KR20200001583A - Gender-specific markers for diagnosing prognosis and determining treatment strategies of patient of clear cell renal cell carcinoma - Google Patents

Abstract

The present invention relates to markers for diagnosing the difference in effects of renal cancer treatment or the prognosis of renal cancer patients depending on the gender of renal cancer patients. The survival rate and recurrence rate of renal cancer of a particular gender respectively relate to the mutation of genes, of the present invention, in renal cancer patients, and thus the mutated genes of the present invention can be used as markers in predicting, on the basis of gender, the difference in effects of renal cancer treatment or the prognosis of renal cancer patients.

Description

Gender-specific markers for diagnosing prognosis and determining treatment strategies of patient of clear cell renal cell carcinoma

The present invention is a method for providing information necessary for prognosis diagnosis and treatment strategy of kidney cancer using a prognostic diagnostic marker of a kidney cancer patient, a kit for prognostic diagnosis of a kidney cancer patient comprising the same, and a marker for prognostic diagnosis of a kidney cancer patient It is about.

The kidney is an important urinary system that has a role of excreting waste products from the body by filtering blood to produce urine. It is also an important endocrine organ that produces hormones such as angiotensin, which controls blood pressure, and erythropoietin, which is a red blood cell hematopoietic factor.

Tumors occurring in the kidney include kidney cell carcinoma in adults, Wilms' tumor in children, and sarcoma as a rare tumor, but renal cell carcinoma, which is a malignant tumor with the highest incidence, is called kidney cancer. The incidence of kidney cancer in Japan is about 2.5 per 100,000 people, and the male to female ratio is 2 to 3:1, which tends to be a lot for men. Among the urological malignancies, there are many tumors following prostate cancer and bladder cancer. Kidney cancer refers to kidney cell cancer that occurs mostly in the parenchyma of the kidney (the part where the cells that make urine in the kidney are gathered and consists of the medulla and the cortex).

Genetic factors are also known as risk factors for kidney cancer, but in general, smoking and excessive fat intake are included. It is also known that patients undergoing long-term dialysis have a high incidence of the tumor.

In kidney cancer, when the maximum diameter of the tumor is less than 5 cm, there are rarely any subjective symptoms, and it is often detected by CT scans during examination. Large-sized tumors include hematuria, abdominal tumors, and pain. In addition, as systemic symptoms, fever, weight loss, anemia, etc. may be caused, and in rare cases, erythropoiesis, hypertension, and hypercalcemia may occur due to endocrine factors. On the other hand, due to the progression of kidney cancer into the inferior vena cava, the veins of the abdominal body surface may be deteriorated or varicose veins may occur. About 20% of kidney cancer is found from lung or bone metastases. In renal cancer, the tumor has a strong tendency to spread into the veins, and metastasis to other organs is likely to occur.

Kidney cancer has almost no symptoms when the tumor is small, and symptoms appear only when the tumor grows to a certain extent and pushes the organs out. Therefore, since diagnosis is often delayed, about 30% of patients appear to have already metastasized when first diagnosed. The most common symptom is hematuria, but it also appears in only 60% of patients. Rather, symptoms such as shortness of breath, cough, and headache appear depending on the metastasized site, and renal cancer is diagnosed due to these metastases, accounting for 30% of all patients. Because kidney cancer can cause high blood pressure, hypercalcemia, and liver dysfunction due to specific hormones produced by cancer cells, in some cases, tumors are found during testing for these other symptoms. However, in recent years, while undergoing a medical examination without any symptoms, there are many cases that are accidentally found on the imaging examination, and these cases are mainly found early, so the treatment results are relatively good. Therefore, it will be said that early diagnosis of kidney cancer as described above is very important.

Kidney cancer accounts for about 3% of adult cancers in the United States, and about 32,000 new patients occur annually. It is also estimated that about 12,000 people die from kidney cancer, and the incidence is increasing every year worldwide. In Korea, the incidence is lower than this, and according to the 2002 central cancer registration data, 1,578 newly registered patients account for 1.6% of the total cancer incidence. Kidney cancer is common in the 40s to 60s, and according to the gender incidence (2002 central cancer registration data), 60s are the most common (479, 30.2%), 50s (412, 26.0%), and 40s. It occurs in the order of (268 people, 16.9%). Renal cancer has a high survival rate due to the tumor removal procedure after onset, but it is difficult to diagnose at an early stage because there are no clear symptoms. For this reason, there is a need for early diagnosis and development of markers that can check the remaining lifespan after cancer onset.

Transglutaminase 2 (Patent Document 1) is disclosed as a marker used for detection or diagnosis of human kidney cancer. Markers for diagnosing cancer, including kidney cancer, are being developed, but a marker that can measure the prognosis of kidney cancer patients, in particular, the relationship between the sex of kidney cancer patients and mutations in specific genes, has not been studied yet. to be.

In order to diagnose kidney cancer or discover a therapeutic agent for kidney cancer patients and determine a treatment strategy, the present inventors focus on the necessity of developing a marker capable of diagnosing the prognosis of kidney cancer patients, and The relationship between the variability and the sex of the patient was studied.

Korean Patent Registration No. 1267580

In order to apply an appropriate therapeutic strategy for renal cancer patients, it is necessary to develop markers that predict the prognosis of renal cancer patients and help determine treatment strategies. An object of the present invention is to provide a marker that helps in diagnosing prognosis and determining a treatment strategy of a kidney cancer patient based on the sex of a kidney cancer patient.

In order to achieve the above object, one aspect of the present invention is ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, Kidney cancer patients capable of detecting a sex-specific marker that is a mutation of a gene encoding at least one selected from the group consisting of SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1 It provides a kit that provides information necessary for predicting the effect of renal cancer treatment according to the sex of the patient or for prognosing the prognosis of a renal cancer patient.

Another aspect of the present invention comprises the steps of preparing sample DNA from a sample of a kidney cancer patient whose sex is known; Amplifying the sample DNA using the kit; Confirming the presence or absence of a gender-specific marker specific to the gender group of the target patient from the amplification result; Treating a kidney cancer patient whose sex-specific marker has been identified with any candidate for treatment of kidney cancer or by any method; And if any of the kidney cancer treatment candidate material or any treatment method to treat kidney cancer, the step of adopting a suitable treatment candidate material or treatment method for the sex group of the kidney cancer patient whose sex-specific marker has been identified; kidney cancer comprising a. It provides a method of providing information necessary to determine the difference in the treatment effect of kidney cancer according to the sex of a patient.

Another aspect of the present invention comprises the steps of preparing a sample DNA from a sample of a kidney cancer patient; Amplifying the sample DNA using the kit; And determining the presence or absence of a gender-specific marker from the amplification result; providing a method of providing information necessary for prognosis diagnosis of kidney cancer according to the sex of a kidney cancer patient comprising.

Genes discovered in the present invention ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TCB, TBC1D13, TBC1 Since mutation of at least one gene selected from the gene group consisting of ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1 is related to the sex of the kidney cancer patient, kidney cancer patients by confirming the mutation of the gene It is possible to predict the difference in the treatment effect and survival rate of kidney cancer according to the sex of the patient.

In addition, mutations in one gene selected from the gene group consisting of the genes ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449 and SCRN1 discovered in the present invention, and the survival rate of a kidney cancer patient of a specific sex, or the above Since the mutation of the gene and the recurrence rate of renal cancer are each correlated, the mutation of the genes of the present invention can be used as a marker to predict the prognosis of a patient with renal cancer.

However, the effects of the present invention are not limited to the above-mentioned effects, and other effects not mentioned will be clearly understood by those skilled in the art from the following description.

1 shows a sex-specific mutant gene that was specifically shown when comparing kidney cancer patients classified by sex among candidate genes. The number represents the number of kidney cancer patients for which the mutated gene has been identified.
2 to 10 are for each of the genes ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1, kidney cancer patients with mutations in the corresponding gene (red) and kidneys without mutations in the corresponding gene It is a graph of the total or disease-free survival rate of cancer patients (blue).

In the present specification, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. In general, the nomenclature used herein and the experimental methods described below are well known and commonly used in the art.

Hereinafter, the present invention will be described in detail.

1. A set of primers capable of detecting gender-specific mutant genes and these mutant genes in kidney cancer patients

One aspect of the present invention is ACSS3 (Gene bank accession number: NM_024560.3), ADAM21 (Gene bank accession number: NM_003813.3), AFF2 (Gene bank accession number: NM_002025.3), ALG13 (Gene bank accession number: NM_001099922) .2), ARSF (Gene bank accession number: NM_001201538.1), BAP1 (Gene bank accession number: NM_004656.3), BRWD3 (Gene bank accession number: NM_153252.4), CFP (Gene bank accession number: NM_001145252.1) ), COL4A5 (Gene bank accession number: NM_000495.4), CPEB1 (Gene bank accession number: NM_030594.4), ERBB2 (Gene bank accession number: NM_004448.3), FAM47A (Gene bank accession number: NM_203408.3), HSP90AA1(Gene bank accession number: NM_001017963.2), IRAK1(Gene bank accession number: NM_001569.3), KDM5C(Gene bank accession number: NM_004187.3), KDM6A(Gene bank accession number: NM_021140.3), LRP12( Gene bank accession number: NM_013437.4), NCOA6 (Gene bank accession number: NM_001242539.2), NHS (Gene bank accession number: NM_198270.3), PHF16(JADE3) (Gene bank accession number: NM_001077445.2), RGAG 1(Gene bank accession number: NM_020769.2), SCAF1(Gene bank accession number: NM_021228.2), SCRN1(Gene bank accession number: NM_001145514.1), SH3TC1(Gene bank accession number: NM_018986.4), TBC1D8B( Gene bank accession number: NM_017752.2), TET2 (Gene bank accession number: NM_001127208.2), TEX13A (Gene bank accession number: NM_001291277.1), ULK3 (Gene bank accession number: NM_001099436.3), WNK3 (Gene bank Accession number: NM_001002838.3), ZNF449 (Gene bank accession number: NM_152695.5). It provides a kit that provides information necessary for predicting a difference in the effect of cancer treatment or for prognostic diagnosis of a kidney cancer patient.

The full names of the abbreviations of the genes are ACSS3 (Homo sapiens acyl-CoA synthetase short chain family member 3), ADAM21 (Homo sapiens ADAM metallopeptidase domain 21), AFF2 (Homo sapiens AF4/FMR2 family member 2), ALG13 (UDP- N-acetylglucosaminyltransferase subunit), BAP1 (BRCA1 associated protein 1), BRWD3 (bromodomain and WD repeat domain containing 3), COL4A5 (collagen type IV alpha 5 chain), CPEB1 (cytoplasmic polyadenylation element binding protein 1), ERBB2 (erb-b2) receptor tyrosine kinase 2), HSP90AA1 (heat shock protein 90 alpha family class A member 1), IRAK1 (interleukin 1 receptor associated kinase 1), KDM5C (lysine demethylase 5C), KDM6A (lysine demethylase 6A), LRP12 (LDL receptor related protein) 12), NCOA6 (nuclear receptor coactivator 6), NHS (NHS actin remodeling regulator), RGAG1 (retrotransposon Gag like 9), SCAF1 (SR-related CTD associated factor 1), SH3TC1 (SH3 domain and tetratricopeptide repeats 1), TBC1D8B ( TBC1 domain family member 8B), TET2 (tet methylcytosine dioxygenase 2), TEX13A (testis expressed 13 A), ULK3 (unc-51 like kinase 3), WNK3 (WNK lysine deficient protein kinase 3), ARSF (arylsulfatase F), CFP (complement factor properdin), FAM47A (family with sequence similarity 47 member A), PHF16 (jade family PHD finger 3), zinc finger protein 449 (ZNF449), and secernin 1 (SCRN1).

In one embodiment of the present invention, predicting the difference in the effect of kidney cancer treatment according to the sex of a kidney cancer patient capable of detecting a mutation of at least one gene selected from mutations of the following genes or diagnosing the prognosis of a kidney cancer patient Provides a kit that provides the necessary information for:

ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TBC1D8B, ARKSF, A mutation of a gene encoding at least one selected from the group consisting of CFP, FAM47A, PHF16, ZNF449 and SCRN1.

In the present invention, the term'diagnosis' is to confirm the presence or characteristics of a pathological condition, and for the purposes of the present invention, not only to confirm the difference in cancer treatment effect according to the sex of a cancer patient, but also to confirm the It means determining whether there is recurrence, metastasis, drug responsiveness, resistance, etc. Preferably, in the case of using the mutation of the gene of the present invention, the difference in the effect of renal cancer treatment according to the sex of the renal cancer patient and the difference in survival rate that can determine the prognosis of the patient in the future by checking the mutation from a sample of a renal cancer patient It can also be predicted.

In the present invention, the term'prognosis' refers to the course of and cure of a neoplastic disease such as cancer, for example, recurrence, metastatic spread, and the likelihood of cancer-caused death or progression, including drug resistance. For the purpose of the present invention, it may be to predict the prognosis of renal cancer, and preferably, to predict disease-free survival or survival of renal cancer patients.

In the present invention, the term'cancer' includes any member of the class of diseases characterized by the uncontrolled growth of abnormal cells. The term includes all known cancers and neoplastic states, whether characterized as malignant, benign, soft tissue or solid, and cancers of all stages and grades, including pre/post metastasis.

In the present invention, the term'gene' and its modifications include DNA fragments involved in the production of a polypeptide chain; It includes sites before and after the coding site, such as promoters and 3′-untranslated sites, respectively, as well as intervening sequences (introns) between individual coding fragments (exons).

The mutation of the gene may include any one or more mutations, for example, a truncating mutation, a missense mutation (or a mistake mutation), a nonsense mutation, a frame shift. ) Mutations, in-frame mutations (or in-frame mutations), splice mutations, and splice_region mutations. The frame shift mutation may be at least one of a frame shift insert (FS ins) mutation and a frame shift deletion mutation (frame shift delete, FS del). The in-frame mutation may be at least one of an in-frame insertion (IF ins) mutation and an in-frame deletion (IF del) mutation.

The term "X#Y" with respect to a mutation in a polypeptide sequence is clearly recognized in the art, where "#" represents the position of the mutation in relation to the amino acid number of the polypeptide, and "X" is the wild-type amino acid sequence. It represents the amino acid found at that position, and "Y" represents the mutant amino acid at that position. For example, the designation “G1717V” with respect to the BAZ2B polypeptide indicates that glycine is present at amino acid number 1717 of the wild-type BAZ2B sequence, and that glycine has been replaced by valine in the mutant BAZ2B sequence. The mutations of these genes are as follows:

The mutation of the gene encoding ACSS3 is a nonsense mutation of R634* in the amino acid sequence of SEQ ID NO: 1, a splice mutation of X152_splice (replacement of T with C at the chromosome 81503485 position), or a missense mutation of G268D, and nonsense. In the mutation, * indicates that the amino acid synthesis at the corresponding amino acid position is terminated (a description will be omitted hereinafter);

The mutation of the gene encoding ADAM21 is at least one mutation selected from the group consisting of N265Y, R408C, T589S and I161V in the amino acid sequence of SEQ ID NO: 2;

The mutation of the gene encoding AFF2 is at least one missense mutation selected from the group consisting of S770F, P513H, T640N and I149K in the amino acid sequence of SEQ ID NO: 3;

The mutation of the gene encoding ALG13 is a missense mutation of at least one of P925T and V456E in the amino acid sequence of SEQ ID NO: 4, or a frame shift deletion (FS del) mutation of L195Pfs*23, and a frame shift mutation The notation method of is the amino acid type (amino acid position) amino acid type fs* (the number of nucleotides from the amino acid position to the stop codon in the downstream direction) (the frame shift insertion mutation and the frame shift deletion mutation are both in the same notation system. Omitted);

In the amino acid sequence of SEQ ID NO: 5, the mutation of the gene encoding BAP1 is M1? (T is substituted for C at chromosome position 52443894, C is substituted for T at 52443892), or G128*, E402*, At least one nonsense mutation selected from the group consisting of Q253*, Q267*, S460*, Y627*, S279*, R60*, Q40*, Q156* and K626*, or E283Gfs*52, V335Efs*56, K711Sfs*25 , At least one FS del mutation selected from the group consisting of R700Gfs*36, D74Efs*4 and D407Vfs*23, or F170V, F170C, E31A, N78S, L49V, D75G, S10T, N229H, G109V, L17P, A145G and A1061T. At least one missense mutation selected from the group consisting of, or X23_splice (C is substituted with T at chromosome position 52443729), X41_splice (A is substituted with G at chromosome position 52443568), X41_splice (A is substituted with T at chromosome position 52443568) ), X23_splice (ACCTGCGATGAGGAAAGGAAAGCAG is deleted at chromosome positions 52443623 to 52443647), and X311_splice (C is substituted for A at chromosome position 52439311). -frame delete, IF del) mutation, and del in the notation method of in-frame insertion mutation indicates that the corresponding amino acid has been deleted at the position of the corresponding amino acid sequence (a description will be omitted hereinafter);

The mutation of the gene encoding BRWD3 is a missense mutation of at least one of G287A and I1747N in the amino acid sequence of SEQ ID NO: 6;

The mutation of the gene encoding COL4A5 is at least one missense mutation selected from the group consisting of P1184L, P756S, P1365S, G1427V, and A1656T in the amino acid sequence of SEQ ID NO: 7, or X1510_splice (G at chromosome position 107935977 to T Substitution) is a splice mutation;

The mutation of the gene encoding CPEB1 is a missense mutation of at least one of S393R and G136V in the amino acid sequence of SEQ ID NO: 8, or a splice mutation of X499_splice (C is substituted for A at chromosome position 83215272);

The mutation of the gene encoding ERBB2 is at least one missense mutation selected from the group consisting of E1114G, S649T, and V219I in the amino acid sequence of SEQ ID NO: 9, or a frame shift insertion mutation of N388Qfs*14;

The mutation of the gene encoding HSP90AA1 is at least one missense mutation selected from the group consisting of D512N, H806R, I325T and L167V in the amino acid sequence of SEQ ID NO: 10;

The mutation of the gene encoding IRAK1 is a nonsense mutation of Q280* or a missense mutation of at least one of V548M and Q584K in the amino acid sequence of SEQ ID NO: 11;

The mutation of the gene encoding KDM5C is at least one nonsense selected from the group consisting of R681*, Q813*, E284*, E798*, Y639*, S1110*, K459* and R215* in the amino acid sequence of SEQ ID NO: 12. Mutant, at least one missense mutation selected from the group consisting of E1152K, R1458W, G536W, C730R, E592V, C512W, C730F and H733P, or a splice mutation with X321_splice (A is substituted for G at chromosome position 53244975), or At least one frame shift deletion mutation selected from the group consisting of T471Vfs*5, Q1427Pfs*50, E122Vfs*14, E1131Sfs*16, H988Tfs*18, P27Lfs*46, F56Cfs*18, D1414Efs*54 and G845Rfs*2;

The mutation of the gene encoding KDM6A is a missense mutation of A30V, a frame shift mutation of A1246Pfs*19, or a V156del in-frame deletion mutation in the amino acid sequence of SEQ ID NO: 13;

The mutation of the gene encoding LRP12 is at least one missense mutation selected from the group consisting of S622L, E639K and V671I in the amino acid sequence of SEQ ID NO: 14;

The mutation of the gene encoding NCOA6 is at least one missense mutation selected from the group consisting of G164E, N877I, N864Y and V1444A in the amino acid sequence of SEQ ID NO: 15, or a frame shift insertion mutation of H832Sfs*47;

The mutation of the gene encoding NHS is at least one missense mutation selected from the group consisting of C360R, P1107A, and D1069H in the amino acid sequence of SEQ ID NO: 16;

The mutation of the gene encoding RGAG1 is at least one missense mutation selected from the group consisting of A1015G, M858V, and G1053R in the amino acid sequence of SEQ ID NO: 17;

The mutation of the gene encoding SCAF1 is at least one frame shift insertion mutation selected from the group consisting of A219Sfs*11, P211Tfs*19, P211Tfs*19, and A216Pfs*94 in the amino acid sequence of SEQ ID NO: 18, or A216Pfs*94 Is an in frame shift deletion mutation;

The mutation of the gene encoding SH3TC1 is a missense mutation of at least one of A375V and L180F, or a frame shift deletion mutation of R238Sfs*38 in the amino acid sequence of SEQ ID NO: 19;

The mutation of the gene encoding TBC1D8B is at least one missense mutation selected from the group consisting of G1059V, A614T, and Y815F in the amino acid sequence of SEQ ID NO: 20, or a nonsense mutation of S861*;

The mutation of the gene encoding TET2 is at least one missense mutation selected from the group consisting of Q317K, L757V, V449E, N1714K, D194E, N1390H, R1451Q, M600I and P554S in the amino acid sequence of SEQ ID NO: 21, or K326* Is an in nonsense mutation;

The mutation of the gene encoding TEX13A is a missense mutation of at least one of R393S and Y257D in the amino acid sequence of SEQ ID NO: 22, or a splice mutation of X199_splice (C is deleted at chromosome position 104464282);

The mutation of the gene encoding ULK3 is a frame shift deletion mutation of Q81Sfs*41 in the amino acid sequence of SEQ ID NO: 23, and a missense mutation of at least one of D79H and L77V;

The mutation of the gene encoding WNK3 is a nonsense mutation of at least one of S865* and Y589*, and a missense mutation of E537G in the amino acid sequence of SEQ ID NO: 24;

The mutation of the gene encoding ARSF is a missense mutation of I42F in the amino acid sequence of SEQ ID NO: 25;

The mutation of the gene encoding the CFP is at least one missense mutation selected from the group consisting of S27L, R359Q and E135K in the amino acid sequence of SEQ ID NO: 26, or a frame shift insertion mutation of E323Gfs*34;

The mutation of the gene encoding FAM47A is a missense mutation of at least one of R505H and E507Q, or an in-frame deletion mutation of at least one of L235_H246del and L235_H246del in the amino acid sequence of SEQ ID NO: 27;

The mutation of the gene encoding PHF16 is a missense mutation of at least one of K656Q and R207W in the amino acid sequence of SEQ ID NO: 28;

The mutation of the gene encoding ZNF449 is a missense mutation of F183I in the amino acid sequence of SEQ ID NO: 29;

The mutation of the gene encoding SCRN1 is a missense mutation of D427Y or a frame shift insertion mutation of A257Cfs*34 in the amino acid sequence of SEQ ID NO: 30.

Next generation sequencing (NGS), RT-PCR, direct nucleic acid sequencing, and microarrays may be used as analysis methods for diagnosing the prognosis of kidney cancer using mutations in the gene. Any method that can confirm the existence of a mutation using a mutation in a gene can be applied without limitation. In one embodiment, the presence of a mutation is determined using an anti-(mutation of each gene) antibody or nucleic acid probe that hybridizes to the polynucleotide of the mutation of each gene under stringent conditions. In another embodiment, the antibody or nucleic acid probe is detectably labeled. In another embodiment, the label is selected from the group consisting of an immunofluorescent label, a chemiluminescent label, a phosphorescent label, an enzyme label, a radioactive label, avidin/biotin, colloidal gold particles, colored particles and magnetic particles. In another embodiment, the presence of the mutation is a radioimmunoassay, western blot assay, immunofluorescence assay, enzyme immunoassay, immunoprecipitation assay, chemiluminescence assay, immunohistochemistry assay, dot blot assay, slot blot assay or flow cytometry. Determined by testing. In another embodiment, the presence of the mutation is determined by RT-PCR. In another embodiment, the presence of the mutation is determined by nucleic acid sequencing.

In the present invention, the term'polynucleotide' generally refers to any polyribonucleotide or polydeoxyribonucleotide that may be unmodified RNA or DNA or modified RNA or DNA. Thus, for example, polynucleotides as defined herein include, but are not limited to, single- and double-stranded DNA, DNA comprising single- and double-stranded regions, single- and double-stranded RNA, and single- and double-stranded RNA. RNA comprising -stranded regions, hybrid molecules comprising DNA and RNA, which may be single-stranded or more typically double-stranded or may include single- and double-stranded regions. Thus, DNA or RNA having a modified backbone for stability or other reasons is a'polynucleotide' as the term intended herein. In addition, DNA or RNA comprising unconventional bases such as inosine or modified bases such as tritiated bases are included in the term'polynucleotide' as defined herein. In general, the term'polynucleotide' includes all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides. Polynucleotides can be prepared by a variety of methods, including in vitro recombinant DNA-mediated techniques, and by expression of DNA in cells and organisms.

The set of primers capable of detecting the mutation, that is, for diagnosing the prognosis of kidney cancer, is as follows:

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 31 and SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34, and SEQ ID NO: 35 and SEQ ID NO: 36 for detecting mutations of ACSS3;

SEQ ID NO: 37 and SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42 for detection of mutations in ADAM21, and At least one primer set selected from the group consisting of a nucleotide sequence pair represented by SEQ ID NO: 43 and SEQ ID NO: 44;

At least one selected from the group consisting of a base sequence pair represented by SEQ ID NO: 45 and SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, and SEQ ID NO: 51 and SEQ ID NO: 52 for detection of mutations of AFF2 Primer set of;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 53 and SEQ ID NO: 54, SEQ ID NO: 55 and SEQ ID NO: 56, and SEQ ID NO: 57 and SEQ ID NO: 58 for detection of mutations in ALG13;

SEQ ID NO: 59 and SEQ ID NO: 60, SEQ ID NO: 61 and SEQ ID NO: 62, SEQ ID NO: 63 and SEQ ID NO: 64, SEQ ID NO: 65 and SEQ ID NO: 66, SEQ ID NO: 67 and SEQ ID NO: 68, SEQ ID NO: 69 and SEQ ID NO: 70, SEQ ID NO: 71 and SEQ ID NO: 72, SEQ ID NO: 73 and SEQ ID NO: 74, SEQ ID NO: 75 and SEQ ID NO: 76, SEQ ID NO: 77 and SEQ ID NO: 78, SEQ ID NO: 79 and SEQ ID NO: 80, SEQ ID NO: 81 and SEQ ID NO 82, SEQ ID NO: 83 and SEQ ID NO: 84, SEQ ID NO: 85 and SEQ ID NO: 86, SEQ ID NO: 87 and SEQ ID NO: 88, SEQ ID NO: 89 and SEQ ID NO: 90, SEQ ID NO: 91 and SEQ ID NO: 92, and SEQ ID NO: 93 and SEQ ID NO: 94 At least one primer set selected from the group consisting of nucleotide sequence pairs represented by;

At least one primer set of SEQ ID NO: 95 and SEQ ID NO: 96, and nucleotide sequence pairs represented by SEQ ID NO: 97 and SEQ ID NO: 98 for detecting mutations of BRWD3;

SEQ ID NO: 99 and SEQ ID NO: 100, SEQ ID NO: 101 and SEQ ID NO: 102, SEQ ID NO: 103 and SEQ ID NO: 104, SEQ ID NO: 105 and SEQ ID NO: 106, SEQ ID NO: 107 and SEQ ID NO: 108, and SEQ ID NO: 109 for detection of mutations in COL4A5 And at least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 110;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 111 and SEQ ID NO: 112, SEQ ID NO: 113 and SEQ ID NO: 114, and SEQ ID NO: 115 and SEQ ID NO: 116 for detecting mutations in CPEB1;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 117 and SEQ ID NO: 118, SEQ ID NO: 119 and SEQ ID NO: 120, and SEQ ID NO: 121 and SEQ ID NO: 122 for detecting mutations of ERBB2;

SEQ ID NO: 123 and SEQ ID NO: 124, SEQ ID NO: 125 and SEQ ID NO: 126, SEQ ID NO: 127 and SEQ ID NO: 128 for detection of mutations in HSP90AA1, and At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 129 and SEQ ID NO: 130;

SEQ ID NO: 131 and SEQ ID NO: 132 for detection of a mutation of IRAK1, and at least one of the nucleotide sequence pairs represented by SEQ ID NO: 133 and SEQ ID NO: 134 a primer set;

SEQ ID NO: 135 and SEQ ID NO: 136, SEQ ID NO: 137 and SEQ ID NO: 138, SEQ ID NO: 139 and SEQ ID NO: 140, SEQ ID NO: 141 and SEQ ID NO: 142, SEQ ID NO: 143 and SEQ ID NO: 144, SEQ ID NO: 145 and SEQ ID NO: 146, SEQ ID NO: 147 and SEQ ID NO: 148, SEQ ID NO: 149 and SEQ ID NO: 150, SEQ ID NO: 151 and SEQ ID NO: 152, SEQ ID NO: 153 and SEQ ID NO: 154, SEQ ID NO: 155 and SEQ ID NO: 156, SEQ ID NO: 157 and SEQ ID NO: 158, SEQ ID NO: 159 and SEQ ID NO: 160, SEQ ID NO: 161 and SEQ ID NO: 162, SEQ ID NO: 163 and SEQ ID NO: 164, SEQ ID NO: 165 and SEQ ID NO: 166, SEQ ID NO: 167 and SEQ ID NO: 168, SEQ ID NO: 169 and SEQ ID NO: 170, At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 171 and SEQ ID NO: 172, SEQ ID NO: 173 and SEQ ID NO: 174, and SEQ ID NO: 175 and SEQ ID NO: 176;

SEQ ID NO: 177 and SEQ ID NO: 178 for detecting mutations of KDM6A, and at least one primer set of base sequence pairs represented by SEQ ID NO: 179 and SEQ ID NO: 180;

SEQ ID NO: 181 and SEQ ID NO: 182 for detection of mutations in LRP12, and at least one primer set of the base sequence pair represented by SEQ ID NO: 183 and SEQ ID NO: 184;

At least one selected from the group consisting of a nucleotide sequence pair represented by SEQ ID NO: 185 and SEQ ID NO: 186, SEQ ID NO: 187 and SEQ ID NO: 188, SEQ ID NO: 189 and SEQ ID NO: 190, and SEQ ID NO: 191 and SEQ ID NO: 192 for detection of mutations in NCOA6 Primer set of;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 193 and SEQ ID NO: 194, SEQ ID NO: 195 and SEQ ID NO: 196, and SEQ ID NO: 197 and SEQ ID NO: 198 for detection of mutations in NHS;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 199 and SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, and SEQ ID NO: 203 and SEQ ID NO: 204 for detecting mutations of RGAG1;

Base sequences represented by SEQ ID NO: 205 and SEQ ID NO: 206, SEQ ID NO: 207 and SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, SEQ ID NO: 211 and SEQ ID NO: 212, and SEQ ID NO: 213 and SEQ ID NO: 214 for detection of mutations in SCAF1 At least one primer set selected from the group consisting of pairs;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 215 and SEQ ID NO: 216, SEQ ID NO: 217 and SEQ ID NO: 218, and SEQ ID NO: 219 and SEQ ID NO: 220 for detection of a mutation of SH3TC1;

At least one selected from the group consisting of a base sequence pair represented by SEQ ID NO: 221 and SEQ ID NO: 222, SEQ ID NO: 223 and SEQ ID NO: 224, SEQ ID NO: 225 and SEQ ID NO: 226, and SEQ ID NO: 227 and SEQ ID NO: 228 for detection of mutations in TBC1D8B Primer set of;

SEQ ID NO: 229 and SEQ ID NO: 230, SEQ ID NO: 231 and SEQ ID NO: 232, SEQ ID NO: 233 and SEQ ID NO: 234 for detection of mutations in TET2, SEQ ID NO: 235 and SEQ ID NO: 236, SEQ ID NO: 237 and SEQ ID NO: 238, SEQ ID NO: 239 and SEQ ID NO: 240, At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 241 and SEQ ID NO: 242, SEQ ID NO: 243 and SEQ ID NO: 244, and SEQ ID NO: 245 and SEQ ID NO: 246;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 247 and SEQ ID NO: 248, SEQ ID NO: 249 and SEQ ID NO: 250, and SEQ ID NO: 251 and SEQ ID NO: 252 for detecting mutations of TEX13A;

A primer set that is a pair of base sequences represented by SEQ ID NO: 253 and SEQ ID NO: 254 for detection of mutations in ULK3;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 255 and SEQ ID NO: 256, SEQ ID NO: 257 and SEQ ID NO: 258, and SEQ ID NO: 259 and SEQ ID NO: 260 for detection of mutations in WNK3;

A primer set that is a base sequence pair represented by SEQ ID NO: 261 and SEQ ID NO: 262 for detection of mutations in ARSF;

At least one selected from the group consisting of a base sequence pair represented by SEQ ID NO: 263 and SEQ ID NO: 264, SEQ ID NO: 265 and SEQ ID NO: 266, SEQ ID NO: 267 and SEQ ID NO: 268, and SEQ ID NO: 269 and SEQ ID NO: 270 for detection of mutations in CFP Primer set of;

A primer set that is a nucleotide sequence pair represented by SEQ ID NO: 271 and SEQ ID NO: 272 for detection of mutations in FAM47A;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 273 and SEQ ID NO: 274, and SEQ ID NO: 275 and SEQ ID NO: 276 for detection of a mutation of PHF16;

A primer set that is a base sequence pair represented by SEQ ID NO: 277 and SEQ ID NO: 278 for detecting mutations of ZNF449;

SEQ ID NO: 279 and SEQ ID NO: 280 for detection of the mutation of SCRN1, and at least one of the base sequence pairs represented by SEQ ID NO: 281 and SEQ ID NO: 282 primer set.

The kit of the present invention produced as described above is very economical because it saves time and cost compared to the conventional general gene mutation search method. To test all of a gene using conventional gene mutation detection methods such as SSCP (Single Strand Conformational Polymorphism), PTT (Protein Truncation Test), cloning, direct sequencing, etc., it takes a few days on average. It takes several months. In addition, through next generation sequencing (NGS), gene mutations can be quickly and simply examined precisely. When the mutation is tested by conventional analysis methods such as SSCP, cloning, direct sequencing, and RFLP (Restriction Fragment Length Polymorphism), it takes about a month to complete the test, whereas sample DNA is prepared using the kit of the present invention. If so, results can be obtained within about 10 to 11 hours, and since a set of primers capable of detecting mutations is integrated on one chip, it is possible to save not only time but also cost compared to conventional methods. Compared to the existing method, less than half of the reagent cost per experiment is consumed on average, so when considering the labor cost of the researcher, further cost reduction can be expected.

2. A method of providing necessary information for prognosis diagnosis of kidney cancer using a survival-specific mutant gene

Another aspect of the present invention comprises the steps of preparing sample DNA from a sample of a kidney cancer patient whose sex is known; Amplifying the sample DNA using the kit; And determining the presence or absence of a gender-specific marker specific to the gender group of the target patient from the amplification result. Treating a kidney cancer patient whose sex-specific marker has been identified with any candidate for treatment of kidney cancer or by any method; And if any of the kidney cancer treatment candidate material or any treatment method to treat kidney cancer, the step of adopting a suitable treatment candidate material or treatment method for the sex group of the kidney cancer patient whose sex-specific marker has been identified; kidney cancer comprising a. It provides a method of providing information necessary to determine the difference in the treatment effect of kidney cancer according to the sex of a patient.

Another aspect of the present invention is to prepare a sample DNA from a sample of a kidney cancer patient; Amplifying the sample DNA using the kit; And determining the presence or absence of a gender-specific marker from the amplification result; providing a method of providing information necessary for prognosis diagnosis of kidney cancer according to the sex of a kidney cancer patient comprising.

The description of the'kidney cancer prognosis diagnostic kit' is the same as described in ' 1. Sex-specific mutant genes and primer sets capable of detecting these mutant genes in kidney cancer patients, and thus a detailed description thereof will be omitted.

The optional therapeutic agent may be a therapeutic agent commonly used for the treatment of kidney cancer or a novel material whose therapeutic effect on kidney cancer is unknown, but is not limited thereto. By treating the renal cancer patient having a gender-specific marker with any of the above-described therapeutic candidate substances and then confirming the therapeutic effect, it is possible to know whether the therapeutic candidate substance has an effect on a specific patient group. If there is a renal cancer treatment effect, it can be predicted that the treatment effect is high when applied to a patient group having the same gender-specific marker, thus providing useful information for determining a treatment strategy. In addition, if the treatment effect does not appear when using any of the candidates for treatment, the treatment strategy can be efficiently designed because unnecessary treatment is not required by not proceeding any further treatment to the patient group having the same gender-specific marker. have.

Any renal cancer treatment method is also applicable instead of any of the treatment candidates, and whether to apply to a patient group having the same sex-specific marker can be determined by confirming the therapeutic effect in a patient group having a specific sex-specific marker. When confirming the therapeutic effect in the patient group having a gender-specific marker, any candidate for treatment and any renal cancer treatment method may be combined.

As used herein, the term'sample' includes any biological specimen obtained from a patient. Samples include whole blood, plasma, serum, red blood cells, white blood cells (e.g., peripheral blood mononuclear cells), milk ducts, ascites, pleural efflux, nipple aspirate, lymph fluid (e.g. disseminated tumors of lymph nodes). Cells), bone marrow aspirate, saliva, urine, feces (i.e. feces), sputum, bronchial lavage fluid, tears, microneedle aspirate (e.g. harvested by random mammary gland microneedle aspiration), any other body fluid, tissue Sample (e.g. tumor tissue), such as a tumor biopsy (e.g., a puncture biopsy) or lymph node (e.g., a sentinel lymph node biopsy), a tissue sample (e.g., tumor tissue), such as a surgical resection of a tumor , And cell extracts thereof. In some embodiments, the sample is whole blood or some component thereof, such as plasma, serum or cell pellets. In another embodiment, a sample is obtained by isolating circulating cells of a solid tumor from whole blood or a cell fraction thereof using any technique known in the art. In another embodiment, the sample is a formalin fixed paraffin embedded (FFPE) tumor tissue sample from a solid tumor such as, for example, colorectal cancer.

In certain embodiments, the sample is a tumor lysate or extract prepared from frozen tissue obtained from a subject having colorectal cancer.

The term'patient' usually includes humans as well as other animals, such as other primates, rodents, dogs, cats, horses, sheep, pigs, and the like.

The term'subject' includes subjects other than humans that are judged or suspected of renal cancer.

The method can predict the total survival rate or disease-free survival rate of kidney cancer patients.

In the present invention, the term'overall survival' includes a clinical endpoint describing a patient who survives for a limited time after being diagnosed with or treated for a disease, such as cancer, and who survives regardless of recurrence of cancer. Means possibility.

In the present invention, the term'disease-free survival (DFS)' includes a period in which a patient survives without recurrence of cancer after treatment for a specific disease (eg, cancer).

In the present invention, by analyzing the presence of a mutation of the gene of the present invention in a sample of a kidney cancer patient, it is possible to determine what prognosis for cancer is an individual having a target sample. In addition, such a method can be achieved by comparing the total survival rate or disease-free survival rate of individuals of a control group in which mutations known to have a good prognosis are not present. In the present invention, an individual known to have a good prognosis refers to an individual who has no history of metastasis, recurrence, or death after the onset of cancer.

The sample of an individual suspected of cancer refers to a sample of an individual or tissue whose cancer or tumor has already occurred or is expected to occur, and means a target sample for which the prognosis is to be diagnosed.

The gender-specific markers are ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TCB1, TBC1D13, TBC1 It may be a mutation of a gene encoding one selected from the group consisting of ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1.

The gender-specific markers are ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TCB1, TBC1D13, TBC1 A method that is a mutation of a gene encoding one selected from the group consisting of ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1.

Sex-specific markers for women among kidney cancer patients are ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1D8 , TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and may be a mutation of a gene encoding one selected from the group consisting of SCRN1.

Among kidney cancer patients, a male-specific marker may be a mutation in a gene encoding TET2.

The method of providing information necessary for prognostic diagnosis of kidney cancer according to the sex of the kidney cancer patient may predict the total survival rate or disease-free survival rate of the kidney cancer patient. For example, the method includes a mutation in a gene encoding one selected from the group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449 and SCRN1, and when the kidney cancer patient is a female, the It may further include a step of determining that the survival rate of the kidney cancer patient is not good or that the recurrence rate of the kidney cancer patient is high.

The method of providing necessary information for the prognosis diagnosis of kidney cancer according to the sex of the kidney cancer patient is the sex of the kidney cancer patient is female, and the group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, and ZNF449 When a mutation in the gene encoding one selected from is identified, determining that the survival rate of kidney cancer of the kidney cancer patient is not good; may further include.

The method of providing necessary information for the prognosis diagnosis of kidney cancer according to the sex of the kidney cancer patient is that the sex of the kidney cancer patient is female, and one selected from the group consisting of ACSS3, ARSF, CFP, FAM47A, ZNF449 and SCRN1 When the mutation in the encoding gene is confirmed, determining that the renal cancer recurrence rate of the kidney cancer patient is high. It may further include.

As such, mutations of the genes of the present invention ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1 By using mutation of at least one gene selected from the gene group consisting of TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1, there is a difference in genetic variation according to the onset sex of cancer, especially kidney cancer. It has not been revealed yet. In addition, it is possible to diagnose the prognosis for cancer, particularly kidney cancer, in a specific sex by using mutation of at least one gene selected from the gene group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449 and SCRN1. The contents have yet to be revealed. In addition, it has not been reported that the total survival rate or disease-free survival rate may be different in each gene. The present inventors were the first to find out that mutations of the genes can be used as diagnostic markers capable of predicting the difference in the therapeutic effect of kidney cancer according to the sex of a kidney cancer patient or diagnosing the prognosis of a kidney cancer patient.

The method of providing the information necessary to predict the difference in the effect of kidney cancer treatment according to the sex of the kidney cancer patient of the present invention diagnoses genetic mutation of kidney cancer based on the sex, or increases the survival rate of the kidney cancer patient, or It can be used to lower the recurrence rate. Through the method for prognosis diagnosis of kidney cancer of the present invention, it is possible to predict the therapeutic effect of kidney cancer or predict the survival rate or recurrence rate of kidney cancer patients using mutation information of genes that differ depending on the sex of the onset of kidney cancer, In addition to discovering suitable therapeutic agents for each patient, information can be provided in the selection of treatment, so that therapeutic strategies for kidney cancer can be efficiently designed.

Hereinafter, the present invention will be described in detail by examples and experimental examples.

However, the following Examples and Experimental Examples are for illustrative purposes only, and the contents of the present invention are not limited by the following Examples and Experimental Examples.

Securing genetic and clinical information

Genes of the present invention (ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TCB, TBC1D13, TBC1D13, TBC1 In order to check whether ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, SCRN1) can be used as a gender-specific kidney cancer marker, both genetic and clinical information are obtained from TCGA (The Cancer Genome Atlas). Data on recurrence, metastasis, death, and observation time of 417 patients with transparent kidney cancer were obtained and used for analysis. Table 1 below shows data on recurrence, metastasis, and death of patients with transparent kidney cancer.

gender Sum male female Number of patients (persons) ratio(%) Relapse

0 148 (54.6%) 81 (55.5%) 229 55.2% One 77 (28.4%) 32 (21.9%) 109 26.1% Not observed 46 (17.0%) 33 (22.6%) 79 18.7% transition
0 224 (82.7%) 127 (87.0%) 351 84.2% One 47 (17.3%) 19 (13.0%) 66 15.8% Dead
0 181 (66.8%) 89 (61.0%) 270 65.0% One 90 (33.2%) 57 (39.0%) 147 35.0% Total number of patients 271 146 417 people

Confirmation of utility as a gender-specific marker

417 patients were classified into two groups by sex, and the correlation between mutation of candidate genes of Example 1 and sex was confirmed by three Feature Selections (Information Gain, Chi-Square, MR). The mutated positions of the genes are shown in Tables 2 to 6 below.

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var ACSS3 NM_024560.3 R634* Nonsense Diploid 4 chr12 81647354 81647354 C T X152_splice Splice Gain chr12 81503485 81503485 T C G268D Missense Gain One Low chr12 81536908 81536908 G A ADAM21 NM_003813.3 N265Y Missense ShallowDel 2 Medium chr14 70925009 70925009 A T R408C Missense Diploid 3 Medium chr14 70925438 70925438 C T T589S Missense Diploid One Low chr14 70925981 70925981 A T I161V Missense Diploid 3 Low chr14 70924697 70924697 A G AFF2 NM_002025.3 S770F Missense DeepDel One Low chr23 148037884 148037884 C T P513H Missense Diploid One Medium chr23 148035250 148035250 C A T640N Missense Gain One Low chr23 148037494 148037494 C A I149K Missense Diploid One Neutral chr23 147743694 147743694 T A I149K Missense Diploid One Neutral chr23 147743694 147743694 T A I149K Missense Diploid One Neutral chr23 147743694 147743694 T A ALG13 NM_001099922.2 P925T Missense Diploid Low chr23 110987973 110987973 C A L195Pfs*23 FS del Diploid chr23 110951455 110951455 T - V456E Missense Diploid Medium chr23 110964871 110964871 T A BAP1 NM_004656.3 M1? Nonstart ShallowDel 6 chr3 52443894 52443894 T C G128* Nonsense ShallowDel 2 chr3 52441470 52441470 C A E402* Nonsense ShallowDel chr3 52438515 52438515 C A E283Gfs*52 FS del ShallowDel One chr3 52439864 52439864 T - V335Efs*56 FS del ShallowDel One chr3 52439219 52439238 GCTGCCTG
GAGGCTTCACCA - Q253* Nonsense ShallowDel 2 chr3 52440295 52440295 G A Q267* Nonsense ShallowDel One chr3 52439913 52439913 G A

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var BAP1 NM_004656.3 S460* Nonsense ShallowDel 3 chr3 52437782 52437782 G C F170V Missense ShallowDel 4 High chr3 52441262 52441262 A C K711Sfs*25 FS del ShallowDel One chr3 52436362 52436362 T - Y627* Nonsense ShallowDel One chr3 52437163 52437163 G C R717Gfs*19 FS del ShallowDel One chr3 52436345 52436345 G - X23_splice Splice ShallowDel chr3 52443729 52443729 C T S279* Nonsense ShallowDel One chr3 52439876 52439876 G T BAP1 NM_004656.3 R60* Nonsense DeepDel 4 chr3 52442567 52442567 G A M1? Nonstart ShallowDel 6 chr3 52443892 52443892 C T M1? Nonstart ShallowDel 6 chr3 52443892 52443892 C T R700Gfs*36 FS del ShallowDel One chr3 52436397 52436397 C - X41_splice Splice ShallowDel chr3 52443568 52443568 A G Q40* Nonsense ShallowDel 2 chr3 52443574 52443574 G A Q156* Nonsense ShallowDel One chr3 52441304 52441304 G A K626* Nonsense ShallowDel One chr3 52437168 52437168 T A D74Efs*4 FS del ShallowDel One chr3 52442523 52442523 A - X41_splice Splice ShallowDel chr3 52443568 52443568 A T D407Vfs*23 FS del ShallowDel 2 chr3 52438499 52438499 T - F170C Missense ShallowDel 4 High chr3 52441261 52441261 A C X23_splice Splice ShallowDel chr3 52443623 52443647 ACCTGCG
ATGAGGAAAGGAAAGCAG - X311_splice Splice ShallowDel chr3 52439311 52439311 C A E31A Missense ShallowDel 5 High chr3 52443600 52443600 T G N78S Missense ShallowDel 2 Neutral chr3 52442512 52442512 T C N78S Missense ShallowDel 2 Neutral chr3 52442512 52442512 T C L49V Missense ShallowDel 2 High chr3 52442600 52442600 G C D75G Missense ShallowDel One Neutral chr3 52442521 52442521 T C S10T Missense ShallowDel 4 High chr3 52443866 52443866 C G N229H Missense ShallowDel One Medium chr3 52440367 52440367 T G G109V Missense ShallowDel One High chr3 52442023 52442023 C A L17P Missense ShallowDel One Medium chr3 52443747 52443747 A G A145G Missense ShallowDel One Medium chr3 52441418 52441418 G C K659del IF del DeepDel chr3 52436801 52436803 CTT - A1061T Missense Diploid 2 Medium chr23 79948521 79948521 C T

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var BRWD3 NM_153252.4 G287A Missense Diploid One Neutral chr23 79991541 79991541 C G I1747N Missense Diploid One Neutral chr23 79932277 79932277 A T COL4A5 NM_000495.4 P1184L Missense Diploid One Medium chr23 107909822 107909822 C T P756S Missense Diploid One Medium chr23 107849993 107849993 C T P1365S Missense Diploid Medium chr23 107924995 107924995 C T G1427V Missense Diploid High chr23 107929324 107929324 G T X1510_splice Splice Diploid chr23 107935977 107935977 G T A1656T Missense Diploid Neutral chr23 107938641 107938641 G A CPEB1 NM_030594.4 S393R Missense Diploid Medium chr15 83221251 83221251 G C G136V Missense Diploid Neutral chr15 83226709 83226709 C A X499_splice Splice Diploid chr15 83215272 83215272 C A ERBB2 NM_004448.3 E1114G Missense Diploid One Low chr17 37883729 37883729 A G S649T Missense Diploid One Low chr17 37876087 37876087 G C V219I Missense Diploid One Neutral chr17 37866350 37866350 G A N388Qfs*14 FS ins Diploid chr17 37871549 37871550 - C HSP90AA1 NM_001017963.2 D512N Missense ShallowDel 2 High chr14 102550300 102550300 C T H806R Missense Diploid One High chr14 102548486 102548486 T C I325T Missense ShallowDel One High chr14 102551690 102551690 A G L167V Missense ShallowDel One Medium chr14 102552583 102552583 G C

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var IRAK1 NM_001569.3 Q280* Nonsense Diploid One chr23 153283528 153283528 G A V548M Missense Diploid One Neutral chr23 153278782 153278782 C T Q584K Missense Diploid One Low chr23 153278674 153278674 G T KDM5C NM_004187.3 R681* Nonsense Diploid 3 chr23 53230752 53230752 G A Q813* Nonsense Diploid 2 chr23 53227751 53227751 G A E1152K Missense Diploid One Medium chr23 53223905 53223905 C T X321_splice Splice Diploid chr23 53244975 53244975 A G T471Vfs*5 FS del Diploid chr23 53240028 53240031 GGTA - R1458W Missense Diploid One Low chr23 53222460 53222460 G A G536W Missense Diploid One High chr23 53239736 53239736 C A E284* Nonsense Diploid One chr23 53245090 53245090 C A Q1427Pfs*50 FS del Diploid One chr23 53222653 53222656 GGCT - C730R Missense Diploid 2 Medium chr23 53228214 53228214 A G E592V Missense Diploid One High chr23 53231127 53231127 T A E798* Nonsense Diploid One chr23 53227796 53227796 C A C512W Missense Diploid One High chr23 53239905 53239905 G C Y639* Nonsense Diploid One chr23 53230876 53230877 - T S1110* Nonsense Diploid One chr23 53224222 53224222 G C E122Vfs*14 FS del Diploid One chr23 53247129 53247135 CCACCTT - K459* Nonsense Diploid One chr23 53240705 53240705 T A E1131Sfs*16 FS del Diploid One chr23 53224160 53224160 C - C730F Missense Diploid 2 Medium chr23 53228213 53228213 C A H988Tfs*18 FS del Diploid One chr23 53225887 53225887 G - H733P Missense Diploid One Medium chr23 53228204 53228204 T G P27Lfs*46 FS del Diploid One chr23 53253992 53253992 G - F56Cfs*18 FS del Diploid One chr23 53250081 53250082 AA - D1414Efs*54 FS del Diploid One chr23 53222684 53222694 TGTGGTTCTCA - R215* Nonsense Diploid One chr23 53246339 53246339 T A G845Rfs*2 FS del ShallowDel chr23 53227036 53227042 GTAGACC -

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var KDM6A NM_021140.3 A30V Missense Diploid One Medium chr23 44732886 44732886 C T A1246Pfs*19 FS del Diploid chr23 44949174 44949174 A - V156del IF del ShallowDel chr23 44879876 44879878 GGT - LRP12 NM_013437.4 S622L Missense Diploid One Low chr8 105503616 105503616 G A E639K Missense Diploid 2 Neutral chr8 105503566 105503566 C T V671I Missense Gain One Neutral chr8 105503470 105503470 C T NCOA6 NM_001242539.2 G164E Missense Diploid One Low chr20 33356290 33356290 C T N877I Missense Gain One Low chr20 33337368 33337368 T A N864Y Missense Gain One Neutral chr20 33337408 33337408 T A V1444A Missense Diploid One Neutral chr20 33329729 33329729 A G H832Sfs*47 FS ins Gain chr20 33337505 33337506 - G NHS NM_198270.3 C360R Missense Diploid Low chr23 17742451 17742451 T C P1107A Missense Diploid One Low chr23 17745608 17745608 C G D1069H Missense Diploid 2 Medium chr23 17745494 17745494 G C RGAG1 NM_020769.2 A1015G Missense Diploid One Low chr23 109696889 109696889 C G M858V Missense Diploid One Neutral chr23 109696417 109696417 A G G1053R Missense Diploid One Low chr23 109697002 109697002 G C SCAF1 NM_021228.2 A219Sfs*11 FS ins ShallowDel chr19 50154294 50154295 - C P211Tfs*19 FS ins Diploid chr19 50154270 50154271 - C P211Tfs*19 FS ins Diploid chr19 50154270 50154271 - C A216Pfs*94 FS del Diploid chr19 50154291 50154294 TGCA -

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var SH3TC1 NM_018986.4 A375V Missense Diploid One Neutral chr4 8224578 8224578 C T R238Sfs*38 FS del Diploid chr4 8218768 8218768 G - L180F Missense Diploid One Neutral chr4 8217896 8217896 G T TBC1D8B NM_017752.2 G1059V Missense Diploid 2 Neutral chr23 106117008 106117008 G T A614T Missense ShallowDel One Medium chr23 106093257 106093257 G A S861* Nonsense Gain One chr23 106109183 106109183 C G Y815F Missense Diploid 3 Medium chr23 106109045 106109045 A T Y815F Missense Diploid 3 Medium chr23 106109045 106109045 A T Y815F Missense ShallowDel 3 Medium chr23 106109045 106109045 A T TET2 NM_001127208.2 Q317K Missense ShallowDel One Low chr4 106156048 106156048 C A K326* Nonsense Diploid One chr4 106156075 106156075 A T L757V Missense Diploid Neutral chr4 106157368 106157368 C G V449E Missense Diploid Low chr4 106156445 106156445 T A N1714K Missense Diploid One Medium chr4 106196809 106196809 T G D194E Missense Diploid One Low chr4 106155681 106155681 C A N1390H Missense Diploid One Medium chr4 106190890 106190890 A C R1451Q Missense Diploid 2 Medium chr4 106193890 106193890 G A M600I Missense ShallowDel One Neutral chr4 106156899 106156899 G A P554S Missense ShallowDel One Neutral chr4 106156759 106156759 C T TEX13A NM_001291277.1 R393S Missense Diploid Medium chr23 104463697 104463697 C A X199_splice Splice Diploid 2 chr23 104464282 104464282 C - X199_splice Splice Diploid 2 chr23 104464282 104464282 C - Y257D Missense Diploid Low chr23 104464107 104464107 A C ULK3 NM_001099436.3 Q81Sfs*41 FS del Diploid chr15 75134624 75134624 A - D79H Missense Diploid Medium chr15 75134629 75134629 C G L77V Missense Diploid Low chr15 75134635 75134635 G C WNK3 NM_001002838.3 S865* Nonsense Diploid One chr23 54276546 54276546 G T E537G Missense Diploid One Low chr23 54321069 54321069 T C Y589* Nonsense Diploid One chr23 54319687 54319687 A T

For each sex group, the association between mutation incidence of candidate genes and the sex of kidney cancer patients was confirmed. P-values less than 0.05 were considered statistically significant. Information of candidate genes related to Tables 8 and 11 is shown below (M0: no distant metastasis, M1: distant metastasis).

　
　
　 gender
Total number of patients with confirmed gene mutation

Fisher's Mutation Mutation type
Cyto Band

transition
transition(%)

exact (%) M F (P-value) cut Miss Sense (P) Miss Sense (D) In-frame M0 M1 ACSS3 0 3 3 0.042 0.72% 2 One 0 0 12q21.31 One 2 66.70% ADAM21 0 4 4 0.015 0.96% 0 4 0 0 14q24.1 4 0 0.00% AFF2 One 5 6 0.022 1.44% 0 6 0 0 Xq28 5 One 16.70% ALG13 0 3 3 0.042 0.72% One 2 0 0 Xq23 3 0 0.00% AOC2 2 2 4 0.614 0.96% 3 One 0 0 17q21 4 0 0.00% AR 0 One One 0.35 0.24% 0 One 0 0 Xq12 One 0 0.00% ARSF 0 One One 0.35 0.24% 0 One 0 0 Xp22.3 One 0 0.00% ASUN One 2 3 0.281 0.72% One 2 0 0 12p11.23 2 One 33.30% ASXL2 2 4 6 0.19 1.44% 4 One 0 One 2p24.1 4 2 33.30% ASXL3 7 0 7 0.102 1.68% 0 7 0 0 18q12.1 4 3 42.90% AVPR2 0 2 2 0.122 0.48% 0 2 0 0 Xq28 2 0 0.00% BAP1 12 25 37 <0.001 8.87% 25 8 3 One 3p21.1 26 11 29.70% BCOR 2 0 2 0.544 0.48% One One 0 0 Xq25-q26.1 One One 50.00% BHLHB9 3 0 3 0.555 0.72% 0 3 0 0 Xq23 3 0 0.00% BRWD3 0 3 3 0.042 0.72% 0 3 0 0 Xq21.1 3 0 0.00% CDCA7 0 2 2 0.122 0.48% 0 2 0 0 2q31.1 2 0 0.00% CELSR1 7 0 7 0.102 1.68% 3 4 0 0 22q13.31 5 2 28.60% CFP One 3 4 0.126 0.96% One 3 0 0 Xp11.4 3 One 25.00% CLN8 0 2 2 0.122 0.48% 0 2 0 0 8p23 2 0 0.00%

　
　
　 gender
Total number of patients with confirmed gene mutation

Fisher's Mutation Mutation type
Cyto Band

transition
transition(%)

exact (%) M F (P-value) cut Miss Sense (P) Miss Sense (D) In-frame M0 M1 COL4A5 One 5 6 0.022 1.44% One 5 0 0 Xq22 5 One 16.70% CPEB1 0 3 3 0.042 0.72% One 2 0 0 15q25.2 2 One 33.30% CYLC1 0 2 2 0.122 0.48% 0 2 0 0 Xq21.1 2 0 0.00% DYSF 2 4 6 0.19 1.44% 2 3 0 One 2p13.2 4 2 33.30% ERBB2 0 4 4 0.015 0.96% One 3 0 0 17q12 4 0 0.00% FAM47A One 3 4 0.126 0.96% 0 2 0 2 Xp21.1 3 One 25.00% FRMD7 4 0 4 0.302 0.96% 2 2 0 0 Xp22.2 3 One 25.00% FRMPD4 4 0 4 0.302 0.96% 3 One 0 0 Xp22.2 4 0 0.00% GABRQ 2 4 6 0.19 1.44% 2 4 0 0 Xq28 5 One 16.70% GPR45 0 3 3 0.042 0.72% One 2 0 0 2q12.1 2 One 33.30% HAUS7 2 0 2 0.544 0.48% 0 2 0 0 Xq28 One One 50.00% HSP90AA1 0 4 4 0.015 0.96% 0 4 0 0 14q32.31 4 0 0.00% IRAK1 0 3 3 0.042 0.72% One 2 0 0 Xq28 3 0 0.00% ITIH6 0 One One 0.35 0.24% 0 One 0 0 Xp11.22-p11.21 One 0 0.00% KDM5C 3 23 26 <0.001 6.24% 18 8 0 0 Xp11.22-p11.21 22 4 15.40% KDM6A 0 3 3 0.042 0.72% One One 0 One Xp11.2 3 0 0.00% LPAR4 0 2 2 0.122 0.48% One One 0 0 Xq21.1 2 0 0.00% LRP12 0 3 3 0.042 0.72% 0 3 0 0 8q22.2 3 0 0.00% MAGEB10 0 2 2 0.122 0.48% 0 2 0 0 Xp21.1 2 0 0.00%

　
　
　 gender
Total number of patients with confirmed gene mutation

Fisher's Mutation Mutation type
Cyto Band

transition
transition(%)

exact (%) M F (P-value) cut Miss Sense (P) Miss Sense (D) In-frame M0 M1 MAGEB16 0 2 2 0.122 0.48% 0 2 0 0 Xp21.1 2 0 0.00% MAGED1 2 0 2 0.544 0.48% 0 2 0 0 Xp11.23 2 0 0.00% MAP3K15 One 3 4 0.126 0.96% 2 2 0 0 Xp22.12 3 One 25.00% MED14 4 One 5 0.661 1.20% One 4 0 0 Xp11.4 5 0 0.00% NBPF10 4 4 8 0.459 1.92% 2 6 0 0 1q21.1 6 2 25.00% NCOA6 0 4 4 0.015 0.96% One 3 0 0 20q11.22 4 0 0.00% NCOR1P1 null 20p11.1 null NHS 0 3 3 0.042 0.72% 0 3 0 0 Xp22.13 3 0 0.00% NOX1 2 2 4 0.614 0.96% 2 2 0 0 Xq22 4 0 0.00% PABPC3 9 One 10 0.176 2.40% One 9 0 0 13q12-q13 10 0 0.00% PHF16(JADE3)
0 2 2 0.122 0.48% 0 2 0 0 Xp11.23 2 0 0.00% POTEH-AS1 null 22q11.1 null PRRG3 0 2 2 0.122 0.48% 0 2 0 0 Xq28 2 0 0.00% RGAG1 0 3 3 0.042 0.72% 0 3 0 0 Xq23 3 0 0.00% SCAF1 0 4 4 0.015 0.96% 4 0 0 0 19q13.33 3 One 25.00% SCRN1 0 2 2 0.122 0.48% One One 0 0 7p14.3 One One 50.00% SH3TC1 0 3 3 0.042 0.72% One 2 0 0 4p16.1 3 0 0.00% SMC1A 0 2 2 0.122 0.48% One One 0 0 Xp11.22-p11.21 2 0 0.00% SYTL4 0 One One 0.35 0.24% 0 One 0 0 Xq21.33 One 0 0.00%

　
　
　 gender
Total number of patients with confirmed gene mutation

Fisher's Mutation
(%)
Mutation type
Cyto Band

transition
transition(%)

exact M F (P-value) cut Miss Sense (P) Miss Sense (D) In-frame M0 M1 TBC1D8B One 5 6 0.022 1.44% One 5 0 0 Xq22.3 6 0 0.00% TET2 9 0 9 0.03 2.16% One 8 0 0 4q24 3 6 66.70% TEX13A 0 4 4 0.015 0.96% 2 2 0 0 Xq22.3 4 0 0.00% TFDP3 One 2 3 0.281 0.72% 0 3 0 0 Xq26.2 3 0 0.00% TRO 0 2 2 0.122 0.48% One One 0 0 Xp11.22-p11.21 2 0 0.00% ULK3 0 3 3 0.042 0.72% One 2 0 0 15q24.1 3 0 0.00% USP51 One 4 5 0.53 1.20% One 4 0 0 Xp11.21 3 2 40.00% WNK3 0 3 3 0.042 0.72% 2 One 0 0 Xp11.22 2 One 33.30% ZMYM3 One One 2 One 0.48% 0 2 0 0 Xq13.1 2 0 0.00% ZNF318 2 5 7 0.054 1.68% 2 5 0 0 6p21.1 6 One 14.30% ZNF449 0 One One 0.35 0.24% 0 One 0 0 Xq26.3 One 0 0.00%

As a result of the analysis, even though genes with mutations in each gender group were compared with other groups, there were genes with a P-value of 0.05 or more, while genes with mutations and a P-value of less than 0.05 were identified. When compared to other groups, mutant genes with a P-value of less than 0.05 were selected as gender-specific genes because they were correlated with a specific sex group compared to other groups. For example, in AOC2, AR, and ARSF, the total number of mutated patients was large, but the P-value was as high as 0.05 or higher, indicating that there was no correlation between mutations in these genes and sex. On the other hand, when compared between groups, ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TET2, SH3TC1, TEX13A, ULK3, and WNK3 had a P-value of less than 0.05, and it was confirmed that there is a correlation between the occurrence of mutations in these genes and sex. 1 shows the results of analyzing the association between the mutation of the gene and the sex. 1 ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1DTC1, TBC1D It was confirmed that WNK3 had a greater number of patients with mutated genes in the female group than in the male group, and TET2 was found to have more patients with the mutated gene in the male group than in the female group.

From the above results, ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC3BC1D8, and UL It was found that the mutation can be used as a marker specific to the female group, and that the mutation of TET2 can be used as a marker specific to the male group.

Confirmation of the possibility of use as a survival-specific marker according to gender

Among the candidate genes, it was confirmed whether there was a survival-specific mutant gene according to sex. Analysis was performed in the same manner as in Example 2. Table 12 shows the mutated positions of each gene.

Gene Accession No. AA change Type Copy# COSMIC Mutation
Assessor Chr Start Pos End Pos Ref Var ACSS3 NM_024560.3 R634* Nonsense Diploid 4 chr12 81647354 81647354 C T X152_splice Splice Gain chr12 81503485 81503485 T C G268D Missense Gain One Low chr12 81536908 81536908 G A ALG13 NM_001099922.2 P925T Missense Diploid Low chr23 110987973 110987973 C A L195Pfs*23 FS del Diploid chr23 110951455 110951455 T - V456E Missense Diploid Medium chr23 110964871 110964871 T A ARSF NM_001201538.1 I42F Missense Diploid One Medium chr23 2990179 2990179 A T CFP NM_001145252.1 S27L Missense Diploid 2 Medium chr23 47489070 47489070 G A R359Q Missense Diploid One Low chr23 47485783 47485783 C T E135K Missense Diploid One Low chr23 47487501 47487501 C T E323Gfs*34 FS ins Gain One chr23 47485891 47485892 - C FAM47A NM_203408.3 R505H Missense ShallowDel 3 Neutral chr23 34148882 34148882 C T E507Q Missense ShallowDel 6 Low chr23 34148877 34148877 C G L235_H246del IF del Diploid chr23 34149658 34149693 ATGGGACA
CTCCAGTCTCTGGAGGCTCCGGGCGGAG - L235_H246del IF del Diploid chr23 34149658 34149693 ATGGGACA
CTCCAGTCTCTGGAGGCTCCGGGCGGAG - KDM6A NM_021140.3 A30V Missense Diploid One Medium chr23 44732886 44732886 C T A1246Pfs*19 FS del Diploid chr23 44949174 44949174 A - V156del IF del ShallowDel chr23 44879876 44879878 GGT - PHF16
(JADE3) NM_001077445.2 K656Q Missense Diploid Low chr23 46917973 46917973 A C R207W Missense ShallowDel Medium chr23 46887437 46887437 C T ZNF449 NM_152695.5 F183I Missense Diploid One Low chr23 134483227 134483227 T A SCRN1 NM_001145514.1 D427Y Missense Gain Medium chr7 29963599 29963599 C A A257Cfs*34 FS ins Diploid chr7 29980329 29980330 - C

The overall survival kaplan-meier estimate and the disease free survival kaplan-meier estimate were obtained using the Kaplan Meyer survival assay (Spss 21). The 417 target patients obtained in Example 1 were classified into surviving patients (270 patients) and deceased patients (147 patients), and comparative analysis was performed. Based on the clinical information (whether event (death or recurrence), observation time) obtained in Example 1, the total survival period or disease-free survival period was calculated by the Kaplan Meyer survival analysis method. In the total survival period, the event was defined as death, and in the disease-free survival period, the event was defined as recurrence of kidney cancer. In order to determine whether the occurrence of mutations in each of the genes is correlated with death due to renal cancer or recurrence of renal cancer, the occurrence of mutation and The association of the total survival period, and the association between mutation incidence and disease free survival was confirmed by log rank test. P-values less than 0.05 were considered statistically significant. The experimental group was defined as the case with mutations in the genes of the present invention (case with alterations in query gene), and as the control group, the case without alterations in query gene was used as the control group. The median months survival is a value that is located in the middle when the survival periods of patients in the group are listed. The slope in the survival curve by the Kaplan Meyer survival assay is determined by the duration of survival. In order to confirm whether mutation occurrence in each of the candidate genes is related to the survival rate of kidney cancer patients of a specific sex (the null hypothesis), the genetic information of 417 kidney cancer patients obtained in Example 1 was analyzed. Table 13 shows the sex of patients with confirmed mutations in the ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes.

　
　
　
　
Gender group Total number of patients with confirmed gene mutations
M F ACSS3 0 3 3 ALG13 0 3 3 ARSF 0 One One CFP One 3 4 FAM47A One 3 4 KDM6A 0 3 3 PHF16 0 2 2 ZNF449 0 One One SCRN1 0 2 2

As shown in Figures 2 to 10, when comparing between groups, the occurrence of mutations in the ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes is associated with the survival rate of women among kidney cancer patients. Since the probability of the null hypothesis being correct is 99.5% or more, that is, the probability that the null hypothesis is incorrect is less than 0.5%, mutations in ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, SCRN1 genes and kidney cancer patients It can be seen that there is a correlation with the survival rate of the female patient (refer to the sex information in Table 13 and the information on the total number of patients with confirmed gene mutations). In Example 1, when only the association between the occurrence of mutations and sex was confirmed. Some of the mutant genes that were judged to be insignificant because the P-value was greater than or equal to 0.05 were found to have a significant P-value of less than 0.05 when the association between the occurrence of mutation and the survival rate of renal cancer patients of a specific sex was confirmed. For example, in the case of ARSF, it was found that there was no significance when only confirming the association between mutation occurrence and sex in Example 1, but when comparing the association between the mutation and survival rate of ARSF in this example according to sex groups, there is significance. (Refer to the sex information in Table 13 and the P-value in FIGS. 2 to 15).

The results of the survival analysis of renal cancer patients having the mutant gene are shown in FIGS. 2 to 15.

As a result of the analysis, ACSS3, as can be seen in Figure 2 (A), in the case of kidney cancer patients who do not have a mutation in the ACSS3 gene, 50% or more survived for more than 80 months (blue), whereas the ACSS3 gene In the case of renal cancer patients with mutations, more than 50% of renal cancer patients died before 20 months of age, so it was confirmed that the survival rate was lower than that of renal cancer patients without mutations (red). According to (B) of Figure 2, in the case of kidney cancer patients who did not have a mutation in the ACSS3 gene, 50% or more did not have recurrence for more than 100 months (blue), but if there was a mutation in the ACSS3 gene, kidney cancer patients were less than 40 months old. Renal cancer recurred in more than 50% of patients (red). Therefore, if there is a mutation in the ACSS3 gene and the sex of a kidney cancer patient is female, the probability of death or recurrence due to kidney cancer is high, so the mutation of the ACSS3 gene is significant as a predictor of survival rate of kidney cancer patients or recurrence of kidney cancer. Can be seen.

As can be seen in FIG. 3, in the case of renal cancer patients who do not have mutations in the ALG13 gene, more than 50% survive for more than 80 months (blue), whereas in the case of renal cancer patients with mutations in the ALG13 gene, Since more than 50% of renal cancer patients died before 20 months, it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). Therefore, when there is a mutation in the ALG13 gene and the sex of the kidney cancer patient is female, the probability of death due to kidney cancer increases, so that the mutation of the ALG13 gene is significant as a predictive marker for the survival rate of the kidney cancer patient.

As can be seen in (A) of FIG. 4, in the case of kidney cancer patients who do not have mutations in the ARSF gene, 50% or more survived for more than 80 months (blue), whereas mutations occurred in the ARSF gene. In renal cancer patients, more than 50% of renal cancer patients died before 20 months, so it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). According to (B) of Figure 4, in the case of renal cancer patients who did not have a mutation in the ARSF gene, 50% or more had no recurrence for more than 100 months (blue), but if there was a mutation in the ARSF gene, the kidney cancer patient was less than 20 months old. Renal cancer recurred in more than 50% of patients (red). Therefore, if there is a mutation in the ARSF gene and the sex of the kidney cancer patient is female, the probability of death or recurrence due to kidney cancer is high, so the mutation of the ARSF gene is significant as a predictor of survival rate of kidney cancer patient or recurrence of kidney cancer. Can be seen.

As can be seen in (A) of FIG. 5, in the case of kidney cancer patients who do not have mutations in the CFP gene, 50% or more survived for more than 80 months (blue), whereas mutations occurred in the CFP gene. In renal cancer patients, more than 50% of renal cancer patients died before 20 months, so it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). According to (B) of FIG. 5, in the case of kidney cancer patients who did not have a mutation in the CFP gene, more than 50% had no recurrence for more than 100 months (blue), but if there was a mutation in the CFP gene, kidney cancer patients were less than 40 months old. Renal cancer recurred in more than 50% of patients (red). Therefore, if there is a mutation in the CFP gene and the sex of a kidney cancer patient is female, the probability of death or recurrence due to kidney cancer is high, so the mutation of the CFP gene is significant as a predictor of survival rate or recurrence of kidney cancer in kidney cancer patients. Can be seen.

FAM47A, as can be seen in Figure 6 (A), in the case of kidney cancer patients that do not have a mutation in the FAM47A gene survived for more than 80 months (blue), whereas a mutation occurred in the FAM47A gene. In renal cancer patients, more than 50% of renal cancer patients died before 20 months, so it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). According to (B) of Figure 6, in the case of kidney cancer patients who did not have a mutation in the FAM47A gene, 50% or more had no recurrence for more than 100 months (blue), but if there is a mutation in the FAM47A gene, the kidney cancer patient was less than 40 months. Renal cancer recurred in more than 50% of patients (red). Therefore, if there is a mutation in the FAM47A gene and the sex of a kidney cancer patient is female, the probability of death or recurrence due to kidney cancer is high, so the mutation of the FAM47A gene is significant as a predictor of survival rate of kidney cancer patient or recurrence of kidney cancer. Can be seen.

KDM6A, as can be seen in Figure 7, in the case of kidney cancer patients who do not have mutations in the KDM6A gene survive for more than 80 months (blue), whereas in the case of kidney cancer patients with mutations in the KDM6A gene Since more than 50% of renal cancer patients died before 20 months, it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). Therefore, when there is a mutation in the KDM6A gene and the sex of the kidney cancer patient is female, the probability of death due to kidney cancer is increased, so that the mutation of the KDM6A gene is significant as a predictive marker of the survival rate of the kidney cancer patient.

As can be seen in FIG. 8, PHF16 is 50% or more of kidney cancer patients who do not have mutations in the PHF16 gene survive for more than 80 months (blue), whereas kidney cancer patients with mutations in the PHF16 gene have Since more than 50% of renal cancer patients died before 40 months, it was confirmed that the survival rate was lower than that of renal cancer patients without mutation (red). Therefore, when there is a mutation in the PHF16 gene and the sex of the kidney cancer patient is female, the probability of death due to kidney cancer is increased, so that the mutation of the PHF16 gene is significant as a marker for predicting the survival rate of the kidney cancer patient.

According to FIG. 9, in the case of renal cancer patients who did not have a mutation in the SCRN1 gene, more than 50% of SCRN1 had no recurrence for more than 100 months (blue), but if there was a mutation in the SCRN1 gene, it was less than 20 months. Renal cancer recurred in more than% (red). Therefore, when there is a mutation in the SCRN1 gene and the sex of the kidney cancer patient is female, the probability of recurrence due to kidney cancer is increased, so that the mutation of the SCRN1 gene is significant as a predictive marker for recurrence of kidney cancer.

As can be seen in (A) of FIG. 10, in the case of kidney cancer patients who do not have a mutation in the ZNF449 gene, more than 50% survived for more than 80 months (blue), whereas a mutation occurred in the ZNF449 gene. Since more than 50% of kidney cancer patients died before 10 months, the survival rate was lower than that of kidney cancer patients without mutation (red). According to (B) of FIG. 10, in the case of kidney cancer patients who did not have a mutation in the ZNF449 gene, 50% or more had no recurrence for more than 100 months (blue), but if there was a mutation in the ZNF449 gene, kidney cancer patients were less than 20 months old. Renal cancer recurred in more than 50% of patients (red). Therefore, if there is a mutation in the ZNF449 gene and the sex of a kidney cancer patient is female, the probability of death or recurrence due to kidney cancer is high, so the mutation of the ZNF449 gene is significant as a predictor of survival rate of kidney cancer patients or recurrence of kidney cancer. Can be seen.

Through the above results, if there is a mutation in any one gene selected from the group consisting of RACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449 and SCRN1, the survival rate of kidney cancer patients of a specific sex is significantly lowered, or Since it can be seen that the recurrence rate increases, it can be seen that the prognosis of kidney cancer, particularly survival or recurrence, can be predicted by comparing whether or not there is a mutation in the genes of the present invention with the sex of the patient.

Construction of a chip capable of detecting mutations in the genes of Examples 2 and 3

Primer sets for searching for mutations in the genes of Examples 2 and 3 were made with Ion AmpliSeq™ Custom and Community Panels of Thermo fisher with reference to https://tools.thermofisher.com/content/sfs/manuals/MAN0006735_AmpliSeq_DNA_RNA_LibPrep_UG.pdf . In order to easily detect the mutation, the chip type was selected and the depth was increased. Specifically, after inputting the panel information to be produced on Ampliseq.com and receiving feedback on the input information, related matters were discussed to produce a panel equipped with a primer set capable of detecting mutations. Tables 14 to 21 show primer sets capable of detecting mutations in the genes of the present invention.

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop ACSS3 chr12 31 GGGATAAGATTGCTATCATCTATGACAGT 32 GAAGGCTCTACAATGAGAATGTATGCTAT 81503404 81503433 81503537 81503566 ACSS3 chr12 33 TTCAGTCAGATGCTCAGACTTAAATAGATT 34 ACAGTCATGTGACTGGGCTTTT 81536787 81536817 81536938 81536960 ACSS3 chr12 35 CTCTAGATATAAATGCAACAGAGGAGCAA 36 CCATTGACAATGGCAGATAAAGCTG 81647268 81647297 81647411 81647436 ADAM21 chr14 37 GGGCTTTCGAGGAGTATTAAAAATAAGT 38 TGCTACTTCCTTCTCTGTTAAGCC 70924606 70924634 70924735 70924759 ADAM21 chr14 39 GTATTTCTTGTTGTCAACATAGTGGATTCC 40 ATGCTGTAGCTGGGAAAGACTG 70924919 70924949 70925070 70925092 ADAM21 chr14 41 CTTAAACCAGGGATCATGTCTGCAT 42 GTCTTGTTCACACTGCTGTACG 70925377 70925402 70925487 70925509 ADAM21 chr14 43 GATGTCTTTTGTGGGAGAGTTCAATG 44 GGCCACACACAGTACCATCTTT 70925885 70925911 70926037 70926059 AFF2 chrX 45 TCACCAGGATAATACCCATCCTTCA 46 AGTCTGCATCTTGTTTGGCTGA 147743623 147743648 147743775 147743797 AFF2 chrX 47 TCGGAGAGCAGCTCTGAGT 48 CTGTGGGACAGGCAGATCAT 148035180 148035199 148035296 148035316 AFF2 chrX 49 GGCTTTGAAGCATAAGTTGTCAACA 50 GGGTCATGAAGCTCCACACTTT 148037399 148037424 148037550 148037572 AFF2 chrX 51 GCCAAATCCAAGGAAATCTGTGGT 52 AGAGGTTTTTCAGGTTCTCATGATCTC 148037805 148037829 148037952 148037979 ALG13 chrX 53 TCCGGATACCTGCATAAGCAAG 54 CATCCATTGATGCCTCATTCAAAGAC 110951367 110951389 110951515 110951541 ALG13 chrX 55 GAAGACTAAGGATTGTGAGTTTGTAGCA 56 TCCTGTTGATATTTCTTTACCTTTTCTGCT 110964785 110964813 110964929 110964959 ALG13 chrX 57 TCTTTGTTAGTGATTGCCTCACCAT 58 AGTCTCTCCCACATCAAGAGCA 110987886 110987911 110988034 110988056

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop BAP1 chr3 59 GTAGGAGAGAAGAAGACTGAGAGCACT 60 GTGGAGGCTGAGATTGCAAACTA 52436693 52436720 52436840 52436863 BAP1 chr3 61 TTCCAATCAAGAACTTGGCACCT 62 GTCGTGGAAGCCACGGACA 52437065 52437088 52437218 52437237 BAP1 chr3 63 GCCGTGTCTGTACTCTCATTGC 64 CCATCAACGTCTTGGCTGAGAA 52437674 52437696 52437808 52437830 BAP1 chr3 65 AACCTGGTAGCCTTAGAAAGCTG 66 TTGTCCCAGGAGGAAGAAGACCT 52438439 52438462 52438588 52438611 BAP1 chr3 67 GGGACTTGGCATAATTGTGATTGT 68 ATCCCACAGCCCTCCCAACAAA 52439134 52439158 52439248 52439270 BAP1 chr3 69 GCTTCACCACTAGCTTGGGTTT 70 GGGAGACTGTGAGCTTTTCTTGG 52439230 52439252 52439353 52439376 BAP1 chr3 71 GGACTTGTTGCTGGCTGACTT 72 GGGTCTACCCTTTCTCCTCTGA 52439836 52439857 52439948 52439970 BAP1 chr3 73 GTATGTTCACGAATCAGAGACAAATGC 74 CGACCGCAGGATCAAGTATGAG 52440173 52440200 52440325 52440347 BAP1 chr3 75 CAGCCTGGCCTCATACTTGATC 76 CAGGATATCTGCCTCAACCTGATG 52440317 52440339 52440440 52440464 BAP1 chr3 77 CATGGTGCCTACCATGGTCAAT 78 CCTGAGAAGCAGAATGGCCTTA 52441178 52441200 52441291 52441313 BAP1 chr3 79 CGCACTGCACTAAGGCCATT 80 GCCAAGGCCCATAATAGCCATG 52441282 52441302 52441418 52441440 BAP1 chr3 81 CACACACCTGGCATGGCTATTA 82 CCCATAGTCCTACCTGAGGAGAAA 52441408 52441430 52441510 52441534 BAP1 chr3 83 CTGAAACCCTTGGTGAAGTCCT 84 TTGGTTTCACAGCTGATACCCAA 52441981 52442003 52442082 52442105 BAP1 chr3 85 ATCCCACCCTCCAAACAAAGCA 86 CCCAGCCCTGTATATGGATTTATCTT 52442453 52442475 52442601 52442627 BAP1 chr3 87 GCTGCTGCTTTCTGTGAGATTTT 88 GGGTGCAAGTGGAGGAGATCTA 52443443 52443466 52443593 52443615 BAP1 chr3 89 CCCTGACATTTGCTCTGAAGGT 90 TCGGTAAGAGCCTTTTCTCCCT 52443570 52443592 52443710 52443732 BAP1 chr3 91 TCTTACCGAAATCTTCCACGAGC 92 AAGATGAATAAGGGCTGGCTGG 52443724 52443747 52443875 52443897 BAP1 chrX 93 CTTACTGAACACTGTAACACTGGAAAGA 94 GTGGGAACAGAGCTAATATTCTCAAGAG 79948434 79948462 79948580 79948608

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop BRWD3 chrX 95 AGAGGATCCTCAGTGGACACAA 96 CTAGAGGAGCTACCAGAGCCAAAC 79932193 79932215 79932343 79932367 BRWD3 chrX 97 ATTGTTTTTACATGCCATTGCCAGAA 98 TTGATGTTAGGCTGAACATGAAAACTTTTT 79991496 79991522 79991615 79991645 COL4A5 chrX 99 ATTAAATTCTCTGTGGCAAACAATAAGGAC 100 TGGGAAACCACGATCACCTTTT 107849893 107849923 107850045 107850067 COL4A5 chrX 101 CAGCTGGACAGAAGGGTGAA 102 GTGTGTGGTAGCTTAGTAAGAAAGAAGAT 107909801 107909821 107909910 107909939 COL4A5 chrX 103 CAAAAACTGGTTTCTCTCACACCAAT 104 TGGAGGACCAGCATCTCCTTTA 107924880 107924906 107925032 107925054 COL4A5 chrX 105 CCTCATTCTTTTCCTGTAGGTCCAA 106 TCTCTCAGACTCAAAGACTTTCCCT 107929242 107929267 107929388 107929413 COL4A5 chrX 107 CCTTGAAAGGCTGTTTGCTATTGT 108 TCTTGAAGCAAAGTTGCAAACATTATTGA 107935889 107935913 107936034 107936063 COL4A5 chrX 109 CTGCTTGGAAGAGTTTCGTTCAG 110 CCCTAGCATCTCTGAAGGAAGCT 107938550 107938573 107938701 107938724 CPEB1 chr15 111 CCCACCTGATCTCGACAGAAGA 112 TGGCCAATAATGTGCCCTTCTT 83215186 83215208 83215335 83215357 CPEB1 chr15 113 CACAAGAAAATCCAGTGCCTCAA 114 AAGTCTGTCCGATCCTTGCTTC 83221163 83221186 83221315 83221337 CPEB1 chr15 115 CTAACTGAGGGTGCTGGAAACT 116 GCTGTTGGCTGCAAAGAAAACTA 83226619 83226641 83226770 83226793 ERBB2 chr17 117 GTTTGAGTGAAGGCATTCATGGT 118 GATCTCTTCCAGAGTCTCAAACACTT 37871434 37871457 37871582 37871608 ERBB2 chr17 119 CAAGAGGGTGGTTCCCAGAATT 120 GAGTGAAGGGCAATGAAGGGTA 37875993 37876015 37876108 37876130 ERBB2 chr17 121 GGCTGGCTCCGATGTATTTGAT 122 CAACGTAGCCATCAGTCTCAGA 37883628 37883650 37883751 37883773

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop HSP90AA1 chr14 123 ATTACATAGTATAAGGCTTACCCAGACCA 124 CGACAAGTCTGTGAAGGATCTGG 102548427 102548456 102548549 102548572 HSP90AA1 chr14 125 CCTGATAACTTTCAAAATTTTGCTTTGTTGC 126 GTCCTTGGAATGACTCAGTGCAT 102550229 102550260 102550340 102550363 HSP90AA1 chr14 127 CAGACAGAAATTCACTCTGCAATTACATAAAA 128 CAGGTGAACCTATGGGTCGT 102551597 102551629 102551751 102551771 HSP90AA1 chr14 129 CCCAAGAAGTTCACACTGAAACC 130 TGAGACGTTCGCCTTTCAGG 102552499 102552522 102552645 102552665 IRAK1 chrX 131 CGCCTAGGCTCTCGTCACT 132 CCCGCAGGAGAACTCCTAC 153278644 153278663 153278782 153278801 IRAK1 chrX 133 CCAGGTGTCAGGAGTGCTTT 134 ACAGGTTTCGTCACCCAAACA 153283401 153283421 153283554 153283575 KDM5C chrX 135 TCCGTACCCTCTTTGGCTCTAG 136 TGTCTTTCTGCCTGTCTGTAATCAC 53222382 53222404 53222516 53222541 KDM5C chrX 137 CCAGAAGTGTGCGGATCCTC 138 AGTTGACTGGCCCTGTGTTG 53222621 53222641 53222768 53222788 KDM5C chrX 139 CCCACACACACAGATAGAGGTTG 140 CTGTCCTGGGTATGGCAGATC 53223786 53223809 53223917 53223938 KDM5C chrX 141 CCATCTGTGTCGAAGCTCCTT 142 GTTCTCTGCCCATGTGCAGAT 53224090 53224111 53224229 53224250 KDM5C chrX 143 CTCTTCTGGGTCTCCACTCAAC 144 CCTAGCCCTGCTGTGGATAAAG 53225798 53225820 53225943 53225965 KDM5C chrX 145 CAGGTTGTTCATCTGGTCCAGAA 146 AGTCTTAGCATAGACATGGAGGGAA 53226986 53227009 53227102 53227127 KDM5C chrX 147 GCCTCACTCAGGCAGTTCTTTA 148 CCTCTGCCTCTATTCAATACTGCCTA 53227723 53227745 53227847 53227873 KDM5C chrX 149 CTACTGGAGCACTTGCAGAGAT 150 GATGATGAGCGCCAGTGTATCA 53228174 53228196 53228276 53228298

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop KDM5C chrX 151 CCCGAACTTCCACCAGAATAGG 152 CCAGAGAAGCTAGACCTGAACCT 53230683 53230705 53230807 53230830 KDM5C chrX 153 CCATCTTGCAGATAAGCTCCTCA 154 GAAGCAGGAGGGTTGTAGAGAAG 53230839 53230862 53230981 53231004 KDM5C chrX 155 GCAAAGTTGTAGCCTTGGTTGA 156 CAGGAAAATCTCTATCTCAACAGCCAT 53231067 53231089 53231174 53231201 KDM5C chrX 157 GAGGTCAGGCTGGCTATCAAAT 158 CCTGCATGACCAAGGTGTGATT 53239653 53239675 53239789 53239811 KDM5C chrX 159 GGAGCCCACACTGACTTGATTC 160 GTACTGTGCCACATCAATGCAG 53239811 53239833 53239963 53239985 KDM5C chrX 161 ATGCCAGAGATATCTGCATTGATGT 162 GTTCCCTAGGCTAAAGAAAATGACTTAAGA 53239951 53239976 53240094 53240124 KDM5C chrX 163 AGATACTAAATGATTTGCCTAAGCTCACA 164 TAGCATTGAGGAAGATGTGACTGTTG 53240617 53240646 53240764 53240790 KDM5C chrX 165 GGGAATGCTTATTGAAGGGACAAGA 166 CCTAAGACCTTCCTGGAGAGCAA 53244917 53244942 53245055 53245078 KDM5C chrX 167 GTAGCCTCATGGTCATCTTGGT 168 CCATTTTTCTCTCTCCCAGATAAGGA 53245003 53245025 53245151 53245177 KDM5C chrX 169 TCCCTCCACCTCAAAGCTCTAA 170 TAATGAGGAGAAGGACAAGGAATACAAACC 53246280 53246302 53246406 53246436 KDM5C chrX 171 GCAAGGAGCCAATATTTTTGCCT 172 CTACAGGCCTACTCCCTCACATA 53247043 53247066 53247194 53247217 KDM5C chrX 173 ACCACCAGCTCCTAGTCTTCTC 174 CTTTTGGTGACTTCCGGTCTTACA 53249997 53250019 53250144 53250168 KDM5C chrX 175 CGATGGGCCTGATTTTCGC 176 GCGCCATGAGTCCTTAAGG 53253960 53253979 53254115 53254134 KDM6A chrX 177 CCAAGCAAGAATTCATGCACGT 178 AGACTCATAGTCTGTGTTCACTTTGAAC 44879794 44879816 44879938 44879966 KDM6A chrX 179 CACTGTTCATTGGGTTCAGGCTA 180 AAAAAGGAACAGTCCTATTGGATATAATCC 44949108 44949131 44949215 44949245

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop LRP12 chr8 181 ACCTCGGGTACTCTGAGTTGAG 182 AAGTTTGTTTTCCGTGGAGTCTGA 105503375 105503397 105503522 105503546 LRP12 chr8 183 TCCACGGAAAACAAACTTCTGTGA 184 TTCCTATGGCAGGCAGATCAAG 105503529 105503553 105503681 105503703 NCOA6 chr20 185 CTGGGAAGTTTGTTAGGATCCGAA 186 CAAGGAGAGCTTGAATGTGCCT 33329645 33329669 33329793 33329815 NCOA6 chr20 187 CCCAAAATGGCCTGCAGATATG 188 GGCCATGGGATGTCTTTCAATG 33337295 33337317 33337434 33337456 NCOA6 chr20 189 CTCCACTGAAAGGTGCATTGAAA 190 GGTGATCCTGCTACTACAGCAAATAA 33337420 33337443 33337568 33337594 NCOA6 chr20 191 GCAGGGCTCAAATGATCAAATAAGC 192 TTGGCTCAGAACCGAAGCCAAGA 33356193 33356218 33356343 33356366 NHS chrX 193 TCCAAGTAAATGAAAATTTGTTTGCCATTT 194 GGGATACCCGAGATGGTTTTCC 17742356 17742386 17742505 17742527 NHS chrX 195 ACAGCAACCCTCTTTAAAAGATGGAA 196 TCTCCTACTGTGTTCTGCTTATTATGAGTA 17745415 17745441 17745558 17745588 NHS chrX 197 ACCGTCATCCACTGCATGTTTT 198 CTTAACTTCTTCAGACTTGTTGATGGAC 17745537 17745559 17745657 17745685 RGAG1 chrX 199 GAATGATGTCATCCATGCCACAA 200 AGTGTGCACATGTCTCCAGAAG 109696331 109696354 109696483 109696505 RGAG1 chrX 201 GTCCACATTGCAAACCAGTGTT 202 CATGGGCATCGATCCAGAAACT 109696809 109696831 109696949 109696971 RGAG1 chrX 203 CCACATCATTTATGAGAGCCTCAGTT 204 TGTGGTGTGGACATTGTTCCAG 109696928 109696954 109697080 109697102

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop SCAF1 chr19 205 CCATGTGTCCCATTGGCTTCT 206 GGGTTCGTGAGCAAAGGAGG 50145305 50145326 50145424 50145444 SCAF1 chr19 207 CGCTTTAGCTCCGCCTCTC 208 ACTAGCGACCCAACTCCGC 50145405 50145424 50145555 50145574 SCAF1 chr19 209 GGGACCTCCACTCCAAACTCT 210 CTCACCAGGATAAAGGCAGAAGGA 50148240 50148261 50148372 50148396 SCAF1 chr19 211 ATGGTCCGCCAGACAGAGA 212 GTGCTTCAAGGGAGCCAAGAGT 50148342 50148361 50148484 50148506 SCAF1 chr19 213 GCACTTGAGTCTAGCTGTCAGT 214 CCGCCATACCTTTATCATTGGG 50148503 50148525 50148655 50148677 SH3TC1 chr4 215 CCACAGGCTTCACTCATCACTG 216 CAACGCTCACCTTCTTGGATGA 8217832 8217854 8217972 8217994 SH3TC1 chr4 217 CAGTGACCACCTCCATCCTTTT 218 GGCGGTGAAGAGTCTGTTTCC 8218658 8218680 8218804 8218825 SH3TC1 chr4 219 TCTGTCTGTCAAATCAAGGAATGGAAA 220 CCTGGCATCCTCCTCAGAAAAG 8224473 8224500 8224623 8224645 TBC1D8B chrX 221 ATGAGATACATCAGCATGCTAATAGAAGTG 222 CATATCAGTCATGTGTTCTGTCAGCT 106093160 106093190 106093308 106093334 TBC1D8B chrX 223 AGCAGACATGGTTTTTAAAATCTTCCAAA 224 CAGTCAATCTGATACTGTTCCAAATATGG 106108946 106108975 106109091 106109120 TBC1D8B chrX 225 CCATATTTGGAACAGTATCAGATTGACTG 226 TACCAATTGCAGAGGAGAATTCTTTGAA 106109092 106109121 106109238 106109266 TBC1D8B chrX 227 TGGAAGGAAACTACATAGCCCTACA 228 CAACAGCGATGCAAGAATCTGTT 106116919 106116944 106117070 106117093 TET2 chr4 229 TAACTGCAGTGGGCCTGAAAAT 230 AGTTCACCATGTGTGTGTTCCA 106155606 106155628 106155751 106155773 TET2 chr4 231 CCTGTGATGCTGATGATGCTGATA 232 AATTCTTCACCAGACGCTAGCTT 106155983 106156007 106156131 106156154 TET2 chr4 233 GGAAAAAGCACTCTGAATGGTGGA 234 GCCTTTCAGAAAGCATCGGAGAA 106156363 106156387 106156514 106156537

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop TET2 chr4 235 AACTGCCAGCAGTTGATGAGAA 236 TTACGTTTTAGATGGGATTCCGCTT 106156681 106156703 106156819 106156844 TET2 chr4 237 CACCAAGCGGAATCCCATCTAA 238 AGCTGTGTTGTTTTCTGGGTGTA 106156816 106156838 106156956 106156979 TET2 chr4 239 AAACACAACCATCCCAGAGTTCA 240 CCATGAAAACATTCTTCCACTTTAGTCTG 106157285 106157308 106157430 106157459 TET2 chr4 241 GGGTCACTGCATGTTTGGACTT 242 GCAGTGTGAGAACAGACTCAACAG 106190831 106190853 106190932 106190956 TET2 chr4 243 AAGTCTCTGACGTGGATGAGTTTG 244 GAAAGCTTTTCAGCTGCAGCTT 106193803 106193827 106193955 106193977 TET2 chr4 245 AGGTTTGGAAATAGCCAGAGTTTTACA 246 ATCTAGAGGTGGCTCCCATGAA 106196711 106196738 106196863 106196885 TEX13A chrX 247 TCGAGATATACATGCTTCGGTTCTATTTTG 248 CTCATCAGCAAAGACCTCCAGTA 104463605 104463635 104463756 104463779 TEX13A chrX 249 GGGTTCGTGGTTCCAGAGAAAT 250 CCTCCATGGAGACCACAGAGAA 104464028 104464050 104464156 104464178 TEX13A chrX 251 TCTCTCCAGCTTCTCTGTGGT 252 CTGCTGGAGGAAAAGGAGCAGA 104464147 104464168 104464296 104464318 ULK3 chr15 253 GCCTGAAGAGAGTGTCCCTTCT 254 CCAAGAAAAGTCTGAACAAGGCAT 75134560 75134582 75134700 75134724 WNK3 chrX 255 GCTGAAGAGAAGGAGGAGACTGA 256 CCTGGCTTCTTCAGTCAATAAGGTAAATAA 54276466 54276489 54276610 54276640 WNK3 chrX 257 GAAACTTGCTGGTAATGTCCTACTAGT 258 GGCAGGAGCTGCATCAGTTATA 54319571 54319598 54319722 54319744 WNK3 chrX 259 GTGCTGCTGTGGTTTTCTTTGTA 260 GGGATTCTCAGTGCAAGTCTATGG 54321002 54321025 54321135 54321159

Lineitem_Name Chr Sequence number Ion_AmpliSeq_Fwd_Primer* Sequence number Ion_AmpliSeq_Rev_Primer* Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop ARSF chrX 261 GTGCATGACGACAAGCCTAATATTG 262 ACGACTGACGAACGTATGACTG 2990128 2990153 2990234 2990256 CFP chrX 263 GCTGTAGCAGTGCCGGATAT 264 ACATGAAGTCCATCAGCTGTCAAG 47485743 47485763 47485843 47485867 CFP chrX 265 CCGGGATTTCTTGACAGCTGAT 266 TGATTCCCTGCTTTGGTCCAATC 47485835 47485857 47485940 47485963 CFP chrX 267 CCCACTCTGAGGACCTCTGTA 268 GAATGGGCAGTGCTCTGGAA 47487417 47487438 47487563 47487583 CFP chrX 269 GGCAAAGGCAGTGTTGAGAC 270 GTGTCCAGGCCCACCACAT 47488961 47488981 47489116 47489135 FAM47A chrX 271 ACTGGATCTCCGACGAGTGAT 272 GAGACTGGAGTGTCCCATCTAAG 34149619 34149640 34149760 34149783 JADE3 chrX 273 ACGCCATTGCCATGAAAATATGAAC 274 TCCACTCTCACTAACCTGATGCA 46887346 46887371 46887497 46887520 JADE3 chrX 275 CCATTCTAGGAGTGAAGCAAAGGA 276 GCCATTGGATTTGGCAAACTTG 46917837 46917861 46917989 46918011 ZNF449 chrX 277 GGAGCTGAACTATGGTGCTACT 278 CATTGAGTAATTGGTGTTTCTAACCCAAC 134483190 134483212 134483307 134483336 SCRN1 chr7 279 TTTTGCTGGTAATTTAGTAAGGTGGGAA 280 CCTGGAAGCCATGGAAGAAATCC 29963511 29963539 29963658 29963681 SCRN1 chr7 281 AGGGTATGAGAAGGAGAATCGTGA 282 GAACTCAGGAGTTACGCTCAGA 29980257 29980281 29980408 29980430

In order to confirm whether mutation detection is possible with the prepared primer set, the gene mutations identified in Example 2 and samples derived from wild-type kidney cancer cells were targeted, and each of the gene mutations was used as a sample, and corresponding to each sample. After amplification with a primer set, the chip on which the reaction was completed was scanned using a scanner and an application program, and analyzed using a quantitative analysis software. As a result, mutations in the genes of Examples 2 and 3 could be detected with the primer set prepared in Example 4. On the other hand, no mutation was detected in the sample derived from the control kidney cancer cells. As such, using the primer pairs of Tables 14 to 22, ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SHAF1 , TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1, so that the mutation of the gene selected from the gene group consisting of each can be detected, the total survival of kidney cancer patients with the mutation of the genes The duration and disease-free survival period can be predicted, and treatment strategies can be efficiently designed accordingly.

In the above, preferred embodiments of the present invention have been exemplarily described, but the scope of the present invention is not limited to the specific embodiments as described above, and those of ordinary skill in the relevant field have the scope described in the claims of the present invention. It will be possible to change appropriately within

<110> THE CATHOLIC UNIVERSITY OF KOREA INDUSTRYACADEMIC COOPERATION FOUNDATION <120> Gender-specific markers for diagnosing prognosis and determining treatment strategies of patient of clear cell renal cell carcinoma <130> 2019-DPA-3569D <150> KR 10-2016-0124785 <151> 2016-09-28 <160> 282 <170> KoPatentIn 3.0 <210> 1 <211> 686 <212> PRT <213> Homo sapiens <400> 1 Met Lys Pro Ser Trp Leu Gln Cys Arg Lys Val Thr Ser Ala Gly Gly 1 5 10 15 Leu Gly Gly Pro Leu Pro Gly Ser Ser Pro Ala Arg Gly Ala Gly Ala 20 25 30 Ala Leu Arg Ala Leu Val Val Pro Gly Pro Arg Gly Gly Leu Gly Gly 35 40 45 Arg Gly Cys Arg Ala Leu Ser Ser Gly Ser Gly Ser Glu Tyr Lys Thr 50 55 60 His Phe Ala Ala Ser Val Thr Asp Pro Glu Arg Phe Trp Gly Lys Ala 65 70 75 80 Ala Glu Gln Ile Ser Trp Tyr Lys Pro Trp Thr Lys Thr Leu Glu Asn 85 90 95 Lys His Ser Pro Ser Thr Arg Trp Phe Val Glu Gly Met Leu Asn Ile 100 105 110 Cys Tyr Asn Ala Val Asp Arg His Ile Glu Asn Gly Lys Gly Asp Lys 115 120 125 Ile Ala Ile Ile Tyr Asp Ser Pro Val Thr Asn Thr Lys Ala Thr Phe 130 135 140 Thr Tyr Lys Glu Val Leu Glu Gln Val Ser Lys Leu Ala Gly Val Leu 145 150 155 160 Val Lys His Gly Ile Lys Lys Gly Asp Thr Val Val Ile Tyr Met Pro 165 170 175 Met Ile Pro Gln Ala Met Tyr Thr Met Leu Ala Cys Ala Arg Ile Gly 180 185 190 Ala Ile His Ser Leu Ile Phe Gly Gly Phe Ala Ser Lys Glu Leu Ser 195 200 205 Ser Arg Ile Asp His Val Lys Pro Lys Val Val Val Thr Ala Ser Phe 210 215 220 Gly Ile Glu Pro Gly Arg Arg Val Glu Tyr Val Pro Leu Val Glu Glu 225 230 235 240 Ala Leu Lys Ile Gly Gln His Lys Pro Asp Lys Ile Leu Ile Tyr Asn 245 250 255 Arg Pro Asn Met Glu Ala Val Pro Leu Ala Pro Gly Arg Asp Leu Asp 260 265 270 Trp Asp Glu Glu Met Ala Lys Ala Gln Ser His Asp Cys Val Pro Val 275 280 285 Leu Ser Glu His Pro Leu Tyr Ile Leu Tyr Thr Ser Gly Thr Thr Gly 290 295 300 Leu Pro Lys Gly Val Ile Arg Pro Thr Gly Gly Tyr Ala Val Met Leu 305 310 315 320 His Trp Ser Met Ser Ser Ile Tyr Gly Leu Gln Pro Gly Glu Val Trp 325 330 335 Trp Ala Ala Ser Asp Leu Gly Trp Val Val Gly His Ser Tyr Ile Cys 340 345 350 Tyr Gly Pro Leu Leu His Gly Asn Thr Thr Val Leu Tyr Glu Gly Lys 355 360 365 Pro Val Gly Thr Pro Asp Ala Gly Ala Tyr Phe Arg Val Leu Ala Glu 370 375 380 His Gly Val Ala Ala Leu Phe Thr Ala Pro Thr Ala Ile Arg Ala Ile 385 390 395 400 Arg Gln Gln Asp Pro Gly Ala Ala Leu Gly Lys Gln Tyr Ser Leu Thr 405 410 415 Arg Phe Lys Thr Leu Phe Val Ala Gly Glu Arg Cys Asp Val Glu Thr 420 425 430 Leu Glu Trp Ser Lys Asn Val Phe Arg Val Pro Val Leu Asp His Trp 435 440 445 Trp Gln Thr Glu Thr Gly Ser Pro Ile Thr Ala Ser Cys Val Gly Leu 450 455 460 Gly Asn Ser Lys Thr Pro Pro Pro Gly Gln Ala Gly Lys Ser Val Pro 465 470 475 480 Gly Tyr Asn Val Met Ile Leu Asp Asp Asn Met Gln Lys Leu Lys Ala 485 490 495 Arg Cys Leu Gly Asn Ile Val Val Lys Leu Pro Leu Pro Pro Gly Ala 500 505 510 Phe Ser Gly Leu Trp Lys Asn Gln Glu Ala Phe Lys His Leu Tyr Phe 515 520 525 Glu Lys Phe Pro Gly Tyr Tyr Asp Thr Met Asp Ala Gly Tyr Met Asp 530 535 540 Glu Glu Gly Tyr Leu Tyr Val Met Ser Arg Val Asp Asp Val Ile Asn 545 550 555 560 Val Ala Gly His Arg Ile Ser Ala Gly Ala Ile Glu Glu Ser Ile Leu 565 570 575 Ser His Gly Thr Val Ala Asp Cys Ala Val Val Gly Lys Glu Asp Pro 580 585 590 Leu Lys Gly His Val Pro Leu Ala Leu Cys Val Leu Arg Lys Asp Ile 595 600 605 Asn Ala Thr Glu Glu Gln Val Leu Glu Glu Ile Val Lys His Val Arg 610 615 620 Gln Asn Ile Gly Pro Val Ala Ala Phe Arg Asn Ala Val Phe Val Lys 625 630 635 640 Gln Leu Pro Lys Thr Arg Ser Gly Lys Ile Pro Arg Ser Ala Leu Ser 645 650 655 Ala Ile Val Asn Gly Lys Pro Tyr Lys Ile Thr Ser Thr Ile Glu Asp 660 665 670 Pro Ser Ile Phe Gly His Val Glu Glu Met Leu Lys Gln Ala 675 680 685 <210> 2 <211> 722 <212> PRT <213> Homo sapiens <400> 2 Met Ala Val Asp Gly Thr Leu Val Tyr Ile Arg Val Thr Leu Leu Leu 1 5 10 15 Leu Trp Leu Gly Val Phe Leu Ser Ile Ser Gly Tyr Cys Gln Ala Gly 20 25 30 Pro Ser Gln His Phe Thr Ser Pro Glu Val Val Ile Pro Leu Lys Val 35 40 45 Ile Ser Arg Gly Arg Ser Ala Lys Ala Pro Gly Trp Leu Ser Tyr Ser 50 55 60 Leu Arg Phe Gly Gly Gln Lys His Val Val His Met Arg Val Lys Lys 65 70 75 80 Leu Leu Val Ser Arg His Leu Pro Val Phe Thr Tyr Thr Asp Asp Arg 85 90 95 Ala Leu Leu Glu Asp Gln Leu Phe Ile Pro Asp Asp Cys Tyr Tyr His 100 105 110 Gly Tyr Val Glu Ala Ala Pro Glu Ser Leu Val Val Phe Ser Ala Cys 115 120 125 Phe Gly Gly Phe Arg Gly Val Leu Lys Ile Ser Gly Leu Thr Tyr Glu 130 135 140 Ile Glu Pro Ile Arg His Ser Ala Thr Phe Glu His Leu Val Tyr Lys 145 150 155 160 Ile Asn Ser Asn Glu Thr Gln Phe Pro Ala Met Arg Cys Gly Leu Thr 165 170 175 Glu Lys Glu Val Ala Arg Gln Gln Leu Glu Phe Glu Glu Ala Glu Asn 180 185 190 Ser Ala Leu Glu Pro Lys Ser Ala Gly Asp Trp Trp Thr His Ala Trp 195 200 205 Phe Leu Glu Leu Val Val Val Val Asn His Asp Phe Phe Ile Tyr Ser 210 215 220 Gln Ser Asn Ile Ser Lys Val Gln Glu Asp Val Phe Leu Val Val Asn 225 230 235 240 Ile Val Asp Ser Met Tyr Lys Gln Leu Gly Thr Tyr Ile Ile Leu Ile 245 250 255 Gly Ile Glu Ile Trp Asn Gln Gly Asn Val Phe Pro Met Thr Ser Ile 260 265 270 Glu Gln Val Leu Asn Asp Phe Ser Gln Trp Lys Gln Ile Ser Leu Ser 275 280 285 Gln Leu Gln His Asp Ala Ala His Met Phe Ile Lys Asn Ser Leu Ile 290 295 300 Ser Ile Leu Gly Leu Ala Tyr Val Ala Gly Ile Cys Arg Pro Pro Ile 305 310 315 320 Asp Cys Gly Val Asp Asn Phe Gln Gly Asp Thr Trp Ser Leu Phe Ala 325 330 335 Asn Thr Val Ala His Glu Leu Gly His Thr Leu Gly Met Gln His Asp 340 345 350 Glu Glu Phe Cys Phe Cys Gly Glu Arg Gly Cys Ile Met Asn Thr Phe 355 360 365 Arg Val Pro Ala Glu Lys Phe Thr Asn Cys Ser Tyr Ala Asp Phe Met 370 375 380 Lys Thr Thr Leu Asn Gln Gly Ser Cys Leu His Asn Pro Pro Arg Leu 385 390 395 400 Gly Glu Ile Phe Met Leu Lys Arg Cys Gly Asn Gly Val Val Glu Arg 405 410 415 Glu Glu Gln Cys Asp Cys Gly Ser Val Gln Gln Cys Glu Gln Asp Ala 420 425 430 Cys Cys Leu Leu Asn Cys Thr Leu Arg Pro Gly Ala Ala Cys Ala Phe 435 440 445 Gly Leu Cys Cys Lys Asp Cys Lys Phe Met Pro Ser Gly Glu Leu Cys 450 455 460 Arg Gln Glu Val Asn Glu Cys Asp Leu Pro Glu Trp Cys Asn Gly Thr 465 470 475 480 Ser His Gln Cys Pro Glu Asp Arg Tyr Val Gln Asp Gly Ile Pro Cys 485 490 495 Ser Asp Ser Ala Tyr Cys Tyr Gln Lys Arg Cys Asn Asn His Asp Gln 500 505 510 His Cys Arg Glu Ile Phe Gly Lys Asp Ala Lys Ser Ala Ser Gln Asn 515 520 525 Cys Tyr Lys Glu Ile Asn Ser Gln Gly Asn Arg Phe Gly His Cys Gly 530 535 540 Ile Asn Gly Thr Thr Tyr Leu Lys Cys His Ile Ser Asp Val Phe Cys 545 550 555 560 Gly Arg Val Gln Cys Glu Asn Val Arg Asp Ile Pro Leu Leu Gln Asp 565 570 575 His Phe Thr Leu Gln His Thr His Ile Asn Gly Val Thr Cys Trp Gly 580 585 590 Ile Asp Tyr His Leu Arg Met Asn Ile Ser Asp Ile Gly Glu Val Lys 595 600 605 Asp Gly Thr Val Cys Gly Pro Gly Lys Ile Cys Ile His Lys Lys Cys 610 615 620 Val Ser Leu Ser Val Leu Ser His Val Cys Leu Pro Glu Thr Cys Asn 625 630 635 640 Met Lys Gly Ile Cys Asn Asn Lys His His Cys His Cys Gly Tyr Gly 645 650 655 Trp Ser Pro Pro Tyr Cys Gln His Arg Gly Tyr Gly Gly Ser Ile Asp 660 665 670 Ser Gly Pro Ala Ser Ala Lys Arg Gly Val Phe Leu Pro Leu Ile Val 675 680 685 Ile Pro Ser Leu Ser Val Leu Thr Phe Leu Phe Thr Val Gly Leu Leu 690 695 700 Met Tyr Leu Arg Gln Cys Ser Gly Pro Lys Glu Thr Lys Ala His Ser 705 710 715 720 Ser Gly <210> 3 <211> 1311 <212> PRT <213> Homo sapiens <400> 3 Met Asp Leu Phe Asp Phe Phe Arg Asp Trp Asp Leu Glu Gln Gln Cys 1 5 10 15 His Tyr Glu Gln Asp Arg Ser Ala Leu Lys Lys Arg Glu Trp Glu Arg 20 25 30 Arg Asn Gln Glu Val Gln Gln Glu Asp Asp Leu Phe Ser Ser Gly Phe 35 40 45 Asp Leu Phe Gly Glu Pro Tyr Lys Val Ala Glu Tyr Thr Asn Lys Gly 50 55 60 Asp Ala Leu Ala Asn Arg Val Gln Asn Thr Leu Gly Asn Tyr Asp Glu 65 70 75 80 Met Lys Asn Leu Leu Thr Asn His Ser Asn Gln Asn His Leu Val Gly 85 90 95 Ile Pro Lys Asn Ser Val Pro Gln Asn Pro Asn Asn Lys Asn Glu Pro 100 105 110 Ser Phe Phe Pro Glu Gln Lys Asn Arg Ile Ile Pro Pro His Gln Asp 115 120 125 Asn Thr His Pro Ser Ala Pro Met Pro Pro Pro Ser Val Val Ile Leu 130 135 140 Asn Ser Thr Leu Ile His Ser Asn Arg Lys Ser Lys Pro Glu Trp Ser 145 150 155 160 Arg Asp Ser His Asn Pro Ser Thr Val Leu Ala Ser Gln Ala Ser Gly 165 170 175 Gln Pro Asn Lys Met Gln Thr Leu Thr Gln Asp Gln Ser Gln Ala Lys 180 185 190 Leu Glu Asp Phe Phe Val Tyr Pro Ala Glu Gln Pro Gln Ile Gly Glu 195 200 205 Val Glu Glu Ser Asn Pro Ser Ala Lys Glu Asp Ser Asn Pro Asn Ser 210 215 220 Ser Gly Glu Asp Ala Phe Lys Glu Ile Phe Gln Ser Asn Ser Pro Glu 225 230 235 240 Glu Ser Glu Phe Ala Val Gln Ala Pro Gly Ser Pro Leu Val Ala Ser 245 250 255 Ser Leu Leu Ala Pro Ser Ser Gly Leu Ser Val Gln Asn Phe Pro Pro 260 265 270 Gly Leu Tyr Cys Lys Thr Ser Met Gly Gln Gln Lys Pro Thr Ala Tyr 275 280 285 Val Arg Pro Met Asp Gly Gln Asp Gln Ala Pro Asp Ile Ser Pro Thr 290 295 300 Leu Lys Pro Ser Ile Glu Phe Glu Asn Ser Phe Gly Asn Leu Ser Phe 305 310 315 320 Gly Thr Leu Leu Asp Gly Lys Pro Ser Ala Ala Ser Ser Lys Thr Lys 325 330 335 Leu Pro Lys Phe Thr Ile Leu Gln Thr Ser Glu Val Ser Leu Pro Ser 340 345 350 Asp Pro Ser Cys Val Glu Glu Ile Leu Arg Glu Met Thr His Ser Trp 355 360 365 Pro Thr Pro Leu Thr Ser Met His Thr Ala Gly His Ser Glu Gln Ser 370 375 380 Thr Phe Ser Ile Pro Gly Gln Glu Ser Gln His Leu Thr Pro Gly Phe 385 390 395 400 Thr Leu Gln Lys Trp Asn Asp Pro Thr Thr Arg Ala Ser Thr Lys Ser 405 410 415 Val Ser Phe Lys Ser Met Leu Glu Asp Asp Leu Lys Leu Ser Ser Asp 420 425 430 Glu Asp Asp Leu Glu Pro Val Lys Thr Leu Thr Thr Gln Cys Thr Ala 435 440 445 Thr Glu Leu Tyr Gln Ala Val Glu Lys Ala Lys Pro Arg Asn Asn Pro 450 455 460 Val Asn Pro Pro Leu Ala Thr Pro Gln Pro Pro Pro Ala Val Gln Ala 465 470 475 480 Ser Gly Gly Ser Gly Ser Ser Ser Glu Ser Glu Ser Ser Ser Glu Ser 485 490 495 Asp Ser Asp Thr Glu Ser Ser Thr Thr Asp Ser Glu Ser Asn Glu Ala 500 505 510 Pro Arg Val Ala Thr Pro Glu Pro Glu Pro Pro Ser Thr Asn Lys Trp 515 520 525 Gln Leu Asp Lys Trp Leu Asn Lys Val Thr Ser Gln Asn Lys Ser Phe 530 535 540 Ile Cys Gly Gln Asn Glu Thr Pro Met Glu Thr Ile Ser Leu Pro Pro 545 550 555 560 Pro Ile Ile Gln Pro Met Glu Val Gln Met Lys Val Lys Thr Asn Ala 565 570 575 Ser Gln Val Pro Ala Glu Pro Lys Glu Arg Pro Leu Leu Ser Leu Ile 580 585 590 Arg Glu Lys Ala Arg Pro Arg Pro Thr Gln Lys Ile Pro Glu Thr Lys 595 600 605 Ala Leu Lys His Lys Leu Ser Thr Thr Ser Glu Thr Val Ser Gln Arg 610 615 620 Thr Ile Gly Lys Lys Gln Pro Lys Lys Val Glu Lys Asn Thr Ser Thr 625 630 635 640 Asp Glu Phe Thr Trp Pro Lys Pro Asn Ile Thr Ser Ser Thr Pro Lys 645 650 655 Glu Lys Glu Ser Val Glu Leu His Asp Pro Pro Arg Gly Arg Asn Lys 660 665 670 Ala Thr Ala His Lys Pro Ala Pro Arg Lys Glu Pro Arg Pro Asn Ile 675 680 685 Pro Leu Ala Pro Glu Lys Lys Lys Tyr Arg Gly Pro Gly Lys Ile Val 690 695 700 Pro Lys Ser Arg Glu Phe Ile Glu Thr Asp Ser Ser Thr Ser Asp Ser 705 710 715 720 Asn Thr Asp Gln Glu Glu Thr Leu Gln Ile Lys Val Leu Pro Pro Cys 725 730 735 Ile Ile Ser Gly Gly Asn Thr Ala Lys Ser Lys Glu Ile Cys Gly Ala 740 745 750 Ser Leu Thr Leu Ser Thr Leu Met Ser Ser Ser Gly Ser Asn Asn Asn 755 760 765 Leu Ser Ile Ser Asn Glu Glu Pro Thr Phe Ser Pro Ile Pro Val Met 770 775 780 Gln Thr Glu Ile Leu Ser Pro Leu Arg Asp His Glu Asn Leu Lys Asn 785 790 795 800 Leu Trp Val Lys Ile Asp Leu Asp Leu Leu Ser Arg Val Pro Gly His 805 810 815 Ser Ser Leu His Ala Ala Pro Ala Lys Pro Asp His Lys Glu Thr Ala 820 825 830 Thr Lys Pro Lys Arg Gln Thr Ala Val Thr Ala Val Glu Lys Pro Ala 835 840 845 Pro Lys Gly Lys Arg Lys His Lys Pro Ile Glu Val Ala Glu Lys Ile 850 855 860 Pro Glu Lys Lys Gln Arg Leu Glu Glu Ala Thr Thr Ile Cys Leu Leu 865 870 875 880 Pro Pro Cys Ile Ser Pro Ala Pro Pro His Lys Pro Pro Asn Thr Arg 885 890 895 Glu Asn Asn Ser Ser Arg Arg Ala Asn Arg Arg Lys Glu Glu Lys Leu 900 905 910 Phe Pro Pro Pro Leu Ser Pro Leu Pro Glu Asp Pro Pro Arg Arg Arg 915 920 925 Asn Val Ser Gly Asn Asn Gly Pro Phe Gly Gln Asp Lys Asn Ile Ala 930 935 940 Met Thr Gly Gln Ile Thr Ser Thr Lys Pro Lys Arg Thr Glu Gly Lys 945 950 955 960 Phe Cys Ala Thr Phe Lys Gly Ile Ser Val Asn Glu Gly Asp Thr Pro 965 970 975 Lys Lys Ala Ser Ser Ala Thr Ile Thr Val Thr Asn Thr Ala Ile Ala 980 985 990 Thr Ala Thr Val Thr Ala Thr Ala Ile Val Thr Thr Thr Val Thr Ala 995 1000 1005 Thr Ala Thr Ala Thr Ala Thr Thr Thr Thr Thr Thr Thr Thr Ile Ser 1010 1015 1020 Thr Ile Thr Ser Thr Ile Thr Thr Gly Leu Met Asp Ser Ser His Leu 1025 1030 1035 1040 Glu Met Thr Ser Trp Ala Ala Leu Pro Leu Leu Ser Ser Ser Ser Thr 1045 1050 1055 Asn Val Arg Arg Pro Lys Leu Thr Phe Asp Asp Ser Val His Asn Ala 1060 1065 1070 Asp Tyr Tyr Met Gln Glu Ala Lys Lys Leu Lys His Lys Ala Asp Ala 1075 1080 1085 Leu Phe Glu Lys Phe Gly Lys Ala Val Asn Tyr Ala Asp Ala Ala Leu 1090 1095 1100 Ser Phe Thr Glu Cys Gly Asn Ala Met Glu Arg Asp Pro Leu Glu Ala 1105 1110 1115 1120 Lys Ser Pro Tyr Thr Met Tyr Ser Glu Thr Val Glu Leu Leu Arg Tyr 1125 1130 1135 Ala Met Arg Leu Lys Asn Phe Ala Ser Pro Leu Ala Ser Asp Gly Asp 1140 1145 1150 Lys Lys Leu Ala Val Leu Cys Tyr Arg Cys Leu Ser Leu Leu Tyr Leu 1155 1160 1165 Arg Met Phe Lys Leu Lys Lys Asp His Ala Met Lys Tyr Ser Arg Ser 1170 1175 1180 Leu Met Glu Tyr Phe Lys Gln Asn Ala Ser Lys Val Ala Gln Ile Pro 1185 1190 1195 1200 Ser Pro Trp Val Ser Asn Gly Lys Asn Thr Pro Ser Pro Val Ser Leu 1205 1210 1215 Asn Asn Val Ser Pro Ile Asn Ala Met Gly Asn Cys Asn Asn Gly Pro 1220 1225 1230 Val Thr Ile Pro Gln Arg Ile His His Met Ala Ala Ser His Val Asn 1235 1240 1245 Ile Thr Ser Asn Val Leu Arg Gly Tyr Glu His Trp Asp Met Ala Asp 1250 1255 1260 Lys Leu Thr Arg Glu Asn Lys Glu Phe Phe Gly Asp Leu Asp Thr Leu 1265 1270 1275 1280 Met Gly Pro Leu Thr Gln His Ser Ser Met Thr Asn Leu Val Arg Tyr 1285 1290 1295 Val Arg Gln Gly Leu Cys Trp Leu Arg Ile Asp Ala His Leu Leu 1300 1305 1310 <210> 4 <211> 1137 <212> PRT <213> Homo sapiens <400> 4 Met Lys Cys Val Phe Val Thr Val Gly Thr Thr Ser Phe Asp Asp Leu 1 5 10 15 Ile Ala Cys Val Ser Ala Pro Asp Ser Leu Gln Lys Ile Glu Ser Leu 20 25 30 Gly Tyr Asn Arg Leu Ile Leu Gln Ile Gly Arg Gly Thr Val Val Pro 35 40 45 Glu Pro Phe Ser Thr Glu Ser Phe Thr Leu Asp Val Tyr Arg Tyr Lys 50 55 60 Asp Ser Leu Lys Glu Asp Ile Gln Lys Ala Asp Leu Val Ile Ser His 65 70 75 80 Ala Gly Ala Gly Ser Cys Leu Glu Thr Leu Glu Lys Gly Lys Pro Leu 85 90 95 Val Val Val Ile Asn Glu Lys Leu Met Asn Asn His Gln Leu Glu Leu 100 105 110 Ala Lys Gln Leu His Lys Glu Gly His Leu Phe Tyr Cys Thr Cys Arg 115 120 125 Val Leu Thr Cys Pro Gly Gln Ala Lys Ser Ile Ala Ser Ala Pro Gly 130 135 140 Lys Cys Gln Asp Ser Ala Ala Leu Thr Ser Thr Ala Phe Ser Gly Leu 145 150 155 160 Asp Phe Gly Leu Leu Ser Gly Tyr Leu His Lys Gln Ala Leu Val Thr 165 170 175 Ala Thr His Pro Thr Cys Thr Leu Leu Phe Pro Ser Cys His Ala Phe 180 185 190 Phe Pro Leu Pro Leu Thr Pro Thr Leu Tyr Lys Met His Lys Gly Trp 195 200 205 Lys Asn Tyr Cys Ser Gln Lys Ser Leu Asn Glu Ala Ser Met Asp Glu 210 215 220 Tyr Leu Gly Ser Leu Gly Leu Phe Arg Lys Leu Thr Ala Lys Asp Ala 225 230 235 240 Ser Cys Leu Phe Arg Ala Ile Ser Glu Gln Leu Phe Cys Ser Gln Val 245 250 255 His His Leu Glu Ile Arg Lys Ala Cys Val Ser Tyr Met Arg Glu Asn 260 265 270 Gln Gln Thr Phe Glu Ser Tyr Val Glu Gly Ser Phe Glu Lys Tyr Leu 275 280 285 Glu Arg Leu Gly Asp Pro Lys Glu Ser Ala Gly Gln Leu Glu Ile Arg 290 295 300 Ala Leu Ser Leu Ile Tyr Asn Arg Asp Phe Ile Leu Tyr Arg Phe Pro 305 310 315 320 Gly Lys Pro Pro Thr Tyr Val Thr Asp Asn Gly Tyr Glu Asp Lys Ile 325 330 335 Leu Leu Cys Tyr Ser Ser Ser Gly His Tyr Asp Ser Val Tyr Ser Lys 340 345 350 Gln Phe Gln Ser Ser Ala Ala Val Cys Gln Ala Val Leu Tyr Glu Ile 355 360 365 Leu Tyr Lys Asp Val Phe Val Val Asp Glu Glu Glu Leu Lys Thr Ala 370 375 380 Ile Lys Leu Phe Arg Ser Gly Ser Lys Lys Asn Arg Asn Asn Ala Val 385 390 395 400 Thr Gly Ser Glu Asp Ala His Thr Asp Tyr Lys Ser Ser Asn Gln Asn 405 410 415 Arg Met Glu Glu Trp Gly Ala Cys Tyr Asn Ala Glu Asn Ile Pro Glu 420 425 430 Gly Tyr Asn Lys Gly Thr Glu Glu Thr Lys Ser Pro Glu Asn Pro Ser 435 440 445 Lys Met Pro Phe Pro Tyr Lys Val Leu Lys Ala Leu Asp Pro Glu Ile 450 455 460 Tyr Arg Asn Val Glu Phe Asp Val Trp Leu Asp Ser Arg Lys Glu Leu 465 470 475 480 Gln Lys Ser Asp Tyr Met Glu Tyr Ala Gly Arg Gln Tyr Tyr Leu Gly 485 490 495 Asp Lys Cys Gln Val Cys Leu Glu Ser Glu Gly Arg Tyr Tyr Asn Ala 500 505 510 His Ile Gln Glu Val Gly Asn Glu Asn Asn Ser Val Thr Val Phe Ile 515 520 525 Glu Glu Leu Ala Glu Lys His Val Val Pro Leu Ala Asn Leu Lys Pro 530 535 540 Val Thr Gln Val Met Ser Val Pro Ala Trp Asn Ala Met Pro Ser Arg 545 550 555 560 Lys Gly Arg Gly Tyr Gln Lys Met Pro Gly Gly Tyr Val Pro Glu Ile 565 570 575 Val Ile Ser Glu Met Asp Ile Lys Gln Gln Lys Lys Met Phe Lys Lys 580 585 590 Ile Arg Gly Lys Glu Val Tyr Met Thr Met Ala Tyr Gly Lys Gly Asp 595 600 605 Pro Leu Leu Pro Pro Arg Leu Gln His Ser Met His Tyr Gly His Asp 610 615 620 Pro Pro Met His Tyr Ser Gln Thr Ala Gly Asn Val Met Ser Asn Glu 625 630 635 640 His Phe His Pro Gln His Pro Ser Pro Arg Gln Gly Arg Gly Tyr Gly 645 650 655 Met Pro Arg Asn Ser Ser Arg Phe Ile Asn Arg His Asn Met Pro Gly 660 665 670 Pro Lys Val Asp Phe Tyr Pro Gly Pro Gly Lys Arg Cys Cys Gln Ser 675 680 685 Tyr Asp Asn Phe Ser Tyr Arg Ser Arg Ser Phe Arg Arg Ser His Arg 690 695 700 Gln Met Ser Cys Val Asn Lys Glu Ser Gln Tyr Gly Phe Thr Pro Gly 705 710 715 720 Asn Gly Gln Met Pro Arg Gly Leu Glu Glu Thr Ile Thr Phe Tyr Glu 725 730 735 Val Glu Glu Gly Asp Glu Thr Ala Tyr Pro Thr Leu Pro Asn His Gly 740 745 750 Gly Pro Ser Thr Met Val Pro Ala Thr Ser Gly Tyr Cys Val Gly Arg 755 760 765 Arg Gly His Ser Ser Gly Lys Gln Thr Leu Asn Leu Glu Glu Gly Asn 770 775 780 Gly Gln Ser Glu Asn Gly Arg Tyr His Glu Glu Tyr Leu Tyr Arg Ala 785 790 795 800 Glu Pro Asp Tyr Glu Thr Ser Gly Val Tyr Ser Thr Thr Ala Ser Thr 805 810 815 Ala Asn Leu Ser Leu Gln Asp Arg Lys Ser Cys Ser Met Ser Pro Gln 820 825 830 Asp Thr Val Thr Ser Tyr Asn Tyr Pro Gln Lys Met Met Gly Asn Ile 835 840 845 Ala Ala Val Ala Ala Ser Cys Ala Asn Asn Val Pro Ala Pro Val Leu 850 855 860 Ser Asn Gly Ala Ala Ala Asn Gln Ala Ile Ser Thr Thr Ser Val Ser 865 870 875 880 Ser Gln Asn Ala Ile Gln Pro Leu Phe Val Ser Pro Pro Thr His Gly 885 890 895 Arg Pro Val Ile Ala Ser Pro Ser Tyr Pro Cys His Ser Ala Ile Pro 900 905 910 His Ala Gly Ala Ser Leu Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro 915 920 925 Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro 930 935 940 Pro Ala Leu Asp Val Gly Glu Thr Ser Asn Leu Gln Pro Pro Pro Pro 945 950 955 960 Leu Pro Pro Pro Pro Tyr Ser Cys Asp Pro Ser Gly Ser Asp Leu Pro 965 970 975 Gln Asp Thr Lys Val Leu Gln Tyr Tyr Phe Asn Leu Gly Leu Gln Cys 980 985 990 Tyr Tyr His Ser Tyr Trp His Ser Met Val Tyr Val Pro Gln Met Gln 995 1000 1005 Gln Gln Leu His Val Glu Asn Tyr Pro Val Tyr Thr Glu Pro Pro Leu 1010 1015 1020 Val Asp Gln Thr Val Pro Gln Cys Tyr Ser Glu Val Arg Arg Glu Asp 1025 1030 1035 1040 Gly Ile Gln Ala Glu Ala Ser Ala Asn Asp Thr Phe Pro Asn Ala Asp 1045 1050 1055 Ser Ser Ser Val Pro His Gly Ala Val Tyr Tyr Pro Val Met Ser Asp 1060 1065 1070 Pro Tyr Gly Gln Pro Pro Leu Pro Gly Phe Asp Ser Cys Leu Pro Val 1075 1080 1085 Val Pro Asp Tyr Ser Cys Val Pro Pro Trp His Pro Val Gly Thr Ala 1090 1095 1100 Tyr Gly Gly Ser Ser Gln Ile His Gly Ala Ile Asn Pro Gly Pro Ile 1105 1110 1115 1120 Gly Cys Ile Ala Pro Ser Pro Pro Ala Ser His Tyr Val Pro Gln Gly 1125 1130 1135 Met <210> 5 <211> 729 <212> PRT <213> Homo sapiens <400> 5 Met Asn Lys Gly Trp Leu Glu Leu Glu Ser Asp Pro Gly Leu Phe Thr 1 5 10 15 Leu Leu Val Glu Asp Phe Gly Val Lys Gly Val Gln Val Glu Glu Ile 20 25 30 Tyr Asp Leu Gln Ser Lys Cys Gln Gly Pro Val Tyr Gly Phe Ile Phe 35 40 45 Leu Phe Lys Trp Ile Glu Glu Arg Arg Ser Arg Arg Lys Val Ser Thr 50 55 60 Leu Val Asp Asp Thr Ser Val Ile Asp Asp Asp Ile Val Asn Asn Met 65 70 75 80 Phe Phe Ala His Gln Leu Ile Pro Asn Ser Cys Ala Thr His Ala Leu 85 90 95 Leu Ser Val Leu Leu Asn Cys Ser Ser Val Asp Leu Gly Pro Thr Leu 100 105 110 Ser Arg Met Lys Asp Phe Thr Lys Gly Phe Ser Pro Glu Ser Lys Gly 115 120 125 Tyr Ala Ile Gly Asn Ala Pro Glu Leu Ala Lys Ala His Asn Ser His 130 135 140 Ala Arg Pro Glu Pro Arg His Leu Pro Glu Lys Gln Asn Gly Leu Ser 145 150 155 160 Ala Val Arg Thr Met Glu Ala Phe His Phe Val Ser Tyr Val Pro Ile 165 170 175 Thr Gly Arg Leu Phe Glu Leu Asp Gly Leu Lys Val Tyr Pro Ile Asp 180 185 190 His Gly Pro Trp Gly Glu Asp Glu Glu Trp Thr Asp Lys Ala Arg Arg 195 200 205 Val Ile Met Glu Arg Ile Gly Leu Ala Thr Ala Gly Glu Pro Tyr His 210 215 220 Asp Ile Arg Phe Asn Leu Met Ala Val Val Pro Asp Arg Arg Ile Lys 225 230 235 240 Tyr Glu Ala Arg Leu His Val Leu Lys Val Asn Arg Gln Thr Val Leu 245 250 255 Glu Ala Leu Gln Gln Leu Ile Arg Val Thr Gln Pro Glu Leu Ile Gln 260 265 270 Thr His Lys Ser Gln Glu Ser Gln Leu Pro Glu Glu Ser Lys Ser Ala 275 280 285 Ser Asn Lys Ser Pro Leu Val Leu Glu Ala Asn Arg Ala Pro Ala Ala 290 295 300 Ser Glu Gly Asn His Thr Asp Gly Ala Glu Glu Ala Ala Gly Ser Cys 305 310 315 320 Ala Gln Ala Pro Ser His Ser Pro Pro Asn Lys Pro Lys Leu Val Val 325 330 335 Lys Pro Pro Gly Ser Ser Leu Asn Gly Val His Pro Asn Pro Thr Pro 340 345 350 Ile Val Gln Arg Leu Pro Ala Phe Leu Asp Asn His Asn Tyr Ala Lys 355 360 365 Ser Pro Met Gln Glu Glu Glu Asp Leu Ala Ala Gly Val Gly Arg Ser 370 375 380 Arg Val Pro Val Arg Pro Pro Gln Gln Tyr Ser Asp Asp Glu Asp Asp 385 390 395 400 Tyr Glu Asp Asp Glu Glu Asp Asp Val Gln Asn Thr Asn Ser Ala Leu 405 410 415 Arg Tyr Lys Gly Lys Gly Thr Gly Lys Pro Gly Ala Leu Ser Gly Ser 420 425 430 Ala Asp Gly Gln Leu Ser Val Leu Gln Pro Asn Thr Ile Asn Val Leu 435 440 445 Ala Glu Lys Leu Lys Glu Ser Gln Lys Asp Leu Ser Ile Pro Leu Ser 450 455 460 Ile Lys Thr Ser Ser Gly Ala Gly Ser Pro Ala Val Ala Val Pro Thr 465 470 475 480 His Ser Gln Pro Ser Pro Thr Pro Ser Asn Glu Ser Thr Asp Thr Ala 485 490 495 Ser Glu Ile Gly Ser Ala Phe Asn Ser Pro Leu Arg Ser Pro Ile Arg 500 505 510 Ser Ala Asn Pro Thr Arg Pro Ser Ser Pro Val Thr Ser His Ile Ser 515 520 525 Lys Val Leu Phe Gly Glu Asp Asp Ser Leu Leu Arg Val Asp Cys Ile 530 535 540 Arg Tyr Asn Arg Ala Val Arg Asp Leu Gly Pro Val Ile Ser Thr Gly 545 550 555 560 Leu Leu His Leu Ala Glu Asp Gly Val Leu Ser Pro Leu Ala Leu Thr 565 570 575 Glu Gly Gly Lys Gly Ser Ser Pro Ser Ile Arg Pro Ile Gln Gly Ser 580 585 590 Gln Gly Ser Ser Ser Pro Val Glu Lys Glu Val Val Glu Ala Thr Asp 595 600 605 Ser Arg Glu Lys Thr Gly Met Val Arg Pro Gly Glu Pro Leu Ser Gly 610 615 620 Glu Lys Tyr Ser Pro Lys Glu Leu Leu Ala Leu Leu Lys Cys Val Glu 625 630 635 640 Ala Glu Ile Ala Asn Tyr Glu Ala Cys Leu Lys Glu Glu Val Glu Lys 645 650 655 Arg Lys Lys Phe Lys Ile Asp Asp Gln Arg Arg Thr His Asn Tyr Asp 660 665 670 Glu Phe Ile Cys Thr Phe Ile Ser Met Leu Ala Gln Glu Gly Met Leu 675 680 685 Ala Asn Leu Val Glu Gln Asn Ile Ser Val Arg Arg Arg Gln Gly Val 690 695 700 Ser Ile Gly Arg Leu His Lys Gln Arg Lys Pro Asp Arg Arg Lys Arg 705 710 715 720 Ser Arg Pro Tyr Lys Ala Lys Arg Gln 725 <210> 6 <211> 1802 <212> PRT <213> Homo sapiens <400> 6 Met Ala Ala Ala Pro Thr Gln Ile Glu Ala Glu Leu Tyr Tyr Leu Ile 1 5 10 15 Ala Arg Phe Leu Gln Ser Gly Pro Cys Asn Lys Ser Ala Gln Val Leu 20 25 30 Val Gln Glu Leu Glu Glu His Gln Leu Ile Pro Arg Arg Leu Asp Trp 35 40 45 Glu Gly Lys Glu His Arg Arg Ser Phe Glu Asp Leu Val Ala Ala Asn 50 55 60 Ala His Ile Pro Pro Asp Tyr Leu Leu Lys Ile Cys Glu Arg Ile Gly 65 70 75 80 Pro Leu Leu Asp Lys Glu Ile Pro Gln Ser Val Pro Gly Val Gln Thr 85 90 95 Leu Leu Gly Val Gly Arg Gln Ser Leu Leu Arg Asp Ala Lys Asp Cys 100 105 110 Lys Ser Thr Leu Trp Asn Gly Ser Ala Phe Ala Ala Leu His Arg Gly 115 120 125 Arg Pro Pro Glu Leu Pro Val Asn Tyr Val Lys Pro Pro Asn Val Val 130 135 140 Asn Ile Thr Ser Ala Arg Gln Leu Thr Gly Cys Ser Arg Phe Gly His 145 150 155 160 Ile Phe Pro Ser Ser Ala Tyr Gln His Ile Lys Met His Lys Arg Ile 165 170 175 Leu Gly His Leu Ser Ser Val Tyr Cys Val Ala Phe Asp Arg Ser Gly 180 185 190 Arg Arg Ile Phe Thr Gly Ser Asp Asp Cys Leu Val Lys Ile Trp Ala 195 200 205 Thr Asp Asp Gly Arg Leu Leu Ala Thr Leu Arg Gly His Ser Ala Glu 210 215 220 Ile Ser Asp Met Ala Val Asn Tyr Glu Asn Thr Leu Ile Ala Ala Gly 225 230 235 240 Ser Cys Asp Lys Val Val Arg Val Trp Cys Leu Arg Thr Cys Ala Pro 245 250 255 Val Ala Val Leu Gln Gly His Ser Ala Ser Ile Thr Ser Ile Gln Phe 260 265 270 Cys Pro Ser Thr Lys Gly Thr Asn Arg Tyr Leu Thr Ser Thr Gly Ala 275 280 285 Asp Gly Thr Ile Cys Phe Trp Gln Trp His Val Lys Thr Met Lys Phe 290 295 300 Arg Asp Arg Pro Val Lys Phe Thr Glu Arg Ser Arg Pro Gly Val Gln 305 310 315 320 Ile Ser Cys Ser Ser Phe Ser Ser Gly Gly Met Phe Ile Thr Thr Gly 325 330 335 Ser Thr Asp His Val Ile Arg Ile Tyr Tyr Leu Gly Ser Glu Val Pro 340 345 350 Glu Lys Ile Ala Glu Leu Glu Ser His Thr Asp Lys Val Val Ala Val 355 360 365 Gln Phe Cys Asn Asn Gly Asp Ser Leu Arg Phe Val Ser Gly Ser Arg 370 375 380 Asp Gly Thr Ala Arg Ile Trp Gln Tyr Gln Gln Gln Glu Trp Lys Ser 385 390 395 400 Ile Val Leu Asp Met Ala Thr Lys Met Thr Gly Asn Asn Leu Pro Ser 405 410 415 Gly Glu Asp Lys Ile Thr Lys Leu Lys Val Thr Met Val Ala Trp Asp 420 425 430 Arg Tyr Asp Thr Thr Val Ile Thr Ala Val Asn Asn Phe Leu Leu Lys 435 440 445 Val Trp Asn Ser Ile Thr Gly Gln Leu Leu His Thr Leu Ser Gly His 450 455 460 Asp Asp Glu Val Phe Val Leu Glu Ala His Pro Phe Asp Gln Arg Ile 465 470 475 480 Ile Leu Ser Ala Gly His Asp Gly Asn Ile Phe Ile Trp Asp Leu Asp 485 490 495 Arg Gly Thr Lys Ile Arg Asn Tyr Phe Asn Met Ile Glu Gly Gln Gly 500 505 510 His Gly Ala Val Phe Asp Cys Lys Phe Ser Pro Asp Gly Asn His Phe 515 520 525 Ala Cys Thr Asp Ser His Gly His Leu Leu Leu Phe Gly Phe Gly Cys 530 535 540 Ser Lys Tyr Tyr Glu Lys Ile Pro Asp Gln Met Phe Phe His Thr Asp 545 550 555 560 Tyr Arg Pro Leu Ile Arg Asp Ala Asn Asn Tyr Val Leu Asp Glu Gln 565 570 575 Thr Gln Gln Ala Pro His Leu Met Pro Pro Pro Phe Leu Val Asp Val 580 585 590 Asp Gly Asn Pro His Pro Thr Lys Phe Gln Arg Leu Val Pro Gly Arg 595 600 605 Glu Asn Cys Lys Asp Glu Gln Leu Ile Pro Gln Leu Gly Tyr Val Ala 610 615 620 Asn Gly Asp Gly Glu Val Val Glu Gln Val Ile Gly Gln Gln Thr Asn 625 630 635 640 Asp Gln Asp Glu Ser Ile Leu Asp Gly Ile Ile Arg Glu Leu Gln Arg 645 650 655 Glu Gln Asp Leu Arg Leu Ile Asn Glu Gly Asp Val Pro His Leu Pro 660 665 670 Val Asn Arg Ala Tyr Ser Val Asn Gly Ala Leu Arg Ser Pro Asn Met 675 680 685 Asp Ile Ser Ser Ser Pro Asn Ile Arg Leu Arg Arg His Ser Ser Gln 690 695 700 Ile Glu Gly Val Arg Gln Met His Asn Asn Ala Pro Arg Ser Gln Met 705 710 715 720 Ala Thr Glu Arg Asp Leu Met Ala Trp Ser Arg Arg Val Val Val Asn 725 730 735 Glu Leu Asn Asn Gly Val Ser Arg Val Gln Glu Glu Cys Arg Thr Ala 740 745 750 Lys Gly Asp Ile Glu Ile Ser Leu Tyr Thr Val Glu Lys Lys Lys Lys 755 760 765 Pro Ser Tyr Thr Thr Gln Arg Asn Asp Tyr Glu Pro Ser Cys Gly Arg 770 775 780 Ser Leu Arg Arg Thr Gln Arg Lys Arg Gln His Thr Tyr Gln Thr Arg 785 790 795 800 Ser Asn Ile Glu His Asn Ser Gln Ala Ser Cys Gln Asn Ser Gly Val 805 810 815 Gln Glu Asp Ser Asp Ser Ser Ser Glu Glu Asp Glu Thr Val Gly Thr 820 825 830 Ser Asp Ala Ser Val Glu Asp Pro Val Val Glu Trp Gln Ser Glu Ser 835 840 845 Ser Ser Ser Asp Ser Ser Ser Glu Tyr Ser Asp Trp Thr Ala Asp Ala 850 855 860 Gly Ile Asn Leu Gln Pro Pro Lys Arg Gln Thr Arg Gln Thr Thr Arg 865 870 875 880 Lys Ile Cys Ser Ser Ser Asp Glu Glu Asn Leu Lys Ser Leu Glu Glu 885 890 895 Arg Gln Lys Lys Pro Lys Gln Thr Arg Lys Lys Lys Gly Gly Leu Val 900 905 910 Ser Ile Ala Gly Glu Pro Asn Glu Glu Trp Phe Ala Pro Gln Trp Ile 915 920 925 Leu Asp Thr Ile Pro Arg Arg Ser Pro Phe Val Pro Gln Met Gly Asp 930 935 940 Glu Leu Ile Tyr Phe Arg Gln Gly His Glu Ala Tyr Val Arg Ala Val 945 950 955 960 Arg Lys Ser Lys Ile Tyr Ser Val Asn Leu Gln Lys Gln Pro Trp Asn 965 970 975 Lys Met Asp Leu Arg Glu Gln Glu Phe Val Lys Ile Val Gly Ile Lys 980 985 990 Tyr Glu Val Gly Pro Pro Thr Leu Cys Cys Leu Lys Leu Ala Phe Leu 995 1000 1005 Asp Pro Ile Ser Gly Lys Met Thr Gly Glu Ser Phe Ser Ile Lys Tyr 1010 1015 1020 His Asp Met Pro Asp Val Ile Asp Phe Leu Val Leu His Gln Phe Tyr 1025 1030 1035 1040 Asn Glu Ala Lys Glu Arg Asn Trp Gln Ile Gly Asp Arg Phe Arg Ser 1045 1050 1055 Ile Ile Asp Asp Ala Trp Trp Phe Gly Thr Val Glu Ser Gln Gln Pro 1060 1065 1070 Phe Gln Pro Glu Tyr Pro Asp Ser Ser Phe Gln Cys Tyr Ser Val His 1075 1080 1085 Trp Asp Asn Asn Glu Arg Glu Lys Met Ser Pro Trp Asp Met Glu Pro 1090 1095 1100 Ile Pro Glu Gly Thr Ala Phe Pro Asp Glu Val Gly Ala Gly Val Pro 1105 1110 1115 1120 Val Ser Gln Glu Glu Leu Thr Ala Leu Leu Tyr Lys Pro Gln Glu Gly 1125 1130 1135 Glu Trp Gly Ala His Ser Arg Asp Glu Glu Glu Cys Glu Arg Val Ile Gln 1140 1145 1150 Gly Ile Asn His Leu Leu Ser Leu Asp Phe Ala Ser Pro Phe Ala Val 1155 1160 1165 Pro Val Asp Leu Ser Ala Tyr Pro Leu Tyr Cys Thr Val Val Ala Tyr 1170 1175 1180 Pro Thr Asp Leu Asn Thr Ile Arg Arg Arg Leu Glu Asn Arg Phe Tyr 1185 1190 1195 1200 Arg Arg Ile Ser Ala Leu Met Trp Glu Val Arg Tyr Ile Glu His Asn 1205 1210 1215 Ala Arg Thr Phe Asn Glu Pro Asp Ser Pro Ile Val Lys Ala Ala Lys 1220 1225 1230 Ile Val Thr Asp Val Leu Leu Arg Phe Ile Gly Asp Gln Ser Cys Thr 1235 1240 1245 Asp Ile Leu Asp Thr Tyr Asn Lys Ile Lys Ala Glu Glu Arg Asn Ser 1250 1255 1260 Thr Asp Ala Glu Glu Asp Thr Glu Ile Val Asp Leu Asp Ser Asp Gly 1265 1270 1275 1280 Pro Gly Thr Ser Ser Gly Arg Arg Val Lys Cys Arg Gly Arg Arg Gln 1285 1290 1295 Ser Leu Lys Cys Asn Pro Asp Ala Trp Lys Lys Gln Cys Lys Glu Leu 1300 1305 1310 Leu Ser Leu Ile Tyr Glu Arg Glu Asp Ser Glu Pro Phe Arg Gln Pro 1315 1320 1325 Ala Asp Leu Leu Ser Tyr Pro Gly His Gln Glu Gln Glu Gly Glu Ser 1330 1335 1340 Ser Glu Ser Val Val Pro Glu Arg Gln Gln Asp Ser Ser Leu Ser Glu 1345 1350 1355 1360 Asp Tyr Gln Asp Val Ile Asp Thr Pro Val Asp Phe Ser Thr Val Lys 1365 1370 1375 Glu Thr Leu Glu Ala Gly Asn Tyr Gly Ser Pro Leu Glu Phe Tyr Lys 1380 1385 1390 Asp Val Arg Gln Ile Phe Asn Asn Ser Lys Ala Tyr Thr Ser Asn Lys 1395 1400 1405 Lys Ser Arg Ile Tyr Ser Met Met Leu Arg Leu Ser Ala Leu Phe Glu 1410 1415 1420 Ser His Ile Lys Asn Ile Ile Ser Glu Tyr Lys Ser Ala Ile Gln Ser 1425 1430 1435 1440 Gln Lys Arg Arg Arg Pro Arg Tyr Arg Lys Arg Leu Arg Ser Ser Ser 1445 1450 1455 Ser Ser Leu Ser Ser Ser Gly Ala Pro Ser Pro Lys Gly Lys Gln Lys 1460 1465 1470 Gln Met Lys Leu Gln Pro Lys Asn Asp Gln Asn Thr Ser Val Ser His 1475 1480 1485 Ala Arg Thr Ser Ser Pro Phe Ser Ser Pro Val Ser Asp Ala Ala Glu 1490 1495 1500 Gly Leu Ser Leu Tyr Leu Leu Asp Asp Glu Pro Asp Gly Pro Phe Ser 1505 1510 1515 1520 Ser Ser Ser Phe Gly Gly Tyr Ser Arg Ser Gly Asn Ser His Asp Pro 1525 1530 1535 Gly Lys Ala Lys Ser Phe Arg Asn Arg Val Leu Pro Val Lys Gln Asp 1540 1545 1550 His Ser Leu Asp Gly Pro Leu Thr Asn Gly Asp Gly Arg Glu Pro Arg 1555 1560 1565 Thr Gly Ile Lys Arg Lys Leu Leu Ser Ala Ser Glu Glu Asp Glu Asn 1570 1575 1580 Met Gly Gly Glu Asp Lys Glu Lys Lys Glu Thr Lys Glu Lys Ser His 1585 1590 1595 1600 Leu Ser Thr Ser Glu Ser Gly Glu Leu Gly Ser Ser Leu Ser Ser Glu 1605 1610 1615 Ser Thr Cys Gly Ser Asp Ser Asp Ser Glu Ser Thr Ser Arg Thr Asp 1620 1625 1630 Gln Asp Tyr Val Asp Gly Asp His Asp Tyr Ser Lys Phe Ile Gln Thr 1635 1640 1645 Arg Pro Lys Arg Lys Leu Arg Lys Gln His Gly Asn Gly Lys Arg Asn 1650 1655 1660 Trp Lys Thr Arg Gly Thr Gly Gly Arg Gly Arg Trp Gly Arg Trp Gly 1665 1670 1675 1680 Arg Trp Ser Arg Gly Gly Arg Gly Arg Gly Gly Arg Gly Arg Gly Ser 1685 1690 1695 Arg Gly Arg Gly Gly Gly Gly Thr Arg Gly Arg Gly Arg Gly Arg Gly 1700 1705 1710 Gly Arg Gly Ala Ser Arg Gly Ala Thr Arg Ala Lys Arg Ala Arg Ile 1715 1720 1725 Ala Asp Asp Glu Phe Asp Thr Met Phe Ser Gly Arg Phe Ser Arg Leu 1730 1735 1740 Pro Arg Ile Lys Thr Arg Asn Gln Gly Arg Arg Thr Val Leu Tyr Asn 1745 1750 1755 1760 Asp Asp Ser Asp Asn Asp Asn Phe Val Ser Thr Glu Asp Pro Leu Asn 1765 1770 1775 Leu Gly Thr Ser Arg Ser Gly Arg Val Arg Lys Met Thr Glu Lys Ala 1780 1785 1790 Arg Val Ser His Leu Met Gly Trp Asn Tyr 1795 1800 <210> 7 <211> 1685 <212> PRT <213> Homo sapiens <400> 7 Met Lys Leu Arg Gly Val Ser Leu Ala Ala Gly Leu Phe Leu Leu Ala 1 5 10 15 Leu Ser Leu Trp Gly Gln Pro Ala Glu Ala Ala Ala Cys Tyr Gly Cys 20 25 30 Ser Pro Gly Ser Lys Cys Asp Cys Ser Gly Ile Lys Gly Glu Lys Gly 35 40 45 Glu Arg Gly Phe Pro Gly Leu Glu Gly His Pro Gly Leu Pro Gly Phe 50 55 60 Pro Gly Pro Glu Gly Pro Pro Gly Pro Arg Gly Gln Lys Gly Asp Asp 65 70 75 80 Gly Ile Pro Gly Pro Pro Gly Pro Lys Gly Ile Arg Gly Pro Pro Gly 85 90 95 Leu Pro Gly Phe Pro Gly Thr Pro Gly Leu Pro Gly Met Pro Gly His 100 105 110 Asp Gly Ala Pro Gly Pro Gln Gly Ile Pro Gly Cys Asn Gly Thr Lys 115 120 125 Gly Glu Arg Gly Phe Pro Gly Ser Pro Gly Phe Pro Gly Leu Gln Gly 130 135 140 Pro Pro Gly Pro Pro Gly Ile Pro Gly Met Lys Gly Glu Pro Gly Ser 145 150 155 160 Ile Ile Met Ser Leu Pro Gly Pro Lys Gly Asn Pro Gly Tyr Pro 165 170 175 Gly Pro Pro Gly Ile Gln Gly Leu Pro Gly Pro Thr Gly Ile Pro Gly 180 185 190 Pro Ile Gly Pro Pro Gly Pro Pro Gly Leu Met Gly Pro Pro Gly Pro 195 200 205 Pro Gly Leu Pro Gly Pro Lys Gly Asn Met Gly Leu Asn Phe Gln Gly 210 215 220 Pro Lys Gly Glu Lys Gly Glu Gln Gly Leu Gln Gly Pro Pro Gly Pro 225 230 235 240 Pro Gly Gln Ile Ser Glu Gln Lys Arg Pro Ile Asp Val Glu Phe Gln 245 250 255 Lys Gly Asp Gln Gly Leu Pro Gly Asp Arg Gly Pro Pro Gly Pro Pro 260 265 270 Gly Ile Arg Gly Pro Pro Gly Pro Pro Gly Gly Glu Lys Gly Glu Lys 275 280 285 Gly Glu Gln Gly Glu Pro Gly Lys Arg Gly Lys Pro Gly Lys Asp Gly 290 295 300 Glu Asn Gly Gln Pro Gly Ile Pro Gly Leu Pro Gly Asp Pro Gly Tyr 305 310 315 320 Pro Gly Glu Pro Gly Arg Asp Gly Glu Lys Gly Gln Lys Gly Asp Thr 325 330 335 Gly Pro Pro Gly Pro Pro Gly Leu Val Ile Pro Arg Pro Gly Thr Gly 340 345 350 Ile Thr Ile Gly Glu Lys Gly Asn Ile Gly Leu Pro Gly Leu Pro Gly 355 360 365 Glu Lys Gly Glu Arg Gly Phe Pro Gly Ile Gln Gly Pro Pro Gly Leu 370 375 380 Pro Gly Pro Pro Gly Ala Ala Val Met Gly Pro Pro Gly Pro Pro Gly 385 390 395 400 Phe Pro Gly Glu Arg Gly Gln Lys Gly Asp Glu Gly Pro Pro Gly Ile 405 410 415 Ser Ile Pro Gly Pro Pro Gly Leu Asp Gly Gln Pro Gly Ala Pro Gly 420 425 430 Leu Pro Gly Pro Pro Gly Pro Ala Gly Pro His Ile Pro Pro Ser Asp 435 440 445 Glu Ile Cys Glu Pro Gly Pro Pro Gly Pro Pro Gly Ser Pro Gly Asp 450 455 460 Lys Gly Leu Gln Gly Glu Gln Gly Val Lys Gly Asp Lys Gly Asp Thr 465 470 475 480 Cys Phe Asn Cys Ile Gly Thr Gly Ile Ser Gly Pro Pro Gly Gln Pro 485 490 495 Gly Leu Pro Gly Leu Pro Gly Pro Pro Gly Ser Leu Gly Phe Pro Gly 500 505 510 Gln Lys Gly Glu Lys Gly Gln Ala Gly Ala Thr Gly Pro Lys Gly Leu 515 520 525 Pro Gly Ile Pro Gly Ala Pro Gly Ala Pro Gly Phe Pro Gly Ser Lys 530 535 540 Gly Glu Pro Gly Asp Ile Leu Thr Phe Pro Gly Met Lys Gly Asp Lys 545 550 555 560 Gly Glu Leu Gly Ser Pro Gly Ala Pro Gly Leu Pro Gly Leu Pro Gly 565 570 575 Thr Pro Gly Gln Asp Gly Leu Pro Gly Leu Pro Gly Pro Lys Gly Glu 580 585 590 Pro Gly Gly Ile Thr Phe Lys Gly Glu Arg Gly Pro Pro Gly Asn Pro 595 600 605 Gly Leu Pro Gly Leu Pro Gly Asn Ile Gly Pro Met Gly Pro Pro Gly 610 615 620 Phe Gly Pro Pro Gly Pro Val Gly Glu Lys Gly Ile Gln Gly Val Ala 625 630 635 640 Gly Asn Pro Gly Gln Pro Gly Ile Pro Gly Pro Lys Gly Asp Pro Gly 645 650 655 Gln Thr Ile Thr Gln Pro Gly Lys Pro Gly Leu Pro Gly Asn Pro Gly 660 665 670 Arg Asp Gly Asp Val Gly Leu Pro Gly Asp Pro Gly Leu Pro Gly Gln 675 680 685 Pro Gly Leu Pro Gly Ile Pro Gly Ser Lys Gly Glu Pro Gly Ile Pro 690 695 700 Gly Ile Gly Leu Pro Gly Pro Pro Gly Pro Lys Gly Phe Pro Gly Ile 705 710 715 720 Pro Gly Pro Pro Gly Ala Pro Gly Thr Pro Gly Arg Ile Gly Leu Glu 725 730 735 Gly Pro Pro Gly Pro Pro Gly Phe Pro Gly Pro Lys Gly Glu Pro Gly 740 745 750 Phe Ala Leu Pro Gly Pro Pro Gly Pro Pro Gly Leu Pro Gly Phe Lys 755 760 765 Gly Ala Leu Gly Pro Lys Gly Asp Arg Gly Phe Pro Gly Pro Pro Gly 770 775 780 Pro Pro Gly Arg Thr Gly Leu Asp Gly Leu Pro Gly Pro Lys Gly Asp 785 790 795 800 Val Gly Pro Asn Gly Gln Pro Gly Pro Met Gly Pro Pro Gly Leu Pro 805 810 815 Gly Ile Gly Val Gln Gly Pro Pro Gly Pro Pro Gly Ile Pro Gly Pro 820 825 830 Ile Gly Gln Pro Gly Leu His Gly Ile Pro Gly Glu Lys Gly Asp Pro 835 840 845 Gly Pro Pro Gly Leu Asp Val Pro Gly Pro Pro Gly Glu Arg Gly Ser 850 855 860 Pro Gly Ile Pro Gly Ala Pro Gly Pro Ile Gly Pro Pro Gly Ser Pro 865 870 875 880 Gly Leu Pro Gly Lys Ala Gly Ala Ser Gly Phe Pro Gly Thr Lys Gly 885 890 895 Glu Met Gly Met Met Gly Pro Pro Gly Pro Pro Gly Pro Leu Gly Ile 900 905 910 Pro Gly Arg Ser Gly Val Pro Gly Leu Lys Gly Asp Asp Gly Leu Gln 915 920 925 Gly Gln Pro Gly Leu Pro Gly Pro Thr Gly Glu Lys Gly Ser Lys Gly 930 935 940 Glu Pro Gly Leu Pro Gly Pro Pro Gly Pro Met Asp Pro Asn Leu Leu 945 950 955 960 Gly Ser Lys Gly Glu Lys Gly Glu Pro Gly Leu Pro Gly Ile Pro Gly 965 970 975 Val Ser Gly Pro Lys Gly Tyr Gln Gly Leu Pro Gly Asp Pro Gly Gln 980 985 990 Pro Gly Leu Ser Gly Gln Pro Gly Leu Pro Gly Pro Pro Gly Pro Lys 995 1000 1005 Gly Asn Pro Gly Leu Pro Gly Gln Pro Gly Leu Ile Gly Pro Pro Gly 1010 1015 1020 Leu Lys Gly Thr Ile Gly Asp Met Gly Phe Pro Gly Pro Gln Gly Val 1025 1030 1035 1040 Glu Gly Pro Pro Gly Pro Ser Gly Val Pro Gly Gln Pro Gly Ser Pro 1045 1050 1055 Gly Leu Pro Gly Gln Lys Gly Asp Lys Gly Asp Pro Gly Ile Ser Ser 1060 1065 1070 Ile Gly Leu Pro Gly Leu Pro Gly Pro Lys Gly Glu Pro Gly Leu Pro 1075 1080 1085 Gly Tyr Pro Gly Asn Pro Gly Ile Lys Gly Ser Val Gly Asp Pro Gly 1090 1095 1100 Leu Pro Gly Leu Pro Gly Thr Pro Gly Ala Lys Gly Gln Pro Gly Leu 1105 1110 1115 1120 Pro Gly Phe Pro Gly Thr Pro Gly Pro Pro Gly Pro Lys Gly Ile Ser 1125 1130 1135 Gly Pro Pro Gly Asn Pro Gly Leu Pro Gly Glu Pro Gly Pro Val Gly 1140 1145 1150 Gly Gly Gly His Pro Gly Gln Pro Gly Pro Pro Gly Glu Lys Gly Lys 1155 1160 1165 Pro Gly Gln Asp Gly Ile Pro Gly Pro Ala Gly Gln Lys Gly Glu Pro 1170 1175 1180 Gly Gln Pro Gly Phe Gly Asn Pro Gly Pro Pro Gly Leu Pro Gly Leu 1185 1190 1195 1200 Ser Gly Gln Lys Gly Asp Gly Gly Leu Pro Gly Ile Pro Gly Asn Pro 1205 1210 1215 Gly Leu Pro Gly Pro Lys Gly Glu Pro Gly Phe His Gly Phe Pro Gly 1220 1225 1230 Val Gln Gly Pro Pro Gly Pro Pro Gly Ser Pro Gly Pro Ala Leu Glu 1235 1240 1245 Gly Pro Lys Gly Asn Pro Gly Pro Gln Gly Pro Pro Gly Arg Pro Gly 1250 1255 1260 Leu Pro Gly Pro Glu Gly Pro Pro Gly Leu Pro Gly Asn Gly Gly Ile 1265 1270 1275 1280 Lys Gly Glu Lys Gly Asn Pro Gly Gln Pro Gly Leu Pro Gly Leu Pro 1285 1290 1295 Gly Leu Lys Gly Asp Gln Gly Pro Pro Gly Leu Gln Gly Asn Pro Gly 1300 1305 1310 Arg Pro Gly Leu Asn Gly Met Lys Gly Asp Pro Gly Leu Pro Gly Val 1315 1320 1325 Pro Gly Phe Pro Gly Met Lys Gly Pro Ser Gly Val Pro Gly Ser Ala 1330 1335 1340 Gly Pro Glu Gly Glu Pro Gly Leu Ile Gly Pro Pro Gly Pro Pro Gly 1345 1350 1355 1360 Leu Pro Gly Pro Ser Gly Gln Ser Ile Ile Ile Lys Gly Asp Ala Gly 1365 1370 1375 Pro Pro Gly Ile Pro Gly Gln Pro Gly Leu Lys Gly Leu Pro Gly Pro 1380 1385 1390 Gln Gly Pro Gln Gly Leu Pro Gly Pro Thr Gly Pro Pro Gly Asp Pro 1395 1400 1405 Gly Arg Asn Gly Leu Pro Gly Phe Asp Gly Ala Gly Gly Arg Lys Gly 1410 1415 1420 Asp Pro Gly Leu Pro Gly Gln Pro Gly Thr Arg Gly Leu Asp Gly Pro 1425 1430 1435 1440 Pro Gly Pro Asp Gly Leu Gln Gly Pro Pro Gly Pro Pro Gly Thr Ser 1445 1450 1455 Ser Val Ala His Gly Phe Leu Ile Thr Arg His Ser Gln Thr Thr Asp 1460 1465 1470 Ala Pro Gln Cys Pro Gln Gly Thr Leu Gln Val Tyr Glu Gly Phe Ser 1475 1480 1485 Leu Leu Tyr Val Gln Gly Asn Lys Arg Ala His Gly Gln Asp Leu Gly 1490 1495 1500 Thr Ala Gly Ser Cys Leu Arg Arg Phe Ser Thr Met Pro Phe Met Phe 1505 1510 1515 1520 Cys Asn Ile Asn Asn Val Cys Asn Phe Ala Ser Arg Asn Asp Tyr Ser 1525 1530 1535 Tyr Trp Leu Ser Thr Pro Glu Pro Met Pro Met Ser Met Gln Pro Leu 1540 1545 1550 Lys Gly Gln Ser Ile Gln Pro Phe Ile Ser Arg Cys Ala Val Cys Glu 1555 1560 1565 Ala Pro Ala Val Val Ile Ala Val His Ser Gln Thr Ile Gln Ile Pro 1570 1575 1580 His Cys Pro Gln Gly Trp Asp Ser Leu Trp Ile Gly Tyr Ser Phe Met 1585 1590 1595 1600 Met His Thr Ser Ala Gly Ala Glu Gly Ser Gly Gln Ala Leu Ala Ser 1605 1610 1615 Pro Gly Ser Cys Leu Glu Glu Phe Arg Ser Ala Pro Phe Ile Glu Cys 1620 1625 1630 His Gly Arg Gly Thr Cys Asn Tyr Tyr Ala Asn Ser Tyr Ser Phe Trp 1635 1640 1645 Leu Ala Thr Val Asp Val Ser Asp Met Phe Ser Lys Pro Gln Ser Glu 1650 1655 1660 Thr Leu Lys Ala Gly Asp Leu Arg Thr Arg Ile Ser Arg Cys Gln Val 1665 1670 1675 1680 Cys Met Lys Arg Thr 1685 <210> 8 <211> 561 <212> PRT <213> Homo sapiens <400> 8 Met Ala Phe Pro Leu Glu Glu Glu Ala Gly Arg Ile Lys Asp Cys Trp 1 5 10 15 Asp Asn Gln Glu Ala Pro Ala Leu Ser Thr Cys Ser Asn Ala Asn Ile 20 25 30 Phe Arg Arg Ile Asn Ala Ile Leu Asp Asn Ser Leu Asp Phe Ser Arg 35 40 45 Val Cys Thr Thr Pro Ile Asn Arg Gly Ile His Asp His Leu Pro Asp 50 55 60 Phe Gln Asp Ser Glu Glu Thr Val Thr Ser Arg Met Leu Phe Pro Thr 65 70 75 80 Ser Ala Gln Glu Ser Ser Arg Gly Leu Pro Asp Ala Asn Asp Leu Cys 85 90 95 Leu Gly Leu Gln Ser Leu Ser Leu Thr Gly Trp Asp Arg Pro Trp Ser 100 105 110 Thr Gln Asp Ser Asp Ser Ser Ala Gln Ser Ser Thr His Ser Val Leu 115 120 125 Ser Met Leu His Asn Pro Leu Gly Asn Val Leu Gly Lys Pro Pro Leu 130 135 140 Ser Phe Leu Pro Leu Asp Pro Leu Gly Ser Asp Leu Val Asp Lys Phe 145 150 155 160 Pro Ala Pro Ser Val Arg Gly Ser Arg Leu Asp Thr Arg Pro Ile Leu 165 170 175 Asp Ser Arg Ser Ser Ser Pro Ser Asp Ser Asp Thr Ser Gly Phe Ser 180 185 190 Ser Gly Ser Asp His Leu Ser Asp Leu Ile Ser Ser Leu Arg Ile Ser 195 200 205 Pro Pro Leu Pro Phe Leu Ser Leu Ser Gly Gly Gly Pro Arg Asp Pro 210 215 220 Leu Lys Met Gly Val Gly Ser Arg Met Asp Gln Glu Gln Ala Ala Leu 225 230 235 240 Ala Ala Val Thr Pro Ser Pro Thr Ser Ala Ser Lys Arg Trp Pro Gly 245 250 255 Ala Ser Val Trp Pro Ser Trp Asp Leu Leu Glu Ala Pro Lys Asp Pro 260 265 270 Phe Ser Ile Glu Arg Glu Ala Arg Leu His Arg Gln Ala Ala Ala Val 275 280 285 Asn Glu Ala Thr Cys Thr Trp Ser Gly Gln Leu Pro Pro Arg Asn Tyr 290 295 300 Lys Asn Pro Ile Tyr Ser Cys Lys Val Phe Leu Gly Gly Val Pro Trp 305 310 315 320 Asp Ile Thr Glu Ala Gly Leu Val Asn Thr Phe Arg Val Phe Gly Ser 325 330 335 Leu Ser Val Glu Trp Pro Gly Lys Asp Gly Lys His Pro Arg Cys Pro 340 345 350 Pro Lys Gly Tyr Val Tyr Leu Val Phe Glu Leu Glu Lys Ser Val Arg 355 360 365 Ser Leu Leu Gln Ala Cys Ser His Asp Pro Leu Ser Pro Asp Gly Leu 370 375 380 Ser Glu Tyr Tyr Phe Lys Met Ser Ser Arg Arg Met Arg Cys Lys Glu 385 390 395 400 Val Gln Val Ile Pro Trp Val Leu Ala Asp Ser Asn Phe Val Arg Ser 405 410 415 Pro Ser Gln Arg Leu Asp Pro Ser Arg Thr Val Phe Val Gly Ala Leu 420 425 430 His Gly Met Leu Asn Ala Glu Ala Leu Ala Ala Ile Leu Asn Asp Leu 435 440 445 Phe Gly Gly Val Val Tyr Ala Gly Ile Asp Thr Asp Lys His Lys Tyr 450 455 460 Pro Ile Gly Ser Gly Arg Val Thr Phe Asn Asn Gln Arg Ser Tyr Leu 465 470 475 480 Lys Ala Val Ser Ala Ala Phe Val Glu Ile Lys Thr Thr Lys Phe Thr 485 490 495 Lys Lys Val Gln Ile Asp Pro Tyr Leu Glu Asp Ser Leu Cys His Ile 500 505 510 Cys Ser Ser Gln Pro Gly Pro Phe Phe Cys Arg Asp Gln Val Cys Phe 515 520 525 Lys Tyr Phe Cys Arg Ser Cys Trp His Trp Arg His Ser Met Glu Gly 530 535 540 Leu Arg His His Ser Pro Leu Met Arg Asn Gln Lys Asn Arg Asp Ser 545 550 555 560 Ser <210> 9 <211> 1255 <212> PRT <213> Homo sapiens <400> 9 Met Glu Leu Ala Ala Leu Cys Arg Trp Gly Leu Leu Leu Ala Leu Leu 1 5 10 15 Pro Pro Gly Ala Ala Ser Thr Gln Val Cys Thr Gly Thr Asp Met Lys 20 25 30 Leu Arg Leu Pro Ala Ser Pro Glu Thr His Leu Asp Met Leu Arg His 35 40 45 Leu Tyr Gln Gly Cys Gln Val Val Gln Gly Asn Leu Glu Leu Thr Tyr 50 55 60 Leu Pro Thr Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln Glu Val 65 70 75 80 Gln Gly Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val Pro Leu 85 90 95 Gln Arg Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr 100 105 110 Ala Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr Thr Pro 115 120 125 Val Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu Arg Ser 130 135 140 Leu Thr Glu Ile Leu Lys Gly Gly Val Leu Ile Gln Arg Asn Pro Gln 145 150 155 160 Leu Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile Phe His Lys Asn 165 170 175 Asn Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn Arg Ser Arg Ala Cys 180 185 190 His Pro Cys Ser Pro Met Cys Lys Gly Ser Arg Cys Trp Gly Glu Ser 195 200 205 Ser Glu Asp Cys Gln Ser Leu Thr Arg Thr Val Cys Ala Gly Gly Cys 210 215 220 Ala Arg Cys Lys Gly Pro Leu Pro Thr Asp Cys Cys His Glu Gln Cys 225 230 235 240 Ala Ala Gly Cys Thr Gly Pro Lys His Ser Asp Cys Leu Ala Cys Leu 245 250 255 His Phe Asn His Ser Gly Ile Cys Glu Leu His Cys Pro Ala Leu Val 260 265 270 Thr Tyr Asn Thr Asp Thr Phe Glu Ser Met Pro Asn Pro Glu Gly Arg 275 280 285 Tyr Thr Phe Gly Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu 290 295 300 Ser Thr Asp Val Gly Ser Cys Thr Leu Val Cys Pro Leu His Asn Gln 305 310 315 320 Glu Val Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys 325 330 335 Pro Cys Ala Arg Val Cys Tyr Gly Leu Gly Met Glu His Leu Arg Glu 340 345 350 Val Arg Ala Val Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys 355 360 365 Lys Ile Phe Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp 370 375 380 Pro Ala Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln Val Phe 385 390 395 400 Glu Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro 405 410 415 Asp Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val Ile Arg 420 425 430 Gly Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln Gly Leu 435 440 445 Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu Gly Ser Gly 450 455 460 Leu Ala Leu Ile His His Asn Thr His Leu Cys Phe Val His Thr Val 465 470 475 480 Pro Trp Asp Gln Leu Phe Arg Asn Pro His Gln Ala Leu Leu His Thr 485 490 495 Ala Asn Arg Pro Glu Asp Glu Cys Val Gly Glu Gly Leu Ala Cys His 500 505 510 Gln Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro Thr Gln Cys 515 520 525 Val Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys Val Glu Glu Cys 530 535 540 Arg Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg His Cys 545 550 555 560 Leu Pro Cys His Pro Glu Cys Gln Pro Gln Asn Gly Ser Val Thr Cys 565 570 575 Phe Gly Pro Glu Ala Asp Gln Cys Val Ala Cys Ala His Tyr Lys Asp 580 585 590 Pro Pro Phe Cys Val Ala Arg Cys Pro Ser Gly Val Lys Pro Asp Leu 595 600 605 Ser Tyr Met Pro Ile Trp Lys Phe Pro Asp Glu Glu Gly Ala Cys Gln 610 615 620 Pro Cys Pro Ile Asn Cys Thr His Ser Cys Val Asp Leu Asp Asp Lys 625 630 635 640 Gly Cys Pro Ala Glu Gln Arg Ala Ser Pro Leu Thr Ser Ile Ile Ser 645 650 655 Ala Val Val Gly Ile Leu Leu Val Val Val Leu Gly Val Val Phe Gly 660 665 670 Ile Leu Ile Lys Arg Arg Gln Gln Lys Ile Arg Lys Tyr Thr Met Arg 675 680 685 Arg Leu Leu Gln Glu Thr Glu Leu Val Glu Pro Leu Thr Pro Ser Gly 690 695 700 Ala Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr Glu Leu 705 710 715 720 Arg Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys 725 730 735 Gly Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile 740 745 750 Lys Val Leu Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu 755 760 765 Asp Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg 770 775 780 Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu 785 790 795 800 Met Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg Gly Arg 805 810 815 Leu Gly Ser Gln Asp Leu Leu Asn Trp Cys Met Gln Ile Ala Lys Gly 820 825 830 Met Ser Tyr Leu Glu Asp Val Arg Leu Val His Arg Asp Leu Ala Ala 835 840 845 Arg Asn Val Leu Val Lys Ser Pro Asn His Val Lys Ile Thr Asp Phe 850 855 860 Gly Leu Ala Arg Leu Leu Asp Ile Asp Glu Thr Glu Tyr His Ala Asp 865 870 875 880 Gly Gly Lys Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile Leu Arg 885 890 895 Arg Arg Phe Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr Val 900 905 910 Trp Glu Leu Met Thr Phe Gly Ala Lys Pro Tyr Asp Gly Ile Pro Ala 915 920 925 Arg Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro 930 935 940 Pro Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val Lys Cys Trp Met 945 950 955 960 Ile Asp Ser Glu Cys Arg Pro Arg Phe Arg Glu Leu Val Ser Glu Phe 965 970 975 Ser Arg Met Ala Arg Asp Pro Gln Arg Phe Val Val Ile Gln Asn Glu 980 985 990 Asp Leu Gly Pro Ala Ser Pro Leu Asp Ser Thr Phe Tyr Arg Ser Leu 995 1000 1005 Leu Glu Asp Asp Asp Met Gly Asp Leu Val Asp Ala Glu Glu Tyr Leu 1010 1015 1020 Val Pro Gln Gln Gly Phe Phe Cys Pro Asp Pro Ala Pro Gly Ala Gly 1025 1030 1035 1040 Gly Met Val His His Arg His Arg Ser Ser Ser Thr Arg Ser Gly Gly 1045 1050 1055 Gly Asp Leu Thr Leu Gly Leu Glu Pro Ser Glu Glu Glu Ala Pro Arg 1060 1065 1070 Ser Pro Leu Ala Pro Ser Glu Gly Ala Gly Ser Asp Val Phe Asp Gly 1075 1080 1085 Asp Leu Gly Met Gly Ala Ala Lys Gly Leu Gln Ser Leu Pro Thr His 1090 1095 1100 Asp Pro Ser Pro Leu Gln Arg Tyr Ser Glu Asp Pro Thr Val Pro Leu 1105 1110 1115 1120 Pro Ser Glu Thr Asp Gly Tyr Val Ala Pro Leu Thr Cys Ser Pro Gln 1125 1130 1135 Pro Glu Tyr Val Asn Gln Pro Asp Val Arg Pro Gln Pro Pro Ser Pro 1140 1145 1150 Arg Glu Gly Pro Leu Pro Ala Ala Arg Pro Ala Gly Ala Thr Leu Glu 1155 1160 1165 Arg Pro Lys Thr Leu Ser Pro Gly Lys Asn Gly Val Val Lys Asp Val 1170 1175 1180 Phe Ala Phe Gly Gly Ala Val Glu Asn Pro Glu Tyr Leu Thr Pro Gln 1185 1190 1195 1200 Gly Gly Ala Ala Pro Gln Pro His Pro Pro Pro Ala Phe Ser Pro Ala 1205 1210 1215 Phe Asp Asn Leu Tyr Tyr Trp Asp Gln Asp Pro Pro Glu Arg Gly Ala 1220 1225 1230 Pro Pro Ser Thr Phe Lys Gly Thr Pro Thr Ala Glu Asn Pro Glu Tyr 1235 1240 1245 Leu Gly Leu Asp Val Pro Val 1250 1255 <210> 10 <211> 854 <212> PRT <213> Homo sapiens <400> 10 Met Pro Pro Cys Ser Gly Gly Asp Gly Ser Thr Pro Pro Gly Pro Ser 1 5 10 15 Leu Arg Asp Arg Asp Cys Pro Ala Gln Ser Ala Glu Tyr Pro Arg Asp 20 25 30 Arg Leu Asp Pro Arg Pro Gly Ser Pro Ser Glu Ala Ser Ser Pro Pro 35 40 45 Phe Leu Arg Ser Arg Ala Pro Val Asn Trp Tyr Gln Glu Lys Ala Gln 50 55 60 Val Phe Leu Trp His Leu Met Val Ser Gly Ser Thr Thr Leu Leu Cys 65 70 75 80 Leu Trp Lys Gln Pro Phe His Val Ser Ala Phe Pro Val Thr Ala Ser 85 90 95 Leu Ala Phe Arg Gln Ser Gln Gly Ala Gly Gln His Leu Tyr Lys Asp 100 105 110 Leu Gln Pro Phe Ile Leu Leu Arg Leu Leu Met Pro Glu Glu Thr Gln 115 120 125 Thr Gln Asp Gln Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe 130 135 140 Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr 145 150 155 160 Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp 165 170 175 Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu 180 185 190 Asp Ser Gly Lys Glu Leu His Ile Asn Leu Ile Pro Asn Lys Gln Asp 195 200 205 Arg Thr Leu Thr Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp 210 215 220 Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe 225 230 235 240 Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe 245 250 255 Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Thr Val 260 265 270 Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala 275 280 285 Gly Gly Ser Phe Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg 290 295 300 Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu 305 310 315 320 Glu Glu Arg Arg Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile 325 330 335 Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val 340 345 350 Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu 355 360 365 Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro Glu Ile Glu Asp Val Gly 370 375 380 Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys 385 390 395 400 Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys 405 410 415 Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly 420 425 430 Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val 435 440 445 Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe 450 455 460 Val Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys 465 470 475 480 Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys 485 490 495 Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp 500 505 510 Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser 515 520 525 Lys Ile Leu Lys Val Ile Arg Lys Asn Leu Val Lys Lys Cys Leu Glu 530 535 540 Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr 545 550 555 560 Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln 565 570 575 Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser 580 585 590 Gly Asp Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu 595 600 605 Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys Asp Gln Val 610 615 620 Ala Asn Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val 625 630 635 640 Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys 645 650 655 Glu Phe Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu 660 665 670 Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr 675 680 685 Lys Phe Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys 690 695 700 Val Glu Lys Val Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys 705 710 715 720 Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met 725 730 735 Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala 740 745 750 Lys Lys His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu 755 760 765 Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu 770 775 780 Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu 785 790 795 800 Glu Asp Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu 805 810 815 Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr Ala Asp Asp Thr Ser Ala 820 825 830 Ala Val Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser 835 840 845 Arg Met Glu Glu Val Asp 850 <210> 11 <211> 712 <212> PRT <213> Homo sapiens <400> 11 Met Ala Gly Gly Pro Gly Pro Gly Glu Pro Ala Ala Pro Gly Ala Gln 1 5 10 15 His Phe Leu Tyr Glu Val Pro Pro Trp Val Met Cys Arg Phe Tyr Lys 20 25 30 Val Met Asp Ala Leu Glu Pro Ala Asp Trp Cys Gln Phe Ala Ala Leu 35 40 45 Ile Val Arg Asp Gln Thr Glu Leu Arg Leu Cys Glu Arg Ser Gly Gln 50 55 60 Arg Thr Ala Ser Val Leu Trp Pro Trp Ile Asn Arg Asn Ala Arg Val 65 70 75 80 Ala Asp Leu Val His Ile Leu Thr His Leu Gln Leu Leu Arg Ala Arg 85 90 95 Asp Ile Ile Thr Ala Trp His Pro Pro Ala Pro Leu Pro Ser Pro Gly 100 105 110 Thr Thr Ala Pro Arg Pro Ser Ser Ile Pro Ala Pro Ala Glu Ala Glu 115 120 125 Ala Trp Ser Pro Arg Lys Leu Pro Ser Ser Ala Ser Thr Phe Leu Ser 130 135 140 Pro Ala Phe Pro Gly Ser Gln Thr His Ser Gly Pro Glu Leu Gly Leu 145 150 155 160 Val Pro Ser Pro Ala Ser Leu Trp Pro Pro Pro Pro Ser Pro Ala Pro 165 170 175 Ser Ser Thr Lys Pro Gly Pro Glu Ser Ser Ser Val Ser Leu Leu Gln Gly 180 185 190 Ala Arg Pro Phe Pro Phe Cys Trp Pro Leu Cys Glu Ile Ser Arg Gly 195 200 205 Thr His Asn Phe Ser Glu Glu Leu Lys Ile Gly Glu Gly Gly Phe Gly 210 215 220 Cys Val Tyr Arg Ala Val Met Arg Asn Thr Val Tyr Ala Val Lys Arg 225 230 235 240 Leu Lys Glu Asn Ala Asp Leu Glu Trp Thr Ala Val Lys Gln Ser Phe 245 250 255 Leu Thr Glu Val Glu Gln Leu Ser Arg Phe Arg His Pro Asn Ile Val 260 265 270 Asp Phe Ala Gly Tyr Cys Ala Gln Asn Gly Phe Tyr Cys Leu Val Tyr 275 280 285 Gly Phe Leu Pro Asn Gly Ser Leu Glu Asp Arg Leu His Cys Gln Thr 290 295 300 Gln Ala Cys Pro Pro Leu Ser Trp Pro Gln Arg Leu Asp Ile Leu Leu 305 310 315 320 Gly Thr Ala Arg Ala Ile Gln Phe Leu His Gln Asp Ser Pro Ser Leu 325 330 335 Ile His Gly Asp Ile Lys Ser Ser Asn Val Leu Leu Asp Glu Arg Leu 340 345 350 Thr Pro Lys Leu Gly Asp Phe Gly Leu Ala Arg Phe Ser Arg Phe Ala 355 360 365 Gly Ser Ser Pro Ser Gln Ser Ser Met Val Ala Arg Thr Gln Thr Val 370 375 380 Arg Gly Thr Leu Ala Tyr Leu Pro Glu Glu Tyr Ile Lys Thr Gly Arg 385 390 395 400 Leu Ala Val Asp Thr Asp Thr Phe Ser Phe Gly Val Val Val Leu Glu 405 410 415 Thr Leu Ala Gly Gln Arg Ala Val Lys Thr His Gly Ala Arg Thr Lys 420 425 430 Tyr Leu Lys Asp Leu Val Glu Glu Glu Ala Glu Glu Ala Gly Val Ala 435 440 445 Leu Arg Ser Thr Gln Ser Thr Leu Gln Ala Gly Leu Ala Ala Asp Ala 450 455 460 Trp Ala Ala Pro Ile Ala Met Gln Ile Tyr Lys Lys His Leu Asp Pro 465 470 475 480 Arg Pro Gly Pro Cys Pro Pro Glu Leu Gly Leu Gly Leu Gly Gln Leu 485 490 495 Ala Cys Cys Cys Leu His Arg Arg Ala Lys Arg Arg Pro Pro Met Thr 500 505 510 Gln Val Tyr Glu Arg Leu Glu Lys Leu Gln Ala Val Val Ala Gly Val 515 520 525 Pro Gly His Ser Glu Ala Ala Ser Cys Ile Pro Pro Ser Pro Gln Glu 530 535 540 Asn Ser Tyr Val Ser Ser Thr Gly Arg Ala His Ser Gly Ala Ala Pro 545 550 555 560 Trp Gln Pro Leu Ala Ala Pro Ser Gly Ala Ser Ala Gln Ala Ala Glu 565 570 575 Gln Leu Gln Arg Gly Pro Asn Gln Pro Val Glu Ser Asp Glu Ser Leu 580 585 590 Gly Gly Leu Ser Ala Ala Leu Arg Ser Trp His Leu Thr Pro Ser Cys 595 600 605 Pro Leu Asp Pro Ala Pro Leu Arg Glu Ala Gly Cys Pro Gln Gly Asp 610 615 620 Thr Ala Gly Glu Ser Ser Trp Gly Ser Gly Pro Gly Ser Arg Pro Thr 625 630 635 640 Ala Val Glu Gly Leu Ala Leu Gly Ser Ser Ala Ser Ser Ser Ser Glu 645 650 655 Pro Pro Gln Ile Ile Ile Asn Pro Ala Arg Gln Lys Met Val Gln Lys 660 665 670 Leu Ala Leu Tyr Glu Asp Gly Ala Leu Asp Ser Leu Gln Leu Leu Ser 675 680 685 Ser Ser Ser Leu Pro Gly Leu Gly Leu Glu Gln Asp Arg Gln Gly Pro 690 695 700 Glu Glu Ser Asp Glu Phe Gln Ser 705 710 <210> 12 <211> 1560 <212> PRT <213> Homo sapiens <400> 12 Met Glu Pro Gly Ser Asp Asp Phe Leu Pro Pro Pro Glu Cys Pro Val 1 5 10 15 Phe Glu Pro Ser Trp Ala Glu Phe Arg Asp Pro Leu Gly Tyr Ile Ala 20 25 30 Lys Ile Arg Pro Ile Ala Glu Lys Ser Gly Ile Cys Lys Ile Arg Pro 35 40 45 Pro Ala Asp Trp Gln Pro Pro Phe Ala Val Glu Val Asp Asn Phe Arg 50 55 60 Phe Thr Pro Arg Ile Gln Arg Leu Asn Glu Leu Glu Ala Gln Thr Arg 65 70 75 80 Val Lys Leu Asn Tyr Leu Asp Gln Ile Ala Lys Phe Trp Glu Ile Gln 85 90 95 Gly Ser Ser Leu Lys Ile Pro Asn Val Glu Arg Arg Ile Leu Asp Leu 100 105 110 Tyr Ser Leu Ser Lys Ile Val Val Glu Glu Gly Gly Tyr Glu Ala Ile 115 120 125 Cys Lys Asp Arg Arg Trp Ala Arg Val Ala Gln Arg Leu Asn Tyr Pro 130 135 140 Pro Gly Lys Asn Ile Gly Ser Leu Leu Arg Ser His Tyr Glu Arg Ile 145 150 155 160 Val Tyr Pro Tyr Glu Met Tyr Gln Ser Gly Ala Asn Leu Val Gln Cys 165 170 175 Asn Thr Arg Pro Phe Asp Asn Glu Glu Lys Asp Lys Glu Tyr Lys Pro 180 185 190 His Ser Ile Pro Leu Arg Gln Ser Val Gln Pro Ser Lys Phe Asn Ser 195 200 205 Tyr Gly Arg Arg Ala Lys Arg Leu Gln Pro Asp Pro Glu Pro Thr Glu 210 215 220 Glu Asp Ile Glu Lys Asn Pro Glu Leu Lys Lys Leu Gln Ile Tyr Gly 225 230 235 240 Ala Gly Pro Lys Met Met Gly Leu Gly Leu Met Ala Lys Asp Lys Thr 245 250 255 Leu Arg Lys Lys Asp Lys Glu Gly Pro Glu Cys Pro Pro Thr Val Val 260 265 270 Val Lys Glu Glu Leu Gly Gly Asp Val Lys Val Glu Ser Thr Ser Pro 275 280 285 Lys Thr Phe Leu Glu Ser Lys Glu Glu Leu Ser His Ser Pro Glu Pro 290 295 300 Cys Thr Lys Met Thr Met Arg Leu Arg Arg Asn His Ser Asn Ala Gln 305 310 315 320 Phe Ile Glu Ser Tyr Val Cys Arg Met Cys Ser Arg Gly Asp Glu Asp 325 330 335 Asp Lys Leu Leu Leu Cys Asp Gly Cys Asp Asp Asn Tyr His Ile Phe 340 345 350 Cys Leu Leu Pro Pro Leu Pro Glu Ile Pro Lys Gly Val Trp Arg Cys 355 360 365 Pro Lys Cys Val Met Ala Glu Cys Lys Arg Pro Pro Glu Ala Phe Gly 370 375 380 Phe Glu Gln Ala Thr Arg Glu Tyr Thr Leu Gln Ser Phe Gly Glu Met 385 390 395 400 Ala Asp Ser Phe Lys Ala Asp Tyr Phe Asn Met Pro Val His Met Val 405 410 415 Pro Thr Glu Leu Val Glu Lys Glu Phe Trp Arg Leu Val Asn Ser Ile 420 425 430 Glu Glu Asp Val Thr Val Glu Tyr Gly Ala Asp Ile His Ser Lys Glu 435 440 445 Phe Gly Ser Gly Phe Pro Val Ser Asp Ser Lys Arg His Leu Thr Pro 450 455 460 Glu Glu Glu Glu Tyr Ala Thr Ser Gly Trp Asn Leu Asn Val Met Pro 465 470 475 480 Val Leu Glu Gln Ser Val Leu Cys His Ile Asn Ala Asp Ile Ser Gly 485 490 495 Met Lys Val Pro Trp Leu Tyr Val Gly Met Val Phe Ser Ala Phe Cys 500 505 510 Trp His Ile Glu Asp His Trp Ser Tyr Ser Ile Asn Tyr Leu His Trp 515 520 525 Gly Glu Pro Lys Thr Trp Tyr Gly Val Pro Ser Leu Ala Ala Glu His 530 535 540 Leu Glu Glu Val Met Lys Lys Leu Thr Pro Glu Leu Phe Asp Ser Gln 545 550 555 560 Pro Asp Leu Leu His Gln Leu Val Thr Leu Met Asn Pro Asn Thr Leu 565 570 575 Met Ser His Gly Val Pro Val Val Arg Thr Asn Gln Cys Ala Gly Glu 580 585 590 Phe Val Ile Thr Phe Pro Arg Ala Tyr His Ser Gly Phe Asn Gln Gly 595 600 605 Tyr Asn Phe Ala Glu Ala Val Asn Phe Cys Thr Ala Asp Trp Leu Pro 610 615 620 Ala Gly Arg Gln Cys Ile Glu His Tyr Arg Arg Leu Arg Arg Tyr Cys 625 630 635 640 Val Phe Ser His Glu Glu Leu Ile Cys Lys Met Ala Ala Cys Pro Glu 645 650 655 Lys Leu Asp Leu Asn Leu Ala Ala Ala Val His Lys Glu Met Phe Ile 660 665 670 Met Val Gln Glu Glu Arg Arg Leu Arg Lys Ala Leu Leu Glu Lys Gly 675 680 685 Ile Thr Glu Ala Glu Arg Glu Ala Phe Glu Leu Leu Pro Asp Asp Glu 690 695 700 Arg Gln Cys Ile Lys Cys Lys Thr Thr Cys Phe Leu Ser Ala Leu Ala 705 710 715 720 Cys Tyr Asp Cys Pro Asp Gly Leu Val Cys Leu Ser His Ile Asn Asp 725 730 735 Leu Cys Lys Cys Ser Ser Ser Arg Gln Tyr Leu Arg Tyr Arg Tyr Thr 740 745 750 Leu Asp Glu Leu Pro Ala Met Leu His Lys Leu Lys Val Arg Ala Glu 755 760 765 Ser Phe Asp Thr Trp Ala Asn Lys Val Arg Val Ala Leu Glu Val Glu 770 775 780 Asp Gly Arg Lys Arg Ser Leu Glu Glu Leu Arg Ala Leu Glu Ser Glu 785 790 795 800 Ala Arg Glu Arg Arg Phe Pro Asn Ser Glu Leu Leu Gln Gln Leu Lys 805 810 815 Asn Cys Leu Ser Glu Ala Glu Ala Cys Val Ser Arg Ala Leu Gly Leu 820 825 830 Val Ser Gly Gln Glu Ala Gly Pro His Arg Val Ala Gly Leu Gln Met 835 840 845 Thr Leu Thr Glu Leu Arg Ala Phe Leu Asp Gln Met Asn Asn Leu Pro 850 855 860 Cys Ala Met His Gln Ile Gly Asp Val Lys Gly Val Leu Glu Gln Val 865 870 875 880 Glu Ala Tyr Gln Ala Glu Ala Arg Glu Ala Leu Ala Ser Leu Pro Ser 885 890 895 Ser Pro Gly Leu Leu Gln Ser Leu Leu Glu Arg Gly Arg Gln Leu Gly 900 905 910 Val Glu Val Pro Glu Ala Gln Gln Leu Gln Arg Gln Val Glu Gln Ala 915 920 925 Arg Trp Leu Asp Glu Val Lys Arg Thr Leu Ala Pro Ser Ala Arg Arg 930 935 940 Gly Thr Leu Ala Val Met Arg Gly Leu Leu Val Ala Gly Ala Ser Val 945 950 955 960 Ala Pro Ser Pro Ala Val Asp Lys Ala Gln Ala Glu Leu Gln Glu Leu 965 970 975 Leu Thr Ile Ala Glu Arg Trp Glu Glu Lys Ala His Leu Cys Leu Glu 980 985 990 Ala Arg Gln Lys His Pro Pro Ala Thr Leu Glu Ala Ile Ile Arg Glu 995 1000 1005 Ala Glu Asn Ile Pro Val His Leu Pro Asn Ile Gln Ala Leu Lys Glu 1010 1015 1020 Ala Leu Ala Lys Ala Arg Ala Trp Ile Ala Asp Val Asp Glu Ile Gln 1025 1030 1035 1040 Asn Gly Asp His Tyr Pro Cys Leu Asp Asp Leu Glu Gly Leu Val Ala 1045 1050 1055 Val Gly Arg Asp Leu Pro Val Gly Leu Glu Glu Leu Arg Gln Leu Glu 1060 1065 1070 Leu Gln Val Leu Thr Ala His Ser Trp Arg Glu Lys Ala Ser Lys Thr 1075 1080 1085 Phe Leu Lys Lys Asn Ser Cys Tyr Thr Leu Leu Glu Val Leu Cys Pro 1090 1095 1100 Cys Ala Asp Ala Gly Ser Asp Ser Thr Lys Arg Ser Arg Trp Met Glu 1105 1110 1115 1120 Lys Glu Leu Gly Leu Tyr Lys Ser Asp Thr Glu Leu Leu Gly Leu Ser 1125 1130 1135 Ala Gln Asp Leu Arg Asp Pro Gly Ser Val Ile Val Ala Phe Lys Glu 1140 1145 1150 Gly Glu Gln Lys Glu Lys Glu Gly Ile Leu Gln Leu Arg Arg Thr Asn 1155 1160 1165 Ser Ala Lys Pro Ser Pro Leu Ala Ser Ser Ser Thr Ala Ser Ser Thr 1170 1175 1180 Thr Ser Ile Cys Val Cys Gly Gln Val Leu Ala Gly Ala Gly Ala Leu 1185 1190 1195 1200 Gln Cys Asp Leu Cys Gln Asp Trp Phe His Gly Arg Cys Val Ser Val 1205 1210 1215 Pro Arg Leu Leu Ser Ser Pro Arg Pro Asn Pro Thr Ser Ser Pro Leu 1220 1225 1230 Leu Ala Trp Trp Glu Trp Asp Thr Lys Phe Leu Cys Pro Leu Cys Met 1235 1240 1245 Arg Ser Arg Arg Pro Arg Leu Glu Thr Ile Leu Ala Leu Leu Val Ala 1250 1255 1260 Leu Gln Arg Leu Pro Val Arg Leu Pro Glu Gly Glu Ala Leu Gln Cys 1265 1270 1275 1280 Leu Thr Glu Arg Ala Ile Ser Trp Gln Gly Arg Ala Arg Gln Ala Leu 1285 1290 1295 Ala Ser Glu Asp Val Thr Ala Leu Leu Gly Arg Leu Ala Glu Leu Arg 1300 1305 1310 Gln Arg Leu Gln Ala Glu Pro Arg Pro Glu Glu Pro Pro Asn Tyr Pro 1315 1320 1325 Ala Ala Pro Ala Ser Asp Pro Leu Arg Glu Gly Ser Gly Lys Asp Met 1330 1335 1340 Pro Lys Val Gln Gly Leu Leu Glu Asn Gly Asp Ser Val Thr Ser Pro 1345 1350 1355 1360 Glu Lys Val Ala Pro Glu Glu Gly Ser Gly Lys Arg Asp Leu Glu Leu 1365 1370 1375 Leu Ser Ser Leu Leu Pro Gln Leu Thr Gly Pro Val Leu Glu Leu Pro 1380 1385 1390 Glu Ala Thr Arg Ala Pro Leu Glu Glu Leu Met Met Glu Gly Asp Leu 1395 1400 1405 Leu Glu Val Thr Leu Asp Glu Asn His Ser Ile Trp Gln Leu Leu Gln 1410 1415 1420 Ala Gly Gln Pro Pro Asp Leu Glu Arg Ile Arg Thr Leu Leu Glu Leu 1425 1430 1435 1440 Glu Lys Ala Glu Arg His Gly Ser Arg Ala Arg Gly Arg Ala Leu Glu 1445 1450 1455 Arg Arg Arg Arg Arg Lys Val Asp Arg Gly Gly Glu Gly Asp Asp Pro 1460 1465 1470 Ala Arg Glu Glu Leu Glu Pro Lys Arg Val Arg Ser Ser Gly Pro Glu 1475 1480 1485 Ala Glu Glu Val Gln Glu Glu Glu Glu Leu Glu Glu Glu Glu Thr Gly Gly 1490 1495 1500 Glu Gly Pro Pro Ala Pro Ile Pro Thr Thr Gly Ser Pro Ser Thr Gln 1505 1510 1515 1520 Glu Asn Gln Asn Gly Leu Glu Pro Ala Glu Gly Thr Thr Ser Gly Pro 1525 1530 1535 Ser Ala Pro Phe Ser Thr Leu Thr Pro Arg Leu His Leu Pro Cys Pro 1540 1545 1550 Gln Gln Pro Pro Gln Gln Gln Leu 1555 1560 <210> 13 <211> 1401 <212> PRT <213> Homo sapiens <400> 13 Met Lys Ser Cys Gly Val Ser Leu Ala Thr Ala Ala Ala Ala Ala Ala 1 5 10 15 Ala Phe Gly Asp Glu Glu Lys Lys Met Ala Ala Gly Lys Ala Ser Gly 20 25 30 Glu Ser Glu Glu Ala Ser Pro Ser Leu Thr Ala Glu Glu Arg Glu Ala 35 40 45 Leu Gly Gly Leu Asp Ser Arg Leu Phe Gly Phe Val Arg Phe His Glu 50 55 60 Asp Gly Ala Arg Thr Lys Ala Leu Leu Gly Lys Ala Val Arg Cys Tyr 65 70 75 80 Glu Ser Leu Ile Leu Lys Ala Glu Gly Lys Val Glu Ser Asp Phe Phe 85 90 95 Cys Gln Leu Gly His Phe Asn Leu Leu Leu Glu Asp Tyr Pro Lys Ala 100 105 110 Leu Ser Ala Tyr Gln Arg Tyr Tyr Ser Leu Gln Ser Asp Tyr Trp Lys 115 120 125 Asn Ala Ala Phe Leu Tyr Gly Leu Gly Leu Val Tyr Phe His Tyr Asn 130 135 140 Ala Phe Gln Trp Ala Ile Lys Ala Phe Gln Glu Val Leu Tyr Val Asp 145 150 155 160 Pro Ser Phe Cys Arg Ala Lys Glu Ile His Leu Arg Leu Gly Leu Met 165 170 175 Phe Lys Val Asn Thr Asp Tyr Glu Ser Ser Leu Lys His Phe Gln Leu 180 185 190 Ala Leu Val Asp Cys Asn Pro Cys Thr Leu Ser Asn Ala Glu Ile Gln 195 200 205 Phe His Ile Ala His Leu Tyr Glu Thr Gln Arg Lys Tyr His Ser Ala 210 215 220 Lys Glu Ala Tyr Glu Gln Leu Leu Gln Thr Glu Asn Leu Ser Ala Gln 225 230 235 240 Val Lys Ala Thr Val Leu Gln Gln Leu Gly Trp Met His His Thr Val 245 250 255 Asp Leu Leu Gly Asp Lys Ala Thr Lys Glu Ser Tyr Ala Ile Gln Tyr 260 265 270 Leu Gln Lys Ser Leu Glu Ala Asp Pro Asn Ser Gly Gln Ser Trp Tyr 275 280 285 Phe Leu Gly Arg Cys Tyr Ser Ser Ile Gly Lys Val Gln Asp Ala Phe 290 295 300 Ile Ser Tyr Arg Gln Ser Ile Asp Lys Ser Glu Ala Ser Ala Asp Thr 305 310 315 320 Trp Cys Ser Ile Gly Val Leu Tyr Gln Gln Gln Asn Gln Pro Met Asp 325 330 335 Ala Leu Gln Ala Tyr Ile Cys Ala Val Gln Leu Asp His Gly His Ala 340 345 350 Ala Ala Trp Met Asp Leu Gly Thr Leu Tyr Glu Ser Cys Asn Gln Pro 355 360 365 Gln Asp Ala Ile Lys Cys Tyr Leu Asn Ala Thr Arg Ser Lys Ser Cys 370 375 380 Ser Asn Thr Ser Ala Leu Ala Ala Arg Ile Lys Tyr Leu Gln Ala Gln 385 390 395 400 Leu Cys Asn Leu Pro Gln Gly Ser Leu Gln Asn Lys Thr Lys Leu Leu 405 410 415 Pro Ser Ile Glu Glu Ala Trp Ser Leu Pro Ile Pro Ala Glu Leu Thr 420 425 430 Ser Arg Gln Gly Ala Met Asn Thr Ala Gln Gln Asn Thr Ser Asp Asn 435 440 445 Trp Ser Gly Gly His Ala Val Ser His Pro Pro Val Gln Gln Gln Ala 450 455 460 His Ser Trp Cys Leu Thr Pro Gln Lys Leu Gln His Leu Glu Gln Leu 465 470 475 480 Arg Ala Asn Arg Asn Asn Leu Asn Pro Ala Gln Lys Leu Met Leu Glu 485 490 495 Gln Leu Glu Ser Gln Phe Val Leu Met Gln Gln His Gln Met Arg Pro 500 505 510 Thr Gly Val Ala Gln Val Arg Ser Thr Gly Ile Pro Asn Gly Pro Thr 515 520 525 Ala Asp Ser Ser Leu Pro Thr Asn Ser Val Ser Gly Gln Gln Pro Gln 530 535 540 Leu Ala Leu Thr Arg Val Pro Ser Val Ser Gln Pro Gly Val Arg Pro 545 550 555 560 Ala Cys Pro Gly Gln Pro Leu Ala Asn Gly Pro Phe Ser Ala Gly His 565 570 575 Val Pro Cys Ser Thr Ser Arg Thr Leu Gly Ser Thr Asp Thr Ile Leu 580 585 590 Ile Gly Asn Asn His Ile Thr Gly Ser Gly Ser Asn Gly Asn Val Pro 595 600 605 Tyr Leu Gln Arg Asn Ala Leu Thr Leu Pro His Asn Arg Thr Asn Leu 610 615 620 Thr Ser Ser Ala Glu Glu Pro Trp Lys Asn Gln Leu Ser Asn Ser Thr 625 630 635 640 Gln Gly Leu His Lys Gly Gln Ser Ser His Ser Ala Gly Pro Asn Gly 645 650 655 Glu Arg Pro Leu Ser Ser Thr Gly Pro Ser Gln His Leu Gln Ala Ala 660 665 670 Gly Ser Gly Ile Gln Asn Gln Asn Gly His Pro Thr Leu Pro Ser Asn 675 680 685 Ser Val Thr Gln Gly Ala Ala Leu Asn His Leu Ser Ser His Thr Ala 690 695 700 Thr Ser Gly Gly Gln Gln Gly Ile Thr Leu Thr Lys Glu Ser Lys Pro 705 710 715 720 Ser Gly Asn Ile Leu Thr Val Pro Glu Thr Ser Arg His Thr Gly Glu 725 730 735 Thr Pro Asn Ser Thr Ala Ser Val Glu Gly Leu Pro Asn His Val His 740 745 750 Gln Met Thr Ala Asp Ala Val Cys Ser Pro Ser His Gly Asp Ser Lys 755 760 765 Ser Pro Gly Leu Leu Ser Ser Asp Asn Pro Gln Leu Ser Ala Leu Leu 770 775 780 Met Gly Lys Ala Asn Asn Asn Val Gly Thr Gly Thr Cys Asp Lys Val 785 790 795 800 Asn Asn Ile His Pro Ala Val His Thr Lys Thr Asp Asn Ser Val Ala 805 810 815 Ser Ser Pro Ser Ser Ala Ile Ser Thr Ala Thr Pro Ser Pro Lys Ser 820 825 830 Thr Glu Gln Thr Thr Thr Asn Ser Val Thr Ser Leu Asn Ser Pro His 835 840 845 Ser Gly Leu His Thr Ile Asn Gly Glu Gly Met Glu Glu Ser Gln Ser 850 855 860 Pro Met Lys Thr Asp Leu Leu Leu Val Asn His Lys Pro Ser Pro Gln 865 870 875 880 Ile Ile Pro Ser Met Ser Val Ser Ile Tyr Pro Ser Ser Ala Glu Val 885 890 895 Leu Lys Ala Cys Arg Asn Leu Gly Lys Asn Gly Leu Ser Asn Ser Ser 900 905 910 Ile Leu Leu Asp Lys Cys Pro Pro Pro Arg Pro Pro Ser Ser Pro Tyr 915 920 925 Pro Pro Leu Pro Lys Asp Lys Leu Asn Pro Pro Thr Pro Ser Ile Tyr 930 935 940 Leu Glu Asn Lys Arg Asp Ala Phe Phe Pro Pro Leu His Gln Phe Cys 945 950 955 960 Thr Asn Pro Asn Asn Pro Val Thr Val Ile Arg Gly Leu Ala Gly Ala 965 970 975 Leu Lys Leu Asp Leu Gly Leu Phe Ser Thr Lys Thr Leu Val Glu Ala 980 985 990 Asn Asn Glu His Met Val Glu Val Arg Thr Gln Leu Leu Gln Pro Ala 995 1000 1005 Asp Glu Asn Trp Asp Pro Thr Gly Thr Lys Lys Ile Trp His Cys Glu 1010 1015 1020 Ser Asn Arg Ser His Thr Thr Ile Ala Lys Tyr Ala Gln Tyr Gln Ala 1025 1030 1035 1040 Ser Ser Phe Gln Glu Ser Leu Arg Glu Glu Asn Glu Lys Arg Ser His 1045 1050 1055 His Lys Asp His Ser Asp Ser Glu Ser Thr Ser Ser Asp Asn Ser Gly 1060 1065 1070 Arg Arg Arg Lys Gly Pro Phe Lys Thr Ile Lys Phe Gly Thr Asn Ile 1075 1080 1085 Asp Leu Ser Asp Asp Lys Lys Trp Lys Leu Gln Leu His Glu Leu Thr 1090 1095 1100 Lys Leu Pro Ala Phe Val Arg Val Val Ser Ala Gly Asn Leu Leu Ser 1105 1110 1115 1120 His Val Gly His Thr Ile Leu Gly Met Asn Thr Val Gln Leu Tyr Met 1125 1130 1135 Lys Val Pro Gly Ser Arg Thr Pro Gly His Gln Glu Asn Asn Asn Phe 1140 1145 1150 Cys Ser Val Asn Ile Asn Ile Gly Pro Gly Asp Cys Glu Trp Phe Val 1155 1160 1165 Val Pro Glu Gly Tyr Trp Gly Val Leu Asn Asp Phe Cys Glu Lys Asn 1170 1175 1180 Asn Leu Asn Phe Leu Met Gly Ser Trp Trp Pro Asn Leu Glu Asp Leu 1185 1190 1195 1200 Tyr Glu Ala Asn Val Pro Val Tyr Arg Phe Ile Gln Arg Pro Gly Asp 1205 1210 1215 Leu Val Trp Ile Asn Ala Gly Thr Val His Trp Val Gln Ala Ile Gly 1220 1225 1230 Trp Cys Asn Asn Ile Ala Trp Asn Val Gly Pro Leu Thr Ala Cys Gln 1235 1240 1245 Tyr Lys Leu Ala Val Glu Arg Tyr Glu Trp Asn Lys Leu Gln Ser Val 1250 1255 1260 Lys Ser Ile Val Pro Met Val His Leu Ser Trp Asn Met Ala Arg Asn 1265 1270 1275 1280 Ile Lys Val Ser Asp Pro Lys Leu Phe Glu Met Ile Lys Tyr Cys Leu 1285 1290 1295 Leu Arg Thr Leu Lys Gln Cys Gln Thr Leu Arg Glu Ala Leu Ile Ala 1300 1305 1310 Ala Gly Lys Glu Ile Ile Trp His Gly Arg Thr Lys Glu Glu Pro Ala 1315 1320 1325 His Tyr Cys Ser Ile Cys Glu Val Glu Val Phe Asp Leu Leu Phe Val 1330 1335 1340 Thr Asn Glu Ser Asn Ser Arg Lys Thr Tyr Ile Val His Cys Gln Asp 1345 1350 1355 1360 Cys Ala Arg Lys Thr Ser Gly Asn Leu Glu Asn Phe Val Val Leu Glu 1365 1370 1375 Gln Tyr Lys Met Glu Asp Leu Met Gln Val Tyr Asp Gln Phe Thr Leu 1380 1385 1390 Ala Pro Pro Leu Pro Ser Ala Ser Ser 1395 1400 <210> 14 <211> 859 <212> PRT <213> Homo sapiens <400> 14 Met Ala Cys Arg Trp Ser Thr Lys Glu Ser Pro Arg Trp Arg Ser Ala 1 5 10 15 Leu Leu Leu Leu Phe Leu Ala Gly Val Tyr Gly Asn Gly Ala Leu Ala 20 25 30 Glu His Ser Glu Asn Val His Ile Ser Gly Val Ser Thr Ala Cys Gly 35 40 45 Glu Thr Pro Glu Gln Ile Arg Ala Pro Ser Gly Ile Ile Thr Ser Pro 50 55 60 Gly Trp Pro Ser Glu Tyr Pro Ala Lys Ile Asn Cys Ser Trp Phe Ile 65 70 75 80 Arg Ala Asn Pro Gly Glu Ile Ile Thr Ile Ser Phe Gln Asp Phe Asp 85 90 95 Ile Gln Gly Ser Arg Arg Cys Asn Leu Asp Trp Leu Thr Ile Glu Thr 100 105 110 Tyr Lys Asn Ile Glu Ser Tyr Arg Ala Cys Gly Ser Thr Ile Pro Pro 115 120 125 Pro Tyr Ile Ser Ser Gln Asp His Ile Trp Ile Arg Phe His Ser Asp 130 135 140 Asp Asn Ile Ser Arg Lys Gly Phe Arg Leu Ala Tyr Phe Ser Gly Lys 145 150 155 160 Ser Glu Glu Pro Asn Cys Ala Cys Asp Gln Phe Arg Cys Gly Asn Gly 165 170 175 Lys Cys Ile Pro Glu Ala Trp Lys Cys Asn Asn Met Asp Glu Cys Gly 180 185 190 Asp Ser Ser Asp Glu Glu Ile Cys Ala Lys Glu Ala Asn Pro Pro Thr 195 200 205 Ala Ala Ala Phe Gln Pro Cys Ala Tyr Asn Gln Phe Gln Cys Leu Ser 210 215 220 Arg Phe Thr Lys Val Tyr Thr Cys Leu Pro Glu Ser Leu Lys Cys Asp 225 230 235 240 Gly Asn Ile Asp Cys Leu Asp Leu Gly Asp Glu Ile Asp Cys Asp Val 245 250 255 Pro Thr Cys Gly Gln Trp Leu Lys Tyr Phe Tyr Gly Thr Phe Asn Ser 260 265 270 Pro Asn Tyr Pro Asp Phe Tyr Pro Pro Gly Ser Asn Cys Thr Trp Leu 275 280 285 Ile Asp Thr Gly Asp His Arg Lys Val Ile Leu Arg Phe Thr Asp Phe 290 295 300 Lys Leu Asp Gly Thr Gly Tyr Gly Asp Tyr Val Lys Ile Tyr Asp Gly 305 310 315 320 Leu Glu Glu Asn Pro His Lys Leu Leu Arg Val Leu Thr Ala Phe Asp 325 330 335 Ser His Ala Pro Leu Thr Val Val Ser Ser Ser Gly Gln Ile Arg Val 340 345 350 His Phe Cys Ala Asp Lys Val Asn Ala Ala Arg Gly Phe Asn Ala Thr 355 360 365 Tyr Gln Val Asp Gly Phe Cys Leu Pro Trp Glu Ile Pro Cys Gly Gly 370 375 380 Asn Trp Gly Cys Tyr Thr Glu Gln Gln Arg Cys Asp Gly Tyr Trp His 385 390 395 400 Cys Pro Asn Gly Arg Asp Glu Thr Asn Cys Thr Met Cys Gln Lys Glu 405 410 415 Glu Phe Pro Cys Ser Arg Asn Gly Val Cys Tyr Pro Arg Ser Asp Arg 420 425 430 Cys Asn Tyr Gln Asn His Cys Pro Asn Gly Ser Asp Glu Lys Asn Cys 435 440 445 Phe Phe Cys Gln Pro Gly Asn Phe His Cys Lys Asn Asn Arg Cys Val 450 455 460 Phe Glu Ser Trp Val Cys Asp Ser Gln Asp Asp Cys Gly Asp Gly Ser 465 470 475 480 Asp Glu Glu Asn Cys Pro Val Ile Val Pro Thr Arg Val Ile Thr Ala 485 490 495 Ala Val Ile Gly Ser Leu Ile Cys Gly Leu Leu Leu Val Ile Ala Leu 500 505 510 Gly Cys Thr Cys Lys Leu Tyr Ser Leu Arg Met Phe Glu Arg Arg Ser 515 520 525 Phe Glu Thr Gln Leu Ser Arg Val Glu Ala Glu Leu Leu Arg Arg Glu 530 535 540 Ala Pro Pro Ser Tyr Gly Gln Leu Ile Ala Gln Gly Leu Ile Pro Pro 545 550 555 560 Val Glu Asp Phe Pro Val Cys Ser Pro Asn Gln Ala Ser Val Leu Glu 565 570 575 Asn Leu Arg Leu Ala Val Arg Ser Gln Leu Gly Phe Thr Ser Val Arg 580 585 590 Leu Pro Met Ala Gly Arg Ser Ser Asn Ile Trp Asn Arg Ile Phe Asn 595 600 605 Phe Ala Arg Ser Arg His Ser Gly Ser Leu Ala Leu Val Ser Ala Asp 610 615 620 Gly Asp Glu Val Val Pro Ser Gln Ser Thr Ser Arg Glu Pro Glu Arg 625 630 635 640 Asn His Thr His Arg Ser Leu Phe Ser Val Glu Ser Asp Asp Thr Asp 645 650 655 Thr Glu Asn Glu Arg Arg Asp Met Ala Gly Ala Ser Gly Gly Val Ala 660 665 670 Ala Pro Leu Pro Gln Lys Val Pro Pro Thr Thr Ala Val Glu Ala Thr 675 680 685 Val Gly Ala Cys Ala Ser Ser Ser Thr Gln Ser Thr Arg Gly Gly His 690 695 700 Ala Asp Asn Gly Arg Asp Val Thr Ser Val Glu Pro Pro Ser Val Ser 705 710 715 720 Pro Ala Arg His Gln Leu Thr Ser Ala Leu Ser Arg Met Thr Gln Gly 725 730 735 Leu Arg Trp Val Arg Phe Thr Leu Gly Arg Ser Ser Ser Leu Ser Gln 740 745 750 Asn Gln Ser Pro Leu Arg Gln Leu Asp Asn Gly Val Ser Gly Arg Glu 755 760 765 Asp Asp Asp Asp Val Glu Met Leu Ile Pro Ile Ser Asp Gly Ser Ser 770 775 780 Asp Phe Asp Val Asn Asp Cys Ser Arg Pro Leu Leu Asp Leu Ala Ser 785 790 795 800 Asp Gln Gly Gln Gly Leu Arg Gln Pro Tyr Asn Ala Thr Asn Pro Gly 805 810 815 Val Arg Pro Ser Asn Arg Asp Gly Pro Cys Glu Arg Cys Gly Ile Val 820 825 830 His Thr Ala Gln Ile Pro Asp Thr Cys Leu Glu Val Thr Leu Lys Asn 835 840 845 Glu Thr Ser Asp Asp Glu Ala Leu Leu Leu Cys 850 855 <210> 15 <211> 1070 <212> PRT <213> Homo sapiens <400> 15 Met Val Leu Asp Asp Leu Pro Asn Leu Glu Asp Ile Tyr Thr Ser Leu 1 5 10 15 Cys Ser Ser Thr Met Glu Asp Ser Glu Met Asp Phe Asp Ser Gly Leu 20 25 30 Glu Asp Asp Asp Thr Lys Ser Asp Ser Ile Leu Glu Asp Ser Thr Ile 35 40 45 Phe Val Ala Phe Lys Gly Asn Ile Asp Asp Lys Asp Phe Lys Trp Lys 50 55 60 Leu Asp Ala Ile Leu Lys Asn Val Pro Asn Leu Leu His Met Glu Ser 65 70 75 80 Ser Lys Leu Lys Val Gln Lys Val Glu Pro Trp Asn Ser Val Arg Val 85 90 95 Thr Phe Asn Ile Pro Arg Glu Ala Ala Glu Arg Leu Arg Ile Leu Ala 100 105 110 Gln Ser Asn Asn Gln Gln Leu Arg Asp Leu Gly Ile Leu Ser Val Gln 115 120 125 Ile Glu Gly Glu Gly Ala Ile Asn Leu Ala Leu Ala Gln Asn Arg Ser 130 135 140 Gln Asp Val Arg Met Asn Gly Pro Met Gly Ala Gly Asn Ser Val Arg 145 150 155 160 Met Glu Ala Gly Phe Pro Met Ala Ser Gly Pro Gly Ile Ile Arg Met 165 170 175 Asn Asn Pro Ala Thr Val Met Ile Pro Pro Gly Gly Asn Val Ser Ser 180 185 190 Ser Met Met Ala Pro Gly Pro Asn Pro Glu Leu Gln Pro Arg Thr Pro 195 200 205 Arg Pro Ala Ser Gln Ser Asp Ala Met Asp Pro Leu Leu Ser Gly Leu 210 215 220 His Ile Gln Gln Gln Ser His Pro Ser Gly Ser Leu Ala Pro Pro His 225 230 235 240 His Pro Met Gln Pro Val Ser Val Asn Arg Gln Met Asn Pro Ala Asn 245 250 255 Phe Pro Gln Leu Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 260 265 270 Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Leu Gln Ala 275 280 285 Arg Pro Pro Gln Gln His Gln Gln Gln Gln Pro Gln Gly Ile Arg Pro 290 295 300 Gln Phe Thr Ala Pro Thr Gln Val Pro Val Pro Pro Gly Trp Asn Gln 305 310 315 320 Leu Pro Ser Gly Ala Leu Gln Pro Pro Pro Ala Gln Gly Ser Leu Gly 325 330 335 Thr Met Thr Ala Asn Gln Gly Trp Lys Lys Ala Pro Leu Pro Gly Pro 340 345 350 Met Gln Gln Gln Leu Gln Ala Arg Pro Ser Leu Ala Thr Val Gln Thr 355 360 365 Pro Ser His Pro Pro Pro Pro Tyr Pro Phe Gly Ser Gln Gln Ala Ser 370 375 380 Gln Ala His Thr Asn Phe Pro Gln Met Ser Asn Pro Gly Gln Phe Thr 385 390 395 400 Ala Pro Gln Met Lys Ser Leu Gln Gly Gly Pro Ser Arg Val Pro Thr 405 410 415 Pro Leu Gln Gln Pro His Leu Thr Asn Lys Ser Pro Ala Ser Ser Pro 420 425 430 Ser Ser Phe Gln Gln Gly Ser Pro Ala Ser Ser Pro Thr Val Asn Gln 435 440 445 Thr Gln Gln Gln Met Gly Pro Arg Pro Pro Gln Asn Asn Pro Leu Pro 450 455 460 Gln Gly Phe Gln Gln Pro Val Ser Ser Pro Gly Arg Asn Pro Met Val 465 470 475 480 Gln Gln Gly Asn Val Pro Pro Asn Phe Met Val Met Gln Gln Gln Pro 485 490 495 Pro Asn Gln Gly Pro Gln Ser Leu His Pro Gly Leu Gly Gly Met Pro 500 505 510 Lys Arg Leu Pro Pro Gly Phe Ser Ala Gly Gln Ala Asn Pro Asn Phe 515 520 525 Met Gln Gly Gln Val Pro Ser Thr Thr Ala Thr Thr Pro Gly Asn Ser 530 535 540 Gly Ala Pro Gln Leu Gln Ala Asn Gln Asn Val Gln His Ala Gly Gly 545 550 555 560 Gln Gly Ala Gly Pro Pro Gln Asn Gln Met Gln Val Ser His Gly Pro 565 570 575 Pro Asn Met Met Gln Pro Ser Leu Met Gly Ile His Gly Asn Met Asn 580 585 590 Asn Gln Gln Ala Gly Thr Ser Gly Val Pro Gln Val Asn Leu Ser Asn 595 600 605 Met Gln Gly Gln Pro Gln Gln Gly Pro Pro Ser Gln Leu Met Gly Met 610 615 620 His Gln Gln Ile Val Pro Ser Gln Gly Gln Met Val Gln Gln Gln Gly 625 630 635 640 Thr Leu Asn Pro Gln Asn Pro Met Ile Leu Ser Arg Ala Gln Leu Met 645 650 655 Pro Gln Gly Gln Met Met Val Asn Pro Pro Ser Gln Asn Leu Gly Pro 660 665 670 Ser Pro Gln Arg Met Thr Pro Pro Lys Gln Met Leu Ser Gln Gln Gly 675 680 685 Pro Gln Met Met Ala Pro His Asn Gln Met Met Gly Pro Gln Gly Gln 690 695 700 Val Leu Leu Gln Gln Asn Pro Met Ile Glu Gln Ile Met Thr Asn Gln 705 710 715 720 Met Gln Gly Asn Lys Gln Gln Phe Asn Thr Gln Asn Gln Ser Asn Val 725 730 735 Met Pro Gly Pro Ala Gln Ile Met Arg Gly Pro Thr Pro Asn Met Gln 740 745 750 Gly Asn Met Val Gln Phe Thr Gly Gln Met Ser Gly Gln Met Leu Pro 755 760 765 Gln Gln Gly Pro Val Asn Asn Ser Pro Ser Gln Val Met Gly Ile Gln 770 775 780 Gly Gln Val Leu Arg Pro Pro Gly Pro Ser Pro His Met Ala Gln Gln 785 790 795 800 His Gly Asp Pro Ala Thr Thr Ala Asn Asn Asp Val Ser Leu Ser Gln 805 810 815 Met Met Pro Asp Val Ser Ile Gln Gln Thr Asn Met Val Pro Pro His 820 825 830 Val Gln Ala Met Gln Gly Asn Ser Ala Ser Gly Asn His Phe Ser Gly 835 840 845 His Gly Met Ser Phe Asn Ala Pro Phe Ser Gly Ala Pro Asn Gly Asn 850 855 860 Gln Met Ser Cys Gly Gln Asn Pro Gly Phe Pro Val Asn Lys Asp Val 865 870 875 880 Thr Leu Thr Ser Pro Leu Leu Val Asn Leu Leu Gln Ser Asp Ile Ser 885 890 895 Ala Gly His Phe Gly Val Asn Asn Lys Gln Asn Asn Thr Asn Ala Asn 900 905 910 Lys Pro Lys Lys Lys Lys Pro Pro Arg Lys Lys Lys Asn Ser Gln Gln 915 920 925 Asp Leu Asn Thr Pro Asp Thr Arg Pro Ala Gly Leu Glu Glu Ala Asp 930 935 940 Gln Pro Pro Leu Pro Gly Glu Gln Gly Ile Asn Leu Asp Asn Ser Gly 945 950 955 960 Pro Lys Leu Pro Glu Phe Ser Asn Arg Pro Pro Ala Pro Ser Gln Asn 965 970 975 Leu Val Ser Lys Glu Thr Ser Thr Thr Ala Leu Gln Ala Ser Val Ala 980 985 990 Arg Pro Glu Leu Glu Val Asn Ala Ala Ile Val Ser Gly Gln Ser Ser 995 1000 1005 Glu Pro Lys Glu Ile Val Glu Lys Ser Lys Ile Pro Gly Arg Arg Asn 1010 1015 1020 Ser Arg Thr Glu Glu Pro Thr Val Ala Ser Glu Ser Val Glu Asn Gly 1025 1030 1035 1040 His Arg Lys Arg Ser Ser Arg Pro Ala Ser Ala Ser Ser Ser Thr Lys 1045 1050 1055 Asp Ile Thr Ser Ala Val Gln Ser Lys Arg Arg Lys Ser Lys 1060 1065 1070 <210> 16 <211> 1630 <212> PRT <213> Homo sapiens <400> 16 Met Pro Phe Ala Lys Arg Ile Val Glu Pro Gln Trp Leu Cys Arg Gln 1 5 10 15 Arg Arg Pro Ala Pro Gly Pro Ala Val Asp Ala Ser Gly Gly Ser Ala 20 25 30 Glu Pro Pro Pro Pro Leu Gln Pro Pro Gly Arg Arg Asp Leu Asp Glu 35 40 45 Val Glu Ala Pro Gly Pro Glu Glu Pro Ala Arg Ala Val Pro Ala Pro 50 55 60 Ser Gly Leu Pro Pro Pro Pro Pro Pro Leu Pro Ala Pro Ala Asp Gln 65 70 75 80 Thr Gln Pro Pro His Gly Glu Ala Ser Val Ala Gly Glu Glu Ser Thr 85 90 95 Ala Gly Ile Pro Glu Ala Ala Pro Ala Ala Gly Glu Ala Ser Ser Ala 100 105 110 Ala Ala Ala Ala Ala Val Leu Leu Met Leu Asp Leu Cys Ala Val Ser 115 120 125 Asn Ala Ala Leu Ala Arg Val Leu Arg Gln Leu Ser Asp Val Ala Arg 130 135 140 His Ala Cys Ser Leu Phe Gln Glu Leu Glu Ser Asp Ile Gln Leu Thr 145 150 155 160 His Arg Arg Val Trp Ala Leu Gln Gly Lys Leu Gly Gly Val Gln Arg 165 170 175 Val Leu Ser Thr Leu Asp Pro Lys Gln Glu Ala Val Pro Val Ser Asn 180 185 190 Leu Asp Ile Glu Ser Lys Leu Ser Val Tyr Tyr Arg Ala Pro Trp His 195 200 205 Gln Gln Arg Asn Ile Phe Leu Pro Ala Thr Arg Pro Pro Cys Val Glu 210 215 220 Glu Leu His Arg His Ala Arg Gln Ser Leu Gln Ala Leu Arg Arg Glu 225 230 235 240 His Arg Ser Arg Ser Asp Arg Arg Glu Gln Arg Ala Ala Ala Pro Leu 245 250 255 Ser Ile Ala Ala Pro Pro Leu Pro Ala Tyr Pro Pro Ala His Ser Gln 260 265 270 Arg Arg Arg Glu Phe Lys Asp Arg His Phe Leu Thr Ser His Pro Pro 275 280 285 Glu Asp Glu Asp Thr Asp Val Met Leu Gly Gln Arg Pro Lys Asn Pro 290 295 300 Ile His Asn Ile Pro Ser Thr Leu Asp Lys Gln Thr Asn Trp Ser Lys 305 310 315 320 Ala Leu Pro Leu Pro Thr Pro Glu Glu Lys Met Lys Gln Asp Ala Gln 325 330 335 Val Ile Ser Ser Cys Ile Ile Pro Ile Asn Val Thr Gly Val Gly Phe 340 345 350 Asp Arg Glu Ala Ser Ile Arg Cys Ser Leu Val His Ser Gln Ser Val 355 360 365 Leu Gln Arg Arg Arg Lys Leu Arg Arg Arg Lys Thr Ile Ser Gly Ile 370 375 380 Pro Arg Arg Val Gln Gln Glu Ile Asp Ser Asp Glu Ser Pro Val Ala 385 390 395 400 Arg Glu Arg Asn Val Ile Val His Thr Asn Pro Asp Pro Ser Asn Thr 405 410 415 Val Asn Arg Ile Ser Gly Thr Arg Asp Ser Glu Cys Gln Thr Glu Asp 420 425 430 Ile Leu Ile Ala Ala Pro Ser Arg Arg Arg Ile Arg Ala Gln Arg Gly 435 440 445 Gln Ser Ile Ala Ala Ser Leu Ser His Ser Ala Gly Asn Ile Ser Ala 450 455 460 Leu Ala Asp Lys Gly Asp Thr Met Phe Thr Pro Ala Val Ser Ser Arg 465 470 475 480 Thr Arg Ser Arg Ser Leu Pro Arg Glu Gly Asn Arg Gly Gly Asp Ala 485 490 495 Glu Pro Lys Val Gly Ala Lys Pro Ser Ala Tyr Glu Glu Gly Glu Ser 500 505 510 Phe Val Gly Asp His Glu Arg Thr Pro Asn Asp Phe Ser Glu Ala Pro 515 520 525 Ser Ser Pro Ser Ala Gln Asp His Gln Pro Thr Leu Gly Leu Ala Cys 530 535 540 Ser Gln His Leu His Ser Pro Gln His Lys Leu Ser Glu Arg Gly Arg 545 550 555 560 Ser Arg Leu Ser Arg Met Ala Ala Asp Ser Gly Ser Cys Asp Ile Ser 565 570 575 Ser Asn Ser Asp Thr Phe Gly Ser Pro Ile His Cys Ile Ser Thr Ala 580 585 590 Gly Val Leu Leu Ser Ser His Met Asp Gln Lys Asp Asp His Gln Ser 595 600 605 Ser Ser Gly Asn Trp Ser Gly Ser Ser Ser Thr Cys Pro Ser Gln Thr 610 615 620 Ser Glu Thr Ile Pro Pro Ala Ala Ser Pro Pro Leu Thr Gly Ser Ser 625 630 635 640 His Cys Asp Ser Glu Leu Ser Leu Asn Thr Ala Pro His Ala Asn Glu 645 650 655 Asp Ala Ser Val Phe Val Thr Glu Gln Tyr Asn Asp His Leu Asp Lys 660 665 670 Val Arg Gly His Arg Ala Asn Ser Phe Thr Ser Thr Val Ala Asp Leu 675 680 685 Leu Asp Asp Pro Asn Asn Ser Asn Thr Ser Asp Ser Glu Trp Asn Tyr 690 695 700 Leu His His His His Asp Ala Ser Cys Arg Gln Asp Phe Ser Pro Glu 705 710 715 720 Arg Pro Lys Ala Asp Ser Leu Gly Cys Pro Ser Phe Thr Ser Met Ala 725 730 735 Thr Tyr Asp Ser Phe Leu Glu Lys Ser Pro Ser Asp Lys Ala Asp Thr 740 745 750 Ser Ser His Phe Ser Val Asp Thr Glu Gly Tyr Tyr Thr Ser Met His 755 760 765 Phe Asp Cys Gly Leu Lys Gly Asn Lys Ser Tyr Val Cys His Tyr Ala 770 775 780 Ala Leu Gly Pro Glu Asn Gly Gln Gly Val Gly Ala Ser Pro Gly Leu 785 790 795 800 Pro Asp Cys Ala Trp Gln Asp Tyr Leu Asp His Lys Arg Gln Gly Arg 805 810 815 Pro Ser Ile Ser Phe Arg Lys Pro Lys Ala Lys Pro Thr Pro Pro Lys 820 825 830 Arg Ser Ser Ser Leu Arg Lys Ser Asp Gly Asn Ala Asp Ile Ser Glu 835 840 845 Lys Lys Glu Pro Lys Ile Ser Ser Gly Gln His Leu Pro His Ser Ser 850 855 860 Arg Glu Met Lys Leu Pro Leu Asp Phe Ala Asn Thr Pro Ser Arg Met 865 870 875 880 Glu Asn Ala Asn Leu Pro Thr Lys Gln Glu Pro Ser Trp Ile Asn Gln 885 890 895 Ser Glu Gln Gly Ile Lys Glu Pro Gln Leu Asp Ala Ser Asp Ile Pro 900 905 910 Pro Phe Lys Asp Glu Val Ala Glu Ser Thr His Tyr Ala Asp Leu Trp 915 920 925 Leu Leu Asn Asp Leu Lys Thr Asn Asp Pro Tyr Arg Ser Leu Ser Asn 930 935 940 Ser Ser Thr Ala Thr Gly Thr Thr Val Ile Glu Cys Ile Lys Ser Pro 945 950 955 960 Glu Ser Ser Glu Ser Gln Thr Ser Gln Ser Glu Ser Arg Ala Thr Thr 965 970 975 Pro Ser Leu Pro Ser Val Asp Asn Glu Phe Lys Leu Ala Ser Pro Glu 980 985 990 Lys Leu Ala Gly Leu Ala Ser Pro Ser Ser Gly Tyr Ser Ser Gln Ser 995 1000 1005 Glu Thr Pro Thr Ser Ser Phe Pro Thr Ala Phe Phe Ser Gly Pro Leu 1010 1015 1020 Ser Pro Gly Gly Ser Lys Arg Lys Pro Lys Val Pro Glu Arg Lys Ser 1025 1030 1035 1040 Ser Leu Gln Gln Pro Ser Leu Lys Asp Gly Thr Ile Ser Leu Ser Lys 1045 1050 1055 Asp Leu Glu Leu Pro Ile Ile Pro Pro Thr His Leu Asp Leu Ser Ala 1060 1065 1070 Leu His Asn Val Leu Asn Lys Pro Phe His His Arg His Pro Leu His 1075 1080 1085 Val Phe Thr His Asn Lys Gln Asn Thr Val Gly Glu Thr Leu Arg Ser 1090 1095 1100 Asn Pro Pro Pro Ser Leu Ala Ile Thr Pro Thr Ile Leu Lys Ser Val 1105 1110 1115 1120 Asn Leu Arg Ser Ile Asn Lys Ser Glu Glu Val Lys Gln Lys Glu Glu 1125 1130 1135 Asn Asn Thr Asp Leu Pro Tyr Leu Glu Glu Ser Thr Leu Thr Thr Ala 1140 1145 1150 Ala Leu Ser Pro Ser Lys Ile Arg Pro His Thr Ala Asn Lys Ser Val 1155 1160 1165 Ser Arg Gln Tyr Ser Thr Glu Asp Thr Ile Leu Ser Phe Leu Asp Ser 1170 1175 1180 Ser Ala Val Glu Met Gly Pro Asp Lys Leu His Leu Glu Lys Asn Ser 1185 1190 1195 1200 Thr Phe Asp Val Lys Asn Arg Cys Asp Pro Glu Thr Ile Thr Ser Ala 1205 1210 1215 Gly Ser Ser Leu Leu Asp Ser Asn Val Thr Lys Asp Gln Val Arg Thr 1220 1225 1230 Glu Thr Glu Pro Ile Pro Glu Asn Thr Pro Thr Lys Asn Cys Ala Phe 1235 1240 1245 Pro Thr Glu Gly Phe Gln Arg Val Ser Ala Ala Arg Pro Asn Asp Leu 1250 1255 1260 Asp Gly Lys Ile Ile Gln Tyr Gly Pro Gly Pro Asp Glu Thr Leu Glu 1265 1270 1275 1280 Gln Val Gln Lys Ala Pro Ser Ala Gly Leu Glu Glu Val Ala Gln Pro 1285 1290 1295 Glu Ser Val Asp Val Ile Thr Ser Gln Ser Asp Ser Pro Thr Arg Ala 1300 1305 1310 Thr Asp Val Ser Asn Gln Phe Lys His Gln Phe Val Met Ser Arg His 1315 1320 1325 His Asp Lys Val Pro Gly Thr Ile Ser Tyr Glu Ser Glu Ile Thr Ser 1330 1335 1340 Val Asn Ser Phe Pro Glu Lys Cys Ser Lys Gln Glu Asn Ile Ala Ser 1345 1350 1355 1360 Gly Ile Ser Ala Lys Ser Ala Ser Asp Asn Ser Lys Ala Glu Glu Thr 1365 1370 1375 Gln Gly Asn Val Asp Glu Ala Ser Leu Lys Glu Ser Ser Pro Ser Asp 1380 1385 1390 Asp Ser Ile Ile Ser Pro Leu Ser Glu Asp Ser Gln Ala Glu Ala Glu 1395 1400 1405 Gly Val Phe Val Ser Pro Asn Lys Pro Arg Thr Thr Glu Asp Leu Phe 1410 1415 1420 Ala Val Ile His Arg Ser Lys Arg Lys Val Leu Gly Arg Lys Asp Ser 1425 1430 1435 1440 Gly Asp Met Ser Val Arg Ser Lys Ser Arg Ala Pro Leu Ser Ser Ser 1445 1450 1455 Ser Ser Ser Ala Ser Ser Ile Thr Ser Pro Ser Ser Asn Val Thr Thr 1460 1465 1470 Pro Asn Ser Gln Arg Ser Pro Gly Leu Ile Tyr Arg Asn Ala Lys Lys 1475 1480 1485 Ser Asn Thr Ser Asn Glu Glu Phe Lys Leu Leu Leu Leu Lys Lys Gly 1490 1495 1500 Ser Arg Ser Asp Ser Ser Tyr Arg Met Ser Ala Thr Glu Ile Leu Lys 1505 1510 1515 1520 Ser Pro Ile Leu Pro Lys Pro Pro Gly Glu Leu Thr Ala Glu Ser Pro 1525 1530 1535 Gln Ser Thr Asp Asp Ala His Gln Gly Ser Gln Gly Ala Glu Ala Leu 1540 1545 1550 Ser Pro Leu Ser Pro Cys Ser Pro Arg Val Asn Ala Glu Gly Phe Ser 1555 1560 1565 Ser Lys Ser Phe Ala Thr Ser Ala Ser Ala Arg Val Gly Arg Ser Arg 1570 1575 1580 Ala Pro Pro Ala Ala Ser Ser Ser Arg Tyr Ser Val Arg Cys Arg Leu 1585 1590 1595 1600 Tyr Asn Thr Pro Met Gln Ala Ile Ser Glu Gly Glu Thr Glu Asn Ser 1605 1610 1615 Asp Gly Ser Pro His Asp Asp Arg Ser Ser Gln Ser Ser Thr 1620 1625 1630 <210> 17 <211> 1388 <212> PRT <213> Homo sapiens <400> 17 Met Ser Ile Pro Leu His Ser Leu Arg Phe Asn Asn Thr Met Arg Glu 1 5 10 15 Glu Asn Val Glu Pro Gln Asn Lys Gln Met Ala Phe Cys Arg Pro Met 20 25 30 Thr Glu Thr Arg Ala Asp Val Gln Ile Leu His Ser His Val Gln Leu 35 40 45 Pro Ile Val Ser Thr Ser Ala Ser Asp Pro Gly Gly Thr Ser Thr Gln 50 55 60 Leu Met Thr Ser Pro Val Phe Asp Thr Met Ser Ala Pro Leu Met Gly 65 70 75 80 Val Pro Asn Ser Gly Ala Leu Ser Pro Pro Leu Met Pro Ala Ser Asp 85 90 95 Ser Gly Ala Leu Ser Pro Leu Leu Met Pro Ala Ser Asp Ser Gly Ala 100 105 110 Leu Ser Pro Leu Leu Met Pro Ala Leu Asp Ser Gly Thr Leu Ser Pro 115 120 125 Leu Leu Ser Thr Ser Glu Tyr Gly Val Met Ser Pro Gly Met Met Thr 130 135 140 Ile Pro Asp Phe Gly Thr Met Ser Ala Thr Leu Met Val Ala Pro Asp 145 150 155 160 Ser Ala Glu Ile Ser Pro Leu Ala Met Pro Ala Pro Ser Ser Gly Val 165 170 175 Val Cys Thr Pro Ile Met Ser Thr Ser Ser Ser Glu Ala Met Ser Thr 180 185 190 Pro Leu Met Leu Ala Pro Asp Ser Gly Glu Leu Ser Pro Ile Leu Met 195 200 205 Gln Asp Met Asn Pro Gly Val Met Ser Thr Gln Pro Val Pro Ala Pro 210 215 220 Ser Ser Glu Ala Met Ser Pro Leu Gln Ile Thr Asp Glu Asp Thr Glu 225 230 235 240 Ala Met Ser Lys Val Leu Met Thr Ala Leu Ala Ser Gly Glu Ile Ser 245 250 255 Ser Leu Leu Met Ser Gly Thr Asp Ser Glu Ala Ile Ser Ser Leu Ile 260 265 270 Met Ser Ala Val Ala Ser Gly Gly Thr Ser Pro Gln Pro Thr Ser Thr 275 280 285 Gln Asn Ser Gly Gly Ile Pro Thr Pro Leu Met Ser Asp Leu Asp Ser 290 295 300 Gly Ile Met Ser Ser Leu Leu Met Ser Ser Pro Gly Ser Glu Val Met 305 310 315 320 Ser Thr Pro Leu Leu Ser Val Pro Asp Ala Gly Glu Met Ser Thr Leu 325 330 335 Pro Lys Pro Ala Pro Asp Ala Glu Ala Met Ser Pro Ala Leu Met Thr 340 345 350 Ala Leu Pro Ser Gly Val Met Pro Thr Gln Thr Met Pro Ala Pro Gly 355 360 365 Ser Gly Ala Met Ser Pro Trp Ser Thr Gln Asn Val Asp Ser Glu Met 370 375 380 Met Ser Asn Pro Pro Val Arg Ala Thr Ala Ser Gly Val Met Ser Ala 385 390 395 400 Pro Pro Val Arg Ala Leu Asp Ser Gly Ala Met Ser Thr Pro Leu Met 405 410 415 Gly Ala Pro Ala Ser Gly Asn Met Ser Thr Leu Gln Lys Thr Val Pro 420 425 430 Ala Ser Gly Ala Met Thr Thr Ser Leu Met Thr Val Pro Ser Ser Gly 435 440 445 Val Met Ser Thr Glu Gln Met Ser Ala Thr Ala Ser Arg Val Met Ser 450 455 460 Ala Gln Leu Thr Met Ala Lys Thr Ser Gly Ala Met Pro Thr Gly Ser 465 470 475 480 Met Lys Ala Val Ala Lys Gln Tyr Lys Arg Ala Thr Ala Ser Gly Lys 485 490 495 Met Ser Thr Pro Leu Arg Arg Ala Pro Thr Ser Gly Ala Met Ser Thr 500 505 510 Gln Pro Val Thr Ala Thr Ala Ser Glu Thr Met Ser Met Pro Gln Leu 515 520 525 Thr Val Pro Ala Ser Gly Ser Met Ser Met Leu Gln Met Arg Ala Pro 530 535 540 Val Ser Glu Ala Met Ser Met Pro Gln Met Arg Thr Met Ala Ser Gly 545 550 555 560 Leu Thr Ser Ala Ala Gln Met Lys Ala Met Thr Ser Gly Ala Met Ser 565 570 575 Thr Pro Leu Met Thr Ala Gln Thr Ser Gly Ser Thr Ser Thr Leu Leu 580 585 590 Met Arg Asp Thr Ala Ser Gly Val Met Ser Cys Pro Gln Met Arg Ser 595 600 605 Leu Ala Ser Gly Ala Leu Ser Lys Pro Leu Met Thr Pro Lys Ala Ser 610 615 620 Gly Thr Met Phe Thr Glu Lys Met Thr Thr Thr Ala Ser Glu Ala Met 625 630 635 640 Pro Thr Leu Leu Met Arg Asp Thr Val Ser Gly Ala Leu Ser Met Pro 645 650 655 Gln Met Thr Asp Thr Ala Ser Gly Gly Leu Ser Ala Ser Leu Met Arg 660 665 670 Asp Thr Ala Ser Gly Ala Met Ser Thr Ser Gln Met Thr Ala Thr Val 675 680 685 Ser Gly Gly Met Ser Met Pro Leu Met Arg Ala Gln Asp Pro Gly Val 690 695 700 Met Pro Ala Ser Leu Met Arg Ala Lys Val Ser Gly Lys Met Leu Ser 705 710 715 720 Gln Pro Met Ser Thr Gln Asp Pro Gly Gly Met Ser Met Ser Pro Met 725 730 735 Lys Ser Met Thr Ala Gly Gly Met Gln Met Asn Ser Pro Thr Ser Asp 740 745 750 Val Met Ser Thr Pro Thr Val Arg Ala Trp Thr Ser Glu Thr Met Ser 755 760 765 Thr Pro Leu Met Arg Thr Ser Asp Pro Gly Glu Arg Pro Ser Leu Leu 770 775 780 Thr Arg Ala Ser Ser Ser Gly Glu Met Ser Leu Pro Leu Met Arg Ala 785 790 795 800 Pro Ala Ser Gly Glu Ile Ala Thr Pro Leu Arg Ser Pro Ala Tyr Gly 805 810 815 Ala Met Ser Ala Pro Gln Met Thr Ala Thr Ala Ser Gly Met Met Ser 820 825 830 Ser Met Pro Gln Val Lys Ala Pro Ile Ser Gly Ala Met Ser Met Pro 835 840 845 Leu Thr Arg Ser Thr Ala Ser Gly Gly Met Ser Met Pro Leu Met Arg 850 855 860 Ala Pro Asp Ser Arg Val Thr Ser Thr Ser Gln Met Met Pro Thr Ala 865 870 875 880 Ser Gly Asp Met Cys Thr Leu Pro Val Arg Ala Pro Ala Ser Gly Gly 885 890 895 Val Ser Ser Pro Leu Val Arg Ala Pro Ala Ser Gly Thr Met Ser Thr 900 905 910 Pro Leu Arg Arg Pro Ser Ala Cys Glu Thr Val Ser Thr Glu Leu Met 915 920 925 Arg Ala Ser Ala Ser Gly His Met Ser Thr Ala Gln Thr Thr Ala Met 930 935 940 Val Ser Gly Gly Met Ser Lys Pro Leu Met Arg Ala Pro Ala Ser Gly 945 950 955 960 Thr Met Pro Met Pro Leu Met Ser Ala Met Ala Ser Gly Glu Met Ser 965 970 975 Met Pro Leu Met Glu Thr Met Ala Ser Gly Ala Thr Ser Thr Leu Gln 980 985 990 Thr Ser Val Ala Asn Ser Arg Ser Met Ser Leu Ser Gln Thr Thr Tyr 995 1000 1005 Thr Val Ser Gly Arg Met Ala Thr Ala Pro Ile Arg Ala Ser Ala Ser 1010 1015 1020 Gly Ala Arg Ser Thr Ser Phe Met Arg Ala Ser Val Ser Gly Ser Met 1025 1030 1035 1040 Pro Met Pro Leu Pro Arg Ala Thr Ala Ser Gly Cys Gly Met Gly Met 1045 1050 1055 Ser Met Pro Gln Met Thr Ala Thr Asp Ser Arg Gly Met Ser Thr Pro 1060 1065 1070 Leu Met Arg Ala Ser Gly Pro Gly Thr Met Ser Thr Pro Gln Thr Ala 1075 1080 1085 Phe Gly Val Met Ser Thr Pro Glu Ile Lys Ala Thr Asp Ser Gly Glu 1090 1095 1100 Ala Ser Thr Ser His Ile Asn Ile Thr Ala Ser Gly Ser Lys Pro Thr 1105 1110 1115 1120 Ser His Met Thr Ala Thr Thr Pro Glu Thr Ala Lys Pro Pro Pro Lys 1125 1130 1135 Glu Val Pro Ser Phe Gly Met Leu Thr Pro Ala Leu Cys Tyr Leu Leu 1140 1145 1150 Glu Glu Gln Glu Ala Ala Arg Gly Ser Cys Ser Val Glu Glu Glu Met 1155 1160 1165 Glu Ile Asp Glu Glu Lys Gln Met Lys Gly Phe Leu Asp Asp Ser Glu 1170 1175 1180 Arg Met Ala Phe Leu Val Ser Leu His Leu Gly Ala Ala Glu Arg Trp 1185 1190 1195 1200 Phe Ile Leu Gln Met Glu Val Gly Glu Pro Leu Ser His Glu Asn Lys 1205 1210 1215 Ser Phe Leu Arg Arg Ser Gln Gly Ile Tyr Asp Ser Leu Ser Glu Ile 1220 1225 1230 Asp Ile Leu Ser Ala Val Leu Cys His Pro Lys Gln Gly Gln Lys Ser 1235 1240 1245 Val Arg Gln Tyr Ala Thr Asp Phe Leu Leu Leu Ala Arg His Leu Ser 1250 1255 1260 Trp Ser Asp Ala Ile Leu Arg Thr Arg Phe Leu Glu Gly Leu Ser Glu 1265 1270 1275 1280 Ala Val Thr Thr Lys Met Gly Arg Ile Phe Leu Lys Val Ala Gly Ser 1285 1290 1295 Leu Lys Glu Leu Ile Asp Arg Ser Leu Tyr Thr Glu Cys Gln Leu Ala 1300 1305 1310 Glu Glu Lys Asp Ser Pro Gly Asn Ser Ser Gln Val Leu Pro Thr Ala 1315 1320 1325 Cys Lys Arg Asn Asn Glu Glu Ala Met Gly Asn Glu Leu Ser Ser Gln 1330 1335 1340 Gln Gln Thr Glu Glu His Gln His Val Ser Lys Arg Cys Tyr Tyr Leu 1345 1350 1355 1360 Lys Glu His Gly Asp Pro Gln Glu Gly Leu His Asp His Leu Gly Gln 1365 1370 1375 Ser Thr Gly His His Gln Lys Ala His Thr Asn Lys 1380 1385 <210> 18 <211> 1312 <212> PRT <213> Homo sapiens <400> 18 Met Glu Glu Glu Asp Glu Ser Arg Gly Lys Thr Glu Glu Ser Gly Glu 1 5 10 15 Asp Arg Gly Asp Gly Pro Pro Asp Arg Asp Pro Thr Leu Ser Pro Ser 20 25 30 Ala Phe Ile Leu Arg Ala Ile Gln Gln Ala Val Gly Ser Ser Leu Gln 35 40 45 Gly Asp Leu Pro Asn Asp Lys Asp Gly Ser Arg Cys His Gly Leu Arg 50 55 60 Trp Arg Arg Cys Arg Ser Pro Arg Ser Glu Pro Arg Ser Gln Glu Ser 65 70 75 80 Gly Gly Thr Asp Thr Ala Thr Val Leu Asp Met Ala Thr Asp Ser Phe 85 90 95 Leu Ala Gly Leu Val Ser Val Leu Asp Pro Pro Asp Thr Trp Val Pro 100 105 110 Ser Arg Leu Asp Leu Arg Pro Gly Glu Ser Glu Asp Met Leu Glu Leu 115 120 125 Val Ala Glu Val Arg Ile Gly Asp Arg Asp Pro Ile Pro Leu Pro Val 130 135 140 Pro Ser Leu Leu Pro Arg Leu Arg Ala Trp Arg Thr Gly Lys Thr Val 145 150 155 160 Ser Pro Gln Ser Asn Ser Ser Arg Pro Thr Cys Ala Arg His Leu Thr 165 170 175 Leu Gly Thr Gly Asp Gly Gly Pro Ala Pro Pro Pro Ala Pro Ser Ser 180 185 190 Ala Ser Ser Ser Pro Ser Pro Ser Pro Ser Ser Ser Ser Pro Ser Pro 195 200 205 Pro Pro Pro Pro Pro Pro Pro Ala Pro Pro Ala Pro Pro Ala Pro Arg 210 215 220 Phe Asp Ile Tyr Asp Pro Phe His Pro Thr Asp Glu Ala Tyr Ser Pro 225 230 235 240 Pro Pro Ala Pro Glu Gln Lys Tyr Asp Pro Phe Glu Pro Thr Gly Ser 245 250 255 Asn Pro Ser Ser Ser Ala Gly Thr Pro Ser Pro Glu Glu Glu Glu Glu 260 265 270 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Glu Glu Glu Glu Glu 275 280 285 Gly Leu Ser Gln Ser Ile Ser Arg Ile Ser Glu Thr Leu Ala Gly Ile 290 295 300 Tyr Asp Asp Asn Ser Leu Ser Gln Asp Phe Pro Gly Asp Glu Ser Pro 305 310 315 320 Arg Pro Asp Ala Gln Pro Thr Gln Pro Thr Pro Ala Pro Gly Thr Pro 325 330 335 Pro Gln Val Asp Ser Thr Arg Ala Asp Gly Ala Met Arg Arg Arg Val 340 345 350 Phe Val Val Gly Thr Glu Ala Glu Ala Cys Arg Glu Gly Lys Val Ser 355 360 365 Val Glu Val Val Thr Ala Gly Gly Ala Ala Leu Pro Pro Leu Leu 370 375 380 Pro Pro Gly Asp Ser Glu Ile Glu Glu Gly Glu Ile Val Gln Pro Glu 385 390 395 400 Glu Glu Pro Arg Leu Ala Leu Ser Leu Phe Arg Pro Gly Gly Arg Ala 405 410 415 Ala Arg Pro Thr Pro Ala Ala Ser Ala Thr Pro Thr Ala Gln Pro Leu 420 425 430 Pro Gln Pro Pro Ala Pro Arg Ala Pro Glu Gly Asp Asp Phe Leu Ser 435 440 445 Leu His Ala Glu Ser Asp Gly Glu Gly Ala Leu Gln Val Asp Leu Gly 450 455 460 Glu Pro Ala Pro Ala Pro Pro Ala Ala Asp Ser Arg Trp Gly Gly Leu 465 470 475 480 Asp Leu Arg Arg Lys Ile Leu Thr Gln Arg Arg Glu Arg Tyr Arg Gln 485 490 495 Arg Ser Pro Ser Pro Ala Pro Ala Pro Ala Pro Ala Ala Ala Ala Gly 500 505 510 Pro Pro Thr Arg Lys Lys Ser Arg Arg Glu Arg Lys Arg Ser Gly Glu 515 520 525 Ala Lys Glu Ala Ala Ser Ser Ser Ser Gly Thr Gln Pro Ala Pro Pro 530 535 540 Ala Pro Ala Ser Pro Trp Asp Ser Lys Lys His Arg Ser Arg Asp Arg 545 550 555 560 Lys Pro Gly Ser His Ala Ser Ser Ser Ala Arg Arg Arg Ser Arg Ser 565 570 575 Arg Ser Arg Ser Arg Ser Thr Arg Arg Arg Ser Arg Ser Thr Asp Arg 580 585 590 Arg Arg Gly Gly Ser Arg Arg Ser Arg Ser Arg Glu Lys Arg Arg Arg 595 600 605 Arg Arg Arg Ser Ala Ser Pro Pro Pro Ala Thr Ser Ser Ser Ser Ser 610 615 620 Ser Arg Arg Glu Arg His Arg Gly Lys His Arg Asp Gly Gly Gly Ser 625 630 635 640 Lys Lys Lys Lys Lys Arg Ser Arg Ser Arg Gly Glu Lys Arg Ser Gly 645 650 655 Asp Gly Ser Glu Lys Ala Pro Ala Pro Ala Pro Pro Pro Ser Gly Ser 660 665 670 Thr Ser Cys Gly Asp Arg Asp Ser Arg Arg Arg Gly Ala Val Pro Pro 675 680 685 Ser Ile Gln Asp Leu Thr Asp His Asp Leu Phe Ala Ile Lys Arg Thr 690 695 700 Ile Thr Val Gly Arg Leu Asp Lys Ser Asp Pro Arg Gly Pro Ser Pro 705 710 715 720 Ala Pro Ala Ser Ser Pro Lys Arg Glu Val Leu Tyr Asp Ser Glu Gly 725 730 735 Leu Ser Gly Glu Glu Arg Gly Gly Lys Ser Ser Gln Lys Asp Arg Arg 740 745 750 Arg Ser Gly Ala Ala Ser Ser Ser Ser Ser Ser Ser Arg Glu Lys Gly Ser 755 760 765 Arg Arg Lys Ala Leu Asp Gly Gly Asp Arg Asp Arg Asp Arg Asp Arg 770 775 780 Asp Arg Asp Arg Asp Arg Ser Ser Lys Lys Ala Arg Pro Pro Lys Glu 785 790 795 800 Ser Ala Pro Ser Ser Gly Pro Pro Pro Lys Pro Pro Val Ser Ser Gly 805 810 815 Ser Gly Ser Ser Ser Ser Ser Ser Ser Cys Ser Ser Arg Lys Val Lys 820 825 830 Leu Gln Ser Lys Val Ala Val Leu Ile Arg Glu Gly Val Ser Ser Thr 835 840 845 Thr Pro Ala Lys Asp Ala Ala Ser Ala Gly Leu Gly Ser Ile Gly Val 850 855 860 Lys Phe Ser Arg Asp Arg Glu Ser Arg Ser Pro Phe Leu Lys Pro Asp 865 870 875 880 Glu Arg Ala Pro Thr Glu Met Ala Lys Ala Ala Pro Gly Ser Thr Lys 885 890 895 Pro Lys Lys Thr Lys Val Lys Ala Lys Ala Gly Ala Lys Lys Thr Lys 900 905 910 Gly Thr Lys Gly Lys Thr Lys Pro Ser Lys Thr Arg Lys Lys Val Arg 915 920 925 Ser Gly Gly Gly Ser Gly Gly Ser Gly Gly Gln Val Ser Leu Lys Lys 930 935 940 Ser Lys Ala Asp Ser Cys Ser Gln Ala Ala Gly Thr Lys Gly Ala Glu 945 950 955 960 Glu Thr Ser Trp Ser Gly Glu Glu Arg Ala Ala Lys Val Pro Ser Thr 965 970 975 Pro Pro Pro Lys Ala Ala Pro Pro Pro Pro Ala Leu Thr Pro Asp Ser 980 985 990 Gln Thr Val Asp Ser Ser Cys Lys Thr Pro Glu Val Ser Phe Leu Pro 995 1000 1005 Glu Glu Ala Thr Glu Glu Ala Gly Val Arg Gly Gly Ala Glu Glu Glu 1010 1015 1020 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Gln 1025 1030 1035 1040 Gln Pro Ala Thr Thr Thr Ala Thr Ser Thr Ala Ala Ala Ala Pro Ser 1045 1050 1055 Thr Ala Pro Ser Ala Gly Ser Thr Ala Gly Asp Ser Gly Ala Glu Asp 1060 1065 1070 Gly Pro Ala Ser Arg Val Ser Gln Leu Pro Thr Leu Pro Pro Pro Met 1075 1080 1085 Pro Trp Asn Leu Pro Ala Gly Val Asp Cys Thr Thr Ser Gly Val Leu 1090 1095 1100 Ala Leu Thr Ala Leu Leu Phe Lys Met Glu Glu Ala Asn Leu Ala Ser 1105 1110 1115 1120 Arg Ala Lys Ala Gln Glu Leu Ile Gln Ala Thr Asn Gln Ile Leu Ser 1125 1130 1135 His Arg Lys Pro Pro Ser Ser Leu Gly Met Thr Pro Ala Pro Val Pro 1140 1145 1150 Thr Ser Leu Gly Leu Pro Pro Gly Pro Ser Ser Tyr Leu Leu Pro Gly 1155 1160 1165 Ser Leu Pro Leu Gly Gly Cys Gly Ser Thr Pro Pro Thr Pro Thr Gly 1170 1175 1180 Leu Ala Ala Thr Ser Asp Lys Arg Glu Gly Ser Ser Ser Ser Glu Gly 1185 1190 1195 1200 Arg Gly Asp Thr Asp Lys Tyr Leu Lys Lys Leu His Thr Gln Glu Arg 1205 1210 1215 Ala Val Glu Glu Val Lys Leu Ala Ile Lys Pro Tyr Tyr Gln Lys Lys 1220 1225 1230 Asp Ile Thr Lys Glu Glu Tyr Lys Asp Ile Leu Arg Lys Ala Val His 1235 1240 1245 Lys Ile Cys His Ser Lys Ser Gly Glu Ile Asn Pro Val Lys Val Ser 1250 1255 1260 Asn Leu Val Arg Ala Tyr Val Gln Arg Tyr Arg Tyr Phe Arg Lys His 1265 1270 1275 1280 Gly Arg Lys Pro Gly Asp Pro Pro Gly Pro Pro Arg Pro Pro Lys Glu 1285 1290 1295 Pro Gly Pro Pro Asp Lys Gly Gly Pro Gly Leu Pro Leu Pro Pro Leu 1300 1305 1310 <210> 19 <211> 1336 <212> PRT <213> Homo sapiens <400> 19 Met Glu Asn Leu Pro Ala Val Thr Thr Glu Glu Pro Thr Pro Met Gly 1 5 10 15 Arg Gly Pro Val Gly Pro Ser Gly Gly Gly Ser Thr Arg Asp Gln Val 20 25 30 Arg Thr Val Val Met Arg Pro Ser Val Ser Trp Glu Lys Ala Gly Pro 35 40 45 Glu Glu Ala Lys Ala Pro Val Arg Gly Asp Glu Ala Pro Pro Ala Arg 50 55 60 Val Ala Gly Pro Ala Ala Gly Thr Pro Pro Cys Gln Met Gly Val Tyr 65 70 75 80 Pro Thr Asp Leu Thr Leu Gln Leu Leu Ala Val Arg Arg Lys Ser Arg 85 90 95 Leu Arg Asp Pro Gly Leu Gln Gln Thr Leu Arg Gly Gln Leu Arg Leu 100 105 110 Leu Glu Asn Asp Ser Arg Glu Met Ala Arg Val Leu Gly Glu Leu Ser 115 120 125 Ala Arg Leu Leu Ser Ile His Ser Asp Gln Asp Arg Ile Val Val Thr 130 135 140 Phe Lys Thr Phe Glu Glu Ile Trp Lys Phe Ser Thr Tyr His Ala Leu 145 150 155 160 Gly Phe Thr His His Cys Leu Ala Asn Leu Leu Met Asp Gln Ala Phe 165 170 175 Trp Leu Leu Leu Pro Ser Glu Glu Glu Glu Thr Ala Ile Gln Val His 180 185 190 Val Asp Glu Asn Ala Leu Arg Leu Thr His Glu Ser Leu Leu Ile Gln 195 200 205 Glu Gly Pro Phe Phe Val Leu Cys Pro Asp His His Val Arg Val Met 210 215 220 Thr Gly Pro Arg Asp Ala Gly Asn Gly Pro Gln Ala Leu Arg Gln Ala 225 230 235 240 Ser Gly Ala Pro Gln Gly Glu Ala Ala Pro Glu Thr Asp Ser Ser Pro 245 250 255 Pro Ser Pro Ser Val Ser Ser Glu Glu Val Ala Val Ala Ala Ala Pro 260 265 270 Glu Pro Leu Ile Pro Phe His Gln Trp Ala Leu Arg Ile Pro Gln Asp 275 280 285 Pro Ile Asp Asp Ala Met Gly Gly Pro Val Met Pro Gly Asn Pro Leu 290 295 300 Met Ala Val Gly Leu Ala Ser Ala Leu Ala Asp Phe Gln Gly Ser Gly 305 310 315 320 Pro Glu Glu Met Thr Phe Arg Gly Gly Asp Leu Ile Glu Ile Leu Gly 325 330 335 Ala Gln Val Pro Ser Leu Pro Trp Cys Val Gly Arg His Ala Ala Ser 340 345 350 Gly Arg Val Gly Phe Val Arg Ser Ser Leu Ile Ser Met Gln Gly Pro 355 360 365 Val Ser Glu Leu Glu Ser Ala Ile Phe Leu Asn Glu Glu Glu Lys Ser 370 375 380 Phe Phe Ser Glu Gly Cys Phe Ser Glu Glu Asp Ala Arg Gln Leu Leu 385 390 395 400 Arg Arg Met Ser Gly Thr Asp Val Cys Ser Val Tyr Ser Leu Asp Ser 405 410 415 Val Glu Glu Ala Glu Thr Glu Gln Pro Gln Glu Lys Glu Ile Pro Pro 420 425 430 Pro Cys Leu Ser Pro Glu Pro Gln Glu Thr Leu Gln Lys Val Lys Asn 435 440 445 Val Leu Glu Gln Cys Lys Thr Cys Pro Gly Cys Pro Gln Glu Pro Ala 450 455 460 Ser Trp Gly Leu Cys Ala Ala Ser Ser Asp Val Ser Leu Gln Asp Pro 465 470 475 480 Glu Glu Pro Ser Phe Cys Leu Glu Ala Glu Asp Asp Trp Glu Asp Pro 485 490 495 Glu Ala Leu Ser Ser Leu Leu Leu Phe Leu Asn Ala Pro Gly Tyr Lys 500 505 510 Ala Ser Phe Arg Gly Leu Tyr Asp Val Ala Leu Pro Trp Leu Ser Ser 515 520 525 Val Phe Arg Ser Phe Ser Asp Glu Glu Glu Leu Thr Gly Arg Leu Ala 530 535 540 Gln Ala Arg Gly Ala Ala Lys Lys Ala Gly Leu Leu Met Ala Leu Ala 545 550 555 560 Arg Leu Cys Phe Leu Leu Gly Arg Leu Cys Ser Arg Arg Leu Lys Leu 565 570 575 Ser Gln Ala Arg Val Tyr Phe Glu Glu Ala Leu Gly Ala Leu Glu Gly 580 585 590 Ser Phe Gly Asp Leu Phe Leu Val Val Ala Val Tyr Ala Asn Leu Ala 595 600 605 Ser Ile Tyr Arg Lys Gln Lys Asn Arg Glu Lys Cys Ala Gln Val Val 610 615 620 Pro Lys Ala Met Ala Leu Leu Leu Gly Thr Pro Asp His Ile Cys Ser 625 630 635 640 Thr Glu Ala Glu Gly Glu Leu Leu Gln Leu Ala Leu Arg Arg Ala Val 645 650 655 Gly Gly Gln Ser Leu Gln Ala Glu Ala Arg Ala Cys Phe Leu Leu Ala 660 665 670 Arg His His Val His Leu Lys Gln Pro Glu Glu Ala Leu Pro Phe Leu 675 680 685 Glu Arg Leu Leu Leu Leu His Arg Asp Ser Gly Ala Pro Glu Ala Ala 690 695 700 Trp Leu Ser Asp Cys Tyr Leu Leu Leu Ala Asp Ile Tyr Ser Arg Lys 705 710 715 720 Cys Leu Pro His Leu Val Leu Ser Cys Val Lys Val Ala Ser Leu Arg 725 730 735 Thr Arg Gly Ser Leu Ala Gly Ser Leu Arg Ser Val Asn Leu Val Leu 740 745 750 Gln Asn Ala Pro Gln Pro His Ser Leu Pro Ala Gln Thr Ser His Tyr 755 760 765 Leu Arg Gln Ala Leu Ala Ser Leu Thr Pro Gly Thr Gly Gln Ala Leu 770 775 780 Arg Gly Pro Leu Tyr Thr Ser Leu Ala Gln Leu Tyr Ser His His Gly 785 790 795 800 Cys His Gly Pro Ala Ile Thr Phe Met Thr Gln Ala Val Glu Ala Ser 805 810 815 Ala Ile Ala Gly Val Arg Ala Ile Val Asp His Leu Val Ala Leu Ala 820 825 830 Trp Leu His Val Leu His Gly Gln Ser Pro Val Ala Leu Asp Ile Leu 835 840 845 Gln Ser Val Arg Asp Ala Val Val Ala Ser Glu Asp Gln Glu Gly Val 850 855 860 Ile Ala Asn Met Val Ala Val Ala Leu Lys Arg Thr Gly Arg Thr Arg 865 870 875 880 Gln Ala Ala Glu Ser Tyr Tyr Arg Ala Leu Arg Val Ala Arg Asp Leu 885 890 895 Gly Gln Gln Arg Asn Gln Ala Val Gly Leu Ala Asn Phe Gly Ala Leu 900 905 910 Cys Leu His Ala Gly Ala Ser Arg Leu Ala Gln His Tyr Leu Leu Glu 915 920 925 Ala Val Arg Leu Phe Ser Arg Leu Pro Leu Gly Glu Cys Gly Arg Asp 930 935 940 Phe Thr His Val Leu Leu Gln Leu Gly His Leu Cys Thr Arg Gln Gly 945 950 955 960 Pro Ala Gln Gln Gly Lys Gly Tyr Tyr Glu Trp Ala Leu Leu Val Ala 965 970 975 Val Glu Met Gly His Val Glu Ser Gln Leu Arg Ala Val Gln Arg Leu 980 985 990 Cys His Phe Tyr Ser Ala Val Met Pro Ser Glu Ala Gln Cys Val Ile 995 1000 1005 Tyr His Glu Leu Gln Leu Ser Leu Ala Cys Lys Val Ala Asp Lys Val 1010 1015 1020 Leu Glu Gly Gln Leu Leu Glu Thr Ile Ser Gln Leu Tyr Leu Ser Leu 1025 1030 1035 1040 Gly Thr Glu Arg Ala Tyr Lys Ser Ala Leu Asp Tyr Thr Lys Arg Ser 1045 1050 1055 Leu Gly Ile Phe Ile Asp Leu Gln Lys Lys Glu Lys Glu Ala His Ala 1060 1065 1070 Trp Leu Gln Ala Gly Lys Ile Tyr Tyr Ile Leu Arg Gln Ser Glu Leu 1075 1080 1085 Val Asp Leu Tyr Ile Gln Val Ala Gln Asn Val Ala Leu Tyr Thr Gly 1090 1095 1100 Asp Pro Asn Leu Gly Leu Glu Leu Phe Glu Ala Ala Gly Asp Ile Phe 1105 1110 1115 1120 Phe Asp Gly Ala Trp Glu Arg Glu Lys Ala Val Ser Phe Tyr Arg Asp 1125 1130 1135 Arg Ala Leu Pro Leu Ala Val Thr Thr Gly Asn Arg Lys Ala Glu Leu 1140 1145 1150 Arg Leu Cys Asn Lys Leu Val Ala Leu Leu Ala Thr Leu Glu Glu Pro 1155 1160 1165 Gln Glu Gly Leu Glu Phe Ala His Met Ala Leu Ala Leu Ser Ile Thr 1170 1175 1180 Leu Gly Asp Arg Leu Asn Glu Arg Val Ala Tyr His Arg Leu Ala Ala 1185 1190 1195 1200 Leu Gln His Arg Leu Gly His Gly Glu Leu Ala Glu His Phe Tyr Leu 1205 1210 1215 Lys Ala Leu Ser Leu Cys Asn Ser Pro Leu Glu Phe Asp Glu Glu Thr 1220 1225 1230 Leu Tyr Tyr Val Lys Val Tyr Leu Val Leu Gly Asp Ile Ile Phe Tyr 1235 1240 1245 Asp Leu Lys Asp Pro Phe Asp Ala Ala Gly Tyr Tyr Gln Leu Ala Leu 1250 1255 1260 Ala Ala Ala Val Asp Leu Gly Asn Lys Lys Ala Gln Leu Lys Ile Tyr 1265 1270 1275 1280 Thr Arg Leu Ala Thr Ile Tyr His Asn Phe Leu Leu Asp Arg Glu Lys 1285 1290 1295 Ser Leu Phe Phe Tyr Gln Lys Ala Arg Thr Phe Ala Thr Glu Leu Asn 1300 1305 1310 Val Arg Arg Val Asn Leu Pro Pro Leu Pro Leu Cys Gly Trp Ala Pro 1315 1320 1325 Trp Leu Ala Pro Ser His Pro Arg 1330 1335 <210> 20 <211> 1120 <212> PRT <213> Homo sapiens <400> 20 Met Trp Leu Lys Pro Glu Glu Val Leu Leu Lys Asn Ala Leu Lys Leu 1 5 10 15 Trp Leu Met Glu Arg Ser Asn Asp Tyr Phe Val Leu Gln Arg Arg Arg 20 25 30 Gly Tyr Gly Glu Glu Gly Gly Gly Gly Leu Thr Gly Leu Leu Val Gly 35 40 45 Thr Leu Asp Ser Val Leu Asp Ser Thr Ala Lys Val Ala Pro Phe Arg 50 55 60 Ile Leu His Gln Thr Pro Asp Ser Gln Val Tyr Leu Ser Ile Ala Cys 65 70 75 80 Gly Ala Asn Arg Glu Glu Ile Thr Lys His Trp Asp Trp Leu Glu Gln 85 90 95 Asn Ile Met Lys Thr Leu Ser Val Phe Asp Ser Asn Glu Asp Ile Thr 100 105 110 Asn Phe Val Gln Gly Lys Ile Arg Gly Leu Ile Ala Glu Glu Gly Lys 115 120 125 His Cys Phe Ala Lys Glu Asp Asp Pro Glu Lys Phe Arg Glu Ala Leu 130 135 140 Leu Lys Phe Glu Lys Cys Phe Gly Leu Pro Glu Lys Glu Lys Leu Val 145 150 155 160 Thr Tyr Tyr Ser Cys Ser Tyr Trp Lys Gly Arg Val Pro Cys Gln Gly 165 170 175 Trp Leu Tyr Leu Ser Thr Asn Phe Leu Ser Phe Tyr Ser Phe Leu Leu 180 185 190 Gly Ser Glu Ile Lys Leu Ile Ile Ser Trp Asp Glu Val Ser Lys Leu 195 200 205 Glu Lys Thr Ser Asn Val Ile Leu Thr Glu Ser Ile His Val Cys Ser 210 215 220 Gln Gly Glu Asn His Tyr Phe Ser Met Phe Leu His Ile Asn Gln Thr 225 230 235 240 Tyr Leu Leu Met Glu Gln Leu Ala Asn Tyr Ala Ile Arg Arg Leu Phe 245 250 255 Asp Lys Glu Thr Phe Asp Asn Asp Pro Val Leu Tyr Asn Pro Leu Gln 260 265 270 Ile Thr Lys Arg Gly Leu Glu Asn Arg Ala His Ser Glu Gln Phe Asn 275 280 285 Ala Phe Phe Arg Leu Pro Lys Gly Glu Ser Leu Lys Glu Val His Glu 290 295 300 Cys Phe Leu Trp Val Pro Phe Ser His Phe Asn Thr His Gly Lys Met 305 310 315 320 Cys Ile Ser Glu Asn Tyr Ile Cys Phe Ala Ser Gln Asp Gly Asn Gln 325 330 335 Cys Ser Val Ile Ile Pro Leu Arg Glu Val Leu Ala Ile Asp Lys Thr 340 345 350 Asn Asp Ser Ser Lys Ser Val Ile Ile Ser Ile Lys Gly Lys Thr Ala 355 360 365 Phe Arg Phe His Glu Val Lys Asp Phe Glu Gln Leu Val Ala Lys Leu 370 375 380 Arg Leu Arg Cys Gly Ala Ala Ser Thr Gln Tyr His Asp Ile Ser Thr 385 390 395 400 Glu Leu Ala Ile Ser Ser Glu Ser Thr Glu Pro Ser Asp Asn Phe Glu 405 410 415 Val Gln Ser Leu Thr Ser Gln Arg Glu Cys Ser Lys Thr Val Asn Thr 420 425 430 Glu Ala Leu Met Thr Val Phe His Pro Gln Asn Leu Glu Thr Leu Asn 435 440 445 Ser Lys Met Leu Lys Glu Lys Met Lys Glu Gln Ser Trp Lys Ile Leu 450 455 460 Phe Ala Glu Cys Gly Arg Gly Val Ser Met Phe Arg Thr Lys Lys Thr 465 470 475 480 Arg Asp Leu Val Val Arg Gly Ile Pro Glu Thr Leu Arg Gly Glu Leu 485 490 495 Trp Met Leu Phe Ser Gly Ala Val Asn Asp Met Ala Thr Asn Pro Asp 500 505 510 Tyr Tyr Thr Glu Val Val Glu Gln Ser Leu Gly Thr Cys Asn Leu Ala 515 520 525 Thr Glu Glu Ile Glu Arg Asp Leu Arg Arg Ser Leu Pro Glu His Pro 530 535 540 Ala Phe Gln Ser Asp Thr Gly Ile Ser Ala Leu Arg Arg Val Leu Thr 545 550 555 560 Ala Tyr Ala Tyr Arg Asn Pro Lys Ile Gly Tyr Cys Gln Ala Met Asn 565 570 575 Ile Leu Thr Ser Val Leu Leu Leu Tyr Ala Lys Glu Glu Glu Ala Phe 580 585 590 Trp Leu Leu Val Ala Val Cys Glu Arg Met Leu Pro Asp Tyr Phe Asn 595 600 605 Arg Arg Ile Ile Gly Ala Leu Val Asp Gln Ala Val Phe Glu Glu Leu 610 615 620 Ile Arg Asp His Leu Pro Gln Leu Thr Glu His Met Thr Asp Met Thr 625 630 635 640 Phe Phe Ser Ser Val Ser Leu Ser Trp Phe Leu Thr Leu Phe Ile Ser 645 650 655 Val Leu Pro Ile Glu Ser Ala Val Asn Val Val Asp Cys Phe Phe Tyr 660 665 670 Asp Gly Ile Lys Ala Ile Leu Gln Leu Gly Leu Ala Ile Leu Asp Tyr 675 680 685 Asn Leu Asp Lys Leu Leu Thr Cys Lys Asp Asp Ala Glu Ala Val Thr 690 695 700 Ala Leu Asn Arg Phe Phe Asp Asn Val Thr Asn Lys Asp Ser Pro Leu 705 710 715 720 Pro Ser Asn Val Gln Gln Gly Ser Asn Val Ser Asp Glu Lys Thr Ser 725 730 735 His Thr Arg Val Asp Ile Thr Asp Leu Ile Arg Glu Ser Asn Glu Lys 740 745 750 Tyr Gly Asn Ile Arg Tyr Glu Asp Ile His Ser Met Arg Cys Arg Asn 755 760 765 Arg Leu Tyr Val Ile Gln Thr Leu Glu Glu Thr Thr Lys Gln Asn Val 770 775 780 Leu Arg Val Val Ser Gln Asp Val Lys Leu Ser Leu Gln Glu Leu Asp 785 790 795 800 Glu Leu Tyr Val Ile Phe Lys Lys Glu Leu Phe Leu Ser Cys Tyr Trp 805 810 815 Cys Leu Gly Cys Pro Val Leu Lys His His Asp Pro Ser Leu Pro Tyr 820 825 830 Leu Glu Gln Tyr Gln Ile Asp Cys Gln Gln Phe Arg Ala Leu Tyr His 835 840 845 Leu Leu Ser Pro Trp Ala His Ser Ala Asn Lys Asp Ser Leu Ala Leu 850 855 860 Trp Thr Phe Arg Leu Leu Asp Glu Asn Ser Asp Cys Leu Ile Asn Phe 865 870 875 880 Lys Glu Phe Ser Ser Ala Ile Asp Ile Met Tyr Asn Gly Ser Phe Thr 885 890 895 Glu Lys Leu Lys Leu Leu Phe Lys Leu His Ile Pro Pro Ala Tyr Thr 900 905 910 Glu Val Lys Ser Lys Asp Ala Ser Lys Gly Asp Glu Leu Ser Lys Glu 915 920 925 Glu Leu Leu Tyr Phe Ser Gln Leu His Val Ser Lys Pro Ala Asn Glu 930 935 940 Lys Glu Ala Glu Ser Ala Lys His Ser Pro Glu Lys Gly Lys Gly Lys 945 950 955 960 Ile Asp Ile Gln Ala Tyr Leu Ser Gln Trp Gln Asp Glu Leu Phe Lys 965 970 975 Lys Glu Glu Asn Ile Lys Asp Leu Pro Arg Met Asn Gln Ser Gln Phe 980 985 990 Ile Gln Phe Ser Lys Thr Leu Tyr Asn Leu Phe His Glu Asp Pro Glu 995 1000 1005 Glu Glu Ser Leu Tyr Gln Ala Ile Ala Val Val Thr Ser Leu Leu Leu 1010 1015 1020 Arg Met Glu Glu Val Gly Arg Lys Leu His Ser Pro Thr Ser Ser Ala 1025 1030 1035 1040 Lys Gly Phe Ser Gly Thr Val Cys Gly Ser Gly Gly Pro Ser Glu Glu 1045 1050 1055 Lys Thr Gly Ser His Leu Glu Lys Asp Pro Cys Ser Phe Arg Glu Glu 1060 1065 1070 Pro Gln Trp Ser Phe Ala Phe Glu Gln Ile Leu Ala Ser Leu Leu Asn 1075 1080 1085 Glu Pro Ala Leu Val Arg Phe Phe Glu Lys Pro Ile Asp Val Lys Ala 1090 1095 1100 Lys Leu Glu Asn Ala Arg Ile Ser Gln Leu Arg Ser Arg Thr Lys Met 1105 1110 1115 1120 <210> 21 <211> 2002 <212> PRT <213> Homo sapiens <400> 21 Met Glu Gln Asp Arg Thr Asn His Val Glu Gly Asn Arg Leu Ser Pro 1 5 10 15 Phe Leu Ile Pro Ser Pro Pro Ile Cys Gln Thr Glu Pro Leu Ala Thr 20 25 30 Lys Leu Gln Asn Gly Ser Pro Leu Pro Glu Arg Ala His Pro Glu Val 35 40 45 Asn Gly Asp Thr Lys Trp His Ser Phe Lys Ser Tyr Tyr Gly Ile Pro 50 55 60 Cys Met Lys Gly Ser Gln Asn Ser Arg Val Ser Pro Asp Phe Thr Gln 65 70 75 80 Glu Ser Arg Gly Tyr Ser Lys Cys Leu Gln Asn Gly Gly Ile Lys Arg 85 90 95 Thr Val Ser Glu Pro Ser Leu Ser Gly Leu Leu Gln Ile Lys Lys Leu 100 105 110 Lys Gln Asp Gln Lys Ala Asn Gly Glu Arg Arg Asn Phe Gly Val Ser 115 120 125 Gln Glu Arg Asn Pro Gly Glu Ser Ser Gln Pro Asn Val Ser Asp Leu 130 135 140 Ser Asp Lys Lys Glu Ser Val Ser Ser Val Ala Gln Glu Asn Ala Val 145 150 155 160 Lys Asp Phe Thr Ser Phe Ser Thr His Asn Cys Ser Gly Pro Glu Asn 165 170 175 Pro Glu Leu Gln Ile Leu Asn Glu Gln Glu Gly Lys Ser Ala Asn Tyr 180 185 190 His Asp Lys Asn Ile Val Leu Leu Lys Asn Lys Ala Val Leu Met Pro 195 200 205 Asn Gly Ala Thr Val Ser Ala Ser Ser Val Glu His Thr His Gly Glu 210 215 220 Leu Leu Glu Lys Thr Leu Ser Gln Tyr Tyr Pro Asp Cys Val Ser Ile 225 230 235 240 Ala Val Gln Lys Thr Thr Ser His Ile Asn Ala Ile Asn Ser Gln Ala 245 250 255 Thr Asn Glu Leu Ser Cys Glu Ile Thr His Pro Ser His Thr Ser Gly 260 265 270 Gln Ile Asn Ser Ala Gln Thr Ser Asn Ser Glu Leu Pro Pro Lys Pro 275 280 285 Ala Ala Val Val Ser Glu Ala Cys Asp Ala Asp Asp Ala Asp Asn Ala 290 295 300 Ser Lys Leu Ala Ala Met Leu Asn Thr Cys Ser Phe Gln Lys Pro Glu 305 310 315 320 Gln Leu Gln Gln Gln Lys Ser Val Phe Glu Ile Cys Pro Ser Pro Ala 325 330 335 Glu Asn Asn Ile Gln Gly Thr Thr Lys Leu Ala Ser Gly Glu Glu Phe 340 345 350 Cys Ser Gly Ser Ser Ser Asn Leu Gln Ala Pro Gly Gly Ser Ser Glu 355 360 365 Arg Tyr Leu Lys Gln Asn Glu Met Asn Gly Ala Tyr Phe Lys Gln Ser 370 375 380 Ser Val Phe Thr Lys Asp Ser Phe Ser Ala Thr Thr Thr Pro Pro Pro 385 390 395 400 Pro Ser Gln Leu Leu Leu Ser Pro Pro Pro Pro Leu Pro Gln Val Pro 405 410 415 Gln Leu Pro Ser Glu Gly Lys Ser Thr Leu Asn Gly Gly Val Leu Glu 420 425 430 Glu His His His Tyr Pro Asn Gln Ser Asn Thr Thr Leu Leu Arg Glu 435 440 445 Val Lys Ile Glu Gly Lys Pro Glu Ala Pro Pro Ser Gln Ser Pro Asn 450 455 460 Pro Ser Thr His Val Cys Ser Pro Ser Pro Met Leu Ser Glu Arg Pro 465 470 475 480 Gln Asn Asn Cys Val Asn Arg Asn Asp Ile Gln Thr Ala Gly Thr Met 485 490 495 Thr Val Pro Leu Cys Ser Glu Lys Thr Arg Pro Met Ser Glu His Leu 500 505 510 Lys His Asn Pro Pro Ile Phe Gly Ser Ser Gly Glu Leu Gln Asp Asn 515 520 525 Cys Gln Gln Leu Met Arg Asn Lys Glu Gln Glu Ile Leu Lys Gly Arg 530 535 540 Asp Lys Glu Gln Thr Arg Asp Leu Val Pro Pro Thr Gln His Tyr Leu 545 550 555 560 Lys Pro Gly Trp Ile Glu Leu Lys Ala Pro Arg Phe His Gln Ala Glu 565 570 575 Ser His Leu Lys Arg Asn Glu Ala Ser Leu Pro Ser Ile Leu Gln Tyr 580 585 590 Gln Pro Asn Leu Ser Asn Gln Met Thr Ser Lys Gln Tyr Thr Gly Asn 595 600 605 Ser Asn Met Pro Gly Gly Leu Pro Arg Gln Ala Tyr Thr Gln Lys Thr 610 615 620 Thr Gln Leu Glu His Lys Ser Gln Met Tyr Gln Val Glu Met Asn Gln 625 630 635 640 Gly Gln Ser Gln Gly Thr Val Asp Gln His Leu Gln Phe Gln Lys Pro 645 650 655 Ser His Gln Val His Phe Ser Lys Thr Asp His Leu Pro Lys Ala His 660 665 670 Val Gln Ser Leu Cys Gly Thr Arg Phe His Phe Gln Gln Arg Ala Asp 675 680 685 Ser Gln Thr Glu Lys Leu Met Ser Pro Val Leu Lys Gln His Leu Asn 690 695 700 Gln Gln Ala Ser Glu Thr Glu Pro Phe Ser Asn Ser His Leu Leu Gln 705 710 715 720 His Lys Pro His Lys Gln Ala Ala Gln Thr Gln Pro Ser Gln Ser Ser 725 730 735 His Leu Pro Gln Asn Gln Gln Gln Gln Gln Lys Leu Gln Ile Lys Asn 740 745 750 Lys Glu Glu Ile Leu Gln Thr Phe Pro His Pro Gln Ser Asn Asn Asp 755 760 765 Gln Gln Arg Glu Gly Ser Phe Phe Gly Gln Thr Lys Val Glu Glu Cys 770 775 780 Phe His Gly Glu Asn Gln Tyr Ser Lys Ser Ser Glu Phe Glu Thr His 785 790 795 800 Asn Val Gln Met Gly Leu Glu Glu Val Gln Asn Ile Asn Arg Arg Asn 805 810 815 Ser Pro Tyr Ser Gln Thr Met Lys Ser Ser Ala Cys Lys Ile Gln Val 820 825 830 Ser Cys Ser Asn Asn Thr His Leu Val Ser Glu Asn Lys Glu Gln Thr 835 840 845 Thr His Pro Glu Leu Phe Ala Gly Asn Lys Thr Gln Asn Leu His His 850 855 860 Met Gln Tyr Phe Pro Asn Asn Val Ile Pro Lys Gln Asp Leu Leu His 865 870 875 880 Arg Cys Phe Gln Glu Gln Glu Gln Lys Ser Gln Gln Ala Ser Val Leu 885 890 895 Gln Gly Tyr Lys Asn Arg Asn Gln Asp Met Ser Gly Gln Gln Ala Ala 900 905 910 Gln Leu Ala Gln Gln Arg Tyr Leu Ile His Asn His Ala Asn Val Phe 915 920 925 Pro Val Pro Asp Gln Gly Gly Ser His Thr Gln Thr Pro Pro Gln Lys 930 935 940 Asp Thr Gln Lys His Ala Ala Leu Arg Trp His Leu Leu Gln Lys Gln 945 950 955 960 Glu Gln Gln Gln Thr Gln Gln Pro Gln Thr Glu Ser Cys His Ser Gln 965 970 975 Met His Arg Pro Ile Lys Val Glu Pro Gly Cys Lys Pro His Ala Cys 980 985 990 Met His Thr Ala Pro Pro Glu Asn Lys Thr Trp Lys Lys Val Thr Lys 995 1000 1005 Gln Glu Asn Pro Pro Ala Ser Cys Asp Asn Val Gln Gln Lys Ser Ile 1010 1015 1020 Ile Glu Thr Met Glu Gln His Leu Lys Gln Phe His Ala Lys Ser Leu 1025 1030 1035 1040 Phe Asp His Lys Ala Leu Thr Leu Lys Ser Gln Lys Gln Val Lys Val 1045 1050 1055 Glu Met Ser Gly Pro Val Thr Val Leu Thr Arg Gln Thr Thr Ala Ala 1060 1065 1070 Glu Leu Asp Ser His Thr Pro Ala Leu Glu Gln Gln Thr Thr Ser Ser 1075 1080 1085 Glu Lys Thr Pro Thr Lys Arg Thr Ala Ala Ser Val Leu Asn Asn Phe 1090 1095 1100 Ile Glu Ser Pro Ser Lys Leu Leu Asp Thr Pro Ile Lys Asn Leu Leu 1105 1110 1115 1120 Asp Thr Pro Val Lys Thr Gln Tyr Asp Phe Pro Ser Cys Arg Cys Val 1125 1130 1135 Glu Gln Ile Ile Glu Lys Asp Glu Gly Pro Phe Tyr Thr His Leu Gly 1140 1145 1150 Ala Gly Pro Asn Val Ala Ala Ile Arg Glu Ile Met Glu Glu Arg Phe 1155 1160 1165 Gly Gln Lys Gly Lys Ala Ile Arg Ile Glu Arg Val Ile Tyr Thr Gly 1170 1175 1180 Lys Glu Gly Lys Ser Ser Gln Gly Cys Pro Ile Ala Lys Trp Val Val 1185 1190 1195 1200 Arg Arg Ser Ser Ser Glu Glu Lys Leu Leu Cys Leu Val Arg Glu Arg 1205 1210 1215 Ala Gly His Thr Cys Glu Ala Ala Val Ile Val Ile Leu Ile Leu Val 1220 1225 1230 Trp Glu Gly Ile Pro Leu Ser Leu Ala Asp Lys Leu Tyr Ser Glu Leu 1235 1240 1245 Thr Glu Thr Leu Arg Lys Tyr Gly Thr Leu Thr Asn Arg Arg Cys Ala 1250 1255 1260 Leu Asn Glu Glu Arg Thr Cys Ala Cys Gln Gly Leu Asp Pro Glu Thr 1265 1270 1275 1280 Cys Gly Ala Ser Phe Ser Phe Gly Cys Ser Trp Ser Met Tyr Tyr Asn 1285 1290 1295 Gly Cys Lys Phe Ala Arg Ser Lys Ile Pro Arg Lys Phe Lys Leu Leu 1300 1305 1310 Gly Asp Asp Pro Lys Glu Glu Glu Lys Leu Glu Ser His Leu Gln Asn 1315 1320 1325 Leu Ser Thr Leu Met Ala Pro Thr Tyr Lys Lys Leu Ala Pro Asp Ala 1330 1335 1340 Tyr Asn Asn Gln Ile Glu Tyr Glu His Arg Ala Pro Glu Cys Arg Leu 1345 1350 1355 1360 Gly Leu Lys Glu Gly Arg Pro Phe Ser Gly Val Thr Ala Cys Leu Asp 1365 1370 1375 Phe Cys Ala His Ala His Arg Asp Leu His Asn Met Gln Asn Gly Ser 1380 1385 1390 Thr Leu Val Cys Thr Leu Thr Arg Glu Asp Asn Arg Glu Phe Gly Gly 1395 1400 1405 Lys Pro Glu Asp Glu Gln Leu His Val Leu Pro Leu Tyr Lys Val Ser 1410 1415 1420 Asp Val Asp Glu Phe Gly Ser Val Glu Ala Gln Glu Glu Lys Lys Arg 1425 1430 1435 1440 Ser Gly Ala Ile Gln Val Leu Ser Ser Phe Arg Arg Lys Val Arg Met 1445 1450 1455 Leu Ala Glu Pro Val Lys Thr Cys Arg Gln Arg Lys Leu Glu Ala Lys 1460 1465 1470 Lys Ala Ala Ala Glu Lys Leu Ser Ser Leu Glu Asn Ser Ser Asn Lys 1475 1480 1485 Asn Glu Lys Glu Lys Ser Ala Pro Ser Arg Thr Lys Gln Thr Glu Asn 1490 1495 1500 Ala Ser Gln Ala Lys Gln Leu Ala Glu Leu Leu Arg Leu Ser Gly Pro 1505 1510 1515 1520 Val Met Gln Gln Ser Gln Gln Pro Gln Pro Leu Gln Lys Gln Pro Pro 1525 1530 1535 Gln Pro Gln Gln Gln Gln Arg Pro Gln Gln Gln Gln Pro His His Pro 1540 1545 1550 Gln Thr Glu Ser Val Asn Ser Tyr Ser Ala Ser Gly Ser Thr Asn Pro 1555 1560 1565 Tyr Met Arg Arg Pro Asn Pro Val Ser Pro Tyr Pro Asn Ser Ser His 1570 1575 1580 Thr Ser Asp Ile Tyr Gly Ser Thr Ser Pro Met Asn Phe Tyr Ser Thr 1585 1590 1595 1600 Ser Ser Gln Ala Ala Gly Ser Tyr Leu Asn Ser Ser Asn Pro Met Asn 1605 1610 1615 Pro Tyr Pro Gly Leu Leu Asn Gln Asn Thr Gln Tyr Pro Ser Tyr Gln 1620 1625 1630 Cys Asn Gly Asn Leu Ser Val Asp Asn Cys Ser Pro Tyr Leu Gly Ser 1635 1640 1645 Tyr Ser Pro Gln Ser Gln Pro Met Asp Leu Tyr Arg Tyr Pro Ser Gln 1650 1655 1660 Asp Pro Leu Ser Lys Leu Ser Leu Pro Pro Ile His Thr Leu Tyr Gln 1665 1670 1675 1680 Pro Arg Phe Gly Asn Ser Gln Ser Phe Thr Ser Lys Tyr Leu Gly Tyr 1685 1690 1695 Gly Asn Gln Asn Met Gln Gly Asp Gly Phe Ser Ser Cys Thr Ile Arg 1700 1705 1710 Pro Asn Val His His Val Gly Lys Leu Pro Pro Tyr Pro Thr His Glu 1715 1720 1725 Met Asp Gly His Phe Met Gly Ala Thr Ser Arg Leu Pro Pro Asn Leu 1730 1735 1740 Ser Asn Pro Asn Met Asp Tyr Lys Asn Gly Glu His His Ser Pro Ser 1745 1750 1755 1760 His Ile Ile His Asn Tyr Ser Ala Ala Pro Gly Met Phe Asn Ser Ser 1765 1770 1775 Leu His Ala Leu His Leu Gln Asn Lys Glu Asn Asp Met Leu Ser His 1780 1785 1790 Thr Ala Asn Gly Leu Ser Lys Met Leu Pro Ala Leu Asn His Asp Arg 1795 1800 1805 Thr Ala Cys Val Gln Gly Gly Leu His Lys Leu Ser Asp Ala Asn Gly 1810 1815 1820 Gln Glu Lys Gln Pro Leu Ala Leu Val Gln Gly Val Ala Ser Gly Ala 1825 1830 1835 1840 Glu Asp Asn Asp Glu Val Trp Ser Asp Ser Glu Gln Ser Phe Leu Asp 1845 1850 1855 Pro Asp Ile Gly Gly Val Ala Val Ala Pro Thr His Gly Ser Ile Leu 1860 1865 1870 Ile Glu Cys Ala Lys Arg Glu Leu His Ala Thr Thr Pro Leu Lys Asn 1875 1880 1885 Pro Asn Arg Asn His Pro Thr Arg Ile Ser Leu Val Phe Tyr Gln His 1890 1895 1900 Lys Ser Met Asn Glu Pro Lys His Gly Leu Ala Leu Trp Glu Ala Lys 1905 1910 1915 1920 Met Ala Glu Lys Ala Arg Glu Lys Glu Glu Glu Cys Glu Lys Tyr Gly 1925 1930 1935 Pro Asp Tyr Val Pro Gln Lys Ser His Gly Lys Lys Val Lys Arg Glu 1940 1945 1950 Pro Ala Glu Pro His Glu Thr Ser Glu Pro Thr Tyr Leu Arg Phe Ile 1955 1960 1965 Lys Ser Leu Ala Glu Arg Thr Met Ser Val Thr Thr Asp Ser Thr Val 1970 1975 1980 Thr Thr Ser Pro Tyr Ala Phe Thr Arg Val Thr Gly Pro Tyr Asn Arg 1985 1990 1995 2000 Tyr Ile <210> 22 <211> 409 <212> PRT <213> Homo sapiens <400> 22 Met Ala Leu Arg Pro Glu Asp Pro Ser Ser Gly Phe Arg His Ser Asn 1 5 10 15 Val Val Ala Phe Ile Asn Glu Lys Met Ala Arg His Thr Lys Gly Pro 20 25 30 Glu Phe Tyr Leu Glu Asn Ile Ser Leu Ser Trp Glu Lys Val Glu Asp 35 40 45 Lys Leu Arg Ala Ile Leu Glu Asp Ser Glu Val Pro Ser Glu Val Lys 50 55 60 Glu Ala Cys Thr Trp Gly Ser Leu Ala Leu Gly Val Arg Phe Ala His 65 70 75 80 Arg Gln Ala Gln Leu Gln Arg His Arg Val Arg Trp Leu His Gly Phe 85 90 95 Ala Lys Leu His Lys Ser Ala Ala Gln Ala Leu Ala Ser Asp Leu Lys 100 105 110 Lys Leu Arg Glu Gln Gln Glu Thr Glu Arg Lys Glu Ala Ala Ser Arg 115 120 125 Leu Arg Met Ala Gln Thr Ser Leu Val Glu Val Gln Lys Glu Arg Asp 130 135 140 Lys Glu Leu Val Ser Pro His Glu Trp Glu Gln Gly Ala Gly Trp Pro 145 150 155 160 Gly Leu Ala Thr Ala Gly Gly Val Cys Thr Glu Gly Ala Ala Glu Glu 165 170 175 Glu Glu Glu Ala Ala Val Ala Ala Ala Gly Ala Ala Gly Gly Lys Gly 180 185 190 Ala Glu Glu Glu Gln Arg Asp Val Glu Val Val Ala Ala Pro Val Glu 195 200 205 Ala Met Ala Pro Pro Val Glu Ala Gly Ala Ala Pro Met Glu Thr Gln 210 215 220 Phe Pro His Val Glu Ala Arg Ala Ala Ser Met Glu Thr Thr Glu Lys 225 230 235 240 Leu Glu Arg Ile Leu Leu Gln Leu Leu Gly Asp Ala Asp Gln Glu Lys 245 250 255 Tyr Thr Tyr Trp Gly Gln Lys Glu Gly Asp Leu Arg Ser Val Glu Thr 260 265 270 Ala Thr Ser Tyr Phe Ser Gly Thr Thr Asn Pro Trp Ser Arg Ala Ser 275 280 285 Ser Glu Pro Leu Pro Val Gln Leu Pro Ala Ser Tyr Ser Tyr Ser Tyr 290 295 300 Ser Ser Pro Phe Ser Ser Phe Ser Asp Ile Pro Thr Ile Ser Pro Pro 305 310 315 320 Gln Ala Thr Val Thr Ala Pro Val Pro Pro Gln Leu Pro Ser Asp Trp 325 330 335 Glu Ala Phe Asp Thr Ser Leu Trp Ser Asp Gly Gly Pro His Arg Ile 340 345 350 Asp His Gln Glu His Pro Arg Asp Arg Arg Tyr Ser Glu Pro His Gln 355 360 365 Gln Arg Pro Pro Val Tyr Arg Arg Pro Gly Asp Trp Asp Cys Pro Trp 370 375 380 Cys Asn Ala Val Asn Phe Ser Arg Arg Asp Thr Cys Phe Asp Cys Gly 385 390 395 400 Lys Gly Ile Trp Leu Gln Lys Pro His 405 <210> 23 <211> 472 <212> PRT <213> Homo sapiens <400> 23 Met Ala Gly Pro Gly Trp Gly Pro Pro Arg Leu Asp Gly Phe Ile Leu 1 5 10 15 Thr Glu Arg Leu Gly Ser Gly Thr Tyr Ala Thr Val Tyr Lys Ala Tyr 20 25 30 Ala Lys Lys Asp Thr Arg Glu Val Val Ala Ile Lys Cys Val Ala Lys 35 40 45 Lys Ser Leu Asn Lys Ala Ser Val Glu Asn Leu Leu Thr Glu Ile Glu 50 55 60 Ile Leu Lys Gly Ile Arg His Pro His Ile Val Gln Leu Lys Asp Phe 65 70 75 80 Gln Trp Asp Ser Asp Asn Ile Tyr Leu Ile Met Glu Phe Cys Ala Gly 85 90 95 Gly Asp Leu Ser Arg Phe Ile His Thr Arg Arg Ile Leu Pro Glu Lys 100 105 110 Val Ala Arg Val Phe Met Gln Gln Leu Ala Ser Ala Leu Gln Phe Leu 115 120 125 His Glu Arg Asn Ile Ser His Leu Asp Leu Lys Pro Gln Asn Ile Leu 130 135 140 Leu Ser Ser Leu Glu Lys Pro His Leu Lys Leu Ala Asp Phe Gly Phe 145 150 155 160 Ala Gln His Met Ser Pro Trp Asp Glu Lys His Val Leu Arg Gly Ser 165 170 175 Pro Leu Tyr Met Ala Pro Glu Met Val Cys Gln Arg Gln Tyr Asp Ala 180 185 190 Arg Val Asp Leu Trp Ser Met Gly Val Ile Leu Tyr Glu Ala Leu Phe 195 200 205 Gly Gln Pro Pro Phe Ala Ser Arg Ser Phe Ser Glu Leu Glu Glu Lys 210 215 220 Ile Arg Ser Asn Arg Val Ile Glu Leu Pro Leu Arg Pro Leu Leu Ser 225 230 235 240 Arg Asp Cys Arg Asp Leu Leu Gln Arg Leu Leu Glu Arg Asp Pro Ser 245 250 255 Arg Arg Ile Ser Phe Gln Asp Phe Phe Ala His Pro Trp Val Asp Leu 260 265 270 Glu His Met Pro Ser Gly Glu Ser Leu Gly Arg Ala Thr Ala Leu Val 275 280 285 Val Gln Ala Val Lys Lys Asp Gln Glu Gly Asp Ser Ala Ala Ala Leu 290 295 300 Ser Leu Tyr Cys Lys Ala Leu Asp Phe Phe Val Pro Ala Leu His Tyr 305 310 315 320 Glu Val Asp Ala Gln Arg Lys Glu Ala Ile Lys Ala Lys Val Gly Gln 325 330 335 Tyr Val Ser Arg Ala Glu Glu Leu Lys Ala Ile Val Ser Ser Ser Asn 340 345 350 Gln Ala Leu Leu Arg Gln Gly Thr Ser Ala Arg Asp Leu Leu Arg Glu 355 360 365 Met Ala Arg Asp Lys Pro Arg Leu Leu Ala Ala Leu Glu Val Ala Ser 370 375 380 Ala Ala Met Ala Lys Glu Glu Ala Ala Gly Gly Glu Gln Asp Ala Leu 385 390 395 400 Asp Leu Tyr Gln His Ser Leu Gly Glu Leu Leu Leu Leu Leu Ala Ala 405 410 415 Glu Pro Pro Gly Arg Arg Arg Glu Leu Leu His Thr Glu Val Gln Asn 420 425 430 Leu Met Ala Arg Ala Glu Tyr Leu Lys Glu Gln Val Lys Met Arg Glu 435 440 445 Ser Arg Trp Glu Ala Asp Thr Leu Asp Lys Glu Gly Leu Ser Glu Ser 450 455 460 Val Arg Ser Ser Cys Thr Leu Gln 465 470 <210> 24 <211> 1743 <212> PRT <213> Homo sapiens <400> 24 Met Ala Thr Asp Ser Gly Asp Pro Ala Ser Thr Glu Asp Ser Glu Lys 1 5 10 15 Pro Asp Gly Ile Ser Phe Glu Asn Arg Val Pro Gln Val Ala Ala Thr 20 25 30 Leu Thr Val Glu Ala Arg Leu Lys Glu Lys Asn Ser Thr Phe Ser Ala 35 40 45 Ser Gly Glu Thr Val Glu Arg Lys Arg Phe Phe Arg Lys Ser Val Glu 50 55 60 Met Thr Glu Asp Asp Lys Val Ala Glu Ser Pro Lys Asp Glu Arg 65 70 75 80 Ile Lys Ala Ala Met Asn Ile Pro Arg Val Asp Lys Leu Pro Ser Asn 85 90 95 Val Leu Arg Gly Gly Gln Glu Val Lys Tyr Glu Gln Cys Ser Lys Ser 100 105 110 Thr Ser Glu Ile Ser Lys Asp Cys Phe Lys Glu Lys Asn Glu Lys Glu 115 120 125 Met Glu Glu Glu Ala Glu Met Lys Ala Val Ala Thr Ser Pro Ser Gly 130 135 140 Arg Phe Leu Lys Phe Asp Ile Glu Leu Gly Arg Gly Ala Phe Lys Thr 145 150 155 160 Val Tyr Lys Gly Leu Asp Thr Glu Thr Trp Val Glu Val Ala Trp Cys 165 170 175 Glu Leu Gln Asp Arg Lys Leu Thr Lys Ala Glu Gln Gln Arg Phe Lys 180 185 190 Glu Glu Ala Glu Met Leu Lys Gly Leu Gln His Pro Asn Ile Val Arg 195 200 205 Phe Tyr Asp Ser Trp Glu Ser Ile Leu Lys Gly Lys Lys Cys Ile Val 210 215 220 Leu Val Thr Glu Leu Met Thr Ser Gly Thr Leu Lys Thr Tyr Leu Lys 225 230 235 240 Arg Phe Lys Val Met Lys Pro Lys Val Leu Arg Ser Trp Cys Arg Gln 245 250 255 Ile Leu Lys Gly Leu Gln Phe Leu His Thr Arg Thr Pro Pro Ile Ile 260 265 270 His Arg Asp Leu Lys Cys Asp Asn Ile Phe Ile Thr Gly Pro Thr Gly 275 280 285 Ser Val Lys Ile Gly Asp Leu Gly Leu Ala Thr Leu Met Arg Thr Ser 290 295 300 Phe Ala Lys Ser Val Ile Gly Thr Pro Glu Phe Met Ala Pro Glu Met 305 310 315 320 Tyr Glu Glu His Tyr Asp Glu Ser Val Asp Val Tyr Ala Phe Gly Met 325 330 335 Cys Met Leu Glu Met Ala Thr Ser Glu Tyr Pro Tyr Ser Glu Cys Gln 340 345 350 Asn Ala Ala Gln Ile Tyr Arg Lys Val Thr Ser Gly Ile Lys Pro Ala 355 360 365 Ser Phe Asn Lys Val Thr Asp Pro Glu Val Lys Glu Ile Ile Glu Gly 370 375 380 Cys Ile Arg Gln Asn Lys Ser Glu Arg Leu Ser Ile Arg Asp Leu Leu 385 390 395 400 Asn His Ala Phe Phe Ala Glu Asp Thr Gly Leu Arg Val Glu Leu Ala 405 410 415 Glu Glu Asp Asp Cys Ser Asn Ser Ser Leu Ala Leu Arg Leu Trp Val 420 425 430 Glu Asp Pro Lys Lys Leu Lys Gly Lys His Lys Asp Asn Glu Ala Ile 435 440 445 Glu Phe Ser Phe Asn Leu Glu Thr Asp Thr Pro Glu Glu Val Ala Tyr 450 455 460 Glu Met Val Lys Ser Gly Phe Phe His Glu Ser Asp Ser Lys Ala Val 465 470 475 480 Ala Lys Ser Ile Arg Asp Arg Val Thr Pro Ile Lys Lys Thr Arg Glu 485 490 495 Lys Lys Pro Ala Gly Cys Leu Glu Glu Arg Arg Asp Ser Gln Cys Lys 500 505 510 Ser Met Gly Asn Val Phe Pro Gln Pro Gln Asn Thr Thr Leu Pro Leu 515 520 525 Ala Pro Ala Gln Gln Thr Gly Ala Glu Cys Glu Glu Thr Glu Val Asp 530 535 540 Gln His Val Arg Gln Gln Leu Leu Gln Arg Lys Pro Gln Gln His Cys 545 550 555 560 Ser Ser Val Thr Gly Asp Asn Leu Ser Glu Ala Gly Ala Ala Ser Val 565 570 575 Ile His Ser Asp Thr Ser Ser Gln Pro Ser Val Ala Tyr Ser Ser Asn 580 585 590 Gln Thr Met Gly Ser Gln Met Val Ser Asn Ile Pro Gln Ala Glu Val 595 600 605 Asn Val Pro Gly Gln Ile Tyr Ser Ser Gln Gln Leu Val Gly His Tyr 610 615 620 Gln Gln Val Ser Gly Leu Gln Lys His Ser Lys Leu Thr Gln Pro Gln 625 630 635 640 Ile Leu Pro Leu Val Gln Gly Gln Ser Thr Val Leu Pro Val His Val 645 650 655 Leu Gly Pro Thr Val Val Ser Gln Pro Gln Val Ser Pro Leu Thr Val 660 665 670 Gln Lys Val Pro Gln Ile Lys Pro Val Ser Gln Pro Val Gly Ala Glu 675 680 685 Gln Gln Ala Ala Leu Leu Lys Pro Asp Leu Val Arg Ser Leu Asn Gln 690 695 700 Asp Val Ala Thr Thr Lys Glu Asn Val Ser Ser Pro Asp Asn Pro Ser 705 710 715 720 Gly Asn Gly Lys Gln Asp Arg Ile Lys Gln Arg Arg Ala Ser Cys Pro 725 730 735 Arg Pro Glu Lys Gly Thr Lys Phe Gln Leu Thr Val Leu Gln Val Ser 740 745 750 Thr Ser Gly Asp Asn Met Val Glu Cys Gln Leu Glu Thr His Asn Asn 755 760 765 Lys Met Val Thr Phe Lys Phe Asp Val Asp Gly Asp Ala Pro Glu Asp 770 775 780 Ile Ala Asp Tyr Met Val Glu Asp Asn Phe Val Leu Glu Ser Glu Lys 785 790 795 800 Glu Lys Phe Val Glu Glu Leu Arg Ala Ile Val Gly Gln Ala Gln Glu 805 810 815 Ile Leu His Val His Phe Ala Thr Glu Arg Ala Thr Gly Val Asp Ser 820 825 830 Ile Thr Val Asp Ser Asn Ser Ser Gln Thr Gly Ser Ser Glu Gln Val 835 840 845 Gln Ile Asn Ser Thr Ser Thr Gln Thr Ser Asn Glu Ser Ala Pro Gln 850 855 860 Ser Ser Pro Val Gly Arg Trp Arg Phe Cys Ile Asn Gln Thr Ile Arg 865 870 875 880 Asn Arg Glu Thr Gln Ser Pro Pro Ser Leu Gln His Ser Met Ser Ala 885 890 895 Val Pro Gly Arg His Pro Leu Pro Ser Pro Lys Asn Thr Ser Asn Lys 900 905 910 Glu Ile Ser Arg Asp Thr Leu Leu Thr Ile Glu Asn Asn Pro Cys His 915 920 925 Arg Ala Leu Phe Thr Ser Lys Ser Glu His Lys Asp Val Val Asp Gly 930 935 940 Lys Ile Ser Glu Cys Ala Ser Val Glu Thr Lys Gln Pro Ala Ile Leu 945 950 955 960 Tyr Gln Val Glu Asp Asn Arg Gln Ile Met Ala Pro Val Thr Asn Ser 965 970 975 Ser Ser Tyr Ser Thr Thr Ser Val Arg Ala Val Pro Ala Glu Cys Glu 980 985 990 Gly Leu Thr Lys Gln Ala Ser Ile Phe Ile Pro Val Tyr Pro Cys His 995 1000 1005 Gln Thr Ala Ser Gln Ala Asp Ala Leu Met Ser His Pro Gly Glu Ser 1010 1015 1020 Thr Gln Thr Ser Gly Asn Ser Leu Thr Thr Leu Ala Phe Asp Gln Lys 1025 1030 1035 1040 Pro Gln Thr Leu Ser Val Gln Gln Pro Ala Met Asp Ala Glu Phe Ile 1045 1050 1055 Ser Gln Glu Gly Glu Thr Thr Val Asn Thr Glu Ala Ser Ser Pro Lys 1060 1065 1070 Thr Val Ile Pro Thr Gln Thr Pro Gly Leu Glu Pro Thr Thr Leu Gln 1075 1080 1085 Pro Thr Thr Val Leu Glu Ser Asp Gly Glu Arg Pro Pro Lys Leu Glu 1090 1095 1100 Phe Ala Asp Asn Arg Ile Lys Thr Leu Asp Glu Lys Leu Arg Asn Leu 1105 1110 1115 1120 Leu Tyr Gln Glu His Ser Ile Ser Ser Ile Tyr Pro Glu Ser Gln Lys 1125 1130 1135 Asp Thr Gln Ser Ile Asp Ser Pro Phe Ser Ser Ser Ala Glu Asp Thr 1140 1145 1150 Leu Ser Cys Pro Val Thr Glu Val Ile Ala Ile Ser His Cys Gly Ile 1155 1160 1165 Lys Asp Ser Pro Val Gln Ser Pro Asn Phe Gln Gln Thr Gly Ser Lys 1170 1175 1180 Leu Leu Ser Asn Val Ala Ala Ser Gln Pro Ala Asn Ile Ser Val Phe 1185 1190 1195 1200 Lys Arg Asp Leu Asn Val Ile Thr Ser Val Pro Ser Glu Leu Cys Leu 1205 1210 1215 His Glu Met Ser Ser Asp Ala Ser Leu Pro Gly Asp Pro Glu Ala Tyr 1220 1225 1230 Pro Ala Ala Val Ser Ser Gly Gly Ala Ile His Leu Gln Thr Gly Val 1235 1240 1245 Glu Thr Glu Glu Met Arg Ser Ala Ile Ala Pro Asp Pro Ile Pro Leu 1250 1255 1260 Thr Arg Glu Ser Thr Ala Asp Thr Arg Ala Leu Asn Arg Cys Lys Ala 1265 1270 1275 1280 Met Ser Gly Ser Phe Gln Arg Gly Arg Phe Gln Val Ile Thr Ile Pro 1285 1290 1295 Gln Gln Gln Ser Ala Lys Met Thr Ser Phe Gly Ile Glu His Ile Ser 1300 1305 1310 Val Phe Ser Glu Thr Asn His Ser Ser Glu Glu Ala Phe Ile Lys Thr 1315 1320 1325 Ala Lys Ser Gln Leu Val Glu Ile Glu Pro Ala Thr Gln Asn Pro Lys 1330 1335 1340 Thr Ser Phe Ser Tyr Glu Lys Leu Gln Ala Leu Gln Glu Thr Cys Lys 1345 1350 1355 1360 Glu Asn Lys Gly Val Pro Lys Gln Gly Asp Asn Phe Leu Ser Phe Ser 1365 1370 1375 Ala Ala Cys Glu Thr Asp Val Ser Ser Val Thr Pro Glu Lys Glu Phe 1380 1385 1390 Glu Glu Thr Ser Ala Thr Gly Ser Ser Met Gln Ser Gly Ser Glu Leu 1395 1400 1405 Leu Leu Lys Glu Arg Glu Ile Leu Thr Ala Gly Lys Gln Pro Ser Ser 1410 1415 1420 Asp Ser Glu Phe Ser Ala Ser Leu Ala Gly Ser Gly Lys Ser Val Ala 1425 1430 1435 1440 Lys Thr Gly Pro Glu Ser Asn Gln Cys Leu Pro His His Glu Glu Gln 1445 1450 1455 Ala Tyr Ala Gln Thr Gln Ser Ser Leu Phe Tyr Ser Pro Ser Ser Pro 1460 1465 1470 Met Ser Ser Asp Asp Glu Ser Glu Ile Glu Asp Glu Asp Leu Lys Val 1475 1480 1485 Glu Leu Gln Arg Leu Arg Glu Lys His Ile Gln Glu Val Val Asn Leu 1490 1495 1500 Gln Thr Gln Gln Asn Lys Glu Leu Gln Glu Leu Tyr Glu Arg Leu Arg 1505 1510 1515 1520 Ser Ile Lys Asp Ser Lys Thr Gln Ser Thr Glu Ile Pro Leu Pro Pro 1525 1530 1535 Ala Ser Pro Arg Arg Pro Arg Ser Phe Lys Ser Lys Leu Arg Ser Arg 1540 1545 1550 Pro Gln Ser Leu Thr His Val Asp Asn Gly Ile Val Ala Thr Asp Pro 1555 1560 1565 Leu Cys Val Glu Ser Asn Ala Ala Ser Cys Gln Gln Ser Pro Ala Ser 1570 1575 1580 Lys Lys Gly Met Phe Thr Asp Asp Leu His Lys Leu Val Asp Asp Trp 1585 1590 1595 1600 Thr Lys Glu Ala Val Gly Asn Ser Leu Ile Lys Pro Ser Leu Asn Gln 1605 1610 1615 Leu Lys Gln Ser Gln His Lys Leu Glu Thr Glu Asn Trp Asn Lys Val 1620 1625 1630 Ser Glu Asn Thr Pro Ser Thr Met Gly Tyr Thr Ser Thr Trp Ile Ser 1635 1640 1645 Ser Leu Ser Gln Ile Arg Gly Ala Val Pro Thr Ser Leu Pro Gln Gly 1650 1655 1660 Leu Ser Leu Pro Ser Phe Pro Gly Pro Leu Ser Ser Tyr Gly Met Pro 1665 1670 1675 1680 His Val Cys Gln Tyr Asn Ala Val Ala Gly Ala Gly Tyr Pro Val Gln 1685 1690 1695 Trp Val Gly Ile Ser Gly Thr Thr Gln Gln Ser Val Val Ile Pro Ala 1700 1705 1710 Gln Ser Gly Gly Pro Phe Gln Pro Gly Met Asn Met Gln Ala Phe Pro 1715 1720 1725 Thr Ser Ser Val Gln Asn Pro Ala Thr Ile Pro Pro Gly Pro Lys 1730 1735 1740 <210> 25 <211> 590 <212> PRT <213> Homo sapiens <400> 25 Met Arg Pro Arg Arg Pro Leu Val Phe Met Ser Leu Val Cys Ala Leu 1 5 10 15 Leu Asn Thr Cys Gln Ala His Arg Val His Asp Asp Lys Pro Asn Ile 20 25 30 Val Leu Ile Met Val Asp Asp Leu Gly Ile Gly Asp Leu Gly Cys Tyr 35 40 45 Gly Asn Asp Thr Met Arg Thr Pro His Ile Asp Arg Leu Ala Arg Glu 50 55 60 Gly Val Arg Leu Thr Gln His Ile Ser Ala Ala Ser Leu Cys Ser Pro 65 70 75 80 Ser Arg Ser Ala Phe Leu Thr Gly Arg Tyr Pro Ile Arg Ser Gly Met 85 90 95 Val Ser Ser Gly Asn Arg Arg Val Ile Gln Asn Leu Ala Val Pro Ala 100 105 110 Gly Leu Pro Leu Asn Glu Thr Thr Leu Ala Ala Leu Leu Lys Lys Gln 115 120 125 Gly Tyr Ser Thr Gly Leu Ile Gly Lys Trp His Gln Gly Leu Asn Cys 130 135 140 Asp Ser Arg Ser Asp Gln Cys His His Pro Tyr Asn Tyr Gly Phe Asp 145 150 155 160 Tyr Tyr Tyr Gly Met Pro Phe Thr Leu Val Asp Ser Cys Trp Pro Asp 165 170 175 Pro Ser Arg Asn Thr Glu Leu Ala Phe Glu Ser Gln Leu Trp Leu Cys 180 185 190 Val Gln Leu Val Ala Ile Ala Ile Leu Thr Leu Thr Phe Gly Lys Leu 195 200 205 Ser Gly Trp Val Ser Val Pro Trp Leu Leu Ile Phe Ser Met Ile Leu 210 215 220 Phe Ile Phe Leu Leu Gly Tyr Ala Trp Phe Ser Ser His Thr Ser Pro 225 230 235 240 Leu Tyr Trp Asp Cys Leu Leu Met Arg Gly His Glu Ile Thr Glu Gln 245 250 255 Pro Met Lys Ala Glu Arg Ala Gly Ser Ile Met Val Lys Glu Ala Ile 260 265 270 Ser Phe Leu Glu Arg His Ser Lys Glu Thr Phe Leu Leu Phe Phe Ser 275 280 285 Phe Leu His Val His Thr Pro Leu Pro Thr Thr Asp Asp Phe Thr Gly 290 295 300 Thr Ser Lys His Gly Leu Tyr Gly Asp Asn Val Glu Glu Met Asp Ser 305 310 315 320 Met Val Gly Lys Ile Leu Asp Ala Ile Asp Asp Phe Gly Leu Arg Asn 325 330 335 Asn Thr Leu Val Tyr Phe Thr Ser Asp His Gly Gly His Leu Glu Ala 340 345 350 Arg Arg Gly His Ala Gln Leu Gly Gly Trp Asn Gly Ile Tyr Lys Gly 355 360 365 Gly Lys Gly Met Gly Gly Trp Glu Gly Gly Ile Arg Val Pro Gly Ile 370 375 380 Val Arg Trp Pro Gly Lys Val Pro Ala Gly Arg Leu Ile Lys Glu Pro 385 390 395 400 Thr Ser Leu Met Asp Ile Leu Pro Thr Val Ala Ser Val Ser Gly Gly 405 410 415 Ser Leu Pro Gln Asp Arg Val Ile Asp Gly Arg Asp Leu Met Pro Leu 420 425 430 Leu Gln Gly Asn Val Arg His Ser Glu His Glu Phe Leu Phe His Tyr 435 440 445 Cys Gly Ser Tyr Leu His Ala Val Arg Trp Ile Pro Lys Asp Asp Ser 450 455 460 Gly Ser Val Trp Lys Ala His Tyr Val Thr Pro Val Phe Gln Pro Pro 465 470 475 480 Ala Ser Gly Gly Cys Tyr Val Thr Ser Leu Cys Arg Cys Phe Gly Glu 485 490 495 Gln Val Thr Tyr His Asn Pro Pro Leu Leu Phe Asp Leu Ser Arg Asp 500 505 510 Pro Ser Glu Ser Thr Pro Leu Thr Pro Ala Thr Glu Pro Leu His Asp 515 520 525 Phe Val Ile Lys Lys Val Ala Asn Ala Leu Lys Glu His Gln Glu Thr 530 535 540 Ile Val Pro Val Thr Tyr Gln Leu Ser Glu Leu Asn Gln Gly Arg Thr 545 550 555 560 Trp Leu Lys Pro Cys Cys Gly Val Phe Pro Phe Cys Leu Cys Asp Lys 565 570 575 Glu Glu Glu Val Ser Gln Pro Arg Gly Pro Asn Glu Lys Arg 580 585 590 <210> 26 <211> 469 <212> PRT <213> Homo sapiens <400> 26 Met Ile Thr Glu Gly Ala Gln Ala Pro Arg Leu Leu Leu Pro Pro Leu 1 5 10 15 Leu Leu Leu Leu Thr Leu Pro Ala Thr Gly Ser Asp Pro Val Leu Cys 20 25 30 Phe Thr Gln Tyr Glu Glu Ser Ser Gly Lys Cys Lys Gly Leu Leu Gly 35 40 45 Gly Gly Val Ser Val Glu Asp Cys Cys Leu Asn Thr Ala Phe Ala Tyr 50 55 60 Gln Lys Arg Ser Gly Gly Leu Cys Gln Pro Cys Arg Ser Pro Arg Trp 65 70 75 80 Ser Leu Trp Ser Thr Trp Ala Pro Cys Ser Val Thr Cys Ser Glu Gly 85 90 95 Ser Gln Leu Arg Tyr Arg Arg Cys Val Gly Trp Asn Gly Gln Cys Ser 100 105 110 Gly Lys Val Ala Pro Gly Thr Leu Glu Trp Gln Leu Gln Ala Cys Glu 115 120 125 Asp Gln Gln Cys Cys Pro Glu Met Gly Gly Trp Ser Gly Trp Gly Pro 130 135 140 Trp Glu Pro Cys Ser Val Thr Cys Ser Lys Gly Thr Arg Thr Arg Arg 145 150 155 160 Arg Ala Cys Asn His Pro Ala Pro Lys Cys Gly Gly His Cys Pro Gly 165 170 175 Gln Ala Gln Glu Ser Glu Ala Cys Asp Thr Gln Gln Val Cys Pro Thr 180 185 190 His Gly Ala Trp Ala Thr Trp Gly Pro Trp Thr Pro Cys Ser Ala Ser 195 200 205 Cys His Gly Gly Pro His Glu Pro Lys Glu Thr Arg Ser Arg Lys Cys 210 215 220 Ser Ala Pro Glu Pro Ser Gln Lys Pro Pro Gly Lys Pro Cys Pro Gly 225 230 235 240 Leu Ala Tyr Glu Gln Arg Arg Cys Thr Gly Leu Pro Pro Cys Pro Val 245 250 255 Ala Gly Gly Trp Gly Pro Trp Gly Pro Val Ser Pro Cys Pro Val Thr 260 265 270 Cys Gly Leu Gly Gln Thr Met Glu Gln Arg Thr Cys Asn His Pro Val 275 280 285 Pro Gln His Gly Gly Pro Phe Cys Ala Gly Asp Ala Thr Arg Thr His 290 295 300 Ile Cys Asn Thr Ala Val Pro Cys Pro Val Asp Gly Glu Trp Asp Ser 305 310 315 320 Trp Gly Glu Trp Ser Pro Cys Ile Arg Arg Asn Met Lys Ser Ile Ser 325 330 335 Cys Gln Glu Ile Pro Gly Gln Gln Ser Arg Gly Arg Thr Cys Arg Gly 340 345 350 Arg Lys Phe Asp Gly His Arg Cys Ala Gly Gln Gln Gln Asp Ile Arg 355 360 365 His Cys Tyr Ser Ile Gln His Cys Pro Leu Lys Gly Ser Trp Ser Glu 370 375 380 Trp Ser Thr Trp Gly Leu Cys Met Pro Pro Cys Gly Pro Asn Pro Thr 385 390 395 400 Arg Ala Arg Gln Arg Leu Cys Thr Pro Leu Leu Pro Lys Tyr Pro Pro 405 410 415 Thr Val Ser Met Val Glu Gly Gln Gly Glu Lys Asn Val Thr Phe Trp 420 425 430 Gly Arg Pro Leu Pro Arg Cys Glu Glu Leu Gln Gly Gln Lys Leu Val 435 440 445 Val Glu Glu Lys Arg Pro Cys Leu His Val Pro Ala Cys Lys Asp Pro 450 455 460 Glu Glu Glu Glu Leu 465 <210> 27 <211> 791 <212> PRT <213> Homo sapiens <400> 27 Met Gly Asp Gln Arg Leu Gln Asp Trp Leu Arg Ser Pro Gly Met Asp 1 5 10 15 Ser Lys Pro Trp Tyr Cys Asn Lys Arg Pro Ser Lys Cys Phe Ala Lys 20 25 30 Cys Lys His Arg Arg Leu Arg Phe Pro Pro Met Asp Thr Gln Asn Trp 35 40 45 Val Phe Val Lys Glu Gly Met Asp Asp Phe Arg Tyr Gly Cys Pro Ser 50 55 60 Pro Glu Asp Thr Leu Val Cys Arg Arg Asp Glu Phe Leu Leu Pro Lys 65 70 75 80 Ile Ser Leu Arg Gly Pro Gln Ala Asp Pro Lys Ser Gly Gln Lys Lys 85 90 95 Leu Leu Lys Lys Ala Ala Leu Phe Ser Lys Leu Ser Pro Ala Gln Leu 100 105 110 Ala Arg Lys Ala Phe Val Glu Gln Val Glu Ala Gln Leu Met Ala Lys 115 120 125 His Pro Leu Ala Met Tyr Pro Asn Leu Gly Glu Asp Met Pro Pro Asp 130 135 140 Leu Leu Leu Gln Val Leu Lys His Leu Asp Pro Glu Arg Glu Leu Glu 145 150 155 160 Asp Ala Trp Ala Cys Cys Glu Thr Gln Glu Lys Thr Thr Glu Val Pro 165 170 175 Thr Glu Pro Gly Lys His Pro Cys Gly Glu Phe Cys Leu Lys Pro Pro 180 185 190 Glu Thr Pro Val Ser His Leu Leu Pro Glu Pro Pro Glu Thr Gly Val 195 200 205 Ser His Leu Ser Pro Glu Pro Pro Lys Thr Pro Val Ser Ser Leu Arg 210 215 220 Pro Glu Pro Pro Glu Thr Gly Val Ser His Leu Arg Pro Glu Pro Pro 225 230 235 240 Glu Thr Gly Val Ser His Ile Arg Pro Gly Pro Pro Ile Thr Arg Arg 245 250 255 Arg Ser Ser Leu Leu Arg Gln Leu Leu Lys Leu Asp Ser Glu Arg Lys 260 265 270 Leu Glu Asp Ala Arg Ala Pro Cys Glu Gly Arg Glu Lys Thr Thr Asp 275 280 285 Glu Pro Thr Glu Pro Gly Lys Tyr Pro Cys Gly Lys Phe Cys Pro Arg 290 295 300 Pro Phe Glu Thr Pro Leu Ser His Leu Arg Gln Glu Pro Pro Lys Thr 305 310 315 320 Pro Val Ser Ser Leu Arg Pro Glu Pro Pro Glu Thr Gly Glu Ser His 325 330 335 Leu Arg Leu Glu His Ser Lys Thr Arg Arg Gly Ser Ser Leu Arg Ser 340 345 350 Glu Pro Ser Glu Thr Gly Val Ser Arg Leu Arg Leu Ala Pro Pro Lys 355 360 365 Thr Arg Arg Gly Ser Ser Leu His Ala Glu Pro Ser Lys Thr Gly Val 370 375 380 Ser His Leu Ser Pro Glu Pro Pro Lys Thr Glu Val Ser His Leu His 385 390 395 400 Pro Val Pro Pro Lys Thr Gly Val Cys His Leu Arg Leu Glu Pro Pro 405 410 415 Asp Thr Ser Gln Val Ser Asn Leu Leu Leu Tyr Ile Leu Lys Val Leu 420 425 430 Asp Ser Gly Arg Thr Leu Lys Asp Val Trp Asp Arg Cys Glu Ala Arg 435 440 445 Val Lys Lys Thr Lys Glu Pro Thr Glu Pro His Lys Ser Pro Cys Gly 450 455 460 Glu Pro Cys Leu Gln Pro Pro Glu Thr Gln Val Ser His Pro His Pro 465 470 475 480 Glu His Pro Lys Thr Arg Arg Arg Ser Ser Leu His Ser Gln Pro Pro 485 490 495 Lys Thr Arg Arg Thr Ser Ser Leu Arg Ser Glu Pro Pro Lys Thr Arg 500 505 510 Arg Thr Ser Ser Leu Arg Ser Glu Pro Pro Lys Thr Arg Arg Thr Ser 515 520 525 Ser Leu Gly Pro Glu Pro Pro Lys Thr Arg Arg Val Ser Ser Leu Arg 530 535 540 Pro Glu Leu Pro Lys Ser Arg Arg Val Ser Ser Leu His Pro Glu Pro 545 550 555 560 Pro Lys Ala Pro Glu Ser His Gln Phe Ser Glu Pro Pro Lys Ile Arg 565 570 575 Ala Ser Tyr Ile Lys Glu Leu Leu Gln Glu Asp Thr Pro Ser Thr Lys 580 585 590 Glu Cys Val Ser Asp Ser Leu Gln Tyr Arg Tyr Thr Ser Glu Lys Leu 595 600 605 Arg Glu Phe Phe Lys Trp Ala Gly Asp Leu Gly Ala Asp Glu Glu Ser 610 615 620 Ile Arg Asn Leu Phe Asp Phe Thr Pro Lys Tyr Arg Ala Thr His Glu 625 630 635 640 Asp Gln Lys Phe Lys Lys Val Lys Glu Cys Ser Ser Glu Leu Lys Tyr 645 650 655 Ser Met Glu Leu Asp Glu Lys Asp Glu Asp Lys Phe Phe Ser Gln Glu 660 665 670 Lys Tyr Trp Gly Arg Lys Phe His Thr Pro Ser Asn Ser Tyr Thr Ala 675 680 685 Gln Arg Val Lys Met Lys Tyr Gly Ala Trp Tyr Leu Lys Pro Lys Leu 690 695 700 Trp Lys Lys Leu Arg Ser Asp Glu Pro Leu Ile Asp Pro Lys Leu Leu 705 710 715 720 Leu Lys Lys Pro Asp Glu Pro Asp Val Leu Asp Asp Leu Tyr Gly Pro 725 730 735 Ile Ala Phe Lys Asp Phe Ile Leu Ser Lys Gly Tyr Glu Met Pro Gly 740 745 750 Ile Ile Gln Arg Leu Phe Ala Arg Arg Gly Trp Thr Tyr Asp Ser Val 755 760 765 Lys Thr Pro Ile Gln Arg Ala Met Ile Phe Tyr Lys Tyr Lys Glu Ile 770 775 780 Val Glu Ala Ser Glu Glu Asp 785 790 <210> 28 <211> 823 <212> PRT <213> Homo sapiens <400> 28 Met Lys Arg His Arg Pro Val Ser Ser Ser Asp Ser Ser Asp Glu Ser 1 5 10 15 Pro Ser Thr Ser Phe Thr Ser Gly Ser Met Tyr Arg Ile Lys Ser Lys 20 25 30 Ile Pro Asn Glu His Lys Lys Pro Ala Glu Val Phe Arg Lys Asp Leu 35 40 45 Ile Ser Ala Met Lys Leu Pro Asp Ser His His Ile Asn Pro Asp Ser 50 55 60 Tyr Tyr Leu Phe Ala Asp Thr Trp Lys Glu Glu Trp Glu Lys Gly Val 65 70 75 80 Gln Val Pro Ala Ser Pro Asp Thr Val Pro Gln Pro Ser Leu Arg Ile 85 90 95 Ile Ala Glu Lys Val Lys Asp Val Leu Phe Ile Arg Pro Arg Lys Tyr 100 105 110 Ile His Cys Ser Ser Pro Asp Thr Thr Glu Pro Gly Tyr Ile Asn Ile 115 120 125 Met Glu Leu Ala Ala Ser Val Cys Arg Tyr Asp Leu Asp Asp Met Asp 130 135 140 Ile Phe Trp Leu Gln Glu Leu Asn Glu Asp Leu Ala Glu Met Gly Cys 145 150 155 160 Gly Pro Val Asp Glu Asn Leu Met Glu Lys Thr Val Glu Val Leu Glu 165 170 175 Arg His Cys His Glu Asn Met Asn His Ala Ile Glu Thr Glu Glu Gly 180 185 190 Leu Gly Ile Glu Tyr Asp Glu Asp Val Ile Cys Asp Val Cys Arg Ser 195 200 205 Pro Asp Ser Glu Glu Gly Asn Asp Met Val Phe Cys Asp Lys Cys Asn 210 215 220 Val Cys Val His Gln Ala Cys Tyr Gly Ile Leu Lys Val Pro Glu Gly 225 230 235 240 Ser Trp Leu Cys Arg Ser Cys Val Leu Gly Ile Tyr Pro Gln Cys Val 245 250 255 Leu Cys Pro Lys Lys Gly Gly Ala Leu Lys Thr Thr Lys Thr Gly Thr 260 265 270 Lys Trp Ala His Val Ser Cys Ala Leu Trp Ile Pro Glu Val Ser Ile 275 280 285 Ala Cys Pro Glu Arg Met Glu Pro Ile Thr Lys Ile Ser His Ile Pro 290 295 300 Pro Ser Arg Trp Ala Leu Val Cys Asn Leu Cys Lys Leu Lys Thr Gly 305 310 315 320 Ala Cys Ile Gln Cys Ser Ile Lys Ser Cys Ile Thr Ala Phe His Val 325 330 335 Thr Cys Ala Phe Glu His Gly Leu Glu Met Lys Thr Ile Leu Asp Glu 340 345 350 Gly Asp Glu Val Lys Phe Lys Ser Tyr Cys Leu Lys His Ser Gln Asn 355 360 365 Arg Gln Lys Leu Gly Glu Ala Glu Tyr Pro His His Arg Ala Lys Glu 370 375 380 Gln Ser Gln Ala Lys Ser Glu Lys Thr Ser Leu Arg Ala Gln Lys Leu 385 390 395 400 Arg Glu Leu Glu Glu Glu Phe Tyr Ser Leu Val Arg Val Glu Asp Val 405 410 415 Ala Ala Glu Leu Gly Met Pro Thr Leu Ala Val Asp Phe Ile Tyr Asn 420 425 430 Tyr Trp Lys Leu Lys Arg Lys Ser Asn Phe Asn Lys Pro Leu Phe Pro 435 440 445 Pro Lys Glu Asp Glu Glu Asn Gly Leu Val Gln Pro Lys Glu Glu Ser 450 455 460 Ile His Thr Arg Met Arg Met Phe Met His Leu Arg Gln Asp Leu Glu 465 470 475 480 Arg Val Arg Asn Leu Cys Tyr Met Ile Ser Arg Arg Glu Lys Leu Lys 485 490 495 Leu Ser His Asn Lys Ile Gln Glu Gln Ile Phe Gly Leu Gln Val Gln 500 505 510 Leu Leu Asn Gln Glu Ile Asp Ala Gly Leu Pro Leu Thr Asn Ala Leu 515 520 525 Glu Asn Ser Leu Phe Tyr Pro Pro Pro Arg Ile Thr Leu Lys Leu Lys 530 535 540 Met Pro Lys Ser Thr Pro Glu Asp His Arg Asn Ser Ser Thr Glu Thr 545 550 555 560 Asp Gln Gln Pro His Ser Pro Asp Ser Ser Ser Ser Val His Ser Ile 565 570 575 Arg Asn Met Gln Val Pro Gln Glu Ser Leu Glu Met Arg Thr Lys Ser 580 585 590 Tyr Pro Arg Tyr Pro Leu Glu Ser Lys Asn Asn Arg Leu Leu Ala Ser 595 600 605 Leu Ser His Ser Arg Ser Glu Ala Lys Glu Ser Ser Pro Ala Trp Arg 610 615 620 Thr Pro Ser Ser Glu Cys Tyr His Gly Gln Ser Leu Gly Lys Pro Leu 625 630 635 640 Val Leu Gln Ala Ala Leu His Gly Gln Ser Ser Ile Gly Asn Gly Lys 645 650 655 Ser Gln Pro Asn Ser Lys Phe Ala Lys Ser Asn Gly Leu Glu Gly Ser 660 665 670 Trp Ser Gly Asn Val Thr Gln Lys Asp Ser Ser Ser Glu Met Phe Cys 675 680 685 Asp Gln Glu Pro Val Phe Ser Pro His Leu Val Ser Gln Gly Ser Phe 690 695 700 Arg Lys Ser Thr Val Glu His Phe Ser Arg Ser Phe Lys Glu Thr Thr 705 710 715 720 Asn Arg Trp Val Lys Asn Thr Glu Asp Leu Gln Cys Tyr Val Lys Pro 725 730 735 Thr Lys Asn Met Ser Pro Lys Glu Gln Phe Trp Gly Arg Gln Val Leu 740 745 750 Arg Arg Ser Ala Gly Arg Ala Pro Tyr Gln Glu Asn Asp Gly Tyr Cys 755 760 765 Pro Asp Leu Glu Leu Ser Asp Ser Glu Ala Glu Ser Asp Gly Asn Lys 770 775 780 Glu Lys Val Arg Val Arg Lys Asp Ser Ser Asp Arg Glu Asn Pro Pro 785 790 795 800 His Asp Ser Arg Arg Asp Cys His Gly Lys Ser Lys Thr His Pro Leu 805 810 815 Ser His Ser Ser Met Gln Arg 820 <210> 29 <211> 518 <212> PRT <213> Homo sapiens <400> 29 Met Ala Val Ala Leu Gly Cys Ala Ile Gln Ala Ser Leu Asn Gln Gly 1 5 10 15 Ser Val Phe Gln Glu Tyr Asp Thr Asp Cys Glu Val Phe Arg Gln Arg 20 25 30 Phe Arg Gln Phe Gln Tyr Arg Glu Ala Ala Gly Pro His Glu Ala Phe 35 40 45 Asn Lys Leu Trp Glu Leu Cys Cys Gln Trp Leu Lys Pro Lys Met Arg 50 55 60 Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr 65 70 75 80 Ile Leu Pro Thr Glu Ile Glu Thr Trp Val Arg Glu His Cys Pro Glu 85 90 95 Asn Arg Glu Arg Val Val Ser Leu Ile Glu Asp Leu Gln Arg Glu Leu 100 105 110 Glu Ile Pro Glu Gln Gln Val Asp Met His Asp Met Leu Leu Glu Glu 115 120 125 Leu Ala Pro Val Gly Thr Ala His Ile Pro Pro Thr Met His Leu Glu 130 135 140 Ser Pro Ala Leu Gln Val Met Gly Pro Ala Gln Glu Ala Pro Val Ala 145 150 155 160 Glu Ala Trp Ile Pro Gln Ala Gly Pro Pro Glu Leu Asn Tyr Gly Ala 165 170 175 Thr Gly Glu Cys Gln Asn Phe Leu Asp Pro Gly Tyr Pro Leu Pro Lys 180 185 190 Leu Asp Met Asn Phe Ser Leu Glu Asn Arg Glu Glu Pro Trp Val Lys 195 200 205 Glu Leu Gln Asp Ser Lys Glu Met Lys Gln Leu Leu Asp Ser Lys Ile 210 215 220 Gly Phe Glu Ile Gly Ile Glu Asn Glu Glu Asp Thr Ser Lys Gln Lys 225 230 235 240 Lys Met Glu Thr Met Tyr Pro Phe Ile Val Thr Leu Glu Gly Asn Ala 245 250 255 Leu Gln Gly Pro Ile Leu Gln Lys Asp Tyr Val Gln Leu Glu Asn Gln 260 265 270 Trp Glu Thr Pro Pro Glu Asp Leu Gln Thr Asp Leu Ala Lys Leu Val 275 280 285 Asp Gln Gln Asn Pro Thr Leu Gly Glu Thr Pro Glu Asn Ser Asn Leu 290 295 300 Glu Glu Pro Leu Asn Pro Lys Pro His Lys Lys Lys Ser Pro Gly Glu 305 310 315 320 Lys Pro His Arg Cys Pro Gln Cys Gly Lys Cys Phe Ala Arg Lys Ser 325 330 335 Gln Leu Thr Gly His Gln Arg Ile His Ser Gly Glu Glu Pro His Lys 340 345 350 Cys Pro Glu Cys Gly Lys Arg Phe Leu Arg Ser Ser Asp Leu Tyr Arg 355 360 365 His Gln Arg Leu His Thr Gly Glu Arg Pro Tyr Glu Cys Thr Val Cys 370 375 380 Lys Lys Arg Phe Thr Arg Arg Ser His Leu Ile Gly His Gln Arg Thr 385 390 395 400 His Ser Glu Glu Glu Thr Tyr Lys Cys Leu Glu Cys Gly Lys Ser Phe 405 410 415 Cys His Gly Ser Ser Leu Lys Arg His Leu Lys Thr His Thr Gly Glu 420 425 430 Lys Pro His Arg Cys His Asn Cys Gly Lys Ser Phe Ser Arg Leu Thr 435 440 445 Ala Leu Thr Leu His Gln Arg Thr His Thr Glu Glu Arg Pro Phe Lys 450 455 460 Cys Asn Tyr Cys Gly Lys Ser Phe Arg Gln Arg Pro Ser Leu Val Ile 465 470 475 480 His Leu Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Thr His Cys 485 490 495 Ser Lys Ser Phe Arg Gln Arg Ala Gly Leu Ile Met His Gln Val Thr 500 505 510 His Phe Arg Gly Leu Ile 515 <210> 30 <211> 434 <212> PRT <213> Homo sapiens <400> 30 Met Val Gln Asp Gly Thr Phe Lys Thr Arg Asp Ser Thr Trp Thr Cys 1 5 10 15 Glu Ser Thr Arg Met Ala Ala Ala Pro Pro Ser Tyr Cys Phe Val Ala 20 25 30 Phe Pro Pro Arg Ala Lys Asp Gly Leu Val Val Phe Gly Lys Asn Ser 35 40 45 Ala Arg Pro Arg Asp Glu Val Gln Glu Val Val Tyr Phe Ser Ala Ala 50 55 60 Asp His Glu Pro Glu Ser Lys Val Glu Cys Thr Tyr Ile Ser Ile Asp 65 70 75 80 Gln Val Pro Arg Thr Tyr Ala Ile Met Ile Ser Arg Pro Ala Trp Leu 85 90 95 Trp Gly Ala Glu Met Gly Ala Asn Glu His Gly Val Cys Ile Ala Asn 100 105 110 Glu Ala Ile Asn Thr Arg Glu Pro Ala Ala Glu Ile Glu Ala Leu Leu 115 120 125 Gly Met Asp Leu Val Arg Leu Gly Leu Glu Arg Gly Glu Thr Ala Lys 130 135 140 Glu Ala Leu Asp Val Ile Val Ser Leu Leu Glu Glu His Gly Gln Gly 145 150 155 160 Gly Asn Tyr Phe Glu Asp Ala Asn Ser Cys His Ser Phe Gln Ser Ala 165 170 175 Tyr Leu Ile Val Asp Arg Asp Glu Ala Trp Val Leu Glu Thr Ile Gly 180 185 190 Lys Tyr Trp Ala Ala Glu Lys Val Thr Glu Gly Val Arg Cys Ile Cys 195 200 205 Ser Gln Leu Ser Leu Thr Thr Lys Met Asp Ala Glu His Pro Glu Leu 210 215 220 Arg Ser Tyr Ala Gln Ser Gln Gly Trp Trp Thr Gly Glu Gly Glu Phe 225 230 235 240 Asn Phe Ser Glu Val Phe Ser Pro Val Glu Asp His Leu Asp Cys Gly 245 250 255 Ala Gly Lys Asp Ser Leu Glu Lys Gln Glu Glu Ser Ile Thr Val Gln 260 265 270 Thr Met Met Asn Thr Leu Arg Asp Lys Ala Ser Gly Val Cys Ile Asp 275 280 285 Ser Glu Phe Phe Leu Thr Thr Ala Ser Gly Val Ser Val Leu Pro Gln 290 295 300 Asn Arg Ser Ser Pro Cys Ile His Tyr Phe Thr Gly Thr Pro Asp Pro 305 310 315 320 Ser Arg Ser Ile Phe Lys Pro Phe Ile Phe Val Asp Asp Val Lys Leu 325 330 335 Val Pro Lys Thr Gln Ser Pro Cys Phe Gly Asp Asp Asp Pro Ala Lys 340 345 350 Lys Glu Pro Arg Phe Gln Glu Lys Pro Asp Arg Arg His Glu Leu Tyr 355 360 365 Lys Ala His Glu Trp Ala Arg Ala Ile Ile Glu Ser Asp Gln Glu Gln 370 375 380 Gly Arg Lys Leu Arg Ser Thr Met Leu Glu Leu Glu Lys Gln Gly Leu 385 390 395 400 Glu Ala Met Glu Glu Ile Leu Thr Ser Ser Glu Pro Leu Asp Pro Ala 405 410 415 Glu Val Gly Asp Leu Phe Tyr Asp Cys Val Asp Thr Glu Ile Lys Phe 420 425 430 Phe Lys <210> 31 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 31 gggataagat tgctatcatc tatgacagt 29 <210> 32 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 32 gaaggctcta caatgagaat gtatgctat 29 <210> 33 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 33 ttcagtcaga tgctcagact taaatagatt 30 <210> 34 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 34 acagtcatgt gactgggctt tt 22 <210> 35 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 35 ctctagatat aaatgcaaca gaggagcaa 29 <210> 36 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ACSS3 <400> 36 ccattgacaa tggcagataa agctg 25 <210> 37 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 37 gggctttcga ggagtattaa aaataagt 28 <210> 38 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 38 tgctacttcc ttctctgtta agcc 24 <210> 39 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 39 gtatttcttg ttgtcaacat agtggattcc 30 <210> 40 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 40 atgctgtagc tgggaaagac tg 22 <210> 41 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 41 cttaaaccag ggatcatgtc tgcat 25 <210> 42 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 42 gtcttgttca cactgctgta cg 22 <210> 43 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 43 gatgtctttt gtgggagagt tcaatg 26 <210> 44 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ADAM21 <400> 44 ggccacacac agtaccatct tt 22 <210> 45 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 45 tcaccaggat aatacccatc cttca 25 <210> 46 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 46 agtctgcatc ttgtttggct ga 22 <210> 47 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 47 tcggagagca gctctgagt 19 <210> 48 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 48 ctgtgggaca ggcagatcat 20 <210> 49 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 49 ggctttgaag cataagttgt caaca 25 <210> 50 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 50 gggtcatgaa gctccacact tt 22 <210> 51 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 51 gccaaatcca aggaaatctg tggt 24 <210> 52 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> AFF2 <400> 52 agaggttttt caggttctca tgatctc 27 <210> 53 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 53 tccggatacc tgcataagca ag 22 <210> 54 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 54 catccattga tgcctcattc aaagac 26 <210> 55 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 55 gaagactaag gattgtgagt ttgtagca 28 <210> 56 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 56 tcctgttgat atttctttac cttttctgct 30 <210> 57 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 57 tctttgttag tgattgcctc accat 25 <210> 58 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ALG13 <400> 58 agtctctccc acatcaagag ca 22 <210> 59 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 59 gtaggagaga agaagactga gagcact 27 <210> 60 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 60 gtggaggctg agattgcaaa cta 23 <210> 61 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 61 ttccaatcaa gaacttggca cct 23 <210> 62 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 62 gtcgtggaag ccacggaca 19 <210> 63 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 63 gccgtgtctg tactctcatt gc 22 <210> 64 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 64 ccatcaacgt cttggctgag aa 22 <210> 65 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 65 aacctggtag ccttagaaag ctg 23 <210> 66 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 66 ttgtcccagg aggaagaaga cct 23 <210> 67 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 67 gggacttggc ataattgtga ttgt 24 <210> 68 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 68 atcccacagc cctcccaaca aa 22 <210> 69 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 69 gcttcaccac tagcttgggt tt 22 <210> 70 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 70 gggagactgt gagcttttct tgg 23 <210> 71 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 71 ggacttgttg ctggctgact t 21 <210> 72 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 72 gggtctaccc tttctcctct ga 22 <210> 73 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 73 gtatgttcac gaatcagaga caaatgc 27 <210> 74 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 74 cgaccgcagg atcaagtatg ag 22 <210> 75 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 75 cagcctggcc tcatacttga tc 22 <210> 76 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 76 caggatatct gcctcaacct gatg 24 <210> 77 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 77 catggtgcct accatggtca at 22 <210> 78 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 78 cctgagaagc agaatggcct ta 22 <210> 79 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 79 cgcactgcac taaggccatt 20 <210> 80 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 80 gccaaggccc ataatagcca tg 22 <210> 81 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 81 cacacacctg gcatggctat ta 22 <210> 82 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 82 cccatagtcc tacctgagga gaaa 24 <210> 83 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 83 ctgaaaccct tggtgaagtc ct 22 <210> 84 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 84 ttggtttcac agctgatacc caa 23 <210> 85 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 85 atcccaccct ccaaacaaag ca 22 <210> 86 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 86 cccagccctg tatatggatt tatctt 26 <210> 87 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 87 gctgctgctt tctgtgagat ttt 23 <210> 88 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 88 gggtgcaagt ggaggagatc ta 22 <210> 89 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 89 ccctgacatt tgctctgaag gt 22 <210> 90 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 90 tcggtaagag ccttttctcc ct 22 <210> 91 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 91 tcttaccgaa atcttccacg agc 23 <210> 92 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 92 aagatgaata agggctggct gg 22 <210> 93 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 93 cttactgaac actgtaacac tggaaaga 28 <210> 94 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> BAP1 <400> 94 gtgggaacag agctaatatt ctcaagag 28 <210> 95 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> BRWD3 <400> 95 agaggatcct cagtggacac aa 22 <210> 96 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> BRWD3 <400> 96 ctagaggagc taccagagcc aaac 24 <210> 97 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> BRWD3 <400> 97 attgttttta catgccattg ccagaa 26 <210> 98 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> BRWD3 <400> 98 ttgatgttag gctgaacatg aaaacttttt 30 <210> 99 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 99 attaaattct ctgtggcaaa caataaggac 30 <210> 100 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 100 tgggaaacca cgatcacctt tt 22 <210> 101 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 101 cagctggaca gaagggtgaa 20 <210> 102 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 102 gtgtgtggta gcttagtaag aaagaagat 29 <210> 103 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 103 caaaaactgg tttctctcac accaat 26 <210> 104 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 104 tggaggacca gcatctcctt ta 22 <210> 105 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 105 cctcattctt ttcctgtagg tccaa 25 <210> 106 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 106 tctctcagac tcaaagactt tccct 25 <210> 107 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 107 ccttgaaagg ctgtttgcta ttgt 24 <210> 108 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 108 tcttgaagca aagttgcaaa cattattga 29 <210> 109 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 109 ctgcttggaa gagtttcgtt cag 23 <210> 110 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> COL4A5 <400> 110 ccctagcatc tctgaaggaa gct 23 <210> 111 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 111 cccacctgat ctcgacagaa ga 22 <210> 112 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 112 tggccaataa tgtgcccttc tt 22 <210> 113 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 113 cacaagaaaa tccagtgcct caa 23 <210> 114 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 114 aagtctgtcc gatccttgct tc 22 <210> 115 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 115 ctaactgagg gtgctggaaa ct 22 <210> 116 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CPEB1 <400> 116 gctgttggct gcaaagaaaa cta 23 <210> 117 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 117 gtttgagtga aggcattcat ggt 23 <210> 118 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 118 gatctcttcc agagtctcaa acactt 26 <210> 119 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 119 caagagggtg gttcccagaa tt 22 <210> 120 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 120 gagtgaaggg caatgaaggg ta 22 <210> 121 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 121 ggctggctcc gatgtatttg at 22 <210> 122 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ERBB2 <400> 122 caacgtagcc atcagtctca ga 22 <210> 123 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 123 attacatagt ataaggctta cccagacca 29 <210> 124 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 124 cgacaagtct gtgaaggatc tgg 23 <210> 125 <211> 31 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 125 cctgataact ttcaaaattt tgctttgttg c 31 <210> 126 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 126 gtccttggaa tgactcagtg cat 23 <210> 127 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 127 cagacagaaa ttcactctgc aattacataa aa 32 <210> 128 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 128 caggtgaacc tatgggtcgt 20 <210> 129 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 129 cccaagaagt tcacactgaa acc 23 <210> 130 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> HSP90AA1 <400> 130 tgagacgttc gcctttcagg 20 <210> 131 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> IRAK1 <400> 131 cgcctaggct ctcgtcact 19 <210> 132 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> IRAK1 <400> 132 cccgcaggag aactcctac 19 <210> 133 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IRAK1 <400> 133 ccaggtgtca ggagtgcttt 20 <210> 134 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IRAK1 <400> 134 acaggtttcg tcacccaaac a 21 <210> 135 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 135 tccgtaccct ctttggctct ag 22 <210> 136 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 136 tgtctttctg cctgtctgta atcac 25 <210> 137 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 137 ccagaagtgt gcggatcctc 20 <210> 138 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 138 agttgactgg ccctgtgttg 20 <210> 139 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 139 cccacacaca cagatagagg ttg 23 <210> 140 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 140 ctgtcctggg tatggcagat c 21 <210> 141 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 141 ccatctgtgt cgaagctcct t 21 <210> 142 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 142 gttctctgcc catgtgcaga t 21 <210> 143 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 143 ctcttctggg tctccactca ac 22 <210> 144 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 144 cctagccctg ctgtggataa ag 22 <210> 145 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 145 caggttgttc atctggtcca gaa 23 <210> 146 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 146 agtcttagca tagacatgga gggaa 25 <210> 147 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 147 gcctcactca ggcagttctt ta 22 <210> 148 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 148 cctctgcctc tattcaatac tgccta 26 <210> 149 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 149 ctactggagc acttgcagag at 22 <210> 150 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 150 gatgatgagc gccagtgtat ca 22 <210> 151 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 151 cccgaacttc caccagaata gg 22 <210> 152 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 152 ccagagaagc tagacctgaa cct 23 <210> 153 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 153 ccatcttgca gataagctcc tca 23 <210> 154 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 154 gaagcaggag ggttgtagag aag 23 <210> 155 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 155 gcaaagttgt agccttggtt ga 22 <210> 156 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 156 caggaaaatc tctatctcaa cagccat 27 <210> 157 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 157 gaggtcaggc tggctatcaa at 22 <210> 158 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 158 cctgcatgac caaggtgtga tt 22 <210> 159 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 159 ggagcccaca ctgacttgat tc 22 <210> 160 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 160 gtactgtgcc acatcaatgc ag 22 <210> 161 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 161 atgccagaga tatctgcatt gatgt 25 <210> 162 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 162 gttccctagg ctaaagaaaa tgacttaaga 30 <210> 163 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 163 agatactaaa tgatttgcct aagctcaca 29 <210> 164 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 164 tagcattgag gaagatgtga ctgttg 26 <210> 165 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 165 gggaatgctt attgaaggga caaga 25 <210> 166 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 166 cctaagacct tcctggagag caa 23 <210> 167 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 167 gtagcctcat ggtcatcttg gt 22 <210> 168 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 168 ccatttttct ctctcccaga taagga 26 <210> 169 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 169 tccctccacc tcaaagctct aa 22 <210> 170 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 170 taatgaggag aaggacaagg aatacaaacc 30 <210> 171 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 171 gcaaggagcc aatatttttg cct 23 <210> 172 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 172 ctacaggcct actccctcac ata 23 <210> 173 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 173 accaccagct cctagtcttc tc 22 <210> 174 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 174 cttttggtga cttccggtct taca 24 <210> 175 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 175 cgatgggcct gattttcgc 19 <210> 176 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> KDM5C <400> 176 gcgccatgag tccttaagg 19 <210> 177 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM6A <400> 177 ccaagcaaga attcatgcac gt 22 <210> 178 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> KDM6A <400> 178 agactcatag tctgtgttca ctttgaac 28 <210> 179 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM6A <400> 179 cactgttcat tgggttcagg cta 23 <210> 180 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> KDM6A <400> 180 aaaaaggaac agtcctattg gatataatcc 30 <210> 181 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LRP12 <400> 181 acctcgggta ctctgagttg ag 22 <210> 182 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LRP12 <400> 182 aagtttgttt tccgtggagt ctga 24 <210> 183 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LRP12 <400> 183 tccacggaaa acaaacttct gtga 24 <210> 184 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LRP12 <400> 184 ttcctatggc aggcagatca ag 22 <210> 185 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 185 ctgggaagtt tgttaggatc cgaa 24 <210> 186 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 186 caaggagagc ttgaatgtgc ct 22 <210> 187 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 187 cccaaaatgg cctgcagata tg 22 <210> 188 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 188 ggccatggga tgtctttcaa tg 22 <210> 189 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 189 ctccactgaa aggtgcattg aaa 23 <210> 190 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 190 ggtgatcctg ctactacagc aaataa 26 <210> 191 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 191 gcagggctca aatgatcaaa taagc 25 <210> 192 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> NCOA6 <400> 192 ttggctcaga accgaagcca aga 23 <210> 193 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 193 tccaagtaaa tgaaaatttg tttgccattt 30 <210> 194 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 194 gggatacccg agatggtttt cc 22 <210> 195 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 195 acagcaaccc tctttaaaag atggaa 26 <210> 196 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 196 tctcctactg tgttctgctt attatgagta 30 <210> 197 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 197 accgtcatcc actgcatgtt tt 22 <210> 198 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> NHS <400> 198 cttaacttct tcagacttgt tgatggac 28 <210> 199 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 199 gaatgatgtc atccatgcca caa 23 <210> 200 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 200 agtgtgcaca tgtctccaga ag 22 <210> 201 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 201 gtccacattg caaaccagtg tt 22 <210> 202 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 202 catgggcatc gatccagaaa ct 22 <210> 203 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 203 ccacatcatt tatgagagcc tcagtt 26 <210> 204 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RGAG1 <400> 204 tgtggtgtgg acattgttcc ag 22 <210> 205 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 205 ccatgtgtcc cattggcttc t 21 <210> 206 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 206 gggttcgtga gcaaaggagg 20 <210> 207 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 207 cgctttagct ccgcctctc 19 <210> 208 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 208 actagcgacc caactccgc 19 <210> 209 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 209 gggacctcca ctccaaactc t 21 <210> 210 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 210 ctcaccagga taaaggcaga agga 24 <210> 211 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 211 atggtccgcc agacagaga 19 <210> 212 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 212 gtgcttcaag ggagccaaga gt 22 <210> 213 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 213 gcacttgagt ctagctgtca g 21 <210> 214 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SCAF1 <400> 214 ccgccatacc tttatcattg gg 22 <210> 215 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 215 ccacaggctt cactcatcac tg 22 <210> 216 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 216 caacgctcac cttcttggat ga 22 <210> 217 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 217 cagtgaccac ctccatcctt tt 22 <210> 218 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 218 ggcggtgaag agtctgtttc c 21 <210> 219 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 219 tctgtctgtc aaatcaagga atggaaa 27 <210> 220 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SH3TC1 <400> 220 cctggcatcc tcctcagaaa ag 22 <210> 221 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 221 atgagataca tcagcatgct aatagaagtg 30 <210> 222 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 222 catatcagtc atgtgttctg tcagct 26 <210> 223 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 223 agcagacatg gtttttaaaa tcttccaaa 29 <210> 224 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 224 cagtcaatct gatactgttc caaatatgg 29 <210> 225 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 225 ccatatttgg aacagtatca gattgactg 29 <210> 226 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 226 taccaattgc agaggagaat tctttgaa 28 <210> 227 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 227 tggaaggaaa ctacatagcc ctaca 25 <210> 228 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TBC1D8B <400> 228 caacagcgat gcaagaatct gtt 23 <210> 229 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 229 taactgcagt gggcctgaaa at 22 <210> 230 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 230 agttcaccat gtgtgtgttc ca 22 <210> 231 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 231 cctgtgatgc tgatgatgct gata 24 <210> 232 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 232 aattcttcac cagacgctag ctt 23 <210> 233 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 233 ggaaaaagca ctctgaatgg tgga 24 <210> 234 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 234 gcctttcaga aagcatcgga gaa 23 <210> 235 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 235 aactgccagc agttgatgag aa 22 <210> 236 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 236 ttacgtttta gatgggattc cgctt 25 <210> 237 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 237 caccaagcgg aatcccatct aa 22 <210> 238 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 238 agctgtgttg ttttctgggt gta 23 <210> 239 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 239 aaacacaacc atcccagagt tca 23 <210> 240 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 240 ccatgaaaac attcttccac tttagtctg 29 <210> 241 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 241 gggtcactgc atgtttggac tt 22 <210> 242 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 242 gcagtgtgag aacagactca acag 24 <210> 243 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 243 aagtctctga cgtggatgag tttg 24 <210> 244 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 244 gaaagctttt cagctgcagc tt 22 <210> 245 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 245 aggtttggaa atagccagag ttttaca 27 <210> 246 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TET2 <400> 246 atctagaggt ggctcccatg aa 22 <210> 247 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 247 tcgagatata catgcttcgg ttctattttg 30 <210> 248 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 248 ctcatcagca aagacctcca gta 23 <210> 249 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 249 gggttcgtgg ttccagagaa at 22 <210> 250 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 250 cctccatgga gaccacagag aa 22 <210> 251 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 251 tctctccagc ttctctgtgg t 21 <210> 252 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TEX13A <400> 252 ctgctggagg aaaaggagca ga 22 <210> 253 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ULK3 <400> 253 gcctgaagag agtgtccctt ct 22 <210> 254 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ULK3 <400> 254 ccaagaaaag tctgaacaag gcat 24 <210> 255 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 255 gctgaagaga aggaggagac tga 23 <210> 256 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 256 cctggcttct tcagtcaata aggtaaataa 30 <210> 257 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 257 gaaacttgct ggtaatgtcc tactagt 27 <210> 258 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 258 ggcaggagct gcatcagtta ta 22 <210> 259 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 259 gtgctgctgt ggttttcttt gta 23 <210> 260 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> WNK3 <400> 260 gggattctca gtgcaagtct atgg 24 <210> 261 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> ARSF <400> 261 gtgcatgacg acaagcctaa tattg 25 <210> 262 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ARSF <400> 262 acgactgacg aacgtatgac tg 22 <210> 263 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 263 gctgtagcag tgccggatat 20 <210> 264 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 264 acatgaagtc catcagctgt caag 24 <210> 265 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 265 ccgggatttc ttgacagctg at 22 <210> 266 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 266 tgattccctg ctttggtcca atc 23 <210> 267 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 267 cccactctga ggacctctgt a 21 <210> 268 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 268 gaatgggcag tgctctggaa 20 <210> 269 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 269 ggcaaaggca gtgttgagac 20 <210> 270 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> CFP <400> 270 gtgtccaggc ccaccacat 19 <210> 271 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> FAM47A <400> 271 actggatctc cgacgagtga t 21 <210> 272 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> FAM47A <400> 272 gagactggag tgtcccatct aag 23 <210> 273 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> PHF16 (JADE3) <400> 273 acgccattgc catgaaaata tgaac 25 <210> 274 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> PHF16 (JADE3) <400> 274 tccactctca ctaacctgat gca 23 <210> 275 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> PHF16 (JADE3) <400> 275 ccattctagg agtgaagcaa agga 24 <210> 276 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> PHF16 (JADE3) <400> 276 gccattggat ttggcaaact tg 22 <210> 277 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ZNF449 <400> 277 ggagctgaac tatggtgcta ct 22 <210> 278 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ZNF449 <400> 278 cattgagtaa ttggtgtttc taacccaac 29 <210> 279 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> SCRN1 <400> 279 ttttgctggt aatttagtaa ggtgggaa 28 <210> 280 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> SCRN1 <400> 280 cctggaagcc atggaagaaa tcc 23 <210> 281 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> SCRN1 <400> 281 agggtatgag aaggagaatc gtga 24 <210> 282 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SCRN1 <400> 282 gaactcagga gttacgctca ga 22

Claims (9)

A kit comprising an agent capable of detecting a gender specific marker, which is a mutation of a gene encoding ACSS3,
The agent comprises a primer, a probe or an antibody to the marker, the kit for providing information necessary for the prediction of the difference in the effects of renal cancer treatment according to the sex of renal cancer patients or for prognostic diagnosis of renal cancer patients.
The method according to claim 1,
The gender specific markers are ADAM21, AFF2, ALG13, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM5C, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TANK3, TET2, And further comprises a mutation of a gene encoding at least one selected from the group consisting of ARSF, CFP, FAM47A, PHF16, ZNF449 and SCRN1.
The method according to claim 2,
A mutation of the gene encoding ACSS3 is a nonsense mutation of R634 *, a splice mutation of X152_splice (T replaces C at chromosome 81503485), or a missense mutation of G268D in the amino acid sequence of SEQ ID NO: 1;
The mutation of the gene encoding ADAM21 is at least one mutation selected from the group consisting of N265Y, R408C, T589S and I161V in the amino acid sequence of SEQ ID NO: 2;
The mutation of the gene encoding AFF2 is at least one missense mutation selected from the group consisting of S770F, P513H, T640N and I149K in the amino acid sequence of SEQ ID NO: 3;
The mutation of the gene encoding ALG13 is a missense mutation of at least one of P925T and V456E or a frame shift delete (FS del) mutation of L195Pfs * 23 in the amino acid sequence of SEQ ID NO: 4;
In the amino acid sequence of SEQ ID NO: 5, a mutation of the gene encoding BAP1 is a non-start mutation of M1? (T replaces C at chromosome position 52443894, C replaces T with 52443892), or G128 *, E402 *, At least one nonsense mutation selected from the group consisting of Q253 *, Q267 *, S460 *, Y627 *, S279 *, R60 *, Q40 *, Q156 * and K626 *, or E283Gfs * 52, V335Efs * 56, K711Sfs * 25 At least one FS del mutant selected from the group consisting of R700Gfs * 36, D74Efs * 4 and D407Vfs * 23, or F170V, F170C, E31A, N78S, L49V, D75G, S10T, N229H, G109V, L17P, A145G and A1061T At least one missense mutation selected from the group consisting of: X23_splice (C replaces T at chromosome position 52443729), X41_splice (A replaces G at chromosome position 52443568), X41_splice (A replaces T at chromosome position 52443568) ), X23_splice (ACCTGCGATGAG at chromosome positions 52443623 to 52443647) GAAAGGAAAGCAG is deleted), and at least one splice mutation selected from the group consisting of X311_splice (C replaces A with chromosome position 52439311) or an in-frame delete (IF del) mutation that is K659del;
The mutation of the gene encoding BRWD3 is a missense mutation of at least one of G287A and I1747N in the amino acid sequence of SEQ ID NO: 6;
The mutation of the gene encoding COL4A5 is at least one missense mutation selected from the group consisting of P1184L, P756S, P1365S, G1427V and A1656T in the amino acid sequence of SEQ ID NO: 7, or X1510_splice (G at chromosome position 107935977) A splice mutation);
The mutation of the gene encoding CPEB1 is a missense mutation of at least one of S393R and G136V, or a splice mutation of X499_splice (substituted C at chromosome position 83215272) in the amino acid sequence of SEQ ID NO: 8;
The mutation of the gene encoding ERBB2 is at least one missense mutation selected from the group consisting of E1114G, S649T and V219I in the amino acid sequence of SEQ ID NO: 9, or a frame shift insertion mutation of N388Qfs * 14;
The mutation of the gene encoding HSP90AA1 is at least one missense mutation selected from the group consisting of D512N, H806R, I325T and L167V in the amino acid sequence of SEQ ID NO: 10;
The mutation of the gene encoding IRAK1 is a nonsense mutation of Q280 * or a missense mutation of at least one of V548M and Q584K in the amino acid sequence of SEQ ID NO: 11;
The mutation of the gene encoding KDM5C is at least one nonsense selected from the group consisting of R681 *, Q813 *, E284 *, E798 *, Y639 *, S1110 *, K459 * and R215 * in amino acid sequence of SEQ ID NO: 12 A mutant, at least one missense mutation selected from the group consisting of E1152K, R1458W, G536W, C730R, E592V, C512W, C730F, and H733P, or a splice mutation that is X321_splice (substituted with G at chromosome position 53244975), At least one frame shift deletion mutation selected from the group consisting of T471Vfs * 5, Q1427Pfs * 50, E122Vfs * 14, E1131Sfs * 16, H988Tfs * 18, P27Lfs * 46, F56Cfs * 18, D1414Efs * 54 and G845Rfs * 2;
A mutation of the gene encoding KDM6A is a missense mutation of A30V, a frame shift mutation of A1246Pfs * 19, or a V156del inframe deletion mutation in the amino acid sequence of SEQ ID NO: 13;
The mutation of the gene encoding LRP12 is at least one missense mutation selected from the group consisting of S622L, E639K and V671I in the amino acid sequence of SEQ ID NO: 14;
The mutation of the gene encoding NCOA6 is at least one missense mutation selected from the group consisting of G164E, N877I, N864Y and V1444A in the amino acid sequence of SEQ ID NO: 15, or a frame shift insertion mutation which is H832Sfs * 47;
The mutation of the gene encoding NHS is at least one missense mutation selected from the group consisting of C360R, P1107A and D1069H in the amino acid sequence of SEQ ID NO: 16;
The mutation of the gene encoding RGAG1 is at least one missense mutation selected from the group consisting of A1015G, M858V and G1053R in the amino acid sequence of SEQ ID NO: 17;
The mutation of the gene encoding SCAF1 is at least one frame shift insertion mutation selected from the group consisting of A219Sfs * 11, P211Tfs * 19, P211Tfs * 19 and A216Pfs * 94 in the amino acid sequence of SEQ ID NO: 18, or A216Pfs * 94 In frame shift deletion mutations;
The mutation of the gene encoding SH3TC1 is a missense mutation of at least one of A375V and L180F in the amino acid sequence of SEQ ID NO: 19, or a frame shift deletion mutation of R238Sfs * 38;
The mutation of the gene encoding TBC1D8B is at least one missense mutation selected from the group consisting of G1059V, A614T and Y815F in the amino acid sequence of SEQ ID NO: 20, or a nonsense mutation of S861 *;
The mutation of the gene encoding TET2 is at least one missense mutation selected from the group consisting of Q317K, L757V, V449E, N1714K, D194E, N1390H, R1451Q, M600I, and P554S in the amino acid sequence of SEQ ID NO: 21, or K326 * Phosphorous nonsense mutation;
The mutation of the gene encoding TEX13A is a missense mutation of at least one of R393S and Y257D in the amino acid sequence of SEQ ID NO: 22, or a splice mutation of X199_splice (deleting C at chromosome position 104464282);
The mutation of the gene encoding ULK3 is a frame shift deletion mutation of Q81Sfs * 41 in the amino acid sequence of SEQ ID NO: 23 and a missense mutation of at least one of D79H and L77V;
The mutation of the gene encoding WNK3 is a nonsense mutation of at least one of S865 * and Y589 * in the amino acid sequence of SEQ ID NO: 24, and a missense mutation of E537G;
The mutation of the gene encoding ARSF is a missense mutation that is I42F in the amino acid sequence of SEQ ID 25;
The mutation of the gene encoding CFP is at least one missense mutation selected from the group consisting of S27L, R359Q and E135K in the amino acid sequence of SEQ ID NO: 26, or a frame shift insertion mutation which is E323Gfs * 34;
The mutation of the gene encoding FAM47A is a missense mutation of at least one of R505H and E507Q, or an inframe deletion mutation of at least one of L235_H246del and L235_H246del in the amino acid sequence of SEQ ID NO: 27;
The mutation of the gene encoding PHF16 is a missense mutation of at least one of K656Q and R207W in the amino acid sequence of SEQ ID NO: 28;
The mutation of the gene encoding ZNF449 is a missense mutation of F183I in the amino acid sequence of SEQ ID 29;
Wherein the mutation of the gene encoding SCRN1 is a missense mutation of D427Y or a frame shift insertion mutation of A257Cfs * 34 in the amino acid sequence of SEQ ID NO: 30;
The method according to claim 2,
At least one primer set selected from the group consisting of SEQ ID NO: 31 and SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34, and base sequence pairs represented by SEQ ID NO: 35 and SEQ ID NO: 36 for mutation detection of ACSS3;
At least one selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42, and base sequence pairs represented by SEQ ID NO: 43 and SEQ ID NO: 44 for detecting a mutation of ADAM21; Primer set;
At least one selected from the group consisting of SEQ ID NO: 45 and SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, and base sequence pairs represented by SEQ ID NO: 51 and SEQ ID NO: 52 for mutation detection of AFF2 Primer set;
At least one primer set selected from the group consisting of SEQ ID NO: 53 and SEQ ID NO: 54, SEQ ID NO: 55 and SEQ ID NO: 56, and base sequence pairs represented by SEQ ID NO: 57 and SEQ ID NO: 58 for mutation detection of ALG13;
SEQ ID NO: 59 and SEQ ID NO: 60, SEQ ID NO: 61 and SEQ ID NO: 62, SEQ ID NO: 63 and SEQ ID NO: 64, SEQ ID NO: 65 and SEQ ID NO: 66, SEQ ID NO: 67 and SEQ ID NO: 68, SEQ ID NO: 69, and for detecting a mutation of BAP1 SEQ ID NO: 70, SEQ ID NO: 71 and SEQ ID NO: 72, SEQ ID NO: 73 and SEQ ID NO: 74, SEQ ID NO: 75 and SEQ ID NO: 76, SEQ ID NO: 77 and SEQ ID NO: 78, SEQ ID NO: 79 and SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, SEQ ID NO: 83 and SEQ ID NO: 84, SEQ ID NO: 85 and SEQ ID NO: 86, SEQ ID NO: 87 and SEQ ID NO: 88, SEQ ID NO: 89 and SEQ ID NO: 90, SEQ ID NO: 91 and SEQ ID NO: 92, and SEQ ID NO: 93 and SEQ ID NO: 94 At least one primer set selected from the group consisting of nucleotide sequence pairs represented by;
At least one primer set selected from SEQ ID NO: 95 and SEQ ID NO: 96, and SEQ ID NO: 97 and SEQ ID NO: 98 for detecting a mutation of BRWD3;
SEQ ID NO: 99 and SEQ ID NO: 100, SEQ ID NO: 101 and SEQ ID NO: 102, SEQ ID NO: 103 and SEQ ID NO: 104, SEQ ID NO: 105 and SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 108, and SEQ ID NO: 109 for mutation detection of COL4A5 And at least one primer set selected from the group consisting of a nucleotide sequence pair represented by SEQ ID NO: 110;
At least one primer set selected from the group consisting of SEQ ID NO: 111 and SEQ ID NO: 112, SEQ ID NO: 113 and SEQ ID NO: 114, and base sequence pairs represented by SEQ ID NO: 115 and SEQ ID NO: 116 for mutation detection of CPEB1;
At least one primer set selected from the group consisting of SEQ ID NO: 117 and SEQ ID NO: 118, SEQ ID NO: 119 and SEQ ID NO: 120, and base sequence pairs represented by SEQ ID NO: 121 and SEQ ID NO: 122 for mutation detection of ERBB2;
At least one selected from the group consisting of SEQ ID NO: 123 and SEQ ID NO: 124, SEQ ID NO: 125 and SEQ ID NO: 126, SEQ ID NO: 127 and SEQ ID NO: 128, and base sequence pairs represented by SEQ ID NO: 129 and SEQ ID NO: 130 for mutation detection of HSP90AA1; Primer set;
A primer set of at least one of a pair of nucleotide sequences represented by SEQ ID NO: 131 and SEQ ID NO: 132 and SEQ ID NO: 133 and SEQ ID NO: 134 for mutation detection of IRAK1;
SEQ ID NO: 135 and SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, SEQ ID NO: 139 and SEQ ID NO: 140, SEQ ID NO: 141 and SEQ ID NO: 142, SEQ ID NO: 143, and SEQ ID NO: 144, SEQ ID NO: 145, for mutation detection of KDM5C; SEQ ID NO: 146, SEQ ID NO: 147 and SEQ ID NO: 148, SEQ ID NO: 149 and SEQ ID NO: 150, SEQ ID NO: 151 and SEQ ID NO: 152, SEQ ID NO: 153 and SEQ ID NO: 154, SEQ ID NO: 155, and SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158, SEQ ID NO: 159 and SEQ ID NO: 160, SEQ ID NO: 161 and SEQ ID NO: 162, SEQ ID NO: 163 and SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO: 166, SEQ ID NO: 167 and SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, At least one primer set selected from the group consisting of SEQ ID NO: 171 and SEQ ID NO: 172, SEQ ID NO: 173 and SEQ ID NO: 174, and base sequence pairs represented by SEQ ID NO: 175 and SEQ ID NO: 176;
A primer set of at least one of a pair of nucleotide sequences represented by SEQ ID NO: 177 and SEQ ID NO: 178, and SEQ ID NO: 179 and SEQ ID NO: 180 for mutation detection of KDM6A;
A primer set of at least one of a pair of nucleotide sequences represented by SEQ ID NO: 181 and SEQ ID NO: 182, and SEQ ID NO: 183, and SEQ ID NO: 184 for mutation detection of LRP12;
At least one selected from the group consisting of SEQ ID NO: 185 and SEQ ID NO: 186, SEQ ID NO: 187 and SEQ ID NO: 188, SEQ ID NO: 189 and SEQ ID NO: 190, and base sequence pairs represented by SEQ ID NO: 191 and SEQ ID NO: 192 for mutation detection of NCOA6; Primer set;
At least one primer set selected from the group consisting of SEQ ID NO: 193 and SEQ ID NO: 194, SEQ ID NO: 195 and SEQ ID NO: 196, and base sequence pairs represented by SEQ ID NO: 197 and SEQ ID NO: 198 for mutation detection of NHS;
At least one primer set selected from the group consisting of SEQ ID NO: 199 and SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, and base sequence pairs represented by SEQ ID NO: 203 and SEQ ID NO: 204 for mutation detection of RGAG1;
SEQ ID NO: 205 and SEQ ID NO: 206, SEQ ID NO: 207 and SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, SEQ ID NO: 211 and SEQ ID NO: 212, and SEQ ID NO: 213 and SEQ ID NO: 214 for mutation detection of SCAF1 At least one primer set selected from the group consisting of a pair;
At least one primer set selected from the group consisting of a sequence pair represented by SEQ ID NO: 215 and SEQ ID NO: 216, SEQ ID NO: 217 and SEQ ID NO: 218, and SEQ ID NO: 219 and SEQ ID NO: 220 for mutation detection of SH3TC1;
At least one selected from the group consisting of SEQ ID NO: 221 and SEQ ID NO: 222, SEQ ID NO: 223 and SEQ ID NO: 224, SEQ ID NO: 225 and SEQ ID NO: 226, and base sequence pairs represented by SEQ ID NO: 227 and SEQ ID NO: 228 for mutation detection of TBC1D8B; Primer set;
SEQ ID NO: 229 and SEQ ID NO: 230, SEQ ID NO: 231 and SEQ ID NO: 232, SEQ ID NO: 233 and SEQ ID NO: 234, SEQ ID NO: 235 and SEQ ID NO: 236, SEQ ID NO: 237 and SEQ ID NO: 238, SEQ ID NO: 239 and At least one primer set selected from the group consisting of SEQ ID NO: 240, SEQ ID NO: 241 and SEQ ID NO: 242, SEQ ID NO: 243 and SEQ ID NO: 244, and base sequence pairs represented by SEQ ID NO: 245 and SEQ ID NO: 246;
At least one primer set selected from the group consisting of SEQ ID NO: 247 and SEQ ID NO: 248, SEQ ID NO: 249 and SEQ ID NO: 250, and base sequence pairs represented by SEQ ID NO: 251 and SEQ ID NO: 252 for mutation detection of TEX13A;
A primer set which is a nucleotide sequence pair represented by SEQ ID NO: 253 and SEQ ID NO: 254 for mutation detection of ULK3;
At least one primer set selected from the group consisting of SEQ ID NO: 255 and SEQ ID NO: 256, SEQ ID NO: 257 and SEQ ID NO: 258, and SEQ ID NO: 259 and SEQ ID NO: 260 for mutation detection of WNK3;
A primer set which is a nucleotide sequence pair represented by SEQ ID NO: 261 and SEQ ID NO: 262 for mutation detection of ARSF;
At least one selected from the group consisting of SEQ ID NO: 263 and SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 266, SEQ ID NO: 267, and SEQ ID NO: 268, and base sequence pairs represented by SEQ ID NO: 269 and SEQ ID NO: 270 for mutation detection of CFP; Primer set;
A primer set which is a nucleotide sequence pair represented by SEQ ID NO: 271 and SEQ ID NO: 272 for detecting a mutation of FAM47A;
At least one primer set selected from the group consisting of SEQ ID NO: 273 and SEQ ID NO: 274, and a base sequence pair represented by SEQ ID NO: 275 and SEQ ID NO: 276 for mutation detection of PHF16;
A primer set which is a nucleotide sequence pair represented by SEQ ID NO: 277 and SEQ ID NO: 278 for mutation detection of ZNF449;
A kit comprising at least one primer set selected from SEQ ID NO: 279 and SEQ ID NO: 280, and at least one primer set from SEQ ID NO: 281 and SEQ ID NO: 282 for mutation detection of SCRN1.
Preparing a sample DNA from a sample of a kidney cancer patient;
Amplifying the sample DNA using the kit of claim 1; And
Identifying the presence or absence of a gender specific marker from the amplification result; and providing information necessary for prognostic diagnosis of renal cancer according to the gender of the kidney cancer patient comprising a.
The method according to claim 5,
The method is for predicting the total survival or disease free survival of kidney cancer patients.
The method according to claim 6,
A gene encoding the ACSS3; And a gene encoding one selected from the group consisting of ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1; when the mutation is identified and the kidney cancer patient is female, the survival rate of the kidney cancer patient is good. Or not, determining that the recurrence rate of renal cancer in the kidney cancer patient is high.
The method according to claim 7,
A gene encoding the ACSS3; And a gene encoding one selected from the group consisting of ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1; when the mutation is identified and the kidney cancer patient is female, the survival rate of the kidney cancer patient is good. Determining not to; further comprising.
The method according to claim 7,
A gene encoding the ACSS3; And a gene encoding one selected from the group consisting of ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1; when a mutation is identified and the kidney cancer patient is female, Determining that the recurrence rate is high.

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