leu

625 630 635 640

Ser Val Ala Gly Pro Gly Lys Pro Gln Glu Glu Asp Gln Pro Leu Pro

645 650 655

Ala Arg Arg Leu Ser Ser Asp Cys Ser Val Thr Gln Glu Arg Lys Gln

660 665 670

Ile His Cys Leu Ser Glu Asp Glu Leu Ser Ser Ser Thr Ser Ser Ser Thr

675 680 685

Asp Lys Ser Asp Gly Asp Tyr Gly Glu Gly Lys Gly Gln Thr Asn Glu

690 695 700

Ile Asn Ala Leu Val Gln Leu Met Thr Gln Thr Leu Lys Leu Asp Ser

705 710 715 720

Lys Glu Ser Cys Glu Asp Val Pro Val Ala Asn Pro Val Ser Glu Phe

725 730 735

Lys Leu His Arg Lys Tyr Arg Asp Thr Leu Ile Leu His Gly Lys Val

740 745 750

Ala Glu Glu Ala Glu Glu Ile His Phe Lys Glu Leu Pro Ser Ala Ile

755 760 765

Met Pro Gly Ser Glu Lys Ile Arg Arg Leu Val Glu Val Leu Arg Thr

770 775 780

Asp Val Ile Arg Gly Leu Gly Val Gln Leu Leu Glu Gln Val Tyr Asp

785 790 795 800

Leu Leu Glu Glu Glu Asp Glu Phe Asp Arg Glu Val Arg Leu Arg Glu

805 810 815

His Met Gly Glu Lys Tyr Thr Thr Tyr Ser Val Lys Ala Arg Gln Leu

820 825 830

Lys Phe Phe Glu Glu Asn Met Asn Phe

835 840

<210>88

<211>759

<212>PRT

<213> Homo sapiens

<400>88

Met Met Ala Ala Leu Tyr Pro Ser Thr Asp Leu Ser Gly Ala Ser Ser

1 5 10 15

Ser Ser Leu Pro Ser Ser Ser Pro Ser Ser Ser Ser Ser Pro Asn Glu Val Met

20 25 30

Ala Leu Lys Asp Val Arg Glu Val Lys Glu Glu Asn Thr Leu Asn Glu

35 40 45

Lys Leu Phe Leu Leu Ala Cys Asp Lys Gly Asp Tyr Tyr Met Val Lys

50 55 60

Lys Ile Leu Glu Glu Asn Ser Ser Gly Asp Leu Asn Ile Asn Cys Val

65 70 75 80

Asp Val Leu Gly Arg Asn Ala Val Thr Ile Thr Ile Glu Asn Glu Asn

85 90 95

Leu Asp Ile Leu Gln Leu Leu Leu Asp Tyr Gly Cys Gln Lys Leu Met

100 105 110

Glu Arg Ile Gln Asn Pro Glu Tyr Ser Thr Thr Met Asp Val Ala Pro

115 120 125

Val Ile Leu Ala Ala His Arg Asn Asn Tyr Glu Ile Leu Thr Met Leu

130 135 140

Leu Lys Gln Asp Val Ser Leu Pro Lys Pro His Ala Val Gly Cys Glu

145 150 155 160

Cys Thr Leu Cys Ser Ala Lys Asn Lys Lys Asp Ser Leu Arg His Ser

165 170 175

Arg Phe Arg Leu Asp Ile Tyr Arg Cys Leu Ala Ser Pro Ala Leu Ile

180 185 190

Met Leu Thr Glu Glu Asp Pro Ile Leu Arg Ala Phe Glu Leu Ser Ala

195 200 205

Asp Leu Lys Glu Leu Ser Leu Val Glu Val Glu Phe Arg Asn Asp Tyr

210 215 220

Glu Glu Leu Ala Arg Gln Cys Lys Met Phe Ala Lys Asp Leu Leu Ala

225 230 235 240

Gln Ala Arg Asn Ser Arg Glu Leu Glu Val Ile Leu Asn His Thr Ser

245 250 255

Ser Asp Glu Pro Leu Asp Lys Arg Gly Leu Leu Glu Glu Arg Met Asn

260 265 270

Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Asn Gln Lys Glu Phe Val

275 280 285

Ser Gln Ser Asn Cys Gln Gln Phe Leu Asn Thr Val Trp Phe Gly Gln

290 295 300

Met Ser Gly Tyr Arg Arg Lys Pro Thr Cys Lys Lys Ile Met Thr Val

305 310 315 320

Leu Thr Val Gly Ile Phe Trp Pro Val Leu Ser Leu Cys Tyr Leu Ile

325 330 335

Ala Pro Lys Ser Gln Phe Gly Arg Ile Ile His Thr Pro Phe Met Lys

340 345 350

Phe Ile Ile His Gly Ala Ser Tyr Phe Thr Phe Leu Leu Leu Leu Asn

355 360 365

Leu Tyr Ser Leu Val Tyr Asn Glu Asp Lys Lys Asn Thr Met Gly Pro

370 375 380

Ala Leu Glu Arg Ile Asp Tyr Leu Leu Ile Leu Trp Ile Ile Gly Met

385 390 395 400

Ile Trp Ser Asp Ile Lys Arg Leu Trp Tyr Glu Gly Leu Glu Asp Phe

405 410 415

Leu Glu Glu Ser Arg Asn Gln Leu Ser Phe Val Met Asn Ser Leu Tyr

420 425 430

Leu Ala Thr Phe Ala Leu Lys Val Val Ala His Asn Lys Phe His Asp

435 440 445

Phe Ala Asp Arg Lys Asp Trp Asp Ala Phe His Pro Thr Leu Val Ala

450 455 460

Glu Gly Leu Phe Ala Phe Ala Asn Val Leu Ser Tyr Leu Arg Leu Phe

465 470 475 480

Phe Met Tyr Thr Thr Ser Ser Ser Ile Leu Gly Pro Leu Gln Ile Ser Met

485 490 495

Gly Gln Met Leu Gln Asp Phe Gly Lys Phe Leu Gly Met Phe Leu Leu

500 505 510

Val Leu Phe Ser Phe Thr Ile Gly Leu Thr Gln Leu Tyr Asp Lys Gly

515 520 525

Tyr Thr Ser Lys Glu Gln Lys Asp Cys Val Gly Ile Phe Cys Glu Gln

530 535 540

Gln Ser Asn Asp Thr Phe His Ser Phe Ile Gly Thr Cys Phe Ala Leu

545 550 555 560

Phe Trp Tyr Ile Phe Ser Leu Ala His Val Ala Ile Phe Val Thr Arg

565 570 575

Phe Ser Tyr Gly Glu Glu Leu Gln Ser Phe Val Gly Ala Val Ile Val

580 585 590

Gly Thr Tyr Asn Val Val Val Val Ile Val Leu Thr Lys Leu Leu Val

595 600 605

Ala Met Leu His Lys Ser Phe Gln Leu Ile Ala Asn His Glu Asp Lys

610 615 620

Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Leu Ser Tyr Phe Asp Asp

625 630 635 640

Lys Cys Thr Leu Pro Pro Pro Phe Asn Ile Ile Pro Ser Pro Lys Thr

645 650 655

Ile Cys Tyr Met Ile Ser Ser Leu Ser Lys Trp Ile Cys Ser His Thr

660 665 670

Ser Lys Gly Lys Val Lys Arg Gln Asn Ser Leu Lys Glu Trp Arg Asn

675 680 685

Leu Lys Gln Lys Arg Asp Glu Asn Tyr Gln Lys Val Met Cys Cys Leu

690 695 700

Val His Arg Tyr Leu Thr Ser Met Arg Gln Lys Met Gln Ser Thr Asp

705 710 715 720

Gln Ala Thr Val Glu Asn Leu Asn Glu Leu Arg Gln Asp Leu Ser Lys

725 730 735

Phe Arg Asn Glu Ile Arg Asp Leu Leu Gly Phe Arg Thr Ser Lys Tyr

740 745 750

Ala Met Phe Tyr Pro Arg Asn

755

<210>89

<211>848

<212>PRT

<213> Homo sapiens

<400>89

Met Glu Gly Ser Pro Ser Leu Arg Arg Met Thr Val Met Arg Glu Lys

1 5 10 15

Gly Arg Arg Gln Ala Val Arg Gly Pro Ala Phe Met Phe Asn Asp Arg

20 25 30

Gly Thr Ser Leu Thr Ala Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu

35 40 45

Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu Glu Ser Lys Thr

50 55 60

Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu

65 70 75 80

Ala Val Gly Asn Glu His Leu Glu Val Thr Glu Leu Leu Leu Lys Lys

85 90 95

Glu Asn Leu Ala Arg Ile Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys

100 105 110

Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His Pro Gly Phe Ala

115 120 125

Ala Ser Lys Arg Leu Thr Leu Ser Pro Cys Glu Gln Glu Leu Gln Asp

130 135 140

Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg Phe Ser Pro Asp

145 150 155 160

Ile Thr Pro Ile Ile Leu Ala Ala His Cys Gln Lys Tyr Glu Val Val

165 170 175

His Met Leu Leu Met Lys Gly Ala Arg Ile Glu Arg Pro His Asp Tyr

180 185 190

Phe Cys Lys Cys Gly Asp Cys Met Glu Lys Gln Arg His Asp Ser Phe

195 200 205

Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro

210 215 220

Ala Tyr Leu Ser Leu Ser Ser Ser Glu Asp Pro Val Leu Thr Ala Leu Glu

225 230 235 240

Leu Ser Asn Glu Leu Ala Lys Leu Ala Asn Ile Glu Lys Glu Phe Lys

245 250 255

Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp Phe Val Val Gly

260 265 270

Val Leu Asp Leu Cys Arg Asp Ser Glu Glu Val Glu Ala Ile Leu Asn

275 280 285

Gly Asp Leu Glu Ser Ala Glu Pro Leu Glu Val His Arg His Lys Ala

290 295 300

Ser Leu Ser Arg Val Lys Leu Ala Ile Lys Tyr Glu Val Lys Lys Phe

305 310 315 320

Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Thr Ile Trp Tyr Glu

325 330 335

Asn Leu Ser Gly Leu Arg Glu Gln Thr Ile Ala Ile Lys Cys Leu Val

340 345 350

Val Leu Val Val Ala Leu Gly Leu Pro Phe Leu Ala Ile Gly Tyr Trp

355 360 365

Ile Ala Pro Cys Ser Arg Leu Gly Lys Ile Leu Arg Ser Pro Phe Met

370 375 380

Lys Phe Val Ala His Ala Ala Ser Phe Ile Ile Phe Leu Gly Leu Leu

385 390 395 400

Val Phe Asn Ala Ser Asp Arg Phe Glu Gly Ile Thr Thr Leu Pro Asn

405 410 415

Ile Thr Val Thr Asp Tyr Pro Lys Gln Ile Phe Arg Val Lys Thr Thr

420 425 430

Gln Phe Thr Trp Thr Glu Met Leu Ile Met Val Trp Val Leu Gly Met

435 440 445

Met Trp Ser Glu Cys Lys Glu Leu Trp Leu Glu Gly Pro Arg Glu Tyr

450 455 460

Ile Leu Gln Leu Trp Asn Val Leu Asp Phe Gly Met Leu Ser Ile Phe

465 470 475 480

Ile Ala Ala Phe Thr Ala Arg Phe Leu Ala Phe Leu Gln Ala Thr Lys

485 490 495

Ala Gln Gln Tyr Val Asp Ser Tyr Val Gln Glu Ser Asp Leu Ser Glu

500 505 510

Val Thr Leu Pro Pro Glu Ile Gln Tyr Phe Thr Tyr Ala Arg Asp Lys

515 520 525

Trp Leu Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr Ala Ile

530 535 540

Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro Ala Asn

545 550 555 560

Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val Lys Asp

565 570 575

Ile Phe Lys Phe Met Val Leu Phe Ile Met Val Phe Phe Ala Phe Met

580 585 590

Ile Gly Met Phe Ile Leu Tyr Ser Tyr Tyr Leu Gly Ala Lys Val Asn

595 600 605

Ala Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe Trp Ser

610 615 620

Ile Phe Gly Leu Ser Glu Val Thr Ser Val Val Leu Lys Tyr Asp His

625 630 635 640

Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Ile Tyr Asn Val

645 650 655

Thr Met Val Val Val Leu Leu Asn Met Leu Ile Ala Met Ile Asn Ser

660 665 670

Ser Tyr Gln Glu Ile Glu Asp Asp Ser Asp Val Glu Trp Lys Phe Ala

675 680 685

Arg Ser Lys Leu Trp Leu Ser Tyr Phe Asp Asp Gly Lys Thr Leu Pro

690 695 700

Pro Pro Phe Ser Leu Val Pro Ser Pro Lys Ser Phe Val Tyr Phe Ile

705 710 715 720

Met Arg Ile Val Asn Phe Pro Lys Cys Arg Arg Arg Arg Leu Gln Lys

725 730 735

Asp Ile Glu Met Gly Met Gly Asn Ser Lys Ser Arg Leu Asn Leu Phe

740 745 750

Thr Gln Ser Asn Ser Arg Val Phe Glu Ser His Ser Phe Asn Ser Ile

755 760 765

Leu Asn Gln Pro Thr Arg Tyr Gln Gln Ile Met Lys Arg Leu Ile Lys

770 775 780

Arg Tyr Val Leu Lys Ala Gln Val Asp Lys Glu Asn Asp Glu Val Asn

785 790 795 800

Glu Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr

805 810 815

Glu Leu Leu Glu Asp Lys Ser Gln Ala Thr Glu Glu Leu Ala Ile Leu

820 825 830

Ile His Lys Leu Ser Glu Lys Leu Asn Pro Ser Met Leu Arg Cys Glu

835 840 845

<210>90

<211>215

<212>PRT

<213> Homo sapiens

<400>90

Met Ser Glu Thr Val Pro Pro Ala Pro Ala Ala Ser Ala Ala Pro Glu

1 5 10 15

Lys Pro Leu Ala Gly Lys Lys Ala Lys Lys Pro Ala Lys Ala Ala Ala

20 25 30

Ala Ser Lys Lys Lys Pro Ala Gly Pro Ser Val Ser Glu Leu Ile Val

35 40 45

Gln Ala Ala Ser Ser Ser Lys Glu Arg Gly Gly Val Ser Leu Ala Ala

50 55 60

Leu Lys Lys Ala Leu Ala Ala Ala Gly Tyr Asp Val Glu Lys Asn Asn

65 70 75 80

Ser Arg Ile Lys Leu Gly Ile Lys Ser Leu Val Ser Lys Gly Thr Leu

85 90 95

Val Gln Thr Lys Gly Thr Gly Ala Ser Gly Ser Phe Lys Leu Asn Lys

100 105 110

Lys Ala Ser Ser Val Glu Thr Lys Pro Gly Ala Ser Lys Val Ala Thr

115 120 125

Lys Thr Lys Ala Thr Gly Ala Ser Lys Lys Leu Lys Lys Ala Thr Gly

130 135 140

Ala Ser Lys Lys Ser Val Lys Thr Pro Lys Lys Ala Lys Lys Pro Ala

145 150 155 160

Ala Thr Arg Lys Ser Ser Lys Asn Pro Lys Lys Pro Lys Thr Val Lys

165 170 175

Pro Lys Lys Val Ala Lys Ser Pro Ala Lys Ala Lys Ala Val Lys Pro

180 185 190

Lys Ala Ala Lys Ala Arg Val Thr Lys Pro Lys Thr Ala Lys Pro Lys

195 200 205

Lys Ala Ala Pro Lys Lys Lys

210 215

<210>91

<211>931

<212>PRT

<213> Homo sapiens

<400>91

Met Ser Gln Ser Pro Ala Phe Gly Pro Arg Arg Gly Ser Ser Pro Arg

1 5 10 15

Gly Ala Ala Gly Ala Ala Ala Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Ser Glu Leu Gly Glu Asp Gly Cys Pro Gln Ala Pro Leu

35 40 45

Pro Cys Tyr Gly Tyr Tyr Pro Cys Phe Arg Gly Ser Asp Asn Arg Leu

50 55 60

Ala His Arg Arg Gln Thr Val Leu Arg Glu Lys Gly Arg Arg Leu Ala

65 70 75 80

Asn Arg Gly Pro Ala Tyr Met Phe Ser Asp Arg Ser Thr Ser Leu Ser

85 90 95

Ile Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro

100 105 110

Val Val Arg Lys Met Leu Glu Glu Cys His Ser Leu Asn Val Asn Cys

115 120 125

Val Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu

130 135 140

His Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg

145 150 155 160

Val Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile

165 170 175

Val Glu Ala Ile Leu Ser His Pro Ala Phe A1a Glu Gly Lys Arg Leu

180 185 190

Ala Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala

195 200 205

Tyr Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile

210 215 220

Leu Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg

225 230 235 240

Lys Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Asn

245 250 255

Asp Cys Asn Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser

260 265 270

Arg Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu

275 280 285

Ser Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu

290 295 300

Ala Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys

305 310 315 320

Leu Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Cys

325 330 335

Arg Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Val Glu Thr

340 345 350

Leu Gln Ser Gly Asp His Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu

355 360 365

Ala Ile Lys Tyr Glu Val Lys Lys Phe Val Ala His Pro Asn Cys Gln

370 375 380

Gln Gln Leu Leu Ser Ile Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln

385 390 395 400

Gln Thr Met Ala Val Lys Phe Leu Val Val Leu Ala Val Ala Ile Gly

405 410 415

Leu Pro Phe Leu Ala Leu Ile Tyr Trp Phe Ala Pro Cys Ser Lys Met

420 425 430

Gly Lys Ile Met Arg Gly Pro Phe Met Lys Phe Val Ala His Ala Ala

435 440 445

Ser Phe Thr Ile Phe Leu Gly Leu Leu Val Met Asn Ala Ala Asp Arg

450 455 460

Phe Glu Gly Thr Lys Leu Leu Pro Asn Glu Thr Ser Thr Asp Asn Ala

465 470 475 480

Lys Gln Leu Phe Arg Met Lys Thr Ser Cys Phe Ser Trp Met Glu Met

485 490 495

Leu Ile Ile Ser Trp Val Ile Gly Met Ile Trp Ala Glu Cys Lys Glu

500 505 510

Ile Trp Thr Gln Gly Pro Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met

515 520 525

Leu Asp Phe Gly Met Leu Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg

530 535 540

Phe Met Ala Phe Trp His Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala

545 550 555 560

Asn Asp Thr Leu Lys Asp Leu Thr Lys Val Thr Leu Gly Asp Asn Val

565 570 575

Lys Tyr Tyr Asn Leu Ala Arg Ile Lys Trp Asp Pro Ser Asp Pro Gln

580 585 590

Ile Ile Ser Glu Gly Leu Tyr Ala Ile Ala Val Val Leu Ser Phe Ser

595 600 605

Arg Ile Ala Tyr Ile Leu Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln

610 615 620

Ile Ser Leu Gly Arg Thr Val Lys Asp Ile Phe Lys Phe Met Val Ile

625 630 635 640

Phe Ile Met Val Phe Val Ala Phe Met Ile Gly Met Phe Asn Leu Tyr

645 650 655

Ser Tyr Tyr Ile Gly Ala Lys Gln Asn Glu Ala Phe Thr Thr Val Glu

660 665 670

Glu Ser Phe Lys Thr Leu Phe Trp Ala Ile Phe Gly Leu Ser Glu Val

675 680 685

Lys Ser Val Val IIe Asn Tyr Asn His Lys Phe Ile Glu Asn Ile Gly

690 695 700

Tyr Val Leu Tyr Gly Val Tyr Asn Val Thr Met Val Ile Val Leu Leu

705 710 715 720

Asn Met Leu Ile Ala Met Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp

725 730 735

Asp Ala Asp Val Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser

740 745 750

Tyr Phe Glu Glu Gly Arg Thr Leu Pro Val Pro Phe Asn Leu Val Pro

755 760 765

Ser Pro Lys Ser Leu Phe Tyr Leu Leu Leu Lys Leu Lys Lys Trp Ile

770 775 780

Ser Glu Leu Phe Gln Gly His Lys Lys Gly Phe Gln Glu Asp Ala Glu

785 790 795 800

Met Asn Lys Ile Asn Glu Glu Lys Lys Leu Gly Ile Leu Gly Ser His

805 810 815

Glu Asp Leu Ser Lys Leu Ser Leu Asp Lys Lys Gln Val Gly His Asn

820 825 830

Lys Gln Pro Ser Ile Arg Ser Ser Glu Asp Phe His Leu Asn Ser Phe

835 840 845

Asn Asn Pro Pro Arg Gln Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys

850 855 860

Arg Tyr Val Leu Gln Ala Gln Ile Asp Lys Glu Ser Asp Glu Val Asn

865 870 875 880

Glu Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr

885 890 895

Glu Leu Leu Glu Glu Lys Ser Gln Asn Thr Glu Asp Leu Ala Glu Leu

900 905 910

Ile Arg Glu Leu Gly Glu Lys Leu Ser Met Glu Pro Asn Gln Glu Glu

915 920 925

Thr Asn Arg

930

<210>92

<400>92

000

<210>93

<211>15

<212>PRT

<213> Homo sapiens

<400>93

Ser Arg Asp Pro Pro Ala Ser Ala Ser Gln Val Thr Gly Ile Arg

1 5 10 15

<210>94

<211>396

<212>PRT

<213> Homo sapiens

<400>94

Met Ala Ser Leu Ser Arg Ala Leu Arg Val Ala Ala Ala His Pro Arg

1 5 10 15

Gln Ser Pro Thr Arg Gly Met Gly Pro Cys Asn Leu Ser Ser Ala Ala

20 25 30

Gly Pro Thr Ala Glu Lys Ser Val Pro Tyr Gln Arg Thr Leu Lys Glu

35 40 45

Gly Gln Gly Thr Ser Val Val Ala Gln Gly Pro Ser Arg Pro Leu Pro

50 55 60

Ser Thr Ala Asn Val Val Val Ile Gly Gly Gly Ser Leu Gly Cys Gln

65 70 75 80

Thr Leu Tyr His Leu Ala Lys Leu Gly Met Ser Gly Ala Val Leu Leu

85 90 95

Glu Arg Glu Arg Leu Thr Ser Gly Thr Thr Trp His Thr Ala Gly Leu

100 105 110

Leu Trp Gln Leu Arg Pro Ser Asp Val Glu Val Glu Leu Leu Ala His

115 120 125

Thr Arg Arg Val Val Ser Arg Glu Leu Glu Glu Glu Thr Gly Leu His

130 135 140

Thr Gly Trp Ile Gln Asn Gly Gly Leu Phe Ile Ala Ser Asn Arg Gln

145 150 155 160

Arg Leu Asp Glu Tyr Lys Arg Leu Met Ser Leu Gly Lys Ala Tyr Gly

165 170 175

Val Glu Ser His Val Leu Ser Pro Ala Glu Thr Lys Thr Leu Tyr Pro

180 185 190

Leu Met Asn Val Asp Asp Leu Tyr Gly Thr Leu Tyr Val Pro His Asp

195 200 205

Gly Thr Met Asp Pro Ala Gly Thr Cys Thr Thr Leu Ala Arg Ala Ala

210 215 220

Ser Ala Arg Gly Ala Gln Val Ile Glu Asn Cys Pro Val Thr Gly Ile

225 230 235 240

Arg Val Trp Thr Asp Asp Phe Gly Val Arg Arg Val Ala Gly Val Glu

245 250 255

Thr Gln His Gly Ser Ile Gln Thr Pro Cys Val Val Asn Cys Ala Gly

260 265 270

Val Trp Ala Ser Ala Val Gly Arg Met Ala Gly Val Lys Val Pro Leu

275 280 285

Val Ala Met His His Ala Tyr Val Val Thr Glu Arg Ile Glu Gly Ile

290 295 300

Gln Ser Phe Thr Leu Leu Pro Thr Leu Glu Tyr Ser Gly Thr Val Ser

305 310 315 320

Ala His Cys Asn Leu Arg Leu Pro Gly Ser Ser Asn Ser Arg Ala Ser

325 330 335

Ala Ser His Val Ala Gly Ile Lys Cys Ala Arg His His Thr Arg Leu

340 345 350

Ile Phe Phe Cys Ile Leu Val Glu Thr Glu Phe His His Val Ala Lys

355 360 365

Ala Gly Leu Glu Leu Leu Ser Ser Gly Asn Pro Pro Ile Ser Asp Phe

370 375 380

Gln Ser Ala Arg Ile Thr Gly Val Ser His His Ala

385 390 395

<210>95

<211>72

<212>PRT

<213> Homo sapiens

<400>95

Leu Leu Trp Val Leu Leu Trp Ala Thr Val Leu Gly Leu Leu Cys Gln

1 5 10 15

Arg Leu Ala Ala Arg Leu Gly Val Val Thr Gly Lys Asp Leu Gly Glu

20 25 30

Val Cys His Leu Tyr Tyr Pro Lys Ser Glu Ser Arg Ser Val Ala Gln

35 40 45

Ser Gly Val Gln Trp Cys Asp Val Ser Ser Leu Gln Pro Leu Pro Pro

50 55 60

Arg Cys Pro Ala Pro Ser Ser Gly

65 70

<210>96

<211>84

<212>PRT

<213> Homo sapiens

<400>96

Met Glu Thr Glu Ser Gly Ser Val Ala Gln Ala Gly Val Gln Trp His

1 5 10 15

Asn Leu Gly Ser Leu Gln Pro Pro Pro Ser Arg Leu Lys Gln Leu Ser

20 25 30

Tyr Leu Ser Leu Pro Ser Ser Trp Asp Tyr Arg Cys Thr Pro Pro His

35 40 45

Pro Ala Asn Phe Leu Tyr Phe Asn Arg Asp Gly Ile Ser Pro Cys Cys

50 55 60

Pro Gly Trp Ser Pro Thr Pro Lys Leu Thr Gln Ser Thr His Leu Gly

65 70 75 80

Leu Ser Lys Cys

<210>97

<211>836

<212>PRT

<213> Homo sapiens

<400>97

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Val Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Phe Val Ala Gln Pro

290 295 300

Asn Cys Gln Gln Leu Leu Ala Ser Arg Trp Tyr Asp Glu Phe Pro Gly

305 310 315 320

Trp Arg Arg Arg His Trp Ala Val Lys Met Val Thr Cys Phe Ile Ile

325 330 335

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

340 345 350

Ser Pro Leu Gly Leu Phe Ile Arg Lys Pro Phe Ile Lys Phe Ile Cys

355 360 365

His Thr Ala Ser Tyr Leu Thr Phe Leu Phe Leu Leu Leu Leu Ala Ser

370 375 380

Gln His Ile Asp Arg Ser Asp Leu Asn Arg Gln Gly Pro Pro Pro Thr

385 390 395 400

Ile Val Glu Trp Met Ile Leu Pro Trp Val Leu Gly Phe Ile Trp Gly

405 410 415

Glu Ile Lys Gln Met Trp Asp Gly Gly Leu Gln Asp Tyr Ile His Asp

420 425 430

Trp Trp Asn Leu Met Asp Phe Val Met Asn Ser Leu Tyr Leu Ala Thr

435 440 445

Ile Ser Leu Lys Ile Val Ala Phe Val Lys Tyr Ser Ala Leu Asn Pro

450 455 460

Arg Glu Ser Trp Asp Met Trp His Pro Thr Leu Val Ala Glu Ala Leu

465 470 475 480

Phe Ala Ile Ala Asn Ile Phe Ser Ser Leu Arg Leu Ile Ser Leu Phe

485 490 495

Thr Ala Asn Ser His Leu Gly Pro Leu Gln Ile Ser Leu Gly Arg Met

500 505 510

Leu Leu Asp Ile Leu Lys Phe Leu Phe Ile Tyr Cys Leu Val Leu Leu

515 520 525

Ala Phe Ala Asn Gly Leu Asn Gln Leu Tyr Phe Tyr Tyr Glu Glu Thr

530 535 540

Lys Gly Leu Thr Cys Lys Gly Ile Arg Cys Glu Lys Gln Asn Asn Ala

545 550 555 560

Phe Ser Thr Leu Phe Glu Thr Leu Gln Ser Leu Phe Trp Ser Ile Phe

565 570 575

Gly Leu Ile Asn Leu Tyr Val Thr Asn Val Lys Ala Gln His Glu Phe

580 585 590

Thr Glu Phe Val Gly Ala Thr Met Phe Gly Thr Tyr Asn Val Ile Ser

595 600 605

Leu Val Val Leu Leu Asn Met Leu Ile Ala Met Met Asn Asn Ser Tyr

610 615 620

Gln Leu Ile Ala Asp His Ala Asp Ile Glu Trp Lys Phe Ala Arg Thr

625 630 635 640

Lys Leu Trp Met Ser Tyr Phe Glu Glu Gly Gly Thr Leu Pro Thr Pro

645 650 655

Phe Asn Val Ile Pro Ser Pro Lys Ser Leu Trp Tyr Leu Ile Lys Trp

660 665 670

Ile Trp Thr His Leu Cys Lys Lys Lys Met Arg Arg Lys Pro Glu Ser

675 680 685

Phe Gly Thr Ile Gly Arg Arg Ala Ala Asp Asn Leu Arg Arg His His

690 695 700

Gln Tyr Gln Glu Val Met Arg Asn Leu Val Lys Arg Tyr Val Ala Ala

705 710 715 720

Met Ile Arg Asp Ala Lys Thr Glu Glu Val Ala Arg Gln Gln Ala Ala

725 730 735

Gly Pro Leu Glu Arg Asn Ile Gln Leu Glu Ser Arg Gly Leu Ala Ser

740 745 750

Arg Gly Asp Leu Ser Ile Pro Gly Leu Ser Glu Gln Cys Val Leu Val

755 760 765

Asp His Arg Glu Arg Asn Thr Asp Thr Leu Gly Leu Gln Val Gly Lys

770 775 780

Arg Val Cys Pro Phe Lys Ser Glu Lys Val Val Val Glu Asp Thr Val

785 790 795 800

Pro Ile Ile Pro Lys Glu Lys His Ala Lys Glu Glu Asp Ser Ser Ile

805 810 815

Asp Tyr Asp Leu Asn Leu Pro Asp Thr Val Thr His Glu Asp Tyr Val

820 825 830

Thr Thr Arg Leu

835

<210>98

<211>828

<212>PRT

<213> Homo sapiens

<400>98

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Val Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Phe Val Ala Gln Pro

290 295 300

Asn Cys Gln Gln Leu Leu Ala Ser Arg Trp Tyr Asp Glu Phe Pro Gly

305 310 315 320

Trp Arg Arg Arg His Trp Ala Val Lys Met Val Thr Cys Phe Ile Ile

325 330 335

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

340 345 350

Ser Pro Leu Gly Leu Phe Ile Arg Lys Pro Phe Ile Lys Phe Ile Cys

355 360 365

His Thr Ala Ser Tyr Leu Thr Phe Leu Phe Leu Leu Leu Leu Ala Ser

370 375 380

Gln His Ile Asp Arg Ser Asp Leu Asn Arg Gln Gly Pro Pro Pro Thr

385 390 395 400

Ile Val Glu Trp Met Ile Leu Pro Trp Val Leu Gly Phe Ile Trp Gly

405 410 415

Glu Ile Lys Gln Met Trp Asp Gly Gly Leu Gln Asp Tyr Ile His Asp

420 425 430

Trp Trp Asn Leu Met Asp Phe Val Met Asn Ser Leu Tyr Leu Ala Thr

435 440 445

Ile Ser Leu Lys Ile Val Ala Phe Val Lys Tyr Ser Ala Leu Asn Pro

450 455 460

Arg Glu Ser Trp Asp Met Trp His Pro Thr Leu Val Ala Glu Ala Leu

465 470 475 480

Phe Ala Ile Ala Asn Ile Phe Ser Ser Leu Arg Leu Ile Ser Leu Phe

485 490 495

Thr Ala Asn Ser His Leu Gly Pro Leu Gln Ile Ser Leu Gly Arg Met

500 505 510

Leu Leu Asp Ile Leu Lys Phe Leu Phe Ile Tyr Cys Leu Val Leu Leu

515 520 525

Ala Phe Ala Asn Gly Leu Asn Gln Leu Tyr Phe Tyr Tyr Glu Glu Thr

530 535 540

Lys Gly Leu Thr Cys Lys Gly Ile Arg Cys Glu Lys Gln Asn Asn Ala

545 550 555 560

Phe Ser Thr Leu Phe Glu Thr Leu Gln Ser Leu Phe Trp Ser Ile Phe

565 570 575

Gly Leu Ile Asn Leu Tyr Val Thr Asn Val Lys Ala Gln His Glu Phe

580 585 590

Thr Glu Phe Val Gly Ala Thr Met Phe Gly Thr Tyr Asn Val Ile Ser

595 600 605

Leu Val Val Leu Leu Asn Met Leu Ile Ala Met Met Asn Asn Ser Tyr

610 615 620

Gln Leu Ile Ala Arg Arg Ala Ala Asp Asn Leu Arg Arg His His Gln

625 630 635 640

Tyr Gln Glu Val Met Arg Asn Leu Val Lys Arg Tyr Val Ala Ala Met

645 650 655

Ile Arg Asp Ala Lys Thr Glu Glu Gly Leu Thr Glu Glu Asn Phe Lys

660 665 670

Glu Leu Lys Gln Asp Ile Ser Ser Phe Arg Phe Glu Val Leu Gly Leu

675 680 685

Leu Arg Gly Ser Lys Leu Ser Thr Ile Gln Ser Ala Asn Ala Ser Lys

690 695 700

Glu Ser Ser Asn Ser Ala Asp Ser Asp Glu Lys Ser Asp Ser Glu Glu

705 710 715 720

Glu Val Ala Arg Gln Gln Ala Ala Gly Pro Leu Gl uArg Asn Ile Gln

725 730 735

Leu Glu Ser Arg Gly Leu Ala Ser Arg Gly Asp Leu Ser Ile Pro Gly

740 745 750

Leu Ser Glu Gln Cys Val Leu Val Asp His Arg Glu Arg Asn Thr Asp

755 760 765

Thr Leu Gly Leu Gln Val Gly Lys Arg Val Cys Pro Phe Lys Ser Glu

770 775 780

Lys Val Val Val Glu Asp Thr Val Pro Ile Ile Pro Lys Glu Lys His

785 790 795 800

Ala Lys Glu Glu Asp Ser Ser Ile Asp Tyr Asp Leu Asn Leu Pro Asp

805 810 815

Thr Val Thr His Glu Asp Tyr Val Thr Thr Arg Leu

820 825

<210>99

<211>73

<212>PRT

<213> Homo sapiens

<220>

<221>MOD_RES

<222>(18)

<223> variable amino acid

<400>99

Met Arg Thr Lys Ser Glu Arg Glu Ile His Leu Cys Val Leu Gly Phe

1 5 10 15

Phe Xaa Phe Phe Phe Glu Thr Gly Ser Arg Ser Val Ala Gln Ala Gly

20 25 30

Val Gln Arg His Ser His Gly Ser Leu Gln Pro Arg Pro Pro Gly Leu

35 40 45

Ile Gln Phe Ser His Leu Ser Leu Pro Ser Ser Trp Asp Tyr Arg His

50 55 60

Ala Pro Pro His Leu Val Asn Phe Leu

65 70

<210>100

<211>61

<212>PRT

<213> Homo sapiens

<400>100

Arg Phe Phe Phe Phe Phe Phe Phe Glu Glu Ser Arg Ser Phe Ala Gln

1 5 10 15

Ala Gly Val Gln Trp Arg Tyr Leu Gly Ser Leu Gln Pro Pro Pro Pro

20 25 30

Gly Phe Thr Arg Phe Ser Cys Leu Ser Leu Leu Ser Ser Trp Asp Tyr

35 40 45

Arg Arg Pro Pro Pro Arg Pro Ala Asn Phe Leu Tyr Phe

50 55 60

<210>101

<211>1258

<212>PRT

<213> Homo sapiens

<400>101

Glu Leu Ser Phe Pro Leu Leu Ser Leu Asp Phe Gly Ala His Gln Gly

1 5 10 15

Leu Gly Ser Ala Asp Met Gly Asp Met Lys Thr Pro Asp Phe Asp Asp

20 25 30

Leu Leu Ala Ala Phe Asp Ile Pro Asp Ile Asp Ala Asn Glu Ala Ile

35 40 45

His Ser Gly Pro Glu Glu Asn Glu Gly Pro Gly Gly Pro Gly Lys Pro

50 55 60

Glu Pro Gly Val Gly Ser Glu Ser Glu Asp Thr Ala Ala Ala Ser Ala

65 70 75 80

Gly Asp Gly Pro Gly Val Pro Ala Gln Ala Ser Asp His Gly Leu Pro

85 90 95

Pro Pro Asp Ile Ser Val Val Ser Val Ile Val Lys Asn Thr Val Cys

100 105 110

Pro Glu Gln Ser Glu Ala Leu Ala Gly Gly Ser Ala Gly Asp Gly Ala

115 120 125

Gln Ala Ala Gly Val Thr Lys Glu Gly Pro Val Gly Pro His Arg Met

130 135 140

Gln Asn Gly Phe Gly Ser Pro Glu Pro Ser Leu Pro Gly Thr Pro His

145 150 155 160

Ser Pro Ala Pro Pro Ser Gly Gly Thr Trp Lys Glu Lys Gly Met Glu

165 170 175

Gly Lys Thr Pro Leu Asp Leu Phe Ala His Phe Gly Pro Glu Pro Gly

180 185 190

Asp His Ser Asp Pro Leu Pro Pro Ser Ala Pro Ser Pro Thr Arg Glu

195 200 205

Gly Ala Leu Thr Pro Pro Pro Phe Pro Ser Ser Ser Phe Glu Leu Ala Gln

210 215 220

Glu Asn Gly Pro Gly Met Gln Pro Pro Val Ser Ser Pro Pro Leu Gly

225 230 235 240

Ala Leu Lys Gln Glu Ser Cys Ser Pro His His Pro Gln Val Leu Ala

245 250 255

Gln Gln Gly Ser Gly Ser Ser Pro Lys Ala Thr Asp Ile Pro Ala Ser

260 265 270

Ala Ser Pro Pro Pro Val Ala Gly Val Pro Phe Phe Lys Gln Ser Pro

275 280 285

Gly His Gln Ser Pro Leu Ala Ser Pro Lys Val Pro Val Cys Gln Pro

290 295 300

Leu Lys Glu Glu Asp Asp Asp Glu Gly Pro Val Asp Lys Ser Ser Pro

305 310 315 320

Gly Ser Pro Gln Ser Pro Ser Ser Ser Gly Ala Glu Ala Ala Asp Glu Asp

325 330 335

Ser Asn Asp Ser Pro Ala Ser Ser Ser Ser Ser Arg Pro Leu Lys Val Arg

340 345 350

Ile Lys Thr Ile Lys Thr Ser Cys Gly Asn Ile Thr Arg Thr Val Thr

355 360 365

Gln Val Pro Ser Asp Pro Asp Pro Pro Ala Pro Leu Ala Glu Gly Ala

370 375 380

Phe Leu Ala Glu Ala Ser Leu Leu Lys Leu Ser Pro Ala Thr Pro Thr

385 390 395 400

Ser Glu Gly Pro Lys Val Val Ser Val Gln Leu Gly Asp Gly Thr Arg

405 410 415

Leu Lys Gly Thr Val Leu Pro Val Ala Thr Ile Gln Asn Ala Ser Thr

420 425 430

Ala Met Leu Met Ala Ala Ser Val Ala Arg Lys Ala Val Val Leu Pro

435 440 445

Gly Gly Thr Ala Thr Ser Pro Lys Met Ile Ala Lys Asn Val Leu Gly

450 455 460

Leu Val Pro Gln Ala Leu Pro Lys Ala Asp Gly Arg Ala Gly Leu Gly

465 470 475 480

Thr Gly Gly Gln Lys Val Asn Gly Ala Ser Val Val Met Val Gln Pro

485 490 495

Ser Lys Thr Ala Thr Gly Pro Ser Thr Gly Gly Gly Thr Val Ile Ser

500 505 510

Arg Thr Gln Ser Ser Leu Val Glu Ala Phe Asn Lys Ile Leu Asn Ser

515 520 525

Lys Asn Leu Leu Pro Ala Tyr Arg Pro Asn Leu Ser Pro Pro Ala Glu

530 535 540

Ala Gly Leu Ala Leu Pro Pro Thr Gly Tyr Arg Cys Leu Glu Cys Gly

545 550 555 560

Asp Ala Phe Ser Leu Glu Lys Ser Leu Ala Arg His Tyr Asp Arg Arg

565 570 575

Ser Met Arg Ile Glu Val Thr Cys Asn His Cys Ala Arg Arg Leu Val

580 585 590

Phe Phe Asn Lys Cys Ser Leu Leu Leu His Ala Arg Glu His Lys Asp

595 600 605

Lys Gly Leu Val Met Gln Cys Ser His Leu Val Met Arg Pro Val Ala

610 615 620

Leu Asp Gln Met Val Gly Gln Pro Asp Ile Thr Pro Leu Leu Pro Val

625 630 635 640

Ala Val Pro Pro Val Ser Gly Pro Leu Ala Leu Pro Ala Leu Gly Lys

645 650 655

Gly Glu Gly Ala Ile Thr Ser Ser Ser Ala Ile Thr Thr Val Ala Ala Glu

660 665 670

Ala Pro Val Leu Pro Leu Ser Thr Glu Pro Pro Ala Ala Pro Ala Thr

675 680 685

Ser Ala Tyr Thr Cys Phe Arg Cys Leu Glu Cys Lys Glu Gln Cys Arg

690 695 700

Asp Lys Ala Gly Met Ala Ala His Phe Gln Gln Leu Gly Pro Pro Ala

705 710 715 720

Pro Gly Ala Thr Ser Asn Val Cys Pro Thr Cys Pro Met Met Leu Pro

725 730 735

Asn Arg Cys Ser Phe Ser Ala His Gln Arg Met His Lys Asn Arg Pro

740 745 750

Pro His Val Cys Pro Glu Cys Gly Gly Asn Phe Leu Gln Ala Asn Phe

755 760 765

Gln Thr His Leu Arg Glu Ala Cys Leu His Val Ser Arg Arg Val Gly

770 775 780

Tyr Arg Cys Pro Ser Cys Ser Val Val Phe Gly Gly Val Asn Ser Ile

785 790 795 800

Lys Ser His Ile Gln Thr Ser His Cys Glu Val Phe His Lys Cys Pro

805 810 815

Ile Cys Pro Met Ala Phe Lys Ser Gly Pro Ser Ala His Ala His Leu

820 825 830

Tyr Ser Gln His Pro Ser Phe Gln Thr Gln Gln Ala Lys Leu Ile Tyr

835 840 845

Lys Cys Ala Met Cys Asp Thr Val Phe Thr His Lys Pro Leu Leu Ser

850 855 860

Ser His Phe Asp Gln His Leu Leu Pro Gln Arg Val Ser Val Phe Lys

865 870 875 880

Cys Pro Ser Cys Pro Leu Leu Phe Ala Gln Lys Arg Thr Met Leu Glu

885 890 895

His Leu Lys Asn Thr His Gln Ser Gly Arg Leu Glu Glu Thr Ala Gly

900 905 910

Lys Gly Ala Gly Gly Ala Leu Leu Thr Pro Lys Thr Glu Pro Glu Glu Glu

915 920 925

Leu Ala Val Ser Gln Gly Gly Ala Ala Pro Ala Thr Glu Glu Ser Ser

930 935 940

Ser Ser Ser Glu Glu Glu Glu Val Pro Ser Ser Pro Glu Pro Pro Arg

945 950 955 960

Pro Ala Lys Arg Pro Arg Arg Glu Leu Gly Ser Lys Gly Leu Lys Gly

965 970 975

Gly Gly Gly Gly Pro Gly Gly Trp Thr Cys Gly Leu Cys His Ser Trp

980 985 990

Phe Pro Glu Arg Asp Glu Tyr Val Ala His Met Lys Lys Glu His Gly

995 1000 1005

Lys Ser Val Lys Lys Phe Pro Cys Arg Leu Cys Glu Arg Ser Phe Cys

1010 1015 1020

Ser Ala Pro Ser Leu Arg Arg His Val Arg Val Asn His Glu Gly Ile

1025 1030 1035 1040

Lys Arg Val Tyr Pro Cys Arg Tyr Cys Thr Glu Gly Lys Arg Thr Phe

                                                                                           

Ser Ser Arg Leu Ile Leu Glu Lys His Val Gln Val Arg His Gly Leu

1060 1065 1070

Gln Leu Gly Ala Gln Ser Pro Gly Arg Gly Thr Thr Leu Ala Arg Gly

1075 1080 1085

Ser Ser Ala Arg Ala Gln Gly Pro Gly Arg Lys Arg Arg Gln Ser Ser

1090 1095 1100

Asp Ser Cys Ser Glu Glu Pro Asp Ser Thr Thr Pro Pro Ala Lys Ser

1105 1110 1115 1120

Pro Arg Gly Gly Pro Gly Ser Gly Gly His Gly Pro Leu Arg Tyr Arg

                                                                                                         

Ser Ser Ser Ser Thr Glu Gln Ser Leu Met Met Gly Leu Arg Val Glu

1140 1145 1150

Asp Gly Ala Gln Gln Cys Leu Asp Cys Gly Leu Cys Phe Ala Ser Pro

1155 1160 1165

Gly Ser Leu Ser Arg His Arg Phe Ile Ser His Lys Lys Arg Arg Gly

1170 1175 1180

Val Gly Lys Ala Ser Ala Leu Gly Leu Gly Asp Gly Glu Glu Glu Ala

1185 1190 1195 1200

Pro Pro Ser Arg Ser Asp Pro Asp Gly Gly Asp Ser Pro Leu Pro Ala

                                                                                                   

Ser Gly Gly Pro Leu Thr Cys Lys Val Cys Gly Lys Ser Cys Asp Ser

1220 1225 1230

Pro Leu Asn Leu Lys Thr His Phe Arg Thr His Gly Met Ala Phe Ile

1235 1240 1245

Arg Ala Arg Gln Gly Ala Val Gly Asp Asn

1250 1255

<210>102

<211>930

<212>PRT

<213> Mus musculus (Mus musculus)

<400>102

Met Ser Gln Ser Pro Arg Phe Val Thr Arg Arg Gly Gly Ser Leu Lys

1 5 10 15

Ala Ala Pro Gly Ala Gly Thr Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Glu Leu Gly Asp Asp Gly Tyr Pro Gln Leu Pro Leu Pro

35 40 45

Pro Tyr Gly Tyr Tyr Pro Ser Phe Arg Gly Asn Glu Asn Arg Leu Thr

50 55 60

His Arg Arg Gln Thr Ile Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn

65 70 75 80

Arg Gly Pro Ala Tyr Met Phe Asn Asp His Ser Thr Ser Leu Ser Ile

85 90 95

Glu Glu Glu Arg Phe Leu Asp Ala Val Glu Tyr Gly Asn Ile Pro Val

100 105 110

Val Trp Lys Met Leu Glu Glu Cys His Ser Leu Asn Val Asn Cys Val

115 120 125

Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His

130 135 140

Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val

145 150 155 160

Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val

165 170 175

Glu Ala Ile Leu Asn His Pro Ser Phe Ala Glu Gly Lys Arg Leu Ala

180 185 190

Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr

195 200 205

Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu

210 215 220

Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys

225 230 235 240

Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Thr Glu

245 250 255

Cys Ser Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser Arg

260 265 270

Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser

275 280 285

Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala

290 295 300

Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Arg Lys Leu

305 310 315 320

Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg

325 330 335

Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Ala Glu Thr Arg

340 345 350

Gln Pro Gly Asp Phe Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala

355 360 365

Ile Lys Asp Glu Val Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln

370 375 380

Gln Leu Leu Ser Ile Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln

385 390 395 400

Thr Met Ala Val Lys Phe Leu Val Val Leu Ala Val Ala Ile Gly Leu

405 410 415

Pro Phe Leu Ala Leu Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly

420 425 430

Lys Ile Leu Pro Arg Pro Phe Met Lys Phe Val Ala His Ala Ala Ser

435 440 445

Phe Thr Ile Phe Leu Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe

450 455 460

Glu Gly Thr Lys Leu Leu Pro Asn Glu Thr Ser Thr Asp Asn Ala Arg

465 470 475 480

Gln Leu Phe Arg Met Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu

485 490 495

Ile Ile Ser Trp Val Ile Gly Met Ile Trp Ala Glu Cys Lys Glu Ile

500 505 510

Trp Thr Gln Gly Pro Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu

515 520 525

Asp Phe Gly Met Leu Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe

530 535 540

Met Ala Phe Trp His Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn

545 550 555 560

Asp Thr Leu Lys Asp Leu Thr Lys Val Thr Leu Gly Asp Asn Val Lys

565 570 575

Tyr Tyr Asn Leu Ala Arg Ile Lys Trp Asp Pro Thr Asp Pro Gln Ile

580 585 590

Ile Ser Glu Gly Leu Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg

595 600 605

Ile Ala Tyr Ile Leu Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile

610 615 620

Ser Leu Gly Arg Thr Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe

625 630 635 640

Ile Met Val Phe Val Ala Phe Met Ile Gly Met Phe Asn Leu Tyr Ser

645 650 655

Tyr Tyr Ile Gly Ala Lys Gln Asn Glu Ala Phe Thr Thr Val Glu Glu

660 665 670

Ser Phe Lys Thr Leu Phe Trp Ala Ile Phe Gly Leu Ser Glu Val Lys

675 680 685

Ser Val Val Ile Asn Tyr Asn His Lys Phe Ile Glu Asn Ile Gly Tyr

690 695 700

Val Leu Tyr Gly Val Tyr Asn Val Thr Met Val Ile Val Leu Leu Asn

705 710 715 720

Met Leu Ile Ala Met Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp

725 730 735

Ala Asp Val Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr

740 745 750

Phe Glu Glu Gly Arg Thr Leu Pro Val Pro Phe Asn Leu Val Pro Ser

755 760 765

Pro Lys Ser Leu Leu Tyr Leu Leu Leu Lys Phe Lys Lys Trp Met Cys

770 775 780

Glu Leu Ile Gln Gly Gln Lys Gln Gly Phe Gln Glu Asp Ala Glu Met

785 790 795 800

Asn Lys Arg Asn Glu Glu Lys Lys Phe Gly Ile Ser Gly Ser His Glu

805 810 815

Asp Leu Ser Lys Phe Ser Leu Asp Lys Asn Gln Leu Ala His Asn Lys

820 825 830

Gln Ser Ser Thr Arg Ser Ser Glu Asp Tyr His Leu Asn Ser Phe Ser

835 840 845

Asn Pro Pro Arg Gln Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys Arg

850 855 860

Tyr Val Leu Gln Ala Gln Ile Asp Lys Glu Ser Asp Glu Val Asn Glu

865 870 875 880

Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu

885 890 895

Leu Leu Glu Glu Lys Ser Gln Asn Ser Glu Asp Leu Ala Glu Leu Ile

900 905 910

Arg Lys Leu Gly Glu Arg Leu Ser Leu Glu Pro Lys Leu Glu Glu Ser

915 920 925

Arg Arg

930

<210>103

<211>522

<212>PRT

<213> Homo sapiens

<400>103

Gly Phe Leu Pro Ala Thr Lys Asn Leu Leu Asn Glu Lys Asn His Gly

1 5 10 15

Val Leu His Thr Ser Val Val Leu Leu Thr Glu Met Cys Glu Arg Ser

20 25 30

Pro Asp Met Leu Ala His Phe Arg Glu Asn Glu Lys Leu Val Pro Gln

35 40 45

Leu Val Arg Ile Leu Lys Asn Leu Ile Met Ser Gly Tyr Ser Pro Gly

50 55 60

His Asp Val Ser Gly Ile Ser Asp Pro Phe Leu Gln Val Arg Ile Leu

65 70 75 80

Arg Leu Leu Arg Ile Leu Gly Arg Asn Asp Asp Asp Ser Ser Glu Ala

85 90 95

Met Asn Asp Ile Leu Ala Gln Val Ala Thr Asn Thr Glu Thr Ser Lys

100 105 110

Asn Val Gly Asn Ala Ile Leu Tyr Glu Thr Val Leu Thr Ile Met Asp

115 120 125

Ile Lys Ser Glu Ser Gly Leu Arg Val Leu Ala Ile Asn Ile Leu Gly

130 135 140

Arg Phe Leu Leu Asn Asn Asp Lys Asn Ile Arg Tyr Val Ala Leu Thr

145 150 155 160

Ser Leu Leu Lys Thr Val Gln Thr Asp His Asn Ala Val Gln Arg His

165 170 175

Arg Ser Thr Ile Val Asp Cys Leu Lys Asp Leu Asp Val Ser Ile Lys

180 185 190

Arg Arg Ala Met Glu Leu Ser Phe Ala Leu Val Asn Gly Asn Asn Ile

195 200 205

Arg Gly Met Met Lys Glu Leu Leu Tyr Phe Leu Asp Ser Cys Glu Pro

210 215 220

Glu Phe Lys Ala Asp Cys Ala Ser Gly Ile Phe Leu Ala Ala Glu Lys

225 230 235 240

Tyr Ala Pro Ser Lys Arg Trp His Ile Asp Thr Ile Met Arg Val Leu

245 250 255

Thr Thr Ala Gly Ser Tyr Val Arg Asp Asp Ala Val Pro Asn Leu Ile

260 265 270

Gln Leu Ile Thr Asn Ser Val Glu Met His Ala Tyr Thr Val Gln Arg

275 280 285

Leu Tyr Lys Ala Ile Leu Gly Asp Tyr Ser Gln Gln Pro Leu Val Gln

290 295 300

Val Ala Ala Trp Cys Ile Gly Glu Tyr Gly Asp Leu Leu Val Ser Gly

305 310 315 320

Gln Cys Glu Glu Glu Glu Pro Ile Gln Val Thr Glu Asp Glu Val Leu

325 330 335

Asp Ile Leu Glu Ser Val Leu Ile Ser Asn Met Ser Thr Ser Val Thr

340 345 350

Arg Gly Tyr Ala Leu Thr Ala Ile Met Lys Leu Ser Thr Arg Phe Thr

355 360 365

Cys Thr Val Asn Arg Ile Lys Lys Val Val Ser Ile Tyr Gly Ser Ser

370 375 380

Ile Asp Val Glu Leu Gln Arg Arg Ala Val Glu Tyr Asn Ala Leu Phe

385 390 395 400

Lys Lys Tyr Asp His Met Arg Ser Ala Leu Leu Glu Arg Met Pro Val

405 410 415

Met Glu Lys Val Thr Thr Asn Gly Pro Thr Glu Ile Val Gln Thr Asn

420 425 430

Gly Glu Thr Glu Pro Ala Pro Leu Glu Thr Lys Pro Pro Pro Ser Gly

435 440 445

Pro Gln Pro Thr Ser Gln Ala Asn Asp Leu Leu Asp Leu Leu Gly Gly

450 455 460

Asn Asp Ile Thr Pro Val Ile Pro Thr Ala Pro Thr Ser Lys Pro Ser

465 470 475 480

Ser Ala Gly Gly Glu Leu Leu Asp Leu Leu Gly Asp Ile Asn Leu Thr

485 490 495

Gly Ser His Ser Val Ser Gln Ala Gly Val Gln Trp Asp Tyr Leu Gly

500 505 510

Ser Leu Gln Pro Leu Pro Pro Ala Phe Arg

515 520

<210>104

<211>407

<212>PRT

<213> Homo sapiens

<400>104

Met Trp Pro Asn Gly Ser Ser Leu Gly Pro Cys Phe Arg Pro Thr Asn

1 5 10 15

Ile Thr Leu Glu Glu Arg Arg Leu Ile Ala Ser Pro Trp Phe Ala Ala

20 25 30

Ser Phe Cys Val Val Gly Leu Ala Ser Asn Leu Leu Ala Leu Ser Val

35 40 45

Leu Ala Gly Ala Arg Gln Gly Gly Ser His Thr Arg Ser Ser Phe Leu

50 55 60

Thr Phe Leu Cys Gly Leu Val Leu Thr Asp Phe Leu Gly Leu Leu Val

65 70 75 80

Thr Gly Thr Ile Val Val Ser Gln His Ala Ala Leu Phe Glu Trp His

85 90 95

Ala Val Asp Pro Gly Cys Arg Leu Cys Arg Phe Met Gly Val Val Met

100 105 110

Ile Phe Phe Gly Leu Ser Pro Leu Leu Leu Gly Ala Ala Met Ala Ser

115 120 125

Glu Arg Tyr Leu Gly Ile Thr Arg Pro Phe Ser Arg Pro Ala Val Ala

130 135 140

Ser Gln Arg Arg Ala Trp Ala Thr Val Gly Leu Val Trp Ala Ala Ala

145 150 155 160

Leu Ala Leu Gly Leu Leu Pro Leu Leu Gly Val Gly Arg Tyr Thr Val

165 170 175

Gln Tyr Pro Gly Ser Trp Cys Phe Leu Thr Leu Gly Ala Glu Ser Gly

180 185 190

Asp Val Ala Phe Gly Leu Leu Phe Ser Met Leu Gly Gly Leu Ser Val

195 200 205

Gly Leu Ser Phe Leu Leu Asn Thr Val Ser Val Ala Thr Leu Cys His

210 215 220

Val Tyr His Gly Gln Glu Ala Ala Gln Gln Arg Pro Arg Asp Ser Glu

225 230 235 240

Val Glu Met Met Ala Gln Leu Leu Gly Ile Met Val Val Ala Ser Val

245 250 255

Cys Trp Leu Pro Leu Leu Val Phe Ile Ala Gln Thr Val Leu Arg Asn

260 265 270

Pro Pro Ala Met Ser Pro Ala Gly Gln Leu Ser Arg Thr Thr Glu Lys

275 280 285

Glu Leu Leu Ile Tyr Leu Arg Val Ala Thr Trp Asn Gln Ile Leu Asp

290 295 300

Pro Trp Val Tyr Ile Leu Phe Arg Arg Ala Val Leu Arg Arg Leu Gln

305 310 315 320

Pro Arg Leu Ser Thr Arg Pro Arg Arg Ser Leu Thr Leu Trp Pro Ser

325 330 335

Leu Glu Tyr Ser Gly Thr Ile Ser Ala His Cys Asn Leu Arg Leu Pro

340 345 350

Gly Ser Ser Asp Ser Arg Ala Ser Ala Ser Arg Ala Ala Gly Ile Thr

355 360 365

Gly Val Ser His Cys Ala Arg Pro Cys Met Leu Phe Asp Pro Glu Phe

370 375 380

Asp Leu Leu Ala Gly Val Gln Leu Leu Pro Phe Glu Pro Pro Thr Gly

385 390 395 400

Lys Ala Leu Ser Arg Lys Asp

405

<210>105

<211>741

<212>PRT

<213> Homo sapiens

<400>105

Met Asp Ile Glu Asp Glu Glu Asn Met Ser Ser Ser Ser Thr Asp Val

1 5 10 15

Lys Glu Asn Arg Asn Leu Asp Asn Val Ser Pro Lys Asp Gly Ser Thr

20 25 30

Pro Gly Pro Gly Glu Gly Ser Gln Leu Ser Asn Gly Gly Gly Gly Gly

35 40 45

Pro Gly Arg Lys Arg Pro Leu Glu Glu Gly Ser Asn Gly His Ser Lys

50 55 60

Tyr Arg Leu Lys Lys Arg Arg Lys Thr Pro Gly Pro Val Leu Pro Lys

65 70 75 80

Asn Ala Leu Met Gln Leu Asn Glu Ile Lys Pro Gly Leu Gln Tyr Thr

85 90 95

Leu Leu Ser Gln Thr Gly Pro Val His Ala Pro Leu Phe Val Met Ser

100 105 110

Val Glu Val Asn Gly Gly Gln Val Phe Glu Gly Ser Gly Pro Thr Lys Lys

115 120 125

Lys Ala Lys Leu His Ala Ala Glu Lys Ala Leu Arg Ser Phe Val Gln

130 135 140

Phe Pro Asn Ala Ser Glu Ala His Leu Ala Met Gly Arg Thr Leu Ser

145 150 155 160

Val Asn Thr Asp Phe Thr Ser Asp Gln Ala Asp Phe Pro Asp Thr Leu

165 170 175

Phe Asn Gly Phe Glu Thr Pro Asp Lys Ala Glu Pro Pro Phe Tyr Val

180 185 190

Gly Ser Asn Gly Asp Asp Ser Phe Ser Ser Ser Ser Gly Asp Leu Ser Leu

195 200 205

Ser Ala Ser Pro Val Pro Ala Ser Leu Ala Gln Pro Pro Leu Pro Val

210 215 220

Leu Pro Pro Phe Pro Pro Pro Ser Gly Lys Asn Pro Val Met Ile Leu

225 230 235 240

Asn Glu Leu Arg Pro Gly Leu Lys Tyr Asp Phe Leu Ser Glu Ser Gly

245 250 255

Glu Ser His Ala Lys Ser Phe Val Met Ser Val Val Val Asp Gly Gln

260 265 270

Phe Phe Glu Gly Ser Gly Arg Asn Lys Lys Leu Ala Lys Ala Arg Ala

275 280 285

Ala Gln Ser Ala Ala Leu Ala Ala Ile Phe Asn Leu His Leu Asp Gln Thr

290 295 300

Pro Ser Arg Gln Pro Ile Pro Ser Glu Gly Leu Gln Leu His Leu Pro

305 310 315 320

Gln Val Leu Ala Asp Ala Val Ser Arg Leu Val Leu Gly Lys Phe Gly

325 330 335

Asp Leu Thr Asp Asn Phe Ser Ser Pro His Ala Arg Arg Lys Val Leu

340 345 350

Ala Gly Val Val Met Thr Thr Gly Thr Asp Val Lys Asp Ala Lys Val

355 360 365

Ile Ser Val Ser Thr Gly Thr Lys Cys Ile Asn Gly Glu Tyr Met Ser

370 375 380

Asp Arg Gly Leu Ala Leu Asn Asp Cys His Ala Glu Ile Ile Ser Arg

385 390 395 400

Arg Ser Leu Leu Arg Phe Leu Tyr Thr Gln Leu Glu Leu Tyr Leu Asn

405 410 415

Asn Lys Asp Asp Gln Lys Arg Ser Ile Phe Gln Lys Ser Glu Arg Gly

420 425 430

Gly Phe Arg Leu Lys Glu Asn Val Gln Phe His Leu Tyr Ile Ser Thr

435 440 445

Ser Pro Cys Gly Asp Ala Arg Ile Phe Ser Pro His Glu Pro Ile Leu

450 455 460

Glu Gly Ser Arg Ser Tyr Thr Gln Ala Gly Val Gln Trp Cys Asn His

465 470 475 480

Gly Ser Leu Gln Pro Arg Pro Pro Gly Leu Leu Ser Asp Pro Ser Thr

485 490 495

Ser Thr Phe Gln Gly Ala Gly Thr Thr Glu Pro Ala Asp Arg His Pro

500 505 510

Asn Arg Lys Ala Arg Gly Gln Leu Arg Thr Lys Ile Glu Ser Gly Glu

515 520 525

Gly Thr Ile Pro Val Arg Ser Asn Ala Ser Ile Gln Thr Trp Asp Gly

530 535 540

Val Leu Gln Gly Glu Arg Leu Leu Thr Met Ser Cys Ser Asp Lys Ile

545 550 555 560

Ala Arg Trp Asn Val Val Gly Ile Gln Gly Ser Leu Leu Ser Ile Phe

565 570 575

Val Glu Pro Ile Tyr Phe Ser Ser Ile Ile Leu Gly Ser Leu Tyr His

580 585 590

Gly Asp His Leu Ser Arg Ala Met Tyr Gln Arg Ile Ser Asn Ile Glu

595 600 605

Asp Leu Pro Pro Leu Tyr Thr Leu Asn Lys Pro Leu Leu Ser Gly Ile

610 615 620

Ser Asn Ala Glu Ala Arg Gln Pro Gly Lys Ala Pro Asn Phe Ser Val

625 630 635 640

Asn Trp Thr Val Gly Asp Ser Ala Ile Glu Val Ile Asn Ala Thr Thr

645 650 655

Gly Lys Asp Glu Leu Gly Arg Ala Ser Arg Leu Cys Lys His Ala Leu

660 665 670

Tyr Cys Arg Trp Met Arg Val His Gly Lys Val Pro Ser His Leu Leu

675 680 685

Arg Ser Lys Ile Thr Lys Pro Asn Val Tyr His Glu Ser Lys Leu Ala

690 695 700

Ala Lys Glu Tyr Gln Ala Ala Lys Ala Arg Leu Phe Thr Ala Phe Ile

705 710 715 720

Lys Ala Gly Leu Gly Ala Trp Val Glu Lys Pro Thr Glu Gln Asp Gln

725 730 735

Phe Ser Leu Thr Pro

740

<210>106

<211>714

<212>PRT

<213> Homo sapiens

<400>106

Met Asp Ile Glu Asp Glu Glu Asn Met Ser Ser Ser Ser Thr Asp Val

1 5 10 15

Lys Glu Asn Arg Asn Leu Asp Asn Val Ser Pro Lys Asp Gly Ser Thr

20 25 30

Pro Gly Pro Gly Glu Gly Ser Gln Leu Ser Asn Gly Gly Gly Gly Gly

35 40 45

Pro Gly Arg Lys Arg Pro Leu Glu Glu Gly Ser Asn Gly His Ser Lys

50 55 60

Tyr Arg Leu Lys Lys Arg Arg Lys Thr Pro Gly Pro Val Leu Pro Lys

65 70 75 80

Asn Ala Leu Met Gln Leu Asn Glu Ile Lys Pro Gly Leu Gln Tyr Thr

85 90 95

Leu Leu Ser Gln Thr Gly Pro Val His Ala Pro Leu Phe Val Met Ser

100 105 110

Val Glu Val Asn Gly Gly Gln Val Phe Glu Gly Ser Gly Pro Thr Lys Lys

115 120 125

Lys Ala Lys Leu His Ala Ala Glu Lys Ala Leu Arg Ser Phe Val Gln

130 135 140

Phe Pro Asn Ala Ser Glu Ala His Leu Ala Met Gly Arg Thr Leu Ser

145 150 155 160

Val Asn Thr Asp Phe Thr Ser Asp Gln Ala Asp Phe Pro Asp Thr Leu

165 170 175

Phe Asn Gly Phe Glu Thr Pro Asp Lys Ala Glu Pro Pro Phe Tyr Val

180 185 190

Gly Ser Asn Gly Asp Asp Ser Phe Ser Ser Ser Ser Gly Asp Leu Ser Leu

195 200 205

Ser Ala Ser Pro Val Pro Ala Ser Leu Ala Gln Pro Pro Leu Pro Val

210 215 220

Leu Pro Pro Phe Pro Pro Pro Ser Gly Lys Asn Pro Val Met Ile Leu

225 230 235 240

Asn Glu Leu Arg Pro Gly Leu Lys Tyr Asp Phe Leu Ser Glu Ser Gly

245 250 255

Glu Ser His Ala Lys Ser Phe Val Met Ser Val Val Val Asp Gly Gln

260 265 270

Phe Phe Glu Gly Ser Gly Arg Asn Lys Lys Leu Ala Lys Ala Arg Ala

275 280 285

Ala Gln Ser Ala Ala Leu Ala Ala Ile Phe Asn Leu His Leu Asp Gln Thr

290 295 300

Pro Ser Arg Gln Pro Ile Pro Ser Glu Gly Leu Gln Leu His Leu Pro

305 310 315 320

Gln Val Leu Ala Asp Ala Val Ser Arg Leu Val Leu Gly Lys Phe Gly

325 330 335

Asp Leu Thr Asp Asn Phe Ser Ser Pro His Ala Arg Arg Lys Val Leu

340 345 350

Ala Gly Val Val Met Thr Thr Gly Thr Asp Val Lys Asp Ala Lys Val

355 360 365

Ile Ser Val Ser Thr Gly Thr Lys Cys Ile Asn Gly Glu Tyr Met Ser

370 375 380

Asp Arg Gly Leu Ala Leu Asn Asp Cys His Ala Glu Ile Ile Ser Arg

385 390 395 400

Arg Ser Leu Leu Arg Phe Leu Tyr Thr Gln Leu Glu Leu Tyr Leu Asn

405 410 415

Asn Lys Asp Asp Gln Lys Arg Ser Ile Phe Gln Lys Ser Glu Arg Gly

420 425 430

Gly Phe Arg Leu Lys Glu Asn Val Gln Phe His Leu Tyr Ile Ser Thr

435 440 445

Ser Pro Cys Gly Asp Ala Arg Ile Phe Ser Pro His Glu Pro Ile Leu

450 455 460

Glu Gly Ser Arg Ser Tyr Thr Gln Ala Gly Val Gln Trp Cys Asn His

465 470 475 480

Gly Ser Leu Gln Pro Arg Pro Pro Gly Leu Leu Ser Asp Pro Ser Thr

485 490 495

Ser Thr Phe Gln Gly Ala Gly Thr Thr Glu Pro Ala Asp Arg His Pro

500 505 510

Asn Arg Lys Ala Arg Gly Gln Leu Arg Thr Lys Ile Glu Ser Gly Glu

515 520 525

Gly Thr Ile Pro Val Arg Ser Asn Ala Ser Ile Gln Thr Trp Asp Gly

530 535 540

Val Leu Gln Gly Glu Arg Leu Leu Thr Met Ser Cys Ser Asp Lys Ile

545 550 555 560

Ala Arg Trp Asn Val Val Gly Ile Gln Gly Ser Leu Leu Ser Ile Phe

565 570 575

Val Glu Pro Ile Tyr Phe Ser Ser Ile Ile Leu Gly Ser Leu Tyr His

580 585 590

Gly Asp His Leu Ser Arg Ala Met Tyr Gln Arg Ile Ser Asn Ile Glu

595 600 605

Asp Leu Pro Pro Leu Tyr Thr Leu Asn Lys Pro Leu Leu Ser Gly Ile

610 615 620

Ser Asn Ala Glu Ala Arg Gln Pro Gly Lys Ala Pro Asn Phe Ser Val

625 630 635 640

Asn Trp Thr Val Gly Asp Ser Ala Ile Glu Val Ile Asn Ala Thr Thr

645 650 655

Gly Lys Asp Glu Leu Gly Arg Ala Ser Arg Leu Cys Lys His Ala Leu

660 665 670

Tyr Cys Arg Trp Met Arg Val His Gly Lys Val Pro Ser His Leu Leu

675 680 685

Arg Ser Lys Ile Thr Lys Pro Asn Val Tyr His Glu Ser Lys Leu Ala

690 695 700

Ala Lys Glu Tyr Gln Ala Ala Lys Val His

705 710

<210>107

<211>76

<212>PRT

<213> Homo sapiens

<400>107

Met Glu Val Leu Leu Phe Leu Phe Ile Phe Glu Thr Glu Ser Cys Ser

1 5 10 15

Val Ile Arg Leu Glu Cys Ser Gly Ser Leu Gln Pro Pro Pro Pro Arg

20 25 30

Phe Lys Gln Phe Ser Cys Leu Ser Leu Pro Ser Ser Trp Asp Tyr Arg

35 40 45

Cys Pro Pro Pro Cys Pro Ile Asn Phe Cys Ile Phe Gly Thr Asp Arg

50 55 60

Val Ser Pro Cys Trp Pro Gly Trp Ser Arg Ser Arg

65 70 75

<210>108

<211>977

<212>PRT

<213> Homo sapiens

<400>108

Met Ala Gln Phe Tyr Tyr Lys Arg Asn Val Asn Ala Pro Tyr Arg Asp

1 5 10 15

Arg Ile Pro Leu Arg Ile Val Arg Ala Glu Ser Glu Leu Ser Pro Ser

20 25 30

Glu Lys Ala Tyr Leu Asn Ala Val Glu Lys Gly Asp Tyr Ala Ser Val

35 40 45

Lys Lys Ser Leu Glu Glu Ala Glu Ile Tyr Phe Lys Ile Asn Ile Asn

50 55 60

Cys Ile Asp Pro Leu Gly Arg Thr Ala Leu Leu Ile Ala Ile Glu Asn

65 70 75 80

Glu Asn Leu Glu Leu Ile Glu Leu Leu Leu Ser Phe Asn Val Tyr Val

85 90 95

Gly Asp Ala Leu Leu His Ala Ile Arg Lys Glu Val Val Gly Ala Val

100 105 110

Glu Leu Leu Leu Asn His Lys Lys Pro Ser Gly Glu Lys Gln Val Pro

115 120 125

Pro Ile Leu Leu Asp Lys Gln Phe Ser Glu Phe Thr Pro Asp Ile Thr

130 135 140

Pro Ile Ile Leu Ala Ala His Thr Asn Asn Tyr Glu Ile Ile Lys Leu

145 150 155 160

Leu Val Gln Lys Gly Val Ser Val Pro Arg Pro His Glu Val Arg Cys

165 170 175

Asn Cys Val Glu Cys Val Ser Ser Ser Asp Val Asp Ser Leu Arg His

180 185 190

Ser Arg Ser Arg Leu Asn Ile Tyr Lys Ala Leu Ala Ser Pro Ser Leu

195 200 205

Ile Ala Leu Ser Ser Glu Asp Pro Phe Leu Thr Ala Phe Gln Leu Ser

210 215 220

Trp Glu Leu Gln Glu Leu Ser Lys Val Glu Asn Glu Phe Lys Ser Glu

225 230 235 240

Tyr Glu Glu Leu Ser Arg Gln Cys Lys Gln Phe Ala Lys Asp Leu Leu

245 250 255

Asp Gln Thr Arg Ser Ser Arg Glu Leu Glu Ile Ile Leu Asn Tyr Arg

260 265 270

Asp Asp Asn Ser Leu Ile Glu Glu Gln Ser Gly Asn Asp Leu Ala Arg

275 280 285

Leu Lys Leu Ala Ile Lys Tyr Arg Gln Lys Glu Phe Val Ala Gln Pro

290 295 300

Asn Cys Gln Gln Leu Leu Ala Ser Arg Trp Tyr Asp Glu Phe Pro Gly

305 310 315 320

Trp Arg Arg Arg His Trp Ala Val Lys Met Val Thr Cys Phe Ile Ile

325 330 335

Gly Leu Leu Phe Pro Val Phe Ser Val Cys Tyr Leu Ile Ala Pro Lys

340 345 350

Ser Pro Leu Gly Leu Phe Ile Arg Lys Pro Phe Ile Lys Phe Ile Cys

355 360 365

His Thr Ala Ser Tyr Leu Thr Phe Leu Phe Leu Leu Leu Leu Ala Ser

370 375 380

Gln His Ile Asp Arg Ser Asp Leu Asn Arg Gln Gly Pro Pro Pro Thr

385 390 395 400

Ile Val Glu Trp Met Ile Leu Pro Trp Val Leu Gly Phe Ile Trp Gly

405 410 415

Glu Ile Lys Gln Met Trp Asp Gly Gly Leu Gln Asp Tyr Ile His Asp

420 425 430

Trp Trp Asn Leu Met Asp Phe Val Met Asn Ser Leu Tyr Leu Ala Thr

435 440 445

Ile Ser Leu Lys Ile Val Ala Phe Val Lys Tyr Ser Ala Leu Asn Pro

450 455 460

Arg Glu Ser Trp Asp Met Trp His Pro Thr Leu Val Ala Glu Ala Leu

465 470 475 480

Phe Ala Ile Ala Asn Ile Phe Ser Ser Leu Arg Leu Ile Ser Leu Phe

485 490 495

Thr Ala Asn Ser His Leu Gly Pro Leu Gln Ile Ser Leu Gly Arg Met

500 505 510

Leu Leu Asp Ile Leu Lys Phe Leu Phe Ile Tyr Cys Leu Val Leu Leu

515 520 525

Ala Phe Ala Asn Gly Leu Asn Gln Leu Tyr Phe Tyr Tyr Glu Glu Thr

530 535 540

Lys Gly Leu Thr Cys Lys Gly Ile Arg Cys Glu Lys Gln Asn Asn Ala

545 550 555 560

Phe Ser Thr Leu Phe Glu Thr Leu Gln Ser Leu Phe Trp Ser Ile Phe

565 570 575

Gly Leu Ile Asn Leu Tyr Val Thr Asn Val Lys Ala Gln His Glu Phe

580 585 590

Thr Glu Phe Val Gly Ala Thr Met Phe Gly Thr Tyr Asn Val Ile Ser

595 600 605

Leu Val Val Leu Leu Asn Met Leu Ile Ala Met Met Asn Asn Ser Tyr

610 615 620

Gln Leu Ile Ala Asp His Ala Asp Ile Glu Trp Lys Phe Ala Arg Thr

625 630 635 640

Lys Leu Trp Met Ser Tyr Phe Glu Glu Gly Gly Thr Leu Pro Thr Pro

645 650 655

Phe Asn Val Ile Pro Ser Pro Lys Ser Leu Trp Tyr Leu Ile Lys Trp

660 665 670

Ile Trp Thr His Leu Cys Lys Lys Lys Met Arg Arg Lys Pro Glu Ser

675 680 685

Phe Gly Thr Ile Gly Arg Arg Ala Ala Asp Asn Leu Arg Arg His His

690 695 700

Gln Tyr Gln Glu Val Met Arg Asn Leu Val Lys Arg Tyr Val Ala Ala

705 710 715 720

Met Ile Arg Asp Ala Lys Thr Glu Glu Gly Leu Thr Glu Glu Asn Phe

725 730 735

Lys Glu Leu Lys Gln Asp Ile Ser Ser Phe Arg Phe Glu Val Leu Gly

740 745 750

Leu Leu Arg Gly Ser Lys Leu Ser Thr Ile Gln Ser Ala Asn Ala Ser

755 760 765

Lys Glu Ser Ser Asn Ser Ala Asp Ser Asp Glu Lys Ser Asp Ser Glu

770 775 780

Gly Asn Ser Lys Asp Lys Lys Lys Asn Phe Ser Leu Phe Asp Leu Thr

785 790 795 800

Thr Leu Ile His Pro Arg Ser Ala Ala Ile Ala Ser Glu Arg His Asn

805 810 815

Ile Ser Asn Gly Ser Ala Leu Val Val Gln Glu Pro Pro Arg Glu Lys

820 825 830

Gln Arg Lys Val Asn Phe Val Thr Asp Ile Lys Asn Phe Gly Leu Phe

835 840 845

His Arg Arg Ser Lys Gln Asn Ala Ala Glu Gln Asn Ala Asn Gln Ile

850 855 860

Phe Ser Val Ser Glu Glu Val Ala Arg Gln Gln Ala Ala Gly Pro Leu

865 870 875 880

Glu Arg Asn Ile Gln Leu Glu Ser Arg Gly Leu Ala Ser Arg Gly Asp

885 890 895

Leu Ser Ile Pro Gly Leu Ser Glu Gln Cys Val Leu Val Asp His Arg

900 905 910

Glu Arg Asn Thr Asp Thr Leu Gly Leu Gln Val Gly Lys Arg Val Cys

915 920 925

Pro Phe Lys Ser Glu Lys Val Val Val Glu Asp Thr Val Pro Ile Ile

930 935 940

Pro Lys Glu Lys His Ala Lys Glu Glu Asp Ser Ser Ile Asp Tyr Asp

945 950 955 960

Leu Asn Leu Pro Asp Thr Val Thr His Glu Asp Tyr Val Thr Thr Arg

965 970 975

Leu

<210>109

<211>275

<212>PRT

<213> Homo sapiens

<400>109

Met Glu Ser Tyr Ser Val Thr Gln Ala Gly Val Gln Trp His Glu Leu

1 5 10 15

Cys Ser Leu Gln Pro Ser Pro Pro Arg Phe Arg Glu Met Cys Ile Glu

20 25 30

Gln Asp Gly Arg Val His Leu Thr Val Val Tyr Phe Gly Lys Glu Glu

35 40 45

Ile Asn Glu Val Lys Gly Val Leu Glu Asn Thr Ser Lys Ala Ala Asn

50 55 60

Phe Arg Asn Phe Thr Phe Ile Gln Leu Asn Gly Glu Phe Ser Arg Gly

65 70 75 80

Lys Gly Leu Asp Val Gly Ala Arg Phe Trp Lys Gly Ser Asn Val Leu

85 90 95

Leu Phe Phe Cys Asp Val Asp Ile Tyr Phe Thr Ser Glu Phe Leu Asn

100 105 110

Thr Cys Arg Leu Asn Thr Gln Pro Gly Lys Lys Val Phe Tyr Pro Val

115 120 125

Leu Phe Ser Gln Tyr Asn Pro Gly Ile Ile Tyr Gly His His Asp Ala

130 135 140

Val Pro Pro Leu Glu Gln Gln Leu Val Ile Lys Lys Glu Thr Gly Phe

145 150 155 160

Trp Arg Asp Phe Gly Phe Gly Met Thr Cys Gln Tyr Arg Ser Asp Phe

165 170 175

Ile Asn Ile Gly Gly Phe Asp Leu Asp Ile Lys Gly Trp Gly Gly Glu

180 185 190

Asp Val His Leu Tyr Arg Lys Tyr Leu His Ser Asn Leu Ile Val Val

195 200 205

Arg Thr Pro Val Arg Gly Leu Phe His Leu Trp His Glu Lys Arg Cys

210 215 220

Met Asp Glu Leu Thr Pro Glu Gln Tyr Lys Met Cys Met Gln Ser Lys

225 230 235 240

Ala Met Asn Glu Ala Ser His Gly Gln Leu Gly Met Leu Val Phe Arg

245 250 255

His Glu Ile Glu Ala His Leu Arg Lys Gln Lys Gln Lys Thr Ser Ser

260 265 270

Lys Lys Thr

275

<210>110

<211>1084

<212>PRT

<213> Homo sapiens

<400>110

Met Asp Ile Thr Leu Val Arg Lys Glu Leu Gln Glu Leu Gln Asn Leu

1 5 10 15

Tyr Lys Gln Asn Ser Thr His Thr Ala Gln Gln Ala Glu Leu Ile Gln

20 25 30

Gln Leu Gln Val Leu Asn Met Asp Thr Gln Lys Val Leu Arg Asn Gln

35 40 45

Glu Asp Val His Thr Ala Glu Ser Ile Ser Tyr Gln Lys Leu Tyr Asn

50 55 60

Glu Leu His Ile Cys Phe Glu Thr Thr Lys Ser Asn Glu Ala Met Leu

65 70 75 80

Arg Gln Ser Val Thr Asn Leu Gln Asp Gln Leu Leu Gln Lys Glu Gln

85 90 95

Glu Asn Ala Lys Leu Lys Glu Lys Leu Gln Glu Ser Gln Gly Ala Pro

100 105 110

Leu Pro Leu Pro Gln Glu Ser Asp Pro Asp Tyr Ser Ala Gln Val Pro

115 120 125

His Arg Pro Ser Leu Ser Ser Ser Leu Glu Thr Leu Met Val Ser Gln Lys

130 135 140

Ser Glu Ile Glu Tyr Leu Gln Glu Lys Leu Lys Ile Ala Asn Glu Lys

145 150 155 160

Leu Ser Glu Asn Ile Ser Ala Asn Lys Gly Phe Ser Arg Lys Ser Ile

165 170 175

Met Thr Ser Ala Glu Gly Lys His Lys Glu Pro Pro Val Lys Arg Ser

180 185 190

Arg Ser Leu Ser Pro Lys Ser Ser Phe Thr Asp Ser Glu Glu Leu Gln

195 200 205

Lys Leu Arg Lys Ala Glu Arg Lys Ile Glu Asn Leu Glu Lys Ala Leu

210 215 220

Gln Leu Lys Ser Gln Glu Asn Asp Glu Leu Arg Asp Ala His Glu Lys

225 230 235 240

Arg Lys Glu Arg Leu Gln Met Leu Gln Thr Asn Tyr Arg Ala Val Lys

245 250 255

Glu Gln Leu Lys Gln Trp Glu Glu Gly Ser Gly Met Thr Glu Ile Arg

260 265 270

Lys Ile Lys Arg Ala Asp Pro Gln Gln Leu Arg Gln Glu Asp Ser Asp

275 280 285

Ala Val Trp Asn Glu Leu Ala Tyr Phe Lys Arg Glu Asn Gln Glu Leu

290 295 300

Met Ile Gln Lys Met Asn Leu Glu Glu Glu Leu Asp Glu Leu Lys Val

305 310 315 320

His Ile Ser Ile Asp Lys Ala Ala Ile Gln Glu Leu Asn Arg Cys Val

325 330 335

Ala Glu Arg Arg Glu Glu Gln Leu Phe Arg Ser Gly Glu Asp Asp Glu

340 345 350

Val Lys Arg Ser Thr Pro Glu Lys Asn Gly Lys Glu Met Leu Glu Gln

355 360 365

Thr Leu Gln Lys Val Ile Glu Leu Glu Asn Arg Leu Lys Ser Phe Glu

370 375 380

Lys Arg Ser Arg Lys Leu Lys Glu Gly Asn Lys Lys Leu Met Lys Glu

385 390 395 400

Asn Asp Phe Leu Lys Ser Leu Leu Lys Gln Gln Gln Glu Asp Thr Glu

405 410 415

Thr Arg Glu Lys Glu Leu Glu Gln Ile Ile Lys Gly Ser Lys Asp Val

420 425 430

Glu Lys Glu Asn Thr Glu Leu Gln Val Lys Ile Ser Glu Leu Glu Thr

435 440 445

Glu Val Thr Ser Leu Arg Arg Gln Val Ala Glu Ala Asn Ala Leu Arg

450 455 460

Asn Glu Asn Glu Glu Leu Ile Asn Pro Met Glu Lys Ser His Gln Ser

465 470 475 480

Ala Asp Arg Ala Lys Ser Glu Met Ala Thr Met Lys Val Arg Ser Gly

485 490 495

Arg Tyr Asp Cys Lys Thr Thr Met Thr Lys Val Lys Phe Lys Ala Ala

500 505 510

Lys Lys Asn Cys Ser Val Gly Arg His His Thr Val Leu Asn His Ser

515 520 525

Ile Lys Val Met Ser Asn Val Phe Glu Asn Leu Ser Lys Asp Gly Trp

530 535 540

Glu Asp Val Ser Glu Ser Ser Ser Ser Asp Ser Glu Ala Gln Thr Ser Gln

545 550 555 560

Thr Leu Gly Thr Ile Ile Val Glu Thr Ser Gln Lys Ile Ser Pro Thr

565 570 575

Glu Asp Gly Lys Asp Gln Lys Glu Ser Asp Pro Thr Glu Asp Ser Gln

580 585 590

Thr Gln Gly Lys Glu Ile Val Gln Thr Tyr Leu Asn Ile Asp Gly Lys

595 600 605

Thr Pro Lys Asp Tyr Phe His Asp Lys Asn Ala Lys Lys Pro Thr Phe

610 615 620

Gln Lys Lys Asn Cys Lys Met Gln Lys Ser Ser His Thr Ala Val Pro

625 630 635 640

Thr Arg Val Asn Arg Glu Lys Tyr Lys Asn Ile Thr Ala Gln Lys Ser

645 650 655

Ser Ser Asn Ile Ile Leu Leu Arg Glu Arg Ile Ile Ser Leu Gln Gln

660 665 670

Gln Asn Ser Val Leu Gln Asn Ala Lys Lys Thr Ala Glu Leu Ser Val

675 680 685

Lys Glu Tyr Lys Glu Val Asn Glu Lys Leu Leu His Gln Gln Gln Val

690 695 700

Ser Asp Gln Arg Phe Gln Thr Ser Arg Gln Thr Ile Lys Lys Leu Asn

705 710 715 720

Leu Asp Leu Ala Gly Leu Arg Lys Glu Lys Glu Asp Leu Leu Lys Lys

725 730 735

Leu Glu Ser Ser Ser Ser Glu Ile Thr Ser Leu Ala Glu Glu Asn Ser Gln

740 745 750

Val Thr Phe Pro Arg Ile Gln Val Thr Ser Leu Ser Pro Ser Arg Ser

755 760 765

Met Asp Leu Glu Met Lys Gln Leu Gln Tyr Lys Leu Lys Asn Ala Thr

770 775 780

Asn Glu Leu Thr Lys Gln Ser Ser Asn Val Lys Thr Leu Lys Phe Glu

785 790 795 800

Leu Leu Ala Lys Glu Glu His Ile Lys Glu Met His Glu Lys Ile Ser

805 810 815

Arg Met Glu Arg Asp Ile Thr Met Lys Arg His Leu Ile Glu Asp Leu

820 825 830

Lys Phe Arg Gln Lys Val Asn Leu Glu Ser Asn Lys Ser Phe Ser Glu

835 840 845

Met Leu Gln Asn Leu Asp Lys Lys Val Lys Thr Leu Thr Glu Glu Cys

850 855 860

Ser Asn Lys Lys Val Ser Ile Asp Ser Leu Lys Gln Arg Leu Asn Val

865 870 875 880

Ala Val Lys Glu Lys Ser Gln Tyr Glu Gln Met Tyr Gln Lys Ser Lys

885 890 895

Glu Glu Leu Glu Lys Lys Asp Leu Lys Leu Thr Leu Leu Val Ser Arg

900 905 910

Ile Ser Glu Thr Glu Ser Ala Met Ala Glu Ile Glu Thr Ala Ala Ser

915 920 925

Lys Gln Leu Gln Glu Leu Ala Leu Gln Ser Glu Gln Val Leu Glu Gly

930 935 940

Ala Gln Lys Thr Leu Leu Leu Ala Asn Glu Lys Val Glu Glu Phe Thr

945 950 955 960

Thr Phe Val Lys Ala Leu Ala Lys Glu Leu Gln Asn Asp Val His Val

965 970 975

Val Arg Arg Gln Ile Arg Glu Leu Lys Lys Met Lys Lys Asn Arg Asp

980 985 990

Ala Cys Lys Thr Ser Thr His Lys Ala Gln Thr Leu Ala Ala Ser Ile

995 1000 1005

Leu Asn Ile Ser Arg Ser Asp Leu Glu Glu Ile Leu Asp Thr Glu Asp

1010 1015 1020

Gln Val Glu Ile Glu Lys Thr Lys Ile Asp Ala Glu Asn Asp Lys Glu

1025 1030 1035 1040

Trp Met Leu Tyr Ile Gln Lys Leu Leu Glu Gly Gln Ser Leu Thr Leu

                                                                                           

Ser Pro Arg Leu Lys Cys Asn Gly Ala Ile Met Ala His Gln Asn Leu

1060 1065 1070

Arg Leu Pro Asp Ser Ser Ser Ser Ser Ala Ser Ala Ser

1075 1080

<210>111

<211>687

<212>PRT

<213> Homo sapiens

<400>111

Met Lys Val Val Pro Glu Lys Asn Ala Val Arg Ile Leu Trp Gly Arg

1 5 10 15

Glu Arg Gly Ala Arg Ala Met Gly Ala Gln Arg Leu Leu Gln Glu Leu

20 25 30

Val Glu Asp Lys Thr Arg Trp Met Lys Trp Glu Gly Lys Arg Val Glu

35 40 45

Leu Pro Asp Ser Pro Arg Ser Thr Phe Leu Leu Ala Phe Ser Pro Asp

50 55 60

Arg Thr Leu Leu Ala Ser Thr His Val Asn His Asn Ile Tyr Ile Thr

65 70 75 80

Glu Val Lys Thr Gly Lys Cys Val His Ser Leu lle Gly His Arg Arg

85 90 95

Thr Pro Trp Cys Val Thr Phe His Pro Thr Ile Ser Gly Leu Ile Ala

100 105 110

Ser Gly Cys Leu Asp Gly Glu Val Arg Ile Trp Asp Leu His Gly Gly

115 120 125

Ser Glu Ser Trp Phe Thr Asp Ser Asn Asn Ala Ile Ala Ser Leu Ala

130 135 140

Phe His Pro Thr Ala Gln Leu Leu Leu Ile Ala Thr Ala Asn Glu Ile

145 150 155 160

His Phe Trp Asp Arg Ser Arg Arg Glu Pro Phe Ala Val Val Lys Thr

165 170 175

Ala Ser Glu Met Glu Arg Val Arg Leu Val Arg Phe Asp Pro Leu Gly

180 185 190

His Tyr Leu Leu Thr Ala Ile Val Asn Pro Ser Asn Gln Gln Gly Asp

195 200 205

Asp Glu Pro Glu Ile Pro Ile Asp Gly Thr Glu Leu Ser His Tyr Arg

210 215 220

Gln Arg Ala Leu Leu Gln Ser Gln Pro Val Arg Arg Thr Pro Leu Leu

225 230 235 240

His Asn Phe Leu His Met Leu Ser Ser Arg Ser Ser Gly Ile Gln Thr

245 250 255

Glu Pro Phe His Pro Pro Glu Gln Ala Ser Ser Thr Gln Gln Asp Gln

260 265 270

Gly Leu Leu Asn Arg Pro Ser Ala Phe Ser Thr Val Gln Ser Ser Thr

275 280 285

Ala Gly Asn Thr Leu Arg Asn Leu Ser Leu Gly Pro Thr Arg Arg Ser

290 295 300

Leu Gly Gly Pro Leu Ser Ser His Pro Ser Arg Tyr His Arg Glu Ile

305 310 315 320

Ala Pro Gly Leu Thr Gly Ser Glu Trp Thr Arg Thr Val Leu Ser Leu

325 330 335

Asn Ser Arg Ser Glu Ala Glu Ser Met Pro Pro Pro Arg Thr Ser Ala

340 345 350

Ser Ser Val Ser Leu Leu Ser Val Leu Arg Gln Gln Glu Gly Gly Ser

355 360 365

Gln Ala Ser Val Tyr Thr Ser Ala Thr Glu Gly Arg Gly Phe Pro Ala

370 375 380

Ser Gly Leu Ala Thr Glu Ser Asp Gly Gly Asn Gly Ser Ser Gln Asn

385 390 395 400

Asn Ser Gly Ser Ile Arg His Glu Leu Gln Cys Asp Leu Arg Arg Phe

405 410 415

Phe Leu Glu Tyr Asp Arg Leu Gln Glu Leu Asp Gln Ser Leu Ser Gly

420 425 430

Glu Ala Pro Gln Thr Gln Gln Ala Gln Glu Met Leu Asn Asn Asn Ile

435 440 445

Glu Ser Glu Arg Pro Gly Pro Ser His Gln Pro Thr Pro His Ser Ser

450 455 460

Glu Asn Asn Ser Asn Leu Ser Arg Gly His Leu Asn Arg Cys Arg Ala

465 470 475 480

Cys His Asn Leu Leu Thr Phe Asn Asn Asp Thr Leu Arg Trp Glu Arg

485 490 495

Thr Thr Pro Asn Tyr Ser Ser Gly Glu Ala Ser Ser Ser Trp Gln Val

500 505 510

Pro Ser Ser Phe Glu Ser Val Pro Ser Ser Gly Ser Gln Leu Pro Pro

515 520 525

Leu Glu Arg Thr Glu Gly Gln Thr Pro Ser Ser Ser Arg Leu Glu Leu

530 535 540

Ser Ser Ser Ala Ser Pro Gln Glu Glu Arg Thr Val Gly Val Ala Phe

545 550 555 560

Asn Gln Glu Thr Gly His Trp Glu Arg Ile Tyr Thr Gln Ser Ser Arg

565 570 575

Ser Gly Thr Val Ser Gln Glu Ala Leu His Gln Asp Met Pro Glu Glu

580 585 590

Ser Ser Glu Glu Asp Ser Leu Arg Arg Arg Ser Leu Ala Leu Ser Pro

595 600 605

Arg Leu Glu Tyr Ser Gly Ala Ile Leu Ala His Cys Lys Leu Arg Leu

610 615 620

Pro Gly Ser Cys His Ser Pro Ala Ser Ala Ser Gln Val Ala Gly Thr

625 630 635 640

Thr Gly Ala His His His Ala Arg Leu Ile Phe Ala Phe Leu Val Glu

645 650 655

Met Glu Phe His His Val Ser Gln Ala Gly Leu Glu Leu Leu Thr Ser

660 665 670

Gly Asp Leu Pro Thr Ser Ala Ser Gln Val Leu Gly Leu Gln Ala

675 680 685

<210>112

<211>152

<212>PRT

<213> Homo sapiens

<400>112

Met Val His Ser Pro Arg Ser Leu Val Ala Asn Pro Ser Gln Val Leu

1 5 10 15

Phe Phe Leu Ser Phe Leu Phe Phe Phe Phe Leu Arg Gln Ser Phe Ala

20 25 30

Leu Val Ala Gln Ala Gly Val Gln Trp Arg Asn Leu Gly Ser Leu Gln

35 40 45

Pro Pro Pro Pro Gly Phe Lys Gln Phe Ser Cys Leu Ser Leu Leu Ser

50 55 60

Ser Trp Asp Tyr Arg His Ala Pro Pro Cys Pro Ala Tyr Phe Val Phe

65 70 75 80

Leu Val Asp Met Gly Phe Pro His Val Gly Gln Thr Gly Leu Glu Leu

85 90 95

Leu Thr Ser Gly Asp Pro Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile

100 105 110

Thr Gly Gly Ser His Arg Ala Gln Pro Thr Ser Ser Asn Pro Tyr Gly

115 120 125

Ile Val Phe Phe Phe Leu Pro Val Lys Thr Phe Ser Gly Met Ser Gln

130 135 140

Glu Ala Gly Asp Cys Arg Glu Thr

145 150

<210>113

<211>239

<212>PRT

<213> Homo sapiens

<400>113

Met Pro Thr Ala Thr Gly Leu Thr Leu Leu Thr Ser Ala Ser Ser Ala

1 5 10 15

Ile Ser Asp Pro Gly Gly Glu Val Ser Ala Pro Trp Gly Gly Leu Arg

20 25 30

Thr Trp Thr Gln Pro Leu Arg Cys Trp Glu Arg Leu Leu Pro Pro Pro

35 40 45

Gly Asp Pro Arg Thr Val Ala Glu Asn Thr Gln Gln Asp Glu Cys Gly

50 55 60

Leu Pro Gly Ser Cys Pro Ala Arg Pro Leu Ser Arg Lys Pro Glu Cys

65 70 75 80

Gly Arg Glu Gly Ile Leu Pro Cys Cys Ser Ser Ser Ala Trp Pro Glu

85 90 95

Gly Ser Phe Arg Pro Phe Gln Met Asn Leu Phe Ser Phe Leu Ser Phe

100 105 110

Phe Phe Leu Phe Phe Phe Phe Leu Arg Trp Ser Leu Thr Leu Ser Pro

115 120 125

Arg Leu Glu Cys Ser Ser Ala Ile 5er Ala His Cys Asn Leu Arg Leu

130 135 140

Pro Gly Ser Ser Asn Ser Pro Ala Leu Ala Ser Gln Val Ala Gly Ile

145 150 155 160

Thr Gly Ile Cys His His Ala Arg Gln Ile Phe Val Phe Leu Val Glu

165 170 175

Thr Gly Phe Cys His Val Gly Gln Ala Gly Leu Glu Leu Leu Ile Ser

180 185 190

Gly Asp Ser Pro Ala Ser Ala Phe Gln Ser Ala Gly Ile Ile Gly Val

195 200 205

Ser His Arg Ala Arg Pro Gly Ser Val Phe Leu Ala Arg Ser Glu Glu

210 215 220

Ser Leu Tyr Leu Arg Pro Gly Gln Gln Ser Gln Glu Val Lys Val

225 230 235

<210>114

<211>181

<212>PRT

<213> Homo sapiens

<400>114

Met Leu Leu Val Asp Ala Asp Gln Pro Glu Pro Met Arg Ser Gly Ala

1 5 10 15

Arg Glu Leu Ala Leu Phe Leu Thr Pro Glu Pro Gly Ala Glu Ala Lys

20 25 30

Glu Val Glu Glu Thr Ile Glu Gly Met Leu Leu Arg Leu Glu Glu Phe

35 40 45

Cys Ser Leu Ala Asp Leu Ile Arg Ser Asp Thr Ser Gln Ile Leu Glu

50 55 60

Glu Asn Ile Pro Val Leu Lys Ala Lys Leu Thr Glu Met Arg Gly Ile

65 70 75 80

Tyr Ala Lys Val Asp Arg Leu Glu Ala Phe Val Lys Met Val Gly His

85 90 95

His Val Ala Phe Leu Glu Ala Asp Val Leu Gln Ala Glu Arg Asp His

100 105 110

Gly Ala Phe Pro Gln Ala Leu Arg Arg Trp Leu Gly Ser Ala Gly Leu

115 120 125

Pro Ser Phe Arg Asn Val Glu Cys Ser Gly Thr Ile Pro Ala Arg Cys

130 135 140

Asn Leu Arg Leu Pro Gly Ser Ser Asp Ser Pro Ala Ser Ala Ser Gln

145 150 155 160

Val Ala Gly Ile Thr Glu Val Thr Cys Thr Gly Ala Arg Asp Val Arg

165 170 175

Ala Ala His Thr Val

                           

<210>115

<211>208

<212>PRT

<213> Homo sapiens

<400>115

Met Ser Val Tyr Ser Gly Lys Val Leu Leu Gln Thr Thr Pro Pro His

1 5 10 15

Val Ile Gly Gln Leu Asp Lys Leu Ile Arg Glu Val Ser Thr Leu Asp

20 25 30

Gly Val Leu Glu Val Arg Asn Glu His Phe Trp Thr Leu Gly Phe Gly

35 40 45

Ser Leu Ala Gly Ser Val His Val Arg Ile Arg Arg Asp Ala Asn Glu

50 55 60

Gln Met Val Leu Ala His Val Thr Asn Arg Leu Tyr Thr Leu Val Ser

65 70 75 80

Thr Leu Thr Val Gln Ile Phe Lys Asp Asp Trp Ile Arg Pro Ala Leu

85 90 95

Leu Ser Gly Pro Val Ala Ala Asn Val Leu Asn Phe Ser Asp His His

100 105 110

Val Ile Pro Met Pro Leu Leu Lys Gly Thr Asp Gly Leu Asn Pro Tyr

115 120 125

Val His Phe Leu Trp Lys Ile Asn Phe Phe Leu Phe Phe Asp Met Glu

130 135 140

Ser Leu Ser Val Ala Gln Ala Gly Val Gln Trp His Asp Leu Gly Ser

145 150 155 160

Leu Gln Pro His Leu Pro Gly Ser Ser Asn Ser Ala Cys Leu Ser Leu

165 170 175

Pro Ser Ser Trp Asp Tyr Arg His Ala Pro Pro His Leu Pro Asn Phe

180 185 190

Cys Ile Ile Ser Lys Asp Gly Val Leu Pro Cys Trp Pro Cys Trp Ser

195 200 205

<210>116

<211>118

<212>PRT

<213> Homo sapiens

<400>116

Met Glu Ser Arg Ser Val Ala Gln Thr Gly Val His Trp His Asn Leu

1 5 10 15

Ser Ser Leu Gln Pro Leu Pro Pro Arg Phe Lys Gln Phe Ser Cys Leu

20 25 30

Ser Leu Arg Ser Ser Trp Asp Tyr Thr His Leu Pro Pro Cys Leu Ala

35 40 45

Asn Phe Phe Val Phe Leu Val Glu Thr Ala Phe Arg His Val Gly Gln

50 55 60

Ala Gly Leu Lys Leu Leu Thr Ser Gly Asp Gln Pro Thr Ser Ala Ser

65 70 75 80

Gln Ser Ala Gly Ile Thr Gly Ile Ser His Arg Thr Gln Pro Val Gly

85 90 95

Arg Phe Leu Ile Thr Asp Ser Ile Phe Leu Phe Val Thr Asp Leu Leu

100 105 110

Lys Phe Ser Ile Ser Ser

115

<210>117

<211>102

<212>PRT

<213> Homo sapiens

<400>117

Met Ser Lys Val Leu Gly Gly Pro Phe Ser Lys Gly His Thr Ala Ser

1 5 10 15

Asp Lys Tyr Phe Gln Ile Phe His Asn Ile Ser Phe Phe Glu Thr Glu

20 25 30

Ser Cys Ser Val Ala Gln Ala Gly Val Gln Trp Cys Asn Leu Gly Ser

35 40 45

Leu Gln Ala Leu Pro Pro Arg Phe Thr Pro Phe Ser Cys Leu Ser Leu

50 55 60

Pro Ser Ser Trp Asp Tyr Arg His Pro Pro Pro Cys Pro Asp Asn Val

65 70 75 80

Phe Val Phe Ser Val Glu Thr Gly Phe His Cys Val Ser Gln Asp Gly

85 90 95

Leu Asn Leu Leu Thr Leu

100

<210>118

<211>214

<212>PRT

<213> Homo sapiens

<400>118

Met Ala Gln Gly Thr Leu Ile Arg Val Thr Pro Glu Gln Pro Thr His

1 5 10 15

Ala Val Cys Val Leu Gly Thr Leu Thr Gln Leu Asp Ile Cys Ser Ser

20 25 30

Ala Pro Glu Asp Cys Thr Ser Phe Ser Ile Asn Ala Ser Pro Gly Val

35 40 45

Val Val Asp Ile Ala His Ser Pro Pro Ala Lys Lys Lys Ser Thr Gly

50 55 60

Ser Ser Thr Trp Pro Leu Asp Pro Gly Val Glu Val Thr Leu Thr Met

65 70 75 80

Lys Ala Ala Ser Gly Ser Thr Gly Asp Gln Lys Val Gln Ile Ser Tyr

85 90 95

Tyr Gly Pro Lys Thr Pro Pro Val Lys Ala Leu Leu Tyr Leu Thr Ala

100 105 110

Val Asp Gly Val Ser Pro Cys His Pro Gly Trp Ser Ala Met His Asp

115 120 125

Leu Ala His Cys Asn Leu Arg Leu Gln Val Gln Ala Ile Leu Cys Phe

130 135 140

Ser Val Pro Ser Ser Ser Trp Thr Thr Gly Ala Cys His His Ala Trp Leu

145 150 155 160

Ile Phe Val Phe Leu Val Glu Met Glu Phe His His Val Gly Gln Ala

165 170 175

Gly Leu Glu Leu Leu Thr Ser Gly Asp Leu Pro Ala Ser Gly Ser Gln

180 185 190

Ser Ala Arg Ile Thr Gly Met Asn His Cys Ala Arg Pro Ser Ile Phe

195 200 205

Leu Ile Leu Lys Tyr Leu

210

<210>119

<211>876

<212>PRT

<213> Homo sapiens

<400>119

Met Ser Gln Ser Pro Ala Phe Gly Pro Arg Arg Gly Ser Ser Pro Arg

1 5 10 15

Gly Ala Ala Gly Ala Ala Ala Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Ser Glu Leu Gly Glu Asp Gly Cys Pro Gln Ala Pro Leu

35 40 45

Pro Cys Tyr Gly Tyr Tyr Pro Cys Phe Arg Gly Ser Asp Asn Arg Leu

50 55 60

Ala His Arg Arg Gln Thr Val Leu Arg Glu Lys Gly Arg Arg Leu Ala

65 70 75 80

Asn Arg Gly Pro Ala Tyr Met Phe Ser Asp Arg Ser Thr Ser Leu Ser

85 90 95

Ile Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro

100 105 110

Val Val Arg Lys Met Leu Glu Glu Cys His Ser Leu Asn Val Asn Cys

115 120 125

Val Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu

130 135 140

His Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg

145 150 155 160

Val Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile

165 170 175

Val Glu Ala Ile Leu Ser His Pro Ala Phe Ala Glu Gly Lys Arg Leu

180 185 190

Ala Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala

195 200 205

Tyr Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile

210 215 220

Leu Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg

225 230 235 240

Lys Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Asn

245 250 255

Asp Cys Asn Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser

260 265 270

Arg Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu

275 280 285

Ser Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu

290 295 300

Ala Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys

305 310 315 320

Leu Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Arg

325 330 335

Arg Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Val Glu Thr

340 345 350

Leu Gln Ser Gly Asp His Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu

355 360 365

Ala Ile Lys Tyr Glu Val Lys Lys Met Gly Lys Ile Met Arg Gly Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu Leu

405 410 415

Pro Asn Glu Thr Ser Thr Asp Asn Ala Lys Gln Leu Phe Arg Met Lys

420 425 430

Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val Ile

435 440 445

Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Thr Gln Gly Pro Lys

450 455 460

Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu Ala

465 470 475 480

Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His Ala

485 490 495

Ser Lys Ala Gln Ser Ile Ile Asp Ala ASn Asp Thr Leu Lys Asp Leu

500 505 510

Thr Lys Val Thr Leu Gly Asp Asn Val Lys Tyr Tyr Asn Leu Ala Arg

515 520 525

Ile Lys Trp Asp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Thr Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala Lys

595 600 605

Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val Ile Asn Tyr

625 630 635 640

Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu Gly Arg Thr

690 695 700

Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Leu Phe Tyr

705 710 715 720

Leu Leu Leu Lys Leu Lys Lys Trp Ile Ser Glu Leu Phe Gln Gly His

725 730 735

Lys Lys Gly Phe Gln Glu Asp Ala Glu Met Asn Lys Ile Asn Glu Glu

740 745 750

Lys Lys Leu Gly Ile Leu Gly Ser His Glu Asp Leu Ser Lys Leu Ser

755 760 765

Leu Asp Lys Lys Gln Val Gly His Asn Lys Gln Pro Ser Ile Arg Ser

770 775 780

Ser Glu Asp Phe His Leu Asn Ser Phe Asn Asn Pro Pro Arg Gln Tyr

785 790 795 800

Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala Gln

805 810 815

Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile

820 825 830

Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser

835 840 845

Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Glu Leu Gly Glu Lys

850 855 860

Leu Ser Met Glu Pro Asn Gln Glu Glu Thr Asn Arg

865 870 875

<210>120

<211>862

<212>PRT

<213> Homo sapiens

<400>120

Met Leu Arg Asn Ser Thr Phe Lys Asn Met Gln Arg Arg His Thr Thr

1 5 10 15

Leu Arg Glu Lys Gly Arg Arg Gln Ala Ile Arg Gly Pro Ala Tyr Met

20 25 30

Phe Asn Glu Lys Gly Thr Ser Leu Thr Pro Glu Glu Glu Arg Phe Leu

35 40 45

Asp Ser Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu Glu

50 55 60

Glu Ser Lys Thr Leu Asn Phe Asn Cys Val Asp Tyr Met Gly Gln Asn

65 70 75 80

Ala Leu Gln Leu Ala Val Gly Asn Glu His Leu Glu Val Thr Glu Leu

85 90 95

Leu Leu Lys Lys Glu Asn Leu Ala Arg Val Gly Asp Ala Leu Leu Leu

100 105 110

Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Asn His

115 120 125

Pro Ala Phe Ala Gln Gly Gln Arg Leu Thr Leu Ser Pro Leu Glu Gln

130 135 140

Glu Leu Arg Asp Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr Arg

145 150 155 160

Phe Ser His Asp Ile Thr Pro Ile Ile Leu Ala Ala His Cys Gln Glu

165 170 175

Tyr Glu Ile Val His Ile Leu Leu Leu Lys Gly Ala Arg Ile Glu Arg

180 185 190

Pro His Asp Tyr Phe Cys Lys Cys Asn Glu Cys Thr Glu Lys Gln Arg

195 200 205

Lys Asp Ser Phe Ser His Ser Arg Ser Arg Met Asn Ala Tyr Lys Gly

210 215 220

Leu Ala Ser Ala Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val Leu

225 230 235 240

Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Arg Leu Ala Asn Ile Glu

245 250 255

Thr Glu Phe Lys Asn Asp Tyr Arg Lys Leu Ser Met Gln Cys Lys Asp

260 265 270

Phe Val Val Gly Val Leu Asp Leu Cys Arg Asp Thr Glu Glu Val Glu

275 280 285

Ala Ile Leu Asn Gly Asp Val Asn Phe Gln Val Trp Ser Asp His His

290 295 300

Arg Pro Ser Leu Ser Arg Ile Lys Leu Ala Ile Lys Tyr Glu Val Lys

305 310 315 320

Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Thr Met Trp

325 330 335

Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Ser Ile Ala Val Lys Phe

340 345 350

Leu Ala Val Phe Gly Val Ser Ile Gly Leu Pro Phe Leu Ala Ile Ala

355 360 365

Tyr Trp Ile Ala Pro Cys Ser Lys Leu Gly Arg Thr Leu Arg Ser Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Val Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Val Asn Ala Ser Asp Arg Phe Glu Gly Val Lys Thr Leu

405 410 415

Pro Asn Glu Thr Phe Thr Asp Tyr Pro Lys Gln Ile Phe Arg Val Lys

420 425 430

Thr Thr Gln Phe Ser Trp Thr Glu Met Leu Ile Met Lys Trp Val Leu

435 440 445

Gly Met Ile Trp Ser Glu Cys Lys Glu Ile Trp Glu Glu Gly Pro Arg

450 455 460

Glu Tyr Val Leu His Leu Trp Asn Leu Leu Asp Phe Gly Met Leu Ser

465 470 475 480

Ile Phe Val Ala Ser Phe Thr Ala Arg Phe Met Ala Phe Leu Lys Ala

485 490 495

Thr Glu Ala Gln Leu Tyr Val Asp Gln His Val Gln Asp Asp Thr Leu

500 505 510

His Asn Val Ser Leu Pro Pro Glu Val Ala Tyr Phe Thr Tyr Ala Arg

515 520 525

Asp Lys Trp Trp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Arg Gly Ala Lys

595 600 605

Tyr Asn Pro Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ser Ile Phe Gly Leu Ser Glu Val Ile Ser Val Val Leu Lys Tyr

625 630 635 640

Asp His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Val Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Asn Ser Tyr Gln Glu Ile Glu Glu Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Leu Ser Tyr Phs Asp Glu Gly Arg Thr

690 695 700

Leu Pro Ala Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Phe Tyr Tyr

705 710 715 720

Leu Ile Met Arg Ile Lys Met Cys Leu Ile Lys Leu Cys Lys Ser Lys

725 730 735

Ala Lys Ser Cys Glu Asn Asp Leu Glu Met Gly Met Leu Asn Ser Lys

740 745 750

Phe Lys Lys Thr Arg Tyr Gln Ala Gly Met Arg Asn Ser Glu Asn Leu

755 760 765

Thr Ala Asn Asn Thr Leu Ser Lys Pro Thr Arg Tyr Gln Lys Ile Met

770 775 780

Lys Arg Leu Ile Lys Arg Tyr Val Leu Lys Ala Gln Val Asp Arg Glu

785 790 795 800

Asn Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile Lys Gln Asp Ile

805 810 815

Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser Gln Ala Thr Gly

820 825 830

Glu Leu Ala Asp Leu Ile Gln Gln Leu Ser Glu Lys Phe Gly Lys Asn

835 840 845

Leu Asn Lys Asp His Leu Arg Val Asn Lys Gly Lys Asp Ile

850 855 860

<210>121

<211>893

<212>PRT

<213> Guinea pig (Cavia porcellus)

<400>121

Met Asp Asp Gly Cys Pro Gln Leu Pro Leu Pro Pro His Gly Tyr Tyr

1 5 10 15

Pro Ser Leu Arg Gly Thr Asp Asn Arg Leu Thr His Arg Arg Gln Thr

20 25 30

Val Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn Arg Gly Pro Ala Tyr

35 40 45

Met Phe Asn Asp His Ser Thr Thr Leu Ser Ile Glu Glu Glu Arg Phe

50 55 60

Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu

65 70 75 80

Glu Glu Cys Leu Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln

85 90 95

Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu

100 105 110

Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu

115 120 125

Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Ser

130 135 140

His Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Pro Ser Gln

145 150 155 160

Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr

165 170 175

Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln

180 185 190

Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu

195 200 205

Arg Pro His Asp Tyr Phe Cys Lys Cys Ser Glu Cys Asn Gln Lys Gln

210 215 220

Lys His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys

225 230 235 240

Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val

245 250 255

Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile

260 265 270

Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys Leu Ser Met Gln Cys Lys

275 280 285

Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val

290 295 300

Glu Ala Ile Leu Asn Gly Asp Val Glu Thr Cys Gln Ser Gly Asp Gln

305 310 315 320

Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val

325 330 335

Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile

340 345 350

Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys

355 360 365

Phe Leu Val Val Leu Gly Val Ala Ile Gly Leu Pro Phe Leu Ala Leu

370 375 380

Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Met Arg Gly

385 390 395 400

Pro Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu

405 410 415

Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu

420 425 430

Arg Pro Asn Glu Thr Ser Thr Asp Asn Ala Lys Gln Leu Phe Arg Met

435 440 445

Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val

450 455 460

Ile Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Ala Gln Gly Pro

465 470 475 480

Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu

485 490 495

Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His

500 505 510

Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp

515 520 525

Leu Thr Lys Val Thr Leu Gly Glu Asp Val Lys Tyr Tyr Asn Leu Ala

530 535 540

Arg Ile Lys Trp Asp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu

545 550 555 560

Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu

565 570 575

Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr

580 585 590

Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val

595 600 605

Ala Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala

610 615 620

Lys Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu

625 630 635 640

Phe Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val Ile Asn

645 650 655

Tyr Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val

660 665 670

Tyr Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met

675 680 685

Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val Glu Trp

690 695 700

Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu Gly Arg

705 710 715 720

Thr Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Leu Leu

725 730 735

Tyr Leu Leu Leu Lys Phe Lys Lys Trp Gly Phe Glu Leu Phe Gln Gly

740 745 750

His Lys Lys Ala Phe Gln Glu Asp Ala Glu Met Asn Lys Arg Asn Glu

755 760 765

Glu Lys Lys Phe Gly Ile Leu Gly Ser His Glu Asp Leu Ser Lys Leu

770 775 780

Ser Val Asp Lys Lys Gln Leu Gly Gln Asn Lys Gln Ser Ser Ile Arg

785 790 795 800

Ser Ser Glu Asp Phe His Leu Asn Ser Phe Asn Asn Pro Pro Arg Gln

805 810 815

Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala

820 825 830

Gln Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu

835 840 845

Ile Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys

850 855 860

Ser Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Lys Leu Gly Glu

865 870 875 880

Lys Leu Ser Ser Ser Glu Pro Lys Gln Glu Glu Ile Asn Arg

885 890

<210>122

<211>597

<212>PRT

<213> Guinea pig (Cavia porcellus)

<400>122

Met Phe Asn Asp His Ser Thr Thr Leu Ser Ile Glu Glu Glu Arg Phe

1 5 10 15

Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu

20 25 30

Glu Glu Cys Leu Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln

35 40 45

Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu

50 55 60

Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu

65 70 75 80

Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Ser

85 90 95

His Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Leu Ser Gln

100 105 110

Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr

115 120 125

Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln

130 135 140

Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu

145 150 155 160

Arg Pro His Asp Tyr Phe Cys Lys Cys Ser Glu Cys Asn Gln Lys Gln

165 170 175

Lys His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys

180 185 190

Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val

195 200 205

Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile

210 215 220

Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys Leu Ser Met Gln Cys Lys

225 230 235 240

Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val

245 250 255

Glu Ala Ile Leu Asn Gly Asp Ile Glu Thr Cys Gln Pro Gly Asp Gln

260 265 270

Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val

275 280 285

Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile

290 295 300

Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys

305 310 315 320

Phe Leu Val Val Leu Gly Val Ala Ile Gly Leu Pro Phe Leu Ala Leu

325 330 335

Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Met Arg Gly

340 345 350

Pro Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu

355 360 365

Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu

370 375 380

Arg Pro Asn Glu Thr Ser Thr Asp Asn Ala Lys Gln Leu Phe Arg Met

385 390 395 400

Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val

405 410 415

Ile Gly Met Val Trp Ala Glu Cys Lys Glu Ile Trp Ala Gln Gly Pro

420 425 430

Lys Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu

435 440 445

Ala Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His

450 455 460

Ala Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp

465 470 475 480

Leu Thr Lys Val Thr Leu Gly Glu Asp Val Lys Tyr Tyr Asn Leu Ala

485 490 495

Arg Ile Lys Trp Asp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu

500 505 510

Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Ile Leu

515 520 525

Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr

530 535 540

Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val

545 550 555 560

Ala Phe Met Ile Gly Met Phe Asn Leu Tyr Ser His Tyr Ile Gly Ala

565 570 575

Lys Gln Asn Glu Ala Phe Thr Thr Tyr Val Ile Ser Asp Val Leu Thr

580 585 590

Met Glu Ile Ala Asp

595

<210>123

<211>815

<212>PRT

<213> Guinea pig (Cavia porcellus)

<400>123

Met Asp Asp Gly Cys Pro Gln Leu Pro Leu Pro Pro His Gly Tyr Tyr

1 5 10 15

Pro Ser Leu Arg Gly Thr Asp Asn Arg Leu Thr His Arg Arg Gln Thr

20 25 30

Val Leu Arg Glu Lys Gly Arg Arg Leu Ala Asn Arg Gly Pro Ala Tyr

35 40 45

Met Phe Asn Asp His Ser Thr Thr Leu Ser Ile Glu Glu Glu Arg Phe

50 55 60

Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro Val Val Arg Lys Met Leu

65 70 75 80

Glu Glu Cys Leu Ser Leu Asn Val Asn Cys Val Asp Tyr Met Gly Gln

85 90 95

Asn Ala Leu Gln Leu Ala Val Ala Asn Glu His Leu Glu Ile Thr Glu

100 105 110

Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg Val Gly Asp Ala Leu Leu

115 120 125

Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile Val Glu Ala Ile Leu Ser

130 135 140

His Pro Ala Phe Ala Glu Gly Lys Arg Leu Ala Thr Ser Pro Ser Gln

145 150 155 160

Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala Tyr Asp Glu Asp Gly Thr

165 170 175

Arg Phe Ser His Asp Val Thr Pro Ile Ile Leu Ala Ala His Cys Gln

180 185 190

Glu Tyr Glu Ile Val His Thr Leu Leu Arg Lys Gly Ala Arg Ile Glu

195 200 205

Arg Pro His Asp Tyr Phe Cys Glu Cys Ser Glu Cys Asn Gln Lys Gln

210 215 220

Lys His Asp Ser Phe Ser His Ser Arg Ser Arg Ile Asn Ala Tyr Lys

225 230 235 240

Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu Ser Ser Glu Asp Pro Val

245 250 255

Met Thr Ala Leu Glu Leu Ser Asn Glu Leu Ala Val Leu Ala Asn Ile

260 265 270

Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys Leu Ser Met Gln Cys Lys

275 280 285

Asp Phe Val Val Gly Leu Leu Asp Leu Cys Arg Asn Thr Glu Glu Val

290 295 300

Glu Ala Ile Leu Asn Gly Asp Val Glu Thr Cys Gln Pro Gly Asp Gln

305 310 315 320

Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu Ala Ile Lys Tyr Glu Val

325 330 335

Lys Lys Phe Val Ala His Pro Asn Cys Gln Gln Gln Leu Leu Ser Ile

340 345 350

Trp Tyr Glu Asn Leu Ser Gly Leu Arg Gln Gln Thr Met Ala Val Lys

355 360 365

Phe Leu Val Val Leu Gly Val Ala Ile Gly Leu Pro Phe Leu Ala Leu

370 375 380

Ile Tyr Trp Cys Ala Pro Cys Ser Lys Met Gly Lys Ile Met Arg Gly

385 390 395 400

Pro Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu

405 410 415

Gly Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu

420 425 430

Arg Pro Asn Glu Thr Ser Thr Asp Asn Ala Lys Gln Leu Phe Arg Met

435 440 445

Lys Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val

450 455 460

Ile Ala Arg Ile Lys Trp Asp Pro Ser Asp Pro Gln Ile Ile Ser Glu

465 470 475 480

Gly Leu Tyr Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr

485 490 495

Ile Leu Pro Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly

500 505 510

Arg Thr Val Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val

515 520 525

Phe Val Ala Phe Met Ile Gly Met Phe His Leu Tyr Ser Tyr Tyr Ile

530 535 540

Gly Ala Lys Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys

545 550 555 560

Thr Leu Phe Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val

565 570 575

Ile Asn Tyr Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr

580 585 590

Gly Val Tyr Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile

595 600 605

Ala Met Ile Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val

610 615 620

Glu Trp Lys Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu

625 630 635 640

Gly Arg Thr Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser

645 650 655

Leu Leu Tyr Leu Leu Leu Lys Phe Lys Lys Trp Gly Phe Glu Leu Phe

660 665 670

Gln Gly His Lys Lys Ala Phe Gln Glu Asp Ala Glu Met Asn Lys Arg

675 680 685

Asn Glu Glu Lys Lys Phe Gly Ile Leu Gly Ser His Glu Asp Leu Ser

690 695 700

Lys Leu Ser Val Asp Lys Lys Gln Leu Gly Gln Asn Lys Gln Ser Ser

705 710 715 720

Ile Arg Ser Ser Glu Asp Phe His Leu Asn Ser Phe Asn Asn Pro Pro

725 730 735

Arg Gln Tyr Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu

740 745 750

Gln Ala Gln Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu

755 760 765

Lys Glu Ile Lys Gln Asp Ile Ser Ser Ser Leu Arg Tyr Glu Leu Leu Glu

770 775 780

Glu Lys Ser Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Lys Leu

785 790 795 800

Gly Glu Lys Leu Ser Ser Glu Pro Lys Gln Glu Glu Ile Asn Arg

805 810 815

<210>124

<211>876

<212>PRT

<213> Homo sapiens

<400>124

Met Ser Gln Ser Pro Ala Phe Gly Pro Arg Arg Gly Ser Ser Pro Arg

1 5 10 15

Gly Ala Ala Gly Ala Ala Ala Arg Arg Asn Glu Ser Gln Asp Tyr Leu

20 25 30

Leu Met Asp Ser Glu Leu Gly Glu Asp Gly Cys Pro Gln Ala Pro Leu

35 40 45

Pro Cys Tyr Gly Tyr Tyr Pro Cys Phe Arg Gly Ser Asp Asn Arg Leu

50 55 60

Ala His Arg Arg Gln Thr Val Leu Arg Glu Lys Gly Arg Arg Leu Ala

65 70 75 80

Asn Arg Gly Pro Ala Tyr Met Phe Ser Asp Arg Ser Thr Ser Leu Ser

85 90 95

Ile Glu Glu Glu Arg Phe Leu Asp Ala Ala Glu Tyr Gly Asn Ile Pro

100 105 110

Val Val Arg Lys Met Leu Glu Glu Cys His Ser Leu Asn Val Asn Cys

115 120 125

Val Asp Tyr Met Gly Gln Asn Ala Leu Gln Leu Ala Val Ala Asn Glu

130 135 140

His Leu Glu Ile Thr Glu Leu Leu Leu Lys Lys Glu Asn Leu Ser Arg

145 150 155 160

Val Gly Asp Ala Leu Leu Leu Ala Ile Ser Lys Gly Tyr Val Arg Ile

165 170 175

Val Glu Ala Ile Leu Ser His Pro Ala Phe Ala Glu Gly Lys Arg Leu

180 185 190

Ala Thr Ser Pro Ser Gln Ser Glu Leu Gln Gln Asp Asp Phe Tyr Ala

195 200 205

Tyr Asp Glu Asp Gly Thr Arg Phe Ser His Asp Val Thr Pro Ile Ile

210 215 220

Leu Ala Ala His Cys Gln Glu Tyr Glu Ile Val His Thr Leu Leu Arg

225 230 235 240

Lys Gly Ala Arg Ile Glu Arg Pro His Asp Tyr Phe Cys Lys Cys Asn

245 250 255

Asp Cys Asn Gln Lys Gln Lys His Asp Ser Phe Ser His Ser Arg Ser

260 265 270

Arg Ile Asn Ala Tyr Lys Gly Leu Ala Ser Pro Ala Tyr Leu Ser Leu

275 280 285

Ser Ser Glu Asp Pro Val Met Thr Ala Leu Glu Leu Ser Asn Glu Leu

290 295 300

Ala Val Leu Ala Asn Ile Glu Lys Glu Phe Lys Asn Asp Tyr Lys Lys

305 310 315 320

Leu Ser Met Gln Cys Lys Asp Phe Val Val Gly Leu Leu Asp Leu Arg

325 330 335

Arg Asn Thr Glu Glu Val Glu Ala Ile Leu Asn Gly Asp Val Glu Thr

340 345 350

Leu Gln Ser Gly Asp His Gly Arg Pro Asn Leu Ser Arg Leu Lys Leu

355 360 365

Ala Ile Lys Tyr Glu Val Lys Lys Met Gly Lys Ile Met Arg Gly Pro

370 375 380

Phe Met Lys Phe Val Ala His Ala Ala Ser Phe Thr Ile Phe Leu Gly

385 390 395 400

Leu Leu Val Met Asn Ala Ala Asp Arg Phe Glu Gly Thr Lys Leu Leu

405 410 415

Pro Asn Glu Thr Ser Thr Asp Asn Ala Lys Gln Leu Phe Arg Met Lys

420 425 430

Thr Ser Cys Phe Ser Trp Met Glu Met Leu Ile Ile Ser Trp Val Ile

435 440 445

Gly Met Ile Trp Ala Glu Cys Lys Glu Ile Trp Thr Gln Gly Pro Lys

450 455 460

Glu Tyr Leu Phe Glu Leu Trp Asn Met Leu Asp Phe Gly Met Leu Ala

465 470 475 480

Ile Phe Ala Ala Ser Phe Ile Ala Arg Phe Met Ala Phe Trp His Ala

485 490 495

Ser Lys Ala Gln Ser Ile Ile Asp Ala Asn Asp Thr Leu Lys Asp Leu

500 505 510

Thr Lys Val Thr Leu Gly Asp Asn Val Lys Tyr Tyr Asn Leu Ala Arg

515 520 525

Ile Lys Trp Asp Pro Ser Asp Pro Gln Ile Ile Ser Glu Gly Leu Tyr

530 535 540

Ala Ile Ala Val Val Leu Ser Phe Ser Arg Ile Ala Tyr Thr Leu Pro

545 550 555 560

Ala Asn Glu Ser Phe Gly Pro Leu Gln Ile Ser Leu Gly Arg Thr Val

565 570 575

Lys Asp Ile Phe Lys Phe Met Val Ile Phe Ile Met Val Phe Val Ala

580 585 590

Phe Met Ile Gly Met Phe Asn Leu Tyr Ser Tyr Tyr Ile Gly Ala Lys

595 600 605

Gln Asn Glu Ala Phe Thr Thr Val Glu Glu Ser Phe Lys Thr Leu Phe

610 615 620

Trp Ala Ile Phe Gly Leu Ser Glu Val Lys Ser Val Val Ile Asn Tyr

625 630 635 640

Asn His Lys Phe Ile Glu Asn Ile Gly Tyr Val Leu Tyr Gly Val Tyr

645 650 655

Asn Val Thr Met Val Ile Val Leu Leu Asn Met Leu Ile Ala Met Ile

660 665 670

Asn Ser Ser Phe Gln Glu Ile Glu Asp Asp Ala Asp Val Glu Trp Lys

675 680 685

Phe Ala Arg Ala Lys Leu Trp Phe Ser Tyr Phe Glu Glu Gly Arg Thr

690 695 700

Leu Pro Val Pro Phe Asn Leu Val Pro Ser Pro Lys Ser Leu Phe Tyr

705 710 715 720

Leu Leu Leu Lys Leu Lys Lys Trp Ile Ser Glu Leu Phe Gln Gly His

725 730 735

Lys Lys Gly Phe Gln Glu Asp Ala Glu Met Asn Lys Ile Asn Glu Glu

740 745 750

Lys Lys Leu Gly Ile Leu Gly Ser His Glu Asp Leu Ser Lys Leu Ser

755 760 765

Leu Asp Lys Lys Gln Val Gly His Asn Lys Gln Pro Ser Ile Arg Ser

770 775 780

Ser Glu Asp Phe His Leu Asn Ser Phe Asn Asn Pro Pro Arg Gln Tyr

785 790 795 800

Gln Lys Ile Met Lys Arg Leu Ile Lys Arg Tyr Val Leu Gln Ala Gln

805 810 815

Ile Asp Lys Glu Ser Asp Glu Val Asn Glu Gly Glu Leu Lys Glu Ile

820 825 830

Lys Gln Asp Ile Ser Ser Leu Arg Tyr Glu Leu Leu Glu Glu Lys Ser

835 840 845

Gln Asn Thr Glu Asp Leu Ala Glu Leu Ile Arg Glu Leu Gly Glu Lys

850 855 860

Leu Ser Met Glu Pro Asn Gln Glu Glu Thr Asn Arg

865 870 875

<210>125

<211>1442

<212>DNA

<213> Homo sapiens

<220>

<221> CDS

<222>(15)..(1139)

<400>125

tttttttttt tgag atg gag ttt tcg ctc ttg ttg ccc agg ctg gag tgc 50

           Met Glu Phe Ser Leu Leu Leu Pro Arg Leu Glu Cys

1 5 10

aat ggc gca atc tca gct cac cgc aac ctc cgc ctc ccg ggt tca agc 98

Asn Gly Ala Ile Ser Ala His Arg Asn Leu Arg Leu Pro Gly Ser Ser

15 20 25

gat tct cct gcc tca gcc tcc cca gta gct ggg att aca ggc atg tgc 146

Asp Ser Pro Ala Ser Ala Ser Pro Val Ala Gly Ile Thr Gly Met Cys

30 35 40

acc cac gct cgg cta att ttg tat ttt ttt tta gta gag atg gag ttt 194

Thr His Ala Arg Leu Ile Leu Tyr Phe Phe Leu Val Glu Met Glu Phe

45 50 55 60

ctc cat gtt ggt cag gct ggt ctc gaa ctc ccg acc tca gat gat ccc 242

Leu His Val Gly Gln Ala Gly Leu Glu Leu Pro Thr Ser Asp Asp Pro

65 70 75

tcc gtc tcg gcc tcc caa agt gct aga tac agg act ggc cac cat gcc 290

Ser Val Ser Ala Ser Gln Ser Ala Arg Tyr Arg Thr Gly His His Ala

80 85 90

cgg ctc tgc ctg gct aat ttt tgt ggt aga aac agg gtt tca ctg atg 338

Arg Leu Cys Leu Ala Asn Phe Cys Gly Arg Asn Arg Val Ser Leu Met

95 100 105

tgc cca agc tgg tct cct gag ctc aag cag tcc acc tgc ctc agc ctc 386

Cys Pro Ser Trp Ser Pro Glu Leu Lys Gln Ser Thr Cys Leu Ser Leu

110 115 120

cca aag tgc tgg gat tac agg cgt gca gcc gtg cct ggc ctt ttt att 434

Pro Lys Cys Trp Asp Tyr Arg Arg Ala Ala Val Pro Gly Leu Phe Ile

125 130 135 140

tta ttt ttt tta aga cac agg tgt ccc act ctt acc cag gat gaa gtg 482

Leu Phe Phe Leu Arg His Arg Cys Pro Thr Leu Thr Gln Asp Glu Val

145 150 155

cag tgg tgt gat cac agc tca ctg cag cct tca act cct gag atc aag 530

Gln Trp Cys Asp His Ser Ser Leu Gln Pro Ser Thr Pro Glu Ile Lys

160 165 170

cat cct cct gcc tca gcc tcc caa gta gct ggg acc aaa gac atg cac 578

His Pro Pro Ala Ser Ala Ser Gln Val Ala Gly Thr Lys Asp Met His

175 180 185

cac tac acc tgg cta att ttt att ttt att ttt aat ttt ttg aga cag 626

His Tyr Thr Trp Leu Ile Phe Ile Phe Ile Phe Asn Phe Leu Arg Gln

190 195 200

agt ctc aac tct gtc acc cag gct gga gtg cag tgg cgc aat ctt ggc 674

Ser Leu Asn Ser Val Thr Gln Ala Gly Val Gln Trp Arg Asn Leu Gly

205 210 215 220

tca ctg caa cct ctg cct ccc ggg ttc aag tta ttc tcc tgc ccc agc 722

Ser Leu Gln Pro Leu Pro Pro Gly Phe Lys Leu Phe Ser Cys Pro Ser

225 230 235

ctc ctg agt agc tgg gac tac agg cgc cca cca cgc cta gct aat ttt 770

Leu Leu Ser Ser Trp Asp Tyr Arg Arg Pro Pro Arg Leu Ala Asn Phe

240 245 250

ttt gta ttt tta gta gag atg ggg ttc acc atg ttc gcc agg ttg atc 818

Phe Val Phe Leu Val Glu Met Gly Phe Thr Met Phe Ala Arg Leu Ile

255 260 265

ttg atc tct gga cct tgt gat ctg cct gcc tcg gcc tcc caa agt gct 866

Leu Ile Ser Gly Pro Cys Asp Leu Pro Ala Ser Ala Ser Gln Ser Ala

270 275 280

ggg att aca ggc gtg agc cac cac gcc cgg ctt att ttt aat ttt tgt 914

Gly Ile Thr Gly Val Ser His His His Ala Arg Leu Ile Phe Asn Phe Cys

285 290 295 300

ttg ttt gaa atg gaa tct cac tct gtt acc cag gct gga gtg caa tgg 962

Leu Phe Glu Met Glu Ser His Ser Val Thr Gln Ala Gly Val Gln Trp

305 310 315

cca aat ctc ggc tca ctg caa cct ctg cct ccc ggg ctc aag cga ttc 1010

Pro Asn Leu Gly Ser Leu Gln Pro Leu Pro Pro Gly Leu Lys Arg Phe

320 325 330

tcc tgt ctc agc ctc cca agc agc tgg gat tac ggg cac ctg cca cca 1058

Ser Cys Leu Ser Leu Pro Ser Ser Trp Asp Tyr Gly His Leu Pro Pro

335 340 345

cac ccc gct aat ttt tgt att ttc att aga ggc ggg gtt tca cca tat 1106

His Pro Ala Asn Phe Cys Ile Phe Ile Arg Gly Gly Val Ser Pro Tyr

350 355 360

ttg tca ggc tgg tct caa act cct gac ctc agg tgacccacct gcctcagcct 1159

Leu Ser Gly Trp Ser Gln Thr Pro Asp Leu Arg

365 370 375

tccaaagtgc tgggattaca ggcgtgagcc acctcaccca gccggctaat ttagataaaa 1219

aaatatgtag caatgggggg tcttgctatg ttgcccaggc tggtctcaaa cttctggctt 1279

catgcaatcc ttccaaatga gccacaacac ccagccagtc aatttttta aacagttaca 1339

tctttatttt agtatactag aaagtaatac aataaacatg tcaaacctgc aaattcagta 1399

gtaacagagt tcttttataa cttttaaaca aagctttaga gca 1442

Claims (30)

1. peptide that is selected among SEQ ID NO:18, SEQ ID NO:68 and the SEQ ID NO:120 one or more.

2. a composition is characterized in that, described composition contains described peptide of one or more claims 1 and carrier thereof.

3. a protein is characterized in that, described protein comprises the described peptide of claim 1,3 of described peptide ' or 5 ' terminal flank have 1 to 25 extra amino acid modified.

4. a protein is characterized in that, described protein comprises described at least two peptides of claim 1.

5. a protein is characterized in that, described protein comprises the repetition of described at least two peptides of claim 1.

6. a protein is characterized in that, described protein comprises the described peptide of claim 1 that merges with antibody, antibody fragment or antibody molecule.

7. a nucleic acid is characterized in that, the corresponding aminoacid sequence of the described peptide of described nucleic acid encoding and claim 1.

8. a composition is characterized in that, described composition comprise described one or more nucleic acid of claim 7 with and pharmaceutically acceptable carrier.

9. claim 1,2,7 and 8 arbitrary described peptides, nucleic acid or composition are used for the treatment of application in the medicine of patient disease in preparation, and cell need be removed or destroy to described disease.

10. application as claimed in claim 9, it is characterized in that described disease is the optimum or malignant tumour that is selected from undertissue: i.e. lung, breast, stomach, pancreas, prostate gland, bladder, bone, ovary, skin, kidney, hole, colon, intestines, stomach, rectum, esophagus, the heart, spleen, sialisterium, blood, brain and its coverture, spinal cord and its coverture, muscle, reticular tissue, suprarenal gland, Parathyroid, Tiroidina, uterus, testis, hypophysis, sexual organ, liver, gall-bladder, Eye Ear Nose And Throat, tonsil, mouth, lymphoglandula and Lymphoid tissue.

11. application as claimed in claim 9, it is characterized in that described disease is hyperplasia, hypertrophy or the hypertrophy that is selected from undertissue: i.e. lung, breast, stomach, pancreas, prostate gland, bladder, bone, ovary, skin, kidney, hole, colon, intestines, stomach, rectum, esophagus, the heart, spleen, sialisterium, blood, brain and its coverture, spinal cord and its coverture, muscle, reticular tissue, suprarenal gland, Parathyroid, Tiroidina, uterus, testis, hypophysis, sexual organ, liver, gall-bladder, Eye Ear Nose And Throat, tonsil, mouth, lymphoglandula and Lymphoid tissue.

12. application as claimed in claim 9, it is characterized in that, described disease is to be subjected to virus, the tissue that bacterium or parasite change, these tissues are selected from lung, breast, stomach, pancreas, prostate gland, bladder, bone, ovary, skin, kidney, hole, colon, intestines, stomach, rectum, esophagus, the heart, spleen, sialisterium, blood, brain and its coverture, spinal cord and its coverture, muscle, reticular tissue, suprarenal gland, Parathyroid, Tiroidina, the uterus, testis, hypophysis, sexual organ, liver, gall-bladder, eye, ear, nose, larynx, tonsil, mouthful, lymphoglandula and Lymphoid tissue.

13. application as claimed in claim 9, it is characterized in that described disease is the deformity that is selected from undertissue: i.e. lung, breast, stomach, pancreas, prostate gland, bladder, bone, ovary, skin, kidney, hole, colon, intestines, stomach, rectum, esophagus, the heart, spleen, sialisterium, blood, brain and its coverture, spinal cord and its coverture, muscle, reticular tissue, suprarenal gland, Parathyroid, Tiroidina, uterus, testis, hypophysis, sexual organ, liver, gall-bladder, Eye Ear Nose And Throat, tonsil, mouth, lymphoglandula and Lymphoid tissue.

14. application as claimed in claim 10 is characterized in that, described tissue is a Lymphoid tissue.

15. application as claimed in claim 9 is characterized in that, described disease is the hypertrophy of tonsils.

16. application as claimed in claim 9 is characterized in that, described disease is a hyperplasia of prostate.

17. application as claimed in claim 9 is characterized in that, described disease is a psoriatic.

18. application as claimed in claim 9 is characterized in that, described disease is an eczema.

19. application as claimed in claim 9 is characterized in that, described disease is a tetter.

20. application as claimed in claim 9 is characterized in that, described disease is that the lift face of tissue is modified.

21. application as claimed in claim 10 is characterized in that, described tissue is skin, Eye Ear Nose And Throat, mouth, muscle, reticular tissue and breast.

22. application as claimed in claim 9 is characterized in that, described disease is a vascular disease.

23. application as claimed in claim 9 is characterized in that, described disease is hemorrhoid.

24. application as claimed in claim 9 is characterized in that, described disease is a varix.

25. application as claimed in claim 22 is characterized in that, described vascular disease is atherosclerosis or arteriosclerosis.

26. application as claimed in claim 9, it is characterized in that described disease is selected from inflammatory diseases, autoimmune disease, metabolic trouble, genetic diseases, trauma or the damage of body reason, deficiency disease, transmissible disease, amyloidosis disease, fibrosis disease, thesaurismosis, congenital abnormality, enzymatic defect disease, poisoning, intoxicating, 20th-century disease, Radiation sickness, endocrinopathy, degenerative disease and mechanical injuries disease.

27. application as claimed in claim 9 is characterized in that, described peptide is derived from the aminoacid sequence of pancreas silk-like proteins.

28. application as claimed in claim 9, it is characterized in that, described peptide is coupled to, is connected in or be incorporated into the molecule that is selected from antibody, antibody fragment and antibody sample binding molecule, and wherein said molecule and tumour or other target bonded avidity are higher than and other cell bonded avidity.

29. application as claimed in claim 9, it is characterized in that, described peptide is the part of the recombinant molecule of a new clone, this recombinant molecule is by described peptide and the molecular composition that is selected from antibody, antibody fragment and antibody sample binding molecule, and wherein said molecule and tumour or other target bonded avidity are higher than and other cell bonded avidity.

30. a peptide is characterized in that, described peptide contains the peptide of the aminoacid sequence with SEQ ID NO:18:Gln-Gln-Ser-Ile-Ala-Val-Lys-Phe-Leu-Ala-Val-Phe-Gl y-Val-Ser-Ile representative.

Images