KR102084658B1 - Metastasis-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 a difference in renal cancer treatment effects or prognostic markers according to metastasis of renal cancer patients, and the mutation of the gene of the present invention and the survival rate or recurrence rate of metastatic renal cancer patients, respectively, are related to the metastasis. The mutated genes of the present invention can be used as markers to predict differences in the therapeutic effects of kidney cancer or the prognosis of kidney cancer patients.

Description

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

The present invention provides a method for providing information necessary for prognostic diagnosis and treatment strategy of renal cancer using a marker for diagnosing prognosis of kidney cancer patient, kit for diagnosing prognosis of renal cancer patient, and marker for diagnosing prognosis of renal cancer patient. It is about.

The kidney is an important urinary system that has the role of excreting waste products in vitro by filtering blood to produce urine. It is also an important endocrine organ that produces hormones such as angiotensin and erythropoietin, erythropoietin, which regulate blood pressure.

Tumors occurring in the kidney include renal cell carcinoma (RCC) occurring in adults, Wilms' tumors occurring in children, and sarcomas as rare tumors. Kidney cancer is a renal cell carcinoma that occurs mostly in the parenchyma of the kidneys (the part of the kidney where the cells that make urine are composed of the medulla and the cortex). Genetic factors are also known risk factors for kidney cancer, but generally include smoking and excessive fat intake. It is also known that the incidence of tumors is high in patients undergoing long-term dialysis.

Renal cell carcinoma includes clear cell RCC, papillary RCC, chromophobe RCC, medullary RCC, and unclassifiable renal cell carcinoma. (unclassified RCC), kidney transitional cell carcinoma (TCC), and renal oncocytoma, among which clear cell type renal cell carcinoma accounts for 66-75% of all renal cell carcinomas. Papillary renal cell carcinoma accounts for about 15%, and anachromosomal renal cell carcinoma accounts for about 5%.

Kidney cancer has little symptoms when the tumor is small, and symptoms do not appear until the tumor is large enough to push the organs. Therefore, the diagnosis is often delayed, and when the first diagnosis is made, about 30% of the patients are already metastasized. The most common symptom is hematuria, but this only occurs in 60% of patients. Rather, depending on the site of metastasis, symptoms such as shortness of breath, cough, headache, etc., the diagnosis of renal cancer due to the metastasis is 30% of the patients. Kidney cancers can cause high blood pressure, hypercalcemia, and liver dysfunction due to certain hormones produced by cancer cells. Recently, during a medical examination without any symptoms, it is often found on an imaging test, and in such a case, it is mainly found early, so the treatment result is relatively good.

Kidney cancer has a high survival rate due to tumor removal after onset, but it is difficult to diagnose early because there is no clear symptom. For this reason, there is a need for early diagnosis of kidney cancer and the development of markers to check the life remaining after the onset of cancer.

In patent document 1, transglutaminase 2 is disclosed as a marker used for the detection or diagnosis of human kidney cancer. Although markers for diagnosing cancer, including kidney cancer, have been developed, there is no research yet on the association between mutations in specific genes and markers that can measure the prognosis of kidney cancer patients, particularly kidney cancer patients. to be.

In order to diagnose metastasis of kidney cancer, or to find a therapeutic agent for a kidney cancer patient and to determine a treatment strategy, the present inventors focus on the necessity of developing a marker capable of diagnosing the prognosis of a kidney cancer patient. We investigated the association between gene mutation and metastasis.

Korean Patent No. 1267580

In order to apply appropriate therapeutic strategies for renal cancer patients, the development of markers that can provide information in predicting the prognosis of renal cancer patients and in determining treatment strategies is needed. An object of the present invention is to provide a marker that helps to determine the prognostic diagnosis and treatment strategy of a kidney cancer patient, based on whether or not the kidney cancer patient has metastasized.

In order to achieve the above object, an aspect of the present invention provides information necessary for predicting the difference in the effects of renal cancer treatment or prognostic diagnosis of renal cancer patients according to the metastasis of renal cancer patients capable of detecting metastasis specific markers. Provides a kit providing ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA3, SLC35 SMO, SNRNP27, ST7L, STAMBP, SUPV3L1, TADA2A, UBE2D1, UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPLF, KDM2, KDM2 And ZFP69 is a mutation of a gene encoding at least one selected from the group consisting of.

Another aspect of the present invention provides a method for preparing a sample of metastatic kidney cancer, comprising the steps of preparing sample DNA; Amplifying the sample DNA using the kit; Identifying the presence of a transition specific marker from the amplification result; Treating any kidney cancer treatment candidate substance, or treating by any method, a kidney cancer patient for whom metastasis specific markers have been identified; And adopting any kidney cancer treatment candidate substance or any treatment method as a treatment candidate substance or treatment method suitable for metastatic kidney cancer patients whose metastasis specific marker has been identified when treating or treating kidney cancer. It provides a method for providing information necessary for determining the difference in the effects of renal cancer treatment according to the metastasis of cancer patients.

Another aspect of the invention comprises the steps of preparing a sample DNA from a sample of a kidney cancer patient; Amplifying the sample DNA using the kit of claim 1; And confirming the presence or absence of a metastasis specific marker from the amplification result. The method provides a method for providing information necessary for prognostic diagnosis of kidney cancer according to metastasis of a kidney cancer patient.

ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35BNP, SMO7 Consisting of STAMBP, SUPV3L1, TADA2A, UBE2D1, UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPL2, KDM2A, KDM5, ZFP5, NFPIX, PI, and TP53 Since the mutation of at least one gene selected from the group and the metastasis of the renal cancer patient are related, it is possible to predict the difference in the renal cancer treatment effect and the survival rate according to the metastasis of the renal cancer patient by confirming the mutation of the gene.

In addition, the mutant genes found in the present invention, ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, ITGB7, KDM2A, KDMC7, L2, K2 Mutation of one gene selected from the gene family consisting of MUTYH, NFIX, OR5W2, PICK1, PITPNB, RELN, SAA1, SLC35B3, SMO, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, ZFP69, and ZNF699 Since the survival rate of metastatic kidney cancer patients, or the mutation of the gene and the recurrence rate of kidney cancer, respectively, are related, mutations of the genes of the present invention can be used as markers to predict the prognosis of kidney cancer patients.

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 to 38 show ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, ITGB7, KDM2A, KDM5MIX, LOX3 Kidney cancer patients (red) with mutations in the respective genes for OR5W2, PICK1, PITPNB, RELN, SAA1, SLC35B3, SMO, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, ZFP69, and ZNF699 And total survival or disease free survival for kidney cancer patients (blue) without mutations in the gene.

In this 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 this 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. Metastasis-specific mutant genes in kidney cancer patients, and those capable of detecting these mutant genes primer  set

One aspect of the present invention is ADAMTS10 (Gene bank accession number: NM_030957.3.), ASB15 (Gene bank accession number: NM_080928.4.), C8orf37 (Gene bank accession number: NM_177965.3.), CHSY3 (Gene bank accession) number: NM_175856.4.), CPSF3 (Gene bank accession number: NM_016207.3.), EHBP1L1 (Gene bank accession number: NM_001099409.1.), GPR148 (Gene bank accession number: NM_207364.2.), ITGB7 (Gene Bank accession number: NM_000889.2.), KLHL24 (Gene bank accession number: NM_017644.3.), LOXL3 (Gene bank accession number: NM_032603.4.), LTBR (Gene bank accession number: NM_001270987.1.), LUC7L2 (Gene bank accession number: NM_001244585.1.), MUTYH (Gene bank accession number: NM_001048171.1.), OR5W2 (Gene bank accession number: NM_001001960.1.), POMZP3 (Gene bank accession number: NM_012230.3.) Gene bank accession number: NM_005045.3., SAA1 (Gene bank accession number: NM_000331.5.), SLC35B3 (Gene bank accession number: NM_001142541.2.), SMO (Gene bank accession number: NM_005631.4 .), SNRNP27 (Gene ba nk accession number: NM_006857.2.), ST7L (Gene bank accession number: NM_017744.4.), STAMBP (Gene bank accession number: NM_006463.4.), SUPV3L1 (Gene bank accession number: NM_003171.4.), TADA2A (Gene bank accession number: NM_001166105.2.), UBE2D1 (Gene bank accession number: NM_003338.4.), UGT2A3 (Gene bank accession number: NM_024743.3. ), ZNF320 (Gene bank accession number: NM_207333.2.), ZNF699 (Gene bank accession number: NM_198535.2.), ADAM33 (Gene bank accession number: NM_025220.4.), B3GNT2 (Gene bank accession number: NM_006577. 5.), BFSP1 (Gene bank accession number: NM_001161705.1.), CARD6 (Gene bank accession number: NM_032587.3.), CHRM2 (Gene bank accession number: NM_000739.2.), EPB41L5 (Gene bank accession number: NM_001184937.1.), FBXW5 (Gene bank accession number: NM_018998.3.), GPR173 (Gene bank accession number: NM_018969.5.), HHIPL2 (Gene bank accession number: NM_024746.3.), KDM2A (Gene bank accession number: NM_001256405.1.), KDM5A (Gene bank accession number: NM_001042603.2.), NFIX (Gene bank accession number: NM_001271044.2.), PICK1 (Gene bank accession number: NM_001039583.1.), PITPNB (Gene at least one gene selected from the group of genes consisting of bank accession number: NM_012399.4.), TP53TG5 (Gene bank accession number: NM_014477.2.), and ZNF642 (ZFP69) (Gene bank accession number: NM_198494.2.) And of providing a specific marker mutation is a transition effect of kidney cancer treatment in accordance with the transition of kidney cancer that can detect differences in predictive or kit which provides the information needed to diagnose the prognosis of kidney cancer.

The full names of the abbreviations of the genes are ADAMTS10 (ADAM metallopeptidase with thrombospondin type 1 motif 10), ASB15 (ankyrin repeat and SOCS box containing 15), C8orf37 (chromosome 8 open reading frame 37), CHSY3 (chondroitin sulfate synthase 3), Cleavage and polyadenylation specific factor 3 (CPSF3), EH domain binding protein 1 like 1 (EHBP1L1), G protein-coupled receptor 148 (GPR148), integrin subunit beta 7 (ITGB7), Kelch like family member 24 (KLHL24), LOXL3 ( lysyl oxidase like 3), LTBR (lymphotoxin beta receptor), LUC7L2 (LUC7 like 2, pre-mRNA splicing factor), MUTYH (mutY DNA glycosylase), OR5W2 (olfactory receptor family 5 subfamily W member 2), POMZP3 (POM121 and ZP3) fusion), RELN (reelin), SAA1 (serum amyloid A1), SLC35B3 (solute carrier family 35 member B3), SMO (smoothened, frizzled class receptor), SNRNP27 (small nuclear ribonucleoprotein U4 / U6.U5 subunit 27), ST7L ( suppression of tumorigenicity 7 like), STAMP (STAM binding protein), SUPV3L1 (Suv3 like RNA helicase), TADA2A ( transcriptional adapter 2A), UBE2D1 (ubiquitin conjugating enzyme E2 D1), UGT2A3 (UDP glucuronosyltransferase family 2 member A3), ZNF320 (zinc finger protein 320), ZNF699 (zinc finger protein 699), ADAM33 (ADAM metallopeptidase domain 33), B3GNT2 UDP-GlcNAc: betaGal beta-1,3-N-acetylglucosaminyltransferase 2, BFSP1 (beaded filament structural protein 1), CARD6 (caspase recruitment domain family member 6), CHRM2 (cholinergic receptor muscarinic 2), EPB41L5 (erythrocyte membrane protein band) 4.1 like 5), FBXW5 (F-box and WD repeat domain containing 5), GPR173 (G protein-coupled receptor 173), HHIPL2 (HHIP like 2), KDM2A (lysine demethylase 2A), KDM5A (lysine demethylase 5A), NFIX (nuclear factor IX), PICK1 (protein interacting with PRKCA 1), PITPNB (phosphatidylinositol transfer protein beta), TP53TG5 (TP53 target 5), ZFP69 (ZFP69 zinc finger protein).

In one embodiment of the present invention, predicting the difference in effect of renal cancer treatment according to metastasis of renal cancer patients capable of detecting mutations in at least one gene selected from among the following mutations or prognostic diagnosis of renal cancer patients Provide kits that provide the necessary information to:

ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMO, SNRNP2, STNL2B Genes selected from the group consisting of UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPL2, KDM2A, KDM5A, NFIX, PICK1, PITPNB, TP53TG5, and ZFP69 Mutation.

In the present invention, the term 'diagnosis' refers to confirming the presence or characteristics of a pathological condition, and for the purpose of the present invention, not only confirming the difference in the effects of cancer treatment according to the metastasis of cancer patients, but also subjects after treatment of cancer. Means to determine whether or not relapse, drug reactivity, resistance, and the like. Preferably, when using the mutation of the gene of the present invention, by checking whether the mutation from the sample of the kidney cancer patient to the difference in the effect of renal cancer treatment according to the metastasis of the kidney cancer patient and the difference in survival rate to know the future prognosis of the patient Prediction is also possible.

As used herein, the term 'prognosis' refers to the progress and cure of a disease such as cancer-causing death or progression, including, for example, recurrence, metastatic spread and drug resistance of neoplastic diseases such as cancer. For the purposes of the present invention may be to predict the prognosis of renal cancer, preferably to predict disease free survival or survival of kidney cancer patients.

The term 'cancer' in the present invention includes any member of the class of diseases characterized by the unregulated growth of abnormal cells. The term includes all known cancers and neoplastic states, and cancers of any time and grade, including cancer before and after metastasis, whether characterized as malignant, benign, soft tissue or solid.

As used herein, the term 'gene' and variants thereof includes DNA fragments involved in polypeptide chain production; This includes the sites before and after the coding sites, eg, promoters and 3'-untranslated sites, respectively, as well as intervening sequences (introns) between individual coding fragments (exons).

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

With respect to mutations in the polypeptide sequence, the term "X # Y" is obviously recognized in the art, where "#" represents the mutation position in relation to the amino acid number of the polypeptide, and "X" represents the wild type amino acid sequence. Represents an amino acid found at that position, and "Y" represents a mutant amino acid at that position. For example, in the context of a BAZ2B polypeptide, the designation "G1717V" indicates that glycine is present at amino acid number 1717 of the wild type BAZ2B sequence and that glycine has been replaced with valine in the mutant BAZ2B sequence. Mutations of the genes are as follows:

The mutation of the gene encoding ADAMTS10 is a missense mutation in the amino acid sequence of SEQ ID 1, which is at least one of L872M and D439N;

The mutation of the gene encoding ASB15 is a nonsense mutation of E105 * or a missense mutation of V246L in the amino acid sequence of SEQ ID NO: 2, and * in the nonsense mutation indicates that the amino acid synthesis at the amino acid position is terminated (hereinafter, Description is omitted);

The mutation of the gene encoding C8orf37 is an in-frame delete (IF del) mutation of L66_I67del or a missense mutation of L100I in the amino acid sequence of SEQ ID NO: 3, and an in-frame deletion mutation. Del represents the deletion of the amino acid at the amino acid sequence position (hereinafter, the description is omitted);

The mutation of the gene encoding CHSY3 is at least one missense mutation selected from the group consisting of K619N, H622N and I628M in the amino acid sequence of SEQ ID NO: 4;

The mutation of the gene encoding CPSF3 is a missense mutation of at least one of A453T and D291N in the amino acid sequence of SEQ ID NO: 5;

The mutation of the gene encoding EHBP1L1 is a missense mutation of at least one of P75S and D212A in the amino acid sequence of SEQ ID NO: 6;

The mutation of the gene encoding GPR148 is a missense mutation of at least one of P45S and R258L in the amino acid sequence of SEQ ID NO: 7;

The mutation of the gene encoding ITGB7 is a missense mutation of at least one of G175A and A671G in the amino acid sequence of SEQ ID NO: 8;

The mutation of the gene encoding KLHL24 is a missense mutation of at least one of E141D and E521D in the amino acid sequence of SEQ ID NO: 9;

The mutation of the gene encoding LOXL3 is a missense mutation of at least one of C376Y and H398Q in the amino acid sequence of SEQ ID NO: 10;

The mutation of the gene encoding the LTBR is a missense mutation of at least one of M221I and H55Q in the amino acid sequence of SEQ ID NO: 11;

The mutation of the gene encoding LUC7L2 is a nonsense mutation of at least one of S263 * and K106 * in the amino acid sequence of SEQ ID NO: 12;

The mutation of the gene encoding MUTYH is a missense mutation of L448P or a frame shift delete (FS del) mutation of T501Pfs * 67 in the amino acid sequence of SEQ ID NO: 13, and the method of writing a frame shift mutation is Amino acid type (amino acid position) amino acid type fs * (number of nucleotides from amino acid position to stop codon in the downstream direction) (both frame shift insertion mutations and frame shift deletion mutations are the same notation and will not be described below);

The mutation of the gene encoding OR5W2 is a missense mutation of at least one of R165H and D70E in the amino acid sequence of SEQ ID NO: 14;

The mutation of the gene encoding POMZP3 is a missense mutation of at least one of A109P and P96T in the amino acid sequence of SEQ ID NO: 15;

The mutation of the gene encoding RELN is a missense mutation of A535P in the amino acid sequence of SEQ ID NO: 16, an FS del mutation of at least one of C1098Sfs * 18 and F558Sfs * 14, or an X3123_splice (T is A in chromosome 103132475) Splice mutations)

The mutation of the gene encoding SAA1 is a missense mutation of at least one of D109H and G15S in the amino acid sequence of SEQ ID NO: 17;

The mutation of the gene encoding SLC35B3 is a nonsense mutation of L317 * or a missense mutation of G155D in the amino acid sequence of SEQ ID NO: 18;

The mutation of the gene encoding the SMO is a missense mutation of at least one of A235T and S699R in the amino acid sequence of SEQ ID NO: 19, or a splice mutation of X422_splice (substituting A for T at chromosome 128848598);

A mutation of the gene encoding SNRNP27 is a missense mutation of at least one of R21W and E100D in the amino acid sequence of SEQ ID NO: 20;

The mutation of the gene encoding ST7L is at least one missense mutation selected from the group consisting of K542N, P325S and D435N in the amino acid sequence of SEQ ID NO: 21;

The mutation of the gene encoding STAMBP is a missense mutation of at least one of C390R and Q156L in the amino acid sequence of SEQ ID NO: 22;

The mutation of the gene encoding SUPV3L1 is a missense mutation of at least one of K495Q and M295I in the amino acid sequence of SEQ ID NO: 23;

A mutation of the gene encoding TADA2A is a nonsense mutation of Y397 * or a missense mutation of N181K in the amino acid sequence of SEQ ID NO: 24;

A mutation of the gene encoding UBE2D1 is a missense mutation of A146P in the amino acid sequence of SEQ ID NO: 25, or a splice mutation of X133_splice (substituted G for T at chromosome 60128479);

The mutation of the gene encoding UGT2A3 is a missense mutation of at least one of H448D and N211T in the amino acid sequence of SEQ ID NO: 26;

The mutation of the gene encoding ZNF320 is at least one missense mutation selected from the group consisting of C219G, T120A and L119F in the amino acid sequence of SEQ ID NO: 27;

The mutation of the gene encoding ZNF699 is a nonsense mutation of Q224 * or a missense mutation of S516T in the amino acid sequence of SEQ ID NO: 28;

The mutation of the gene encoding ADAM33 is a missense mutation of A408V in the amino acid sequence of SEQ ID 29;

The mutation of the gene encoding B3GNT2 is a missense mutation of at least one of N260S and P330S, or a frame shift insert (FS ins) mutation of E83Gfs * 17 in the amino acid sequence of SEQ ID NO: 30;

The mutation of the gene encoding BFSP1 is a missense mutation of R362S in the amino acid sequence of SEQ ID NO: 31;

A mutation of the gene encoding CARD6 is an IF del mutation of S1016del, a missense mutation of E274K, or an FS ins mutation of T557Hfs * 2 in the amino acid sequence of SEQ ID NO: 32;

The mutation of the gene encoding CHRM2 is a missense mutation of at least one of V344M and V171M, or an FS ins mutation of S182Ffs * 65 in the amino acid sequence of SEQ ID 33;

The mutation of the gene encoding EPB41L5 is an IF del mutation of L303_P306del in the amino acid sequence of SEQ ID NO: 34;

The mutation of the gene encoding FBXW5 is a nonsense mutation of E84 * in the amino acid sequence of SEQ ID 35;

The mutation of the gene encoding GPR173 is a missense mutation of F167C in the amino acid sequence of SEQ ID 36;

The mutation of the gene encoding HHIPL2 is at least one missense mutation selected from the group consisting of D84H, L528I and V262M in the amino acid sequence of SEQ ID NO: 37;

The mutation of the gene encoding KDM2A is a missense mutation of at least one of S1072R and T802M or an FS ins mutation of P597Afs * 34 in the amino acid sequence of SEQ ID NO: 38;

The mutation of the gene encoding KDM5A is an FS ins mutation of E499Gfs * 29, or at least one missense mutation selected from the group consisting of V537I, D1339V and R1217W in the amino acid sequence of SEQ ID NO: 39;

The mutation of the gene encoding NFIX is a missense mutation of R80L in the amino acid sequence of SEQ ID 40;

The mutation of the gene encoding PICK1 is a missense mutation of Q182L in the amino acid sequence of SEQ ID 41;

The mutation of the gene encoding PITPNB is an FS del mutation of Q189Rfs * 8 in the amino acid sequence of SEQ ID NO: 42;

The mutation of the gene encoding TP53TG5 is a missense mutation of K108R in the amino acid sequence of SEQ ID 43;

The mutation of the gene encoding ZFP69 is at least one missense mutation selected from the group consisting of E27D, D84E and R471H in the amino acid sequence of SEQ ID NO: 44.

Next generation sequencing (NGS), RT-PCR, direct nucleic acid sequencing method, microarray may be used as an analytical method for diagnosing the prognosis of renal cancer using the mutation of the gene. Any method that can confirm the presence of a mutation using a mutation of the gene can be applied without limitation. In one embodiment, the presence of the mutation is determined using 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 immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin / biotin, colloidal gold particles, colored particles and magnetic particles. In another embodiment, the presence of the mutation is radioimmuno assay, western blot assay, immunofluorescence assay, enzyme immunoassay assay, immunoprecipitation assay, chemiluminescence assay, immunohistochemistry assay, dot blot assay, slot blot assay or flow cytometry Determined by the assay. 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.

The term 'polynucleotide' in the present invention generally refers to any polyribonucleotide or polydeoxyribonucleotide that can 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, including a stranded region, hybrids comprising DNA and RNA, which may be single-stranded or more typically double-stranded, or may comprise single- and double-stranded regions. Thus, DNA or RNA having a backbone modified for stability or for other reasons is a 'polynucleotide' as the term is intended herein. Also included in the term 'polynucleotide' as defined herein is DNA or RNA comprising an unusual base such as inosine or a modified base such as tritiated base. In general, the term 'polynucleotide' includes all chemically, enzymatically and / or metabolically modified forms of an unmodified polynucleotide. 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.

A set of primers capable of detecting the mutation, ie, prognostic diagnosis of kidney cancer, are as follows:

At least one primer set selected from the group consisting of SEQ ID NO: 45 and SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, and base sequence pairs represented by SEQ ID NO: 49 and SEQ ID NO: 50 for detecting a mutation of ADAMTS10;

At least one primer set selected from the group consisting of SEQ ID NO: 51 and SEQ ID NO: 52, SEQ ID NO: 53 and SEQ ID NO: 54, and base sequence pairs represented by SEQ ID NO: 55 and SEQ ID NO: 56 for mutation detection of ASB15;

At least one primer set selected from the group consisting of SEQ ID NO: 57 and SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60, and base sequence pairs represented by SEQ ID NO: 61 and SEQ ID NO: 62 for mutation detection of C8orf37;

At least one primer set selected from the group consisting of SEQ ID NO: 63 and SEQ ID NO: 64, and a nucleotide sequence pair represented by SEQ ID NO: 65 and SEQ ID NO: 66 for mutation detection of CHSY3;

At least one primer set selected from the group consisting of SEQ ID NO: 67 and SEQ ID NO: 68, and base sequence pairs represented by SEQ ID NO: 69 and SEQ ID NO: 70 for mutation detection of CPSF3;

At least one primer set selected from the group consisting of SEQ ID NO: 71 and SEQ ID NO: 72, SEQ ID NO: 73 and SEQ ID NO: 74, and base sequence pairs represented by SEQ ID NO: 75 and SEQ ID NO: 76 for mutation detection of EHBP1L1;

At least one primer set selected from the group consisting of SEQ ID NO: 77 and SEQ ID NO: 78, SEQ ID NO: 79 and SEQ ID NO: 80, and base sequence pairs represented by SEQ ID NO: 81 and SEQ ID NO: 82 for mutation detection of GPR148;

At least one primer set selected from the group consisting of SEQ ID NO: 83 and SEQ ID NO: 84, SEQ ID NO: 85 and SEQ ID NO: 86, and base sequence pairs represented by SEQ ID NO: 87 and SEQ ID NO: 88 for mutation detection of ITGB7;

At least one primer set selected from the group consisting of SEQ ID NO: 89 and SEQ ID NO: 90, and base sequence pairs represented by SEQ ID NO: 91 and SEQ ID NO: 92 for mutation detection of KLHL24;

At least one primer set selected from the group consisting of SEQ ID NO: 93 and SEQ ID NO: 94, SEQ ID NO: 95 and SEQ ID NO: 96, and base sequence pairs represented by SEQ ID NO: 97 and SEQ ID NO: 98 for mutation detection of LOXL3;

At least one primer set selected from the group consisting of SEQ ID NO: 99 and SEQ ID NO: 100, SEQ ID NO: 101 and SEQ ID NO: 102, and base sequence pairs represented by SEQ ID NO: 103 and SEQ ID NO: 104 for mutation detection of LTBR;

At least one primer set selected from the group consisting of SEQ ID NO: 105 and SEQ ID NO: 106, SEQ ID NO: 107 and SEQ ID NO: 108, and base sequence pairs represented by SEQ ID NO: 109 and SEQ ID NO: 110 for mutation detection of LUC7L2;

At least one selected from the group consisting of SEQ ID NO: 111 and SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO: 114, SEQ ID NO: 115 and SEQ ID NO: 116, and base sequence pairs represented by SEQ ID NO: 117 and SEQ ID NO: 118 for mutation detection of MUTYH Primer set of;

At least one primer set selected from the group consisting of SEQ ID NO: 119 and SEQ ID NO: 120, SEQ ID NO: 121 and SEQ ID NO: 122, and base sequence pairs represented by SEQ ID NO: 123 and SEQ ID NO: 124 for mutation detection of OR5W2;

At least one primer set selected from the group consisting of SEQ ID NO: 125 and SEQ ID NO: 126, and a nucleotide sequence pair represented by SEQ ID NO: 127 and SEQ ID NO: 128 for mutation detection of POMZP3;

At least one selected from the group consisting of SEQ ID NO: 129 and SEQ ID NO: 130, SEQ ID NO: 131 and SEQ ID NO: 132, SEQ ID NO: 133 and SEQ ID NO: 134, and base sequence pairs represented by SEQ ID NO: 135 and SEQ ID NO: 136 for mutation detection of RELN; Primer set of;

At least one primer set selected from the group consisting of SEQ ID NO: 137 and SEQ ID NO: 138, and a base sequence pair represented by SEQ ID NO: 139 and SEQ ID NO: 140 for mutation detection of SAA1;

At least one primer set selected from the group consisting of SEQ ID NO: 141 and SEQ ID NO: 142, SEQ ID NO: 143 and SEQ ID NO: 144, and base sequence pairs represented by SEQ ID NO: 145 and SEQ ID NO: 146 for mutation detection of SLC35B3;

At least one selected from the group consisting of 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, and base sequence pairs represented by SEQ ID NO: 153 and SEQ ID NO: 154 for mutation detection of SMO; Primer set of;

At least one primer set selected from the group consisting of SEQ ID NO: 155 and SEQ ID NO: 156, SEQ ID NO: 157 and SEQ ID NO: 158, and SEQ ID NO: 159 and SEQ ID NO: 160 for detecting a mutation of SNRNP27;

At least one primer set selected from the group consisting of SEQ ID NO: 161 and SEQ ID NO: 162, SEQ ID NO: 163 and SEQ ID NO: 164, and a base sequence pair represented by SEQ ID NO: 165 and SEQ ID NO: 166 for mutation detection of ST7L;

At least one primer set selected from the group consisting of SEQ ID NO: 167 and SEQ ID NO: 168, SEQ ID NO: 169 and SEQ ID NO: 170, and base sequence pairs represented by SEQ ID NO: 171 and SEQ ID NO: 172 for mutation detection of STAMBP;

At least one selected from the group consisting of SEQ ID NO: 173 and SEQ ID NO: 174, SEQ ID NO: 175 and SEQ ID NO: 176, SEQ ID NO: 177 and SEQ ID NO: 178, and base sequence pairs represented by SEQ ID NO: 179 and SEQ ID NO: 180 for mutation detection of SUPV3L1; Primer set of;

At least one primer set selected from the group consisting of SEQ ID NO: 181 and SEQ ID NO: 182, SEQ ID NO: 183, and SEQ ID NO: 184, and base sequence pairs represented by SEQ ID NO: 185 and SEQ ID NO: 186 for mutation detection of TADA2A;

At least one primer set selected from the group consisting of SEQ ID NO: 187 and SEQ ID NO: 188, and SEQ ID NO: 189 and SEQ ID NO: 190 for detecting mutations in UBE2D1;

At least one selected from the group consisting of SEQ ID NO: 191 and SEQ ID NO: 192, 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 detecting a mutation of UGT2A3; Primer set of;

At least one selected from the group consisting of SEQ ID NO: 199 and SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, SEQ ID NO: 203 and SEQ ID NO: 204, and base sequence pairs represented by SEQ ID NO: 205 and SEQ ID NO: 206 for mutation detection of ZNF320 Primer set of;

At least one primer set selected from the group consisting of SEQ ID NO: 207 and SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, and base sequence pairs represented by SEQ ID NO: 211 and SEQ ID NO: 212 for mutation detection of ZNF699;

At least one primer set selected from the group consisting of SEQ ID NO: 213 and SEQ ID NO: 214, SEQ ID NO: 215 and SEQ ID NO: 216, and base sequence pairs represented by SEQ ID NO: 217 and SEQ ID NO: 218 for mutation detection of ADAM33;

At least one selected from the group consisting of SEQ ID NO: 219 and SEQ ID NO: 220, SEQ ID NO: 221 and SEQ ID NO: 222, SEQ ID NO: 223 and SEQ ID NO: 224, and base sequence pairs represented by SEQ ID NO: 225 and SEQ ID NO: 226 for mutation detection of B3GNT2 Primer set of;

At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 227 and SEQ ID NO: 228 for mutation detection of BFSP1;

At least one primer set selected from the group consisting of SEQ ID NO: 229 and SEQ ID NO: 230, SEQ ID NO: 231 and SEQ ID NO: 232, and base sequence pairs represented by SEQ ID NO: 233 and SEQ ID NO: 234 for mutation detection of CARD6;

At least one primer set selected from the group consisting of SEQ ID NO: 235 and SEQ ID NO: 236, and a base sequence pair represented by SEQ ID NO: 237 and SEQ ID NO: 238 for mutation detection of CHRM2;

At least one primer set selected from the group consisting of a sequence pair represented by SEQ ID NO: 239 and SEQ ID NO: 240 for detecting a mutation of EPB41L5;

At least one primer set selected from the group consisting of SEQ ID NO: 241 and SEQ ID NO: 242, and a base sequence pair represented by SEQ ID NO: 243 and SEQ ID NO: 244 for mutation detection of FBXW5;

At least one primer set selected from the group consisting of SEQ ID NO: 245 and SEQ ID NO: 246, and a nucleotide sequence pair represented by SEQ ID NO: 247 and SEQ ID NO: 248 for mutation detection of GPR173;

At least one selected from the group consisting of SEQ ID NO: 249 and SEQ ID NO: 250, SEQ ID NO: 251 and SEQ ID NO: 252, SEQ ID NO: 253 and SEQ ID NO: 254, and base sequence pairs represented by SEQ ID NO: 255 and SEQ ID NO: 256 for mutation detection of HHIPL2 Primer set of;

SEQ ID NO: 257 and SEQ ID NO: 258, SEQ ID NO: 259 and SEQ ID NO: 260, SEQ ID NO: 261 and SEQ ID NO: 262, SEQ ID NO: 263 and SEQ ID NO: 264, and SEQ ID NO: 265 and SEQ ID NO: 266 for detecting a mutation of KDM2A At least one primer set selected from the group consisting of a pair;

SEQ ID NO: 267 and SEQ ID NO: 268, SEQ ID NO: 269 and SEQ ID NO: 270, SEQ ID NO: 271 and SEQ ID NO: 272, SEQ ID NO: 273 and SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 277 for detecting mutations of KDM5A; And at least one primer set selected from the group consisting of a nucleotide sequence pair represented by SEQ ID NO: 278;

At least one primer set selected from the group consisting of SEQ ID NO: 279 and SEQ ID NO: 280, and base sequence pairs represented by SEQ ID NO: 281 and SEQ ID NO: 282 for mutation detection of NFIX;

At least one primer set selected from the group consisting of a sequence pair represented by SEQ ID NO: 283 and SEQ ID NO: 284 for mutation detection of PICK1;

At least one primer set selected from the group consisting of SEQ ID NO: 285 and SEQ ID NO: 286, and SEQ ID NO: 287 and SEQ ID NO: 288 for mutation detection of PITPNB;

At least one primer set selected from the group consisting of SEQ ID NO: 289 and SEQ ID NO: 290, and a nucleotide sequence pair represented by SEQ ID NO: 291 and SEQ ID NO: 292 for mutation detection of TP53TG5; And

SEQ ID NO: 293 and SEQ ID NO: 294, SEQ ID NO: 295 and SEQ ID NO: 296, SEQ ID NO: 297 and SEQ ID NO: 298, SEQ ID NO: 299 and SEQ ID NO: 300, and SEQ ID NO: 301 and SEQ ID NO: 302 for detecting mutations in ZFP69 At least one primer set selected from the group consisting of pairs.

The kit of the present invention manufactured as described above is very economical because it saves time and cost as compared to the conventional method of searching for mutations of genes. On average, several days to test all genes using conventional genetic mutation detection methods such as Single Strand Conformational Polymorphism (SSCP), Protein Truncation Test (PTT), cloning, direct sequencing, etc. It takes several months. In addition, next generation sequencing (NGS) enables rapid and simple screening of gene mutations. When mutations are tested by conventional methods such as SSCP, cloning, direct sequencing, and Restriction Fragment Length Polymorphism (RFLP), it takes about one month to complete the test. In this case, the result can be obtained in about 10 to 11 hours, and since the primer set for detecting mutations is integrated in one chip, the time and cost can be reduced compared to the conventional method. Compared to the conventional method, less than half of the reagent cost is consumed per experiment. Therefore, even if the labor cost of the researcher is taken into account, a greater cost reduction can be expected.

 2. Providing information necessary for prognostic diagnosis of kidney cancer using survival-specific mutant genes

Another aspect of the invention comprises the steps of preparing a sample DNA from a sample of metastatic kidney cancer patient; Amplifying the sample DNA using the kit of claim 1; Identifying the presence of a transition specific marker from the amplification result; Treating any kidney cancer treatment candidate substance, or treating by any method, a kidney cancer patient for whom metastasis specific markers have been identified; And adopting any kidney cancer treatment candidate substance or any treatment method as a treatment candidate substance or treatment method suitable for metastatic kidney cancer patients whose metastasis specific marker has been identified when treating or treating kidney cancer. It provides a method for providing information necessary for determining the difference in the effects of renal cancer treatment according to the metastasis of cancer patients.

 Another aspect of the invention comprises the steps of preparing a sample DNA from a sample of a kidney cancer patient; Amplifying the sample DNA using the kit of claim 1; And confirming the presence or absence of a metastasis specific marker from the amplification result. The method provides a method for providing information necessary for prognostic diagnosis of kidney cancer according to metastasis of a kidney cancer patient.

The description of the 'prognostic kit for prognosis of renal cancer' is the same as described in ' 1. Metastasis-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.

Any of the candidate candidates may be a therapeutic agent commonly used for treating kidney cancer or a novel substance whose therapeutic effect on kidney cancer is not known, but is not limited thereto. By treating any of the above candidate candidates for kidney cancer patients with metastasis specific markers and confirming the therapeutic effect, it is possible to know whether the candidate candidates are effective for a particular patient group. If there is a therapeutic effect on renal cancer, it can be predicted that the therapeutic effect is high when applied to a patient group having the same metastasis specific marker, which can provide useful information in determining the treatment strategy. In addition, if there is no therapeutic effect when using any of the candidate candidates, the treatment strategy can be efficiently designed because unnecessary treatment is not required since the treatment is no longer performed on a patient group having the same transition specific marker. have.

Any kidney cancer treatment method may also be applied instead of any of the candidate treatments described above, and whether to apply to a patient group having the same metastasis specific marker by identifying the therapeutic effect in a patient group having a specific metastasis specific marker. In identifying a therapeutic effect in a group of patients with metastasis specific markers, any therapeutic candidate and any method of treating kidney cancer may be combined.

The term 'sample' as used herein includes any biological sample obtained from a patient. The sample may be whole blood, plasma, serum, erythrocytes, leukocytes (e.g. peripheral blood monocytes), ductal fluid, ascites, pleural efflux, nipple aspirate, lymphatic fluid (e.g. disseminated tumors of lymph nodes) Cells), bone marrow aspirate, saliva, urine, feces (i.e. feces), sputum, bronchial lavage fluid, tears, microneedle aspirates (eg harvested by random mammary microneedle aspiration), any other body fluid, tissue Samples (eg tumor tissue) such as tumor biopsies (eg puncture biopsies) or lymph nodes (eg sentinel lymph node biopsies), tissue samples (eg tumor tissue), eg surgical resection of tumors , 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 solid tumors from whole blood or cell fractions 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 kidney cancer.

The term 'patient' typically 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 have been or suspected of having kidney cancer.

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

As used herein, the term 'overall survival' includes clinical endpoints describing patients living for a limited time after being diagnosed with or treated for a disease, such as cancer, and whether or not the cancer recurs. It means the possibility.

As used herein, the term 'disease-free survival (DFS)' includes a period of time during which a patient survives without recurrence of cancer after treatment for a particular disease (eg cancer).

The present invention can determine the prognosis for cancer of an individual with a subject sample by analyzing the presence of mutations in the genes of the invention in a sample of kidney cancer patients. This method can also be accomplished by comparing the total survival or disease free survival of individuals in the control group that do not have mutations known to have a good prognosis. In the present invention, an individual known to have a good prognosis means an individual having no history of metastasis, recurrence, and death after the onset of cancer.

A sample of an individual suspected of cancer is a sample of an individual or tissue in which a cancer or a tumor has already occurred or is expected to occur, and means a sample of which a prognosis is to be diagnosed.

The transition specific markers are ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMBP7 SNRNP Group consisting of SUPV3L1, TADA2A, UBE2D1, UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPL2, KDM2A, KDM5A, NFIX, PITP5, PICK5, PICK1, PICK1, PICK69 It may be a mutation of a gene encoding one.

The method of providing information necessary for prognostic diagnosis of renal cancer according to metastasis of the renal cancer patient may predict the total survival rate or disease free survival rate of the renal cancer patient. For example, the method may have a mutation in a gene encoding one selected from the group consisting of ASB15, CARD6, CHRM2, CHSY3, CPSF3, FBXW5, KDM2A, LOXL3, LUC7L2, MUTYH, RELN, SAA1, SUPV3L1, TP53TG5 and UBE2D1. When it is confirmed that the patient has metastatic kidney cancer, the survival rate of the kidney cancer patient is not good, or determining that the recurrence rate of kidney cancer of the kidney cancer patient is high; may further include a.

The method for providing information necessary for the diagnosis of renal cancer according to the metastasis of the renal cancer patient is metastatic, renal cancer patients, ASB15, B3GNT2, CARD6, CHRM2, CHSY3, CPSF3, FBXW5, GPR173, ITGB7, KDM2A, KDM5A Renal cancer in a renal cancer patient if mutations are identified in a gene encoding one selected from the group consisting of LOXL3, LUC7L2, MUTYH, PITPNB, RELN, SAA1, SMO, SUPV3L1, TP53TG5, UBE2D1 and ZNF642 (ZFP69) Determining that the survival rate is not good; may further include.

The method for providing information necessary for the prognosis of renal cancer according to the metastasis of the renal cancer patient is metastatic, renal cancer patients, ADAM33, ADAMTS10, ASB15, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5 ZNF320 encryption and ZNF320 encryption group consisting of ZNF320 and ZNF320, which are selected from the group consisting of FBXW5, HHIPL2, KDM2A, LOXL3, LUC7L2, MUTYH, NFIX, OR5W2, PICK1, RELN, SAA1, SLC35B3, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZN699 If mutations in the gene is identified, determining that the recurrence rate of kidney cancer of the kidney cancer patient is high; may further comprise a.

Thus, ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3 which are mutations of the gene of the present invention. LTBR. LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMO, SNRNP27, ST7L, STAMBP, SUPV3L1, TADA2A. UBE2D1. The use of mutations in at least one gene selected from the group of genes consisting of UGT2A3 and ZNF699 to determine whether metastasis of cancer, particularly kidney cancer, has not been made yet. In addition, ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, ITGB7, KDM2A, KDM5A, LOXL2, LUC2, LUC2 Prognosis for metastatic renal cancer using mutations in at least one gene selected from the group of genes consisting of PITPNB, RELN, SAA1, SLC35B3, SMO, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, ZFP69, and ZNF699 It is not known yet that the diagnosis is possible. In addition, there has been no report on the difference in total survival or disease free survival in each gene. The present inventors first identified the mutation of the genes can be used as a diagnostic marker for predicting a difference in renal cancer treatment effect according to metastasis of renal cancer patients or for diagnosing the prognosis of renal cancer patients.

The method for providing information necessary for predicting the difference in renal cancer treatment effect according to metastasis of renal cancer patients of the present invention is to diagnose genetic variation of renal cancer, increase survival rate of renal cancer patients, Or to lower the relapse rate. Through the method for diagnosing the prognosis of the kidney cancer of the present invention, it is possible to predict the treatment effect of the kidney cancer, or to predict the survival rate or recurrence rate of the kidney cancer patient by using the mutation occurrence information of the gene according to the metastasis of the kidney cancer, In addition to finding the right treatment for the patient, it is possible to provide information on the selection of treatments, thus effectively designing therapeutic strategies for renal cancer.

Hereinafter, the present invention will be described in detail by Examples and Experimental Examples.

However, the following Examples and Experimental Examples are only for illustrating the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Obtain genetic and clinical information

Genes of the invention (ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, ITGB7, KDM2A, KDM5MIX, LOX3) OR5W2, PICK1, PITPNB, RELN, SAA1, SLC35B3, SMO, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, ZFP69, ZNF699, GPR148, KLHL24, LTBR POMZP3, S2NP genes, SNRNP27, GT To determine whether renal cancer can be used as a marker for predicting recurrence of renal cancer, relapse and metastasis of 417 patients with transparent kidney cancer who have both genetic and clinical information from The Cancer Genome Atlas (TCGA). The data on death, death and observation time were obtained and used for analysis. Table 1 below shows data on relapse, metastasis and death of patients with transparent kidney cancer. The above candidate genes are those whose mutations have occurred in patients with kidney cancer who have metastasized.

Sum Number of patients ratio(%) Relapse

0 229 55.2% One 109 26.1% Not observed 79 18.7% transition
0 350 83.8% One 67 16.2% Dead
0 270 65.0% One 147 35.0% Total number of patients 417 people

Transition specific As a marker  Check availability

417 patients were categorized into two groups, 350 without metastases and 67 with metastases, and the correlations between mutations and metastasis of the candidate genes of Example 1 were evaluated using three feature selection (Information Gain, Chi). -Square, MR). The mutated positions of the genes are shown in Tables 2-7.

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var ADAM33 NM_025220.4. A408V Missense Diploid One 20 3653456 3653456 G A ADAMTS10 NM_030957.3. L872M Missense Diploid One Neutral 19 8651052 8651052 G T D439N Missense Diploid One Low 19 8660979 8660979 C T ASB15 NM_080928.4. E105 * Nonsense Diploid One 7 123257653 123257653 G T V246L Missense Amp Neutral 7 123267202 123267202 G T B3GNT2 NM_006577.5. N260S Missense Diploid One Neutral 2 62450134 62450134 A G P330S Missense Diploid One High 2 62450343 62450343 C T E83Gfs * 17 FS ins Diploid 2 62449597 62449598 - G BFSP1 NM_001161705.1. R362S Missense Diploid One Medium 20 17475631 17475631 T A C8orf37 NM_177965.3. L66_I67del IF del Diploid 8 96275957 96275962 AATAAG - L100I Missense Diploid Medium 8 96272706 96272706 G T CARD6 NM_032587.3. S1016del IF del ShallowDel One 5 40854473 40854475 GTC - E274K Missense Diploid One Medium 5 40843790 40843790 G A T557Hfs * 2 FS ins Gain One 5 40853093 40853094 - T

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var CHRM2 NM_000739.2. V344M Missense Gain One Medium 7 136700642 136700642 G A V171M Missense Diploid One Medium 7 136700123 136700123 G A S182Ffs * 65 FS ins Diploid One 7 136700149 136700150 - T CHSY3 NM_175856.4. K619N Missense Gain 2 Medium 5 129520692 129520692 G C H622N Missense Gain One Neutral 5 129520699 129520699 C A I628M Missense Amp One Neutral 5 129520719 129520719 C G CPSF3 NM_016207.3. A453T Missense Diploid One Neutral 2 9588441 9588441 G A D291N Missense Diploid One Medium 2 9580730 9580730 G A EHBP1L1 NM_001099409.1. P75S Missense Diploid One Low 11 65346872 65346872 C T D212A Missense Diploid One Low 11 65348529 65348529 A C EPB41L5 NM_001184937.1. L303_P306del IF del Gain 2 120847955 120847966 ACTGGATCATCC - FBXW5 NM_018998.3. E84 * Nonsense Diploid One 9 139837902 139837902 C A GPR148 NM_207364.2. P45S Missense Diploid One Low 2 131486857 131486857 C T R258L Missense Gain One Medium 2 131487497 131487497 G T GPR173 NM_018969.5. F167C Missense Diploid One Low X 53106303 53106303 T G

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var HHIPL2 NM_024746.3. D84H Missense Diploid One Low One 222721137 222721137 C G L528I Missense Diploid One Low One 222705449 222705449 G T V262M Missense Diploid 2 Medium One 222717069 222717069 C T ITGB7 NM_000889.2. G175A Missense Diploid 3 Medium 12 53591327 53591327 C G A671G Missense Gain One Low 12 53586257 53586257 G C KDM2A NM_001256405.1. S1072R Missense ShallowDel One Medium 11 67021798 67021798 T G T802M Missense Diploid One Low 11 67017906 67017906 C T P597Afs * 34 FS ins Diploid 11 67012878 67012879 - G KDM5A NM_001042603.2. E499Gfs * 29 FS ins Diploid 12 442810 442811 - C V537I Missense Gain One Medium 12 442697 442697 C T D1339 V Missense Gain One Low 12 416170 416170 T A R1217W Missense Diploid One Medium 12 416901 416901 G A KLHL24 NM_017644.3. E141D Missense Gain One Low 3 183368567 183368567 G C E521D Missense Diploid One Low 3 183390233 183390233 A C LOXL3 NM_032603.4. C376Y Missense Diploid One High 2 74763244 74763244 C T H398Q Missense Diploid One Medium 2 74763177 74763177 A C

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var LTBR NM_001270987.1. M221I Missense Diploid One Medium 12 6495606 6495606 G T H55Q Missense Gain One Medium 12 6493822 6493822 C G LUC7L2 NM_001244585.1. S263 * Nonsense Diploid One 7 139097305 139097305 C A K106 * Nonsense Diploid One 7 139086943 139086943 A T MUTYH NM_001048171.1. L448P Missense Diploid One Medium One 45796978 45796978 A G T501Pfs * 67 FS del Diploid One 45796197 45796197 C - NFIX NM_001271044.2. R80L Missense Gain 2 Medium 19 13136046 13136046 G T OR5W2 NM_001001960.1. R165H Missense Diploid 9 Low 11 55681565 55681565 C T D70E Missense Diploid One Medium 11 55681849 55681849 A T PICK1 NM_001039583.1. Q182L Missense Diploid One Medium 22 38467740 38467740 A T PITPNB NM_012399.4. Q189Rfs * 8 FS del Diploid 22 28256199 28256199 G - POMZP3 NM_012230.3. A109P Missense Diploid 2 Medium 7 76247520 76247520 C G P96T Missense Gain One Medium 7 76247559 76247559 G T RELN NM_005045.3. A535P Missense Diploid One Neutral 7 103293158 103293158 C G C1098Sfs * 18 FS del Gain 7 103243784 103243793 GACACCACAC - F558Sfs * 14 FS del Amp 7 103293088 103293088 A - X3123_splice Splice Diploid 7 103132475 103132475 T A

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var SAA1 NM_000331.5. D109H Missense Diploid One Medium 11 18291358 18291358 G C G15S Missense Diploid One Medium 11 18288477 18288477 G A SLC35B3 NM_001142541.2. L317 * Nonsense ShallowDel One 6 8417152 8417152 A T G155D Missense Diploid One Medium 6 8422813 8422813 C T SMO NM_005631.4. A235T Missense Diploid 3 Low 7 128845209 128845209 G A S699R Missense Gain One Low 7 128852025 128852025 T G X422_splice Splice Gain 7 128848598 128848598 A T SNRNP27 NM_006857.2. R21W Missense Diploid 2 Medium 2 70122252 70122252 C T E100D Missense Diploid One Medium 2 70124540 70124540 A C ST7L NM_017744.4. K542N Missense Diploid One Medium One 113084576 113084576 T G P325S Missense Diploid 2 Neutral One 113124710 113124710 G A D435N Missense Diploid One Medium One 113098583 113098583 C T STAMBP NM_006463.4. C390R Missense Diploid One Medium 2 74087228 74087228 T C Q156L Missense Diploid 2 Medium 2 74074605 74074605 A T SUPV3L1 NM_003171.4. K495Q Missense Diploid One Low 10 70960220 70960220 A C M295I Missense Diploid One Medium 10 70954975 70954975 G A

Gene Accession No. AA change Type Copy # COSMIC Mutation
Assessor Chr Start pos End pos Ref Var TADA2A NM_001166105.2. Y397 * Nonsense Diploid One 17 35836946 35836946 C A N181K Missense Diploid One Medium 17 35804809 35804809 T G TP53TG5 NM_014477.2. K108R Missense Diploid One Low 20 44004124 44004124 T C UBE2D1 NM_003338.4. A146P Missense Diploid One High 10 60128517 60128517 G C X133_splice Splice Diploid 10 60128479 60128479 G T UGT2A3 NM_024743.3. H448D Missense Diploid One High 4 69795773 69795773 G C N211T Missense Diploid 3 High 4 69816847 69816847 T G ZNF320 NM_207333.2. C219G Missense Diploid One High 19 53384724 53384724 A C T120A Missense Diploid One Medium 19 53385021 53385021 T C L119F Missense Diploid One Low 19 53385022 53385022 C A ZNF642 (ZFP69) NM_198494.2. E27D Missense Diploid Low One 40945114 40945114 G T D84E Missense Gain Low One 40954792 40954792 C G R471H Missense Diploid Neutral One 40961562 40961562 G A ZNF699 NM_198535.2. Q224 * Nonsense Diploid One 19 9407410 9407410 G A S516T Missense Diploid 2 Low 19 9406534 9406534 A T

Based on the number of patients with genes with mutations included in the metastasized group or the non-metastatic group, respectively (see "Mutation number" in Tables 8-11, below), mutation of candidate genes and metastasis of kidney cancer patients Was confirmed. P-values less than 0.05 were considered statistically significant. Information on candidate genes related to Tables 8-11 is shown below (M0: no distant metastasis, M1: distant metastasis).

Meta group Metastasis (%) Mutation Number Mutation / 417 (%) Mutation Type
Fisher ’s exact (p-value) cytoband M0 M1 Truncating Missense (P) Missense Inframe ADAM23 5 2 28.57% 7 1.68% 5 2 0 0 0.313 2q33.3 ADAM33 0 One 100.00% One 0.24% 0 One 0 0 0.161 20p13 ADAMTS10 0 2 100.00% 2 0.48% 0 2 0 0 0.025 19p13.2 ASB15 0 2 100.00% 2 0.48% One One 0 0 0.025 7q31.32 B3GNT2 One 2 66.67% 3 0.72% One 2 0 0 0.068 2p15 BAG6 10 2 16.67% 12 2.88% 11 One 0 0 One 6p21.33 BFSP1 0 One 100.00% One 0.24% 0 One 0 0 0.161 20p12.1 C8orf37 0 2 100.00% 2 0.48% 0 One 0 One 0.025 8q22.1 C9orf91 0 One 100.00% One 0.24% 0 One 0 0 0.161 9q32 CARD6 One 2 66.67% 3 0.72% One One 0 One 0.068 5p13.1 CHRM2 One 2 66.67% 3 0.72% One 2 0 0 0.068 7q33 CHSY3 0 3 100.00% 3 0.72% 0 3 0 0 0.004 5q23.3 CPSF3 0 2 100.00% 2 0.48% 0 2 0 0 0.025 2p25.1 DNMT1 12 3 20.00% 15 3.60% 10 5 0 0 0.718 19p13.2 EHBP1L1 0 2 100.00% 2 0.48% 0 2 0 0 0.025 11q13.1 EPB41L5 0 One 100.00% One 0.24% 0 0 0 One 0.161 2q14.2

Meta group Metastasis (%) Mutation Number Mutation / 417 (%) Mutation Type
Fisher ’s exact (p-value) cytoband M0 M1 Truncating Missense (P) Missense Inframe FBXW5 0 One 100.00% One 0.24% One 0 0 0 0.161 9q34.3 GPR148 0 2 100.00% 2 0.48% 0 2 0 0 0.025 2q21.1 GPR173 0 One 100.00% One 0.24% 0 One 0 0 0.161 Xp11.22 GRM3 3 2 40.00% 5 1.20% 3 2 0 0 0.184 7q21.11-q21.12 HHIPL2 One 2 66.67% 3 0.72% 0 3 0 0 0.068 1q41 HSPA4 3 2 40.00% 5 1.20% 3 2 0 0 0.184 5q31.1 IGDCC4 5 One 16.67% 6 1.44% 5 One 0 0 One 15q22.31 ITGB7 0 2 100.00% 2 0.48% 0 2 0 0 0.025 12q13.13 KDM2A One 2 66.67% 3 0.72% One 2 0 0 0.068 11q13.2 KDM5A 2 2 50.00% 4 0.96% One 3 0 0 0.123 12p13.33 KLHL24 0 2 100.00% 2 0.48% 0 2 0 0 0.025 3q27.1 LONRF2 One 0 0.00% One 0.24% 0 0 0 One One 2q11.2 LOXL3 0 2 100.00% 2 0.48% 0 2 0 0 0.025 2p13.1 LTBR 0 2 100.00% 2 0.48% 0 2 0 0 0.025 12p13.31

Meta group Metastasis (%) Mutation Number Mutation (%) Mutation Type
Fisher ’s exact (p-value) cytoband M0 M1 Truncating Missense (P) Missense (D) Inframe LUC7L2 0 2 100.00% 2 0.48% 2 0 0 0 0.025 7q34 MUTYH 0 2 100.00% 2 0.48% One One 0 0 0.025 1p34.1 NFIX 0 One 100.00% One 0.24% 0 One 0 0 0.161 19p13.13 NSUN4 One 0 0.00% One 0.24% 0 One 0 0 One 1p33 OR5W2 0 2 100.00% 2 0.48% 0 2 0 0 0.025 11q12.1 PICK1 0 One 100.00% One 0.24% 0 One 0 0 0.161 22q13.1 PITPNB 0 One 100.00% One 0.24% One 0 0 0 0.161 22q12.1 PJA2 0 One 100.00% One 0.24% 0 One 0 0 0.161 5q21.3 PLOD3 6 2 25.00% 8 1.92% 6 2 0 0 0.666 7q22.1 POMZP3 0 2 100.00% 2 0.48% 0 2 0 0 0.025 7q11.23 RELN One 3 75.00% 4 0.96% 3 One 0 0 0.014 7q22.1 SAA1 0 2 100.00% 2 0.48% 0 2 0 0 0.025 11p15.1 SLC35B3 0 2 100.00% 2 0.48% One One 0 0 0.025 6p24.3

Meta group Metastasis (%) Mutation Number Mutation (%) Mutation Type
Fisher ’s exact (p-value) cytoband M0 M1 Truncating Missense (P) Missense (D) Inframe SMO 0 3 100.00% 3 0.72% One 2 0 0 0.004 7q32.1 SNRNP27 0 2 100.00% 2 0.48% 0 2 0 0 0.025 2p13.3 ST7L 0 3 100.00% 3 0.72% 0 3 0 0 0.004 1p13.2 STAMBP 0 2 100.00% 2 0.48% 0 2 0 0 0.025 2p13.1 SUPV3L1 0 2 100.00% 2 0.48% 0 2 0 0 0.025 10q22.1 TADA2A 0 2 100.00% 2 0.48% One One 0 0 0.025 17q12 TP53TG5 0 One 100.00% One 0.24% 0 One 0 0 0.161 20q13.12 UBE2D1 0 2 100.00% 2 0.48% One One 0 0 0.025 10q21.1 UGT2A3 0 2 100.00% 2 0.48% One One 0 0 0.025 4q13.2 ZBTB16 0 One 100.00% One 0.24% 0 One 0 0 0.161 11q23.2 ZNF320 0 2 100.00% 2 0.48% 0 2 0 0 0.025 19q13.41 ZNF642 One 2 66.67% 3 0.72% 0 3 0 0 0.068 1p34.2 ZNF699 0 2 100.00% 2 0.48% One One 0 0 0.025 19p13.2

As a result of the analysis, when a gene is mutated, there are genes with a P-value of less than 0.05 when comparing the transition group and an untransferred group. Confirmed. Mutant genes with a P-value of less than 0.05 were selected as transition specific genes because they were correlated with the transition group compared to the untranslated group. ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMOP7 SNRNP , TADA2A, UBE2D1, UGT2A3, ZNF320, and ZNF699 have a P-value of less than 0.05, and these genes have been identified to correlate with mutation and metastasis. On the other hand, ADAM23 had a large number of mutated patients, but the P-value was higher than 0.05, indicating that there was no correlation between mutation and metastasis of this gene.

From the above results, ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMO, SNRV3 It can be seen that mutations of TADA2A, UBE2D1, UGT2A3, ZNF320, and ZNF699 can be used as markers specific for metastasis of kidney cancer.

Survival Specific of Metastasis-Related Genes As a marker  Check availability

Among the candidate genes of Example 1, it was confirmed whether there was a survival-specific mutant gene. The 417 subjects obtained in Example 1 were classified into surviving patients (270) and deceased patients (147) and based on the clinical information (case (death or recurrence), observation time) obtained in Example 1 The overall survival kaplan-meier estimate and disease free survival kaplan-meier estimate were determined by Kaplan Meier survival analysis (Spss 21). Death was defined as an event in total survival and relapse of kidney cancer as an event in disease free survival. To determine whether mutations in each of these genes correlate with renal cancer death or recurrence of kidney cancer in metastatic kidney cancer patients, the event time of each group obtained from Kaplan Meier survival assays. ), The association between mutation incidence and total survival, and the association between mutation incidence and disease-free survival were confirmed by log rank test. P-values less than 0.05 were considered statistically significant. The experimental group was a case with alterations in query gene, the gene of the present invention, the control group was a case without alterations in query gene. Median months survival means the value that is centered when listing the survival periods of patients in the group. Median months desease free refers to the central value of the survival of patients in the group. The slope in the survival curve by Kaplan Meier survival assay is determined by the survival time.

The prognosis of 417 kidney cancer patients obtained in Example 1 was analyzed to determine whether mutations in each of the candidate genes correlated with survival of metastatic kidney cancer patients (the null hypothesis).

As a result of the analysis, as shown in Fig. 1 to Fig. 38, ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, Occurrence of ZGB, ZN, ZF320N, ZN mutation The probability that the null hypothesis that is related to survival of patients with metastatic kidney cancer is correct is 99.5% or more, that is, the probability that the null hypothesis is incorrect is less than 0.5% .Therefore, there is no correlation between the mutation of these genes and the survival rate of patients with metastatic kidney cancer. It can be seen that (for information on patients with metastatic kidney cancer, refer to the metastasis information (M0, M1) of Table 8 to Table 11 and the total number of patients (Mutation Number) in which the mutation of the gene was confirmed).

In Example 1, when only the correlation between mutation and metastasis was confirmed, some mutant genes determined to be insignificant because the P-value was 0.05 or more, P- when the correlation between survival and survival of patients with metastatic kidney cancer was confirmed. The value was found to be less than 0.05. For example, in the case of ADAM33, it was confirmed that there was no significance in confirming only the association between mutation and metastasis in Example 1, but in this example, the significance of the association between the mutation of ADAM33 and the survival time of patients with metastatic kidney cancer was not significant. The presence or absence of metastasis information (M0, M1) in Tables 8 to 11, the total number of patients (Mutation Number) in which the mutation of the gene was identified, and the P-value of FIG.

Survival analysis of the metastatic kidney cancer patients having the mutant gene is shown in FIGS. 1 to 38.

As a result, ADAM33 showed renal cancer according to FIG. 1 in 50% or more of the renal cancer patients without mutation of ADAM33 gene but no recurrence for more than 100 months (blue). Kidney cancer recurred in more than 50% of patients (red). Therefore, it is understood that mutation of the ADAM33 gene is significant as a predictive marker of recurrence of kidney cancer since the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the ADAM33 gene.

According to FIG. 2, ADAMTS10 was not recurrent for more than 100 months in renal cancer patients without mutations in the ADAMTS10 gene (blue). However, 50% of kidney cancer patients were less than 20 months with mutations in the ADAMTS10 gene. Renal cancer recurred in more than% (red). Therefore, it is understood that mutation of the ADAMTS10 gene is significant as a predictive marker of recurrence of kidney cancer since the probability of recurrence of kidney cancer is increased in patients with metastatic kidney cancer having a mutation in the ADAMTS10 gene.

As can be seen in (A) of FIG. 3, ASB15 has a mutation in the ASB15 gene, whereas at least 50% of kidney cancer patients without mutation in the ASB15 gene survived for 80 months or more (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to (B) of FIG. 3, more than 50% of renal cancer patients without mutations in the ASB15 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the ASB15 gene increases, it can be seen that the mutation of the ASB15 gene is significant as a predictor of survival or recurrence of renal cancer. .

As can be seen in FIG. 4, B3GNT2 is a kidney cancer patient without mutation in the B3GNT2 gene, whereas 50% or more survived for 80 months or more (blue), whereas a kidney cancer patient with the mutation in the B3GNT2 gene was Since more than 50% of kidney cancer patients died before 40 months of age, the survival rate was lower than that of kidney cancer patients without mutation (red). Therefore, since the probability of death of metastatic kidney cancer patients with mutations in the B3GNT2 gene increases, it can be seen that the mutation of the B3GNT2 gene is significant as a predictor of survival of kidney cancer patients.

According to FIG. 5, BFSP1 did not recur for more than 100 months in renal cancer patients without mutations in the BFSP1 gene (blue), but in 50 years of renal cancer patients in less than 20 months with mutations in the BFSP1 gene. Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic renal cancer having a mutation in the BFSP1 gene increases, it can be seen that the mutation of the BFSP1 gene is significant as a predictive marker for recurrence of renal cancer.

According to FIG. 6, more than 50% of renal cancer patients without mutations in the C8orf37 gene had no recurrence for more than 100 months (blue) .However, mutations in the C8orf37 gene resulted in less than 20 months. Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic kidney cancer having a mutation in the C8orf37 gene increases, it can be seen that the mutation of the C8orf37 gene is significant as a predictor of recurrence of renal cancer.

As can be seen in (A) of FIG. 7, CARD6 survived more than 80 months in kidney cancer patients without mutation in the CARD6 gene (blue), whereas mutation in the CARD6 gene occurred. Since more than 50% of kidney cancer patients died before 30 months of age, they were found to have a lower survival rate than kidney cancer patients without mutations (red). According to FIG. 7B, more than 50% of renal cancer patients without mutations in the CARD6 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the CARD6 gene is increased, it can be seen that the mutation of the CARD6 gene is significant as a survival predictor for renal cancer patients or as a marker for predicting recurrence of renal cancer. .

As shown in (A) of FIG. 8, CHRM2 is over 50% surviving more than 60 months in kidney cancer patients without mutation of the CHRM2 gene (blue), but mutation of the CHRM2 gene occurs. Since more than 50% of kidney cancer patients died before 30 months of age, they were found to have a lower survival rate than kidney cancer patients without mutations (red). According to FIG. 8B, more than 50% of renal cancer patients without mutations in the CHRM2 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the CHRM2 gene increases, it can be seen that the mutation of the CHRM2 gene is significant as a predictor of survival or recurrence of renal cancer patients. .

As can be seen in (A) of FIG. 9, CHSY3 is over 50% of kidney cancer patients without mutations in the CHSY3 gene, which is surviving for 60 months or more (blue), but the mutation of the CHSY3 gene is generated. Since more than 50% of kidney cancer patients died before 40 months of age, they were found to have a lower survival rate than kidney cancer patients without mutations (red). According to FIG. 9B, more than 50% of renal cancer patients without a mutation in the CHSY3 gene did not have recurrence for more than 100 months (blue), but a mutation in the CHSY3 gene does not occur in 20 months or less. Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic kidney cancer patients with mutations in the CHSY3 gene is increased, it can be seen that the mutation of the CHSY3 gene is significant as a survival predictor for renal cancer patients or as a marker for predicting recurrence of renal cancer. .

As can be seen in (A) of FIG. 10, CPSF3 has a mutation in the CPSF3 gene, whereas at least 50% of kidney cancer patients without mutation in the CPSF3 gene survive for 60 months or more (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 10B, more than 50% of renal cancer patients without mutations in the CPSF3 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the CPSF3 gene is increased, it can be seen that the mutation of the CPSF3 gene is significant as a predictor of survival or recurrence of renal cancer. .

According to FIG. 11, EHBP1L1 was not recurrent for more than 100 months in renal cancer patients without mutations in the EHBP1L1 gene (blue), but mutations in the EHBP1L1 gene did not occur in 20 months. Renal cancer recurred in more than% (red). Therefore, since the recurrence probability of patients with metastatic kidney cancer having a mutation in the EHBP1L1 gene increases, it can be seen that the mutation of the EHBP1L1 gene is significant as a predictive marker for recurrence of renal cancer.

According to FIG. 12, more than 50% of renal cancer patients without mutations in the EPB41L5 gene had no recurrence for more than 80 months (blue), but the mutation of the EPB41L5 gene was less than 20 months. Renal cancer recurred in more than% (red). Therefore, it is understood that the mutation of the EPB41L5 gene is significant as a predictive marker of recurrence of kidney cancer since the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the EPB41L5 gene.

As can be seen in FIG. 13A, FBXW5 has a mutation in the FBXW5 gene, whereas more than 50% of kidney cancer patients without mutation in the FBXW5 gene survive more than 60 months (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 13B, more than 50% of renal cancer patients without mutations in the FBXW5 gene did not have recurrence for more than 100 months (blue), but renal cancer patients were less than 20 months with mutations in the FBXW5 gene. Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence of renal cancer in metastatic renal cancer patients with mutations in the FBXW5 gene is increased, it can be seen that the mutation of the FBXW5 gene is significant as a predictor of survival or recurrence of renal cancer patients. .

As can be seen in FIG. 14, GPR173 is a kidney cancer patient without mutations in the GPR173 gene, whereas 50% or more survived for 80 months or more (blue), whereas a kidney cancer patient having a mutation in the GPR173 gene is present. Since more than 50% of kidney cancer patients died before 20 months of age, survival rates were lower than those of kidney cancer patients without mutations (red). Therefore, it is understood that mutation of the GPR173 gene is significant as a predictor of survival of kidney cancer patients since the death probability of metastatic kidney cancer patients with mutations in the GPR173 gene is increased.

According to FIG. 15, HHIPL2 was not recurrent for more than 80 months in renal cancer patients without mutations in the HHIPL2 gene (blue). Renal cancer recurred in more than% (red). Therefore, it is understood that the mutation of the HHIPL2 gene is significant as a predictive marker of recurrence of renal cancer because the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the HHIPL2 gene.

As can be seen in FIG. 16, in the kidney cancer patients without mutation in the ITGB7 gene, 50% or more survived for 60 months or more (blue), whereas the kidney cancer patients in which the mutation of the ITGB7 gene occurred Since more than 50% of kidney cancer patients died before 20 months of age, survival rates were lower than those of kidney cancer patients without mutations (red). Therefore, it is understood that the mutation of the ITGB7 gene is significant as a predictor of survival rate of kidney cancer patients since the death probability of metastatic kidney cancer patients with mutations in the ITGB7 gene is increased.

As can be seen in (A) of FIG. 17, KDM2A has a mutation in the KDM2A gene, whereas blue kidney patients without mutation in the KDM2A gene survive more than 60 months (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 17 (B), more than 50% of renal cancer patients without mutations in the KDM2A gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to kidney cancer in metastatic kidney cancer patients with mutations in the KDM2A gene is increased, it can be seen that the mutation of the KDM2A gene is significant as a survival predictor for renal cancer patients or as a marker for predicting recurrence of kidney cancer. .

As can be seen in FIG. 18, KDM5A survives more than 60 months in kidney cancer patients without mutations in the KDM5A gene (blue), whereas kidney cancer patients in which the mutations in the KDM5A gene have occurred. Since more than 50% of kidney cancer patients died before 20 months of age, survival rates were lower than those of kidney cancer patients without mutations (red). Therefore, it can be seen that the mutation probability of the KDM5A gene is significant as a predictor of survival of kidney cancer patients since the death probability of metastatic kidney cancer patients with mutations in the KDM5A gene is increased.

As shown in FIG. 19 (A), LOXL3 is more than 50% survived for 60 months or more in the kidney cancer patients without mutation of the LOXL3 gene (blue), but the mutation of the LOXL3 gene is generated. Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 19B, more than 50% of renal cancer patients without mutations in the LOXL3 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the LOXL3 gene increases, it can be seen that the mutation of the LOXL3 gene is significant as a survival predictor for renal cancer patients or as a predictive marker for recurrence of renal cancer. .

As can be seen in FIG. 20A, LUC7L2 has a mutation in the LUC7L2 gene, whereas at least 50% of the renal cancer patients without mutation in the LUC7L2 gene survived 60 months or longer (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 20B, more than 50% of renal cancer patients without mutations in the LUC7L2 gene did not have recurrence for more than 100 months (blue), but renal cancer patients were less than 20 months with mutations in the LUC7L2 gene. Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the LUC7L2 gene increases, it can be seen that the mutation of the LUC7L2 gene is significant as a survival predictor for renal cancer patients or as a marker for predicting recurrence of renal cancer. .

MUTYH is a mutation in the MUTYH gene, as shown in (A) of FIG. 21, whereas more than 50% of kidney cancer patients without mutation in the MUTYH gene survive for 60 months or more (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to (B) of FIG. 21, more than 50% of renal cancer patients without mutations in the MUTYH gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the MUTYH gene increases, it can be seen that the mutation of the MUTYH gene is significant as a predictor of survival or recurrence of renal cancer. .

According to FIG. 22, NFIX showed no recurrence for more than 80 months in renal cancer patients without mutations in the NFIX gene (blue). Renal cancer recurred in more than% (red). Therefore, it is understood that mutation of the NFIX gene is significant as a predictive marker of recurrence of renal cancer because the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the NFIX gene.

According to FIG. 23, OR5W2 showed no recurrence for more than 80 months in renal cancer patients without mutations in the OR5W2 gene (blue). Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic kidney cancer having a mutation in the OR5W2 gene increases, it can be seen that the mutation of the OR5W2 gene is significant as a predictor of recurrence of renal cancer.

According to Figure 24, PICK1 is more than 80 months in renal cancer patients without mutations in the PICK1 gene did not relapse for more than 80 months (blue), 50% of kidney cancer patients in less than 20 months if there is a mutation in the PICK1 gene Renal cancer recurred in more than% (red). Therefore, it is understood that the mutation of the PICK1 gene is significant as a predictive marker of recurrence of kidney cancer since the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the PICK1 gene.

As shown in FIG. 25, the PITPNB is renal cancer patients without mutation in the PITPNB gene, whereas 50% or more survived for 60 months or more (blue). Since more than 50% of kidney cancer patients died before 20 months of age, survival rates were lower than those of kidney cancer patients without mutations (red). Therefore, since the probability of death of metastatic kidney cancer patients with mutations in the PITPNB gene increases, it can be seen that the mutation of the PITPNB gene is significant as a predictor of survival rate of kidney cancer patients.

As shown in (A) of FIG. 26, RELN is 50% or more survived for 60 months or more in the kidney cancer patients without mutation in the RELN gene (blue), but the mutation in the RELN gene occurs. Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to (B) of FIG. 26, in the case of renal cancer patients without mutations in the RELN gene, more than 50% did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the RELN gene increases, indicating that the mutation of the RELN gene is significant as a marker for predicting survival or recurrence of renal cancer. .

As can be seen in (A) of FIG. 27, SAA1 has a mutation in the SAA1 gene, whereas at least 50% of patients with kidney cancer without mutation in the SAA1 gene survived for 60 months or more (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 27B, more than 50% of renal cancer patients without mutations in the SAA1 gene did not have recurrences for more than 100 months (blue), but renal cancer patients were less than 20 months with mutations in the SAA1 gene. Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the SAA1 gene increases, it can be seen that the mutation of the SAA1 gene is significant as a predictor of survival or recurrence of renal cancer. .

According to FIG. 28, SLC35B3 showed no recurrence for more than 80 months in renal cancer patients without mutations in the SLC35B3 gene (blue). Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic kidney cancer having a mutation in the SLC35B3 gene increases, it can be seen that the mutation of the SLC35B3 gene is significant as a predictive marker for recurrence of renal cancer.

As can be seen in FIG. 29, SMO is a kidney cancer patient without mutations in the SMO gene 50% or more surviving for more than 80 months (blue), the kidney cancer patients with mutations in the SMO gene Since more than 50% of kidney cancer patients died before the age of 50 months, the survival rate was lower than that of kidney cancer patients without mutation (red). Therefore, since the probability of death of metastatic kidney cancer patients with mutations in the SMO gene is increased, it can be seen that the mutation of the SMO gene is significant as a predictor of survival rate of kidney cancer patients.

According to FIG. 30, more than 50% of renal cancer patients without mutations in the ST7L gene did not have recurrence for more than 80 months (blue). Renal cancer recurred in more than% (red). Therefore, it is understood that mutation of the ST7L gene is significant as a predictive marker of recurrence of renal cancer since the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the ST7L gene.

According to FIG. 31, 50% of renal cancer patients without mutations in the STAMBP gene did not have recurrence for more than 80 months (blue). Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic kidney cancer with mutations in the STAMBP gene increases, it can be seen that the mutation of the STAMBP gene is significant as a predictive marker for recurrence of kidney cancer.

As shown in FIG. 32 (A), SUPV3L1 has a mutation in the SUPV3L1 gene, whereas more than 50% of kidney cancer patients without mutation in the SUPV3L1 gene survived for 60 months or more (blue). Since more than 50% of kidney cancer patients died before 30 months of age, they were found to have a lower survival rate than kidney cancer patients without mutations (red). According to (B) of FIG. 32, more than 50% of renal cancer patients without mutations in the SUPV3L1 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, since the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the SUPV3L1 gene is increased, it can be seen that the mutation of the SUPV3L1 gene is significant as a predictor of survival or recurrence of renal cancer. .

According to FIG. 33, more than 50% of renal cancer patients without mutations in the TADA2A gene had no recurrence for more than 80 months (blue). Renal cancer recurred in more than% (red). Therefore, since the probability of recurrence in patients with metastatic kidney cancer having a mutation in the TADA2A gene increases, it can be seen that the mutation of the TADA2A gene is significant as a predictor of recurrence of renal cancer.

As can be seen in (A) of FIG. 34, TP53TG5 has a mutation in the TP53TG5 gene, whereas more than 50% of the renal cancer patients without mutation in the TP53TG5 gene survive for 60 months or more (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 34B, more than 50% of renal cancer patients without mutations in the TP53TG5 gene did not have recurrence for more than 100 months (blue). Renal cancer recurred in more than 50% of patients (red). Therefore, the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the TP53TG5 gene increases, indicating that the mutation of the TP53TG5 gene is significant as a predictor of survival or recurrence of renal cancer. .

As can be seen in (A) of FIG. 35, UBE2D1 has a mutation in the UBE2D1 gene, whereas more than 50% of kidney cancer patients who do not have the mutation in the UBE2D1 gene survive more than 60 months (blue). Since more than 50% of kidney cancer patients died before the age of 20 months, the survival rate of the kidney cancer patients was lower than that of the kidney cancer patients without mutation (red). According to FIG. 35B, more than 50% of renal cancer patients without mutations in the UBE2D1 gene did not have recurrence for more than 100 months (blue), but renal cancer patients were less than 20 months with mutations in the UBE2D1 gene. Renal cancer recurred in more than 50% of patients (red). Therefore, the probability of death or recurrence due to renal cancer in metastatic renal cancer patients with mutations in the UBE2D1 gene increases, indicating that the mutation of the UBE2D1 gene is significant as a survival predictor for renal cancer patients or as a marker for predicting recurrence of renal cancer. .

According to FIG. 36, ZNF320 showed no recurrence for more than 80 months in renal cancer patients without mutation in the ZNF320 gene (blue), but the mutation in the ZNF320 gene resulted in less than 20 months. Renal cancer recurred in more than% (red). Therefore, it is understood that the mutation of the ZNF320 gene is significant as a predictive marker of recurrence of renal cancer because the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the ZNF320 gene.

As can be seen in FIG. 37, ZFP69 is a renal cancer patient without mutation in the ZFP69 gene, whereas 50% or more survived for 60 months or more (blue), whereas a kidney cancer patient with the mutation in the ZFP69 gene was Since more than 50% of kidney cancer patients died before 20 months of age, survival rates were lower than those of kidney cancer patients without mutations (red). Therefore, since the probability of death of metastatic kidney cancer patients with mutations in the ZFP69 gene increases, it can be seen that the mutation of the ZFP69 gene is significant as a predictor of survival rate of kidney cancer patients.

According to FIG. 38, ZNF699 showed no recurrence for more than 80 months in renal cancer patients without mutation in the ZNF699 gene (blue), but the mutation in the ZNF699 gene resulted in less than 20 months. Renal cancer recurred in more than% (red). Therefore, it is understood that the mutation of the ZNF699 gene is significant as a predictive marker of recurrence of renal cancer since the probability of recurrence is increased in patients with metastatic kidney cancer having a mutation in the ZNF699 gene.

Through the above results, ADAM33, ADAMTS10, ASB15, B3GNT2, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, GPR173, HHIPL2, ITGB7, KDM2A, KDM5A, LOLF, LOXL3 Metastatic kidney cancer patient if there is a mutation in any of the genes selected from the group consisting of, PICK1, PITPNB, RELN, SAA1, SLC35B3, SMO, ST7L, STAMBP, SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, ZFP69, and ZNF699 It can be seen that the survival rate of remarkably lower or increase the recurrence rate, so that the prognosis of renal cancer, especially survival or recurrence can be predicted by comparing the mutation of the genes of the present invention with the metastasis of the patient. .

Example  2, 3 gene mutations Detectable  Chip making

Primer sets for mutation detection of the genes of Examples 2 and 3 were prepared with Ion AmpliSeq ™ Custom and Community Panels of Thermo fisher, referring to https://tools.thermofisher.com/content/sfs/manuals/MAN0006735_AmpliSeq_DNA_RNA_LibPrep_UG.pdf. . To easily detect mutations, the chip type was selected and the depth was increased. Specifically, after inputting panel information to be produced on Ampliseq.com, receiving feedback on the inputted information, and discussing related matters, a panel equipped with a primer set for detecting mutations was manufactured. Tables 12 to 19 show primer sets capable of detecting mutations of the genes of the invention.

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop ADAMTS10 chr19 45 CTGTGGGCACTGCAGTAGT 46 ATACCTGGGCTGAGGTTCTCT 8651057 8651076 8651177 8651198 ADAMTS10 chr19 47 CCTCACTCTAGAAAGCTGGTGATGTA 48 CAGATTCGGCATGAACCATGAC 8660951 8660977 8661084 8661106 ADAMTS10 chr19 49 CCAGGGAGCATCCCTGATTTCTA 50 ATGAAGACCAACCCATTCGTGT 8660865 8660888 8660996 8661018 ASB15 chr7 51 CCCACAACAGGCTGTTTTTAAGG 52 TATTCCAGCAGGAGGGAAATGCA 123267086 123267109 123267237 123267260 ASB15 chr7 53 ATTTTCATCAATTGACTTTGTTCAATCCGA 54 AGGTCTTGAATTCCCAGAGTGTCT 123257516 123257546 123257641 123257665 ASB15 chr7 55 CAACTTTTCAACATAATGCTTTCATGTCAC 56 GCCACACTCCCTTTTCTAATAAAGTTCTTA 123257601 123257631 123257719 123257749 C8orf37 chr8 57 AACCAATGCTTTGTTGTTCAATGTCA 58 AATCTAAATCTTCAGGTAACACATCTGTCAG 96272579 96272605 96272722 96272753 C8orf37 chr8 59 TTTGTCCAAGTTGGGCTCTTCA 60 CTCATAAACCTCAGGTAAGTTTTCTTTGTG 96275924 96275946 96276018 96276048 C8orf37 chr8 61 AGGCCTTCAATGGAAGCTCTG 62 TGCCATGAAAATTTGTATTTAAGTCATTTAGAA 96272705 96272726 96272846 96272879 CHSY3 chr5 63 GCCTTTCTTCAGAGAGACCGAA 64 AGGAACGAGAATGTGTACTTTCTTTTCA 129520542 129520564 129520685 129520713 CHSY3 chr5 65 TTATCTTCTTTTCAAGGTGCCAAAGAAATG 66 CCAACTTTACATTCTGCTTTGGGATAAGA 129520645 129520675 129520769 129520798 CPSF3 chr2 67 ACCCAGAACTACATGACATTCCAATATAC 68 CTTCCACAAGCACTCACCTTGA 9580638 9580667 9580790 9580812 CPSF3 chr2 69 AGAATGAAATGGCCAGATTGAAAGC 70 AAAACATGGATTGGACAGACAGGAA 9588346 9588371 9588493 9588518

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop EHBP1L1 chr11 71 CCAGGTAGGACCTGCACTGTA 72 CCTCCTCACAAAGCGTCTTCA 65348431 65348452 65348543 65348564 EHBP1L1 chr11 73 TCCTACCATTCCCAGATCCCTC 74 CTGGCAACTGAGAAGAAAGAGGG 65348514 65348536 65348665 65348688 EHBP1L1 chr11 75 GGGAGGACTCAGATTGTCCCTT 76 CTGTGTTGCAATTGCCATCCAT 65346786 65346808 65346928 65346950 GPR148 chr2 77 GCCTCCTGGTCATTGTTACCTA 78 GTGATCAGCACTGAGTGGATCA 131487365 131487387 131487514 131487536 GPR148 chr2 79 GCTCATCAGCAAGACACCCT 80 GGTTCCGCAGGATGGTCAC 131486784 131486804 131486937 131486956 GPR148 chr2 81 CTATGCAGAGGCCAAGACTTCA 82 TCCCAGAGTCAATGTGGTGGTA 131487450 131487472 131487588 131487610 ITGB7 chr12 83 CACCAGCCATCATCCAAGATAGG 84 GGTAACCTATTGGCATCTACTACACAG 53586206 53586229 53586322 53586349 ITGB7 chr12 85 GTGGTTGAATAGGCAAGGGCTAA 86 CCGGTGGACCTGTACTACCTTA 53591227 53591250 53591378 53591400 ITGB7 chr12 87 GCATCCCTGCCCACTTACTTTC 88 CTTGTGCCCATACCAATGTGAC 53586096 53586118 53586241 53586263 KLHL24 chr3 89 AGATCAATGGTATTTTAGCTGAAGCTATGG 90 CAAGGATCAAGTTGCTCCTCCAA 183368467 183368497 183368618 183368641 KLHL24 chr3 91 AAAAGGTGTATAACAGCTGTATCCCTAAAC 92 GTCCCTCTTAGATTTATTTTTCTTTTGTACTGC 183390144 183390174 183390285 183390318 LOXL3 chr2 93 GGGCCATTGGACTGTAGATTGG 94 CCCACAAGAACATCACAGCTGA 74763044 74763066 74763189 74763211 LOXL3 chr2 95 GTCCAGAGCAGCGAACTTCACT 96 CATATTCCTTCGGAAGGTTAGGTGT 74763236 74763258 74763337 74763362 LOXL3 chr2 97 GGCATCCTGGCTATGTGAACAA 98 TTAATTACAACTTCCTGATCTTTGCCATCT 74763165 74763187 74763285 74763315

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop LTBR chr12 99 GTCCGACACAACCTGCAAAAAT 100 GGAGGGAAGTGTTCATCTTTTCCC 6495558 6495580 6495686 6495710 LTBR chr12 101 CTGACTAATTCTTCTCTCCTCTTCTCCA 102 TTCCGAGGCCCAGGTTCGT 6493713 6493741 6493868 6493887 LTBR chr12 103 TTTTTCCTCTGCAGGTGTGAGAA 104 GGAGCATTAAGGCATTTTCAGAGG 6495499 6495522 6495645 6495669 LUC7L2 chr7 105 ACTTTGTAGGCCATGGATCATCTG 106 AAACAAAAGGAGTCGAAATAATACTTTGTACTA 139086874 139086898 139087015 139087048 LUC7L2 chr7 107 CCCACCATGGTAGCATTTTAAAAAGC 108 CTTCTGTTCTACGATCACAATCTGCA 139086778 139086804 139086908 139086934 LUC7L2 chr7 109 AAATCAGGAAGAATATAATGTAACACTGCACT 110 AAAAACTACCTTTGAAAAAGACAACTTCACTA 139097214 139097246 139097355 139097387 MUTYH chr1 111 CCAAGGCCAGCCCATATACTTG 112 TAGCCAAGGATGTTGGCTTTTGA 45796949 45796971 45797051 45797074 MUTYH chr1 113 GCCTAGGAGACTTACCATACAGGT 114 TAAGGGCAGAACACCGGTTTATC 45796173 45796197 45796276 45796299 MUTYH chr1 115 GAAGCCTGGAGTGGAGAATGTT 116 TTGTCTAGGTTTTCCGTGTGTATCAG 45796080 45796102 45796211 45796237 MUTYH chr1 117 ACAAAGACAACAAAGGTAGTGCCTT 118 GTCCACACCTTCTCTCACATCA 45796832 45796857 45796981 45797003 OR5W2 chr11 119 GCAGTAGAATAGCAGAGATCACAGAA 120 CCCTATTTGCTGTATTCTTGGCTGTTTATA 55681832 55681858 55681952 55681982 OR5W2 chr11 121 CCTGTGTATCTGAGCGAGAGAGT 122 ATGTCTAGCAGAGTGTGCTATCTACT 55681479 55681502 55681627 55681653 OR5W2 chr11 123 AGACACTCAGAATCTGCAAAGATACAG 124 TTCACACACCAATGTATTTCTTCCTCA 55681721 55681748 55681868 55681895 POMZP3 chr7 125 CCCATTCAGTAGGATATGAAGGTTG 126 TCACTGATGCCTCTTCTGCATTC 76247438 76247463 76247577 76247600 POMZP3 chr7 127 TGTTAAAGCTCTTACCATGTTTCTGGA 128 GCCCACCTGTCTGGCTTTAAC 76247485 76247512 76247638 76247659

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop RELN chr7 129 TCCTACCTGTTACCAGGCTGAT 130 ACTCCTGCTACCAAATTTTGTCTCA 103292992 103293014 103293139 103293164 RELN chr7 131 TCACAAACCTTGCATCCTTAGTGT 132 CAGAGTAATAAATGGACGGATGGGATTTT 103132392 103132416 103132535 103132564 RELN chr7 133 CCGATGACTTATCCCAGCTGTT 134 TCAGATTTTGAGAACCAGAATGGCT 103243721 103243743 103243848 103243873 RELN chr7 135 AGGCAAGACATGGAAAAAGTCTACA 136 CTAGAAAGGATTTTGAGTGATTCTGGTCT 103293075 103293100 103293220 103293249 SAA1 chr11 137 CGACTGCCTGACTTCTCCTTTC 138 CAGAAATCCTGCAAACCTTCTGAAG 18288402 18288424 18288531 18288556 SAA1 chr11 139 GAGAATATCCAGAGATTCTTTGGCCAT 140 GCCTCACAGCCAGATCTCCT 18291274 18291301 18291424 18291444 SLC35B3 chr6 141 AAAGGAGATGTTGCCCTTATGTTTTG 142 TCTGGCTTTGATTAAAATTTTTGGTGCA 8417027 8417053 8417132 8417160 SLC35B3 chr6 143 CAGGAATCAATTTGCAGCACTTGA 144 GAATTGGGTCCCAAAATGAAGGTTTTAA 8422730 8422754 8422873 8422901 SLC35B3 chr6 145 GCAAGTAAATCCCTCCTACCTGTT 146 CCAGTTCGGACCTATGGTTATGC 8417098 8417122 8417202 8417225 SMO chr7 147 CCCAGTACCATTCCTCGACT 148 CTGGGCAGAATGGGTTGGA 128852020 128852040 128852127 128852146 SMO chr7 149 TAGGACCCTCCTCCCACTCAC 150 TGGTCTCGTTGATCTTGCTGG 128848518 128848539 128848659 128848680 SMO chr7 151 GCCCTTGGTTCGGACAGAC 152 CTGACCAGGGTGAAGAGCGT 128845091 128845110 128845238 128845258 SMO chr7 153 GCTGGTTGAGGCAGAGATCTC 154 GCTGAGGCAGTCGAGGAAT 128851893 128851914 128852028 128852047

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop SNRNP27 chr2 155 GTGAGGTGGAATGACTATTAATCTGTTACC 156 TGTGGAGTCAAAGGAGGCAAATC 70124412 70124442 70124562 70124585 SNRNP27 chr2 157 GGCGCAGCTCTAGATATTTGAG 158 GGCTCCTTCTCCGATCTCTCT 70122165 70122187 70122294 70122315 SNRNP27 chr2 159 GCAATTTGTGTGCGTTTGCATT 160 AACTCTTGGCTTATTTTCTGCCCTTA 70122202 70122224 70122347 70122373 ST7L chr1 161 GTTAGCACAGGCAGATCAGAGA 162 TCACAGCAGGATTTTGCTCTTCT 113084496 113084518 113084635 113084658 ST7L chr1 163 GCTAGGACTGCCTGAACATCTG 164 AATGAATCTGGCTCAGCTCTATTGAG 113124625 113124647 113124773 113124799 ST7L chr1 165 CCATGTACACTGTAACAGATTAAGAGCA 166 GTGTATATGTGTCTGTGTGTTACTCTTTCA 113098497 113098525 113098641 113098671 STAMBP chr2 167 GTGCGTGCATATGTTTGGGATG 168 TTTCTGGCGACAGGAAGAAATCT 74087110 74087132 74087216 74087239 STAMBP chr2 169 CAGAACTGGATTCTTTAAACTAACTGACCA 170 GTCCTCCCTGCTTGAAGCATAG 74087176 74087206 74087306 74087328 STAMBP chr2 171 GTAGAAGAAGGAAGCAGAGGAATTGG 172 ACAATTTTCAGTCGCTCTTTTTCTAGC 74074510 74074536 74074656 74074683 SUPV3L1 chr10 173 TGGTGATGCTTGAATTTTGGTGTTG 174 ACCACCAACCTAGAAGTGCTCT 70954857 70954882 70955008 70955030 SUPV3L1 chr10 175 AAAGCCCAGTATCAATGAAAAGGGA 176 CACAGGCCTCTTCAAAATTTCCTTTAATAA 70960069 70960094 70960213 70960243 SUPV3L1 chr10 177 ATGATTAGAGATCCAGCCAGAGGAT 178 CAATGGCAAGCAGATAAAAATGCATC 70954973 70954998 70955071 70955097 SUPV3L1 chr10 179 AGAAGGAGAGGTTACAACAATGAATCATG 180 CTCTCCTCCACAGAGAAGCAGTA 70960174 70960203 70960275 70960298 TADA2A chr17 181 TGTTTATTAAATTTGCCGTGTCTTGCA 182 TTCACATCTATCTTGATGAGTGCTCTTG 35836874 35836901 35837001 35837029

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop TADA2A chr17 183 GGCTGCTGTAAAGACACTAATCAAAG 184 CGCTCGATAAACATTTGACAAAATAAACTG 35804730 35804756 35804874 35804904 TADA2A chr17 185 AGCCACCCATCAGCTCCTATAA 186 CTCCAGGGACCAACCTCACCAT 35836774 35836796 35836910 35836932 UBE2D1 chr10 187 ATGTGTGATTATTGCAATTAAGTATAAGAAGGT 188 TGATTTTTACATTGCATATTTCTGAGTCCATTC 60128365 60128398 60128498 60128531 UBE2D1 chr10 189 TTTGTGTATCTACAGATACAACAGACATG 190 AGTGCTCAATTTACTGCTAATGTTGAAAAA 60128465 60128494 60128573 60128603 UGT2A3 chr4 191 ACCCAATCACATCTATAGAGTAGTGCT 192 AAAGAGAATGCTATGAGATTATCAAGAATTCA 69795635 69795662 69795774 69795806 UGT2A3 chr4 193 AAAAATAAAACAAAAGTGTCTTACCTAATGCCT 194 CTAACAGACAGAATGACCTTTCTGGAAA 69816740 69816773 69816856 69816884 UGT2A3 chr4 195 GGGCTTTACAGGTTGATCATGG 196 GGCTTGCATAACATATACTACGGTTTATCTAC 69795753 69795775 69795871 69795903 UGT2A3 chr4 197 GAAGTGGAACAAAACTGAAAGCATTGA 198 GTAGGAGGCAATATGGAGCGAA 69816819 69816846 69816937 69816959 ZNF320 chr19 199 CTCCAGTATGCAGTCTATGATGGTAC 200 GGGAGACAAACATTACACATGTAATGAAT 53384571 53384597 53384714 53384743 ZNF320 chr19 201 CAAGATGTGATTTGCAACTGAAAACTTTC 202 ACTAGTAGTACAGACCGATATGATCAAAGG 53384850 53384879 53384991 53385021 ZNF320 chr19 203 GATTCAAGCTGACCTTTAATAGGCTTG 204 CATTTTGCTCCCAGGAAATTGAGAAAG 53384954 53384981 53385101 53385128 ZNF320 chr19 205 ATGCAAGGGTTGCTTTTTGATCAAA 206 AAGGTTTGCGACAAGGCTTTTAAG 53384679 53384704 53384781 53384805 ZNF699 chr19 207 GTTTGTCTTTCCGATGTGAATCTTCATATG 208 CAAACCCTATCAGTGCAAGGAATG 9407246 9407276 9407396 9407420 ZNF699 chr19 209 GGGCTGAGGGATAAATAAAGGCT 210 TCATCCCTCACCGAACACCTAA 9406444 9406467 9406596 9406618 ZNF699 chr19 211 GCTTCTTGAAACAAGCAAGAAAATGGA 212 GTGAATGCCATGAGTGTGGAAAG 9407359 9407386 9407473 9407496

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop ADAM33 chr20 213 GGAACCTGAGGGCACCAATT 214 CGACCTCTGCTGCTTTGCT 3653097 3653117 3653246 3653265 ADAM33 chr20 215 CGTCCTCACCTTGAAGCACC 216 CTAGAGGCCGAGGAGCTCAC 3662546 3662566 3662655 3662675 ADAM33 chr20 217 CCCGCACAGATCTGTGTCAG 218 TTTCTTGCCCAGGTCTCGAAG 3657637 3657657 3657781 3657802 B3GNT2 chr2 219 CATACTGGAACCGAGAGCAAGA 220 GCAAGTTGTTAAAACCCGTAACCA 62449525 62449547 62449668 62449692 B3GNT2 chr2 221 CATCGGGATAAGAAGCTGAAGTACTAC 222 GGCACATTCCAGTATAAACGTCATCA 62450199 62450226 62450347 62450373 B3GNT2 chr2 223 TGCCCAGACACTGAGTTTGTTT 224 TAGTACTTCAGCTTCTTATCCCGATGA 62450058 62450080 62450197 62450224 B3GNT2 chr2 225 TACCATATCACTGACCAGGTCCAT 226 TTTTCTCCTCGATATCAAATGTCCTGAAG 62450313 62450337 62450410 62450439 BFSP1 chr20 227 ACCTTTTAATGGTGCATCTTCCAGA 228 CAATTATACTTGAATTTCTGCCTGTGTGT 17475538 17475563 17475682 17475711 CARD6 chr5 229 CTTCGAGAATTCAGAAACCACAGAGT 230 CCATTATGTCATGGCAAGCTTATTAACTT 40843708 40843734 40843853 40843882 CARD6 chr5 231 TCCATGCAAATCTACTCAGCCTAAG 232 TCTGGAGTTAGCTCTTTAATGCTTCC 40854389 40854414 40854537 40854563 CARD6 chr5 233 CTCTGGCTAATCTCCGTGGAAA 234 GAACAAAGTAGCATCTTTCAATGGCA 40853017 40853039 40853155 40853181 CHRM2 chr7 235 TTCCAAAGATGAGAACTCTAAGCAAACA 236 AGGCTGCTTAGTCATCTTCACAATC 136700554 136700582 136700703 136700728 CHRM2 chr7 237 GGCAGGTATGATGATTGCAGCT 238 AAATAGAAGGCTGCAATAGCCGTA 136700029 136700051 136700178 136700202 EPB41L5 chr2 239 ATCTCAGAAATAGGAGATAGGACTGTTTGA 240 CTCGAAGGCGGAAGAAAGCATG 120847854 120847884 120848006 120848028

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop FBXW5 chr9 241 CCGTCCTCACCTTCACAGTG 242 GCCATGTCCTGGTACGAGGA 139837791 139837811 139837936 139837956 FBXW5 chr9 243 GTGTCATACAGCCGCTGGAA 244 GCCATGACTAGTGGGTTCCAG 139837916 139837936 139838059 139838080 GPR173 chrX 245 CTACGCCAAGCGCATGACACT 246 TAGCGATGCTCAAAGATGCACT 53106193 53106214 53106320 53106342 GPR173 chrX 247 GTGGGCACCTACAAGTTTATTCG 248 GATACTCGAAGAGGAGCAGCTT 53106287 53106310 53106418 53106440 HHIPL2 chr1 249 GGCACTTTTCACTACCTGGCAA 250 CCTCTGCACCTTGAGTTTTGCT 222721051 222721073 222721202 222721224 HHIPL2 chr1 251 CAGGCAAAGATCCTGCTTCTTC 252 CTCTGATTCTAGGAGAAAAAGTATTCTGCA 222705390 222705412 222705500 222705530 HHIPL2 chr1 253 GCAGAAATCAAACAACTCTGTACATTTGT 254 ACTTATGGCTTTGCAGGAAGATAGAAAA 222705276 222705305 222705422 222705450 HHIPL2 chr1 255 CTTGCGATTGTGGCGGAAT 256 TCTTTGTTGCCGAGCAGGTAG 222716989 222717008 222717137 222717158 KDM2A chr11 257 TTGAGAAAGCCAAGATCCGGG 258 ATGGCGAAGGTTGGCAGAGG 67017867 67017888 67017974 67017994 KDM2A chr11 259 AGACGAGTGCGATGTCGAAAAT 260 CCCAAAATTCTTTACCCAGCAGATCA 67012795 67012817 67012934 67012960 KDM2A chr11 261 TCTCGACTCGACCTCAGTCA 262 TGATTATGAACAACTGTAGCGGCATA 67021781 67021801 67021890 67021916 KDM2A chr11 263 GCCTGTACAGGTCAGGACAATC 264 TGAGTAGATTGGAGGACTGATCTGTAA 67021664 67021686 67021811 67021838 KDM2A chr11 265 CGCGATGAGCGCTTCAAA 266 CTCTTTGGTGGGCCTCTGTA 67017758 67017776 67017908 67017928 KDM5A chr12 267 ACTGAAGGAAGACACCAAAAGACTC 268 CAACTGGAGGAGGTGATGAGAG 442626 442651 442747 442769

Lineitem_name Chr SEQ ID NO: Ion_AmpliSeq_Fwd_Primer * SEQ ID NO: Ion_AmpliSeq_Rev_Primer * Amplicon_Start Insert_Start Insert_Stop Amplicon_Stop KDM5A chr12 269 CGGGCAACTTCTGAAGGGATAC 270 TTCCTCTTCCTAAATCAAGTTCCCAAAAA 416838 416860 416955 416984 KDM5A chr12 271 CCACACAGCTTGTCCATGTAACT 272 GTTTAGGGACACTTACCTAGTTTCCAG 416087 416110 416234 416261 KDM5A chr12 273 CAATGAGCAATCATCGTGCCG 274 CCCAACGTGCTAATGGAGCAT 442525 442546 442661 442682 KDM5A chr12 275 CCAGGGCAGAGGATAGTTCATC 276 AGGCCCAGGCTAGAGACTATTC 416730 416752 416870 416892 KDM5A chr12 277 AGATCAGGCTGGGATTCAAATAACTC 278 TTGGAATCAGATACCCTAGCCTCAT 442711 442737 442859 442884 NFIX chr19 279 CAAGAAGCATGAAAAGCGGATGT 280 CTTCTTGCCCGTGATGGTCA 13135930 13135953 13136084 13136104 NFIX chr19 281 CGAGTTCCGCGAGGACTTC 282 AAAATCACCATGACCAGGTCCA 13136062 13136081 13136192 13136214 PICK1 chr22 283 CATGTATCAGGGCCTAGCAGAG 284 GTGAGTCTGCGACAGCTCA 38467573 38467595 38467728 38467747 PITPNB chr22 285 ATAGCTAGCTCCGATCTCATCCTAAAT 286 ATCTAGAAGGAGCTGGCAAACAG 28256062 28256089 28256212 28256235 PITPNB chr22 287 ACCAGCTTATAGGCACACATCTG 288 CATGTATGTCTATGATGTCGTTATACAACA 28256177 28256200 28256294 28256324 TP53TG5 chr20 289 CCCGATCTCCTGGAACTCTTCA 290 GCTGGCTACATAGCAACTGTCT 44004135 44004157 44004246 44004268 TP53TG5 chr20 291 CCTGGGACTTCCACTCCTTGTA 292 GGAAAACAGTGCCTGCAATAAAACA 44004050 44004072 44004167 44004192 ZFP69 chr1 293 GAGGTGGTCTCCGGCTAAAAAT 294 CTGACACCAAGTTGCTGTAGTTCT 40954718 40954740 40954859 40954883 ZFP69 chr1 295 CCTCACCAGAAGTGGACAAGTC 296 TTCTCCTTCAAACATTTTAGTCACATCCT 40944996 40945018 40945130 40945159 ZFP69 chr1 297 CAGAGGATACACCTTAGCAACCA 298 GTTATAGCTGAAGGCTTTTCCACATTC 40961498 40961521 40961644 40961671 ZFP69 chr1 299 GCATGCACTGCATGTTGTAAAAC 300 TGCATTCATATGCTTTCACTCCTGTAT 40961384 40961407 40961531 40961558 ZFP69 chr1 301 GAAGCTGCAACATCCAAAGAAGG 302 TACCTATCTTTTCACACACAAATGAGATCC 40945084 40945107 40945191 40945221

In order to confirm whether mutation detection is possible with the prepared primer set, gene mutations identified in Example 2 and samples derived from wild-type kidney cancer cells were used. Gene mutations were sampled, amplified with primer sets corresponding to each sample, and the completed chip was scanned using a scanner and application program and analyzed using quantitative analysis software.

As a result, mutations in the genes of Examples 2 and 3 could be detected using the primer set prepared in Example 4. On the other hand, no mutations were detected in samples from control kidney cancer cells. Using the primer pairs of Tables 16-24, ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B , SNRNP27, ST7L, STAMBP, SUPV3L1, TADA2A, UBE2D1, UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPL2, KDMA, KDM2, KDM2 Since mutations of genes selected from the gene group consisting of ZFP69 can be detected respectively, it is possible to predict the total survival time and disease-free survival time of kidney cancer patients in which the mutations of the genes are indicated, thereby efficiently designing a treatment strategy. .

In the above described exemplary embodiments of the present invention by way of example, the scope of the present invention is not limited only to the specific embodiments as described above, those skilled in the art to the scope described in the claims of the present invention It will be possible to change accordingly.

<110> THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION <120> Metastasis-specific markers for diagnosing prognosis and          determining treatment strategies of patient of clear cell renal          cell carcinoma <130> 2017-DPA-2540 <160> 302 <170> KoPatentIn 3.0 <210> 1 <211> 1103 <212> PRT <213> Homo sapiens <400> 1 Met Ala Pro Ala Cys Gln Ile Leu Arg Trp Ala Leu Ala Leu Gly Leu   1 5 10 15 Gly Leu Met Phe Glu Val Thr His Ala Phe Arg Ser Gln Asp Glu Phe              20 25 30 Leu Ser Ser Leu Glu Ser Tyr Glu Ile Ala Phe Pro Thr Arg Val Asp          35 40 45 His Asn Gly Ala Leu Leu Ala Phe Ser Pro Pro Pro Arg Arg Gln      50 55 60 Arg Arg Gly Thr Gly Ala Thr Ala Glu Ser Arg Leu Phe Tyr Lys Val  65 70 75 80 Ala Ser Pro Ser Thr His Phe Leu Leu Asn Leu Thr Arg Ser Ser Arg                  85 90 95 Leu Leu Ala Gly His Val Ser Val Glu Tyr Trp Thr Arg Glu Gly Leu             100 105 110 Ala Trp Gln Arg Ala Ala Arg Pro His Cys Leu Tyr Ala Gly His Leu         115 120 125 Gln Gly Gln Ala Ser Ser Ser His Val Ala Ile Ser Thr Cys Gly Gly     130 135 140 Leu His Gly Leu Ile Val Ala Asp Glu Glu Glu Tyr Leu Ile Glu Pro 145 150 155 160 Leu His Gly Gly Pro Lys Gly Ser Arg Ser Pro Glu Glu Ser Gly Pro                 165 170 175 His Val Val Tyr Lys Arg Ser Ser Leu Arg His Pro His Leu Asp Thr             180 185 190 Ala Cys Gly Val Arg Asp Glu Lys Pro Trp Lys Gly Arg Pro Trp Trp         195 200 205 Leu Arg Thr Leu Lys Pro Pro Pro Ala Arg Pro Leu Gly Asn Glu Thr     210 215 220 Glu Arg Gly Gln Pro Gly Leu Lys Arg Ser Val Ser Arg Glu Arg Tyr 225 230 235 240 Val Glu Thr Leu Val Val Ala Asp Lys Met Met Val Ala Tyr His Gly                 245 250 255 Arg Arg Asp Val Glu Gln Tyr Val Leu Ala Ile Met Asn Ile Val Ala             260 265 270 Lys Leu Phe Gln Asp Ser Ser Leu Gly Ser Thr Val Asn Ile Leu Val         275 280 285 Thr Arg Leu Ile Leu Leu Thr Glu Asp Gln Pro Thr Leu Glu Ile Thr     290 295 300 His His Ala Gly Lys Ser Leu Asp Ser Phe Cys Lys Trp Gln Lys Ser 305 310 315 320 Ile Val Asn His Ser Gly His Gly Asn Ala Ile Pro Glu Asn Gly Val                 325 330 335 Ala Asn His Asp Thr Ala Val Leu Ile Thr Arg Tyr Asp Ile Cys Ile             340 345 350 Tyr Lys Asn Lys Pro Cys Gly Thr Leu Gly Leu Ala Pro Val Gly Gly         355 360 365 Met Cys Glu Arg Glu Arg Ser Cys Ser Val Asn Glu Asp Ile Gly Leu     370 375 380 Ala Thr Ala Phe Thr Ile Ala His Glu Ile Gly His Thr Phe Gly Met 385 390 395 400 Asn His Asp Gly Val Gly Asn Ser Cys Gly Ala Arg Gly Gln Asp Pro                 405 410 415 Ala Lys Leu Met Ala Ala His Ile Thr Met Lys Thr Asn Pro Phe Val             420 425 430 Trp Ser Ser Cys Ser Arg Asp Tyr Ile Thr Ser Phe Leu Asp Ser Gly         435 440 445 Leu Gly Leu Cys Leu Asn Asn Arg Pro Pro Arg Gln Asp Phe Val Tyr     450 455 460 Pro Thr Val Ala Pro Gly Gln Ala Tyr Asp Ala Asp Glu Gln Cys Arg 465 470 475 480 Phe Gln His Gly Val Lys Ser Arg Gln Cys Lys Tyr Gly Glu Val Cys                 485 490 495 Ser Glu Leu Trp Cys Leu Ser Lys Ser Asn Arg Cys Ile Thr Asn Ser             500 505 510 Ile Pro Ala Ala Glu Gly Thr Leu Cys Gln Thr His Thr Ile Asp Lys         515 520 525 Gly Trp Cys Tyr Lys Arg Val Cys Val Pro Phe Gly Ser Arg Pro Glu     530 535 540 Gly Val Asp Gly Ala Trp Gly Pro Trp Thr Pro Trp Gly Asp Cys Ser 545 550 555 560 Arg Thr Cys Gly Gly Gly Val Ser Ser Ser Ser Arg His Cys Asp Ser                 565 570 575 Pro Arg Pro Thr Ile Gly Gly Lys Tyr Cys Leu Gly Glu Arg Arg Arg             580 585 590 His Arg Ser Cys Asn Thr Asp Asp Cys Pro Pro Gly Ser Gln Asp Phe         595 600 605 Arg Glu Val Gln Cys Ser Glu Phe Asp Ser Ile Pro Phe Arg Gly Lys     610 615 620 Phe Tyr Lys Trp Lys Thr Tyr Arg Gly Gly Gly Val Lys Ala Cys Ser 625 630 635 640 Leu Thr Cys Leu Ala Glu Gly Phe Asn Phe Tyr Thr Glu Arg Ala Ala                 645 650 655 Ala Val Val Asp Gly Thr Pro Cys Arg Pro Asp Thr Val Asp Ile Cys             660 665 670 Val Ser Gly Glu Cys Lys His Val Gly Cys Asp Arg Val Leu Gly Ser         675 680 685 Asp Leu Arg Glu Asp Lys Cys Arg Val Cys Gly Gly Asp Gly Ser Ala     690 695 700 Cys Glu Thr Ile Glu Gly Val Phe Ser Pro Ala Ser Pro Gly Ala Gly 705 710 715 720 Tyr Glu Asp Val Val Trp Ile Pro Lys Gly Ser Val His Ile Phe Ile                 725 730 735 Gln Asp Leu Asn Leu Ser Leu Ser His Leu Ala Leu Lys Gly Asp Gln             740 745 750 Glu Ser Leu Leu Leu Glu Gly Leu Pro Gly Thr Pro Gln Pro His Arg         755 760 765 Leu Pro Leu Ala Gly Thr Thr Phe Gln Leu Arg Gln Gly Pro Asp Gln     770 775 780 Val Gln Ser Leu Glu Ala Leu Gly Pro Ile Asn Ala Ser Leu Ile Val 785 790 795 800 Met Val Leu Ala Arg Thr Glu Leu Pro Ala Leu Arg Tyr Arg Phe Asn                 805 810 815 Ala Pro Ile Ala Arg Asp Ser Leu Pro Pro Tyr Ser Trp His Tyr Ala             820 825 830 Pro Trp Thr Lys Cys Ser Ala Gln Cys Ala Gly Gly Ser Gln Val Gln         835 840 845 Ala Val Glu Cys Arg Asn Gln Leu Asp Ser Ser Ala Val Ala Pro His     850 855 860 Tyr Cys Ser Ala His Ser Lys Leu Pro Lys Arg Gln Arg Ala Cys Asn 865 870 875 880 Thr Glu Pro Cys Pro Pro Asp Trp Val Val Gly Asn Trp Ser Leu Cys                 885 890 895 Ser Arg Ser Cys Asp Ala Gly Val Arg Ser Arg Ser Val Val Cys Gln             900 905 910 Arg Arg Val Ser Ala Ala Glu Glu Lys Ala Leu Asp Asp Ser Ala Cys         915 920 925 Pro Gln Pro Arg Pro Pro Val Leu Glu Ala Cys His Gly Pro Thr Cys     930 935 940 Pro Pro Glu Trp Ala Ala Leu Asp Trp Ser Glu Cys Thr Pro Ser Cys 945 950 955 960 Gly Pro Gly Leu Arg His Arg Val Val Leu Cys Lys Ser Ala Asp His                 965 970 975 Arg Ala Thr Leu Pro Pro Ala His Cys Ser Pro Ala Ala Lys Pro Pro             980 985 990 Ala Thr Met Arg Cys Asn Leu Arg Arg Cys Pro Pro Ala Arg Trp Val         995 1000 1005 Ala Gly Glu Trp Gly Glu Cys Ser Ala Gln Cys Gly Val Gly Gln Arg    1010 1015 1020 Gln Arg Ser Val Arg Cys Thr Ser His Thr Gly Gln Ala Ser His Glu 1025 1030 1035 1040 Cys Thr Glu Ala Leu Arg Pro Pro Thr Thr Gln Gln Cys Glu Ala Lys                1045 1050 1055 Cys Asp Ser Pro Thr Pro Gly Asp Gly Pro Glu Glu Cys Lys Asp Val            1060 1065 1070 Asn Lys Val Ala Tyr Cys Pro Leu Val Leu Lys Phe Gln Phe Cys Ser        1075 1080 1085 Arg Ala Tyr Phe Arg Gln Met Cys Cys Lys Thr Cys His Gly His    1090 1095 1100 <210> 2 <211> 588 <212> PRT <213> Homo sapiens <400> 2 Met Asp Thr Asn Asp Asp Pro Asp Glu Asp His Leu Thr Ser Tyr Asp   1 5 10 15 Ile Gln Leu Ser Ile Gln Glu Ser Ile Glu Ala Ser Lys Thr Ala Leu              20 25 30 Cys Pro Glu Arg Phe Val Pro Leu Ser Ala Gln Asn Arg Lys Leu Val          35 40 45 Glu Ala Ile Lys Gln Gly His Ile Pro Glu Leu Gln Glu Tyr Val Lys      50 55 60 Tyr Lys Tyr Ala Met Asp Glu Ala Asp Glu Lys Gly Trp Phe Pro Leu  65 70 75 80 His Glu Ala Val Val Gln Pro Ile Gln Gln Ile Leu Glu Ile Val Leu                  85 90 95 Asp Ala Ser Tyr Lys Thr Leu Trp Glu Phe Lys Thr Cys Asp Gly Glu             100 105 110 Thr Pro Leu Thr Leu Ala Val Lys Ala Gly Leu Val Glu Asn Val Arg         115 120 125 Thr Leu Leu Glu Lys Gly Val Trp Pro Asn Thr Lys Asn Asp Lys Gly     130 135 140 Glu Thr Pro Leu Leu Ile Ala Val Lys Lys Gly Ser Tyr Asp Met Val 145 150 155 160 Ser Thr Leu Ile Lys His Asn Thr Ser Leu Asp Gln Pro Cys Val Lys                 165 170 175 Arg Trp Ser Ala Met His Glu Ala Ala Lys Gln Gly Arg Lys Asp Ile             180 185 190 Val Ala Leu Leu Leu Lys His Gly Gly Asn Val His Leu Arg Asp Gly         195 200 205 Phe Gly Val Thr Pro Leu Gly Val Ala Ala Glu Tyr Gly His Cys Asp     210 215 220 Val Leu Glu His Leu Ile His Lys Gly Gly Asp Val Leu Ala Leu Ala 225 230 235 240 Asp Asp Gly Ala Ser Val Leu Phe Glu Ala Ala Gly Gly Gly Asn Pro                 245 250 255 Asp Cys Ile Ser Leu Leu Leu Glu Tyr Gly Gly Ser Gly Asn Val Pro             260 265 270 Asn Arg Ala Gly His Leu Pro Ile His Arg Ala Ala Tyr Glu Gly His         275 280 285 Tyr Leu Ala Leu Lys Tyr Leu Ile Pro Val Thr Ser Lys Asn Ala Ile     290 295 300 Arg Lys Ser Gly Leu Thr Pro Ile His Ser Ala Ala Asp Gly Gln Asn 305 310 315 320 Ala Gln Cys Leu Glu Leu Leu Ile Glu Asn Gly Phe Asp Val Asn Thr                 325 330 335 Leu Leu Ala Asp His Ile Ser Gln Ser Tyr Asp Asp Glu Arg Lys Thr             340 345 350 Ala Leu Tyr Phe Gly Val Ser Asn Asn Asp Val His Cys Thr Glu Val         355 360 365 Leu Leu Ala Ala Gly Ala Asp Pro Asn Leu Asp Pro Leu Asn Cys Leu     370 375 380 Leu Val Ala Val Arg Ala Asn Asn Tyr Glu Ile Val Arg Leu Leu Leu 385 390 395 400 Ser His Gly Ala Asn Val Asn Cys Tyr Phe Met His Val Asn Asp Thr                 405 410 415 Arg Phe Pro Ser Val Ile Gln Tyr Ala Leu Asn Asp Glu Val Met Leu             420 425 430 Arg Leu Leu Leu Asn Asn Gly Tyr Gln Val Glu Met Cys Phe Asp Cys         435 440 445 Met His Gly Asp Ile Phe Gly Asn Ser Phe Val Trp Ser Glu Ile Gln     450 455 460 Glu Glu Val Leu Pro Gly Trp Thr Ser Cys Val Ile Lys Asp Asn Pro 465 470 475 480 Phe Cys Glu Phe Ile Thr Val Pro Trp Met Lys His Leu Val Gly Arg                 485 490 495 Val Thr Arg Val Leu Ile Asp Tyr Met Asp Tyr Val Pro Leu Cys Ala             500 505 510 Lys Leu Lys Ser Ala Leu Glu Val Gln Arg Glu Trp Pro Glu Ile Arg         515 520 525 Gln Ile Leu Glu Asn Pro Cys Ser Leu Lys His Leu Cys Arg Leu Lys     530 535 540 Ile Arg Arg Leu Met Gly Leu Gln Lys Leu Cys Gln Pro Ala Ser Val 545 550 555 560 Glu Lys Leu Pro Leu Pro Pro Ala Ile Gln Arg Tyr Ile Leu Phe Lys                 565 570 575 Glu Tyr Asp Leu Tyr Gly Gln Glu Leu Lys Leu Thr             580 585 <210> 3 <211> 207 <212> PRT <213> Homo sapiens <400> 3 Met Ala Glu Asp Leu Asp Glu Leu Leu Asp Glu Val Glu Ser Lys Phe   1 5 10 15 Cys Thr Pro Asp Leu Leu Arg Arg Gly Met Val Glu Gln Pro Lys Gly              20 25 30 Cys Gly Gly Gly Thr His Ser Ser Asp Arg Asn Gln Ala Lys Ala Lys          35 40 45 Glu Thr Leu Arg Ser Thr Glu Thr Phe Lys Lys Glu Asp Asp Leu Asp      50 55 60 Ser Leu Ile Asn Glu Ile Leu Glu Glu Pro Asn Leu Asp Lys Lys Pro  65 70 75 80 Ser Lys Leu Lys Ser Lys Ser Ser Gly Asn Thr Ser Val Arg Ala Ser                  85 90 95 Ile Glu Gly Leu Gly Lys Ser Cys Ser Pro Val Tyr Leu Gly Gly Ser             100 105 110 Ser Ile Pro Cys Gly Ile Gly Thr Asn Ile Ser Trp Arg Ala Cys Asp         115 120 125 His Leu Arg Cys Ile Ala Cys Asp Phe Leu Val Val Ser Tyr Asp Asp     130 135 140 Tyr Met Trp Asp Lys Ser Cys Asp Tyr Leu Phe Phe Arg Asn Asn Met 145 150 155 160 Pro Glu Phe His Lys Leu Lys Ala Lys Leu Ile Lys Lys Lys Gly Thr                 165 170 175 Arg Ala Tyr Ala Cys Gln Cys Ser Trp Arg Thr Ile Glu Glu Val Thr             180 185 190 Asp Leu Gln Thr Asp His Gln Leu Arg Trp Val Cys Gly Lys His         195 200 205 <210> 4 <211> 882 <212> PRT <213> Homo sapiens <400> 4 Met Ala Val Arg Ser Arg Arg Pro Trp Met Ser Val Ala Leu Gly Leu   1 5 10 15 Val Leu Gly Phe Thr Ala Ala Ser Trp Leu Ile Ala Pro Arg Val Ala              20 25 30 Glu Leu Ser Glu Arg Lys Arg Arg Gly Ser Ser Leu Cys Ser Tyr Tyr          35 40 45 Gly Arg Ser Ala Ala Gly Pro Arg Ala Gly Ala Gln Gln Pro Leu Pro      50 55 60 Gln Pro Gln Ser Arg Pro Arg Gln Glu Gln Ser Pro Pro Ala Arg  65 70 75 80 Gln Asp Leu Gln Gly Pro Pro Leu Pro Glu Ala Ala Pro Gly Ile Thr                  85 90 95 Ser Phe Arg Ser Ser Pro Trp Gln Gln Pro Pro Pro Leu Gln Gln Arg             100 105 110 Arg Arg Gly Arg Glu Pro Glu Gly Ala Thr Gly Leu Pro Gly Ala Pro         115 120 125 Ala Ala Glu Gly Glu Pro Glu Glu Glu Asp Gly Gly Ala Ala Gly Gln     130 135 140 Arg Arg Asp Gly Arg Pro Gly Ser Ser His Asn Gly Ser Gly Asp Gly 145 150 155 160 Gly Ala Ala Ala Pro Ser Ala Arg Pro Arg Asp Phe Leu Tyr Val Gly                 165 170 175 Val Met Thr Ala Gln Lys Tyr Leu Gly Ser Arg Ala Leu Ala Ala Gln             180 185 190 Arg Thr Trp Ala Arg Phe Ile Pro Gly Arg Val Glu Phe Phe Ser Ser         195 200 205 Gln Gln Pro Pro Asn Ala Gly Gln Pro Pro Pro Pro Leu Pro Val Ile     210 215 220 Ala Leu Pro Gly Val Asp Asp Ser Tyr Pro Pro Gln Lys Lys Ser Phe 225 230 235 240 Met Met Ile Lys Tyr Met His Asp His Tyr Leu Asp Lys Tyr Glu Trp                 245 250 255 Phe Met Arg Ala Asp Asp Asp Val Tyr Ile Lys Gly Asp Lys Leu Glu             260 265 270 Glu Phe Leu Arg Ser Leu Asn Ser Ser Lys Pro Leu Tyr Leu Gly Gln         275 280 285 Thr Gly Leu Gly Asn Ile Glu Glu Leu Gly Lys Leu Gly Leu Glu Pro     290 295 300 Gly Glu Asn Phe Cys Met Gly Gly Pro Gly Met Ile Phe Ser Arg Glu 305 310 315 320 Val Leu Arg Arg Met Val Pro His Ile Gly Glu Cys Leu Arg Glu Met                 325 330 335 Tyr Thr Thr His Glu Asp Val Glu Val Gly Arg Cys Val Arg Arg Phe             340 345 350 Gly Gly Thr Gln Cys Val Trp Ser Tyr Glu Met Gln Gln Leu Phe His         355 360 365 Glu Asn Tyr Glu His Asn Arg Lys Gly Tyr Ile Gln Asp Leu His Asn     370 375 380 Ser Lys Ile His Ala Ala Ile Thr Leu His Pro Asn Lys Arg Pro Ala 385 390 395 400 Tyr Gln Tyr Arg Leu His Asn Tyr Met Leu Ser Arg Lys Ile Ser Glu                 405 410 415 Leu Arg Tyr Arg Thr Ile Gln Leu His Arg Glu Ser Ala Leu Met Ser             420 425 430 Lys Leu Ser Asn Thr Glu Val Ser Lys Glu Asp Gln Gln Leu Gly Val         435 440 445 Ile Pro Ser Phe Asn His Phe Gln Pro Arg Glu Arg Asn Glu Val Ile     450 455 460 Glu Trp Glu Phe Leu Thr Gly Lys Leu Leu Tyr Ser Ala Ala Glu Asn 465 470 475 480 Gln Pro Pro Arg Gln Ser Leu Ser Ser Ile Leu Arg Thr Ala Leu Asp                 485 490 495 Asp Thr Val Leu Gln Val Met Glu Met Ile Asn Glu Asn Ala Lys Ser             500 505 510 Arg Gly Arg Leu Ile Asp Phe Lys Glu Ile Gln Tyr Gly Tyr Arg Arg         515 520 525 Val Asn Pro Met His Gly Val Glu Tyr Ile Leu Asp Leu Leu Leu Leu     530 535 540 Tyr Lys Arg His Lys Gly Arg Lys Leu Thr Val Pro Val Arg Arg His 545 550 555 560 Ala Tyr Leu Gln Gln Leu Phe Ser Lys Pro Phe Phe Arg Glu Thr Glu                 565 570 575 Glu Leu Asp Val Asn Ser Leu Val Glu Ser Ile Asn Ser Glu Thr Gln             580 585 590 Ser Phe Ser Phe Ile Ser Asn Ser Leu Lys Ile Leu Ser Ser Phe Gln         595 600 605 Gly Ala Lys Glu Met Gly Gly His Asn Glu Lys Lys Val His Ile Leu     610 615 620 Val Pro Leu Ile Gly Arg Tyr Asp Ile Phe Leu Arg Phe Met Glu Asn 625 630 635 640 Phe Glu Asn Met Cys Leu Ile Pro Lys Gln Asn Val Lys Leu Val Ile                 645 650 655 Ile Leu Phe Ser Arg Asp Ser Gly Gln Asp Ser Ser Lys His Ile Glu             660 665 670 Leu Ile Lys Gly Tyr Gln Asn Lys Tyr Pro Lys Ala Glu Met Thr Leu         675 680 685 Ile Pro Met Lys Gly Glu Phe Ser Arg Gly Leu Gly Leu Glu Met Ala     690 695 700 Ser Ala Gln Phe Asp Asn Asp Thr Leu Leu Leu Phe Cys Asp Val Asp 705 710 715 720 Leu Ile Phe Arg Glu Asp Phe Leu Gln Arg Cys Arg Asp Asn Thr Ile                 725 730 735 Gln Gly Gln Gln Val Tyr Tyr Pro Ile Ile Phe Ser Gln Tyr Asp Pro             740 745 750 Lys Val Thr Asn Gly Gly Asn Pro Pro Thr Asp Asp Tyr Phe Ile Phe         755 760 765 Ser Lys Lys Thr Gly Phe Trp Arg Asp Tyr Gly Tyr Gly Ile Thr Cys     770 775 780 Ile Tyr Lys Ser Asp Leu Leu Gly Ala Gly Gly Phe Asp Thr Ser Ile 785 790 795 800 Gln Gly Trp Gly Leu Glu Asp Val Asp Leu Tyr Asn Lys Val Ile Leu                 805 810 815 Ser Gly Leu Arg Pro Phe Arg Ser Gln Glu Val Gly Val Val His Ile             820 825 830 Phe His Pro Val His Cys Asp Pro Asn Leu Asp Pro Lys Gln Tyr Lys         835 840 845 Met Cys Leu Gly Ser Lys Ala Ser Thr Phe Ala Ser Thr Met Gln Leu     850 855 860 Ala Glu Leu Trp Leu Glu Lys His Leu Gly Val Arg Tyr Asn Arg Thr 865 870 875 880 Leu ser         <210> 5 <211> 684 <212> PRT <213> Homo sapiens <400> 5 Met Ser Ala Ile Pro Ala Glu Glu Ser Asp Gln Leu Leu Ile Arg Pro   1 5 10 15 Leu Gly Ala Gly Gln Glu Val Gly Arg Ser Cys Ile Ile Leu Glu Phe              20 25 30 Lys Gly Arg Lys Ile Met Leu Asp Cys Gly Ile His Pro Gly Leu Glu          35 40 45 Gly Met Asp Ala Leu Pro Tyr Ile Asp Leu Ile Asp Pro Ala Glu Ile      50 55 60 Asp Leu Leu Leu Ile Ser His Phe His Leu Asp His Cys Gly Ala Leu  65 70 75 80 Pro Trp Phe Leu Gln Lys Thr Ser Phe Lys Gly Arg Thr Phe Met Thr                  85 90 95 His Ala Thr Lys Ala Ile Tyr Arg Trp Leu Leu Ser Asp Tyr Val Lys             100 105 110 Val Ser Asn Ile Ser Ala Asp Asp Met Leu Tyr Thr Glu Thr Asp Leu         115 120 125 Glu Glu Ser Met Asp Lys Ile Glu Thr Ile Asn Phe His Glu Val Lys     130 135 140 Glu Val Ala Gly Ile Lys Phe Trp Cys Tyr His Ala Gly His Val Leu 145 150 155 160 Gly Ala Ala Met Phe Met Ile Glu Ile Ala Gly Val Lys Leu Leu Tyr                 165 170 175 Thr Gly Asp Phe Ser Arg Gln Glu Asp Arg His Leu Met Ala Ala Glu             180 185 190 Ile Pro Asn Ile Lys Pro Asp Ile Leu Ile Ile Glu Ser Thr Tyr Gly         195 200 205 Thr His Ile His Glu Lys Arg Glu Glu Arg Glu Ala Arg Phe Cys Asn     210 215 220 Thr Val His Asp Ile Val Asn Arg Gly Gly Arg Gly Leu Ile Pro Val 225 230 235 240 Phe Ala Leu Gly Arg Ala Gln Glu Leu Leu Leu Ile Leu Asp Glu Tyr                 245 250 255 Trp Gln Asn His Pro Glu Leu His Asp Ile Pro Ile Tyr Tyr Ala Ser             260 265 270 Ser Leu Ala Lys Lys Cys Met Ala Val Tyr Gln Thr Tyr Val Asn Ala         275 280 285 Met Asn Asp Lys Ile Arg Lys Gln Ile Asn Ile Asn Asn Pro Phe Val     290 295 300 Phe Lys His Ile Ser Asn Leu Lys Ser Met Asp His Phe Asp Asp Ile 305 310 315 320 Gly Pro Ser Val Val Met Ala Ser Pro Gly Met Met Gln Ser Gly Leu                 325 330 335 Ser Arg Glu Leu Phe Glu Ser Trp Cys Thr Asp Lys Arg Asn Gly Val             340 345 350 Ile Ile Ala Gly Tyr Cys Val Glu Gly Thr Leu Ala Lys His Ile Met         355 360 365 Ser Glu Pro Glu Glu Ile Thr Thr Met Ser Gly Gln Lys Leu Pro Leu     370 375 380 Lys Met Ser Val Asp Tyr Ile Ser Phe Ser Ala His Thr Asp Tyr Gln 385 390 395 400 Gln Thr Ser Glu Phe Ile Arg Ala Leu Lys Pro Pro His Val Ile Leu                 405 410 415 Val His Gly Glu Gln Asn Glu Met Ala Arg Leu Lys Ala Ala Leu Ile             420 425 430 Arg Glu Tyr Glu Asp Asn Asp Glu Val His Ile Glu Val His Asn Pro         435 440 445 Arg Asn Thr Glu Ala Val Thr Leu Asn Phe Arg Gly Glu Lys Leu Ala     450 455 460 Lys Val Met Gly Phe Leu Ala Asp Lys Lys Pro Glu Gln Gly Gln Arg 465 470 475 480 Val Ser Gly Ile Leu Val Lys Arg Asn Phe Asn Tyr His Ile Leu Ser                 485 490 495 Pro Cys Asp Leu Ser Asn Tyr Thr Asp Leu Ala Met Ser Thr Val Lys             500 505 510 Gln Thr Gln Ala Ile Pro Tyr Thr Gly Pro Phe Asn Leu Leu Cys Tyr         515 520 525 Gln Leu Gln Lys Leu Thr Gly Asp Val Glu Glu Leu Glu Ile Gln Glu     530 535 540 Lys Pro Ala Leu Lys Val Phe Lys Asn Ile Thr Val Ile Gln Glu Pro 545 550 555 560 Gly Met Val Val Leu Glu Trp Leu Ala Asn Pro Ser Asn Asp Met Tyr                 565 570 575 Ala Asp Thr Val Thr Thr Val Ile Leu Glu Val Gln Ser Asn Pro Lys             580 585 590 Ile Arg Lys Gly Ala Val Gln Lys Val Ser Lys Lys Leu Glu Met His         595 600 605 Val Tyr Ser Lys Arg Leu Glu Ile Met Leu Gln Asp Ile Phe Gly Glu     610 615 620 Asp Cys Val Ser Val Lys Asp Asp Ser Ile Leu Ser Val Thr Val Asp 625 630 635 640 Gly Lys Thr Ala Asn Leu Asn Leu Glu Thr Arg Thr Val Glu Cys Glu                 645 650 655 Glu Gly Ser Glu Asp Asp Glu Ser Leu Arg Glu Met Val Glu Leu Ala             660 665 670 Ala Gln Arg Leu Tyr Glu Ala Leu Thr Pro Val His         675 680 <210> 6 <211> 1523 <212> PRT <213> Homo sapiens <400> 6 Met Thr Ser Val Trp Lys Arg Leu Gln Arg Val Gly Lys Arg Ala Ala   1 5 10 15 Lys Phe Gln Phe Val Ala Cys Tyr His Glu Leu Val Leu Glu Cys Thr              20 25 30 Lys Lys Trp Gln Pro Asp Lys Leu Val Val Val Trp Thr Arg Arg Asn          35 40 45 Arg Arg Ile Cys Ser Lys Ala His Ser Trp Gln Pro Gly Ile Gln Asn      50 55 60 Pro Tyr Arg Gly Thr Val Val Trp Met Val Pro Glu Asn Val Asp Ile  65 70 75 80 Ser Val Thr Leu Tyr Arg Asp Pro His Val Asp Gln Tyr Glu Ala Lys                  85 90 95 Glu Trp Thr Phe Ile Ile Glu Asn Glu Ser Lys Gly Gln Arg Lys Val             100 105 110 Leu Ala Thr Ala Glu Val Asp Leu Ala Arg His Ala Gly Pro Val Pro         115 120 125 Val Gln Val Pro Val Arg Leu Arg Leu Lys Pro Lys Ser Val Lys Val     130 135 140 Val Gln Ala Glu Leu Ser Leu Thr Leu Ser Gly Val Leu Leu Arg Glu 145 150 155 160 Gly Arg Ala Thr Asp Asp Asp Met Gln Ser Leu Ala Ser Leu Met Ser                 165 170 175 Val Lys Pro Ser Asp Val Gly Asn Leu Asp Asp Phe Ala Glu Ser Asp             180 185 190 Glu Asp Glu Ala His Gly Pro Gly Ala Pro Glu Ala Arg Ala Arg Val         195 200 205 Pro Gln Pro Asp Pro Ser Arg Glu Leu Lys Thr Leu Cys Glu Glu Glu     210 215 220 Glu Glu Gly Gln Gly Arg Pro Gln Gln Ala Val Ala Ser Pro Ser Asn 225 230 235 240 Ala Glu Asp Thr Ser Pro Ala Pro Val Ser Ala Pro Ala Pro Pro Ala                 245 250 255 Arg Thr Ser Arg Gly Gln Gly Ser Glu Arg Ala Asn Glu Ala Gly Gly             260 265 270 Gln Val Gly Pro Glu Ala Pro Arg Pro Pro Glu Thr Ser Pro Glu Met         275 280 285 Arg Ser Ser Arg Gln Pro Ala Gln Asp Thr Ala Pro Thr Pro Ala Pro     290 295 300 Arg Leu Arg Lys Gly Ser Asp Ala Leu Arg Pro Pro Val Pro Gln Gly 305 310 315 320 Glu Asp Glu Val Pro Lys Ala Ser Gly Ala Pro Pro Ala Gly Leu Gly                 325 330 335 Ser Ala Arg Glu Thr Gln Ala Gln Ala Cys Pro Gln Glu Gly Thr Glu             340 345 350 Ala His Gly Ala Arg Leu Gly Pro Ser Ile Glu Asp Lys Gly Ser Gly         355 360 365 Asp Pro Phe Gly Arg Gln Arg Leu Lys Ala Glu Glu Met Asp Thr Glu     370 375 380 Asp Arg Pro Glu Ala Ser Gly Val Asp Thr Glu Pro Arg Ser Gly Gly 385 390 395 400 Arg Glu Ala Asn Thr Lys Arg Ser Gly Val Arg Ala Gly Glu Ala Glu                 405 410 415 Glu Ser Ser Ala Val Cys Gln Val Asp Ala Glu Gln Arg Ser Lys Val             420 425 430 Arg His Val Asp Thr Lys Gly Pro Glu Ala Thr Gly Val Met Pro Glu         435 440 445 Ala Arg Cys Arg Gly Thr Pro Glu Ala Pro Pro Arg Gly Ser Gln Gly     450 455 460 Arg Leu Gly Val Arg Thr Arg Asp Glu Ala Pro Ser Gly Leu Ser Leu 465 470 475 480 Pro Pro Ala Glu Pro Ala Gly His Ser Gly Gln Leu Gly Asp Leu Glu                 485 490 495 Gly Ala Arg Ala Ala Ala Gly Gln Glu Arg Glu Gly Ala Glu Val Arg             500 505 510 Gly Gly Ala Pro Gly Ile Glu Gly Thr Gly Leu Glu Gln Gly Pro Ser         515 520 525 Val Gly Ala Ile Ser Thr Arg Pro Gln Val Ser Ser Trp Gln Gly Ala     530 535 540 Leu Leu Ser Thr Ala Gln Gly Ala Ile Ser Arg Gly Leu Gly Gly Trp 545 550 555 560 Glu Ala Glu Ala Gly Gly Ser Gly Asp Leu Glu Thr Glu Thr Glu Val                 565 570 575 Val Gly Leu Glu Val Leu Gly Thr Gln Glu Lys Glu Val Glu Gly Ser             580 585 590 Gly Phe Pro Glu Thr Arg Thr Leu Glu Ile Glu Ile Leu Gly Ala Leu         595 600 605 Glu Lys Glu Ala Ala Arg Ser Arg Val Leu Glu Ser Glu Val Ala Gly     610 615 620 Thr Ala Gln Cys Glu Gly Leu Glu Thr Gln Glu Thr Glu Val Gly Val 625 630 635 640 Ile Glu Thr Pro Gly Thr Glu Thr Glu Val Leu Gly Thr Gln Lys Thr                 645 650 655 Glu Ala Gly Gly Ser Gly Val Leu Gln Thr Arg Thr Thr Ile Ala Glu             660 665 670 Thr Glu Val Leu Val Thr Gln Glu Ile Ser Gly Asp Leu Gly Pro Leu         675 680 685 Lys Ile Glu Asp Thr Ile Gln Ser Glu Met Leu Gly Thr Gln Glu Thr     690 695 700 Glu Val Glu Ala Ser Arg Val Pro Glu Ser Glu Ala Glu Gly Thr Glu 705 710 715 720 Ala Lys Ile Leu Gly Thr Gln Glu Ile Thr Ala Arg Asp Ser Gly Val                 725 730 735 Arg Glu Ile Glu Ala Glu Ile Ala Glu Ser Asp Ile Leu Val Ala Gln             740 745 750 Glu Ile Glu Val Gly Leu Leu Gly Val Leu Gly Ile Glu Thr Gly Ala         755 760 765 Ala Glu Gly Ala Ile Leu Gly Thr Gln Glu Ile Ala Ser Arg Asp Ser     770 775 780 Gly Val Pro Gly Leu Glu Ala Asp Thr Thr Gly Ile Gln Val Lys Glu 785 790 795 800 Val Gly Gly Ser Glu Val Pro Glu Ile Ala Thr Gly Thr Ala Glu Thr                 805 810 815 Glu Ile Leu Gly Thr Gln Glu Ile Ala Ser Arg Ser Ser Gly Val Pro             820 825 830 Gly Leu Glu Ser Glu Val Ala Gly Ala Gln Glu Thr Glu Val Gly Gly         835 840 845 Ser Gly Ile Ser Gly Pro Glu Ala Gly Met Ala Glu Ala Arg Val Leu     850 855 860 Met Thr Arg Lys Thr Glu Ile Ile Val Pro Glu Ala Glu Lys Glu Glu 865 870 875 880 Ala Gln Thr Ser Gly Val Gln Glu Ala Glu Thr Arg Val Gly Ser Ala                 885 890 895 Leu Lys Tyr Glu Ala Leu Arg Ala Pro Val Thr Gln Pro Arg Val Leu             900 905 910 Gly Ser Gln Glu Ala Lys Ala Glu Ile Ser Gly Val Gln Gly Ser Glu         915 920 925 Thr Gln Val Leu Arg Val Gln Glu Ala Glu Ala Gly Val Trp Gly Met     930 935 940 Ser Glu Gly Lys Ser Gly Ala Trp Gly Ala Gln Glu Ala Glu Met Lys 945 950 955 960 Val Leu Glu Ser Pro Glu Asn Lys Ser Gly Thr Phe Lys Ala Gln Glu                 965 970 975 Ala Glu Ala Gly Val Leu Gly Asn Glu Lys Gly Lys Glu Ala Glu Gly             980 985 990 Ser Leu Thr Glu Ala Ser Leu Pro Glu Ala Gln Val Ala Ser Gly Ala         995 1000 1005 Gly Ala Gly Ala Pro Arg Ala Ser Ser Pro Glu Lys Ala Glu Glu Asp    1010 1015 1020 Arg Arg Leu Pro Gly Ser Gln Ala Pro Pro Ala Leu Val Ser Ser Ser 1025 1030 1035 1040 Gln Ser Leu Leu Glu Trp Cys Gln Glu Val Thr Thr Gly Tyr Arg Gly                1045 1050 1055 Val Arg Ile Thr Asn Phe Thr Thr Ser Trp Arg Asn Gly Leu Ala Phe            1060 1065 1070 Cys Ala Ile Leu His Arg Phe Tyr Pro Asp Lys Ile Asp Tyr Ala Ser        1075 1080 1085 Leu Asp Pro Leu Asn Ile Lys Gln Asn Asn Lys Gln Ala Phe Asp Gly    1090 1095 1100 Phe Ala Ala Leu Gly Val Ser Arg Leu Leu Glu Pro Ala Asp Met Val 1105 1110 1115 1120 Leu Leu Ser Val Pro Asp Lys Leu Ile Val Met Thr Tyr Leu Cys Gln                1125 1130 1135 Ile Arg Ala Phe Cys Thr Gly Gln Glu Leu Gln Leu Val Gln Leu Glu            1140 1145 1150 Gly Gly Gly Gly Ala Gly Thr Tyr Arg Val Gly Ser Ala Gln Pro Ser        1155 1160 1165 Pro Pro Asp Asp Leu Asp Ala Gly Gly Leu Ala Gln Arg Leu Arg Gly    1170 1175 1180 His Gly Ala Glu Gly Pro Gln Glu Pro Lys Glu Ala Ala Asp Arg Ala 1185 1190 1195 1200 Asp Gly Ala Ala Pro Gly Val Ala Ser Arg Asn Ala Val Ala Gly Arg                1205 1210 1215 Ala Ser Lys Asp Gly Gly Ala Glu Ala Pro Arg Glu Ser Arg Pro Ala            1220 1225 1230 Glu Val Pro Ala Glu Gly Leu Val Asn Gly Ala Gly Ala Pro Gly Gly        1235 1240 1245 Gly Gly Val Arg Leu Arg Arg Pro Ser Val Asn Gly Glu Pro Gly Ser    1250 1255 1260 Val Pro Pro Pro Arg Ala His Gly Ser Phe Ser His Val Arg Asp Ala 1265 1270 1275 1280 Asp Leu Leu Lys Lys Arg Arg Ser Arg Leu Arg Asn Ser Ser Ser Phe                1285 1290 1295 Ser Met Asp Asp Pro Asp Ala Gly Ala Met Gly Ala Ala Ala Ala Glu            1300 1305 1310 Gly Gln Ala Pro Asp Pro Ser Pro Ala Pro Gly Pro Pro Thr Ala Ala        1315 1320 1325 Asp Ser Gln Gln Pro Pro Gly Gly Ser Ser Pro Ser Glu Glu Pro Pro    1330 1335 1340 Pro Ser Pro Gly Glu Glu Ala Gly Leu Gln Arg Phe Gln Asp Thr Ser 1345 1350 1355 1360 Gln Tyr Val Cys Ala Glu Leu Gln Ala Leu Glu Gln Glu Gln Arg Gln                1365 1370 1375 Ile Asp Gly Arg Ala Ala Glu Val Glu Met Gln Leu Arg Ser Leu Met            1380 1385 1390 Glu Ser Gly Ala Asn Lys Leu Gln Glu Glu Val Leu Ile Gln Glu Trp        1395 1400 1405 Phe Thr Leu Val Asn Lys Lys Asn Ala Leu Ile Arg Arg Gln Asp Gln    1410 1415 1420 Leu Gln Leu Leu Met Glu Glu Gln Asp Leu Glu Arg Arg Phe Glu Leu 1425 1430 1435 1440 Leu Ser Arg Glu Leu Arg Ala Met Leu Ala Ile Glu Asp Trp Gln Lys                1445 1450 1455 Thr Ser Ala Gln Gln His Arg Glu Gln Leu Leu Leu Glu Glu Leu Val            1460 1465 1470 Ser Leu Val Asn Gln Arg Asp Glu Leu Val Arg Asp Leu Asp His Lys        1475 1480 1485 Glu Arg Ile Ala Leu Glu Glu Asp Glu Arg Leu Glu Arg Gly Leu Glu    1490 1495 1500 Gln Arg Arg Arg Lys Leu Ser Arg Gln Leu Ser Arg Arg Glu Arg Cys 1505 1510 1515 1520 Val Leu Ser             <210> 7 <211> 347 <212> PRT <213> Homo sapiens <400> 7 Met Gly Asp Glu Leu Ala Pro Cys Pro Val Gly Thr Thr Ala Trp Pro   1 5 10 15 Ala Leu Ile Gln Leu Ile Ser Lys Thr Pro Cys Met Pro Gln Ala Ala              20 25 30 Ser Asn Thr Ser Leu Gly Leu Gly Asp Leu Arg Val Pro Ser Ser Met          35 40 45 Leu Tyr Trp Leu Phe Leu Pro Ser Ser Leu Leu Ala Ala Ala Thr Leu      50 55 60 Ala Val Ser Pro Leu Leu Leu Val Thr Ile Leu Arg Asn Gln Arg Leu  65 70 75 80 Arg Gln Glu Pro His Tyr Leu Leu Pro Ala Asn Ile Leu Leu Ser Asp                  85 90 95 Leu Ala Tyr Ile Leu Leu His Met Leu Ile Ser Ser Ser Ser Leu Gly             100 105 110 Gly Trp Glu Leu Gly Arg Met Ala Cys Gly Ile Leu Thr Asp Ala Val         115 120 125 Phe Ala Ala Cys Thr Ser Thr Ile Leu Ser Phe Thr Ala Ile Val Leu     130 135 140 His Thr Tyr Leu Ala Val Ile His Pro Leu Arg Tyr Leu Ser Phe Met 145 150 155 160 Ser His Gly Ala Ala Trp Lys Ala Val Ala Leu Ile Trp Leu Val Ala                 165 170 175 Cys Cys Phe Pro Thr Phe Leu Ile Trp Leu Ser Lys Trp Gln Asp Ala             180 185 190 Gln Leu Glu Glu Gln Gly Ala Ser Tyr Ile Leu Pro Pro Ser Met Gly         195 200 205 Thr Gln Pro Gly Cys Gly Leu Leu Val Ile Val Thr Tyr Thr Ser Ile     210 215 220 Leu Cys Val Leu Phe Leu Cys Thr Ala Leu Ile Ala Asn Cys Phe Trp 225 230 235 240 Arg Ile Tyr Ala Glu Ala Lys Thr Ser Gly Ile Trp Gly Gln Gly Tyr                 245 250 255 Ser Arg Ala Arg Gly Thr Leu Leu Ile His Ser Val Leu Ile Thr Leu             260 265 270 Tyr Val Ser Thr Gly Val Val Phe Ser Leu Asp Met Val Leu Thr Arg         275 280 285 Tyr His His Ile Asp Ser Gly Thr His Thr Trp Leu Leu Ala Ala Asn     290 295 300 Ser Glu Val Leu Met Met Leu Pro Arg Ala Met Leu Thr Tyr Leu Tyr 305 310 315 320 Leu Leu Arg Tyr Arg Gln Leu Leu Gly Met Val Arg Gly His Leu Pro                 325 330 335 Ser Arg Arg His Gln Ala Ile Phe Thr Ile Ser             340 345 <210> 8 <211> 798 <212> PRT <213> Homo sapiens <400> 8 Met Val Ala Leu Pro Met Val Leu Val Leu Leu Leu Val Leu Ser Arg   1 5 10 15 Gly Glu Ser Glu Leu Asp Ala Lys Ile Pro Ser Thr Gly Asp Ala Thr              20 25 30 Glu Trp Arg Asn Pro His Leu Ser Met Leu Gly Ser Cys Gln Pro Ala          35 40 45 Pro Ser Cys Gln Lys Cys Ile Leu Ser His Pro Ser Cys Ala Trp Cys      50 55 60 Lys Gln Leu Asn Phe Thr Ala Ser Gly Glu Ala Glu Ala Arg Arg Cys  65 70 75 80 Ala Arg Arg Glu Glu Leu Leu Ala Arg Gly Cys Pro Leu Glu Glu Leu                  85 90 95 Glu Glu Pro Arg Gly Gln Gln Glu Val Leu Gln Asp Gln Pro Leu Ser             100 105 110 Gln Gly Ala Arg Gly Glu Gly Ala Thr Gln Leu Ala Pro Gln Arg Val         115 120 125 Arg Val Thr Leu Arg Pro Gly Glu Pro Gln Gln Leu Gln Val Arg Phe     130 135 140 Leu Arg Ala Glu Gly Tyr Pro Val Asp Leu Tyr Tyr Leu Met Asp Leu 145 150 155 160 Ser Tyr Ser Met Lys Asp Asp Leu Glu Arg Val Arg Gln Leu Gly His                 165 170 175 Ala Leu Leu Val Arg Leu Gln Glu Val Thr His Ser Val Arg Ile Gly             180 185 190 Phe Gly Ser Phe Val Asp Lys Thr Val Leu Pro Phe Val Ser Thr Val         195 200 205 Pro Ser Lys Leu Arg His Pro Cys Pro Thr Arg Leu Glu Arg Cys Gln     210 215 220 Ser Pro Phe Ser Phe His His Val Leu Ser Leu Thr Gly Asp Ala Gln 225 230 235 240 Ala Phe Glu Arg Glu Val Gly Arg Gln Ser Val Ser Gly Asn Leu Asp                 245 250 255 Ser Pro Glu Gly Gly Phe Asp Ala Ile Leu Gln Ala Ala Leu Cys Gln             260 265 270 Glu Gln Ile Gly Trp Arg Asn Val Ser Arg Leu Leu Val Phe Thr Ser         275 280 285 Asp Asp Thr Phe His Thr Ala Gly Asp Gly Lys Leu Gly Gly Ile Phe     290 295 300 Met Pro Ser Asp Gly His Cys His Leu Asp Ser Asn Gly Leu Tyr Ser 305 310 315 320 Arg Ser Thr Glu Phe Asp Tyr Pro Ser Val Gly Gln Val Ala Gln Ala                 325 330 335 Leu Ser Ala Ala Asn Ile Gln Pro Ile Phe Ala Val Thr Ser Ala Ala             340 345 350 Leu Pro Val Tyr Gln Glu Leu Ser Lys Leu Ile Pro Lys Ser Ala Val         355 360 365 Gly Glu Leu Ser Glu Asp Ser Ser Asn Val Val Gln Leu Ile Met Asp     370 375 380 Ala Tyr Asn Ser Leu Ser Ser Thr Val Thr Leu Glu His Ser Ser Leu 385 390 395 400 Pro Pro Gly Val His Ile Ser Tyr Glu Ser Gln Cys Glu Gly Pro Glu                 405 410 415 Lys Arg Glu Gly Lys Ala Glu Asp Arg Gly Gln Cys Asn His Val Arg             420 425 430 Ile Asn Gln Thr Val Thr Phe Trp Val Ser Leu Gln Ala Thr His Cys         435 440 445 Leu Pro Glu Pro His Leu Leu Arg Leu Arg Ala Leu Gly Phe Ser Glu     450 455 460 Glu Leu Ile Val Glu Leu His Thr Leu Cys Asp Cys Asn Cys Ser Asp 465 470 475 480 Thr Gln Pro Gln Ala Pro His Cys Ser Asp Gly Gln Gly His Leu Gln                 485 490 495 Cys Gly Val Cys Ser Cys Ala Pro Gly Arg Leu Gly Arg Leu Cys Glu             500 505 510 Cys Ser Val Ala Glu Leu Ser Ser Pro Asp Leu Glu Ser Gly Cys Arg         515 520 525 Ala Pro Asn Gly Thr Gly Pro Leu Cys Ser Gly Lys Gly His Cys Gln     530 535 540 Cys Gly Arg Cys Ser Cys Ser Gly Gln Ser Ser Gly His Leu Cys Glu 545 550 555 560 Cys Asp Asp Ala Ser Cys Glu Arg His Glu Gly Ile Leu Cys Gly Gly                 565 570 575 Phe Gly Arg Cys Gln Cys Gly Val Cys His Cys His Ala Asn Arg Thr             580 585 590 Gly Arg Ala Cys Glu Cys Ser Gly Asp Met Asp Ser Cys Ile Ser Pro         595 600 605 Glu Gly Gly Leu Cys Ser Gly His Gly Arg Cys Lys Cys Asn Arg Cys     610 615 620 Gln Cys Leu Asp Gly Tyr Tyr Gly Ala Leu Cys Asp Gln Cys Pro Gly 625 630 635 640 Cys Lys Thr Pro Cys Glu Arg His Arg Asp Cys Ala Glu Cys Gly Ala                 645 650 655 Phe Arg Thr Gly Pro Leu Ala Thr Asn Cys Ser Thr Ala Cys Ala His             660 665 670 Thr Asn Val Thr Leu Ala Leu Ala Pro Ile Leu Asp Asp Gly Trp Cys         675 680 685 Lys Glu Arg Thr Leu Asp Asn Gln Leu Phe Phe Phe Leu Val Glu Asp     690 695 700 Asp Ala Arg Gly Thr Val Val Leu Arg Val Arg Pro Gln Glu Lys Gly 705 710 715 720 Ala Asp His Thr Gln Ala Ile Val Leu Gly Cys Val Gly Gly Ile Val                 725 730 735 Ala Val Gly Leu Gly Leu Val Leu Ala Tyr Arg Leu Ser Val Glu Ile             740 745 750 Tyr Asp Arg Arg Glu Tyr Ser Arg Phe Glu Lys Glu Gln Gln Gln Leu         755 760 765 Asn Trp Lys Gln Asp Ser Asn Pro Leu Tyr Lys Ser Ala Ile Thr Thr     770 775 780 Thr Ile Asn Pro Arg Phe Gln Glu Ala Asp Ser Pro Thr Leu 785 790 795 <210> 9 <211> 600 <212> PRT <213> Homo sapiens <400> 9 Met Val Leu Ile Leu Gly Arg Arg Leu Asn Arg Glu Asp Leu Gly Val   1 5 10 15 Arg Asp Ser Pro Ala Thr Lys Arg Lys Val Phe Glu Met Asp Pro Lys              20 25 30 Ser Leu Thr Gly His Glu Phe Phe Asp Phe Ser Ser Gly Ser Ser His          35 40 45 Ala Glu Asn Ile Leu Gln Ile Phe Asn Glu Phe Arg Asp Ser Arg Leu      50 55 60 Phe Thr Asp Val Ile Ile Cys Val Glu Gly Lys Glu Phe Pro Cys His  65 70 75 80 Arg Ala Val Leu Ser Ala Cys Ser Ser Tyr Phe Arg Ala Met Phe Cys                  85 90 95 Asn Asp His Arg Glu Ser Arg Glu Met Leu Val Glu Ile Asn Gly Ile             100 105 110 Leu Ala Glu Ala Met Glu Cys Phe Leu Gln Tyr Val Tyr Thr Gly Lys         115 120 125 Val Lys Ile Thr Thr Glu Asn Val Gln Tyr Leu Phe Glu Thr Ser Ser     130 135 140 Leu Phe Gln Ile Ser Val Leu Arg Asp Ala Cys Ala Lys Phe Leu Glu 145 150 155 160 Glu Gln Leu Asp Pro Cys Asn Cys Leu Gly Ile Gln Arg Phe Ala Asp                 165 170 175 Thr His Ser Leu Lys Thr Leu Phe Thr Lys Cys Lys Asn Phe Ala Leu             180 185 190 Gln Thr Phe Glu Asp Val Ser Gln His Glu Glu Phe Leu Glu Leu Asp         195 200 205 Lys Asp Glu Leu Ile Asp Tyr Ile Cys Ser Asp Glu Leu Val Ile Gly     210 215 220 Lys Glu Glu Met Val Phe Glu Ala Val Met Arg Trp Val Tyr Arg Ala 225 230 235 240 Val Asp Leu Arg Arg Pro Leu Leu His Glu Leu Leu Thr His Val Arg                 245 250 255 Leu Pro Leu Leu His Pro Asn Tyr Phe Val Gln Thr Val Glu Val Asp             260 265 270 Gln Leu Ile Gln Asn Ser Pro Glu Cys Tyr Gln Leu Leu His Glu Ala         275 280 285 Arg Arg Tyr His Ile Leu Gly Asn Glu Met Met Ser Pro Arg Thr Arg     290 295 300 Pro Arg Arg Ser Thr Gly Tyr Ser Glu Val Ile Val Val Val Gly Gly 305 310 315 320 Cys Glu Arg Val Gly Gly Phe Asn Leu Pro Tyr Thr Glu Cys Tyr Asp                 325 330 335 Pro Val Thr Gly Glu Trp Lys Ser Leu Ala Lys Leu Pro Glu Phe Thr             340 345 350 Lys Ser Glu Tyr Ala Val Cys Ala Leu Arg Asn Asp Ile Leu Val Ser         355 360 365 Gly Gly Arg Ile Asn Ser Arg Asp Val Trp Ile Tyr Asn Ser Gln Leu     370 375 380 Asn Ile Trp Ile Arg Val Ala Ser Leu Asn Lys Gly Arg Trp Arg His 385 390 395 400 Lys Met Ala Val Leu Leu Gly Lys Val Tyr Val Val Gly Gly Tyr Asp                 405 410 415 Gly Gln Asn Arg Leu Ser Ser Val Glu Cys Tyr Asp Ser Phe Ser Asn             420 425 430 Arg Trp Thr Glu Val Ala Pro Leu Lys Glu Ala Val Ser Ser Pro Ala         435 440 445 Val Thr Ser Cys Val Gly Lys Leu Phe Val Ile Gly Gly Gly Pro Asp     450 455 460 Asp Asn Thr Cys Ser Asp Lys Val Gln Ser Tyr Asp Pro Glu Thr Asn 465 470 475 480 Ser Trp Leu Leu Arg Ala Ala Ile Pro Ile Ala Lys Arg Cys Ile Thr                 485 490 495 Ala Val Ser Leu Asn Asn Leu Ile Tyr Val Ala Gly Gly Leu Thr Lys             500 505 510 Ala Ile Tyr Cys Tyr Asp Pro Val Glu Asp Tyr Trp Met His Val Gln         515 520 525 Asn Thr Phe Ser Arg Gln Glu Asn Cys Gly Met Ser Val Cys Asn Gly     530 535 540 Lys Ile Tyr Ile Leu Gly Gly Arg Arg Glu Asn Gly Glu Ala Thr Asp 545 550 555 560 Thr Ile Leu Cys Tyr Asp Pro Ala Thr Ser Ile Ile Thr Gly Val Ala                 565 570 575 Ala Met Pro Arg Pro Val Ser Tyr His Gly Cys Val Thr Ile His Arg             580 585 590 Tyr Asn Glu Lys Cys Phe Lys Leu         595 600 <210> 10 <211> 753 <212> PRT <213> Homo sapiens <400> 10 Met Arg Pro Val Ser Val Trp Gln Trp Ser Pro Trp Gly Leu Leu Leu   1 5 10 15 Cys Leu Leu Cys Ser Ser Cys Leu Gly Ser Pro Ser Pro Ser Thr Gly              20 25 30 Pro Glu Lys Lys Ala Gly Ser Gln Gly Leu Arg Phe Arg Leu Ala Gly          35 40 45 Phe Pro Arg Lys Pro Tyr Glu Gly Arg Val Glu Ile Gln Arg Ala Gly      50 55 60 Glu Trp Gly Thr Ile Cys Asp Asp Asp Phe Thr Leu Gln Ala Ala His  65 70 75 80 Ile Leu Cys Arg Glu Leu Gly Phe Thr Glu Ala Thr Gly Trp Thr His                  85 90 95 Ser Ala Lys Tyr Gly Pro Gly Thr Gly Arg Ile Trp Leu Asp Asn Leu             100 105 110 Ser Cys Ser Gly Thr Glu Gln Ser Val Thr Glu Cys Ala Ser Arg Gly         115 120 125 Trp Gly Asn Ser Asp Cys Thr His Asp Glu Asp Ala Gly Val Ile Cys     130 135 140 Lys Asp Gln Arg Leu Pro Gly Phe Ser Asp Ser Asn Val Ile Glu Val 145 150 155 160 Glu His His Leu Gln Val Glu Glu Val Arg Ile Arg Pro Ala Val Gly                 165 170 175 Trp Gly Arg Arg Pro Leu Pro Val Thr Glu Gly Leu Val Glu Val Arg             180 185 190 Leu Pro Asp Gly Trp Ser Gln Val Cys Asp Lys Gly Trp Ser Ala His         195 200 205 Asn Ser His Val Val Cys Gly Met Leu Gly Phe Pro Ser Glu Lys Arg     210 215 220 Val Asn Ala Ala Phe Tyr Arg Leu Leu Ala Gln Arg Gln Gln His Ser 225 230 235 240 Phe Gly Leu His Gly Val Ala Cys Val Gly Thr Glu Ala His Leu Ser                 245 250 255 Leu Cys Ser Leu Glu Phe Tyr Arg Ala Asn Asp Thr Ala Arg Cys Pro             260 265 270 Gly Gly Gly Pro Ala Val Val Ser Cys Val Pro Gly Pro Val Tyr Ala         275 280 285 Ala Ser Ser Gly Gln Lys Lys Gln Gln Gln Ser Lys Pro Gln Gly Glu     290 295 300 Ala Arg Val Arg Leu Lys Gly Gly Ala His Pro Gly Glu Gly Arg Val 305 310 315 320 Glu Val Leu Lys Ala Ser Thr Trp Gly Thr Val Cys Asp Arg Lys Trp                 325 330 335 Asp Leu His Ala Ala Ser Val Val Cys Arg Glu Leu Gly Phe Gly Ser             340 345 350 Ala Arg Glu Ala Leu Ser Gly Ala Arg Met Gly Gln Gly Met Gly Ala         355 360 365 Ile His Leu Ser Glu Val Arg Cys Ser Gly Gln Glu Leu Ser Leu Trp     370 375 380 Lys Cys Pro His Lys Asn Ile Thr Ala Glu Asp Cys Ser His Ser Gln 385 390 395 400 Asp Ala Gly Val Arg Cys Asn Leu Pro Tyr Thr Gly Ala Glu Thr Arg                 405 410 415 Ile Arg Leu Ser Gly Gly Arg Ser Gln His Glu Gly Arg Val Glu Val             420 425 430 Gln Ile Gly Gly Pro Gly Pro Leu Arg Trp Gly Leu Ile Cys Gly Asp         435 440 445 Asp Trp Gly Thr Leu Glu Ala Met Val Ala Cys Arg Gln Leu Gly Leu     450 455 460 Gly Tyr Ala Asn His Gly Leu Gln Glu Thr Trp Tyr Trp Asp Ser Gly 465 470 475 480 Asn Ile Thr Glu Val Val Met Ser Gly Val Arg Cys Thr Gly Thr Glu                 485 490 495 Leu Ser Leu Asp Gln Cys Ala His His Gly Thr His Ile Thr Cys Lys             500 505 510 Arg Thr Gly Thr Arg Phe Thr Ala Gly Val Ile Cys Ser Glu Thr Ala         515 520 525 Ser Asp Leu Leu Leu His Ser Ala Leu Val Gln Glu Thr Ala Tyr Ile     530 535 540 Glu Asp Arg Pro Leu His Met Leu Tyr Cys Ala Ala Glu Glu Asn Cys 545 550 555 560 Leu Ala Ser Ser Ala Arg Ser Ala Asn Trp Pro Tyr Gly His Arg Arg                 565 570 575 Leu Leu Arg Phe Ser Ser Gln Ile His Asn Leu Gly Arg Ala Asp Phe             580 585 590 Arg Pro Lys Ala Gly Arg His Ser Trp Val Trp His Glu Cys His Gly         595 600 605 His Tyr His Ser Met Asp Ile Phe Thr His Tyr Asp Ile Leu Thr Pro     610 615 620 Asn Gly Thr Lys Val Ala Glu Gly His Lys Ala Ser Phe Cys Leu Glu 625 630 635 640 Asp Thr Glu Cys Gln Glu Asp Val Ser Lys Arg Tyr Glu Cys Ala Asn                 645 650 655 Phe Gly Glu Gln Gly Ile Thr Val Gly Cys Trp Asp Leu Tyr Arg His             660 665 670 Asp Ile Asp Cys Gln Trp Ile Asp Ile Thr Asp Val Lys Pro Gly Asn         675 680 685 Tyr Ile Leu Gln Val Val Ile Asn Pro Asn Phe Glu Val Ala Glu Ser     690 695 700 Asp Phe Thr Asn Asn Ala Met Lys Cys Asn Cys Lys Tyr Asp Gly His 705 710 715 720 Arg Ile Trp Val His Asn Cys His Ile Gly Asp Ala Phe Ser Glu Glu                 725 730 735 Ala Asn Arg Arg Phe Glu Arg Tyr Pro Gly Gln Thr Ser Asn Gln Ile             740 745 750 Ile     <210> 11 <211> 416 <212> PRT <213> Homo sapiens <400> 11 Met Glu Ala Thr Gly Ile Ser Leu Ala Ser Gln Leu Lys Val Pro Pro   1 5 10 15 Tyr Ala Ser Glu Asn Gln Thr Cys Arg Asp Gln Glu Lys Glu Tyr Tyr              20 25 30 Glu Pro Gln His Arg Ile Cys Cys Ser Arg Cys Pro Pro Gly Thr Tyr          35 40 45 Val Ser Ala Lys Cys Ser Arg Ile Arg Asp Thr Val Cys Ala Thr Cys      50 55 60 Ala Glu Asn Ser Tyr Asn Glu His Trp Asn Tyr Leu Thr Ile Cys Gln  65 70 75 80 Leu Cys Arg Pro Cys Asp Pro Val Met Gly Leu Glu Glu Ile Ala Pro                  85 90 95 Cys Thr Ser Lys Arg Lys Thr Gln Cys Arg Cys Gln Pro Gly Met Phe             100 105 110 Cys Ala Ala Trp Ala Leu Glu Cys Thr His Cys Glu Leu Leu Ser Asp         115 120 125 Cys Pro Pro Gly Thr Glu Ala Glu Leu Lys Asp Glu Val Gly Lys Gly     130 135 140 Asn Asn His Cys Val Pro Cys Lys Ala Gly His Phe Gln Asn Thr Ser 145 150 155 160 Ser Pro Ser Ala Arg Cys Gln Pro His Thr Arg Cys Glu Asn Gln Gly                 165 170 175 Leu Val Glu Ala Ala Pro Gly Thr Ala Gln Ser Asp Thr Thr Cys Lys             180 185 190 Asn Pro Leu Glu Pro Leu Pro Pro Glu Met Ser Gly Thr Met Leu Met         195 200 205 Leu Ala Val Leu Leu Pro Leu Ala Phe Phe Leu Leu Leu Ala Thr Val     210 215 220 Phe Ser Cys Ile Trp Lys Ser His Pro Ser Leu Cys Arg Lys Leu Gly 225 230 235 240 Ser Leu Leu Lys Arg Arg Pro Gln Gly Glu Gly Pro Asn Pro Val Ala                 245 250 255 Gly Ser Trp Glu Pro Pro Lys Ala His Pro Tyr Phe Pro Asp Leu Val             260 265 270 Gln Pro Leu Leu Pro Ile Ser Gly Asp Val Ser Pro Val Ser Thr Gly         275 280 285 Leu Pro Ala Ala Pro Val Leu Glu Ala Gly Val Pro Gln Gln Gln Ser     290 295 300 Pro Leu Asp Leu Thr Arg Glu Pro Gln Leu Glu Pro Gly Glu Gln Ser 305 310 315 320 Gln Val Ala His Gly Thr Asn Gly Ile His Val Thr Gly Gly Ser Met                 325 330 335 Thr Ile Thr Gly Asn Ile Tyr Ile Tyr Asn Gly Pro Val Leu Gly Gly             340 345 350 Pro Pro Gly Pro Gly Asp Leu Pro Ala Thr Pro Glu Pro Pro Tyr Pro         355 360 365 Ile Pro Glu Glu Gly Asp Pro Gly Pro Pro Gly Leu Ser Thr Pro His     370 375 380 Gln Glu Asp Gly Lys Ala Trp His Leu Ala Glu Thr Glu His Cys Gly 385 390 395 400 Ala Thr Pro Ser Asn Arg Gly Pro Arg Asn Gln Phe Ile Thr His Asp                 405 410 415 <210> 12 <211> 389 <212> PRT <213> Homo sapiens <400> 12 Met Val Ile His Ser Gln Leu Lys Lys Ile Gln Gly Ala Ser Glu Arg   1 5 10 15 Met Gly Asp Thr Thr Arg Gln Arg Ile Lys Phe Ser Asp Asp Arg Val              20 25 30 Cys Lys Ser His Leu Leu Asn Cys Cys Pro His Asp Val Leu Ser Gly          35 40 45 Thr Arg Met Asp Leu Gly Glu Cys Leu Lys Val His Asp Leu Ala Leu      50 55 60 Arg Ala Asp Tyr Glu Ile Ala Ser Lys Glu Gln Asp Phe Phe Phe Glu  65 70 75 80 Leu Asp Ala Met Asp His Leu Gln Ser Phe Ile Ala Asp Cys Asp Arg                  85 90 95 Arg Thr Glu Val Ala Lys Lys Arg Leu Ala Glu Thr Gln Glu Glu Ile             100 105 110 Ser Ala Glu Val Ala Ala Lys Ala Glu Arg Val His Glu Leu Asn Glu         115 120 125 Glu Ile Gly Lys Leu Leu Ala Lys Val Glu Gln Leu Gly Ala Glu Gly     130 135 140 Asn Val Glu Glu Ser Gln Lys Val Met Asp Glu Val Glu Lys Ala Arg 145 150 155 160 Ala Lys Lys Arg Glu Ala Glu Glu Val Tyr Arg Asn Ser Met Pro Ala                 165 170 175 Ser Ser Phe Gln Gln Gln Lys Leu Arg Val Cys Glu Val Cys Ser Ala             180 185 190 Tyr Leu Gly Leu His Asp Asn Asp Arg Arg Leu Ala Asp His Phe Gly         195 200 205 Gly Lys Leu His Leu Gly Phe Ile Glu Ile Arg Glu Lys Leu Glu Glu     210 215 220 Leu Lys Arg Val Val Ala Glu Lys Gln Glu Lys Arg Asn Gln Glu Arg 225 230 235 240 Leu Lys Arg Arg Glu Glu Arg Glu Arg Glu Glu Arg Glu Lys Leu Arg                 245 250 255 Arg Ser Arg Ser His Ser Lys Asn Pro Lys Arg Ser Arg Ser Arg Glu             260 265 270 His Arg Arg His Arg Ser Arg Ser Met Ser Arg Glu Arg Lys Arg Arg         275 280 285 Thr Arg Ser Lys Ser Arg Glu Lys Arg His Arg His Arg Ser Arg Ser     290 295 300 Ser Ser Arg Ser Arg Ser Arg Ser His Gln Arg Ser Arg His Ser Ser 305 310 315 320 Arg Asp Arg Ser Arg Glu Arg Ser Lys Arg Arg Ser Ser Lys Glu Arg                 325 330 335 Phe Arg Asp Gln Asp Leu Ala Ser Cys Asp Arg Asp Arg Ser Ser Arg             340 345 350 Asp Arg Ser Pro Arg Asp Arg Asp Arg Lys Asp Lys Lys Arg Ser Tyr         355 360 365 Glu Ser Ala Asn Gly Arg Ser Glu Asp Arg Arg Ser Ser Glu Glu Arg     370 375 380 Glu Ala Gly Glu Ile 385 <210> 13 <211> 535 <212> PRT <213> Homo sapiens <400> 13 Met Thr Pro Leu Val Ser Arg Leu Ser Arg Leu Trp Ala Ile Met Arg   1 5 10 15 Lys Pro Arg Ala Ala Val Gly Ser Gly His Arg Lys Gln Ala Ala Ser              20 25 30 Gln Glu Gly Arg Gln Lys His Ala Lys Asn Asn Ser Gln Ala Lys Pro          35 40 45 Ser Ala Cys Asp Gly Leu Ala Arg Gln Pro Glu Glu Val Val Leu Gln      50 55 60 Ala Ser Val Ser Ser Tyr His Leu Phe Arg Asp Val Ala Glu Val Thr  65 70 75 80 Ala Phe Arg Gly Ser Leu Leu Ser Trp Tyr Asp Gln Glu Lys Arg Asp                  85 90 95 Leu Pro Trp Arg Arg Arg Arla Alu Glu Asp Glu Met Asp Leu Asp Arg Arg             100 105 110 Ala Tyr Ala Val Trp Val Ser Glu Val Met Leu Gln Gln Thr Gln Val         115 120 125 Ala Thr Val Ile Asn Tyr Tyr Thr Gly Trp Met Gln Lys Trp Pro Thr     130 135 140 Leu Gln Asp Leu Ala Ser Ala Ser Leu Glu Glu Val Asn Gln Leu Trp 145 150 155 160 Ala Gly Leu Gly Tyr Tyr Ser Arg Gly Arg Arg Leu Gln Glu Gly Ala                 165 170 175 Arg Lys Val Val Glu Glu Leu Gly Gly His Met Pro Arg Thr Ala Glu             180 185 190 Thr Leu Gln Gln Leu Leu Pro Gly Val Gly Arg Tyr Thr Ala Gly Ala         195 200 205 Ile Ala Ser Ile Ala Phe Gly Gln Ala Thr Gly Val Val Asp Gly Asn     210 215 220 Val Ala Arg Val Leu Cys Arg Val Arg Ala Ile Gly Ala Asp Pro Ser 225 230 235 240 Ser Thr Leu Val Ser Gln Gln Leu Trp Gly Leu Ala Gln Gln Leu Val                 245 250 255 Asp Pro Ala Arg Pro Gly Asp Phe Asn Gln Ala Ala Met Glu Leu Gly             260 265 270 Ala Thr Val Cys Thr Pro Gln Arg Pro Leu Cys Ser Gln Cys Pro Val         275 280 285 Glu Ser Leu Cys Arg Ala Arg Gln Arg Val Glu Gln Glu Gln Leu Leu     290 295 300 Ala Ser Gly Ser Leu Ser Gly Ser Pro Asp Val Glu Glu Cys Ala Pro 305 310 315 320 Asn Thr Gly Gln Cys His Leu Cys Leu Pro Pro Ser Glu Pro Trp Asp                 325 330 335 Gln Thr Leu Gly Val Val Asn Phe Pro Arg Lys Ala Ser Arg Lys Pro             340 345 350 Pro Arg Glu Glu Ser Ser Ala Thr Cys Val Leu Glu Gln Pro Gly Ala         355 360 365 Leu Gly Ala Gln Ile Leu Leu Val Gln Arg Pro Asn Ser Gly Leu Leu     370 375 380 Ala Gly Leu Trp Glu Phe Pro Ser Val Thr Trp Glu Pro Ser Glu Gln 385 390 395 400 Leu Gln Arg Lys Ala Leu Leu Gln Glu Leu Gln Arg Trp Ala Gly Pro                 405 410 415 Leu Pro Ala Thr His Leu Arg His Leu Gly Glu Val Val His Thr Phe             420 425 430 Ser His Ile Lys Leu Thr Tyr Gln Val Tyr Gly Leu Ala Leu Glu Gly         435 440 445 Gln Thr Pro Val Thr Thr Val Pro Pro Gly Ala Arg Trp Leu Thr Gln     450 455 460 Glu Glu Phe His Thr Ala Ala Val Ser Thr Ala Met Lys Lys Val Phe 465 470 475 480 Arg Val Tyr Gln Gly Gln Gln Pro Gly Thr Cys Met Gly Ser Lys Arg                 485 490 495 Ser Gln Val Ser Ser Pro Cys Ser Arg Lys Lys Pro Arg Met Gly Gln             500 505 510 Gln Val Leu Asp Asn Phe Phe Arg Ser His Ile Ser Thr Asp Ala His         515 520 525 Ser Leu Asn Ser Ala Ala Gln     530 535 <210> 14 <211> 310 <212> PRT <213> Homo sapiens <400> 14 Met Asp Trp Glu Asn Cys Ser Ser Leu Thr Asp Phe Phe Leu Leu Gly   1 5 10 15 Ile Thr Asn Asn Pro Glu Met Lys Val Thr Leu Phe Ala Val Phe Leu              20 25 30 Ala Val Tyr Ile Ile Asn Phe Ser Ala Asn Leu Gly Met Ile Val Leu          35 40 45 Ile Arg Met Asp Tyr Gln Leu His Thr Pro Met Tyr Phe Phe Leu Ser      50 55 60 His Leu Ser Phe Cys Asp Leu Cys Tyr Ser Thr Ala Thr Gly Pro Lys  65 70 75 80 Met Leu Val Asp Leu Leu Ala Lys Asn Lys Ser Ile Pro Phe Tyr Gly                  85 90 95 Cys Ala Leu Gln Phe Leu Val Phe Cys Ile Phe Ala Asp Ser Glu Cys             100 105 110 Leu Leu Leu Ser Val Met Ala Phe Asp Arg Tyr Lys Ala Ile Ile Asn         115 120 125 Pro Leu Leu Tyr Thr Val Asn Met Ser Ser Arg Val Cys Tyr Leu Leu     130 135 140 Leu Thr Gly Val Tyr Leu Val Gly Ile Ala Asp Ala Leu Ile His Met 145 150 155 160 Thr Leu Ala Phe Arg Leu Cys Phe Cys Gly Ser Asn Glu Ile Asn His                 165 170 175 Phe Phe Cys Asp Ile Pro Pro Leu Leu Leu Leu Ser Arg Ser Asp Thr             180 185 190 Gln Val Asn Glu Leu Val Leu Phe Thr Val Phe Gly Phe Ile Glu Leu         195 200 205 Ser Thr Ile Ser Gly Val Phe Ile Ser Tyr Cys Tyr Ile Ile Leu Ser     210 215 220 Val Leu Glu Ile His Ser Ala Glu Gly Arg Phe Lys Ala Leu Ser Thr 225 230 235 240 Cys Thr Ser His Leu Ser Ala Val Ala Ile Phe Gln Gly Thr Leu Leu                 245 250 255 Phe Met Tyr Phe Arg Pro Ser Ser Ser Tyr Ser Leu Asp Gln Asp Lys             260 265 270 Met Thr Ser Leu Phe Tyr Thr Leu Val Val Pro Met Leu Asn Pro Leu         275 280 285 Ile Tyr Ser Leu Arg Asn Lys Asp Val Lys Glu Ala Leu Lys Lys Leu     290 295 300 Lys Asn Lys Ile Leu Phe 305 310 <210> 15 <211> 187 <212> PRT <213> Homo sapiens <400> 15 Met Val Cys Ser Pro Val Thr Leu Arg Ile Ala Pro Pro Asp Arg Arg   1 5 10 15 Phe Ser Arg Ser Ala Ile Pro Glu Gln Ile Ile Ser Ser Thr Leu Ser              20 25 30 Ser Pro Ser Ser Asn Ala Pro Asp Pro Cys Ala Lys Glu Thr Val Leu          35 40 45 Ser Ala Leu Lys Glu Lys Lys Lys Lys Arg Thr Val Glu Glu Glu Asp      50 55 60 Gln Ile Phe Leu Asp Gly Gln Glu Asn Lys Arg Ser Cys Leu Val Asp  65 70 75 80 Gly Leu Thr Asp Ala Ser Ser Ala Phe Lys Val Pro Arg Pro Gly Pro                  85 90 95 Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn Asp Ser             100 105 110 Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu Ala Glu         115 120 125 Gln Asp Pro Asp Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys Pro Ser     130 135 140 Asn Ser Trp Phe Pro Val Glu Gly Leu Ala Asp Ile Cys Gln Cys Cys 145 150 155 160 Asn Lys Gly Asp Cys Gly Thr Pro Ser His Ser Arg Arg Gln Pro Arg                 165 170 175 Val Val Ser Gln Trp Ser Thr Ser Ala Ser Leu             180 185 <210> 16 <211> 3460 <212> PRT <213> Homo sapiens <400> 16 Met Glu Arg Ser Gly Trp Ala Arg Gln Thr Phe Leu Leu Ala Leu Leu   1 5 10 15 Leu Gly Ala Thr Leu Arg Ala Arg Ala Ala Ala Gly Tyr Tyr Pro Arg              20 25 30 Phe Ser Pro Phe Phe Phe Leu Cys Thr His His Gly Glu Leu Glu Gly          35 40 45 Asp Gly Glu Gln Gly Glu Val Leu Ile Ser Leu His Ile Ala Gly Asn      50 55 60 Pro Thr Tyr Tyr Val Pro Gly Gln Glu Tyr His Val Thr Ile Ser Thr  65 70 75 80 Ser Thr Phe Phe Asp Gly Leu Leu Val Thr Gly Leu Tyr Thr Ser Thr                  85 90 95 Ser Val Gln Ala Ser Gln Ser Ile Gly Gly Ser Ser Ala Phe Gly Phe             100 105 110 Gly Ile Met Ser Asp His Gln Phe Gly Asn Gln Phe Met Cys Ser Val         115 120 125 Val Ala Ser His Val Ser His Leu Pro Thr Thr Asn Leu Ser Phe Ile     130 135 140 Trp Ile Ala Pro Pro Ala Gly Thr Gly Cys Val Asn Phe Met Ala Thr 145 150 155 160 Ala Thr His Arg Gly Gln Val Ile Phe Lys Asp Ala Leu Ala Gln Gln                 165 170 175 Leu Cys Glu Gln Gly Ala Pro Thr Asp Val Thr Val His Pro His Leu             180 185 190 Ala Glu Ile His Ser Asp Ser Ile Ile Leu Arg Asp Asp Phe Asp Ser         195 200 205 Tyr His Gln Leu Gln Leu Asn Pro Asn Ile Trp Val Glu Cys Asn Asn     210 215 220 Cys Glu Thr Gly Glu Gln Cys Gly Ala Ile Met His Gly Asn Ala Val 225 230 235 240 Thr Phe Cys Glu Pro Tyr Gly Pro Arg Glu Leu Ile Thr Thr Gly Leu                 245 250 255 Asn Thr Thr Thr Ala Ser Val Leu Gln Phe Ser Ile Gly Ser Gly Ser             260 265 270 Cys Arg Phe Ser Tyr Ser Asp Pro Ser Ile Ile Val Leu Tyr Ala Lys         275 280 285 Asn Asn Ser Ala Asp Trp Ile Gln Leu Glu Lys Ile Arg Ala Pro Ser     290 295 300 Asn Val Ser Thr Ile Ile His Ile Leu Tyr Leu Pro Glu Asp Ala Lys 305 310 315 320 Gly Glu Asn Val Gln Phe Gln Trp Lys Gln Glu Asn Leu Arg Val Gly                 325 330 335 Glu Val Tyr Glu Ala Cys Trp Ala Leu Asp Asn Ile Leu Ile Ile Asn             340 345 350 Ser Ala His Arg Gln Val Val Leu Glu Asp Ser Leu Asp Pro Val Asp         355 360 365 Thr Gly Asn Trp Leu Phe Phe Pro Gly Ala Thr Val Lys His Ser Cys     370 375 380 Gln Ser Asp Gly Asn Ser Ile Tyr Phe His Gly Asn Glu Gly Ser Glu 385 390 395 400 Phe Asn Phe Ala Thr Thr Arg Asp Val Asp Leu Ser Thr Glu Asp Ile                 405 410 415 Gln Glu Gln Trp Ser Glu Glu Phe Glu Ser Gln Pro Thr Gly Trp Asp             420 425 430 Val Leu Gly Ala Val Ile Gly Thr Glu Cys Gly Thr Ile Glu Ser Gly         435 440 445 Leu Ser Met Val Phe Leu Lys Asp Gly Glu Arg Lys Leu Cys Thr Pro     450 455 460 Ser Met Asp Thr Thr Gly Tyr Gly Asn Leu Arg Phe Tyr Phe Val Met 465 470 475 480 Gly Gly Ile Cys Asp Pro Gly Asn Ser His Glu Asn Asp Ile Ile Leu                 485 490 495 Tyr Ala Lys Ile Glu Gly Arg Lys Glu His Ile Thr Leu Asp Thr Leu             500 505 510 Ser Tyr Ser Ser Tyr Lys Val Pro Ser Leu Val Ser Val Val Ile Asn         515 520 525 Pro Glu Leu Gln Thr Pro Ala Thr Lys Phe Cys Leu Arg Gln Lys Asn     530 535 540 His Gln Gly His Asn Arg Asn Val Trp Ala Val Asp Phe Phe His Val 545 550 555 560 Leu Pro Val Leu Pro Ser Thr Met Ser His Met Ile Gln Phe Ser Ile                 565 570 575 Asn Leu Gly Cys Gly Thr His Gln Pro Gly Asn Ser Val Ser Leu Glu             580 585 590 Phe Ser Thr Asn His Gly Arg Ser Trp Ser Leu Leu His Thr Glu Cys         595 600 605 Leu Pro Glu Ile Cys Ala Gly Pro His Leu Pro His Ser Thr Val Tyr     610 615 620 Ser Ser Glu Asn Tyr Ser Gly Trp Asn Arg Ile Thr Ile Pro Leu Pro 625 630 635 640 Asn Ala Ala Leu Thr Arg Asn Thr Arg Ile Arg Trp Arg Gln Thr Gly                 645 650 655 Pro Ile Leu Gly Asn Met Trp Ala Ile Asp Asn Val Tyr Ile Gly Pro             660 665 670 Ser Cys Leu Lys Phe Cys Ser Gly Arg Gly Gln Cys Thr Arg His Gly         675 680 685 Cys Lys Cys Asp Pro Gly Phe Ser Gly Pro Ala Cys Glu Met Ala Ser     690 695 700 Gln Thr Phe Pro Met Phe Ile Ser Glu Ser Phe Gly Ser Ser Arg Leu 705 710 715 720 Ser Ser Tyr His Asn Phe Tyr Ser Ile Arg Gly Ala Glu Val Ser Phe                 725 730 735 Gly Cys Gly Val Leu Ala Ser Gly Lys Ala Leu Val Phe Asn Lys Asp             740 745 750 Gly Arg Arg Gln Leu Ile Thr Ser Phe Leu Asp Ser Ser Gln Ser Arg         755 760 765 Phe Leu Gln Phe Thr Leu Arg Leu Gly Ser Lys Ser Val Leu Ser Thr     770 775 780 Cys Arg Ala Pro Asp Gln Pro Gly Glu Gly Val Leu Leu His Tyr Ser 785 790 795 800 Tyr Asp Asn Gly Ile Thr Trp Lys Leu Leu Glu His Tyr Ser Tyr Leu                 805 810 815 Ser Tyr His Glu Pro Arg Ile Ile Ser Val Glu Leu Pro Gly Asp Ala             820 825 830 Lys Gln Phe Gly Ile Gln Phe Arg Trp Trp Gln Pro Tyr His Ser Ser         835 840 845 Gln Arg Glu Asp Val Trp Ala Ile Asp Glu Ile Met Thr Ser Val     850 855 860 Leu Phe Asn Ser Ile Ser Leu Asp Phe Thr Asn Leu Val Glu Val Thr 865 870 875 880 Gln Ser Leu Gly Phe Tyr Leu Gly Asn Val Gln Pro Tyr Cys Gly His                 885 890 895 Asp Trp Thr Leu Cys Phe Thr Gly Asp Ser Lys Leu Ala Ser Ser Met             900 905 910 Arg Tyr Val Glu Thr Gln Ser Met Gln Ile Gly Ala Ser Tyr Met Ile         915 920 925 Gln Phe Ser Leu Val Met Gly Cys Gly Gln Lys Tyr Thr Pro His Met     930 935 940 Asp Asn Gln Val Lys Leu Glu Tyr Ser Thr Asn His Gly Leu Thr Trp 945 950 955 960 His Leu Val Gln Glu Glu Cys Leu Pro Ser Met Pro Ser Cys Gln Glu                 965 970 975 Phe Thr Ser Ala Ser Ile Tyr His Ala Ser Glu Phe Thr Gln Trp Arg             980 985 990 Arg Val Ile Val Leu Leu Pro Gln Lys Thr Trp Ser Ser Ala Thr Arg         995 1000 1005 Phe Arg Trp Ser Gln Ser Tyr Tyr Thr Ala Gln Asp Glu Trp Ala Leu    1010 1015 1020 Asp Ser Ile Tyr Ile Gly Gln Gln Cys Pro Asn Met Cys Ser Gly His 1025 1030 1035 1040 Gly Ser Cys Asp His Gly Ile Cys Arg Cys Asp Gln Gly Tyr Gln Gly                1045 1050 1055 Thr Glu Cys His Pro Glu Ala Ala Leu Pro Ser Thr Ile Met Ser Asp            1060 1065 1070 Phe Glu Asn Gln Asn Gly Trp Glu Ser Asp Trp Gln Glu Val Ile Gly        1075 1080 1085 Gly Glu Ile Val Lys Pro Glu Gln Gly Cys Gly Val Ile Ser Ser Gly    1090 1095 1100 Ser Ser Leu Tyr Phe Ser Lys Ala Gly Lys Arg Gln Leu Val Ser Trp 1105 1110 1115 1120 Asp Leu Asp Thr Ser Trp Val Asp Phe Val Gln Phe Tyr Ile Gln Ile                1125 1130 1135 Gly Gly Glu Ser Ala Ser Cys Asn Lys Pro Asp Ser Arg Glu Glu Gly            1140 1145 1150 Val Leu Leu Gln Tyr Ser Asn Asn Gly Gly Ile Gln Trp His Leu Leu        1155 1160 1165 Ala Glu Met Tyr Phe Ser Asp Phe Ser Lys Pro Arg Phe Val Tyr Leu    1170 1175 1180 Glu Leu Pro Ala Ala Ala Lys Thr Pro Cys Thr Arg Phe Arg Trp Trp 1185 1190 1195 1200 Gln Pro Val Phe Ser Gly Glu Asp Tyr Asp Gln Trp Ala Val Asp Asp                1205 1210 1215 Ile Ile Ile Leu Ser Glu Lys Gln Lys Gln Ile Ile Pro Val Ile Asn            1220 1225 1230 Pro Thr Leu Pro Gln Asn Phe Tyr Glu Lys Pro Ala Phe Asp Tyr Pro        1235 1240 1245 Met Asn Gln Met Ser Val Trp Leu Met Leu Ala Asn Glu Gly Met Val    1250 1255 1260 Lys Asn Glu Thr Phe Cys Ala Ala Thr Pro Ser Ala Met Ile Phe Gly 1265 1270 1275 1280 Lys Ser Asp Gly Asp Arg Phe Ala Val Thr Arg Asp Leu Thr Leu Lys                1285 1290 1295 Pro Gly Tyr Val Leu Gln Phe Lys Leu Asn Ile Gly Cys Ala Asn Gln            1300 1305 1310 Phe Ser Ser Thr Ala Pro Val Leu Leu Gln Tyr Ser His Asp Ala Gly        1315 1320 1325 Met Ser Trp Phe Leu Val Lys Glu Gly Cys Tyr Pro Ala Ser Ala Gly    1330 1335 1340 Lys Gly Cys Glu Gly Asn Ser Arg Glu Leu Ser Glu Pro Thr Met Tyr 1345 1350 1355 1360 His Thr Gly Asp Phe Glu Glu Trp Thr Arg Ile Thr Ile Val Ile Pro                1365 1370 1375 Arg Ser Leu Ala Ser Ser Lys Thr Arg Phe Arg Trp Ile Gln Glu Ser            1380 1385 1390 Ser Ser Gln Lys Asn Val Pro Pro Phe Gly Leu Asp Gly Val Tyr Ile        1395 1400 1405 Ser Glu Pro Cys Pro Ser Tyr Cys Ser Gly His Gly Asp Cys Ile Ser    1410 1415 1420 Gly Val Cys Phe Cys Asp Leu Gly Tyr Thr Ala Ala Gln Gly Thr Cys 1425 1430 1435 1440 Val Ser Asn Val Pro Asn His Asn Glu Met Phe Asp Arg Phe Glu Gly                1445 1450 1455 Lys Leu Ser Pro Leu Trp Tyr Lys Ile Thr Gly Ala Gln Val Gly Thr            1460 1465 1470 Gly Cys Gly Thr Leu Asn Asp Gly Lys Ser Leu Tyr Phe Asn Gly Pro        1475 1480 1485 Gly Lys Arg Glu Ala Arg Thr Val Pro Leu Asp Thr Arg Asn Ile Arg    1490 1495 1500 Leu Val Gln Phe Tyr Ile Gln Ile Gly Ser Lys Thr Ser Gly Ile Thr 1505 1510 1515 1520 Cys Ile Lys Pro Arg Thr Arg Asn Glu Gly Leu Ile Val Gln Tyr Ser                1525 1530 1535 Asn Asp Asn Gly Ile Leu Trp His Leu Leu Arg Glu Leu Asp Phe Met            1540 1545 1550 Ser Phe Leu Glu Pro Gln Ile Ile Ser Ile Asp Leu Pro Gln Asp Ala        1555 1560 1565 Lys Thr Pro Ala Thr Ala Phe Arg Trp Trp Gln Pro Gln His Gly Lys    1570 1575 1580 His Ser Ala Gln Trp Ala Leu Asp Asp Val Leu Ile Gly Met Asn Asp 1585 1590 1595 1600 Ser Ser Gln Thr Gly Phe Gln Asp Lys Phe Asp Gly Ser Ile Asp Leu                1605 1610 1615 Gln Ala Asn Trp Tyr Arg Ile Gln Gly Gly Gln Val Asp Ile Asp Cys            1620 1625 1630 Leu Ser Met Asp Thr Ala Leu Ile Phe Thr Glu Asn Ile Gly Lys Pro        1635 1640 1645 Arg Tyr Ala Glu Thr Trp Asp Phe His Val Ser Ala Ser Thr Phe Leu    1650 1655 1660 Gln Phe Glu Met Ser Met Gly Cys Ser Lys Pro Phe Ser Asn Ser His 1665 1670 1675 1680 Ser Val Gln Leu Gln Tyr Ser Leu Asn Asn Gly Lys Asp Trp His Leu                1685 1690 1695 Val Thr Glu Glu Cys Val Pro Pro Thr Ile Gly Cys Leu His Tyr Thr            1700 1705 1710 Glu Ser Ser Ile Tyr Thr Ser Glu Arg Phe Gln Asn Trp Lys Arg Ile        1715 1720 1725 Thr Val Tyr Leu Pro Leu Ser Thr Ile Ser Pro Arg Thr Arg Phe Arg    1730 1735 1740 Trp Ile Gln Ala Asn Tyr Thr Val Gly Ala Asp Ser Trp Ala Ile Asp 1745 1750 1755 1760 Asn Val Val Leu Ala Ser Gly Cys Pro Trp Met Cys Ser Gly Arg Gly                1765 1770 1775 Ile Cys Asp Ala Gly Arg Cys Val Cys Asp Arg Gly Phe Gly Gly Pro            1780 1785 1790 Tyr Cys Val Pro Val Val Pro Leu Pro Ser Ile Leu Lys Asp Asp Phe        1795 1800 1805 Asn Gly Asn Leu His Pro Asp Leu Trp Pro Glu Val Tyr Gly Ala Glu    1810 1815 1820 Arg Gly Asn Leu Asn Gly Glu Thr Ile Lys Ser Gly Thr Ser Leu Ile 1825 1830 1835 1840 Phe Lys Gly Glu Gly Leu Arg Met Leu Ile Ser Arg Asp Leu Asp Cys                1845 1850 1855 Thr Asn Thr Met Tyr Val Gln Phe Ser Leu Arg Phe Ile Ala Lys Ser            1860 1865 1870 Thr Pro Glu Arg Ser His Ser Ile Leu Leu Gln Phe Ser Ile Ser Gly        1875 1880 1885 Gly Ile Thr Trp His Leu Met Asp Glu Phe Tyr Phe Pro Gln Thr Thr    1890 1895 1900 Asn Ile Leu Phe Ile Asn Val Pro Leu Pro Tyr Thr Ala Gln Thr Asn 1905 1910 1915 1920 Ala Thr Arg Phe Arg Leu Trp Gln Pro Tyr Asn Asn Gly Lys Lys Glu                1925 1930 1935 Glu Ile Trp Ile Val Asp Asp Phe Ile Ile Asp Gly Asn Asn Val Asn            1940 1945 1950 Asn Pro Val Met Leu Leu Asp Thr Phe Asp Phe Gly Pro Arg Glu Asp        1955 1960 1965 Asn Trp Phe Phe Tyr Pro Gly Gly Asn Ile Gly Leu Tyr Cys Pro Tyr    1970 1975 1980 Ser Ser Lys Gly Ala Pro Glu Glu Asp Ser Ala Met Val Phe Val Ser 1985 1990 1995 2000 Asn Glu Val Gly Glu His Ser Ile Thr Thr Arg Asp Leu Asn Val Asn                2005 2010 2015 Glu Asn Thr Ile Ile Gln Phe Glu Ile Asn Val Gly Cys Ser Thr Asp            2020 2025 2030 Ser Ser Ser Ala Asp Pro Val Arg Leu Glu Phe Ser Arg Asp Phe Gly        2035 2040 2045 Ala Thr Trp His Leu Leu Leu Pro Leu Cys Tyr His Ser Ser Ser His    2050 2055 2060 Val Ser Ser Leu Cys Ser Thr Glu His His Pro Ser Ser Thr Tyr Tyr 2065 2070 2075 2080 Ala Gly Thr Met Gln Gly Trp Arg Arg Glu Val Val His Phe Gly Lys                2085 2090 2095 Leu His Leu Cys Gly Ser Val Arg Phe Arg Trp Tyr Gln Gly Phe Tyr            2100 2105 2110 Pro Ala Gly Ser Gln Pro Val Thr Trp Ala Ile Asp Asn Val Tyr Ile        2115 2120 2125 Gly Pro Gln Cys Glu Glu Met Cys Asn Gly Gln Gly Ser Cys Ile Asn    2130 2135 2140 Gly Thr Lys Cys Ile Cys Asp Pro Gly Tyr Ser Gly Pro Thr Cys Lys 2145 2150 2155 2160 Ile Ser Thr Lys Asn Pro Asp Phe Leu Lys Asp Asp Phe Glu Gly Gln                2165 2170 2175 Leu Glu Ser Asp Arg Phe Leu Leu Met Ser Gly Gly Lys Pro Ser Arg            2180 2185 2190 Lys Cys Gly Ile Leu Ser Ser Gly Asn Asn Leu Phe Phe Asn Glu Asp        2195 2200 2205 Gly Leu Arg Met Leu Met Thr Arg Asp Leu Asp Leu Ser His Ala Arg    2210 2215 2220 Phe Val Gln Phe Phe Met Arg Leu Gly Cys Gly Lys Gly Val Pro Asp 2225 2230 2235 2240 Pro Arg Ser Gln Pro Val Leu Leu Gln Tyr Ser Leu Asn Gly Gly Leu                2245 2250 2255 Ser Trp Ser Leu Leu Gln Glu Phe Leu Phe Ser Asn Ser Ser Asn Val            2260 2265 2270 Gly Arg Tyr Ile Ala Leu Glu Ile Pro Leu Lys Ala Arg Ser Gly Ser        2275 2280 2285 Thr Arg Leu Arg Trp Trp Gln Pro Ser Glu Asn Gly His Phe Tyr Ser    2290 2295 2300 Pro Trp Val Ile Asp Gln Ile Leu Ile Gly Gly Asn Ile Ser Gly Asn 2305 2310 2315 2320 Thr Val Leu Glu Asp Asp Phe Thr Thr Leu Asp Ser Arg Lys Trp Leu                2325 2330 2335 Leu His Pro Gly Gly Thr Lys Met Pro Val Cys Gly Ser Thr Gly Asp            2340 2345 2350 Ala Leu Val Phe Ile Glu Lys Ala Ser Thr Arg Tyr Val Val Ser Thr        2355 2360 2365 Asp Val Ala Val Asn Glu Asp Ser Phe Leu Gln Ile Asp Phe Ala Ala    2370 2375 2380 Ser Cys Ser Val Thr Asp Ser Cys Tyr Ala Ile Glu Leu Glu Tyr Ser 2385 2390 2395 2400 Val Asp Leu Gly Leu Ser Trp His Pro Leu Val Arg Asp Cys Leu Pro                2405 2410 2415 Thr Asn Val Glu Cys Ser Arg Tyr His Leu Gln Arg Ile Leu Val Ser            2420 2425 2430 Asp Thr Phe Asn Lys Trp Thr Arg Ile Thr Leu Pro Leu Pro Pro Tyr        2435 2440 2445 Thr Arg Ser Gln Ala Thr Arg Phe Arg Trp His Gln Pro Ala Pro Phe    2450 2455 2460 Asp Lys Gln Gln Thr Trp Ala Ile Asp Asn Val Tyr Ile Gly Asp Gly 2465 2470 2475 2480 Cys Ile Asp Met Cys Ser Gly His Gly Arg Cys Ile Gln Gly Asn Cys                2485 2490 2495 Val Cys Asp Glu Gln Trp Gly Gly Leu Tyr Cys Asp Asp Pro Glu Thr            2500 2505 2510 Ser Leu Pro Thr Gln Leu Lys Asp Asn Phe Asn Arg Ala Pro Ser Ser        2515 2520 2525 Gln Asn Trp Leu Thr Val Asn Gly Gly Lys Leu Ser Thr Val Cys Gly    2530 2535 2540 Ala Val Ala Ser Gly Met Ala Leu His Phe Ser Gly Gly Cys Ser Arg 2545 2550 2555 2560 Leu Leu Val Thr Val Asp Leu Asn Leu Thr Asn Ala Glu Phe Ile Gln                2565 2570 2575 Phe Tyr Phe Met Tyr Gly Cys Leu Ile Thr Pro Asn Asn Arg Asn Gln            2580 2585 2590 Gly Val Leu Leu Glu Tyr Ser Val Asn Gly Gly Ile Thr Trp Asn Leu        2595 2600 2605 Leu Met Glu Ile Phe Tyr Asp Gln Tyr Ser Lys Pro Gly Phe Val Asn    2610 2615 2620 Ile Leu Leu Pro Pro Asp Ala Lys Glu Ile Ala Thr Arg Phe Arg Trp 2625 2630 2635 2640 Trp Gln Pro Arg His Asp Gly Leu Asp Gln Asn Asp Trp Ala Ile Asp                2645 2650 2655 Asn Val Leu Ile Ser Gly Ser Ala Asp Gln Arg Thr Val Met Leu Asp            2660 2665 2670 Thr Phe Ser Ser Ala Pro Val Pro Gln His Glu Arg Ser Pro Ala Asp        2675 2680 2685 Ala Gly Pro Val Gly Arg Ile Ala Phe Asp Met Phe Met Glu Asp Lys    2690 2695 2700 Thr Ser Val Asn Glu His Trp Leu Phe His Asp Asp Cys Thr Val Glu 2705 2710 2715 2720 Arg Phe Cys Asp Ser Pro Asp Gly Val Met Leu Cys Gly Ser His Asp                2725 2730 2735 Gly Arg Glu Val Tyr Ala Val Thr His Asp Leu Thr Pro Thr Glu Gly            2740 2745 2750 Trp Ile Met Gln Phe Lys Ile Ser Val Gly Cys Lys Val Ser Glu Lys        2755 2760 2765 Ile Ala Gln Asn Gln Ile His Val Gln Tyr Ser Thr Asp Phe Gly Val    2770 2775 2780 Ser Trp Asn Tyr Leu Val Pro Gln Cys Leu Pro Ala Asp Pro Lys Cys 2785 2790 2795 2800 Ser Gly Ser Val Ser Gln Pro Ser Val Phe Phe Pro Thr Lys Gly Trp                2805 2810 2815 Lys Arg Ile Thr Tyr Pro Leu Pro Glu Ser Leu Val Gly Asn Pro Val            2820 2825 2830 Arg Phe Arg Phe Tyr Gln Lys Tyr Ser Asp Met Gln Trp Ala Ile Asp        2835 2840 2845 Asn Phe Tyr Leu Gly Pro Gly Cys Leu Asp Asn Cys Arg Gly His Gly    2850 2855 2860 Asp Cys Leu Arg Glu Gln Cys Ile Cys Asp Pro Gly Tyr Ser Gly Pro 2865 2870 2875 2880 Asn Cys Tyr Leu Thr His Thr Leu Lys Thr Phe Leu Lys Glu Arg Phe                2885 2890 2895 Asp Ser Glu Glu Ile Lys Pro Asp Leu Trp Met Ser Leu Glu Gly Gly            2900 2905 2910 Ser Thr Cys Thr Glu Cys Gly Ile Leu Ala Glu Asp Thr Ala Leu Tyr        2915 2920 2925 Phe Gly Gly Ser Thr Val Arg Gln Ala Val Thr Gln Asp Leu Asp Leu    2930 2935 2940 Arg Gly Ala Lys Phe Leu Gln Tyr Trp Gly Arg Ile Gly Ser Glu Asn 2945 2950 2955 2960 Asn Met Thr Ser Cys His Arg Pro Ile Cys Arg Lys Glu Gly Val Leu                2965 2970 2975 Leu Asp Tyr Ser Thr Asp Gly Gly Ile Thr Trp Thr Leu Leu His Glu            2980 2985 2990 Met Asp Tyr Gln Lys Tyr Ile Ser Val Arg His Asp Tyr Ile Leu Leu        2995 3000 3005 Pro Glu Asp Ala Leu Thr Asn Thr Thr Arg Leu Arg Trp Trp Gln Pro    3010 3015 3020 Phe Val Ile Ser Asn Gly Ile Val Val Ser Gly Val Glu Arg Ala Gln 3025 3030 3035 3040 Trp Ala Leu Asp Asn Ile Leu Ile Gly Gly Ala Glu Ile Asn Pro Ser                3045 3050 3055 Gln Leu Val Asp Thr Phe Asp Asp Glu Gly Thr Ser His Glu Glu Asn            3060 3065 3070 Trp Ser Phe Tyr Pro Asn Ala Val Arg Thr Ala Gly Phe Cys Gly Asn        3075 3080 3085 Pro Ser Phe His Leu Tyr Trp Pro Asn Lys Lys Lys Asp Lys Thr His    3090 3095 3100 Asn Ala Leu Ser Ser Arg Glu Leu Ile Ile Gln Pro Gly Tyr Met Met 3105 3110 3115 3120 Gln Phe Lys Ile Val Val Gly Cys Glu Ala Thr Ser Cys Gly Asp Leu                3125 3130 3135 His Ser Val Met Leu Glu Tyr Thr Lys Asp Ala Arg Ser Asp Ser Trp            3140 3145 3150 Gln Leu Val Gln Thr Gln Cys Leu Pro Ser Ser Ser Asn Ser Ile Gly        3155 3160 3165 Cys Ser Pro Phe Gln Phe His Glu Ala Thr Ile Tyr Asn Ser Val Asn    3170 3175 3180 Ser Ser Ser Trp Lys Arg Ile Thr Ile Gln Leu Pro Asp His Val Ser 3185 3190 3195 3200 Ser Ser Ala Thr Gln Phe Arg Trp Ile Gln Lys Gly Glu Glu Thr Glu                3205 3210 3215 Lys Gln Ser Trp Ala Ile Asp His Val Tyr Ile Gly Glu Ala Cys Pro            3220 3225 3230 Lys Leu Cys Ser Gly His Gly Tyr Cys Thr Thr Gly Ala Ile Cys Ile        3235 3240 3245 Cys Asp Glu Ser Phe Gln Gly Asp Asp Cys Ser Val Phe Ser His Asp    3250 3255 3260 Leu Pro Ser Tyr Ile Lys Asp Asn Phe Glu Ser Ala Arg Val Thr Glu 3265 3270 3275 3280 Ala Asn Trp Glu Thr Ile Gln Gly Gly Val Ile Gly Ser Gly Cys Gly                3285 3290 3295 Gln Leu Ala Pro Tyr Ala His Gly Asp Ser Leu Tyr Phe Asn Gly Cys            3300 3305 3310 Gln Ile Arg Gln Ala Ala Thr Lys Pro Leu Asp Leu Thr Arg Ala Ser        3315 3320 3325 Lys Ile Met Phe Val Leu Gln Ile Gly Ser Met Ser Gln Thr Asp Ser    3330 3335 3340 Cys Asn Ser Asp Leu Ser Gly Pro His Ala Val Asp Lys Ala Val Leu 3345 3350 3355 3360 Leu Gln Tyr Ser Val Asn Asn Gly Ile Thr Trp His Val Ile Ala Gln                3365 3370 3375 His Gln Pro Lys Asp Phe Thr Gln Ala Gln Arg Val Ser Tyr Asn Val            3380 3385 3390 Pro Leu Glu Ala Arg Met Lys Gly Val Leu Leu Arg Trp Trp Gln Pro        3395 3400 3405 Arg His Asn Gly Thr Gly His Asp Gln Trp Ala Leu Asp His Val Glu    3410 3415 3420 Val Val Leu Val Ser Thr Arg Lys Gln Asn Tyr Met Met Asn Phe Ser 3425 3430 3435 3440 Arg Gln His Gly Leu Arg His Phe Tyr Asn Arg Arg Arg Arg Ser Leu                3445 3450 3455 Arg Arg Tyr Pro            3460 <210> 17 <211> 122 <212> PRT <213> Homo sapiens <400> 17 Met Lys Leu Leu Thr Gly Leu Val Phe Cys Ser Leu Val Leu Gly Val   1 5 10 15 Ser Ser Arg Ser Phe Phe Ser Phe Leu Gly Glu Ala Phe Asp Gly Ala              20 25 30 Arg Asp Met Trp Arg Ala Tyr Ser Asp Met Arg Glu Ala Asn Tyr Ile          35 40 45 Gly Ser Asp Lys Tyr Phe His Ala Arg Gly Asn Tyr Asp Ala Ala Lys      50 55 60 Arg Gly Pro Gly Gly Ala Trp Ala Ala Glu Val Ile Ser Asp Ala Arg  65 70 75 80 Glu Asn Ile Gln Arg Phe Phe Gly His Gly Ala Glu Asp Ser Leu Ala                  85 90 95 Asp Gln Ala Ala Asn Glu Trp Gly Arg Ser Gly Lys Asp Pro Asn His             100 105 110 Phe Arg Pro Ala Gly Leu Pro Glu Lys Tyr         115 120 <210> 18 <211> 401 <212> PRT <213> Homo sapiens <400> 18 Met Asp Leu Thr Gln Gln Ala Lys Asp Ile Gln Asn Ile Thr Val Gln   1 5 10 15 Glu Thr Asn Lys Asn Asn Ser Glu Ser Ile Glu Cys Ser Lys Ile Thr              20 25 30 Met Asp Leu Lys Phe Asn Asn Ser Arg Lys Tyr Ile Ser Ile Thr Val          35 40 45 Pro Ser Lys Thr Gln Thr Met Ser Pro His Ile Lys Ser Val Asp Asp      50 55 60 Val Val Val Leu Gly Met Asn Leu Ser Lys Phe Asn Lys Leu Thr Gln  65 70 75 80 Phe Phe Ile Cys Val Ala Gly Val Phe Val Phe Tyr Leu Ile Tyr Gly                  85 90 95 Tyr Leu Gln Glu Leu Ile Phe Ser Val Glu Gly Phe Lys Ser Cys Gly             100 105 110 Trp Tyr Leu Thr Leu Val Gln Phe Ala Phe Tyr Ser Ile Phe Gly Leu         115 120 125 Ile Glu Leu Gln Leu Ile Gln Asp Lys Arg Arg Arg Ile Pro Gly Lys     130 135 140 Thr Tyr Met Ile Ile Ala Phe Leu Thr Val Gly Thr Met Gly Leu Ser 145 150 155 160 Asn Thr Ser Leu Gly Tyr Leu Asn Tyr Pro Thr Gln Val Ile Phe Lys                 165 170 175 Cys Cys Lys Leu Ile Pro Val Met Leu Gly Gly Val Phe Ile Gln Gly             180 185 190 Lys Arg Tyr Asn Val Ala Asp Val Ser Ala Ala Ile Cys Met Ser Leu         195 200 205 Gly Leu Ile Trp Phe Thr Leu Ala Asp Ser Thr Thr Ala Pro Asn Phe     210 215 220 Asn Leu Thr Gly Val Val Leu Ile Ser Leu Ala Leu Cys Ala Asp Ala 225 230 235 240 Val Ile Gly Asn Val Gln Glu Lys Ala Met Lys Leu His Asn Ala Ser                 245 250 255 Asn Ser Glu Met Val Leu Tyr Ser Tyr Ser Ile Gly Phe Val Tyr Ile             260 265 270 Leu Leu Gly Leu Thr Cys Thr Ser Gly Leu Gly Pro Ala Val Thr Phe         275 280 285 Cys Ala Lys Asn Pro Val Arg Thr Tyr Gly Tyr Ala Phe Leu Phe Ser     290 295 300 Leu Thr Gly Tyr Phe Gly Ile Ser Phe Val Leu Ala Leu Ile Lys Ile 305 310 315 320 Phe Gly Ala Leu Ile Ala Val Thr Val Thr Thr Gly Arg Lys Ala Met                 325 330 335 Thr Ile Val Leu Ser Phe Ile Phe Phe Ala Lys Pro Phe Thr Phe Gln             340 345 350 Tyr Val Trp Ser Gly Leu Leu Val Val Leu Gly Ile Phe Leu Asn Val         355 360 365 Tyr Ser Lys Asn Met Asp Lys Ile Arg Leu Pro Ser Leu Tyr Asp Leu     370 375 380 Ile Asn Lys Ser Val Glu Ala Arg Lys Ser Arg Thr Leu Ala Gln Thr 385 390 395 400 Val     <210> 19 <211> 787 <212> PRT <213> Homo sapiens <400> 19 Met Ala Ala Ala Arg Pro Ala Arg Gly Pro Glu Leu Pro Leu Leu Gly   1 5 10 15 Leu Leu Leu Leu Leu Leu Leu Gly Asp Pro Gly Arg Gly Ala Ala Ser              20 25 30 Ser Gly Asn Ala Thr Gly Pro Gly Pro Arg Ser Ala Gly Gly Ser Ala          35 40 45 Arg Arg Ser Ala Ala Val Thr Gly Pro Pro Pro Pro Leu Ser His Cys      50 55 60 Gly Arg Ala Ala Pro Cys Glu Pro Leu Arg Tyr Asn Val Cys Leu Gly  65 70 75 80 Ser Val Leu Pro Tyr Gly Ala Thr Ser Thr Leu Leu Ala Gly Asp Ser                  85 90 95 Asp Ser Gln Glu Glu Ala His Gly Lys Leu Val Leu Trp Ser Gly Leu             100 105 110 Arg Asn Ala Pro Arg Cys Trp Ala Val Ile Gln Pro Leu Leu Cys Ala         115 120 125 Val Tyr Met Pro Lys Cys Glu Asn Asp Arg Val Glu Leu Pro Ser Arg     130 135 140 Thr Leu Cys Gln Ala Thr Arg Gly Pro Cys Ala Ile Val Glu Arg Glu 145 150 155 160 Arg Gly Trp Pro Asp Phe Leu Arg Cys Thr Pro Asp Arg Phe Pro Glu                 165 170 175 Gly Cys Thr Asn Glu Val Gln Asn Ile Lys Phe Asn Ser Ser Gly Gln             180 185 190 Cys Glu Val Pro Leu Val Arg Thr Asp Asn Pro Lys Ser Trp Tyr Glu         195 200 205 Asp Val Glu Gly Cys Gly Ile Gln Cys Gln Asn Pro Leu Phe Thr Glu     210 215 220 Ala Glu His Gln Asp Met His Ser Tyr Ile Ala Ala Phe Gly Ala Val 225 230 235 240 Thr Gly Leu Cys Thr Leu Phe Thr Leu Ala Thr Phe Val Ala Asp Trp                 245 250 255 Arg Asn Ser Asn Arg Tyr Pro Ala Val Ile Leu Phe Tyr Val Asn Ala             260 265 270 Cys Phe Phe Val Gly Ser Ile Gly Trp Leu Ala Gln Phe Met Asp Gly         275 280 285 Ala Arg Arg Glu Ile Val Cys Arg Ala Asp Gly Thr Met Arg Leu Gly     290 295 300 Glu Pro Thr Ser Asn Glu Thr Leu Ser Cys Val Ile Phe Val Ile 305 310 315 320 Val Tyr Tyr Ala Leu Met Ala Gly Val Val Trp Phe Val Val Leu Thr                 325 330 335 Tyr Ala Trp His Thr Ser Phe Lys Ala Leu Gly Thr Thr Tyr Gln Pro             340 345 350 Leu Ser Gly Lys Thr Ser Tyr Phe His Leu Leu Thr Trp Ser Leu Pro         355 360 365 Phe Val Leu Thr Val Ala Ile Leu Ala Val Ala Gln Val Asp Gly Asp     370 375 380 Ser Val Ser Gly Ile Cys Phe Val Gly Tyr Lys Asn Tyr Arg Tyr Arg 385 390 395 400 Ala Gly Phe Val Leu Ala Pro Ile Gly Leu Val Leu Ile Val Gly Gly                 405 410 415 Tyr Phe Leu Ile Arg Gly Val Met Thr Leu Phe Ser Ile Lys Ser Asn             420 425 430 His Pro Gly Leu Leu Ser Glu Lys Ala Ala Ser Lys Ile Asn Glu Thr         435 440 445 Met Leu Arg Leu Gly Ile Phe Gly Phe Leu Ala Phe Gly Phe Val Leu     450 455 460 Ile Thr Phe Ser Cys His Phe Tyr Asp Phe Phe Asn Gln Ala Glu Trp 465 470 475 480 Glu Arg Ser Phe Arg Asp Tyr Val Leu Cys Gln Ala Asn Val Thr Ile                 485 490 495 Gly Leu Pro Thr Lys Gln Pro Ile Pro Asp Cys Glu Ile Lys Asn Arg             500 505 510 Pro Ser Leu Leu Val Glu Lys Ile Asn Leu Phe Ala Met Phe Gly Thr         515 520 525 Gly Ile Ala Met Ser Thr Trp Val Trp Thr Lys Ala Thr Leu Leu Ile     530 535 540 Trp Arg Arg Thr Trp Cys Arg Leu Thr Gly Gln Ser Asp Asp Glu Pro 545 550 555 560 Lys Arg Ile Lys Lys Ser Lys Met Ile Ala Lys Ala Phe Ser Lys Arg                 565 570 575 His Glu Leu Leu Gln Asn Pro Gly Gln Glu Leu Ser Phe Ser Met His             580 585 590 Thr Val Ser His Asp Gly Pro Val Ala Gly Leu Ala Phe Asp Leu Asn         595 600 605 Glu Pro Ser Ala Asp Val Ser Ser Ala Trp Ala Gln His Val Thr Lys     610 615 620 Met Val Ala Arg Arg Gly Ala Ile Leu Pro Gln Asp Ile Ser Val Thr 625 630 635 640 Pro Val Ala Thr Pro Val Pro Pro Glu Glu Gln Ala Asn Leu Trp Leu                 645 650 655 Val Glu Ala Glu Ile Ser Pro Glu Leu Gln Lys Arg Leu Gly Arg Lys             660 665 670 Lys Lys Arg Arg Lys Arg Lys Lys Glu Val Cys Pro Leu Ala Pro Pro         675 680 685 Pro Glu Leu His Pro Pro Ala Pro Ala Pro Ser Thr Ile Pro Arg Leu     690 695 700 Pro Gln Leu Pro Arg Gln Lys Cys Leu Val Ala Ala Gly Ala Trp Gly 705 710 715 720 Ala Gly Asp Ser Cys Arg Gln Gly Ala Trp Thr Leu Val Ser Asn Pro                 725 730 735 Phe Cys Pro Glu Pro Ser Pro Pro Gln Asp Pro Phe Leu Pro Ser Ala             740 745 750 Pro Ala Pro Val Ala Trp Ala His Gly Arg Arg Gln Gly Leu Gly Pro         755 760 765 Ile His Ser Arg Thr Asn Leu Met Asp Thr Glu Leu Met Asp Ala Asp     770 775 780 Ser Asp Phe 785 <210> 20 <211> 155 <212> PRT <213> Homo sapiens <400> 20 Met Gly Arg Ser Arg Ser Arg Ser Pro Arg Arg Glu Arg Arg Arg Ser   1 5 10 15 Arg Ser Thr Ser Arg Glu Arg Glu Arg Arg Arg Arg Glu Arg Ser Arg              20 25 30 Ser Arg Glu Arg Asp Arg Arg Arg Ser Arg Ser Arg Ser Pro His Arg          35 40 45 Arg Arg Ser Arg Ser Pro Arg Arg His Arg Ser Thr Ser Pro Ser Pro      50 55 60 Ser Arg Leu Lys Glu Arg Arg Asp Glu Glu Lys Lys Glu Thr Lys Glu  65 70 75 80 Thr Lys Ser Lys Glu Arg Gln Ile Thr Glu Glu Asp Leu Glu Gly Lys                  85 90 95 Thr Glu Glu Glu Ile Glu Met Met Lys Leu Met Gly Phe Ala Ser Phe             100 105 110 Asp Ser Thr Lys Gly Lys Lys Val Asp Gly Ser Val Asn Ala Tyr Ala         115 120 125 Ile Asn Val Ser Gln Lys Arg Lys Tyr Arg Gln Tyr Met Asn Arg Lys     130 135 140 Gly Gly Phe Asn Arg Pro Leu Asp Phe Ile Ala 145 150 155 <210> 21 <211> 575 <212> PRT <213> Homo sapiens <400> 21 Met Ala Asp Arg Gly Gly Val Gly Glu Ala Ala Ala Val Gly Ala Ser   1 5 10 15 Pro Ala Ser Val Pro Gly Leu Asn Pro Thr Leu Gly Trp Arg Glu Arg              20 25 30 Leu Arg Ala Gly Leu Ala Gly Thr Gly Ala Ser Leu Trp Phe Val Ala          35 40 45 Gly Leu Gly Leu Leu Tyr Ala Leu Arg Ile Pro Leu Arg Leu Cys Glu      50 55 60 Asn Leu Ala Ala Val Thr Val Phe Leu Asn Ser Leu Thr Pro Lys Phe  65 70 75 80 Tyr Val Ala Leu Thr Gly Thr Ser Ser Leu Ile Ser Gly Leu Ile Phe                  85 90 95 Ile Phe Glu Trp Trp Tyr Phe His Lys His Gly Thr Ser Phe Ile Glu             100 105 110 Gln Val Ser Val Ser His Leu Gln Pro Leu Met Gly Gly Thr Glu Ser         115 120 125 Ser Ile Ser Glu Pro Gly Ser Pro Ser Arg Asn Arg Glu Asn Glu Thr     130 135 140 Ser Arg Gln Asn Leu Ser Glu Cys Lys Val Trp Arg Asn Pro Leu Asn 145 150 155 160 Leu Phe Arg Gly Ala Glu Tyr Arg Arg Tyr Thr Trp Val Thr Gly Lys                 165 170 175 Glu Pro Leu Thr Tyr Tyr Asp Met Asn Leu Ser Ala Gln Asp His Gln             180 185 190 Thr Phe Phe Thr Cys Asp Thr Asp Phe Leu Arg Pro Ser Asp Thr Val         195 200 205 Met Gln Lys Ala Trp Arg Glu Arg Asn Pro Pro Ala Arg Ile Lys Ala     210 215 220 Ala Tyr Gln Ala Leu Glu Leu Asn Asn Asp Cys Ala Thr Ala Tyr Val 225 230 235 240 Leu Leu Ala Glu Glu Glu Ala Thr Thr Ile Val Asp Ala Glu Arg Leu                 245 250 255 Phe Lys Gln Ala Leu Lys Ala Gly Glu Thr Ile Tyr Arg Gln Ser Gln             260 265 270 Gln Cys Gln His Gln Ser Pro Gln His Glu Ala Gln Leu Arg Arg Asp         275 280 285 Thr Asn Val Leu Val Tyr Ile Lys Arg Arg Leu Ala Met Cys Ala Arg     290 295 300 Lys Leu Gly Arg Ile Arg Glu Ala Val Lys Ile Met Arg Asp Leu Met 305 310 315 320 Lys Glu Phe Pro Pro Leu Thr Met Leu Asn Ile His Glu Asn Leu Leu                 325 330 335 Glu Ser Leu Leu Glu Leu Gln Ala Tyr Pro Asp Val Gln Ala Val Leu             340 345 350 Ala Lys Tyr Asp Asp Ile Ser Leu Pro Lys Ser Ala Ala Ile Cys Tyr         355 360 365 Thr Ala Ala Leu Leu Lys Thr Arg Thr Val Ser Glu Lys Phe Ser Pro     370 375 380 Glu Thr Ala Ser Arg Arg Gly Leu Ser Thr Ala Glu Ile Asn Ala Val 385 390 395 400 Glu Ala Ile His Arg Ala Val Glu Phe Asn Pro His Val Pro Lys Tyr                 405 410 415 Leu Leu Glu Met Lys Ser Leu Ile Leu Pro Pro Glu His Ile Leu Lys             420 425 430 Arg Gly Asp Ser Glu Ala Ile Ala Tyr Ala Phe Phe His Leu Gln His         435 440 445 Trp Lys Arg Ile Glu Gly Ala Leu Asn Leu Leu Gln Cys Thr Trp Glu     450 455 460 Gly Thr Phe Arg Met Ile Pro Tyr Pro Leu Glu Lys Gly His Leu Phe 465 470 475 480 Tyr Pro Tyr Pro Ser Cys Thr Glu Thr Ala Asp Arg Glu Leu Leu Pro                 485 490 495 Thr Phe His His Val Ser Val Tyr Pro Lys Lys Glu Leu Pro Leu Phe             500 505 510 Ile His Phe Thr Ala Gly Phe Cys Ser Ser Thr Ala Met Ile Ala Ile         515 520 525 Leu Thr His Gln Phe Pro Glu Ile Met Gly Ile Phe Ala Lys Ala Val     530 535 540 Leu Gly Leu Trp Cys Pro Gln Pro Trp Ala Ser Ser Gly Phe Glu Glu 545 550 555 560 Asn Thr Gln Asp Leu Lys Ser Glu Asp Leu Gly Leu Ser Ser Gly                 565 570 575 <210> 22 <211> 424 <212> PRT <213> Homo sapiens <400> 22 Met Ser Asp His Gly Asp Val Ser Leu Pro Pro Glu Asp Arg Val Arg   1 5 10 15 Ala Leu Ser Gln Leu Gly Ser Ala Val Glu Val Asn Glu Asp Ile Pro              20 25 30 Pro Arg Arg Tyr Phe Arg Ser Gly Val Glu Ile Ile Arg Met Ala Ser          35 40 45 Ile Tyr Ser Glu Glu Gly Asn Ile Glu His Ala Phe Ile Leu Tyr Asn      50 55 60 Lys Tyr Ile Thr Leu Phe Ile Glu Lys Leu Pro Lys His Arg Asp Tyr  65 70 75 80 Lys Ser Ala Val Ile Pro Glu Lys Lys Asp Thr Val Lys Lys Leu Lys                  85 90 95 Glu Ile Ala Phe Pro Lys Ala Glu Glu Leu Lys Ala Glu Leu Leu Lys             100 105 110 Arg Tyr Thr Lys Glu Tyr Thr Glu Tyr Asn Glu Glu Lys Lys Lys Glu         115 120 125 Ala Glu Glu Leu Ala Arg Asn Met Ala Ile Gln Gln Glu Leu Glu Lys     130 135 140 Glu Lys Gln Arg Val Ala Gln Gln Lys Gln Gln Gln Leu Glu Gln Glu 145 150 155 160 Gln Phe His Ala Phe Glu Glu Met Ile Arg Asn Gln Glu Leu Glu Lys                 165 170 175 Glu Arg Leu Lys Ile Val Gln Glu Phe Gly Lys Val Asp Pro Gly Leu             180 185 190 Gly Gly Pro Leu Val Pro Asp Leu Glu Lys Pro Ser Leu Asp Val Phe         195 200 205 Pro Thr Leu Thr Val Ser Ser Ile Gln Pro Ser Asp Cys His Thr Thr     210 215 220 Val Arg Pro Ala Lys Pro Pro Val Val Asp Arg Ser Leu Lys Pro Gly 225 230 235 240 Ala Leu Ser Asn Ser Glu Ser Ile Pro Thr Ile Asp Gly Leu Arg His                 245 250 255 Val Val Val Pro Gly Arg Leu Cys Pro Gln Phe Leu Gln Leu Ala Ser             260 265 270 Ala Asn Thr Ala Arg Gly Val Glu Thr Cys Gly Ile Leu Cys Gly Lys         275 280 285 Leu Met Arg Asn Glu Phe Thr Ile Thr His Val Leu Ile Pro Lys Gln     290 295 300 Ser Ala Gly Ser Asp Tyr Cys Asn Thr Glu Asn Glu Glu Glu Leu Phe 305 310 315 320 Leu Ile Gln Asp Gln Gln Gly Leu Ile Thr Leu Gly Trp Ile His Thr                 325 330 335 His Pro Thr Gln Thr Ala Phe Leu Ser Ser Val Asp Leu His Thr His             340 345 350 Cys Ser Tyr Gln Met Met Leu Pro Glu Ser Val Ala Ile Val Cys Ser         355 360 365 Pro Lys Phe Gln Glu Thr Gly Phe Phe Lys Leu Thr Asp His Gly Leu     370 375 380 Glu Glu Ile Ser Ser Cys Arg Gln Lys Gly Phe His Pro His Ser Lys 385 390 395 400 Asp Pro Pro Leu Phe Cys Ser Cys Ser His Val Thr Val Val Asp Arg                 405 410 415 Ala Val Thr Ile Thr Asp Leu Arg             420 <210> 23 <211> 786 <212> PRT <213> Homo sapiens <400> 23 Met Ser Phe Ser Arg Ala Leu Leu Trp Ala Arg Leu Pro Ala Gly Arg   1 5 10 15 Gln Ala Gly His Arg Ala Ala Ile Cys Ser Ala Leu Arg Pro His Phe              20 25 30 Gly Pro Phe Pro Gly Val Leu Gly Gln Val Ser Val Leu Ala Thr Ala          35 40 45 Ser Ser Ser Ala Ser Gly Gly Ser Lys Ile Pro Asn Thr Ser Leu Phe      50 55 60 Val Pro Leu Thr Val Lys Pro Gln Gly Pro Ser Ala Asp Gly Asp Val  65 70 75 80 Gly Ala Glu Leu Thr Arg Pro Leu Asp Lys Asn Glu Val Lys Lys Val                  85 90 95 Leu Asp Lys Phe Tyr Lys Arg Lys Glu Ile Gln Lys Leu Gly Ala Asp             100 105 110 Tyr Gly Leu Asp Ala Arg Leu Phe His Gln Ala Phe Ile Ser Phe Arg         115 120 125 Asn Tyr Ile Met Gln Ser His Ser Leu Asp Val Asp Ile His Ile Val     130 135 140 Leu Asn Asp Ile Cys Phe Gly Ala Ala His Ala Asp Asp Leu Phe Pro 145 150 155 160 Phe Phe Leu Arg His Ala Lys Gln Ile Phe Pro Val Leu Asp Cys Lys                 165 170 175 Asp Asp Leu Arg Lys Ile Ser Asp Leu Arg Ile Pro Pro Asn Trp Tyr             180 185 190 Pro Asp Ala Arg Ala Met Gln Arg Lys Ile Ile Phe His Ser Gly Pro         195 200 205 Thr Asn Ser Gly Lys Thr Tyr His Ala Ile Gln Lys Tyr Phe Ser Ala     210 215 220 Lys Ser Gly Val Tyr Cys Gly Pro Leu Lys Leu Leu Ala His Glu Ile 225 230 235 240 Phe Glu Lys Ser Asn Ala Ala Gly Val Pro Cys Asp Leu Val Thr Gly                 245 250 255 Glu Glu Arg Val Thr Val Gln Pro Asn Gly Lys Gln Ala Ser His Val             260 265 270 Ser Cys Thr Val Glu Met Cys Ser Val Thr Thr Pro Tyr Glu Val Ala         275 280 285 Val Ile Asp Glu Ile Gln Met Ile Arg Asp Pro Ala Arg Gly Trp Ala     290 295 300 Trp Thr Arg Ala Leu Leu Gly Leu Cys Ala Glu Glu Val His Leu Cys 305 310 315 320 Gly Glu Pro Ala Ala Ile Asp Leu Val Met Glu Leu Met Tyr Thr Thr                 325 330 335 Gly Glu Glu Val Glu Val Arg Asp Tyr Lys Arg Leu Thr Pro Ile Ser             340 345 350 Val Leu Asp His Ala Leu Glu Ser Leu Asp Asn Leu Arg Pro Gly Asp         355 360 365 Cys Ile Val Cys Phe Ser Lys Asn Asp Ile Tyr Ser Val Ser Arg Gln     370 375 380 Ile Glu Ile Arg Gly Leu Glu Ser Ala Val Ile Tyr Gly Ser Leu Pro 385 390 395 400 Pro Gly Thr Lys Leu Ala Gln Ala Lys Lys Phe Asn Asp Pro Asn Asp                 405 410 415 Pro Cys Lys Ile Leu Val Ala Thr Asp Ala Ile Gly Met Gly Leu Asn             420 425 430 Leu Ser Ile Arg Arg Ile Ile Phe Tyr Ser Leu Ile Lys Pro Ser Ile         435 440 445 Asn Glu Lys Gly Glu Arg Glu Leu Glu Pro Ile Thr Thr Ser Gln Ala     450 455 460 Leu Gln Ile Ala Gly Arg Ala Gly Arg Phe Ser Ser Arg Phe Lys Glu 465 470 475 480 Gly Glu Val Thr Thr Met Asn His Glu Asp Leu Ser Leu Leu Lys Glu                 485 490 495 Ile Leu Lys Arg Pro Val Asp Pro Ile Arg Ala Ala Gly Leu His Pro             500 505 510 Thr Ala Glu Gln Ile Glu Met Phe Ala Tyr His Leu Pro Asp Ala Thr         515 520 525 Leu Ser Asn Leu Ile Asp Ile Phe Val Asp Phe Ser Gln Val Asp Gly     530 535 540 Gln Tyr Phe Val Cys Asn Met Asp Asp Phe Lys Phe Ser Ala Glu Leu 545 550 555 560 Ile Gln His Ile Pro Leu Ser Leu Arg Val Arg Tyr Val Phe Cys Thr                 565 570 575 Ala Pro Ile Asn Lys Lys Gln Pro Phe Val Cys Ser Ser Leu Leu Gln             580 585 590 Phe Ala Arg Gln Tyr Ser Arg Asn Glu Pro Leu Thr Phe Ala Trp Leu         595 600 605 Arg Arg Tyr Ile Lys Trp Pro Leu Leu Pro Pro Lys Asn Ile Lys Asp     610 615 620 Leu Met Asp Leu Glu Ala Val His Asp Val Leu Asp Leu Tyr Leu Trp 625 630 635 640 Leu Ser Tyr Arg Phe Met Asp Met Phe Pro Asp Ala Ser Leu Ile Arg                 645 650 655 Asp Leu Gln Lys Glu Leu Asp Gly Ile Ile Gln Asp Gly Val His Asn             660 665 670 Ile Thr Lys Leu Ile Lys Met Ser Glu Thr His Lys Leu Leu Asn Leu         675 680 685 Glu Gly Phe Pro Ser Gly Ser Gln Ser Arg Leu Ser Gly Thr Leu Lys     690 695 700 Ser Gln Ala Arg Arg Thr Arg Gly Thr Lys Ala Leu Gly Ser Lys Ala 705 710 715 720 Thr Glu Pro Pro Ser Pro Asp Ala Gly Glu Leu Ser Leu Ala Ser Arg                 725 730 735 Leu Val Gln Gln Gly Leu Leu Thr Pro Asp Met Leu Lys Gln Leu Glu             740 745 750 Lys Glu Trp Met Thr Gln Gln Thr Glu His Asn Lys Glu Lys Thr Glu         755 760 765 Ser Gly Thr His Pro Lys Gly Thr Arg Arg Lys Lys Lys Glu Pro Asp     770 775 780 Ser Asp 785 <210> 24 <211> 443 <212> PRT <213> Homo sapiens <400> 24 Met Asp Arg Leu Gly Ser Phe Ser Asn Asp Pro Ser Asp Lys Pro Pro   1 5 10 15 Cys Arg Gly Cys Ser Ser Tyr Leu Met Glu Pro Tyr Ile Lys Cys Ala              20 25 30 Glu Cys Gly Pro Pro Pro Phe Phe Leu Cys Leu Gln Cys Phe Thr Arg          35 40 45 Gly Phe Glu Tyr Lys Lys His Gln Ser Asp His Thr Tyr Glu Ile Met      50 55 60 Thr Ser Asp Phe Pro Val Leu Asp Pro Ser Trp Thr Ala Gln Glu Glu  65 70 75 80 Met Ala Leu Leu Glu Ala Val Met Asp Cys Gly Phe Gly Asn Trp Gln                  85 90 95 Asp Val Ala Asn Gln Met Cys Thr Lys Thr Lys Glu Glu Cys Glu Lys             100 105 110 His Tyr Met Lys His Phe Ile Asn Asn Pro Leu Phe Ala Ser Thr Leu         115 120 125 Leu Asn Leu Lys Gln Ala Glu Glu Ala Lys Thr Ala Asp Thr Ala Ile     130 135 140 Pro Phe His Ser Thr Asp Asp Pro Pro Arg Pro Thr Phe Asp Ser Leu 145 150 155 160 Leu Ser Arg Asp Met Ala Gly Tyr Met Pro Ala Arg Ala Asp Phe Ile                 165 170 175 Glu Glu Phe Asp Asn Tyr Ala Glu Trp Asp Leu Arg Asp Ile Asp Phe             180 185 190 Val Glu Asp Asp Ser Asp Ile Leu His Ala Leu Lys Met Ala Val Val         195 200 205 Asp Ile Tyr His Ser Arg Leu Lys Glu Arg Gln Arg Arg Lys Lys Ile     210 215 220 Ile Arg Asp His Gly Leu Ile Asn Leu Arg Lys Phe Gln Leu Met Glu 225 230 235 240 Arg Arg Tyr Pro Lys Glu Val Gln Asp Leu Tyr Glu Thr Met Arg Arg                 245 250 255 Phe Ala Arg Ile Val Gly Pro Val Glu His Asp Lys Phe Ile Glu Ser             260 265 270 His Ala Leu Glu Phe Glu Leu Arg Arg Glu Ile Lys Arg Leu Gln Glu         275 280 285 Tyr Arg Thr Ala Gly Ile Thr Asn Phe Cys Ser Ala Arg Thr Tyr Asp     290 295 300 His Leu Lys Lys Thr Arg Glu Glu Glu Arg Leu Lys Arg Thr Met Leu 305 310 315 320 Ser Glu Val Leu Gln Tyr Ile Gln Asp Ser Ser Ala Cys Gln Gln Trp                 325 330 335 Leu Arg Arg Gln Ala Asp Ile Asp Ser Gly Leu Ser Pro Ser Ile Pro             340 345 350 Met Ala Ser Asn Ser Gly Arg Arg Ser Ala Pro Pro Leu Asn Leu Thr         355 360 365 Gly Leu Pro Gly Thr Glu Lys Leu Asn Glu Lys Glu Lys Glu Leu Cys     370 375 380 Gln Met Val Arg Leu Val Pro Gly Ala Tyr Leu Glu Tyr Lys Ser Ala 385 390 395 400 Leu Leu Asn Glu Cys Asn Lys Gln Gly Gly Leu Arg Leu Ala Gln Ala                 405 410 415 Arg Ala Leu Ile Lys Ile Asp Val Asn Lys Thr Arg Lys Ile Tyr Asp             420 425 430 Phe Leu Ile Arg Glu Gly Tyr Ile Thr Lys Gly         435 440 <210> 25 <211> 147 <212> PRT <213> Homo sapiens <400> 25 Met Ala Leu Lys Arg Ile Gln Lys Glu Leu Ser Asp Leu Gln Arg Asp   1 5 10 15 Pro Pro Ala His Cys Ser Ala Gly Pro Val Gly Asp Asp Leu Phe His              20 25 30 Trp Gln Ala Thr Ile Met Gly Pro Pro Asp Ser Ala Tyr Gln Gly Gly          35 40 45 Val Phe Phe Leu Thr Val His Phe Pro Thr Asp Tyr Pro Phe Lys Pro      50 55 60 Pro Lys Ile Ala Phe Thr Thr Lys Ile Tyr His Pro Asn Ile Asn Ser  65 70 75 80 Asn Gly Ser Ile Cys Leu Asp Ile Leu Arg Ser Gln Trp Ser Pro Ala                  85 90 95 Leu Thr Val Ser Lys Val Leu Leu Ser Ile Cys Ser Leu Leu Cys Asp             100 105 110 Pro Asn Pro Asp Asp Pro Leu Val Pro Asp Ile Ala Gln Ile Tyr Lys         115 120 125 Ser Asp Lys Glu Lys Tyr Asn Arg His Ala Arg Glu Trp Thr Gln Lys     130 135 140 Tyr ala met 145 <210> 26 <211> 527 <212> PRT <213> Homo sapiens <400> 26 Met Arg Ser Asp Lys Ser Ala Leu Val Phe Leu Leu Leu Gln Leu Phe   1 5 10 15 Cys Val Gly Cys Gly Phe Cys Gly Lys Val Leu Val Trp Pro Cys Asp              20 25 30 Met Ser His Trp Leu Asn Val Lys Val Ile Leu Glu Glu Leu Ile Val          35 40 45 Arg Gly His Glu Val Thr Val Leu Thr His Ser Lys Pro Ser Leu Ile      50 55 60 Asp Tyr Arg Lys Pro Ser Ala Leu Lys Phe Glu Val Val His Met Pro  65 70 75 80 Gln Asp Arg Thr Glu Glu Asn Glu Ile Phe Val Asp Leu Ala Leu Asn                  85 90 95 Val Leu Pro Gly Leu Ser Thr Trp Gln Ser Val Ile Lys Leu Asn Asp             100 105 110 Phe Phe Val Glu Ile Arg Gly Thr Leu Lys Met Met Cys Glu Ser Phe         115 120 125 Ile Tyr Asn Gln Thr Leu Met Lys Lys Leu Gln Glu Thr Asn Tyr Asp     130 135 140 Val Met Leu Ile Asp Pro Val Ile Pro Cys Gly Asp Leu Met Ala Glu 145 150 155 160 Leu Leu Ala Val Pro Phe Val Leu Thr Leu Arg Ile Ser Val Gly Gly                 165 170 175 Asn Met Glu Arg Ser Cys Gly Lys Leu Pro Ala Pro Leu Ser Tyr Val             180 185 190 Pro Val Pro Met Thr Gly Leu Thr Asp Arg Met Thr Phe Leu Glu Arg         195 200 205 Val Lys Asn Ser Met Leu Ser Val Leu Phe His Phe Trp Ile Gln Asp     210 215 220 Tyr Asp Tyr His Phe Trp Glu Glu Phe Tyr Ser Lys Ala Leu Gly Arg 225 230 235 240 Pro Thr Thr Leu Cys Glu Thr Val Gly Lys Ala Glu Ile Trp Leu Ile                 245 250 255 Arg Thr Tyr Trp Asp Phe Glu Phe Pro Gln Pro Tyr Gln Pro Asn Phe             260 265 270 Glu Phe Val Gly Gly Leu His Cys Lys Pro Ala Lys Ala Leu Pro Lys         275 280 285 Glu Met Glu Asn Phe Val Gln Ser Ser Gly Glu Asp Gly Ile Val Val     290 295 300 Phe Ser Leu Gly Ser Leu Phe Gln Asn Val Thr Glu Glu Lys Ala Asn 305 310 315 320 Ile Ile Ala Ser Ala Leu Ala Gln Ile Pro Gln Lys Val Leu Trp Arg                 325 330 335 Tyr Lys Gly Lys Lys Pro Ser Thr Leu Gly Ala Asn Thr Arg Leu Tyr             340 345 350 Asp Trp Ile Pro Gln Asn Asp Leu Leu Gly His Pro Lys Thr Lys Ala         355 360 365 Phe Ile Thr His Gly Gly Met Asn Gly Ile Tyr Glu Ala Ile Tyr His     370 375 380 Gly Val Pro Met Val Gly Val Pro Ile Phe Gly Asp Gln Leu Asp Asn 385 390 395 400 Ile Ala His Met Lys Ala Lys Gly Ala Ala Val Glu Ile Asn Phe Lys                 405 410 415 Thr Met Thr Ser Glu Asp Leu Leu Arg Ala Leu Arg Thr Val Ile Thr             420 425 430 Asp Ser Ser Tyr Lys Glu Asn Ala Met Arg Leu Ser Arg Ile His His         435 440 445 Asp Gln Pro Val Lys Pro Leu Asp Arg Ala Val Phe Trp Ile Glu Phe     450 455 460 Val Met Arg His Lys Gly Ala Lys His Leu Arg Ser Ala Ala His Asp 465 470 475 480 Leu Thr Trp Phe Gln His Tyr Ser Ile Asp Val Ile Gly Phe Leu Leu                 485 490 495 Ala Cys Val Ala Thr Ala Ile Phe Leu Phe Thr Lys Cys Phe Leu Phe             500 505 510 Ser Cys Gln Lys Phe Asn Lys Thr Arg Lys Ile Glu Lys Arg Glu         515 520 525 <210> 27 <211> 509 <212> PRT <213> Homo sapiens <400> 27 Met Ala Leu Ser Gln Gly Leu Leu Thr Phe Arg Asp Val Ala Ile Glu   1 5 10 15 Phe Ser Gln Glu Glu Trp Lys Cys Leu Asp Pro Ala Gln Arg Thr Leu              20 25 30 Tyr Arg Asp Val Met Leu Glu Asn Tyr Arg Asn Leu Val Ser Leu Asp          35 40 45 Ile Ser Ser Lys Cys Met Met Asn Thr Leu Ser Ser Thr Gly Gln Gly      50 55 60 Asn Thr Glu Val Ile His Thr Gly Thr Leu Gln Arg Gln Ala Ser Tyr  65 70 75 80 His Ile Gly Ala Phe Cys Ser Gln Glu Ile Glu Lys Asp Ile His Asp                  85 90 95 Phe Val Phe Gln Trp Gln Glu Asp Glu Thr Asn Asp His Glu Ala Pro             100 105 110 Met Thr Glu Ile Lys Lys Leu Thr Ser Ser Thr Asp Arg Tyr Asp Gln         115 120 125 Arg His Ala Gly Asn Lys Pro Ile Lys Gly Gln Leu Glu Ser Arg Phe     130 135 140 His Leu His Leu Arg Arg His Arg Arg Ile His Thr Gly Glu Lys Pro 145 150 155 160 Tyr Lys Cys Glu Glu Cys Glu Lys Val Phe Ser Cys Lys Ser His Leu                 165 170 175 Glu Ile His Arg Ile Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Lys             180 185 190 Val Cys Asp Lys Ala Phe Lys His Asp Ser His Leu Ala Lys His Thr         195 200 205 Arg Ile His Arg Gly Asp Lys His Tyr Thr Cys Asn Glu Cys Gly Lys     210 215 220 Val Phe Asp Gln Lys Ala Thr Leu Ala Cys His His Arg Ser His Thr 225 230 235 240 Gly Glu Lys Pro Tyr Lys Cys Asn Glu Cys Gly Lys Thr Phe Ser Gln                 245 250 255 Thr Ser His Leu Val Tyr His His Arg Leu His Thr Gly Glu Lys Pro             260 265 270 Tyr Lys Cys Asn Glu Cys Gly Lys Thr Phe Ala Arg Asn Ser Val Leu         275 280 285 Val Ile His Lys Ala Val His Thr Ala Glu Lys Pro Tyr Lys Cys Asn     290 295 300 Glu Cys Gly Lys Val Phe Lys Gln Arg Ala Thr Leu Ala Gly His Arg 305 310 315 320 Arg Val His Thr Gly Glu Lys Pro Tyr Arg Cys Glu Glu Cys Asp Lys                 325 330 335 Val Phe Ser Arg Lys Ser His Leu Glu Arg His Arg Arg Ile His Thr             340 345 350 Gly Glu Lys Pro Tyr Lys Cys Lys Val Cys Asp Lys Ala Phe Arg Ser         355 360 365 Asp Ser Arg Leu Ala Glu His Gln Arg Val His Thr Gly Glu Arg Pro     370 375 380 Tyr Thr Cys Asn Glu Cys Gly Lys Val Phe Ser Thr Lys Ala Tyr Leu 385 390 395 400 Ala Cys His Gln Lys Leu His Thr Gly Glu Lys Leu Tyr Glu Cys Glu                 405 410 415 Glu Cys Asp Lys Val Tyr Ile Arg Lys Ser His Leu Glu Arg His Arg             420 425 430 Arg Ile His Thr Gly Glu Lys Pro His Lys Cys Gly Asp Cys Gly Lys         435 440 445 Ala Phe Asn Ser Pro Ser His Leu Ile Arg His Gln Arg Ile His Thr     450 455 460 Gly Gln Lys Ser Tyr Lys Cys His Gln Cys Gly Lys Val Phe Ser Leu 465 470 475 480 Arg Ser Leu Leu Ala Glu His Gln Lys Ile Pro Phe Gly Asp Asn Cys                 485 490 495 Phe Lys Cys Asn Glu Tyr Ser Lys Pro Ser Ser Ile Asn             500 505 <210> 28 <211> 642 <212> PRT <213> Homo sapiens <400> 28 Met Glu Glu Glu Arg Lys Thr Ala Glu Leu Gln Lys Asn Arg Ile Gln   1 5 10 15 Asp Ser Val Val Phe Glu Asp Val Ala Val Asp Phe Thr Gln Glu Glu              20 25 30 Trp Ala Leu Leu Asp Leu Ala Gln Arg Asn Leu Tyr Arg Asp Val Met          35 40 45 Leu Glu Asn Phe Gln Asn Leu Ala Ser Leu Gly Tyr Pro Leu His Thr      50 55 60 Pro His Leu Ile Ser Gln Trp Glu Gln Glu Glu Asp Leu Gln Thr Val  65 70 75 80 Lys Arg Glu Leu Ile Gln Gly Ile Phe Met Gly Glu His Arg Glu Gly                  85 90 95 Phe Glu Thr Gln Leu Lys Thr Asn Glu Ser Val Ala Ser Gln Asp Ile             100 105 110 Cys Gly Glu Lys Ile Ser Asn Glu Gln Lys Ile Val Arg Phe Lys Arg         115 120 125 Asn Asp Ser Trp Phe Ser Ser Leu His Glu Asn Gln Glu Ser Cys Gly     130 135 140 Ile Asp Tyr Gln Asn Lys Ser His Glu Arg His Leu Arg Asn His Met 145 150 155 160 Val Glu Asn Ile Tyr Glu Cys Tyr Glu Glu Asn Gln Asp Gly Gln Thr                 165 170 175 Phe Ser Gln Val Pro Asn Leu Asp Ser Leu Lys Arg Asn Thr Glu Val             180 185 190 Lys Ser Cys Glu Cys His Glu Cys Gly Lys Ala Phe Val Asp His Ser         195 200 205 Ser Leu Lys Ser His Ile Arg Ser His Thr Gly Ser Lys Pro Tyr Gln     210 215 220 Cys Lys Glu Cys Gly Lys Ala Phe His Phe Leu Ala Cys Phe Lys Lys 225 230 235 240 His Met Lys Thr Pro Thr Glu Glu Lys Pro Tyr Glu Cys Lys Glu Cys                 245 250 255 Thr Lys Ala Phe Ser Cys Ser Ser Phe Phe Arg Ala His Met Lys Ile             260 265 270 His Ile Gly Lys Thr Asn Tyr Glu Cys Lys Glu Cys Gly Lys Gly Phe         275 280 285 Ser Cys Ser Ser Ser Le Leu Thr Glu His Lys Arg Ile His Ser Gly Asp     290 295 300 Lys Pro Tyr Glu Cys Lys Glu Cys Gly Lys Ala Phe Ser Cys Ser Ser 305 310 315 320 Ser Leu Ser Lys His Lys Arg Ile His Ser Gly Asp Lys Pro Tyr Glu                 325 330 335 Cys Lys Glu Cys Gly Lys Ala Phe Ser Ser Ser Ser His Leu Ile Ile             340 345 350 His Ile Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys         355 360 365 Gly Lys Ala Phe Ser Glu Ser Ser Lys Leu Thr Val His Gly Arg Thr     370 375 380 His Thr Gly Glu Lys Pro Tyr Lys Cys Lys Glu Cys Gly Lys Ala Tyr 385 390 395 400 Asn Cys Pro Ser Ser Le Leu Ser Ile His Met Arg Lys His Thr Gly Glu                 405 410 415 Lys Pro Tyr Glu Cys Leu Glu Cys Gly Lys Ala Phe Tyr Leu Pro Thr             420 425 430 Ser Leu Asn Thr His Val Lys Asn Gln Ser Arg Glu Lys Pro Tyr Glu         435 440 445 Cys Lys Glu Cys Gly Lys Ala Phe Ser Cys Pro Ser Ser Phe Arg Ala     450 455 460 His Val Arg Asp His Thr Gly Lys Ile Gln Tyr Glu Cys Lys Glu Cys 465 470 475 480 Gly Lys Thr Phe Ser Arg Ser Ser Ser Leu Thr Glu His Leu Arg Thr                 485 490 495 His Ser Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys Gly Lys Ala Phe             500 505 510 Ile Ser Ser Ser His Leu Thr Val His Ile Arg Thr His Thr Gly Glu         515 520 525 Lys Pro Tyr Glu Cys Lys Lys Cys Gly Lys Ala Phe Ile Tyr Pro Ser     530 535 540 Ala Leu Arg Ile His Met Arg Thr His Thr Gly Glu Lys Pro Tyr Glu 545 550 555 560 Cys Lys Glu Cys Gly Lys Ala Phe Arg His Ser Ser Tyr Leu Thr Val                 565 570 575 His Ala Arg Met His Thr Gly Glu Lys Pro Phe Glu Cys Leu Glu Cys             580 585 590 Gly Lys Ala Phe Ser Cys Pro Ser Ser Phe Arg Arg His Val Arg Ser         595 600 605 His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys Gly Lys Ala Phe     610 615 620 Val Cys Pro Ala Tyr Phe Arg Arg His Val Lys Thr His Thr Arg Glu 625 630 635 640 Asn yle         <210> 29 <211> 813 <212> PRT <213> Homo sapiens <400> 29 Met Gly Trp Arg Pro Arg Arg Ala Arg Gly Thr Pro Leu Leu Leu Leu   1 5 10 15 Leu Leu Leu Leu Leu Leu Trp Pro Val Pro Gly Ala Gly Val Leu Gln              20 25 30 Gly His Ile Pro Gly Gln Pro Val Thr Pro His Trp Val Leu Asp Gly          35 40 45 Gln Pro Trp Arg Thr Val Ser Leu Glu Glu Pro Val Ser Lys Pro Asp      50 55 60 Met Gly Leu Val Ala Leu Glu Ala Glu Gly Gln Glu Leu Leu Leu Glu  65 70 75 80 Leu Glu Lys Asn His Arg Leu Leu Ala Pro Gly Tyr Ile Glu Thr His                  85 90 95 Tyr Gly Pro Asp Gly Gln Pro Val Val Leu Ala Pro Asn His Thr Asp             100 105 110 His Cys His Tyr Gln Gly Arg Val Arg Gly Phe Pro Asp Ser Trp Val         115 120 125 Val Leu Cys Thr Cys Ser Gly Met Ser Gly Leu Ile Thr Leu Ser Arg     130 135 140 Asn Ala Ser Tyr Tyr Leu Arg Pro Trp Pro Pro Arg Gly Ser Lys Asp 145 150 155 160 Phe Ser Thr His Glu Ile Phe Arg Met Glu Gln Leu Leu Thr Trp Lys                 165 170 175 Gly Thr Cys Gly His Arg Asp Pro Gly Asn Lys Ala Gly Met Thr Ser             180 185 190 Leu Pro Gly Gly Pro Gln Ser Arg Gly Arg Arg Glu Ala Arg Arg Thr         195 200 205 Arg Lys Tyr Leu Glu Leu Tyr Ile Val Ala Asp His Thr Leu Phe Leu     210 215 220 Thr Arg His Arg Asn Leu Asn His Thr Lys Gln Arg Leu Leu Glu Val 225 230 235 240 Ala Asn Tyr Val Asp Gln Leu Leu Arg Thr Leu Asp Ile Gln Val Ala                 245 250 255 Leu Thr Gly Leu Glu Val Trp Thr Glu Arg Asp Arg Ser Arg Val Thr             260 265 270 Gln Asp Ala Asn Ala Thr Leu Trp Ala Phe Leu Gln Trp Arg Arg Gly         275 280 285 Leu Trp Ala Gln Arg Pro His Asp Ser Ala Gln Leu Leu Thr Gly Arg     290 295 300 Ala Phe Gln Gly Ala Thr Val Gly Leu Ala Pro Val Glu Gly Met Cys 305 310 315 320 Arg Ala Glu Ser Ser Gly Gly Val Ser Thr Asp His Ser Glu Leu Pro                 325 330 335 Ile Gly Ala Ala Ala Thr Met Ala His Glu Ile Gly His Ser Leu Gly             340 345 350 Leu Ser His Asp Pro Asp Gly Cys Cys Val Glu Ala Ala Ala Glu Ser         355 360 365 Gly Gly Cys Val Met Ala Ala Ala Thr Gly His Pro Phe Pro Arg Val     370 375 380 Phe Ser Ala Cys Ser Arg Arg Gln Leu Arg Ala Phe Phe Arg Lys Gly 385 390 395 400 Gly Gly Ala Cys Leu Ser Asn Ala Pro Asp Pro Gly Leu Pro Val Pro                 405 410 415 Pro Ala Leu Cys Gly Asn Gly Phe Val Glu Ala Gly Glu Glu Cys Asp             420 425 430 Cys Gly Pro Gly Gln Glu Cys Arg Asp Leu Cys Cys Phe Ala His Asn         435 440 445 Cys Ser Leu Arg Pro Gly Ala Gln Cys Ala His Gly Asp Cys Cys Val     450 455 460 Arg Cys Leu Leu Lys Pro Ala Gly Ala Leu Cys Arg Gln Ala Met Gly 465 470 475 480 Asp Cys Asp Leu Pro Glu Phe Cys Thr Gly Thr Ser Ser His Cys Pro                 485 490 495 Pro Asp Val Tyr Leu Leu Asp Gly Ser Pro Cys Ala Arg Gly Ser Gly             500 505 510 Tyr Cys Trp Asp Gly Ala Cys Pro Thr Leu Glu Gln Gln Cys Gln Gln         515 520 525 Leu Trp Gly Pro Gly Ser His Pro Ala Pro Glu Ala Cys Phe Gln Val     530 535 540 Val Asn Ser Ala Gly Asp Ala His Gly Asn Cys Gly Gln Asp Ser Glu 545 550 555 560 Gly His Phe Leu Pro Cys Ala Gly Arg Asp Ala Leu Cys Gly Lys Leu                 565 570 575 Gln Cys Gln Gly Gly Lys Pro Ser Leu Leu Ala Pro His Met Val Pro             580 585 590 Val Asp Ser Thr Val His Leu Asp Gly Gln Glu Val Thr Cys Arg Gly         595 600 605 Ala Leu Ala Leu Pro Ser Ala Gln Leu Asp Leu Leu Gly Leu Gly Leu     610 615 620 Val Glu Pro Gly Thr Gln Cys Gly Pro Arg Met Val Cys Gln Ser Arg 625 630 635 640 Arg Cys Arg Lys Asn Ala Phe Gln Glu Leu Gln Arg Cys Leu Thr Ala                 645 650 655 Cys His Ser His Gly Val Cys Asn Ser Asn His Asn Cys His Cys Ala             660 665 670 Pro Gly Trp Ala Pro Pro Phe Cys Asp Lys Pro Gly Phe Gly Gly Ser         675 680 685 Met Asp Ser Gly Pro Val Gln Ala Glu Asn His Asp Thr Phe Leu Leu     690 695 700 Ala Met Leu Leu Ser Val Leu Leu Pro Leu Leu Pro Gly Ala Gly Leu 705 710 715 720 Ala Trp Cys Cys Tyr Arg Leu Pro Gly Ala His Leu Gln Arg Cys Ser                 725 730 735 Trp Gly Cys Arg Arg Asp Pro Ala Cys Ser Gly Pro Lys Asp Gly Pro             740 745 750 His Arg Asp His Pro Leu Gly Gly Val His Pro Met Glu Leu Gly Pro         755 760 765 Thr Ala Thr Gly Gln Pro Trp Pro Leu Asp Pro Glu Asn Ser His Glu     770 775 780 Pro Ser Ser His Pro Glu Lys Pro Leu Pro Ala Val Ser Pro Asp Pro 785 790 795 800 Gln Ala Asp Gln Val Gln Met Pro Arg Ser Cys Leu Trp                 805 810 <210> 30 <211> 397 <212> PRT <213> Homo sapiens <400> 30 Met Ser Val Gly Arg Arg Arg Ile Lys Leu Leu Gly Ile Leu Met Met   1 5 10 15 Ala Asn Val Phe Ile Tyr Phe Ile Met Glu Val Ser Lys Ser Ser Ser              20 25 30 Gln Glu Lys Asn Gly Lys Gly Glu Val Ile Ile Pro Lys Glu Lys Phe          35 40 45 Trp Lys Ile Ser Thr Pro Pro Glu Ala Tyr Trp Asn Arg Glu Gln Glu      50 55 60 Lys Leu Asn Arg Gln Tyr Asn Pro Ile Leu Ser Met Leu Thr Asn Gln  65 70 75 80 Thr Gly Glu Ala Gly Arg Leu Ser Asn Ile Ser His Leu Asn Tyr Cys                  85 90 95 Glu Pro Asp Leu Arg Val Thr Ser Val Val Thr Gly Phe Asn Asn Leu             100 105 110 Pro Asp Arg Phe Lys Asp Phe Leu Leu Tyr Leu Arg Cys Arg Asn Tyr         115 120 125 Ser Leu Leu Ile Asp Gln Pro Asp Lys Cys Ala Lys Lys Pro Phe Leu     130 135 140 Leu Leu Ala Ile Lys Ser Leu Thr Pro His Phe Ala Arg Arg Gln Ala 145 150 155 160 Ile Arg Glu Ser Trp Gly Gln Glu Ser Asn Ala Gly Asn Gln Thr Val                 165 170 175 Val Arg Val Phe Leu Leu Gly Gln Thr Pro Pro Glu Asp Asn His Pro             180 185 190 Asp Leu Ser Asp Met Leu Lys Phe Glu Ser Glu Lys His Gln Asp Ile         195 200 205 Leu Met Trp Asn Tyr Arg Asp Thr Phe Phe Asn Leu Ser Leu Lys Glu     210 215 220 Val Leu Phe Leu Arg Trp Val Ser Thr Ser Cys Pro Asp Thr Glu Phe 225 230 235 240 Val Phe Lys Gly Asp Asp Asp Val Phe Val Asn Thr His His Ile Leu                 245 250 255 Asn Tyr Leu Asn Ser Leu Ser Lys Thr Lys Ala Lys Asp Leu Phe Ile             260 265 270 Gly Asp Val Ile His Asn Ala Gly Pro His Arg Asp Lys Lys Leu Lys         275 280 285 Tyr Tyr Ile Pro Glu Val Val Tyr Ser Gly Leu Tyr Pro Pro Tyr Ala     290 295 300 Gly Gly Gly Gly Phe Leu Tyr Ser Gly His Leu Ala Leu Arg Leu Tyr 305 310 315 320 His Ile Thr Asp Gln Val His Leu Tyr Pro Ile Asp Asp Val Tyr Thr                 325 330 335 Gly Met Cys Leu Gln Lys Leu Gly Leu Val Pro Glu Lys His Lys Gly             340 345 350 Phe Arg Thr Phe Asp Ile Glu Glu Lys Asn Lys Asn Asn Ile Cys Ser         355 360 365 Tyr Val Asp Leu Met Leu Val His Ser Arg Lys Pro Gln Glu Met Ile     370 375 380 Asp Ile Trp Ser Gln Leu Gln Ser Ala His Leu Lys Cys 385 390 395 <210> 31 <211> 540 <212> PRT <213> Homo sapiens <400> 31 Met Tyr Glu Asn Glu Cys Glu Cys Gln Leu Leu Leu Lys Glu Met Leu   1 5 10 15 Glu Arg Leu Asn Lys Glu Ala Asp Glu Ala Leu Leu His Asn Leu Arg              20 25 30 Leu Gln Leu Glu Ala Gln Phe Leu Gln Asp Asp Ile Ser Ala Ala Lys          35 40 45 Asp Arg His Lys Lys Asn Leu Leu Glu Val Gln Thr Tyr Ile Ser Ile      50 55 60 Leu Gln Gln Ile Ile His Thr Thr Pro Pro Ala Ser Ile Val Thr Ser  65 70 75 80 Gly Met Arg Glu Glu Lys Leu Leu Thr Glu Arg Glu Val Ala Ala Leu                  85 90 95 Arg Ser Gln Leu Glu Glu Gly Arg Glu Val Leu Ser His Leu Gln Ala             100 105 110 Gln Arg Val Glu Leu Gln Ala Gln Thr Thr Thr Leu Glu Gln Ala Ile         115 120 125 Lys Ser Ala His Glu Cys Tyr Asp Asp Glu Ile Gln Leu Tyr Asn Glu     130 135 140 Gln Ile Glu Thr Leu Arg Lys Glu Ile Glu Glu Thr Glu Arg Val Leu 145 150 155 160 Glu Lys Ser Ser Tyr Asp Cys Arg Gln Leu Ala Val Ala Gln Gln Thr                 165 170 175 Leu Lys Asn Glu Leu Asp Arg Tyr His Arg Ile Ile Glu Ile Glu Gly             180 185 190 Asn Arg Leu Thr Ser Ala Phe Ile Glu Thr Pro Ile Pro Leu Phe Thr         195 200 205 Gln Ser His Gly Val Ser Leu Ser Thr Gly Ser Gly Gly Lys Asp Leu     210 215 220 Thr Arg Ala Leu Gln Asp Ile Thr Ala Ala Lys Pro Arg Gln Lys Ala 225 230 235 240 Leu Pro Lys Asn Val Pro Arg Arg Lys Glu Ile Ile Thr Lys Asp Lys                 245 250 255 Thr Asn Gly Ala Leu Glu Asp Ala Pro Leu Lys Gly Leu Glu Asp Thr             260 265 270 Lys Leu Val Gln Val Val Leu Lys Glu Glu Ser Glu Ser Lys Phe Glu         275 280 285 Ser Glu Ser Lys Glu Val Ser Pro Leu Thr Gln Glu Gly Ala Pro Glu     290 295 300 Asp Val Pro Asp Gly Gly Gln Ile Ser Lys Gly Phe Gly Lys Leu Tyr 305 310 315 320 Arg Lys Val Lys Glu Lys Val Arg Ser Pro Lys Glu Pro Glu Thr Pro                 325 330 335 Thr Glu Leu Tyr Thr Lys Glu Arg His Val Leu Val Thr Gly Asp Ala             340 345 350 Asn Tyr Val Asp Pro Arg Phe Tyr Val Ser Ser Ile Thr Ala Lys Gly         355 360 365 Gly Val Ala Val Ser Val Ala Glu Asp Ser Val Leu Tyr Asp Gly Gln     370 375 380 Val Glu Pro Ser Pro Glu Ser Pro Lys Pro Pro Leu Glu Asn Gly Gln 385 390 395 400 Val Gly Leu Gln Glu Lys Glu Asp Gly Gln Pro Ile Asp Gln Gln Pro                 405 410 415 Ile Asp Lys Glu Ile Glu Pro Asp Gly Ala Glu Leu Glu Gly Pro Glu             420 425 430 Glu Lys Arg Glu Gly Glu Glu Arg Asp Glu Glu Ser Arg Arg Pro Cys         435 440 445 Ala Met Val Thr Pro Gly Ala Glu Glu Pro Ser Ile Pro Glu Pro Pro     450 455 460 Lys Pro Ala Ala Asp Gln Asp Gly Ala Glu Val Leu Gly Thr Arg Ser 465 470 475 480 Arg Ser Leu Pro Glu Lys Gly Pro Pro Lys Ala Leu Ala Tyr Lys Thr                 485 490 495 Val Glu Val Val Glu Ser Ile Glu Lys Ile Ser Thr Glu Ser Ile Gln             500 505 510 Thr Tyr Glu Glu Thr Ala Val Ile Val Glu Thr Met Ile Gly Lys Thr         515 520 525 Lys Ser Asp Lys Lys Lys Ser Gly Glu Lys Ser Ser     530 535 540 <210> 32 <211> 1037 <212> PRT <213> Homo sapiens <400> 32 Met Ala Thr Glu Ser Thr Pro Ser Glu Ile Glu Arg Glu Arg Lys   1 5 10 15 Lys Leu Leu Glu Ile Leu Gln His Asp Pro Asp Ser Ile Leu Asp Thr              20 25 30 Leu Thr Ser Arg Arg Leu Ile Ser Glu Glu Glu Tyr Glu Thr Leu Glu          35 40 45 Asn Val Thr Asp Leu Leu Lys Lys Ser Arg Lys Leu Leu Ile Leu Val      50 55 60 Gln Lys Lys Gly Glu Ala Thr Cys Gln His Phe Leu Lys Cys Leu Phe  65 70 75 80 Ser Thr Phe Pro Gln Ser Ala Ala Ile Cys Gly Leu Arg His Glu Val                  85 90 95 Leu Lys His Glu Asn Thr Val Pro Pro Gln Ser Met Gly Ala Ser Ser             100 105 110 Asn Ser Glu Asp Ala Phe Ser Pro Gly Ile Lys Gln Pro Glu Ala Pro         115 120 125 Glu Ile Thr Val Phe Phe Ser Glu Lys Glu His Leu Asp Leu Glu Thr     130 135 140 Ser Glu Phe Phe Arg Asp Lys Lys Thr Ser Tyr Arg Glu Thr Ala Leu 145 150 155 160 Ser Ala Arg Lys Asn Glu Lys Glu Tyr Asp Thr Pro Glu Val Thr Leu                 165 170 175 Ser Tyr Ser Val Glu Lys Val Gly Cys Glu Val Pro Ala Thr Ile Thr             180 185 190 Tyr Ile Lys Asp Gly Gln Arg Tyr Glu Glu Leu Asp Asp Ser Leu Tyr         195 200 205 Leu Gly Lys Glu Glu Tyr Leu Gly Ser Val Asp Thr Pro Glu Asp Ala     210 215 220 Glu Ala Thr Val Glu Glu Glu Val Tyr Asp Asp Pro Glu His Val Gly 225 230 235 240 Tyr Asp Gly Glu Glu Asp Phe Glu Asn Ser Glu Thr Thr Glu Phe Ser                 245 250 255 Gly Glu Glu Pro Ser Tyr Glu Gly Ser Glu Thr Ser Leu Ser Leu Glu             260 265 270 Glu Glu Gln Glu Lys Ser Ile Glu Glu Arg Lys Lys Val Phe Lys Asp         275 280 285 Val Leu Leu Cys Leu Asn Met Asp Arg Ser Arg Lys Val Leu Pro Asp     290 295 300 Phe Val Lys Gln Phe Ser Leu Asp Arg Gly Cys Lys Trp Thr Pro Glu 305 310 315 320 Ser Pro Gly Asp Leu Ala Trp Asn Phe Leu Met Lys Val Gln Ala Arg                 325 330 335 Asp Val Thr Ala Arg Asp Ser Ile Leu Ser His Lys Val Leu Asp Glu             340 345 350 Asp Ser Lys Glu Asp Leu Leu Ala Gly Val Glu Asn Leu Glu Ile Arg         355 360 365 Asp Ile Gln Thr Ile Asn Pro Leu Asp Val Leu Cys Ala Thr Met Leu     370 375 380 Cys Ser Asp Ser Ser Leu Gln Arg Gln Val Met Ser Asn Met Tyr Gln 385 390 395 400 Cys Gln Phe Ala Leu Pro Leu Leu Leu Pro Asp Ala Glu Asn Asn Lys                 405 410 415 Ser Ile Leu Met Leu Gly Ala Met Lys Asp Ile Val Lys Lys Gln Ser             420 425 430 Thr Gln Phe Ser Gly Gly Pro Thr Glu Asp Thr Glu Lys Phe Leu Thr         435 440 445 Leu Met Lys Met Pro Val Ile Ser Phe Val Arg Leu Gly Tyr Cys Ser     450 455 460 Phe Ser Lys Ser Arg Ile Leu Asn Thr Leu Leu Ser Pro Ala Gln Leu 465 470 475 480 Lys Leu His Lys Ile Phe Leu His Gln Asp Leu Pro Leu Leu Val Leu                 485 490 495 Pro Arg Gln Ile Ser Asp Gly Leu Val Glu Ile Thr Trp Cys Phe Pro             500 505 510 Asp Ser Asp Asp Arg Lys Glu Asn Pro Phe Phe Gln Lys Pro Val Ala         515 520 525 Leu Ala Asn Leu Arg Gly Asn Leu Glu Ser Phe Trp Thr Gln Phe Gly     530 535 540 Phe Leu Met Glu Val Ser Ser Ala Val Phe Phe Phe Thr Asp Cys Leu 545 550 555 560 Gly Glu Lys Glu Trp Asp Leu Leu Met Phe Leu Gly Glu Ala Ala Ile                 565 570 575 Glu Arg Cys Tyr Phe Val Leu Ser Ser Gln Ala Arg Glu Ser Glu Glu             580 585 590 Ala Gln Ile Phe Gln Arg Ile Leu Asn Leu Lys Pro Ala Gln Leu Leu         595 600 605 Phe Trp Glu Arg Gly Asp Ala Gly Asp Arg Arg Lys Asn Met Glu Gly     610 615 620 Leu Gln Ala Ala Leu Gln Glu Val Met Phe Ser Ser Cys Leu Arg Cys 625 630 635 640 Val Ser Val Glu Asp Met Ala Ala Leu Ala Arg Glu Leu Gly Ile Gln                 645 650 655 Val Asp Glu Asp Phe Glu Asn Thr Gln Arg Ile Gln Val Ser Ser Gly             660 665 670 Glu Asn Met Ala Gly Thr Ala Glu Gly Glu Gly Gln Gln Arg His Ser         675 680 685 Gln Leu Lys Ser Ser Ser Ly Lys Ser Gln Ala Leu Met Pro Ile Gln Glu     690 695 700 Pro Gly Thr Gln Cys Glu Leu Ser Gln Asn Leu Gln Asn Leu Tyr Gly 705 710 715 720 Thr Pro Val Phe Arg Pro Val Leu Glu Asn Ser Trp Leu Phe Pro Thr                 725 730 735 Arg Ile Gly Gly Asn Phe Asn His Val Ser Leu Lys Ala Ser Trp Val             740 745 750 Met Gly Arg Pro Phe Gly Ser Glu Gln Arg Pro Lys Trp Phe His Pro         755 760 765 Leu Pro Phe Gln Asn Ala Gly Ala Gln Gly Arg Gly Lys Ser Phe Gly     770 775 780 Ile Gln Ser Phe His Pro Gln Ile Phe Tyr Ser Gly Glu Arg Phe Met 785 790 795 800 Lys Phe Ser Arg Val Ala Arg Gly Cys His Ser Asn Gly Thr Phe Gly                 805 810 815 Arg Leu Pro Arg Pro Ile Cys Gln His Val Gln Ala Cys Pro Glu Arg             820 825 830 Pro Gln Met Met Gly Thr Leu Glu Arg Ser Arg Ala Val Ala Ser Lys         835 840 845 Ile Gly His Ser Tyr Ser Leu Asp Ser Gln Pro Ala Arg Ala Val Gly     850 855 860 Lys Pro Trp Pro Gln Gln Ala Cys Thr Arg Val Thr Glu Leu Thr Glu 865 870 875 880 Ala Thr Gly Lys Leu Ile Arg Thr Ser His Ile Gly Lys Pro His Pro                 885 890 895 Gln Ser Phe Gln Pro Ala Ala Ala Thr Gln Lys Leu Arg Pro Ala Ser             900 905 910 Gln Gln Gly Val Gln Met Lys Thr Gln Gly Gly Ala Ser Asn Pro Ala         915 920 925 Leu Gln Ile Gly Ser His Pro Met Cys Lys Ser Ser Gln Phe Lys Ser     930 935 940 Asp Gln Ser Asn Pro Ser Thr Val Lys His Ser Gln Pro Lys Pro Phe 945 950 955 960 His Ser Val Pro Ser Gln Pro Lys Ser Ser Gln Thr Lys Ser Cys Gln                 965 970 975 Ser Gln Pro Ser Gln Thr Lys Pro Ser Pro Cys Lys Ser Thr Gln Pro             980 985 990 Lys Pro Ser Gln Pro Trp Pro Pro Gln Ser Lys Pro Ser Gln Pro Arg         995 1000 1005 Pro Pro Gln Pro Lys Ser Ser Ser Thr Asn Pro Ser Gln Ala Lys Ala    1010 1015 1020 His His Ser Lys Ala Gly Gln Lys Arg Gly Gly Lys His 1025 1030 1035 <210> 33 <211> 466 <212> PRT <213> Homo sapiens <400> 33 Met Asn Asn Ser Thr Asn Ser Ser Asn Asn Ser Leu Ala Leu Thr Ser   1 5 10 15 Pro Tyr Lys Thr Phe Glu Val Val Phe Ile Val Leu Val Ala Gly Ser              20 25 30 Leu Ser Leu Val Thr Ile Ile Gly Asn Ile Leu Val Met Val Ser Ile          35 40 45 Lys Val Asn Arg His Leu Gln Thr Val Asn Asn Tyr Phe Leu Phe Ser      50 55 60 Leu Ala Cys Ala Asp Leu Ile Ile Gly Val Phe Ser Met Asn Leu Tyr  65 70 75 80 Thr Leu Tyr Thr Val Ile Gly Tyr Trp Pro Leu Gly Pro Val Val Cys                  85 90 95 Asp Leu Trp Leu Ala Leu Asp Tyr Val Val Ser Asn Ala Ser Val Met             100 105 110 Asn Leu Leu Ile Ile Ser Phe Asp Arg Tyr Phe Cys Val Thr Lys Pro         115 120 125 Leu Thr Tyr Pro Val Lys Arg Thr Thr Lys Met Ala Gly Met Met Ile     130 135 140 Ala Ala Ala Trp Val Leu Ser Phe Ile Leu Trp Ala Pro Ala Ile Leu 145 150 155 160 Phe Trp Gln Phe Ile Val Gly Val Arg Thr Val Glu Asp Gly Glu Cys                 165 170 175 Tyr Ile Gln Phe Phe Ser Asn Ala Ala Val Thr Phe Gly Thr Ala Ile             180 185 190 Ala Ala Phe Tyr Leu Pro Val Ile Met Thr Val Leu Tyr Trp His         195 200 205 Ile Ser Arg Ala Ser Lys Ser Arg Ile Lys Lys Asp Lys Lys Glu Pro     210 215 220 Val Ala Asn Gln Asp Pro Val Ser Pro Ser Leu Val Gln Gly Arg Ile 225 230 235 240 Val Lys Pro Asn Asn Asn Asn Met Pro Ser Ser Asp Asp Gly Leu Glu                 245 250 255 His Asn Lys Ile Gln Asn Gly Lys Ala Pro Arg Asp Pro Val Thr Glu             260 265 270 Asn Cys Val Gln Gly Glu Glu Lys Glu Ser Ser Asn Asp Ser Thr Ser         275 280 285 Val Ser Ala Val Ala Ser Asn Met Arg Asp Asp Glu Ile Thr Gln Asp     290 295 300 Glu Asn Thr Val Ser Thr Ser Leu Gly His Ser Lys Asp Glu Asn Ser 305 310 315 320 Lys Gln Thr Cys Ile Arg Ile Gly Thr Lys Thr Pro Lys Ser Asp Ser                 325 330 335 Cys Thr Pro Thr Asn Thr Thr Val Glu Val Val Gly Ser Ser Gly Gln             340 345 350 Asn Gly Asp Glu Lys Gln Asn Ile Val Ala Arg Lys Ile Val Lys Met         355 360 365 Thr Lys Gln Pro Ala Lys Lys Lys Pro Pro Pro Ser Arg Glu Lys Lys     370 375 380 Val Thr Arg Thr Ile Leu Ala Ile Leu Leu Ala Phe Ile Ile Thr Trp 385 390 395 400 Ala Pro Tyr Asn Val Met Val Leu Ile Asn Thr Phe Cys Ala Pro Cys                 405 410 415 Ile Pro Asn Thr Val Trp Thr Ile Gly Tyr Trp Leu Cys Tyr Ile Asn             420 425 430 Ser Thr Ile Asn Pro Ala Cys Tyr Ala Leu Cys Asn Ala Thr Phe Lys         435 440 445 Lys Thr Phe Lys His Leu Leu Met Cys His Tyr Lys Asn Ile Gly Ala     450 455 460 Thr arg 465 <210> 34 <211> 687 <212> PRT <213> Homo sapiens <400> 34 Met Leu Ser Phe Phe Arg Arg Thr Leu Gly Arg Arg Ser Met Arg Lys   1 5 10 15 His Ala Glu Lys Glu Arg Leu Arg Glu Ala Gln Arg Ala Ala Thr His              20 25 30 Ile Pro Ala Ala Gly Asp Ser Lys Ser Ile Ile Thr Cys Arg Val Ser          35 40 45 Leu Leu Asp Gly Thr Asp Val Ser Val Asp Leu Pro Lys Lys Ala Lys      50 55 60 Gly Gln Glu Leu Phe Asp Gln Ile Met Tyr His Leu Asp Leu Ile Glu  65 70 75 80 Ser Asp Tyr Phe Gly Leu Arg Phe Met Asp Ser Ala Gln Val Ala His                  85 90 95 Trp Leu Asp Gly Thr Lys Ser Ile Lys Lys Gln Val Lys Ile Gly Ser             100 105 110 Pro Tyr Cys Leu His Leu Arg Val Lys Phe Tyr Ser Ser Glu Pro Asn         115 120 125 Asn Leu Arg Glu Glu Leu Thr Arg Tyr Leu Phe Val Leu Gln Leu Lys     130 135 140 Gln Asp Ile Leu Ser Gly Lys Leu Asp Cys Pro Phe Asp Thr Ala Val 145 150 155 160 Gln Leu Ala Ala Tyr Asn Leu Gln Ala Glu Leu Gly Asp Tyr Asp Leu                 165 170 175 Ala Glu His Ser Pro Glu Leu Val Ser Glu Phe Arg Phe Val Pro Ile             180 185 190 Gln Thr Glu Glu Met Glu Leu Ala Ile Phe Glu Lys Trp Lys Glu Tyr         195 200 205 Arg Gly Gln Thr Pro Ala Gln Ala Glu Thr Asn Tyr Leu Asn Lys Ala     210 215 220 Lys Trp Leu Glu Met Tyr Gly Val Asp Met His Val Val Lys Ala Arg 225 230 235 240 Asp Gly Asn Asp Tyr Ser Leu Gly Leu Thr Pro Thr Gly Val Leu Val                 245 250 255 Phe Glu Gly Asp Thr Lys Ile Gly Leu Phe Phe Trp Pro Lys Ile Thr             260 265 270 Arg Leu Asp Phe Lys Lys Asn Lys Leu Thr Leu Val Val Val Glu Asp         275 280 285 Asp Asp Gln Gly Lys Glu Gln Glu His Thr Phe Val Phe Arg Leu Asp     290 295 300 His Pro Lys Ala Cys Lys His Leu Trp Lys Cys Ala Val Glu His His 305 310 315 320 Ala Phe Phe Arg Leu Arg Gly Pro Val Gln Lys Ser Ser His Arg Ser                 325 330 335 Gly Phe Ile Arg Leu Gly Ser Arg Phe Arg Tyr Ser Gly Lys Thr Glu             340 345 350 Tyr Gln Thr Thr Lys Thr Asn Lys Ala Arg Arg Ser Thr Ser Phe Glu         355 360 365 Arg Arg Pro Ser Lys Arg Tyr Ser Arg Arg Thr Leu Gln Met Lys Ala     370 375 380 Cys Ala Thr Lys Pro Glu Glu Leu Ser Val His Asn Asn Val Ser Thr 385 390 395 400 Gln Ser Asn Gly Ser Gln Gln Ala Trp Gly Met Arg Ser Ala Leu Pro                 405 410 415 Val Ser Pro Ser Ile Ser Ser Ala Pro Val Pro Val Glu Ile Glu Asn             420 425 430 Leu Pro Gln Ser Pro Gly Thr Asp Gln His Asp Arg Lys Cys Ile Pro         435 440 445 Leu Asn Ile Asp Leu Leu Asn Ser Pro Asp Leu Leu Glu Ala Thr Ile     450 455 460 Gly Asp Val Ile Gly Ala Ser Asp Thr Met Glu Thr Ser Gln Ala Leu 465 470 475 480 Asn Asp Val Asn Val Ala Thr Arg Leu Pro Gly Leu Gly Glu Pro Glu                 485 490 495 Val Glu Tyr Glu Thr Leu Lys Asp Thr Ser Glu Lys Leu Lys Gln Leu             500 505 510 Glu Met Glu Asn Ser Pro Leu Leu Ser Pro Arg Ser Asn Ile Asp Val         515 520 525 Asn Ile Asn Ser Gln Glu Glu Val Val Lys Leu Thr Glu Lys Cys Leu     530 535 540 Asn Asn Val Ile Glu Ser Pro Gly Leu Asn Val Met Arg Val Pro Pro 545 550 555 560 Asp Phe Lys Ser Asn Ile Leu Lys Ala Gln Val Glu Ala Val His Lys                 565 570 575 Val Thr Lys Glu Asp Ser Leu Leu Ser His Lys Asn Ala Asn Val Gln             580 585 590 Asp Ala Ala Thr Asn Ser Ala Val Leu Asn Glu Asn Asn Val Pro Leu         595 600 605 Pro Lys Glu Ser Leu Glu Thr Leu Met Leu Ile Thr Pro Ala Asp Ser     610 615 620 Gly Ser Val Leu Lys Glu Ala Thr Asp Glu Leu Asp Ala Leu Leu Ala 625 630 635 640 Ser Leu Thr Glu Asn Leu Ile Asp His Thr Val Ala Pro Gln Val Ser                 645 650 655 Ser Thr Ser Met Ile Thr Pro Arg Trp Ile Val Pro Leu Trp Ser His             660 665 670 Phe Gly Arg Arg Ser Cys Pro Glu Ala Glu Val Phe Thr Asp His         675 680 685 <210> 35 <211> 566 <212> PRT <213> Homo sapiens <400> 35 Met Asp Glu Gly Gly Thr Pro Leu Leu Pro Asp Ser Leu Val Tyr Gln   1 5 10 15 Ile Phe Leu Ser Leu Gly Pro Ala Asp Val Leu Ala Ala Gly Leu Val              20 25 30 Cys Arg Gln Trp Gln Ala Val Ser Arg Asp Glu Phe Leu Trp Arg Glu          35 40 45 Gln Phe Tyr Arg Tyr Tyr Gln Val Ala Arg Asp Val Pro Arg His Pro      50 55 60 Ala Ala Met Ser Trp Tyr Glu Glu Phe Gln Arg Leu Tyr Asp Thr Val  65 70 75 80 Pro Cys Val Glu Val Gln Thr Leu Arg Glu His Thr Asp Gln Val Leu                  85 90 95 His Leu Ser Phe Ser His Ser Gly Tyr Gln Phe Ala Ser Cys Ser Lys             100 105 110 Asp Cys Thr Val Lys Ile Trp Ser Asn Asp Leu Thr Ile Ser Leu Leu         115 120 125 His Ser Ala Asp Met Arg Pro Tyr Asn Trp Ser Tyr Thr Gln Phe Ser     130 135 140 Gln Phe Asn Lys Asp Asp Ser Leu Leu Leu Ala Ser Gly Val Phe Leu 145 150 155 160 Gly Pro His Asn Ser Ser Ser Gly Glu Ile Ala Val Ile Ser Leu Asp                 165 170 175 Ser Phe Ala Leu Leu Ser Arg Val Arg Asn Lys Pro Tyr Asp Val Phe             180 185 190 Gly Cys Trp Leu Thr Glu Thr Ser Leu Ile Ser Gly Asn Leu His Arg         195 200 205 Ile Gly Asp Ile Thr Ser Cys Ser Val Leu Trp Leu Asn Asn Ala Phe     210 215 220 Gln Asp Val Glu Ser Glu Asn Val Asn Val Val Lys Arg Leu Phe Lys 225 230 235 240 Ile Gln Asn Leu Asn Ala Ser Thr Val Arg Thr Val Met Val Ala Asp                 245 250 255 Cys Ser Arg Phe Asp Ser Pro Asp Leu Leu Leu Glu Ala Gly Asp Pro             260 265 270 Ala Thr Ser Pro Cys Arg Ile Phe Asp Leu Gly Ser Asp Asn Glu Glu         275 280 285 Val Val Ala Gly Pro Ala Pro Ala His Ala Lys Glu Gly Leu Arg His     290 295 300 Phe Leu Asp Arg Val Leu Glu Gly Arg Ala Gln Pro Gln Leu Ser Glu 305 310 315 320 Arg Met Leu Glu Thr Lys Val Ala Glu Leu Leu Ala Gln Gly His Thr                 325 330 335 Lys Pro Pro Glu Arg Ser Ala Thr Gly Ala Lys Ser Lys Tyr Leu Ile             340 345 350 Phe Thr Thr Gly Cys Leu Thr Tyr Ser Pro His Gln Ile Gly Ile Lys         355 360 365 Gln Ile Leu Pro His Gln Met Thr Thr Ala Gly Pro Val Leu Gly Glu     370 375 380 Gly Arg Gly Ser Asp Ala Phe Phe Asp Ala Leu Asp His Val Ile Asp 385 390 395 400 Ile His Gly His Ile Ile Gly Met Gly Leu Ser Pro Asp Asn Arg Tyr                 405 410 415 Leu Tyr Val Asn Ser Arg Ala Trp Pro Asn Gly Ala Val Val Ala Asp             420 425 430 Pro Met Gln Pro Pro Pro Ile Ala Glu Glu Ile Asp Leu Leu Val Phe         435 440 445 Asp Leu Lys Thr Met Arg Glu Val Arg Arg Ala Leu Arg Ala His Arg     450 455 460 Ala Tyr Thr Pro Asn Asp Glu Cys Phe Phe Ile Phe Leu Asp Val Ser 465 470 475 480 Arg Asp Phe Val Ala Ser Gly Ala Glu Asp Arg His Gly Tyr Ile Trp                 485 490 495 Asp Arg His Tyr Asn Ile Cys Leu Ala Arg Leu Arg His Glu Asp Val             500 505 510 Val Asn Ser Val Val Phe Ser Pro Gln Glu Gln Glu Leu Leu Leu Thr         515 520 525 Ala Ser Asp Asp Ala Thr Ile Lys Ala Trp Arg Ser Pro Arg Thr Met     530 535 540 Arg Val Leu Gln Ala Pro Arg Pro Arg Pro Arg Thr Phe Phe Ser Trp 545 550 555 560 Leu Ala Ser Gln Arg Arg                 565 <210> 36 <211> 373 <212> PRT <213> Homo sapiens <400> 36 Met Ala Asn Thr Thr Gly Glu Pro Glu Glu Val Ser Gly Ala Leu Ser   1 5 10 15 Pro Pro Ser Ala Ser Ala Tyr Val Lys Leu Val Leu Leu Gly Leu Ile              20 25 30 Met Cys Val Ser Leu Ala Gly Asn Ala Ile Leu Ser Leu Leu Val Leu          35 40 45 Lys Glu Arg Ala Leu His Lys Ala Pro Tyr Tyr Phe Leu Leu Asp Leu      50 55 60 Cys Leu Ala Asp Gly Ile Arg Ser Ala Val Cys Phe Pro Phe Val Leu  65 70 75 80 Ala Ser Val Arg His Gly Ser Ser Trp Thr Phe Ser Ala Leu Ser Cys                  85 90 95 Lys Ile Val Ala Phe Met Ala Val Leu Phe Cys Phe His Ala Ala Phe             100 105 110 Met Leu Phe Cys Ile Ser Val Thr Arg Tyr Met Ala Ile Ala His His         115 120 125 Arg Phe Tyr Ala Lys Arg Met Thr Leu Trp Thr Cys Ala Ala Val Ile     130 135 140 Cys Met Ala Trp Thr Leu Ser Val Ala Met Ala Phe Pro Pro Val Phe 145 150 155 160 Asp Val Gly Thr Tyr Lys Phe Ile Arg Glu Glu Asp Gln Cys Ile Phe                 165 170 175 Glu His Arg Tyr Phe Lys Ala Asn Asp Thr Leu Gly Phe Met Leu Met             180 185 190 Leu Ala Val Leu Met Ala Ala Thr His Ala Val Tyr Gly Lys Leu Leu         195 200 205 Leu Phe Glu Tyr Arg His Arg Lys Met Lys Pro Val Gln Met Val Pro     210 215 220 Ala Ile Ser Gln Asn Trp Thr Phe His Gly Pro Gly Ala Thr Gly Gln 225 230 235 240 Ala Ala Ala Asn Trp Ile Ala Gly Phe Gly Arg Gly Pro Met Pro Pro                 245 250 255 Thr Leu Leu Gly Ile Arg Gln Asn Gly His Ala Ala Ser Arg Arg Leu             260 265 270 Leu Gly Met Asp Glu Val Lys Gly Glu Lys Gln Leu Gly Arg Met Phe         275 280 285 Tyr Ala Ile Thr Leu Leu Phe Leu Leu Leu Trp Ser Pro Tyr Ile Val     290 295 300 Ala Cys Tyr Trp Arg Val Phe Val Lys Ala Cys Ala Val Pro His Arg 305 310 315 320 Tyr Leu Ala Thr Ala Val Trp Met Ser Phe Ala Gln Ala Ala Val Asn                 325 330 335 Pro Ile Val Cys Phe Leu Leu Asn Lys Asp Leu Lys Lys Cys Leu Arg             340 345 350 Thr His Ala Pro Cys Trp Gly Thr Gly Gly Ala Pro Ala Pro Arg Glu         355 360 365 Pro Tyr Cys Val Met     370 <210> 37 <211> 724 <212> PRT <213> Homo sapiens <400> 37 Met Leu Arg Thr Ser Thr Pro Asn Leu Cys Gly Gly Leu His Cys Arg   1 5 10 15 Ala Pro Trp Leu Ser Ser Gly Ile Leu Cys Leu Cys Leu Ile Phe Leu              20 25 30 Leu Gly Gln Val Gly Leu Leu Gln Gly His Pro Gln Cys Leu Asp Tyr          35 40 45 Gly Pro Pro Phe Gln Pro Pro Leu His Leu Glu Phe Cys Ser Asp Tyr      50 55 60 Glu Ser Phe Gly Cys Cys Asp Gln His Lys Asp Arg Arg Ile Ala Ala  65 70 75 80 Arg Tyr Trp Asp Ile Met Glu Tyr Phe Asp Leu Lys Arg His Glu Leu                  85 90 95 Cys Gly Asp Tyr Ile Lys Asp Ile Leu Cys Gln Glu Cys Ser Pro Tyr             100 105 110 Ala Ala His Leu Tyr Asp Ala Glu Asn Thr Gln Thr Pro Leu Arg Asn         115 120 125 Leu Pro Gly Leu Cys Ser Asp Tyr Cys Ser Ala Phe His Ser Asn Cys     130 135 140 His Ser Ala Ile Ser Leu Leu Thr Asn Asp Arg Gly Leu Gln Glu Ser 145 150 155 160 His Gly Arg Asp Gly Thr Arg Phe Cys His Leu Leu Asp Leu Pro Asp                 165 170 175 Lys Asp Tyr Cys Phe Pro Asn Val Leu Arg Asn Asp Tyr Leu Asn Arg             180 185 190 His Leu Gly Met Val Ala Gln Asp Pro Gln Gly Cys Leu Gln Leu Cys         195 200 205 Leu Ser Glu Val Ala Asn Gly Leu Arg Asn Pro Val Ser Met Val His     210 215 220 Ala Gly Asp Gly Thr His Arg Phe Phe Val Ala Glu Gln Val Gly Val 225 230 235 240 Val Trp Val Tyr Leu Pro Asp Gly Ser Arg Leu Glu Gln Pro Phe Leu                 245 250 255 Asp Leu Lys Asn Ile Val Leu Thr Thr Pro Trp Ile Gly Asp Glu Arg             260 265 270 Gly Phe Leu Gly Leu Ala Phe His Pro Lys Phe Arg His Asn Arg Lys         275 280 285 Phe Tyr Ile Tyr Tyr Ser Cys Leu Asp Lys Lys Lys Val Glu Lys Ile     290 295 300 Arg Ile Ser Glu Met Lys Val Ser Arg Ala Asp Pro Asn Lys Ala Asp 305 310 315 320 Leu Lys Ser Glu Arg Val Ile Leu Glu Ile Glu Glu Pro Ala Ser Asn                 325 330 335 His Asn Gly Gly Gln Leu Leu Phe Gly Leu Asp Gly Tyr Met Tyr Ile             340 345 350 Phe Thr Gly Asp Gly Gly Gln Ala Gly Asp Pro Phe Gly Leu Phe Gly         355 360 365 Asn Ala Gln Asn Lys Ser Ser Leu Leu Gly Lys Val Leu Arg Ile Asp     370 375 380 Val Asn Arg Ala Gly Ser His Gly Lys Arg Tyr Arg Val Pro Ser Asp 385 390 395 400 Asn Pro Phe Val Ser Glu Pro Gly Ala His Pro Ala Ile Tyr Ala Tyr                 405 410 415 Gly Ile Arg Asn Met Trp Arg Cys Ala Val Asp Arg Gly Asp Pro Ile             420 425 430 Thr Arg Gln Gly Arg Gly Arg Ile Phe Cys Gly Asp Val Gly Gln Asn         435 440 445 Arg Phe Glu Glu Val Asp Leu Ile Leu Lys Gly Gly Asn Tyr Gly Trp     450 455 460 Arg Ala Lys Glu Gly Phe Ala Cys Tyr Asp Lys Lys Leu Cys His Asn 465 470 475 480 Ala Ser Leu Asp Asp Val Leu Pro Ile Tyr Ala Tyr Gly His Ala Val                 485 490 495 Gly Lys Ser Val Thr Gly Gly Tyr Val Tyr Arg Gly Cys Glu Ser Pro             500 505 510 Asn Leu Asn Gly Leu Tyr Ile Phe Gly Asp Phe Met Ser Gly Arg Leu         515 520 525 Met Ala Leu Gln Glu Asp Arg Lys Asn Lys Lys Trp Lys Lys Gln Asp     530 535 540 Leu Cys Leu Gly Ser Thr Thr Ser Cys Ala Phe Pro Gly Leu Ile Ser 545 550 555 560 Thr His Ser Lys Phe Ile Ile Ser Phe Ala Glu Asp Glu Ala Gly Glu                 565 570 575 Leu Tyr Phe Leu Ala Thr Ser Tyr Pro Ser Ala Tyr Ala Pro Arg Gly             580 585 590 Ser Ile Tyr Lys Phe Val Asp Pro Ser Arg Arg Ala Pro Pro Gly Lys         595 600 605 Cys Lys Tyr Lys Pro Val Pro Val Arg Thr Lys Ser Lys Arg Ile Pro     610 615 620 Phe Arg Pro Leu Ala Lys Thr Val Leu Asp Leu Leu Lys Glu Gln Ser 625 630 635 640 Glu Lys Ala Ala Arg Lys Ser Ser Ser Ala Thr Leu Ala Ser Gly Pro                 645 650 655 Ala Gln Gly Leu Ser Glu Lys Gly Ser Ser Lys Lys Leu Ala Ser Pro             660 665 670 Thr Ser Ser Lys Asn Thr Leu Arg Gly Pro Gly Thr Lys Lys Lys Ala         675 680 685 Arg Val Gly Pro His Val Arg Gln Gly Lys Arg Arg Lys Ser Leu Lys     690 695 700 Ser His Ser Gly Arg Met Arg Pro Ser Ala Glu Gln Lys Arg Ala Gly 705 710 715 720 Arg Ser Leu Pro                 <210> 38 <211> 723 <212> PRT <213> Homo sapiens <400> 38 Met Cys Ser Gly Arg Phe Gln Asn Ile Gln Val Asn Pro Asp Phe Pro   1 5 10 15 Arg Gly Arg Ile Ser Asn Ser Phe Arg Arg Thr Ser Ser Thr Glu Asn              20 25 30 Lys Thr Lys Thr Leu Gly Lys Leu His Gln Glu Pro Arg Gln Leu Gln          35 40 45 Ser Asp Gly Lys Arg Lys Ile Leu Leu Glu Glu Leu Ala Asn Ser Asp      50 55 60 Pro Lys Leu Ala Leu Thr Gly Val Pro Ile Val Gln Trp Pro Lys Arg  65 70 75 80 Asp Lys Leu Lys Phe Pro Thr Arg Pro Lys Val Arg Val Pro Thr Ile                  85 90 95 Pro Ile Thr Lys Pro His Thr Met Lys Pro Ala Pro Arg Leu Thr Pro             100 105 110 Val Arg Pro Ala Ala Ala Ser Pro Ile Val Ser Gly Ala Arg Arg Arg         115 120 125 Arg Val Arg Cys Arg Lys Cys Lys Ala Cys Val Gln Gly Glu Cys Gly     130 135 140 Val Cys His Tyr Cys Arg Asp Met Lys Lys Phe Gly Gly Pro Gly Arg 145 150 155 160 Met Lys Gln Ser Cys Val Leu Arg Gln Cys Leu Ala Pro Arg Leu Pro                 165 170 175 His Ser Val Thr Cys Ser Leu Cys Gly Glu Val Asp Gln Asn Glu Glu             180 185 190 Thr Gln Asp Phe Glu Lys Lys Leu Met Glu Cys Cys Ile Cys Asn Glu         195 200 205 Ile Val His Pro Gly Cys Leu Gln Met Asp Gly Glu Gly Leu Leu Asn     210 215 220 Glu Glu Leu Pro Asn Cys Trp Glu Cys Pro Lys Cys Tyr Gln Glu Asp 225 230 235 240 Ser Ser Glu Lys Ala Gln Lys Arg Lys Met Glu Glu Ser Asp Glu Glu                 245 250 255 Ala Val Gln Ala Lys Val Leu Arg Pro Leu Arg Ser Cys Asp Glu Pro             260 265 270 Leu Thr Pro Pro Pro His Ser Pro Thr Ser Met Leu Gln Leu Ile His         275 280 285 Asp Pro Val Ser Pro Arg Gly Met Val Thr Arg Ser Ser Pro Gly Ala     290 295 300 Gly Pro Ser Asp His His Ser Ala Ser Arg Asp Glu Arg Phe Lys Arg 305 310 315 320 Arg Gln Leu Leu Arg Leu Gln Ala Thr Glu Arg Thr Met Val Arg Glu                 325 330 335 Lys Glu Asn Asn Pro Ser Gly Lys Lys Glu Leu Ser Glu Val Glu Lys             340 345 350 Ala Lys Ile Arg Gly Ser Tyr Leu Thr Val Thr Leu Gln Arg Pro Thr         355 360 365 Lys Glu Leu His Gly Thr Ser Ile Val Pro Lys Leu Gln Ala Ile Thr     370 375 380 Ala Ser Ser Ala Asn Leu Arg His Ser Pro Arg Val Leu Val Gln His 385 390 395 400 Cys Pro Ala Arg Thr Pro Gln Arg Gly Asp Glu Glu Gly Leu Gly Gly                 405 410 415 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Asp Ser Ala Glu             420 425 430 Glu Gly Gly Ala Ala Arg Leu Asn Gly Arg Gly Ser Trp Ala Gln Asp         435 440 445 Gly Asp Glu Ser Trp Met Gln Arg Glu Val Trp Met Ser Val Phe Arg     450 455 460 Tyr Leu Ser Arg Arg Glu Leu Cys Glu Cys Met Arg Val Cys Lys Thr 465 470 475 480 Trp Tyr Lys Trp Cys Cys Asp Lys Arg Leu Trp Thr Lys Ile Asp Leu                 485 490 495 Ser Arg Cys Lys Ala Ile Val Pro Gln Ala Leu Ser Gly Ile Ile Lys             500 505 510 Arg Gln Pro Val Ser Leu Asp Leu Ser Trp Thr Asn Ile Ser Lys Lys         515 520 525 Gln Leu Thr Trp Leu Val Asn Arg Leu Pro Gly Leu Lys Asp Leu Leu     530 535 540 Leu Ala Gly Cys Ser Trp Ser Ala Val Ser Ala Leu Ser Thr Ser Ser 545 550 555 560 Cys Pro Leu Leu Arg Thr Leu Asp Leu Arg Trp Ala Val Gly Ile Lys                 565 570 575 Asp Pro Gln Ile Arg Asp Leu Leu Thr Pro Pro Ala Asp Lys Pro Gly             580 585 590 Gln Asp Asn Arg Ser Lys Leu Arg Asn Met Thr Asp Phe Arg Leu Ala         595 600 605 Gly Leu Asp Ile Thr Asp Ala Thr Leu Arg Leu Ile Ile Arg His Met     610 615 620 Pro Leu Leu Ser Arg Leu Asp Leu Ser His Cys Ser His Leu Thr Asp 625 630 635 640 Gln Ser Ser Asn Leu Leu Thr Ala Val Gly Ser Ser Thr Arg Tyr Ser                 645 650 655 Leu Thr Glu Leu Asn Met Ala Gly Cys Asn Lys Leu Thr Asp Gln Thr             660 665 670 Leu Ile Tyr Leu Arg Arg Ile Ala Asn Val Thr Leu Ile Asp Leu Arg         675 680 685 Gly Cys Lys Gln Ile Thr Arg Lys Ala Cys Glu His Phe Ile Ser Asp     690 695 700 Leu Ser Ile Asn Ser Leu Tyr Cys Leu Ser Asp Glu Lys Leu Ile Gln 705 710 715 720 Lys Ile Ser             <210> 39 <211> 1690 <212> PRT <213> Homo sapiens <400> 39 Met Ala Gly Val Gly Pro Gly Gly Tyr Ala Ala Glu Phe Val Pro Pro   1 5 10 15 Pro Glu Cys Pro Val Phe Glu Pro Ser Trp Glu Glu Phe Thr Asp Pro              20 25 30 Leu Ser Phe Ile Gly Arg Ile Arg Pro Leu Ala Glu Lys Thr Gly Ile          35 40 45 Cys Lys Ile Arg Pro Pro Lys Asp Trp Gln Pro Pro Phe Ala Cys Glu      50 55 60 Val Lys Ser Phe Arg Phe Thr Pro Arg Val Gln Arg Leu Asn Glu Leu  65 70 75 80 Glu Ala Met Thr Arg Val Arg Leu Asp Phe Leu Asp Gln Leu Ala Lys                  85 90 95 Phe Trp Glu Leu Gln Gly Ser Thr Leu Lys Ile Pro Val Val Glu Arg             100 105 110 Lys Ile Leu Asp Leu Tyr Ala Leu Ser Lys Ile Val Ala Ser Lys Gly         115 120 125 Gly Phe Glu Met Val Thr Lys Glu Lys Lys Trp Ser Lys Val Gly Ser     130 135 140 Arg Leu Gly Tyr Leu Pro Gly Lys Gly Thr Gly Ser Leu Leu Lys Ser 145 150 155 160 His Tyr Glu Arg Ile Leu Tyr Pro Tyr Glu Leu Phe Gln Ser Gly Val                 165 170 175 Ser Leu Met Gly Val Gln Met Pro Asn Leu Asp Leu Lys Glu Lys Val             180 185 190 Glu Pro Glu Val Leu Ser Thr Asp Thr Gln Thr Ser Pro Glu Pro Gly         195 200 205 Thr Arg Met Asn Ile Leu Pro Lys Arg Thr Arg Arg Val Lys Thr Gln     210 215 220 Ser Glu Ser Gly Asp Val Ser Arg Asn Thr Glu Leu Lys Lys Leu Gln 225 230 235 240 Ile Phe Gly Ala Gly Pro Lys Val Val Gly Leu Ala Met Gly Thr Lys                 245 250 255 Asp Lys Glu Asp Glu Val Thr Arg Arg Arg Lys Val Thr Asn Arg Ser             260 265 270 Asp Ala Phe Asn Met Gln Met Arg Gln Arg Lys Gly Thr Leu Ser Val         275 280 285 Asn Phe Val Asp Leu Tyr Val Cys Met Phe Cys Gly Arg Gly Asn Asn     290 295 300 Glu Asp Lys Leu Leu Leu Cys Asp Gly Cys Asp Asp Ser Tyr His Thr 305 310 315 320 Phe Cys Leu Ile Pro Pro Leu Pro Asp Val Pro Lys Gly Asp Trp Arg                 325 330 335 Cys Pro Lys Cys Val Ala Glu Glu Cys Ser Lys Pro Arg Glu Ala Phe             340 345 350 Gly Phe Glu Gln Ala Val Arg Glu Tyr Thr Leu Gln Ser Phe Gly Glu         355 360 365 Met Ala Asp Asn Phe Lys Ser Asp Tyr Phe Asn Met Pro Val His Met     370 375 380 Val Pro Thr Glu Leu Val Glu Lys Glu Phe Trp Arg Leu Val Ser Ser 385 390 395 400 Ile Glu Glu Asp Val Ile Val Glu Tyr Gly Ala Asp Ile Ser Ser Lys                 405 410 415 Asp Phe Gly Ser Gly Phe Pro Val Lys Asp Gly Arg Arg Lys Ile Leu             420 425 430 Pro Glu Glu Glu Glu Tyr Ala Leu Ser Gly Trp Asn Leu Asn Asn Met         435 440 445 Pro Val Leu Glu Gln Ser Val Leu Ala His Ile Asn Val Asp Ile Ser     450 455 460 Gly Met Lys Val Pro Trp Leu Tyr Val Gly Met Cys Phe Ser Ser Phe 465 470 475 480 Cys Trp His Ile Glu Asp His Trp Ser Tyr Ser Ile Asn Tyr Leu His                 485 490 495 Trp Gly Glu Pro Lys Thr Trp Tyr Gly Val Pro Ser His Ala Ala Glu             500 505 510 Gln Leu Glu Glu Val Met Arg Glu Leu Ala Pro Glu Leu Phe Glu Ser         515 520 525 Gln Pro Asp Leu Leu His Gln Leu Val Thr Ile Met Asn Pro Asn Val     530 535 540 Leu Met Glu His Gly Val Pro Val Tyr Arg Thr Asn Gln Cys Ala Gly 545 550 555 560 Glu Phe Val Val Thr Phe Pro Arg Ala Tyr His Ser Gly Phe Asn Gln                 565 570 575 Gly Tyr Asn Phe Ala Glu Ala Val Asn Phe Cys Thr Ala Asp Trp Leu             580 585 590 Pro Ile Gly Arg Gln Cys Val Asn His Tyr Arg Arg Leu Arg Arg His         595 600 605 Cys Val Phe Ser His Glu Glu Leu Ile Phe Lys Met Ala Ala Asp Pro     610 615 620 Glu Cys Leu Asp Val Gly Leu Ala Ala Met Val Cys Lys Glu Leu Thr 625 630 635 640 Leu Met Thr Glu Glu Glu Thr Arg Leu Arg Glu Ser Val Val Gln Met                 645 650 655 Gly Val Leu Met Ser Glu Glu Glu Val Phe Glu Leu Val Pro Asp Asp             660 665 670 Glu Arg Gln Cys Ser Ala Cys Arg Thr Thr Cys Phe Leu Ser Ala Leu         675 680 685 Thr Cys Ser Cys Asn Pro Glu Arg Leu Val Cys Leu Tyr His Pro Thr     690 695 700 Asp Leu Cys Pro Cys Pro Met Gln Lys Lys Cys Leu Arg Tyr Arg Tyr 705 710 715 720 Pro Leu Glu Asp Leu Pro Ser Leu Leu Tyr Gly Val Lys Val Arg Ala                 725 730 735 Gln Ser Tyr Asp Thr Trp Val Ser Arg Val Thr Glu Ala Leu Ser Ala             740 745 750 Asn Phe Asn His Lys Lys Asp Leu Ile Glu Leu Arg Val Met Leu Glu         755 760 765 Asp Ala Glu Asp Arg Lys Tyr Pro Glu Asn Asp Leu Phe Arg Lys Leu     770 775 780 Arg Asp Ala Val Lys Glu Ala Glu Thr Cys Ala Ser Val Ala Gln Leu 785 790 795 800 Leu Leu Ser Lys Lys Gln Lys His Arg Gln Ser Pro Asp Ser Gly Arg                 805 810 815 Thr Arg Thr Lys Leu Thr Val Glu Glu Leu Lys Ala Phe Val Gln Gln             820 825 830 Leu Phe Ser Leu Pro Cys Val Ile Ser Gln Ala Arg Gln Val Lys Asn         835 840 845 Leu Leu Asp Asp Val Glu Glu Phe His Glu Arg Ala Gln Glu Ala Met     850 855 860 Met Asp Glu Thr Pro Asp Ser Ser Lys Leu Gln Met Leu Ile Asp Met 865 870 875 880 Gly Ser Ser Leu Tyr Val Glu Leu Pro Glu Leu Pro Arg Leu Lys Gln                 885 890 895 Glu Leu Gln Gln Ala Arg Trp Leu Asp Glu Val Arg Leu Thr Leu Ser             900 905 910 Asp Pro Gln Gln Val Thr Leu Asp Val Met Lys Lys Leu Ile Asp Ser         915 920 925 Gly Val Gly Leu Ala Pro His His Ala Val Glu Lys Ala Met Ala Glu     930 935 940 Leu Gln Glu Leu Leu Thr Val Ser Glu Arg Trp Glu Glu Lys Ala Lys 945 950 955 960 Val Cys Leu Gln Ala Arg Pro Arg His Ser Val Ala Ser Leu Glu Ser                 965 970 975 Ile Val Asn Glu Ala Lys Asn Ile Pro Ala Phe Leu Pro Asn Val Leu             980 985 990 Ser Leu Lys Glu Ala Leu Gln Lys Ala Arg Glu Trp Thr Ala Lys Val         995 1000 1005 Glu Ala Ile Gln Ser Gly Ser Asn Tyr Ala Tyr Leu Glu Gln Leu Glu    1010 1015 1020 Ser Leu Ser Ala Lys Gly Arg Pro Ile Pro Val Arg Leu Glu Ala Leu 1025 1030 1035 1040 Pro Gln Val Glu Ser Gln Val Ala Ala Ala Arg Ala Trp Arg Glu Arg                1045 1050 1055 Thr Gly Arg Thr Phe Leu Lys Lys Asn Ser Ser His Thr Leu Leu Gln            1060 1065 1070 Val Leu Ser Pro Arg Thr Asp Ile Gly Val Tyr Gly Ser Gly Lys Asn        1075 1080 1085 Arg Arg Lys Lys Val Lys Glu Leu Ile Glu Lys Glu Lys Glu Lys Asp    1090 1095 1100 Leu Asp Leu Glu Pro Leu Ser Asp Leu Glu Glu Gly Leu Glu Glu Thr 1105 1110 1115 1120 Arg Asp Thr Ala Met Val Val Ala Val Phe Lys Glu Arg Glu Gln Lys                1125 1130 1135 Glu Ile Glu Ala Met His Ser Leu Arg Ala Ala Asn Leu Ala Lys Met            1140 1145 1150 Thr Met Val Asp Arg Ile Glu Glu Val Lys Phe Cys Ile Cys Arg Lys        1155 1160 1165 Thr Ala Ser Gly Phe Met Leu Gln Cys Glu Leu Cys Lys Asp Trp Phe    1170 1175 1180 His Asn Ser Cys Val Pro Leu Pro Lys Ser Ser Ser Gln Lys Lys Gly 1185 1190 1195 1200 Ser Ser Trp Gln Ala Lys Glu Val Lys Phe Leu Cys Pro Leu Cys Met                1205 1210 1215 Arg Ser Arg Arg Pro Arg Leu Glu Thr Ile Leu Ser Leu Leu Val Ser            1220 1225 1230 Leu Gln Lys Leu Pro Val Arg Leu Pro Glu Gly Glu Ala Leu Gln Cys        1235 1240 1245 Leu Thr Glu Arg Ala Met Ser Trp Gln Asp Arg Ala Arg Gln Ala Leu    1250 1255 1260 Ala Thr Asp Glu Leu Ser Ser Ala Leu Ala Lys Leu Ser Val Leu Ser 1265 1270 1275 1280 Gln Arg Met Val Glu Gln Ala Ala Arg Glu Lys Thr Glu Lys Ile Ile                1285 1290 1295 Ser Ala Glu Leu Gln Lys Ala Ala Ala Asn Pro Asp Leu Gln Gly His            1300 1305 1310 Leu Pro Ser Phe Gln Gln Ser Ala Phe Asn Arg Val Val Ser Ser Val        1315 1320 1325 Ser Ser Ser Pro Arg Gln Thr Met Asp Tyr Asp Asp Glu Glu Thr Asp    1330 1335 1340 Ser Asp Glu Asp Ile Arg Glu Thr Tyr Gly Tyr Asp Met Lys Asp Thr 1345 1350 1355 1360 Ala Ser Val Lys Ser Ser Ser Ser Leu Glu Pro Asn Leu Phe Cys Asp                1365 1370 1375 Glu Glu Ile Pro Ile Lys Ser Glu Glu Val Val Thr His Met Trp Thr            1380 1385 1390 Ala Pro Ser Phe Cys Ala Glu His Ala Tyr Ser Ser Ala Ser Lys Ser        1395 1400 1405 Cys Ser Gln Gly Ser Ser Thr Pro Arg Lys Gln Pro Arg Lys Ser Pro    1410 1415 1420 Leu Val Pro Arg Ser Leu Glu Pro Pro Val Leu Glu Leu Ser Pro Gly 1425 1430 1435 1440 Ala Lys Ala Gln Leu Glu Glu Leu Met Met Val Gly Asp Leu Leu Glu                1445 1450 1455 Val Ser Leu Asp Glu Thr Gln His Ile Trp Arg Ile Leu Gln Ala Thr            1460 1465 1470 His Pro Pro Ser Glu Asp Arg Phe Leu His Ile Met Glu Asp Asp Ser        1475 1480 1485 Met Glu Glu Lys Pro Leu Lys Val Lys Gly Lys Asp Ser Ser Glu Lys    1490 1495 1500 Lys Arg Lys Arg Lys Leu Glu Lys Val Glu Gln Leu Phe Gly Glu Gly 1505 1510 1515 1520 Lys Gln Lys Ser Lys Glu Leu Lys Lys Met Asp Lys Pro Arg Lys Lys                1525 1530 1535 Lys Leu Lys Leu Gly Ala Asp Lys Ser Lys Glu Leu Asn Lys Leu Ala            1540 1545 1550 Lys Lys Leu Ala Lys Glu Glu Glu Arg Lys Lys Lys Lys Glu Lys Ala        1555 1560 1565 Ala Ala Ala Lys Val Glu Leu Val Lys Glu Ser Thr Glu Lys Lys Arg    1570 1575 1580 Glu Lys Lys Val Leu Asp Ile Pro Ser Lys Tyr Asp Trp Ser Gly Ala 1585 1590 1595 1600 Glu Glu Ser Asp Asp Glu Asn Ala Val Cys Ala Ala Gln Asn Cys Gln                1605 1610 1615 Arg Pro Cys Lys Asp Lys Val Asp Trp Val Gln Cys Asp Gly Gly Cys            1620 1625 1630 Asp Glu Trp Phe His Gln Val Cys Val Gly Val Ser Pro Glu Met Ala        1635 1640 1645 Glu Asn Glu Asp Tyr Ile Cys Ile Asn Cys Ala Lys Lys Gln Gly Pro    1650 1655 1660 Val Ser Pro Gly Pro Ala Pro Pro Pro Ser Phe Ile Met Ser Tyr Lys 1665 1670 1675 1680 Leu Pro Met Glu Asp Leu Lys Glu Thr Ser                1685 1690 <210> 40 <211> 433 <212> PRT <213> Homo sapiens <400> 40 Met Asp Glu Phe His Pro Phe Ile Glu Ala Leu Leu Pro His Val Arg   1 5 10 15 Ala Phe Ser Tyr Thr Trp Phe Asn Leu Gln Ala Arg Lys Arg Lys Tyr              20 25 30 Phe Lys Lys His Glu Lys Arg Met Ser Lys Asp Glu Glu Arg Ala Val          35 40 45 Lys Asp Glu Leu Leu Gly Glu Lys Pro Glu Ile Lys Gln Lys Trp Ala      50 55 60 Ser Arg Leu Leu Ala Lys Leu Arg Lys Asp Ile Arg Pro Glu Phe Arg  65 70 75 80 Glu Asp Phe Val Leu Thr Ile Thr Gly Lys Lys Pro Pro Cys Cys Val                  85 90 95 Leu Ser Asn Pro Asp Gln Lys Gly Lys Ile Arg Arg Ile Asp Cys Leu             100 105 110 Arg Gln Ala Asp Lys Val Trp Arg Leu Asp Leu Val Met Val Ile Leu         115 120 125 Phe Lys Gly Ile Pro Leu Glu Ser Thr Asp Gly Glu Arg Leu Tyr Lys     130 135 140 Ser Pro Gln Cys Ser Asn Pro Gly Leu Cys Val Gln Pro His His Ile 145 150 155 160 Gly Val Thr Ile Lys Glu Leu Asp Leu Tyr Leu Ala Tyr Phe Val His                 165 170 175 Thr Pro Glu Ser Gly Gln Ser Asp Ser Ser Asn Gln Gln Gly Asp Ala             180 185 190 Asp Ile Lys Pro Leu Pro Asn Gly His Leu Ser Phe Gln Asp Cys Phe         195 200 205 Val Thr Ser Gly Val Trp Asn Val Thr Glu Leu Val Arg Val Ser Gln     210 215 220 Thr Pro Val Ala Thr Ala Ser Gly Pro Asn Phe Ser Leu Ala Asp Leu 225 230 235 240 Glu Ser Pro Ser Tyr Tyr Asn Ile Asn Gln Val Thr Leu Gly Arg Arg                 245 250 255 Ser Ile Thr Ser Pro Pro Ser Thr Ser Thr Thr Lys Arg Pro Lys Ser             260 265 270 Ile Asp Asp Ser Glu Met Glu Ser Pro Val Asp Asp Val Phe Tyr Pro         275 280 285 Gly Thr Gly Arg Ser Pro Ala Ala Gly Ser Ser Gln Ser Ser Gly Trp     290 295 300 Pro Asn Asp Val Asp Ala Gly Pro Ala Ser Leu Lys Lys Ser Gly Lys 305 310 315 320 Leu Asp Phe Cys Ser Ala Leu Ser Ser Gln Gly Ser Ser Pro Arg Met                 325 330 335 Ala Phe Thr His His Pro Leu Pro Val Leu Ala Gly Val Arg Pro Gly             340 345 350 Ser Pro Arg Ala Thr Ala Ser Ala Leu His Phe Pro Ser Thr Ser Ile         355 360 365 Ile Gln Gln Ser Ser Pro Tyr Phe Thr His Pro Thr Ile Arg Tyr His     370 375 380 His His His Gly Gln Asp Ser Leu Lys Glu Phe Val Gln Phe Val Cys 385 390 395 400 Ser Asp Gly Ser Gly Gln Ala Thr Gly Gln His Ser Gln Arg Gln Ala                 405 410 415 Pro Pro Leu Pro Thr Gly Leu Ser Ala Ser Asp Pro Gly Thr Ala Thr             420 425 430 Phe     <210> 41 <211> 415 <212> PRT <213> Homo sapiens <400> 41 Met Phe Ala Asp Leu Asp Tyr Asp Ile Glu Glu Asp Lys Leu Gly Ile   1 5 10 15 Pro Thr Val Pro Gly Lys Val Thr Leu Gln Lys Asp Ala Gln Asn Leu              20 25 30 Ile Gly Ile Ser Ile Gly Gly Gly Ala Gln Tyr Cys Pro Cys Leu Tyr          35 40 45 Ile Val Gln Val Phe Asp Asn Thr Pro Ala Ala Leu Asp Gly Thr Val      50 55 60 Ala Ala Gly Asp Glu Ile Thr Gly Val Asn Gly Arg Ser Ile Lys Gly  65 70 75 80 Lys Thr Lys Val Glu Val Ala Lys Met Ile Gln Glu Val Lys Gly Glu                  85 90 95 Val Thr Ile His Tyr Asn Lys Leu Gln Ala Asp Pro Lys Gln Gly Met             100 105 110 Ser Leu Asp Ile Val Leu Lys Lys Val Lys His Arg Leu Val Glu Asn         115 120 125 Met Ser Ser Gly Thr Ala Asp Ala Leu Gly Leu Ser Arg Ala Ile Leu     130 135 140 Cys Asn Asp Gly Leu Val Lys Arg Leu Glu Glu Leu Glu Arg Thr Ala 145 150 155 160 Glu Leu Tyr Lys Gly Met Thr Glu His Thr Lys Asn Leu Leu Arg Ala                 165 170 175 Phe Tyr Glu Leu Ser Gln Thr His Arg Ala Phe Gly Asp Val Phe Ser             180 185 190 Val Ile Gly Val Arg Glu Pro Gln Pro Ala Ala Ser Glu Ala Phe Val         195 200 205 Lys Phe Ala Asp Ala His Arg Ser Ile Glu Lys Phe Gly Ile Arg Leu     210 215 220 Leu Lys Thr Ile Lys Pro Met Leu Thr Asp Leu Asn Thr Tyr Leu Asn 225 230 235 240 Lys Ala Ile Pro Asp Thr Arg Leu Thr Ile Lys Lys Tyr Leu Asp Val                 245 250 255 Lys Phe Glu Tyr Leu Ser Tyr Cys Leu Lys Val Lys Glu Met Asp Asp             260 265 270 Glu Glu Tyr Ser Cys Ile Ala Leu Gly Glu Pro Leu Tyr Arg Val Ser         275 280 285 Thr Gly Asn Tyr Glu Tyr Arg Leu Ile Leu Arg Cys Arg Gln Glu Ala     290 295 300 Arg Ala Arg Phe Ser Gln Met Arg Lys Asp Val Leu Glu Lys Met Glu 305 310 315 320 Leu Leu Asp Gln Lys His Val Gln Asp Ile Val Phe Gln Leu Gln Arg                 325 330 335 Leu Val Ser Thr Met Ser Lys Tyr Tyr Asn Asp Cys Tyr Ala Val Leu             340 345 350 Arg Asp Ala Asp Val Phe Pro Ile Glu Val Asp Leu Ala His Thr Thr         355 360 365 Leu Ala Tyr Gly Leu Asn Gln Glu Glu Phe Thr Asp Gly Glu Glu Glu     370 375 380 Glu Glu Glu Glu Asp Thr Ala Ala Gly Glu Pro Ser Arg Asp Thr Arg 385 390 395 400 Gly Ala Ala Gly Pro Leu Asp Lys Gly Gly Ser Trp Cys Asp Ser                 405 410 415 <210> 42 <211> 271 <212> PRT <213> Homo sapiens <400> 42 Met Val Leu Ile Lys Glu Phe Arg Val Val Leu Pro Cys Ser Val Gln   1 5 10 15 Glu Tyr Gln Val Gly Gln Leu Tyr Ser Val Ala Glu Ala Ser Lys Asn              20 25 30 Glu Thr Gly Gly Gly Glu Gly Ile Glu Val Leu Lys Asn Glu Pro Tyr          35 40 45 Glu Lys Asp Gly Glu Lys Gly Gln Tyr Thr His Lys Ile Tyr His Leu      50 55 60 Lys Ser Lys Val Pro Ala Phe Val Arg Met Ile Ala Pro Glu Gly Ser  65 70 75 80 Leu Val Phe His Glu Lys Ala Trp Asn Ala Tyr Pro Tyr Cys Arg Thr                  85 90 95 Ile Val Thr Asn Glu Tyr Met Lys Asp Asp Phe Phe Ile Lys Ile Glu             100 105 110 Thr Trp His Lys Pro Asp Leu Gly Thr Leu Glu Asn Val His Gly Leu         115 120 125 Asp Pro Asn Thr Trp Lys Thr Val Glu Ile Val His Ile Asp Ile Ala     130 135 140 Asp Arg Ser Gln Val Glu Pro Ala Asp Tyr Lys Ala Asp Glu Asp Pro 145 150 155 160 Ala Leu Phe Gln Ser Val Lys Thr Lys Arg Gly Pro Leu Gly Pro Asn                 165 170 175 Trp Lys Lys Glu Leu Ala Asn Ser Pro Asp Cys Pro Gln Met Cys Ala             180 185 190 Tyr Lys Leu Val Thr Ile Lys Phe Lys Trp Trp Gly Leu Gln Ser Lys         195 200 205 Val Glu Asn Phe Ile Gln Lys Gln Glu Lys Arg Ile Phe Thr Asn Phe     210 215 220 His Arg Gln Leu Phe Cys Trp Ile Asp Lys Trp Ile Asp Leu Thr Met 225 230 235 240 Glu Asp Ile Arg Arg Met Glu Asp Glu Thr Gln Lys Glu Leu Glu Thr                 245 250 255 Met Arg Lys Arg Gly Ser Val Arg Gly Thr Ser Ala Ala Asp Val             260 265 270 <210> 43 <211> 290 <212> PRT <213> Homo sapiens <400> 43 Met Ser Pro Ser Ala Lys Lys Arg Pro Lys Asn Ser Arg Val Ser Lys   1 5 10 15 Met Gln Asp Glu Lys Leu Arg Asp Glu Thr Glu Gln Pro Val Ser Lys              20 25 30 Val Ile Glu Arg Asn Arg Leu Arg Thr Val Leu Lys Asn Leu Ser Leu          35 40 45 Leu Lys Leu Leu Lys Ser Ser Asn Arg Arg Ile Gln Glu Leu His Lys      50 55 60 Leu Ala Lys Arg Cys Trp His Ser Leu Leu Ser Val Pro Lys Ile Leu  65 70 75 80 Arg Ile Ser Ser Gly Glu Asn Ser Ala Cys Asn Lys Thr Lys Gln Asn                  85 90 95 Asn Glu Glu Phe Gln Glu Ile Gly Cys Ser Glu Lys Glu Leu Lys Ser             100 105 110 Lys Lys Leu Glu Ser Thr Gly Asp Pro Lys Lys Lys Glu Tyr Lys Glu         115 120 125 Trp Lys Ser Gln Val Gln Ser Gly Met Arg Asn Lys Glu Lys Thr Ser     130 135 140 Leu Ala Ala Met Pro Arg Lys Glu Lys His Ile Glu Pro Glu Val Pro 145 150 155 160 Arg Thr Ser Arg Asp Asp Ser Leu Asn Pro Gly Val Gln Gly Arg Gln                 165 170 175 Pro Leu Thr Glu Gly Pro Arg Val Ile Phe Ile Lys Pro Tyr Arg Asn             180 185 190 Arg Thr Pro Met Gly His Met Lys Gln Leu Asp Val Ala Asp Gln Trp         195 200 205 Ile Trp Phe Glu Gly Leu Pro Thr Arg Ile His Leu Pro Ala Pro Arg     210 215 220 Val Met Cys Arg Ser Ser Thr Leu Arg Trp Val Lys Arg Arg Cys Thr 225 230 235 240 Arg Phe Cys Ser Ala Ser Leu Glu Met Pro Met Trp His Pro Tyr Lys                 245 250 255 Val Asp Val Thr Trp Thr Arg Ala Arg Gly Ala Ser Arg Gly Trp Arg             260 265 270 Ser Arg His Gln Leu Lys Gly Arg Asn Gly Trp Arg Asn Ser Arg Val         275 280 285 Tyr lys     290 <210> 44 <211> 526 <212> PRT <213> Homo sapiens <400> 44 Met Pro Gln Gln Leu Leu Ile Thr Leu Pro Thr Glu Ala Ser Thr Trp   1 5 10 15 Val Lys Leu Gln His Pro Lys Lys Ala Val Glu Gly Ala Pro Leu Trp              20 25 30 Glu Asp Val Thr Lys Met Phe Glu Gly Glu Ala Leu Leu Ser Gln Asp          35 40 45 Ala Glu Asp Val Lys Thr Gln Arg Glu Ser Leu Glu Asp Glu Val Thr      50 55 60 Pro Gly Leu Pro Thr Ala Glu Ser Gln Glu Leu Leu Thr Phe Lys Asp  65 70 75 80 Ile Ser Ile Asp Phe Thr Gln Glu Glu Trp Gly Gln Leu Ala Pro Ala                  85 90 95 His Gln Asn Leu Tyr Arg Glu Val Met Leu Glu Asn Tyr Ser Asn Leu             100 105 110 Val Ser Val Gly Tyr Gln Leu Ser Lys Pro Ser Val Ile Ser Gln Leu         115 120 125 Glu Lys Gly Glu Glu Pro Trp Met Ala Glu Lys Glu Gly Pro Gly Asp     130 135 140 Pro Ser Ser Asp Leu Lys Ser Lys Ile Glu Thr Ile Glu Ser Thr Ala 145 150 155 160 Lys Ser Thr Ile Ser Gln Glu Arg Leu Tyr His Gly Ile Met Met Glu                 165 170 175 Ser Phe Met Arg Asp Asp Ile Ile Tyr Ser Thr Leu Arg Lys Val Ser             180 185 190 Thr Tyr Asp Asp Val Leu Glu Arg His Gln Glu Thr Cys Met Arg Asp         195 200 205 Val Arg Gln Ala Ile Leu Thr His Lys Lys Arg Val Gln Glu Thr Asn     210 215 220 Lys Phe Gly Glu Asn Ile Ile Val His Ser Asn Val Ile Ilu Glu Gln 225 230 235 240 Arg His His Lys Tyr Asp Thr Pro Thr Lys Arg Asn Thr Tyr Lys Leu                 245 250 255 Asp Leu Ile Asn His Pro Thr Ser Tyr Ile Arg Thr Lys Thr Tyr Glu             260 265 270 Cys Asn Ile Cys Glu Lys Ile Phe Lys Gln Pro Ile His Leu Thr Glu         275 280 285 His Met Arg Ile His Thr Gly Glu Lys Pro Phe Arg Cys Lys Glu Cys     290 295 300 Gly Arg Ala Phe Ser Gln Ser Ala Ser Leu Ser Thr His Gln Arg Ile 305 310 315 320 His Thr Gly Glu Lys Pro Phe Glu Cys Glu Glu Cys Gly Lys Ala Phe                 325 330 335 Arg His Arg Ser Ser Leu Asn Gln His His Arg Thr His Thr Gly Glu             340 345 350 Lys Pro Tyr Val Cys Asp Lys Cys Gln Lys Ala Phe Ser Gln Asn Ile         355 360 365 Ser Leu Val Gln His Leu Arg Thr His Ser Gly Glu Lys Pro Phe Thr     370 375 380 Cys Asn Glu Cys Gly Lys Thr Phe Arg Gln Ile Arg His Leu Ser Glu 385 390 395 400 His Ile Arg Ile His Thr Gly Glu Lys Pro Tyr Ala Cys Thr Ala Cys                 405 410 415 Cys Lys Thr Phe Ser His Arg Ala Tyr Leu Thr His His Gln Arg Ile             420 425 430 His Thr Gly Glu Arg Pro Tyr Lys Cys Lys Glu Cys Gly Lys Ala Phe         435 440 445 Arg Gln Arg Ile His Leu Ser Asn His Lys Thr Val His Thr Gly Val     450 455 460 Lys Ala Tyr Glu Cys Asn Arg Cys Gly Lys Ala Tyr Arg His Asp Ser 465 470 475 480 Ser Phe Lys Lys His Gln Arg His His Thr Gly Glu Lys Pro Tyr Glu                 485 490 495 Cys Asn Glu Cys Gly Lys Ala Phe Ser Tyr Asn Ser Ser Leu Ser Arg             500 505 510 His His Glu Ile His Arg Arg Asn Ala Phe Arg Asn Lys Val         515 520 525 <210> 45 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 45 ctgtgggcac tgcagtagt 19 <210> 46 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 46 atacctgggc tgaggttctc t 21 <210> 47 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 47 cctcactcta gaaagctggt gatgta 26 <210> 48 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 48 cagattcggc atgaaccatg ac 22 <210> 49 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 49 ccagggagca tccctgattt cta 23 <210> 50 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ADAMTS10 <400> 50 atgaagacca acccattcgt gt 22 <210> 51 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 51 cccacaacag gctgttttta agg 23 <210> 52 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 52 tattccagca ggagggaaat gca 23 <210> 53 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 53 attttcatca attgactttg ttcaatccga 30 <210> 54 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 54 aggtcttgaa ttcccagagt gtct 24 <210> 55 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 55 caacttttca acataatgct ttcatgtcac 30 <210> 56 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ASB15 <400> 56 gccacactcc cttttctaat aaagttctta 30 <210> 57 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 57 aaccaatgct ttgttgttca atgtca 26 <210> 58 <211> 31 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 58 aatctaaatc ttcaggtaac acatctgtca g 31 <210> 59 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 59 tttgtccaag ttgggctctt ca 22 <210> 60 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 60 ctcataaacc tcaggtaagt tttctttgtg 30 <210> 61 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 61 aggccttcaa tggaagctct g 21 <210> 62 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> C8orf 37 <400> 62 tgccatgaaa atttgtattt aagtcattta gaa 33 <210> 63 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CHSY3 <400> 63 gcctttcttc agagagaccg aa 22 <210> 64 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> CHSY3 <400> 64 aggaacgaga atgtgtactt tcttttca 28 <210> 65 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> CHSY3 <400> 65 ttatcttctt ttcaaggtgc caaagaaatg 30 <210> 66 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> CHSY3 <400> 66 ccaactttac attctgcttt gggataaga 29 <210> 67 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> CPSF3 <400> 67 acccagaact acatgacatt ccaatatac 29 <210> 68 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CPSF3 <400> 68 cttccacaag cactcacctt ga 22 <210> 69 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CPSF3 <400> 69 agaatgaaat ggccagattg aaagc 25 <210> 70 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CPSF3 <400> 70 aaaacatgga ttggacagac aggaa 25 <210> 71 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 71 ccaggtagga cctgcactgt a 21 <210> 72 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 72 cctcctcaca aagcgtcttc a 21 <210> 73 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 73 tcctaccatt cccagatccc tc 22 <210> 74 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 74 ctggcaactg agaagaaaga ggg 23 <210> 75 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 75 gggaggactc agattgtccc tt 22 <210> 76 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> EHBP1L1 <400> 76 ctgtgttgca attgccatcc at 22 <210> 77 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 77 gcctcctggt cattgttacc ta 22 <210> 78 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 78 gtgatcagca ctgagtggat ca 22 <210> 79 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 79 gctcatcagc aagacaccct 20 <210> 80 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 80 ggttccgcag gatggtcac 19 <210> 81 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 81 ctatgcagag gccaagactt ca 22 <210> 82 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR148 <400> 82 tcccagagtc aatgtggtgg ta 22 <210> 83 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 83 caccagccat catccaagat agg 23 <210> 84 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 84 ggtaacctat tggcatctac tacacag 27 <210> 85 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 85 gtggttgaat aggcaagggc taa 23 <210> 86 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 86 ccggtggacc tgtactacct ta 22 <210> 87 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 87 gcatccctgc ccacttactt tc 22 <210> 88 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ITGB7 <400> 88 cttgtgccca taccaatgtg ac 22 <210> 89 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> KLHL24 <400> 89 agatcaatgg tattttagct gaagctatgg 30 <210> 90 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KLHL24 <400> 90 caaggatcaa gttgctcctc caa 23 <210> 91 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> KLHL24 <400> 91 aaaaggtgta taacagctgt atccctaaac 30 <210> 92 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> KLHL24 <400> 92 gtccctctta gatttatttt tcttttgtac tgc 33 <210> 93 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 93 gggccattgg actgtagatt gg 22 <210> 94 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 94 cccacaagaa catcacagct ga 22 <210> 95 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 95 gtccagagca gcgaacttca ct 22 <210> 96 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 96 catattcctt cggaaggtta ggtgt 25 <210> 97 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 97 ggcatcctgg ctatgtgaac aa 22 <210> 98 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> LOXL3 <400> 98 ttaattacaa cttcctgatc tttgccatct 30 <210> 99 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 99 gtccgacaca acctgcaaaa at 22 <210> 100 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 100 ggagggaagt gttcatcttt tccc 24 <210> 101 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 101 ctgactaatt cttctctcct cttctcca 28 <210> 102 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 102 ttccgaggcc caggttcgt 19 <210> 103 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 103 tttttcctct gcaggtgtga gaa 23 <210> 104 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LTBR <400> 104 ggagcattaa ggcattttca gagg 24 <210> 105 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 105 actttgtagg ccatggatca tctg 24 <210> 106 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 106 aaacaaaagg agtcgaaata atactttgta cta 33 <210> 107 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 107 cccaccatgg tagcatttta aaaagc 26 <210> 108 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 108 cttctgttct acgatcacaa tctgca 26 <210> 109 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 109 aaatcaggaa gaatataatg taacactgca ct 32 <210> 110 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> LUC7L2 <400> 110 aaaaactacc tttgaaaaag acaacttcac ta 32 <210> 111 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 111 ccaaggccag cccatatact tg 22 <210> 112 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 112 tagccaagga tgttggcttt tga 23 <210> 113 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 113 gcctaggaga cttaccatac aggt 24 <210> 114 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 114 taagggcaga acaccggttt atc 23 <210> 115 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 115 gaagcctgga gtggagaatg tt 22 <210> 116 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 116 ttgtctaggt tttccgtgtg tatcag 26 <210> 117 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 117 acaaagacaa caaaggtagt gcctt 25 <210> 118 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> MUTYH <400> 118 gtccacacct tctctcacat ca 22 <210> 119 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 119 gcagtagaat agcagagatc acagaa 26 <210> 120 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 120 ccctatttgc tgtattcttg gctgtttata 30 <210> 121 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 121 cctgtgtatc tgagcgagag agt 23 <210> 122 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 122 atgtctagca gagtgtgcta tctact 26 <210> 123 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 123 agacactcag aatctgcaaa gatacag 27 <210> 124 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> OR5W2 <400> 124 ttcacacacc aatgtatttc ttcctca 27 <210> 125 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> POMZP3 <400> 125 cccattcagt aggatatgaa ggttg 25 <210> 126 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> POMZP3 <400> 126 tcactgatgc ctcttctgca ttc 23 <210> 127 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> POMZP3 <400> 127 tgttaaagct cttaccatgt ttctgga 27 <210> 128 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> POMZP3 <400> 128 gcccacctgt ctggctttaa c 21 <210> 129 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 129 tcctacctgt taccaggctg at 22 <210> 130 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 130 actcctgcta ccaaattttg tctca 25 <210> 131 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 131 tcacaaacct tgcatcctta gtgt 24 <210> 132 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 132 cagagtaata aatggacgga tgggatttt 29 <210> 133 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 133 ccgatgactt atcccagctg tt 22 <210> 134 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 134 tcagattttg agaaccagaa tggct 25 <210> 135 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 135 aggcaagaca tggaaaaagt ctaca 25 <210> 136 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> RELN <400> 136 ctagaaagga ttttgagtga ttctggtct 29 <210> 137 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SAA1 <400> 137 cgactgcctg acttctcctt tc 22 <210> 138 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> SAA1 <400> 138 cagaaatcct gcaaaccttc tgaag 25 <139> <211> 27 <212> DNA <213> Artificial Sequence <220> <223> SAA1 <400> 139 gagaatatcc agagattctt tggccat 27 <210> 140 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> SAA1 <400> 140 gcctcacagc cagatctcct 20 <210> 141 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 141 aaaggagatg ttgcccttat gttttg 26 <210> 142 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 142 tctggctttg attaaaattt ttggtgca 28 <210> 143 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 143 caggaatcaa tttgcagcac ttga 24 <210> 144 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 144 gaattgggtc ccaaaatgaa ggttttaa 28 <210> 145 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 145 gcaagtaaat ccctcctacc tgtt 24 <210> 146 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> SLC35B3 <400> 146 ccagttcgga cctatggtta tgc 23 <210> 147 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 147 cccagtacca ttcctcgact 20 <210> 148 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 148 ctgggcagaa tgggttgga 19 <210> 149 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 149 taggaccctc ctcccactca c 21 <210> 150 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 150 tggtctcgtt gatcttgctg g 21 <210> 151 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 151 gcccttggtt cggacagac 19 <210> 152 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 152 ctgaccaggg tgaagagcgt 20 <210> 153 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 153 gctggttgag gcagagatct c 21 <210> 154 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> SMO <400> 154 gctgaggcag tcgaggaat 19 <210> 155 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 155 gtgaggtgga atgactatta atctgttacc 30 <210> 156 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 156 tgtggagtca aaggaggcaa atc 23 <210> 157 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 157 ggcgcagctc tagatatttg ag 22 <210> 158 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 158 ggctccttct ccgatctctc t 21 <210> 159 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 159 gcaatttgtg tgcgtttgca tt 22 <210> 160 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> SNRNP27 <400> 160 aactcttggc ttattttctg ccctta 26 <210> 161 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 161 gttagcacag gcagatcaga ga 22 <210> 162 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 162 tcacagcagg attttgctct tct 23 <210> 163 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 163 gctaggactg cctgaacatc tg 22 <210> 164 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 164 aatgaatctg gctcagctct attgag 26 <210> 165 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 165 ccatgtacac tgtaacagat taagagca 28 <210> 166 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ST7L <400> 166 gtgtatatgt gtctgtgtgt tactctttca 30 <210> 167 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 167 gtgcgtgcat atgtttggga tg 22 <210> 168 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 168 tttctggcga caggaagaaa tct 23 <210> 169 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 169 cagaactgga ttctttaaac taactgacca 30 <210> 170 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 170 gtcctccctg cttgaagcat ag 22 <210> 171 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 171 gtagaagaag gaagcagagg aattgg 26 <210> 172 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> STAMBP <400> 172 acaattttca gtcgctcttt ttctagc 27 <210> 173 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 173 tggtgatgct tgaattttgg tgttg 25 <210> 174 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 174 accaccaacc tagaagtgct ct 22 <175> 175 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 175 aaagcccagt atcaatgaaa aggga 25 <210> 176 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 176 cacaggcctc ttcaaaattt cctttaataa 30 <210> 177 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 177 atgattagag atccagccag aggat 25 <210> 178 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 178 caatggcaag cagataaaaa tgcatc 26 <210> 179 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 179 agaaggagag gttacaacaa tgaatcatg 29 <210> 180 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> SUPV3L1 <400> 180 ctctcctcca cagagaagca gta 23 <210> 181 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 181 tgtttattaa atttgccgtg tcttgca 27 <210> 182 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 182 ttcacatcta tcttgatgag tgctcttg 28 <210> 183 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 183 ggctgctgta aagacactaa tcaaag 26 <210> 184 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 184 cgctcgataa acatttgaca aaataaactg 30 <210> 185 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 185 agccacccat cagctcctat aa 22 <210> 186 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TADA2A <400> 186 ctccagggac caacctcacc at 22 <210> 187 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> UBE2D1 <400> 187 atgtgtgatt attgcaatta agtataagaa ggt 33 <210> 188 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> UBE2D1 <400> 188 tgatttttac attgcatatt tctgagtcca ttc 33 <210> 189 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> UBE2D1 <400> 189 tttgtgtatc tacagataca acagacatg 29 <210> 190 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> UBE2D1 <400> 190 agtgctcaat ttactgctaa tgttgaaaaa 30 <210> 191 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 191 acccaatcac atctatagag tagtgct 27 <210> 192 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 192 aaagagaatg ctatgagatt atcaagaatt ca 32 <210> 193 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 193 aaaaataaaa caaaagtgtc ttacctaatg cct 33 <210> 194 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 194 ctaacagaca gaatgacctt tctggaaa 28 <210> 195 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 195 gggctttaca ggttgatcat gg 22 <210> 196 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 196 ggcttgcata acatatacta cggtttatct ac 32 <210> 197 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 197 gaagtggaac aaaactgaaa gcattga 27 <210> 198 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> UGT2A3 <400> 198 gtaggaggca atatggagcg aa 22 <210> 199 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 199 ctccagtatg cagtctatga tggtac 26 <210> 200 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 200 gggagacaaa cattacacat gtaatgaat 29 <210> 201 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 201 caagatgtga tttgcaactg aaaactttc 29 <210> 202 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 202 actagtagta cagaccgata tgatcaaagg 30 <210> 203 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 203 gattcaagct gacctttaat aggcttg 27 <210> 204 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 204 cattttgctc ccaggaaatt gagaaag 27 <210> 205 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 205 atgcaagggt tgctttttga tca 23 <206> 206 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> ZNF320 <400> 206 aaggtttgcg acaaggcttt t 21 <210> 207 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 207 gtttgtcttt ccgatgtgaa tcttcat 27 <210> 208 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 208 caaaccctat cagtgcaagg aatg 24 <210> 209 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 209 gggctgaggg ataaataaag gct 23 <210> 210 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 210 tcatccctca ccgaacacct aa 22 <210> 211 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 211 gcttcttgaa acaagcaaga aaatgga 27 <210> 212 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZNF699 <400> 212 gtgaatgcca tgagtgtgga aag 23 <210> 213 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 213 ggaacctgag ggcaccaatt 20 <210> 214 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 214 cgacctctgc tgctttgct 19 <210> 215 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 215 cgtcctcacc ttgaagcacc 20 <210> 216 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 216 ctagaggccg aggagctcac 20 <210> 217 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 217 cccgcacaga tctgtgtcag 20 <210> 218 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> ADAM33 <400> 218 tttcttgccc aggtctcgaa g 21 <210> 219 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 219 catactggaa ccgagagcaa ga 22 <210> 220 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 220 gcaagttgtt aaaacccgta acca 24 <210> 221 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 221 catcgggata agaagctgaa gtactac 27 <210> 222 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 222 ggcacattcc agtataaacg tcatca 26 <210> 223 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 223 tgcccagaca ctgagtttgt tt 22 <210> 224 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 224 tagtacttca gcttcttatc ccgatga 27 <210> 225 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 225 taccatatca ctgaccaggt ccat 24 <210> 226 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> B3GNT2 <400> 226 ttttctcctc gatatcaaat gtcctgaag 29 <210> 227 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> BFSP1 <400> 227 accttttaat ggtgcatctt ccaga 25 <210> 228 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> BFSP1 <400> 228 caattatact tgaatttctg cctgtgtgt 29 <210> 229 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 229 cttcgagaat tcagaaacca cagagt 26 <210> 230 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 230 ccattatgtc atggcaagct tattaactt 29 <210> 231 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 231 tccatgcaaa tctactcagc ctaag 25 <210> 232 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 232 tctggagtta gctctttaat gcttcc 26 <210> 233 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 233 ctctggctaa tctccgtgga aa 22 <210> 234 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> CARD6 <400> 234 gaacaaagta gcatctttca atggca 26 <210> 235 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> CHRM2 <400> 235 ttccaaagat gagaactcta agcaaaca 28 <210> 236 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CHRM2 <400> 236 aggctgctta gtcatcttca caatc 25 <210> 237 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> CHRM2 <400> 237 ggcaggtatg atgattgcag ct 22 <210> 238 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CHRM2 <400> 238 aaatagaagg ctgcaatagc cgta 24 <210> 239 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> EPB41L5 <400> 239 atctcagaaa taggagatag gactgtttga 30 <210> 240 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> EPB41L5 <400> 240 ctcgaaggcg gaagaaagca tg 22 <210> 241 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> FBXW5 <400> 241 ccgtcctcac cttcacagtg 20 <210> 242 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> FBXW5 <400> 242 gccatgtcct ggtacgagga 20 <210> 243 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> FBXW5 <400> 243 gtgtcataca gccgctgga 19 <210> 244 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> FBXW5 <400> 244 gccatgacta gtgggttcca g 21 <210> 245 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> GPR173 <400> 245 ctacgccaag cgcatgacac t 21 <210> 246 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR173 <400> 246 tagcgatgct caaagatgca ct 22 <210> 247 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> GPR173 <400> 247 gtgggcacct acaagtttat tcg 23 <210> 248 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> GPR173 <400> 248 gatactcgaa gaggagcagc tt 22 <210> 249 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 249 ggcacttttc actacctggc aa 22 <210> 250 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 250 cctctgcacc ttgagttttg ct 22 <210> 251 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 251 caggcaaaga tcctgcttct tc 22 <210> 252 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 252 ctctgattct aggagaaaaa gtattctgca 30 <210> 253 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 253 gcagaaatca aacaactctg tacatttgt 29 <210> 254 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 254 acttatggct ttgcaggaag atagaaaa 28 <210> 255 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 255 cttgcgattg tggcggaat 19 <210> 256 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> HHIPL2 <400> 256 tctttgttgc cgagcaggta g 21 <210> 257 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 257 ttgagaaagc caagatccgg g 21 <210> 258 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 258 atggcgaagg ttggcagagg 20 <210> 259 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 259 agacgagtgc gatgtcgaaa at 22 <210> 260 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 260 cccaaaattc tttacccagc agatca 26 <210> 261 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 261 tctcgactcg acctcagtca 20 <210> 262 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 262 tgattatgaa caactgtagc ggcata 26 <210> 263 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 263 gcctgtacag gtcaggacaa tc 22 <210> 264 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 264 tgagtagatt ggaggactga tctgtaa 27 <210> 265 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 265 cgcgatgagc gcttcaaa 18 <210> 266 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> KDM2A <400> 266 ctctttggtg ggcctctgta 20 <210> 267 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 267 actgaaggaa gacaccaaaa gactc 25 <210> 268 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 268 caactggagg aggtgatgag ag 22 <210> 269 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 269 cgggcaactt ctgaagggat ac 22 <210> 270 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 270 ttcctcttcc taaatcaagt tcccaaaaa 29 <210> 271 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 271 ccacacagct tgtccatgta act 23 <210> 272 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 272 gtttagggac acttacctag tttccag 27 <210> 273 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 273 caatgagcaa tcatcgtgcc g 21 <210> 274 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 274 cccaacgtgc taatggagca t 21 <210> 275 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 275 ccagggcaga ggatagttca tc 22 <210> 276 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 276 aggcccaggc tagagactat tc 22 <210> 277 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 277 agatcaggct gggattcaaa taact 25 <210> 278 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> KDM5A <400> 278 ttggaatcag ataccctagc ctcat 25 <210> 279 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> NFIX <400> 279 caagaagcat gaaaagcgga tgt 23 <210> 280 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> NFIX <400> 280 cttcttgccc gtgatggtc 19 <210> 281 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> NFIX <400> 281 cgagttccgc gaggacttc 19 <210> 282 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> NFIX <400> 282 aaaatcacca tgaccaggtc ca 22 <210> 283 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> PICK1 <400> 283 catgtatcag ggcctagcag ag 22 <210> 284 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> PICK1 <400> 284 gtgagtctgc gacagctca 19 <210> 285 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> PITPNB <400> 285 atagctagct ccgatctcat cctaaat 27 <210> 286 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> PITPNB <400> 286 atctagaagg agctggcaaa cag 23 <210> 287 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> PITPNB <400> 287 accagcttat aggcacacat ctg 23 <210> 288 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> PITPNB <400> 288 catgtatgtc tatgatgtcg ttatacaaca 30 <210> 289 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TP53TG <400> 289 cccgatctcc tggaactctt ca 22 <210> 290 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TP53TG <400> 290 gctggctaca tagcaactgt ct 22 <210> 291 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> TP53TG <400> 291 cctgggactt ccactccttg ta 22 <210> 292 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> TP53TG <400> 292 ggaaaacagt gcctgcaata aaaca 25 <210> 293 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 293 gaggtggtct ccggctaaaa at 22 <210> 294 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 294 ctgacaccaa gttgctgtag ttct 24 <210> 295 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 295 cctcaccaga agtggacaag tc 22 <210> 296 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 296 ttctccttca aacattttag tcacatcct 29 <210> 297 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 297 cagaggatac accttagcaa cca 23 <210> 298 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 298 gttatagctg aaggcttttc cacattc 27 <210> 299 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 299 gcatgcactg catgttgtaa aac 23 <210> 300 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 300 tgcattcata tgctttcact cctgtat 27 <210> 301 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 301 gaagctgcaa catccaaaga agg 23 <210> 302 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> ZFP69 <400> 302 tacctatctt ttcacacaca aatgagatcc 30

Claims (10)

A kit comprising an agent capable of detecting metastasis specific markers and providing information necessary for predicting the difference in the effects of renal cancer treatment according to metastasis of renal cancer patients or for prognostic diagnosis of renal cancer patients,
The transition specific markers are ADAMTS10, ASB15, C8orf37, CHSY3, CPSF3, EHBP1L1, GPR148, ITGB7, KLHL24, LOXL3, LTBR, LUC7L2, MUTYH, OR5W2, POMZP3, RELN, SAA1, SLC35B3, SMBP7 SNRNP SUPV3L1, TADA2A, UBE2D1, UGT2A3, ZNF320, ZNF699, ADAM33, B3GNT2, BFSP1, CARD6, CHRM2, EPB41L5, FBXW5, GPR173, HHIPL2, KDM2A, KDM5A, NFIX, PITP5, PICK5, PICK1, PICK69 ego,
Wherein said agent comprises a primer, probe or antibody for said marker.
The method according to claim 1,
The mutation of the gene encoding ADAMTS10 is a missense mutation in the amino acid sequence of SEQ ID 1, which is at least one of L872M and D439N;
The mutation of the gene encoding ASB15 is a nonsense mutation of E105 * or a missense mutation of V246L in the amino acid sequence of SEQ ID NO: 2;
The mutation of the gene encoding C8orf37 is an in-frame delete (IF del) mutation of L66_I67del or a missense mutation of L100I in the amino acid sequence of SEQ ID NO: 3;
The mutation of the gene encoding CHSY3 is at least one missense mutation selected from the group consisting of K619N, H622N and I628M in the amino acid sequence of SEQ ID NO: 4;
The mutation of the gene encoding CPSF3 is a missense mutation of at least one of A453T and D291N in the amino acid sequence of SEQ ID NO: 5;
The mutation of the gene encoding EHBP1L1 is a missense mutation of at least one of P75S and D212A in the amino acid sequence of SEQ ID NO: 6;
The mutation of the gene encoding GPR148 is a missense mutation of at least one of P45S and R258L in the amino acid sequence of SEQ ID NO: 7;
The mutation of the gene encoding ITGB7 is a missense mutation of at least one of G175A and A671G in the amino acid sequence of SEQ ID NO: 8;
The mutation of the gene encoding KLHL24 is a missense mutation of at least one of E141D and E521D in the amino acid sequence of SEQ ID NO: 9;
The mutation of the gene encoding LOXL3 is a missense mutation of at least one of C376Y and H398Q in the amino acid sequence of SEQ ID NO: 10;
The mutation of the gene encoding the LTBR is a missense mutation of at least one of M221I and H55Q in the amino acid sequence of SEQ ID NO: 11;
The mutation of the gene encoding LUC7L2 is a nonsense mutation of at least one of S263 * and K106 * in the amino acid sequence of SEQ ID NO: 12;
A mutation of the gene encoding MUTYH is a missense mutation of L448P or a frame shift delete (FS del) mutation of T501Pfs * 67 in the amino acid sequence of SEQ ID NO: 13;
The mutation of the gene encoding OR5W2 is a missense mutation of at least one of R165H and D70E in the amino acid sequence of SEQ ID NO: 14;
The mutation of the gene encoding POMZP3 is a missense mutation of at least one of A109P and P96T in the amino acid sequence of SEQ ID NO: 15;
The mutation of the gene encoding RELN is a missense mutation of A535P in the amino acid sequence of SEQ ID NO: 16, an FS del mutation of at least one of C1098Sfs * 18 and F558Sfs * 14, or X3123_splice (T is A in chromosome 103132475) Splice mutations)
The mutation of the gene encoding SAA1 is a missense mutation of at least one of D109H and G15S in the amino acid sequence of SEQ ID NO: 17;
The mutation of the gene encoding SLC35B3 is a nonsense mutation of L317 * or a missense mutation of G155D in the amino acid sequence of SEQ ID NO: 18;
The mutation of the gene encoding SMO is a missense mutation of at least one of A235T or S699R in the amino acid sequence of SEQ ID NO: 19, or a splice mutation of X422_splice (substituting A for T at chromosome 128848598);
A mutation of the gene encoding SNRNP27 is a missense mutation of at least one of R21W and E100D in the amino acid sequence of SEQ ID NO: 20;
The mutation of the gene encoding ST7L is at least one missense mutation selected from the group consisting of K542N, P325S and D435N in the amino acid sequence of SEQ ID NO: 21;
The mutation of the gene encoding STAMBP is a missense mutation of at least one of C390R and Q156L in the amino acid sequence of SEQ ID NO: 22;
The mutation of the gene encoding SUPV3L1 is a missense mutation of at least one of K495Q and M295I in the amino acid sequence of SEQ ID NO: 23;
A mutation of the gene encoding TADA2A is a nonsense mutation of Y397 * or a missense mutation of N181K in the amino acid sequence of SEQ ID NO: 24;
A mutation of the gene encoding UBE2D1 is a missense mutation of A146P in the amino acid sequence of SEQ ID NO: 25, or a splice mutation of X133_splice (substituted G for T at chromosome 60128479);
The mutation of the gene encoding UGT2A3 is a missense mutation of at least one of H448D and N211T in the amino acid sequence of SEQ ID NO: 26;
The mutation of the gene encoding ZNF320 is at least one missense mutation selected from the group consisting of C219G, T120A and L119F in the amino acid sequence of SEQ ID NO: 27;
The mutation of the gene encoding ZNF699 is a nonsense mutation of Q224 * or a missense mutation of S516T in the amino acid sequence of SEQ ID NO: 28;
The mutation of the gene encoding ADAM33 is a missense mutation of A408V in the amino acid sequence of SEQ ID 29;
The mutation of the gene encoding B3GNT2 is a missense mutation of at least one of N260S and P330S, or a frame shift insert (FS ins) mutation of E83Gfs * 17 in the amino acid sequence of SEQ ID NO: 30;
The mutation of the gene encoding BFSP1 is a missense mutation of R362S in the amino acid sequence of SEQ ID NO: 31;
A mutation of the gene encoding CARD6 is an IF del mutation of S1016del, a missense mutation of E274K, or an FS ins mutation of T557Hfs * 2 in the amino acid sequence of SEQ ID NO: 32;
The mutation of the gene encoding CHRM2 is a missense mutation of at least one of V344M and V171M, or an FS ins mutation of S182Ffs * 65 in the amino acid sequence of SEQ ID 33;
The mutation of the gene encoding EPB41L5 is an IF del mutation of L303_P306del in the amino acid sequence of SEQ ID NO: 34;
The mutation of the gene encoding FBXW5 is a nonsense mutation of E84 * in the amino acid sequence of SEQ ID 35;
The mutation of the gene encoding GPR173 is a missense mutation of F167C in the amino acid sequence of SEQ ID 36;
The mutation of the gene encoding HHIPL2 is at least one missense mutation selected from the group consisting of D84H, L528I and V262M in the amino acid sequence of SEQ ID NO: 37;
The mutation of the gene encoding KDM2A is a missense mutation of at least one of S1072R and T802M or an FS ins mutation of P597Afs * 34 in the amino acid sequence of SEQ ID NO: 38;
The mutation of the gene encoding KDM5A is an FS ins mutation of E499Gfs * 29, or at least one missense mutation selected from the group consisting of V537I, D1339V and R1217W in the amino acid sequence of SEQ ID NO: 39;
The mutation of the gene encoding NFIX is a missense mutation of R80L in the amino acid sequence of SEQ ID 40;
The mutation of the gene encoding PICK1 is a missense mutation of Q182L in the amino acid sequence of SEQ ID 41;
The mutation of the gene encoding PITPNB is an FS del mutation of Q189Rfs * 8 in the amino acid sequence of SEQ ID NO: 42;
The mutation of the gene encoding TP53TG5 is a missense mutation of K108R in the amino acid sequence of SEQ ID 43;
Wherein said mutation of the gene encoding ZFP69 is at least one missense mutation selected from the group consisting of E27D, D84E, and R471H in the amino acid sequence of SEQ ID NO: 44.
The method according to claim 1,
At least one primer set selected from the group consisting of SEQ ID NO: 45 and SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, and base sequence pairs represented by SEQ ID NO: 49 and SEQ ID NO: 50 for detecting a mutation of ADAMTS10;
At least one primer set selected from the group consisting of SEQ ID NO: 51 and SEQ ID NO: 52, SEQ ID NO: 53 and SEQ ID NO: 54, and base sequence pairs represented by SEQ ID NO: 55 and SEQ ID NO: 56 for mutation detection of ASB15;
At least one primer set selected from the group consisting of SEQ ID NO: 57 and SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60, and base sequence pairs represented by SEQ ID NO: 61 and SEQ ID NO: 62 for mutation detection of C8orf37;
At least one primer set selected from the group consisting of SEQ ID NO: 63 and SEQ ID NO: 64, and a nucleotide sequence pair represented by SEQ ID NO: 65 and SEQ ID NO: 66 for mutation detection of CHSY3;
At least one primer set selected from the group consisting of SEQ ID NO: 67 and SEQ ID NO: 68, and base sequence pairs represented by SEQ ID NO: 69 and SEQ ID NO: 70 for mutation detection of CPSF3;
At least one primer set selected from the group consisting of SEQ ID NO: 71 and SEQ ID NO: 72, SEQ ID NO: 73 and SEQ ID NO: 74, and base sequence pairs represented by SEQ ID NO: 75 and SEQ ID NO: 76 for mutation detection of EHBP1L1;
At least one primer set selected from the group consisting of SEQ ID NO: 77 and SEQ ID NO: 78, SEQ ID NO: 79 and SEQ ID NO: 80, and base sequence pairs represented by SEQ ID NO: 81 and SEQ ID NO: 82 for mutation detection of GPR148;
At least one primer set selected from the group consisting of SEQ ID NO: 83 and SEQ ID NO: 84, SEQ ID NO: 85 and SEQ ID NO: 86, and base sequence pairs represented by SEQ ID NO: 87 and SEQ ID NO: 88 for mutation detection of ITGB7;
At least one primer set selected from the group consisting of SEQ ID NO: 89 and SEQ ID NO: 90, and base sequence pairs represented by SEQ ID NO: 91 and SEQ ID NO: 92 for mutation detection of KLHL24;
At least one primer set selected from the group consisting of SEQ ID NO: 93 and SEQ ID NO: 94, SEQ ID NO: 95 and SEQ ID NO: 96, and base sequence pairs represented by SEQ ID NO: 97 and SEQ ID NO: 98 for mutation detection of LOXL3;
At least one primer set selected from the group consisting of SEQ ID NO: 99 and SEQ ID NO: 100, SEQ ID NO: 101 and SEQ ID NO: 102, and base sequence pairs represented by SEQ ID NO: 103 and SEQ ID NO: 104 for mutation detection of LTBR;
At least one primer set selected from the group consisting of SEQ ID NO: 105 and SEQ ID NO: 106, SEQ ID NO: 107 and SEQ ID NO: 108, and base sequence pairs represented by SEQ ID NO: 109 and SEQ ID NO: 110 for mutation detection of LUC7L2;
At least one selected from the group consisting of SEQ ID NO: 111 and SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO: 114, SEQ ID NO: 115 and SEQ ID NO: 116, and base sequence pairs represented by SEQ ID NO: 117 and SEQ ID NO: 118 for mutation detection of MUTYH Primer set of;
At least one primer set selected from the group consisting of SEQ ID NO: 119 and SEQ ID NO: 120, SEQ ID NO: 121 and SEQ ID NO: 122, and base sequence pairs represented by SEQ ID NO: 123 and SEQ ID NO: 124 for mutation detection of OR5W2;
At least one primer set selected from the group consisting of SEQ ID NO: 125 and SEQ ID NO: 126, and a nucleotide sequence pair represented by SEQ ID NO: 127 and SEQ ID NO: 128 for mutation detection of POMZP3;
At least one selected from the group consisting of SEQ ID NO: 129 and SEQ ID NO: 130, SEQ ID NO: 131 and SEQ ID NO: 132, SEQ ID NO: 133 and SEQ ID NO: 134, and base sequence pairs represented by SEQ ID NO: 135 and SEQ ID NO: 136 for mutation detection of RELN; Primer set of;
At least one primer set selected from the group consisting of SEQ ID NO: 137 and SEQ ID NO: 138, and a base sequence pair represented by SEQ ID NO: 139 and SEQ ID NO: 140 for mutation detection of SAA1;
At least one primer set selected from the group consisting of SEQ ID NO: 141 and SEQ ID NO: 142, SEQ ID NO: 143 and SEQ ID NO: 144, and base sequence pairs represented by SEQ ID NO: 145 and SEQ ID NO: 146 for mutation detection of SLC35B3;
At least one selected from the group consisting of 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, and base sequence pairs represented by SEQ ID NO: 153 and SEQ ID NO: 154 for mutation detection of SMO; Primer set of;
At least one primer set selected from the group consisting of SEQ ID NO: 155 and SEQ ID NO: 156, SEQ ID NO: 157 and SEQ ID NO: 158, and SEQ ID NO: 159 and SEQ ID NO: 160 for detecting a mutation of SNRNP27;
At least one primer set selected from the group consisting of SEQ ID NO: 161 and SEQ ID NO: 162, SEQ ID NO: 163 and SEQ ID NO: 164, and a base sequence pair represented by SEQ ID NO: 165 and SEQ ID NO: 166 for mutation detection of ST7L;
At least one primer set selected from the group consisting of SEQ ID NO: 167 and SEQ ID NO: 168, SEQ ID NO: 169 and SEQ ID NO: 170, and base sequence pairs represented by SEQ ID NO: 171 and SEQ ID NO: 172 for mutation detection of STAMBP;
At least one selected from the group consisting of SEQ ID NO: 173 and SEQ ID NO: 174, SEQ ID NO: 175 and SEQ ID NO: 176, SEQ ID NO: 177 and SEQ ID NO: 178, and base sequence pairs represented by SEQ ID NO: 179 and SEQ ID NO: 180 for mutation detection of SUPV3L1; Primer set of;
At least one primer set selected from the group consisting of SEQ ID NO: 181 and SEQ ID NO: 182, SEQ ID NO: 183, and SEQ ID NO: 184, and base sequence pairs represented by SEQ ID NO: 185 and SEQ ID NO: 186 for mutation detection of TADA2A;
At least one primer set selected from the group consisting of SEQ ID NO: 187 and SEQ ID NO: 188, and SEQ ID NO: 189 and SEQ ID NO: 190 for detecting mutations in UBE2D1;
At least one selected from the group consisting of SEQ ID NO: 191 and SEQ ID NO: 192, 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 detecting a mutation of UGT2A3; Primer set of;
At least one selected from the group consisting of SEQ ID NO: 199 and SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, SEQ ID NO: 203 and SEQ ID NO: 204, and base sequence pairs represented by SEQ ID NO: 205 and SEQ ID NO: 206 for mutation detection of ZNF320 Primer set of;
At least one primer set selected from the group consisting of SEQ ID NO: 207 and SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, and base sequence pairs represented by SEQ ID NO: 211 and SEQ ID NO: 212 for mutation detection of ZNF699;
At least one primer set selected from the group consisting of SEQ ID NO: 213 and SEQ ID NO: 214, SEQ ID NO: 215 and SEQ ID NO: 216, and base sequence pairs represented by SEQ ID NO: 217 and SEQ ID NO: 218 for mutation detection of ADAM33;
At least one selected from the group consisting of SEQ ID NO: 219 and SEQ ID NO: 220, SEQ ID NO: 221 and SEQ ID NO: 222, SEQ ID NO: 223 and SEQ ID NO: 224, and base sequence pairs represented by SEQ ID NO: 225 and SEQ ID NO: 226 for mutation detection of B3GNT2 Primer set of;
At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 227 and SEQ ID NO: 228 for mutation detection of BFSP1;
At least one primer set selected from the group consisting of SEQ ID NO: 229 and SEQ ID NO: 230, SEQ ID NO: 231 and SEQ ID NO: 232, and base sequence pairs represented by SEQ ID NO: 233 and SEQ ID NO: 234 for mutation detection of CARD6;
At least one primer set selected from the group consisting of SEQ ID NO: 235 and SEQ ID NO: 236, and a base sequence pair represented by SEQ ID NO: 237 and SEQ ID NO: 238 for mutation detection of CHRM2;
At least one primer set selected from the group consisting of a sequence pair represented by SEQ ID NO: 239 and SEQ ID NO: 240 for detecting a mutation of EPB41L5;
At least one primer set selected from the group consisting of SEQ ID NO: 241 and SEQ ID NO: 242, and a base sequence pair represented by SEQ ID NO: 243 and SEQ ID NO: 244 for mutation detection of FBXW5;
At least one primer set selected from the group consisting of SEQ ID NO: 245 and SEQ ID NO: 246, and a nucleotide sequence pair represented by SEQ ID NO: 247 and SEQ ID NO: 248 for mutation detection of GPR173;
At least one selected from the group consisting of SEQ ID NO: 249 and SEQ ID NO: 250, SEQ ID NO: 251 and SEQ ID NO: 252, SEQ ID NO: 253 and SEQ ID NO: 254, and base sequence pairs represented by SEQ ID NO: 255 and SEQ ID NO: 256 for mutation detection of HHIPL2 Primer set of;
SEQ ID NO: 257 and SEQ ID NO: 258, SEQ ID NO: 259 and SEQ ID NO: 260, SEQ ID NO: 261 and SEQ ID NO: 262, SEQ ID NO: 263 and SEQ ID NO: 264, and SEQ ID NO: 265 and SEQ ID NO: 266 for mutation detection of KDM2A At least one primer set selected from the group consisting of a pair;
SEQ ID NO: 267 and SEQ ID NO: 268, SEQ ID NO: 269 and SEQ ID NO: 270, SEQ ID NO: 271 and SEQ ID NO: 272, SEQ ID NO: 273 and SEQ ID NO: 274, SEQ ID NO: 275 and SEQ ID NO: 276, and SEQ ID NO: 277 for mutation detection of KDM5A And at least one primer set selected from the group consisting of a nucleotide sequence pair represented by SEQ ID NO: 278;
At least one primer set selected from the group consisting of SEQ ID NO: 279 and SEQ ID NO: 280, and a sequence pair represented by SEQ ID NO: 281 and SEQ ID NO: 282 for mutation detection of NFIX;
At least one primer set selected from the group consisting of a base sequence pair represented by SEQ ID NO: 283 and SEQ ID NO: 284 for mutation detection of PICK1;
At least one primer set selected from the group consisting of SEQ ID NO: 285 and SEQ ID NO: 286, and base sequence pairs represented by SEQ ID NO: 287 and SEQ ID NO: 288 for mutation detection of PITPNB;
At least one primer set selected from the group consisting of SEQ ID NO: 289 and SEQ ID NO: 290, and a sequence pair represented by SEQ ID NO: 291 and SEQ ID NO: 292 for mutation detection of TP53TG5; And
SEQ ID NO: 293 and SEQ ID NO: 294, SEQ ID NO: 295, and SEQ ID NO: 296, SEQ ID NO: 297 and SEQ ID NO: 298, SEQ ID NO: 299 and SEQ ID NO: 300, and SEQ ID NO: 301 and SEQ ID NO: 302 for mutation detection of ZFP69 And at least one primer set selected from the group consisting of pairs.
delete delete Preparing sample DNA from a sample of kidney cancer patient;
Amplifying the sample DNA using the kit of claim 1; And
Identifying the presence or absence of a metastasis specific marker from the amplification result; and providing information necessary for prognostic diagnosis of renal cancer following metastasis of a renal cancer patient.
The method according to claim 6,
The method predicts total survival or disease free survival of kidney cancer patients.
The method according to claim 7,
Kidney cancer patients if mutations have been identified in genes encoding ASB15, CARD6, CHRM2, CHSY3, CPSF3, FBXW5, KDM2A, LOXL3, LUC7L2, MUTYH, RELN, SAA1, SUPV3L1, TP53TG5 and UBE2D1 Determining that the survival rate of the renal cancer is lower than the survival rate of a person whose mutation is not identified in the gene, or the recurrence rate of the kidney cancer of the kidney cancer patient is higher than that of the renal cancer of a person in which the mutation is not identified in the gene. How to include more.
The method according to claim 7,
ASB15, B3GNT2, CARD6, CHRM2, CHSY3, CPSF3, FBXW5, GPR173, ITGB7, KDM2A, KDM5A, LOXL3, LUC7L2, MUTYH, PITPNB, RELN, SAA1, SMO, SUPV3L1, TP53TG5 and ZFP2 When the mutation is identified and is a metastatic kidney cancer patient, determining that the survival rate of the kidney cancer patient is lower than the survival rate of the person whose mutation is not identified in the gene.
The method according to claim 7,
ADAM33, ADAMTS10, ASB15, BFSP1, C8orf37, CARD6, CHRM2, CHSY3, CPSF3, EHBP1L1, EPB41L5, FBXW5, HHIPL2, KDM2A, LOXL3, LUC7L2, MUTYH, NFIX, OR5W2, PILCB2, PILCB3 If mutations have been identified in the genes encoding SUPV3L1, TADA2A, TP53TG5, UBE2D1, ZNF320, and ZNF699, and in patients with metastatic kidney cancer, the recurrence rate of kidney cancer in those kidney cancer patients is renal cancer in people whose mutations have not been identified in the gene. Determining that the recurrence rate is higher than.

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