Patent Abstract:
Selection of clones having the kinase and/or phosphatase-like structure from clones which had been isolated and the structures thereof had been determined in the Helix Research Institute (helix clones; Japanese Patent Application No. 2000-183767) was conducted. Two novel genes were provided by carrying out homology search for all the helix clones by using the amino acid sequences of known kinases and phosphatases as queries. The genes are expected to be involved in intracellular signal transduction. The physiological functions of the inventive genes can be tested by using reporter gene assay systems capable of detecting signal transduction. The proteins of the present invention are useful as target molecules in drug discovery and in the development of new pharmaceuticals.

Full Description:
[0001]    This is a continuation-in-part of PCT/JP00/05061, filed Jul. 28, 2000, which claims priority to U.S. Provisional Application No. 60/159,590, filed Oct. 18, 1999, and No. 60/183,322, filed Feb. 17, 2000; and Japanese Patent Application Nos. 11-248036, filed Jul. 29, 1999; 2000-118776, filed Jan. 11, 2000; 2000-183767, filed May 2, 2000; and 2000-241899, filed Jun. 9, 2000. 
     
    
     
       TECHNICAL FIELD  
         [0002]    The present invention relates to novel human protein kinases and protein phosphatases, as well as to genes encoding the proteins.  
         BACKGROUND  
         [0003]    A variety of physiological functions of cells have to be regulated correctly and harmoniously according to need for cells to differtiate/proliferate into normal cells, and further to exert functions at the tissue level. It has been well known that the regulation of the state of protein phosphorylation by protein phosphorylation enzyme/protein kinase (hereinafter referred to as “kinase”) and protein dephosphorylation enzyme/protein phosphatase (hereinafter referred to as “phosphatase”) plays a central role in most of such regulatory mechanisms.  
           [0004]    Many kinase and phosphatase genes have been identified to date. It has been clarified that they form a very large protein family with a well conserved structure (Semin. Cell Biol. 5(6):367-76, 1994; Cell 80(2): 225-36, 1995; Genes Cells 1(2): 147-69, 1996; Trends Biochem. Sci. 22(1):18-22, 1997; Proc Natl Acad Sci USA 96(24):13603-10, 1999). The presence of numerous types of kinases and phosphatases in cells suggests that many types of intracellular physiological functions are precisely regulated by kinases and phosphatases. Thus, there is a possibility that agents acting on kinase or phosphatase can more precisely control physiological functions as compared with known agents represented by receptor agonist or receptor antagonist. Therefore, it is expected that agents acting on kinase or phosphatase are agents, which undesirable side effects can be much easily separated from the main effects, and accordingly, may function as highly useful pharmaceuticals.  
           [0005]    In order to develop such agents acting on kinase or phosphatase, first, it is required to specify the intracellular physiological function associated with each of the kinases and phosphatases, and gain some information indicating the medical usefulness of suppressing or activating the function. Many types of kinases and phosphatases have been already isolated and studied. However, there may exist many unidentified molecules. Furthermore, with respect to kinases and phosphatases the genes of which have been isolated, it can be stated that information on intracellular physiological functions related with each kinase or phosphatase still are poor and has to be clarified. The identification of new kinase and phosphatase as well as clarification of physiological functions thereof is expected to make significant progress in the development of new pharmaceuticals and therapies.  
         SUMMARY  
         [0006]    The object of the present invention is to provide novel human protein kinase and protein phosphatase proteins, genes encoding the proteins, as well as production and uses of the same.  
           [0007]    To accomplish the object described above, the present inventors strenuously carried out researches as follows. First, the present inventors tried to select clones having the kinase/phosphatase-like structure (KP clones) from clones which had been isolated and the structures of which had been determined in the Helix Research Institute (hereinafter referred to as “helix clones”; Japanese Patent Application No. Hei 11-248036; Japanese Patent Application No. 2000-118776; Japanese Patent Application No. 2000-183767). These helix clones are highly expected to have the full-length sequence, which were obtained by the combined use of; [1] preparation of a cDNA library containing sequences of full-length at a high rate achieved by the oligo-capping method; and [2] evaluation system for the completeness in cDNA length based on the 5′-end sequence (the selection is achieved based on the evaluation using ATGpr after eliminating non-full length clones as compared with an EST). In addition, they are highly advantageous since the cDNAs are already inserted into a mammalian expression vector, they can be used promptly in experiments for the expression in cells.  
           [0008]    The present inventors carried out homology search for all the helix clones using the amino acid sequences of known kinases and phosphatases as queries, and selected 2 clones: “C-NT2RP3001938” and “C-OVARC1000945” (hereinafter referred to as “KP clones”). These KP clones contain full-length cDNAs encoding novel human proteins. It has been known that many of known kinases and phosphatases are associated with a variety of signal transduction pathways in cells. Therefore, there is the possibility that the newly found KP clones having the kinase/phosphatase-like structure are also associated with some signal transduction pathways. The potential of the KP clones as target molecules in drug discovery can be explored through evaluating these KP clones in various assay systems using reporter genes and deducing the physiological functions thereof.  
           [0009]    As described above, the present inventors found novel kinase/phosphatase proteins, and thereby accomplished the present invention.  
           [0010]    Specifically, the present invention relates to novel human protein kinase and protein phosphatase proteins, genes encoding the proteins, and production and uses of the proteins and genes. More specifically, the present invention provides the following:  
           [0011]    [1] a DNA of any one of the following (a) to (d):  
           [0012]    (a) a DNA encoding a protein consisting of the amino acid sequence of SEQ ID NO:2 or 4,  
           [0013]    (b) a DNA comprising the coding region of the nucleotide sequence of SEQ ID NO:1 or 3,  
           [0014]    (c) a DNA encoding a protein which (i) comprises the amino acid sequence of SEQ ID NO:2 or 4 in which one or more amino acids are substituted, deleted, inserted and/or added, and (ii) is functionally equivalent to the protein consisting of the amino acid sequence of SEQ ID NO:2 or 4, and  
           [0015]    (d) a DNA hybridizing under a stringent condition to a DNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 3, which encodes a protein functionally equivalent to the protein consisting of the amino acid sequence of SEQ ID NO:2 or 4;  
           [0016]    [2] a DNA encoding a partial peptide of a protein consisting of the amino acid sequence of SEQ ID NO:2 or 4;  
           [0017]    [3] a protein or peptide encoded by the DNA of [α]or [2];  
           [0018]    [4] a vector into which the DNA of [α]or [2] has been inserted;  
           [0019]    [5] a host cell containing the DNA of [1] or [2], or containing the vector of [4];  
           [0020]    [6] a method for producing the protein or peptide of [3], which comprises the steps of culturing the host cell of [5], and recovering the expressed protein from the host cell or the culture supernatant;  
           [0021]    [7] an antibody binding to the protein of [3];  
           [0022]    [8] a polynucleotide containing at least 15 nucleotides complementary to a DNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 3, or the complementary strand thereof, and  
           [0023]    [9] a method of screening for compounds binding to the protein of [3], which comprises the steps of:  
           [0024]    (a) contacting a test sample with the protein or a partial peptide thereof,  
           [0025]    (b) detecting the binding activity of the test sample with the protein or partial peptide thereof, and  
           [0026]    (c) selecting a compound having the activity of binding to the protein or partial peptide thereof.  
           [0027]    The present invention provides human-derived genes “C-NT2RP3001938” and “C-OVARC1000945” encoding novel kinase/phosphatase. The nucleotide sequence of cDNA of the human-derived gene “C-NT2RP3001938” is shown in SEQ ID NO:1, and the amino acid sequence encoded by the cDNA is shown in SEQ ID NO:2. The nucleotide sequence of cDNA of the human-derived gene “C-OVARC1000945” is shown in SEQ ID NO:3, and the amino acid sequence encoded by the cDNA is shown in SEQ ID NO:4.  
           [0028]    The gene “C-NT2RP3001938” shown in SEQ ID NO:1 and “C-OVARC1000945” shown in SEQ ID NO:3 has an ORF encoding a protein consisting of 418 amino acids and 865 amino acids, respectively.  
           [0029]    Hereinafter, unless otherwise stated, the above-mentioned genes of the present invention, “C-NT2RP3001938” and “C-OVARC1000945” are collectively called “KP genes”, and proteins encoded by respective genes are collectively called “KP proteins”.  
           [0030]    The inventive KP proteins were selected as clones having the kinase/phosphatase-like structure from the clones isolated and whose structures had been already determined in the Helix Research Institute. The regulation of the phosphorylation state of proteins by kinase and phosphatase plays central roles in normal differentiation and/or proliferation of cells, as well as in physiological functions at the cellular level. Thus, the inventive proteins are expected to share important functions in living body, and therefore, are useful as target molecules in drug development. In addition, the inventive KP proteins can be used as reagents for phosphorylating or dephosphorylating proteins.  
           [0031]    The helix clones were prepared by a special method, and are expected to contain cDNA of full-length chains in high probability (Japanese Patent Application No. Hei 11-248036; Japanese Patent Application No. 2000-118776; Japanese Patent Application No. 2000-183767). Furthermore, because the cDNAs are already inserted in a mammalian expression vector, they can be used promptly in experiments for the expression in cells. Thus, information on physiological functions of the genes can be gained by successively testing these vectors with various assay systems using reporter genes. It has been known that many of known kinases and phosphatases are associated with a variety of signal transduction pathways in cells, and thus, the inventive KP genes can be also associated with signal transduction. Various potential physiological functions of the inventive genes can be thoroughly examined by functional screening using reporter gene assay systems in which known types of signal transduction can be detected.  
           [0032]    Assay systems using reporter genes are excellent experimental systems which enable assessment of a variety of intracellular physiological functions simply in a single format. Specifically, the functional screening is preformed by the following reporter gene assay. A vector containing the inventive KP gene is introduced into the host cell with reporter genes having a variety of enhancer elements, and the KP gene is expressed in the cell. When the expression level of the reporter gene is altered as compared to that of the control cells in which no vector containing the KP gene had been introduced, it can be concluded that the protein encoded by the KP gene acted on the enhancer element. Useful information on physiological functions of the inventive KP gene is expected to be provided by testing whether the inventive KP gene acts on a variety of enhancer elements or not. Large amount of information on signal transduction systems acting on the elements, functional genes regulated by the enhancer elements, and so on, are known for many enhancer elements. Thus, when a KP gene being tested is proved to act on an enhancer element, it is possible to deduce physiological functions in which the KP gene participates based on known information on the enhancer element.  
           [0033]    In the functional screening, it is also beneficial to study not only actions of a KP gene expressed alone, but also influences of the KP gene on the action after some stimuli. More specifically, even if the KP gene alone does not exhibit any activity, there is the possibility that the activation of a particular element by a known type of stimulus is enhanced or suppressed by the coexpressed KP gene. Such a known type of stimulus includes, for example, ligands of a cell surface receptor (interleukins, growth factors, TGF-β family, TNF-α family, hormones, low-molecular-weight compounds, etc.); expression of factors associated with intracellular signal transduction (various kinases, various phosphatases, low-molecular-weight G protein binding protein family, Smad family, STAT family, TRAF family, cell surface receptors, etc.); stress stimuli (oxidation stress, mechanical stress, heat stress, etc.); and so on.  
           [0034]    The assays using reporter genes can be conducted by those skilled in the art by using a variety of commercially available kits that are used conventionally. For example, Mercury™ Pathway Profiling Systems from Clontech, PathDetectR Trans-Reporting System and PathDetectR Cis-Reporting System from Stratagene, and such are included. The assays can be conducted according to standard methods as described in the literature (“Overview of Genetic Reporter Systems” In Current Protocols in Molecular Biology, Ed. Ausubel, F. M. et al., (Wiley &amp; Sons, NY) Unit 9.6 (1995); Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press (Cold Spring Harbor, N.Y. (1989)).  
           [0035]    When the luciferase gene is used as the reporter gene, the luciferase activity can be measured, for example, by a standard method using Dual-Luciferase™ Reporter Assay System from Promega or the like.  
           [0036]    Reporter genes that can be used in the above-mentioned functional screening include, for example, secretory alkaline phosphatase gene, chloramphenicol acetyltransferase (CAT) gene, α-galactosidase gene, and such in addition to luciferase gene. Further, enhancer elements that are used in the reporter assay can be exemplified by Serum Response Element (SRE), cAMP Response Element (CRE), TPA Response Element (TRE), NFκB (Nuclear factor of κB cell)-binding element, Heat shock Response Element (HRE), Glucocorticoid Response Element (GRE), AP 1 (Activator protein 1: c-jun/c-fos complex)-binding element, NFAT (Nuclear Factor of Activated T-cells)-binding element, p53-binding element, interferon-γ activated element (Interferon Gamma Activated Sequence: GAS), Interferon-Stimulated Response Element (ISRE), E2F-binding element, STAT family-binding element, Smad family-binding element, TCF/LEF-binding element, GATA family-binding element, Sterol Regulatory Element (SRE), IRF (Interferon Regulatory Factor) family-binding element, PPAR γ-binding element and AhR-binding element.  
           [0037]    293 cell, Hela, NIH3T3, CV-1, Jurkat, vascular smooth muscle cell, vascular endothelial cell, and cardiac muscle cell can be exemplified as host cells that are used in the reporter assay.  
           [0038]    Functionally equivalent proteins to the human KP proteins (SEQ ID NOs:2 and 4) are encompassed in the present invention. Such proteins include, for example, mutants, homologues, variants, and so on, of human KP proteins. The term “functionally equivalent” herein means that the protein of interest has a function of phosphorylating proteins and/or dephosphorylating proteins like the KP proteins. According to the following procedure, it can be judged whether or not the protein of interest phosphorylates a protein.  
           [0039]    A kinase protein and a substrate protein are combined together in an appropriate reaction solution. After the reaction is conduced in the presence of ATP, the phosphorylation state of the substrate protein is measured to judge the phosphorylation activity. The kinase protein to be used can be purified from appropriate cell lines or extracts from tissue by commonly used biochemical methods. It is also possible to use kinase proteins obtained by the overexpression of introduced genes encoding kinase proteins into mammalian cells (COS7, CV-1, HEK293, HeLa, Jurkat, NIH3T3, etc.), insect cells (Sf9, etc.),  E. coli , yeast, and so on. The phosphorylation state of the substrate protein can be measured in a liquid scintillation counter, autoradiography, and such, by using ATP labeled with radioisotope, such as [γ- 32 P] ATP.  
           [0040]    Further, the phosphorylation state of the substrate protein can be measured by ELISA (enzyme-linked immunosorbent assay), Western blotting, etc. using phosphorylated protein specific antibodies or the like. Such substrate proteins to be used include proteins specific to particular kinases, as well as a variety of proteins, such as casein, histone, and myelin basic protein (MBP), which are known to be phosphorylated by non-specific kinases. Alternatively, synthetic peptides and such containing sequences that are phosphorylated may be also used.  
           [0041]    Furthermore, the phosphorylation activity can be assessed by measuring the phosphorylation of the kinase protein per se (autophosphorylation). More specifically, the assay can be performed according to conventional methods described in Protein Phosphorylation: A Practical Approach. First Edition (Hardie D G. et al., Oxford University Press, 1993) or others.  
           [0042]    It can be judged whether a protein of interest dephosphorylates a protein or not by using the following procedure.  
           [0043]    A phosphatase protein and a pre-phosphorylated substrate protein are combined together in an appropriate reaction solution. Then, the decrease in the extent of phosphorylation of the substrate protein or the amount of phosphate released from the substrate protein is measured to assess the dephosphorylation activity. Those phosphatase proteins prepared by the same method as those described above for the assessment of the phosphorylation activity can be used as the phosphatase protein in this method. The same substrate protein mentioned above for the judgment of the phosphorylation activity can be used as the substrate protein herein. In addition, phosphorylase, phosphorylase kinase, and such can be also used as substrate proteins. The pre-phosphorylation of the substrate protein can be achieved by using appropriate kinase such as phosphorylase kinase, protein kinase A, tyrosine kinases including EGF receptor and so on. The phosphorylation state of the substrate protein can be assayed by the same method described above for the assessment of the phosphorylation activity. More specifically, the assay can be performed according to conventional methods described in “Protein Phosphorylation: A Practical Approach. First Edition (Hardie et al., Oxford University Press, 1993)”, and so on.  
           [0044]    Further, the substrate protein to be phosphorylated or dephosphorylated by a test protein can be identified by expressing a cDNA expression library composed of phage vectors or the like, and assessing whether a protein expressed from each clone can be a substrate for the test protein or not. More specifically, the identification can be carried out by referring to the method described in “EMBO J. (1997) 16:1921-1933”. Alternatively, the substrate protein can be identified through the identification of proteins binding to the test protein by the yeast two-hybrid screening or the like. More specifically, the identification can be carried out by referring to the method described in “EMBO J. (1997) 16:1909-1920”.  
           [0045]    One method for preparing functionally equivalent proteins well known to those skilled in the art involves the introduction of mutations into the proteins. For example, one skilled in the art can prepare proteins functionally equivalent to the human KP protein (SEQ ID NO:2 or 4) by introducing appropriate mutations into the amino acid sequence of the protein using the site-directed mutagenesis method (Hashimoto-Gotoh et al., Gene 152:271-275, 1995; Zoller et al., Methods Enzymol. 100:468-500, 1983; Kramer et al., Nucleic Acids Res. 12:9441-9456, 1984; Kramer et al., Methods. Enzymol. 154:350-367, 1987; Kunkel, Proc. Natl. Acad. Sci. USA 82:488-492, 1985; Kunkel, Methods Enzymol. 85:2763-2766, 1988) and such. Mutation of amino acids may occur in nature, too. The proteins of the present invention include proteins comprising the amino acid sequence of human KP protein (SEQ ID NO:2 or 4) in which one or more amino acids are mutated, so long as the resulting mutant protein is functionally equivalent to the protein. In such a mutant protein, the number of the amino acids to be mutated is usually 50 residues or less, preferably 30 residues or less, and more preferably 10 residues or less (e.g., 5 residues or less).  
           [0046]    The amino acid residue to be mutated is preferably mutated into a different amino acid that allows the properties of the amino acid side-chain to be conserved. Examples of properties of amino acid side chains include: hydrophobic amino acids (A, I, L, M, F, P, W, Y, V), hydrophilic amino acids (R, D, N, C, E, Q, G, H, K, S, T), and amino acids comprising the following side chains: an aliphatic side-chain (G, A, V, L, I, P); a hydroxyl group containing side-chain (S, T, Y); a sulfur atom containing side-chain (C, M); a carboxylic acid and amide containing side-chain (D, N, E, Q); a base containing side-chain (R, K, H); and an aromatic containing side-chain (H, F, Y, W) (The parenthetic letters indicate the one-letter codes of amino acids).  
           [0047]    It is well known that a protein having deletion, addition, and/or substitution of one or more amino acid residues in the sequence of a protein can retain the original biological activity (Mark et al., Proc. Natl. Acad. Sci. USA 81:5662-5666, 1984; Zoller et al., Nucleic Acids Res. 10:6487-6500, 1982; Wang et al., Science 224:1431-1433; Dalbadie-McFarland et al., Proc. Natl. Acad. Sci. USA 79:6409-6413, 1982).  
           [0048]    A protein having the amino acid sequence of human KP protein to which one or more amino acid residues have been added, is exemplified by a fusion protein containing the human KP protein. Fusion proteins, in which the human KP protein is fused to other peptides or proteins, are included in the present invention. Fusion proteins can be made using techniques well known to those skilled in the art, for example, by linking the DNA encoding the human KP protein (SEQ ID NO:2 or 4) in frame with the DNA encoding other peptides or proteins, followed by inserting the DNA into an expression vector and expressing it in a host. There is no restriction as to the peptides or proteins to be fused to the protein of the present invention.  
           [0049]    For instance, known peptides which may be used for the fusion include the FLAG peptide (Hopp et al., BioTechnology 6:1204-1210, 1988), 6× His that is made up of six histidine residues, 10× His, influenza hemagglutinin (HA), human c-myc fragment, VSV-GP fragment, p18HIV fragment, T7-tag, HSV-tag, E-tag, SV40 T antigen fragment, lck tag, α-tubulin fragment, B-tag, and Protein C fragment. Also, glutathione-S-transferase (GST), influenza hemagglutinin (HA), the constant region of immunoglobulin, β-galactosidase, maltose binding protein (MBP), and the like may be used as a protein to be fused with the protein of this invention. Fusion proteins can be prepared by fusing the DNA encoding these peptides or proteins, which are commercially available, with the DNA encoding the protein of the invention, and expressing the fused DNA.  
           [0050]    An alternative method for preparing functionally equivalent proteins known to those skilled in the art utilizes, for example, the hybridization technique (Sambrook et al., Molecular Cloning 2nd ed. 9.47-9.58, Cold Spring Harbor Lab. Press, 1989). Generally, one skilled in the art can isolate DNAs highly homologous to the whole or part of the DNA sequence encoding the human KP protein (SEQ ID NO: 1 or 3), and then isolate proteins functionally equivalent to the human KP protein based on those DNAs isolated. The present invention includes proteins that are (i) encoded by a DNA hybridizing to a DNA encoding the human KP protein and (ii) functionally equivalent to the human KP protein. Such proteins include, for example, homologues derived from human and other animals (for example, protein encoded by a DNA from mouse, rat, rabbit, cattle, etc.).  
           [0051]    Those skilled in the art can properly select hybridization conditions to be used for the isolation of DNAs encoding proteins functionally equivalent to the human KP protein. Hybridization conditions include low stringent conditions. Low stringent conditions may be, for example, 42° C. in 2× SSC and 0.1% SDS, preferably 50° C. in 2× SSC and 0.1% SDS for washing after hybridization. More preferably, high stringent conditions such as 65° C. in 0.1× SSC and 0.1% SDS may be chosen. DNA with higher homology may be efficiently obtained at higher temperature under these conditions. However, several factors are thought to influence the stringency of hybridization, such as temperatures and salt concentrations, and one skilled in the art can suitably select these factors to accomplish a similar stringency. More guidelines for the hybridization condition are available in the art, for example, in a reference by Sambrook et al., (1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, N.Y.) and in unit 2.10 of the reference by Ausubel et al. (1995, Current Protocols in Molecular Biology, John Wiley &amp; Sons, N.Y.).  
           [0052]    Also, in lieu of hybridization, it is also possible to isolate functionally equivalent proteins by a gene amplification method, such as PCR, by synthesizing sequences based on the sequence information of the DNA encoding the human KP protein (SEQ ID NO: 1 or 3) and using them as primers.  
           [0053]    The proteins functionally equivalent to the human KP proteins encoded by the DNA isolated by the hybridization or gene amplification techniques, usually are highly homologous to the human KP proteins (SEQ ID NO:2 or 4) at the amino acid sequence level. The proteins of the invention include proteins functionally equivalent to the human KP protein and are highly homologous to the amino acid sequence of SEQ ID NO:2 or 4. “Highly homologous” means typically 65% or higher, preferably 75% or higher, more preferably 85% or higher, and even more preferably 95% or higher identity at the amino acid level. Homology between proteins can be determined according to the algorithm described in the literature (Wilbur et al., Proc. Natl. Acad. Sci. USA 80:726-730, 1983).  
           [0054]    The proteins of the present invention may have variations in the amino acid sequence, molecular weight, isoelectric point, presence or absence of sugar chains, or form, depending on the cell or host used to produce them or the purification method utilized as described below. Nevertheless, so long as the protein obtained has a function equivalent to the human KP protein, it is within the scope of the present invention. For example, when the inventive protein is expressed in prokaryotic cells, e.g.,  E. coli , a methionine residue is added at the N-terminus of the original protein. The present invention also includes such proteins.  
           [0055]    The proteins of the present invention can be prepared as recombinant proteins or as naturally occurring proteins, using methods commonly known in the art. The recombinant protein can be, for example, prepared as follows. The DNA encoding the protein of this invention (e.g., DNA having the nucleotide sequence of SEQ ID NO: 1 or 3) is inserted into an appropriate expression vector, and introduced into suitable host cells. Subsequently, the resulting transformants, the host cell inserted with the expression vector, are recovered, extracted and then purified by chromatography utilizing ion exchange, reverse phase, or gel filtration, or by affinity chromatography with a column in which the antibodies against the protein of the present invention are fixed, or by a combination of these columns.  
           [0056]    Alternatively, the protein of the invention can be prepared by expressing the protein in host cells (e.g., animal cells or  E. coli ) as a fusion protein with glutathione S transferase protein, or as a recombinant protein with multiple histidine residues. The expressed protein can be purified using a glutathione column or nickel column. Subsequently, if necessary, regions of the fusion protein (apart from the desired protein) can be digested and removed with thrombin, factor Xa, etc.  
           [0057]    The natural protein corresponding to the protein of the invention can be isolated by methods well known in the art, for example, by purifying tissue or cell extracts containing a protein of the invention with an affinity column to which the antibody that binds to the protein of the present invention described below is bound. The antibody may be a polyclonal antibody or monoclonal antibody.  
           [0058]    The term “substantially pure” as used herein in reference to a given polypeptide means that the polypeptide is substantially free from other biological macromolecules. For example, the substantially pure polypeptide is at least 75%, 80, 85, 95, or 99% pure by dry weight. Purity can be measured by any appropriate standard method known in the art, for example, by column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis.  
           [0059]    Accordingly, the invention includes a polypeptide having a sequence shown as SEQ ID NO:2 or 4. The invention also includes a polypeptide, or fragment thereof, that differs from the corresponding sequence shown as SEQ ID NO:2 or 4. The differences are, preferably, differences or changes at a non-essential residue or a conservative substitution. In one embodiment, the polypeptide includes an amino acid sequence at least about 60% identical to a sequence shown as SEQ ID NO:2 or 4, or a fragment thereof. Preferably, the polypeptide is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more identical to SEQ ID NO:2 or 4 and has at least one phosphorylation-related function or activity described herein, e.g., the polypeptide has a kinase or phosphatase activity. Preferred polypeptide fragments of the invention are at least 10%, preferably at least 20%, 30%, 40%, 50%, 60%, 70%, or more, of the length of the sequence shown as SEQ ID NO:2 or 4 and have at least one cell differentiation-related function or activity described herein. Or alternatively, the fragment can be merely an immunogenic fragment.  
           [0060]    The present invention also includes partial peptides of the proteins of the present invention. The partial peptides of the present invention comprise at least 7 or more amino acids, preferably 8 or more amino acids, more preferably 9 or more amino acids. The partial peptides can be used, for example, for generating antibodies against the protein of the present invention, screening of compounds binding to the protein of the present invention, or screening of promoters or inhibitors for the protein of the present invention. The partial peptides can be used as antagonists or competitive inhibitors for the protein of this invention. The partial peptides of the invention can be produced by genetic engineering, known methods of peptide synthesis, or by digesting the protein of the invention with an appropriate peptidase. For peptide synthesis, for example, solid phase synthesis or liquid phase synthesis may be used.  
           [0061]    DNA encoding an inventive protein can be used for the production of the inventive protein in vivo and in vitro as described above; it is also applicable to, for example, gene therapy for diseases caused by the abnormality in the gene encoding the inventive protein and for diseases that can be treated by the inventive protein. Any type of DNA, such as cDNA synthesized from mRNA, genomic DNA or synthetic DNA, can be used so long as the DNA encodes a protein of the present invention. Also so long as they can encode a protein of the present invention, DNAs comprising arbitrary sequences based on the degeneracy of the genetic code are also included.  
           [0062]    As used herein, an “isolated nucleic acid” is a nucleic acid, the structure of which is not identical to that of any naturally occurring nucleic acid or to that of any fragment of a naturally occurring genomic nucleic acid spanning more than three genes. The term therefore covers, for example, (a) a DNA which has the sequence of part of a naturally occurring genomic DNA molecule but is not flanked by both of the coding sequences that flank that part of the molecule in the genome of the organism in which it naturally occurs; (b) a nucleic acid incorporated into a vector or into the genomic DNA of a prokaryote or eukaryote in a manner such that the resulting molecule is not identical to any naturally occurring vector or genomic DNA; (c) a separate molecule such as a cDNA, a genomic fragment, a fragment produced by polymerase chain reaction (PCR), or a restriction fragment; and (d) a recombinant nucleotide sequence that is part of a hybrid gene, i.e., a gene encoding a fusion protein. Specifically excluded from this definition are nucleic acids present in random, uncharacterized mixtures of different DNA molecules, transfected cells, or cell clones, e.g., as these occur in a DNA library such as a cDNA or genomic DNA library.  
           [0063]    Accordingly, in one aspect, the invention provides an isolated or purified nucleic acid molecule that encodes a polypeptide described herein or a fragment thereof. Preferably, the isolated nucleic acid molecule includes a nucleotide sequence that is at least 60% identical to the nucleotide sequence shown in SEQ ID NO:1 or 3. More preferably, the isolated nucleic acid molecule is at least 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, identical to the nucleotide sequence shown in SEQ ID NO: 1 or 3. In the case of an isolated nucleic acid molecule which is longer than or equivalent in length to the reference sequence, e.g., SEQ ID NO: 1 or 3, the comparison is made with the full length of the reference sequence. Where the isolated nucleic acid molecule is shorter that the reference sequence, e.g., shorter than SEQ ID NO: 1 or 3, the comparison is made to a segment of the reference sequence of the same length (excluding any loop required by the homology calculation).  
           [0064]    As used herein, “% identity” of two amino acid sequences, or of two nucleic acid sequences, is determined using the algorithm of Karlin and Altschul (PNAS USA 87:2264-2268, 1990), modified as in Karlin and Altschul, PNAS USA 90:5873-5877, 1993). Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). BLAST nucleotide searches are performed with the NBLAST program, score=100, wordlength=12. BLAST protein searches are performed with the XBLAST program, score=50, wordlength=3. To obtain gapped alignment for comparison purposes GappedBLAST is utilized as described in Altschul et al (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and GappedBLAST programs the default parameters of the respective programs (e.g., XBLAST and NBLAST) are used to obtain nucleotide sequences homologous to a nucleic acid molecule of the invention.  
           [0065]    The DNA of the present invention can be prepared using methods known in the art. For example, a cDNA library can be constructed from the cells expressing the protein of the present invention, and hybridization can be conducted using a part of the DNA sequence of the present invention (for example, SEQ ID NO: 1 or 3) as a probe. cDNA libraries may be prepared by, for example, the method described in the literature (Sambrook et al., Molecular Cloning, Cold Spring Harbor Laboratory Press, 1989), and also, commercially available ones can be used. Alternatively, the DNA of the present invention can be obtained by preparing the RNA from the cells expressing the protein of the present invention, synthesizing cDNA by reverse transcriptase, synthesizing the oligo-DNAs based on the DNA sequence of the present invention (for example, SEQ ID NO: 1 or 3), and amplifying the cDNA encoding the protein of the present invention by PCR using the oligonucleotides as primers.  
           [0066]    The nucleotide sequence of the obtained cDNA is determined to find an open reading frame, and thereby the amino acid sequence of the protein of the invention can be obtained. The cDNA obtained may also be used as a probe for screening a genomic library to isolate a genomic DNA.  
           [0067]    More specifically, mRNAs may first be prepared from a cell, tissue, or organ in which the protein of the invention is expressed. Known methods can be used to isolate mRNAs; for instance, total RNA can be prepared by guanidine ultracentrifugation (Chirgwin et al., Biochemistry 18:5294-5299, 1979) or the AGPC method (Chomczynski et al., Anal. Biochem. 162:156-159, 1987). mRNA may then be purified from total RNA using mRNA Purification Kit (Pharmacia) and such; alternatively, mRNA may be directly purified by QuickPrep mRNA Purification Kit (Pharmacia).  
           [0068]    The obtained mRNA is used to synthesize cDNA using reverse transcriptase. cDNA may be synthesized by using a kit such as the AMV Reverse Transcriptase First-strand cDNA Synthesis Kit (Seikagaku Kogyo). Alternatively, cDNA may be synthesized and amplified following the 5′-RACE method (Frohman et al., Proc. Natl. Acad. Sci. USA 85:8998-9002, 1988; Belyavsky et al., Nucleic Acids Res. 17:2919-2932, 1989) which uses primers described herein, the 5′-Ampli FINDER RACE Kit (Clontech), and polymerase chain reaction (PCR).  
           [0069]    A desired DNA fragment is prepared from the PCR products and ligated with a vector DNA. The recombinant vectors are used to transform  E. coli  and such, and a desired recombinant vector is prepared from a selected colony. The nucleotide sequence of the desired DNA is verified by conventional methods, such as dideoxynucleotide chain termination.  
           [0070]    A DNA of the invention may be designed to have a sequence that is expressed more efficiently by taking into account the frequency of codon usage in the host to be used for expression (Grantham et al., Nucleic Acids Res. 9:43-74, 1981). The DNA of the present invention may be altered by a commercially available kit or a conventional method. For instance, the DNA may be altered by digestion with restriction enzymes, insertion of a synthetic oligonucleotide or an appropriate DNA fragment, addition of a linker, or insertion of the initiation codon (ATG) and/or the stop codon (TAA, TGA, or TAG).  
           [0071]    The inventive DNA includes, specifically, a DNA comprising a stretch from A at nucleotide residue 366 to C at nucleotide residue 1619 from the nucleotide sequence of SEQ ID NO:1 as well as a stretch from A at nucleotide residue 33 to A at nucleotide residue 2627 from the nucleotide sequence of SEQ ID NO:3.  
           [0072]    The DNA of the present invention also include a DNA hybridizing to a DNA consisting of the nucleotide sequence of SEQ ID NO: 1 or 3 and encoding a protein functionally equivalent to the above-mentioned protein of the present invention. Those skilled in the art can properly select the appropriate hybridization conditions, and specifically the above-mentioned conditions can be used. Under these conditions, the higher the temperature, the higher the homology of the obtained DNA will be. The above-mentioned hybridizing DNA is preferably a naturally occurring DNA, for example, cDNA or chromosomal DNA.  
           [0073]    The present invention also provides a vector into which a DNA of the present invention is inserted. The vectors of the present invention are useful for maintaining the DNA of the present invention within host cells or expressing the protein of the invention.  
           [0074]    When the  E. coli  is used as a host cell, there is no limitation other than that the vector should have an “ori” to amplify and mass-produce the vector in  E. coli  (e.g., JM109, DH5α, HB101, or XL1Blue), and a marker gene for selecting the transformed  E. coli  (e.g., a drug-resistance gene selected by a drug such as ampicillin, tetracycline, kanamycin, or chloramphenicol). For example, M13-series vectors, pUC-series vectors, pBR322, pBluescript, pCR-Script, and such can be used. pGEM-T, pDIRECT, pT7, and so on can also be used for subcloning and excision of the cDNA as well as the vectors described above. When a vector is used to produce a protein of the present invention, an expression vector is especially useful. The expression vector, for example, to be expressed in  E. coli  should have the above characteristics to be amplified in  E. coli . When  E. coli , such as JM109, DH5α, HB101, or XL1 Blue, is used as the host cell, the vector should have a promoter such as lacZ promoter (Ward et al., Nature 341:544-546, 1989; FASEB J. 6:2422-2427, 1992), araB promoter (Better et al., Science 240:1041-1043, 1988), or T7 promoter that can efficiently promote the expression of the desired gene in  E. coli . Other examples of the vectors are pGEX-5×-1 (Pharmacia), “QlAexpress system” (Qiagen), pEGFP, and pET (for this vector, BL21, a strain expressing T7 RNA polymerase, is preferably used as the host).  
           [0075]    Further, the vector may contain a signal sequence for the secretion of polypeptides. The pelB signal sequence (Lei et al., J. Bacteriol. 169:4379, 1987) can be used as a signal sequence for secretion of proteins, when the proteins are intended to be produced in the periplasm of  E. coli . Introduction of the vector into a host cell can be performed, for example, by the calcium chloride method or electroporation.  
           [0076]    In addition to the vectors for  E. coli , for example, the vector for producing the proteins of this invention may be a mammal-derived expression vector (e.g., pcDNA3 (Invitrogen), pEGF-BOS (Nucleic Acids Res. 18(17):5322, 1990), pEF, and pCDM8), an insect cell-derived expression vector (e.g., “Bac-to-BAC baculovairus expression system” (GibcoBRL) and pBacPAK8), a plant-derived expression vector (e.g., pMH1 and pMH2), an animal virus-derived expression vector (e.g., pHSV, pMV, and pAdexLcw), a retrovirus-derived expression vector (e.g., pZIPneo), an yeast-derived expression vector (e.g., “Pichia Expression Kit” (Invitrogen), pNV11, and SP—QO1), a  Bacillus subtilis -derived expression vector (e.g., pPL608 and pKTH50).  
           [0077]    In order to express proteins in animal cells, such as CHO, COS, and NIH3T3 cells, the vector should have a promoter necessary for expression in such cells, e.g., SV40 promoter (Mulligan et al., Nature 277:108, 1979), MMLV-LTR promoter, EF1α promoter (Mizushima et al., Nucleic Acids Res. 18:5322, 1990), CMV promoter, etc., and more preferably it has a marker gene for selecting transformants (for example, a drug resistance gene selected by a drug (e.g., neomycin, G418, etc.)). Examples of vectors with these characteristics include pMAM, pDR2, pBK-RSV, pBK-CMV, pOPRSV, pOP13, and so on.  
           [0078]    The method using CHO cells deficient in nucleic acid synthetic pathways as the host, and incorporating a vector (such as PCHOI) with a DHFR gene that compensates for the deficiency and amplifying the vector with methotrexate (MTX) can be mentioned as an example method for stably expressing a gene and amplifying the copy number in cells. And as a method for transient expression, a method transforming the COS cells, which have the gene for SV40 T antigen on the chromosome, with a vector (such as pcD) having the SV40 replication origin can be mentioned. The origin used for replication may be those of polyomavirus, adenovirus, bovine papilloma virus (BPV), and the like. In addition, the expression vector may include a selection marker gene for amplification of the gene copies in host cells. Examples of such markers include, but are not limited to, the aminoglycoside transferase (APH) gene, the thymidine kinase (TK) gene, the  E. coli  xanthine-guanine phosphoribosyl transferase (Ecogpt) gene, and the dihydrofolate reductase (dhfr) gene.  
           [0079]    The DNA of the present invention can be expressed in animals by, for example, inserting a DNA of the invention into an appropriate vector and introducing the vector into a living body by the retrovirus method, liposome method, cationic liposome method, adenovirus method, and so on. Thus, gene therapy can be conducted for diseases caused by mutations in the KP gene of this invention. The vectors used include, but are not limited to, adenoviral vectors (e.g., pAdexlcw) and retroviral vectors (e.g., pZIPneo). General techniques for gene manipulation, such as insertion of the DNA of the invention into a vector, can be performed according to conventional methods (Molecular Cloning, 5.61-5.63). The DNA of this invention can be administered to the living body by an ex vivo method or in vivo method.  
           [0080]    The present invention also provides a host cell into which the vector of the present invention has been introduced. The host cell into which the vector of the invention is introduced is not particularly limited.  E. coli  and various animal cells can be used. The host cell of this invention can be used as, for example, a production system for producing or expressing the protein of the invention. The production system for producing a protein of the invention may be both in vitro or in vivo production system. For in vitro production, eukaryotic cells or prokaryotic cells can be used.  
           [0081]    Useful eukaryotic host cells may be animal, plant, or fungi cells. As animal cells, mammalian cells such as CHO (J. Exp. Med. 108:945, 1995), COS, 3T3, myeloma, baby hamster kidney (BHK), HeLa, or Vero cells, amphibian cells such as  Xenopus oocytes  (Valle et al., Nature 291:340-358, 1981), or insect cells such as Sf9, Sf21, or Tn5 cells can be used. CHO cells lacking DHFR gene (dhfr-CHO) (Proc. Natl. Acad. Sci. USA 77:4216-4220, 1980) or CHO K-1 (Proc. Natl. Acad. Sci. USA 60:1275, 1968) may also be used. Among the animal cells, CHO cells are particularly preferable for high-level expression. The vector can be introduced into the host cell by, for example, the calcium phosphate method, the DEAE-dextran method, cationic liposome DOTAP (Boehringer Mannheim) method, electroporation, lipofection, etc.  
           [0082]    As plant cells, for example, plant cells originating from  Nicotiana tabacum  are known as protein production system and may be used as callus cultures. As fungi cells, yeast cells such as Saccharomyces, including  Saccharomyces cerevisiae , or filamentous fungi such as Aspergillus, including  Aspergillus niger , are known.  
           [0083]    Useful prokaryotic cells include bacterial cells, such as  E. coli , for example, JM109, DH5 α, and HB101, or  Bacillus subtilis.    
           [0084]    These cells are transformed by a desired DNA, and the resulting transformants are cultured in vitro to obtain the protein. Transformants can be cultured using known methods. Culture medium such as DMEM, MEM, RPMI1640, or IMDM may be used for animal cells. The culture medium can be used with or without serum supplement such as fetal calf serum (FCS). The pH of the culture medium is preferably between about 6 and 8. Cells are typically cultured at about 30 to 40° C. for about 15 to 200 hr, and the culture medium may be replaced, aerated, or stirred if necessary.  
           [0085]    Animal and plant hosts may be used for in vivo production. For example, a desired DNA can be introduced into an animal or plant host. Encoded proteins are produced in vivo, and then are recovered. These animal and plant hosts are included in host cells of the present invention.  
           [0086]    Animals to be used for the production system described above include mammals and insects. Mammals such as goat, porcine, sheep, mouse, and bovine may be used (Vicki Glaser, SPECTRUM Biotechnology Applications, 1993). Alternatively, the mammals may be transgenic animals.  
           [0087]    For instance, a desired DNA may be prepared as a fusion gene, fused with a gene such as goat β casein gene which encodes a protein specifically produced into milk. DNA fragments comprising the fusion gene are injected into goat embryos, which are then transplanted back to female goats. Proteins of interest can be recovered from milk produced by the transgenic goats (i.e., those born from the goats that had received the embryos) or from their offspring. To increase the amount of milk containing the proteins produced by transgenic goats, hormones may be appropriately administered to them (Ebert et al., Bio/Technology 12:699-702, 1994).  
           [0088]    Alternatively, insects, such as the silkworm, may be used. Baculoviruses into which the DNA encoding the protein of interest is inserted can be used to infect silkworms, and the desired protein can be recovered from their body fluid (Susumu et al., Nature 315:592-594, 1985).  
           [0089]    As plants, for example, tobacco can be used. In use of tobacco, DNA encoding the protein of interest may be inserted into a plant expression vector, such as pMON530, which is introduced into bacteria, such as  Agrobacterium tumefaciens . Then the bacteria is used to infect tobacco, such as  Nicotiana tabacum , and a desired polypeptide can be recovered from their leaves (Julian et al., Eur. J. Immunol. 24:131-138, 1994).  
           [0090]    A protein of the present invention obtained as above may be isolated from inside or outside of the host cells (e.g., culture media), and purified as a substantially pure homogeneous protein. The method for protein isolation and purification is not limited to any specific method; in fact, any standard method may be used. For instance, column chromatography, filter, ultrafiltration, salt precipitation, solvent precipitation, solvent extraction, distillation, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, isoelectric point electrophoresis, dialysis, recrystallization, and so on may be appropriately selected and combined to isolate and purify the protein.  
           [0091]    For example, affinity chromatography, ion-exchange chromatography, hydrophobic chromatography, gel filtration, reverse phase chromatography, adsorption chromatography, and such may be used for chromatography (Strategies for Protein Purification and Characterization: A Laboratory Course Manual. Ed. Daniel R. Marshak et al., Cold Spring Harbor Laboratory Press, 1996). These chromatographies may be performed by liquid chromatography such as HPLC and FPLC. Thus, the present invention includes highly purified proteins, purified by the above methods.  
           [0092]    A protein of the present invention may be optionally modified or partially deleted by treating it with an appropriate protein modification enzyme before or after purification. Useful protein modification enzymes include, but are not limited to, trypsin, chymotrypsin, lysylendopeptidase, protein kinase, glucosidase, and so on.  
           [0093]    The present invention also provides antibodies that bind to the protein of the invention. The antibody of the invention may take any form, including monoclonal antibody, as well as polyclonal antibodies. Furthermore, antiserum obtained by immunizing an animal such as rabbit with the protein of the invention, all classes of polyclonal and monoclonal antibodies, human antibodies, and humanized antibodies produced by genetic recombination are included.  
           [0094]    A protein of the invention used as the antigen to obtain antibodies may be derived from any animal species, but preferably it is derived from a mammal, such as a human, mouse, or rat, and more preferably from human. A human-derived protein may be obtained from the nucleotide or amino acid sequences disclosed herein.  
           [0095]    Herein, a protein used as an antigen may be a complete protein or partial peptides thereof.  
           [0096]    A partial peptide may be, for example, an amino (N)-terminal or carboxy (C)-terminal fragment of the protein. Herein, an antibody is defined as an antibody that reacts with either the full-length or a fragment of the protein.  
           [0097]    A gene encoding a protein of the invention or its fragment may be inserted into a known expression vector, which is used to transform a host cell as described herein. The desired protein or its fragment may be recovered from the outside or inside of the host cell by any standard method, and may be used as an antigen. Alternatively, cells expressing the protein or their lysates, or a chemically synthesized protein may be used as an antigen. Short peptides are preferably used as antigens by appropriately combining them with carrier proteins such as keyhole limpet hemocyanin, bovine serum albumin, and ovalbumin.  
           [0098]    Any mammalian animal may be immunized with the antigen, but preferably the compatibility with parental cells used for cell fusion is taken into account. In general, animals of Rodentia, Lagomorpha, or Primates are used.  
           [0099]    Animals of Rodentia include, for example, mouse, rat, and hamster. Animals of Lagomorpha include, for example, rabbit. Animals of Primates include, for example, a monkey of Catarrhini (old world monkey) such as crab-eating monkey, rhesus monkey, sacred baboon, or chimpanzee.  
           [0100]    Methods for immunizing animals with antigens are known in the art. For instance, intraperitoneal injection or subcutaneous injection of antigens is used as a standard method for immunization of mammals. More specifically, antigens may be diluted and suspended in an appropriate amount with phosphate buffered saline (PBS), physiological saline, etc. If desired, the antigen suspension may be mixed with an appropriate amount of a standard adjuvant, such as Freund&#39;s complete adjuvant, made into emulsion, and then administered to mammals. Preferably, it is followed by several administrations of antigen mixed with an appropriately amount of Freund&#39;s incomplete adjuvant every 4 to 21 days. An appropriate carrier may also be used for immunization. After immunization as above, serum is examined for increase of the amount of desired antibodies by a standard method.  
           [0101]    Polyclonal antibodies against the proteins of the present invention may be prepared by collecting blood from the immunized mammal examined for the increase of desired antibodies in the serum, and by separating serum from the blood by any conventional method. Serum containing the polyclonal antibodies, or if necessary, a fraction containing the polyclonal antibodies may be isolated from the serum to be used as the polyclonal antibodies of the present invention. For example, immunoglobulin G or M can be prepared by using an affinity column coupled with the protein of the invention to obtain the fraction exclusively recognizing the protein of the invention, and then, purifying the fraction by using protein A or protein G column.  
           [0102]    To prepare monoclonal antibodies, immune cells are collected from the mammal immunized with the antigen and checked for the increased level of desired antibodies in the serum as described above, and are subjected to cell fusion. The immune cells used for cell fusion are preferably obtained from spleen. The other parent cell which is fused with the above immune cell is preferably a mammalian myeloma cell, and more preferably a myeloma cell that has acquired a special feature that can be used for selection of fusion cells by drugs.  
           [0103]    Cell fusion of the above immune cell and myeloma cell may be performed by any standard method, such as those described in the literature (Galfre et al., Methods Enzymol. 73:3-46, 1981).  
           [0104]    Hybridomas obtained by the cell fusion may be selected by cultivating them in a standard selection medium, such as HAT medium (hypoxanthine, aminopterin, and thymidine containing medium). The cell culture is typically continued in the HAT medium for several days to several weeks, the time being sufficient to allow all the other cells, except desired hybridoma (non-fused cells), to die. Then, the standard limiting dilution is performed to screen and clone a hybridoma cell producing the desired antibody.  
           [0105]    Besides the above method, in which a nonhuman animal is immunized with an antigen for preparing hybridoma, human lymphocytes such as that infected by EB virus may be immunized with a protein, protein expressing cells, or their lysates in vitro. Then, the immunized lymphocytes are fused with human-derived myeloma cells that is capable of indefinitely dividing, such as U266, to yield a hybridoma producing a desired human antibody, able to bind to the protein can be obtained (Unexamined Published Japanese Patent Application (JP-A) No. Sho 63-17688).  
           [0106]    Subsequently, the hybridomas thus obtained are transplanted into the abdominal cavity of a mouse from which the ascites is collected. The monoclonal antibodies thus obtained can be purified by, for example, ammonium sulfate precipitation or by column chromatography using a protein A or protein G column, a DEAE ion exchange column, an affinity column to which the protein of the invention is coupled, and such. The antibody of the invention can be used not only for purifying and detecting the protein of the invention, but also as a candidate for an agonist or antagonist to the protein of the present invention. It is also expected to use the antibody for antibody therapy of diseases associated with the protein of this invention. When the antibody obtained is administered to the human body (antibody therapy), human antibodies or humanized antibodies are preferred to reduce immunogenicity.  
           [0107]    For example, transgenic animals having a repertory of human antibody genes may be immunized with a protein, protein expressing cells, or their lysates as an antigen. Antibody producing cells are collected from the animals, and fused with myeloma cells to obtain hybridoma, from which human antibodies against the protein can be prepared (see WO92-03918, WO93-2227, WO94-02602, WO94-25585, WO96-33735, and WO96-34096).  
           [0108]    Alternatively, an immune cell, such as an immunized lymphocyte, producing antibodies may be immortalized by an oncogene and used for preparing monoclonal antibodies.  
           [0109]    Monoclonal antibodies thus obtained can also be recombinantly prepared using genetic engineering techniques (see, for example, Borrebaeck C. A. K. and Larrick J. W. Therapeutic Monoclonal Antibodies, published in the United Kingdom by MacMillan Publishers LTD (1990)). A DNA encoding an antibody may be cloned from an immune cell, such as hybridomas or immunized lymphocytes producing the antibody; inserted into an appropriate vector; and introduced into host cells to prepare a recombinant antibody. The present invention also includes recombinant antibodies prepared as described above.  
           [0110]    The antibody of the present invention may be a fragment of an antibody or modified antibody, so long as it binds to the protein of the invention. For instance, the antibody fragment may be Fab, F(ab′) 2 , Fv, or single chain Fv (scFv), in which Fv fragments from H and L chains are ligated by an appropriate linker (Huston J. S. et al. Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). More specifically, an antibody fragment may be generated by treating an antibody with an enzyme such as papain or pepsin. Alternatively, a gene encoding the antibody fragment may be constructed; inserted into an expression vector; and expressed in an appropriate host cell (see, for example, Co et al., J. Immunol. 152:2968-2976, 1994; Better et al., Methods Enzymol. 178:476-496, 1989; Pluckthun et al., Methods Enzymol. 178:497-515, 1989; Lamoyi, Methods Enzymol. 121:652-663, 1986; Rousseaux et al. Methods Enzymol. 121:663-669, 1986; Bird et al., Trends Biotechnol. 9:132-137, 1991).  
           [0111]    An antibody may be modified by conjugation with a variety of molecules, such as polyethylene glycol (PEG). The antibody of the present invention includes such modified antibodies. A modified antibody can be obtained by chemically modifying an antibody. These modification methods have been already established in the field.  
           [0112]    Alternatively, the antibody of the present invention may be obtained as a chimeric antibody, between a variable region derived from nonhuman antibody and the constant region derived from human antibody, or as a humanized antibody, comprising the complementarity determining region (CDR) derived from nonhuman antibody, the frame work region (FR) derived from human antibody, and the constant region. Such antibodies can be prepared by using known technology.  
           [0113]    Obtained antibodies may be purified to homogeneity. The antibodies can be separated and purified by using standard methods for protein separation and purification. For instance, column chromatography such as affinity chromatography, filter, ultrafiltration, salt precipitation, dialysis, SDS-polyacrylamide gel electrophoresis, isoelectric point electrophoresis, and so on may be appropriately selected and combined to isolate and purify the antibody (Antibodies: A Laboratory Manual. Ed Harlow and David Lane, Cold Spring Harbor Laboratory, 1988), but methods are not limited to them. The concentration of the antibody obtained as described above can be determined by the measurement of absorbance, enzyme-linked immunosorbent assay (ELISA), or others.  
           [0114]    Columns for affinity chromatography include protein A column and protein G column.  
           [0115]    For example, protein A column includes Hyper D, POROS, Sepharose F. F. (Pharmacia) and the like.  
           [0116]    In addition to affinity chromatography, chromatographic methods include, for example, ion exchange chromatography, hydrophobic chromatography, gel filtration, reverse-phase chromatography, adsorption chromatography and others (“Strategies for Protein Purification and Characterization: A Laboratory Course Manual” Ed Daniel R. Marshak et al., Cold Spring Harbor Laboratory Press, 1996). These chromatographic methods can be conducted by using liquid chromatography such as HPLC and FPLC.  
           [0117]    For example, absorbance measurement, enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), radioimmunoassay (RIA), or immunofluorescence may be used to measure the antigen binding activity of the antibody of the invention. In ELISA, the antibody of the present invention is immobilized on a plate; the protein of the invention is applied to the plate; and then a sample containing a desired antibody, such as culture supernatant of antibody producing cells or purified antibodies, is applied. Then, a secondary antibody that recognizes the primary antibody and which is labeled with an enzyme such as alkaline phosphatase is applied, and the plate is incubated. After washing, an enzyme substrate, such as p-nitrophenyl phosphate, is added to the plate, and the absorbance is measured to evaluate the antigen binding activity of the sample. A fragment of the protein, such as a C-terminal fragment, may be used as a protein. BIAcore (Pharmacia) may be used to evaluate the activity of the antibody according to the present invention.  
           [0118]    The above methods allow for the detection or measurement of the protein of the invention, by exposing the antibody of the invention to a sample assumed to contain the protein of the invention, and detecting or measuring the immune complex formed by the antibody and the protein. Because the method of detection or measurement of the protein according to the invention can specifically detect or measure a protein, the method may be useful in a variety of experiments in which the protein is used.  
           [0119]    The present invention also provides a polynucleotide containing at least 15 nucleotides complementary to the DNA (SEQ ID NO: 1 or 3) encoding the human KP protein or the complementary strand thereof.  
           [0120]    Herein, the term “complementary strand” is defined as one strand of a double strand DNA composed of A:T and G:C base pair to the other strand. Also, “complementary” is defined as not only those completely matching within a continuous region of at least 15 nucleotides, but also having a homology of at least 70%, favorably 80% or higher, more favorably 90% or higher, and most favorably 95% or higher within that region. The homology may be determined using the algorithm described herein.  
           [0121]    Such a nucleic acid includes probes and primers used for the detection and amplification of DNA encoding the inventive protein; probes and primers used for the detection of expression of the DNA; and nucleotide and nucleotide derivatives (e.g., antisense oligonucleotide and ribozyme, or DNAs encoding them, etc.) used for the regulation of expression of the inventive protein. In addition, such a nucleic acid can also be used for the preparation of DNA chip.  
           [0122]    When used as primers, such nucleic acids are complementary at the 3′ end, and restriction enzyme recognition sequences or tags can be added to the 5′ end.  
           [0123]    The antisense oligonucleotides include, for example, antisense oligonucleotides hybridizing to any region of the nucleotide sequence of SEQ ID NO: 1 or 3. The antisense oligonucleotide is preferably an antisense of a continuous sequence of a length of 15 nucleotides or longer within the nucleotide sequence of SEQ ID NO:1 or 3. More preferably, the above continuous sequence of a length of 15 nucleotides or longer contains the translation initiation codon.  
           [0124]    A derivative or modified form of antisense oligonucleotide may also be used. The modified antisense oligonucleotides may be those modified with lower alkylphosphonate such as methylphosphonate and ethylphosphonate; phosphorothioate; phosphoroamidate; and so on.  
           [0125]    Herein, an antisense oligonucleotide is not restricted to those in which all nucleotides are complementary to the corresponding nucleotides within a given region of a DNA or mRNA; so long as it can specifically hybridize with the nucleotide sequences of SEQ ID NO: 1 or 3, it may have one or more nucleotide mismatches.  
           [0126]    A derivative of the antisense oligonucleotide of the present invention may act on cells producing the protein of the invention and may bind to a DNA or mRNA encoding the protein, whereby inhibiting the expression of the protein of the invention by inhibiting its transcription or translation, or by promoting the degradation of mRNA, and thereby inhibiting the function of the protein of the invention.  
           [0127]    A derivative of the antisense oligonucleotide of the present invention may be mixed with appropriate carriers which are inactive against the derivative, and may be used as a medicine for externally application such as salve or poultice.  
           [0128]    If necessary, it may be mixed with an excipient, isotonizing agent, solubilizing agent, stabilizer, preservative, pain-killer, or the like, and prepared as a tablet, powder, granule, capsule, liposome capsule, injectable solution, liquid formulation, nose drops, freeze-dried agent, etc. The above may be achieved according to standard methods.  
           [0129]    For treating patients, a derivative of an antisense oligonucleotide of the present invention may be, for example, directly applied to the affected area of a patient, or administered into blood vessels so as to finally reach the affected area. Moreover, the derivative may be encapsulated in antisense-encapsulating materials such as liposome, poly-L-lysine, lipid, cholesterol, lipofectin, or their derivative in order to increase durability and/or membrane permeability.  
           [0130]    Dose of the derivative of the antisense oligonucleotide of the present invention may be appropriately adjusted depending on the patient&#39;s conditions, and a favorable amount such as 0.1 to 100 mg/kg, or more preferably 0.1 to 50 mg/kg may be administered.  
           [0131]    As the antisense oligonucleotides of the present invention inhibit expression of the protein of the invention, they find utility as inhibitors of the biological activity of the protein of the invention. An inhibitor of expression comprising the antisense oligonucleotide of the present invention is useful because it can inhibit the biological activity of the protein of the invention.  
           [0132]    The protein of the invention may be used to screen for compounds that bind to the protein of the present invention. Specifically, the protein may be used in methods of screening for compounds, which method comprises the steps of exposing the protein of the present invention to a test sample in which a compound binding to the protein is expected to be contained; and selecting the compound having the activity of binding to the protein.  
           [0133]    The proteins of the invention used for screening may be recombinant or natural proteins, or partial peptides. Alternatively, they may be expressed on the surface of cells or in the form of a membrane fraction. There is no particular restriction on the test sample as it includes, for example, cell extract, cell culture supernatant, product of fermentation microorganism, extract from marine organism, extract from plant, purified or crude protein, peptide, non-peptide compound, synthetic low-molecular-weight compound, natural compound, etc. The inventive protein to be contacted with a test sample can be contacted with the test sample, for example, as a purified protein, as a soluble protein, in a form of protein immobilized on carriers, as a fusion protein with other proteins, in a form of protein presented on cell membrane, as a membrane fraction.  
           [0134]    Many methods known to those skilled in the art can be used to screen proteins capable of binding to the inventive protein. Such screening can be carried out, for example, by the immunoprecipitation method. Specifically, the method can be carried out as follows. The gene encoding a protein of this invention is expressed by inserting the gene into a vector for foreign gene expression in pSV2neo, pcDNA I, pCD8, and such, and expressing the gene in animal cells, etc. Any generally used promoters may be employed for the expression, including the SV40 early promoter (Rigby In Williamson (ed.), Genetic Engineering, Vol. 3. Academic Press, London, p.83-141 (1982)), EF-1 α promoter (Kim, et al. Gene 91:217-223, 1990), CAG promoter (Niwa et al., Gene 108:193-200, 1991), RSV LTR promoter (Cullen, Methods Enzymology 152:684-704, 1987), SR a promoter (Takebe et al., Mol. Cell. Biol. 8:466, 1988), CMV immediate early promoter (Seed et al., Proc. Natl. Acad. Sci. USA 84:3365-3369, 1987), SV40 late promoter (Gheysen et al., J. Mol. Appl. Genet. 1:385-394, 1982), Adenovirus late promoter (Kaufman et al., Mol. Cell. Biol. 9:946, 1989), HSV TK promoter, etc.  
           [0135]    Transfer of a foreign gene into animal cells for its expression can be performed by any of the following methods, including the electroporation method (Chu et al., Nucl. Acid Res. 15:1311-1326, 1987), the calcium phosphate method (Chen et al., Mol. Cell. Biol. 7:2745-2752, 1987), the DEAE dextran method (Lopata et al., Nucl. Acids Res. 12:5707-5717, 1984; Sussman et al., Mol. Cell. Biol. 4:1642-1643, 1985), the lipofectin method (Derijard, Cell. 7:1025-1037, 1994; Lamb et al., Nature Genetics 5:22-30, 1993; Rabindran et al., Science 259:230-234, 1993), etc.  
           [0136]    The protein of this invention can be expressed as a fusion protein having a recognition site for a monoclonal antibody by introducing the recognition site (epitope) for the monoclonal antibody, the specificity of which has been established, into the N- or C-terminus of the protein of this invention. For this purpose, commercial epitope-antibody systems can be utilized (Igaku, Experimental Medicine 13:85-90, 1995). Vectors which can express fusion proteins with the β-galactosidase, maltose-binding protein, glutathione S-transferase, green fluorescence protein (GFP), and such, via the multi-cloning site are commercially available.  
           [0137]    There is also a report that a fusion protein may be prepared by introducing only small epitope portions consisting of several to a dozen amino acid residues so as not to change the property of the protein of the present invention by the fusion. For example, epitopes such as polyhistidine (His-tag), influenza hemagglutinin (HA), human c-myc, FLAG, Vesicular stomatitis virus glycoprotein (VSV-GP), T7 gene 10 protein (T7-tag), human herpes simplex virus glycoprotein (HSV-tag), E-tag (epitope on the monoclonal phage), and such, and monoclonal antibodies to recognize them can be utilized as the epitope-antibody system for screening proteins binding to the protein of this invention (Igaku, Experimental Medicine 13:85-90, 1995).  
           [0138]    In immunoprecipitation, immune complexes are formed by adding these antibodies to the cell lysate prepared using suitable surfactants. The immune complex comprises a protein of this invention, a protein comprising the binding ability with the protein, and an antibody. Immunoprecipitation can be also performed by using antibodies against a protein of this invention, besides using antibodies against the above-described epitopes. An antibody to a protein of this invention can be prepared, for example, by inserting a gene encoding the protein of the invention into an appropriate expression vector of  E. coli  to express it in the bacterium, purifying the expressed protein, and immunizing rabbits, mice, rats, goats, chicken, and such against the purified protein. The antibody can be also prepared by immunizing the above-described animals against synthetic partial peptides of the protein of the present invention.  
           [0139]    Immune complexes can be precipitated using, for example, Protein A Sepharose and Protein G Sepharose when the antibody is a murine IgG antibody. In addition, if a protein of this invention is prepared as a fusion protein with the epitope, such as GST, an immune complex can be formed by using a substance specifically binding to these epitopes, such as glutathione-Sepharose 4B, in the same manner as in the use of the antibody against the protein of the present invention.  
           [0140]    Immune precipitation, in general, may be carried out according to, or following the method described in the literature (Harlow, E. and Lane, D.: Antibodies, pp.511-552, Cold Spring Harbor Laboratory publications, New York, 1988).  
           [0141]    SDS-PAGE is generally used for the analysis of immunoprecipitated proteins. Bound proteins can be analyzed based on the molecular weights of proteins using a gel of an appropriate concentration. In this case, although proteins bound to a protein of this invention, in general, are hardly detectable by the usual protein staining method, such as Coomassie staining and silver staining, the detection sensitivity can be improved by culturing cells in a medium containing radioisotopes, such as  35 S-methionine and  35 S-cysteine, to label proteins inside the cells, and detecting the labeled proteins. Once the molecular weight of the protein is determined, the desired protein can be purified directly from the SDS-polyacrylamide gel and can be sequenced.  
           [0142]    In addition, proteins binding to a protein of this invention can be isolated using the West-western blotting method (Skolnik et al., Cell 65:83-90, 1991) with the protein of this invention. Namely, cDNA is isolated from cells, tissues, and organs, in which the protein binding to a protein of this invention is expected to be expressed (e.g., liver and kidney), and transferred into a phage vector (for example, λgt11, ZAP, and such) to prepare a cDNA library, which is then expressed on LB-agarose plates. The protein thus expressed is fixed on a filter; reacted with the labeled, purified protein of this invention; and plaques expressing a protein bound to a protein of this invention can be detected by the label. Methods for labeling the proteins of this invention include methods using the binding activity of biotin and avidin; methods using antibodies specifically binding to the proteins of this invention, or peptides or polypeptides fused with the protein of this invention (e.g., GST); methods using the radioisotopes; methods using fluorescence; etc.  
           [0143]    Alternatively, in another embodiment of the method for screening of the present invention, the two-hybrid system utilizing cells may be used (Fields et al., Trends Genet. 10:286-292, 1994; Dalton et al., Cell 68:597-612, 1992; “MATCHMAKER Two-Hybrid System”, “Mammalian MATCHMAKER Two-Hybrid Assay Kit”, “MATCHMAKER One-Hybrid System (all from Clontech), “HybriZAP Two-Hybrid Vector System” (Stratagene)). In the two-hybrid system, an inventive protein or a partial peptide thereof is fused with the SRF DNA-binding region or GAL4 DNA-binding region, and then is expressed in yeast cells; a cDNA library, which express proteins in the form of fusion protein with the VP 16 or GAL4 transcription activation region, is prepared from cells that are predicted to express a protein binding to an inventive protein; the resulting cDNA library is introduced into the above-mentioned yeast cells; and then a cDNA derived from the library is isolated from a detected positive clone (when a protein binding to the inventive protein is expressed in yeast cells, the reporter gene is activated by the binding of the two proteins, and thus positive clones are detectable). A protein encoded by the cDNA can be prepared after the isolated cDNA is introduced and expressed in  E. coli . Thus it is possible to prepare a protein binding to an inventive protein or the encoding gene. Reporter genes to be used in the two-hybrid system include, but are not limited to, for example, Ade2 gene, LacZ gene, CAT gene, luciferase gene, PAI-1 (Plasminogen activator inhibitor type1) gene in addition to HIS3 gene. The screening by the two-hybrid method can be conduced by using mammalian cells or others in addition to yeast.  
           [0144]    Compounds binding to a protein of the present invention can be screened by affinity chromatography. For example, a protein of the invention is immobilized on a carrier of an affinity column, and a test sample, in which a protein binding to the protein of the invention is supposed to be expressed, is applied to the column. A test sample herein may be, for example, cell extracts, cell lysates, etc. After loading the test sample, the column is washed, and proteins bound to a protein of the invention can be prepared.  
           [0145]    The amino acid sequence of the resulting protein is then analyzed. Based on the result, an oligo-DNA is synthesized and used as the probe to screen a cDNA library. This can provide a DNA encoding the protein.  
           [0146]    In the present invention, a biosensor on the basis of surface plasmon resonance phenomenon can be used as a means to detect or assay the bound compounds. By utilizing the biosensor on the basis of surface plasmon resonance phenomenon, the interaction between the inventive protein and a test compound can be observed as a surface plasmon resonance signal in real time using a small amount of protein without labeling (e.g., BIAcore, Pharmacia). Thus the binding between the inventive protein and the test compound can be assessed by using biosensor of BIAcore, or the like.  
           [0147]    In addition, methods are known in the art for isolating compounds binding to a protein of the invention, which are not limited only to proteins (including agonists and antagonists). Such methods include, for example, the method of screening for a molecule binding to a protein of the invention by contacting a synthetic compound or natural substance bank, or a random phage peptide display library with an immobilized protein of the invention, and the high-throughput screening method using a combinatorial chemistry technique (Wrighton et al., Science 273:458-64, 1996; Verdine G. L., Nature 384:11-13, 1996; Hogan J. C. Jr., Nature 384:17-9, 1996).  
           [0148]    Compounds isolated by the screening of this invention are candidates for agents to regulate the activity of a protein of this invention, and thought to be applied to treatments for disorders caused by expressional and functional abnormalities, and such of the protein, and diseases which can be treated by controlling the activity of the protein. Compounds which can be obtained by the screening method of this invention, the partial structure of which is modified by addition, deletion and/or substitution, are also included in the compounds binding to the protein of this invention.  
           [0149]    When a protein of this invention or compounds isolated by the screening of this invention are used as drugs for humans and other animals, for example, mice, rats, guinea pigs, rabbits, chickens, cats, dogs, sheep, pigs, cattle, monkeys, baboons, and chimpanzees, they can be administered by directly administering the protein or isolated compound itself to a patient or by administering it after formulated according to known pharmaceutical methods. They can be administered, as the occasion demands, for example, orally, as sugar-coated tablets, capsules, elixirs and microcapsules, or parenterally, in the form of sterile solutions in water or other pharmaceutically acceptable liquids, or suspensions for injections. For example, they may be formulated by appropriately mixing with pharmaceutically acceptable carriers or media, specifically sterile water, physiological saline, plant oil, emulsifying agents, suspending agents, surfactants, stabilizers, seasonings, excipients, vehicles, anticeptics, binders, and such, in the unit dosage form required in a generally accepted pharmaceutical procedure. Amounts of effective ingredients in these pharmaceutical preparations are adjusted so as to obtain the appropriate dose in the specified range.  
           [0150]    Additives which can be mixed in tablets and capsules include, for example, binders such as gelatin, corn starch, tragacanth gum and arabic gum; excipients such as crystalline cellulose; bulking agents such as corn starch, gelatin and alginic acid; lubricants such as magnesium stearate; sweetening agents such as sucrose, lactose or saccharine; and flavors such as peppermint,  Gaultheria adenothrix  oil or cherry. When the dispensing unit form is a capsule, liquid carriers, such as oil, can be further added to the above-described materials. Sterile compositions for injection can be prescribed using vehicles such as distilled water for injection according to standard pharmaceutical procedure.  
           [0151]    Aqueous solutions for injections include, for example, physiological saline, and isotonic solutions containing: glucose and other supplements such as D-sorbitol, D-mannose, D-mannitol, sodium chloride, and such; and suitable solubilizers, for example, alcohols, more specifically, ethanol, polyalcohols such as propylene glycol, polyethylene glycol, non-ionic surfactants such as polysorbate 80 (TM) and HCO-50 may be used together.  
           [0152]    Oily solutions, including sesame oil and soybean oil, and benzyl benzoate and benzyl alcohol may be used together as the solubilizer. Injections may be combined with buffers such as phosphate buffer and sodium acetate buffer; soothing agents such as procaine hydrochloride; stabilizers such as benzyl alcohol, phenols and antioxidants. Injections thus prepared are typically filled in suitable ampules.  
           [0153]    The administration to patients is done by methods commonly known to those skilled in the art, such as intraarterial, intravenous, or subcutaneous injections, as well as intranasal, bronchial, intramuscular, percutaneous, or oral administrations. One skilled in the art can suitably select the dosage according to the body-weight or age of a patient, or the method of administration. If the compound can be encoded by DNA, the DNA may be used for gene therapy by incorporating the DNA into a vector for gene therapy. Dosages and administration methods vary depending on the body-weight, age, symptoms, and such of patients, but those skilled in the art can appropriately select them.  
           [0154]    Although the specific dosage of the protein of the invention changes according to the subject to be treated, the target organs, symptoms, and administration methods, it is generally considered to be, for example, about 100 μg to 20 mg one day for an adult (as body-weight 60 kg) in the form of injections.  
           [0155]    Though they vary depending on the symptoms, doses of compounds binding to a protein of this invention or compounds regulating the activity of such a protein may be generally in the range of about 0.1 to 100 mg, preferably about 1.0 to 50 mg, and more preferably about 1.0 to 20 mg per day for adults (based on the body weight 60 kg) in the case of oral administration.  
           [0156]    Though it varies depending on the subject to be administered, target organ, symptom and method of administration, a single dose of the compounds for the parenteral administration is thought to be preferably administered, for example, when it is in the form of injection, intravenously to normal adults (based on the body weight 60 kg) in the range of about 0.01 to 30 mg, preferably about 0.1 to 20 mg, and more preferably about 0.1 to 10 mg or thereabout per day. Doses converted on the 60 kg body weight basis or the body surface area can be similarly administered to other animals.  
           [0157]    All publications and patents cited herein are incorporated by reference in their entirety  
         DETAILED DESCRIPTION  
         [0158]    The invention is illustrated more specifically with reference to the following examples, but is not to be construed as being limited thereto. 
       
    
    
     EXAMPLE 1  
     Construction of a cDNA Library by the Oligo-Capping Method  
       [0159]    The NT-2 neuron progenitor cells (Stratagene), teratocarcinoma cells from human fetal testis, which can be differentiated into neurons by the treatment with retinoic acid were cultured for two weeks after induction treatment by the addition of retinoic acid according to the manufacturer&#39;s instructions.  
         [0160]    After the culture, the respective cells were collected, and mRNA was extracted according to the method described in the literature (Sambrook et al., Molecular Cloning 2nd edition, Cold Spring harbor Laboratory Press, 1989). Then, poly(A) +  RNA was purified by using oligo dT cellulose.  
         [0161]    Similarly, human ovary cancer tissue (OVARC1) was used to extract mRNA by the method described in the literature (Sambrook et al., Molecular Cloning 2nd edition, Cold Spring Harbor Laboratory Press, 1989). Furthermore, poly(A) +  RNA was purified from the mRNA using oligo-dT cellulose.  
         [0162]    This poly(A) +  RNA was used to construct a cDNA library by the oligo-capping method (Maruyama et al., Gene 138:171-174, 1994). Using the Oligo-cap linker (agcaucgagu cggccuuguu ggccuacugg/SEQ ID NO:5) and the Oligo-dT primer (gcggctgaag acggcctatg tggccttttt tttttttt tt/SEQ ID NO:6), bacterial alkaline phosphatase (BAP) treatment, tobacco acid phosphatase (TAP) treatment, RNA ligation, the first strand cDNA synthesis, and removal of RNA were performed according to the references (Suzuki et al., Protein, Nucleic acid and Enzyme, 41:197-201, 1996; Suzuki et al., Gene 200:149-156, 1997). Then, 5′- and 3′-PCR primers (agcatcgagt cggccttgtt g/SEQ ID NO:7, and gcggctgaag acggcctatg t/SEQ ID NO:8, respectively) were used for performing PCR to convert the cDNA into double stranded cDNA, which was then digested with SfiI. Then, the DraIII-cleaved vector pUC19FL3 or pME18SFL3 (GenBank AB009864, expression vector) (NT2RP3, OVARC1) was used for cloning the cDNA in a unidirectional manner, and cDNA libraries were obtained. The nucleotide sequence of the 5′- and 3′-ends of the cDNA clones was analyzed with a DNA sequencer (ABI PRISM 377, PE Biosystems) after sequencing reactions performed with the DNA sequencing reagents (Dye Terminator Cycle Sequencing FS Ready Reaction Kit, dRhodamine Terminator Cycle Sequencing FS Ready Reaction Kit, or BigDye Terminator Cycle Sequencing FS Ready Reaction Kit, PE Biosystems), according to the instructions. The obtained data were used for a database.  
         [0163]    Oligo-cap high full-length ratio cDNA library of NT2RP3 was prepared by using an expression vector, pME18SFL3, which can be expressed in eukaryotic cells. pME18SFL3 vector contains the SRα promoter and SV40 small t intron in the upstream, as well as the SV40 polyA addition signal sequence downstream of the cloning site, respectively. As the cloning site of pME18SFL3 has asymmetrical DraIII sites, and the ends of cDNA fragments contain SfiI sites complementary to the DraIII sites, the cloned cDNA fragments can be unidirectionally inserted downstream of the SRα promoter. Therefore, clones containing full-length cDNA can be expressed transiently by introducing the obtained plasmid directly into COS cells. Thus, the clones can be analyzed very easily in terms of the proteins that are the gene products of the clones, or in terms of the biological activities of the proteins.  
       EXAMPLE 2  
     Estimation of the Completeness at the 5′-ends of the Clones Contained in the cDNA Libraries Constructed by the Oligo-Capping Method  
       [0164]    The full-length ratio at the 5′-end sequence of respective clones in the human cDNA libraries constructed by the oligo-capping method was determined as follows. The clones whose 5′-end sequences were consistent with those of known human mRNA in the public database were judged to be “full-length” if they had a longer 5′-end sequence than that of the known human mRNA; or even though the 5′-end sequence was shorter, if it contained the translation initiation codon it was judged to have the “full-length” sequence. Clones which did not contain the translation initiation codon were judged to be “not-full-length”. The full-length ratio ((the number of full-length clones)/(the number of full-length and not-full-length clones)) at the 5′-end of the cDNA clones from each library was determined by comparing with known human mRNA. As a result, the full-length ratio of the 5′-ends was 63.5%. The result indicates that the full-length ratio at the 5′-end sequence was extremely high in the human cDNA clones obtained by the oligo-capping method.  
       EXAMPLE 3  
     Assessment of the Full-Length Ratio of the 5′-End of the cDNA by the ATGpr and the ESTiMateFL  
       [0165]    The ATGpr, developed by Salamov A. A., Nishikawa T., and Swindells M. B. in the Helix Research Institute, is a program for prediction of the translation initiation codon based on the characteristics of the sequences in the vicinity of the ATG codon (Salamov et al., Bioinformatics 14:384-390, 1998; http://www.hri.cojp/atgpr/). The results are shown with expectations (also mentioned as ATGpr1 below) whether the ATG is a true initiation codon (0.05-0.94). When it was not considered that the sequence was the 5′-end of the cDNA or not, both of the sensitivity and specificity of analytical results by this program were estimated as 66%. When the program was applied to the 5′-end sequences of the clones from the cDNA library that was obtained by the oligo-capping method having 65% full-length ratio, the sensitivity and specificity of the estimation of the full-length clone (clone containing the N-terminus of the ORF) were improved to 82 to 83% by selecting only clones having an ATGpr1 score 0.6 or higher. The maximum ATGpr1 scores for 5′-end sequences of NT2RP3001938 and OVARC1000945 were 0.32 and 0.74, respectively.  
         [0166]    Next, the ESTiMateFL was used for the assessment of the clones. The ESTiMateFL, developed by Nishikawa and Ota in the Helix Research Institute, is a method for selecting clones expected to have a full-length cDNA by comparing with the 5′-end or 3′-end sequences of ESTs in the public database.  
         [0167]    By this method, a cDNA clone is judged to be most likely not to be full-length if there exist any ESTs which have longer 5′-end or 3′-end sequences than the clone. The method is systematized for high throughput analysis. A clone is judged to be full-length if the clone has a longer 5′-end sequence than the ESTs in the public database corresponding thereto. Even if a clone has a shorter 5′-end, the clone is judged to be full-length if the difference in length is within 50 bases, and otherwise judged not to be full-length, for convenience. Those clones whose 5′-end sequence is matching with the known mRNA, about 80% of the clones judged to be full-length by the comparison with ESTs were also judged to be full-length by the assessment of the 5′-end sequence by comparing with known mRNA. Also, about 80% of the clones judged to be not full-length in the 5′-end sequence by comparing with ESTs were also judged to be not full-length in the 5′-end sequence by comparison with known mRNA. The precision of the estimation by comparing with ESTs is improved with increasing numbers of ESTs to be compared. However, in case with limited numbers of ESTs, the reliability becomes low. Thus, the method is effective in excluding clones with high probability of being not-full-length from the cDNA clones that is synthesized by the oligo-capping method having a 5′-end sequence full-length ratio of about 60%. In particular, the ESTiMateFL is efficiently used in estimating the full-length ratio at the 3′-end sequence of cDNA of a human unknown mRNA, a significant number of which are deposited in the public database as EST deposits.  
         [0168]    Results of the above assessment for the full-length ratio showed that the clone “C-OVARC1000945” was a novel clone with a high probability of being full-length and also which shares no sequence identity with any of human EST sequences at least either at the 5′-end sequence or 3′-end sequence, or both ends.  
         [0169]    Furthermore, “C-NT2RP3001938” is also a full-length clone; the number of human EST sequences that shared a common sequence to each of these clones at the 5′-end was 20 or less (clones which do not share sequences with certain human EST sequences at least either at the 5′-end or at 3′-end, or at both ends of the clone; excluding clones in which the number of human EST sequences that shared a common sequence to each of the clones at both of the 5′- and 3-end was 1 or more and 5 or less). Accordingly, they were concluded to be novel clones.  
       EXAMPLE 4  
     Selection of Clones having a Kinase/Phosphatase-Like Sequence  
       [0170]    Clones having a kinase/phosphatase-like sequence were selected from the helix clones. All the helix clones were searched for homology by NCBI TBLASTN2.0 by using the following 31 amino acid sequences of known kinases and phosphatases (also including phospholipid kinases) as queries. Clones with a expectation value (Expect) 1.0e-05 or lower were selected.  
         [0171]    The query sequences used in the homology search as well as their SEQ ID NOs and GenBank accession numbers are as follows.  
                                                     Query sequence No.   SEQ ID NO:   GenBank accession No.                                hLKB1   9   gi|3024670       hVRK1   10   gi|4507903       hCDC2   11   gi|4502709       hAuroraK1   12   gb|AAC12708.1       hAuroraK2   13   gi|4759178       hIKKA   14   gb|AAC51662.1       hMKK3   15   gb|AAB40653.1       hERK1   16   pir|A48082       hRAF1   17   gi|4506401       hAKT   18   gi|4885061       hPIKP85   19   sp|P27986       hATM   20   gi|4502267       hc-src   21   gi|4758078       hJAK1   22   ref|NP_002218.1       hFLT1   23   gb|AAC16449.1       hPP2A   24   gi|4506017       hMKP2   25   gb|AAC50452.1       hVHR   26   gi|4758208       hPTP-SL   27   gi|4506325       hSTEP   28   sp|P54829       hPTEN   29   gi|4506249       Cdc14B1   30   gb|AAD15415.1       DUSP12   31   gi|6005956       AK000449   32   gi|8923413       DUS7   33   sp|Q16829       calcineurin A alpha   34   gi|6715568       PNP1   35   emb|CAA56124.1       TPTE   36   gi|7019559       PPP1CC   37   gi|4506007       PP-1 gamma   38   gb|AAA19823.1       PP2A   39   gi|4506017                  
 
         [0172]    The results of homology search were shown in Table 1.  
                           TABLE 1                               Search score   Expectation       Query   Helix clone   (score)   value (expect)                   hAuroraK1   C-NT2RP3001938   55   4e-08       hAuroraK2   C-NT2RP3001938   51   5e-07       hMKK3   C-NT2RP3001938   80   7e-16       hRAF1   C-NT2RP3001938   62   4e-10       PNP1   C-OVARC1000945   93   5e-19                  
 
         [0173]    Based on the result, non-overlapping 2 clones, C-NT2RP3001938 and C-OVARC 1000945, were selected as clones having kinase/phosphatase-like structure (KP clones). The clones encode novel human proteins, and each of the proteins was deduced to function as a protein kinase and/or a protein phosphatase.  
       EXAMPLE 5  
     Gene Expression Analysis by Hybridization using High Density DNA Filter  
       [0174]    DNA for spotting onto the nylon membranes was prepared according to the following procedure.  E. coli  was cultured in each well of a 96-well plate (in a LB medium at 37° C. for 16 hours). A part of each culture was suspended in 10 μl of sterile water in the well of a 96-well plate. The plate was heated at 100° C. for 10 minutes. Then the samples were analyzed by PCR. PCR was performed in a 20 μl solution per one reaction by using TaKaRa PCR Amplification Kit (Takara) according to the supplier&#39;s protocol. A pair of sequencing primers, ME761FW (5′ tacggaagtgttacttctgc 3′/SEQ ID NO:40) and ME1250RV (5′ tgtgggaggffttttctcta 3′/SEQ ID NO:41), or a pair of primers, M13M4 (5′ gttttcccagtcacgac 3′/SEQ ID NO:42) and M13RV (5′ caggaaacagctatgac 3′/SEQ ID NO:43) were used for the amplification of the insert cDNA in the plasmid. PCR was performed in a thermal cycler, GeneAmp System 9600 (PE Biosystems). The cycling profile consisted of pre-heating at 95° C. for 5 minutes; 10 cycles of denaturation at 95° C. for 10 seconds, and annealing/extension at 68° C. for 1 minute; 20 cycles of denaturation at 98° C. for 20 seconds and annealing/extension at 60° C. for 3 minutes; and final extension at 72° C. for 10 minutes. After the PCR, 2 μl of the reaction solution was electrophoresed on a 1% agarose gel. DNA on the gel was stained with ethidium bromide to confirm the amplification of cDNA. When cDNAs were not amplified by PCR, plasmids containing the corresponding insert cDNAs were prepared by the alkali-extraction method (Sambrook et al., Molecular Cloning, A laboratory manual, 2nd edition, Cold Spring Harbor Laboratory Press, 1989).  
         [0175]    DNA array was prepared by the following procedure. An Aliquot of the DNA solution was added to each well of a 384-well plate. DNA was spotted onto a nylon membrane (Boehringer) by using a 384-pin tool of Biomek 2000 Laboratory Automation System (Beckman-Coulter). More specifically, the 384-well plate containing the DNA was placed under the 384-pin tool. The independent 384 needles of the pin tool were simultaneously dipped into the DNA solution to fix the DNA on the needles. The needles were gently pressed onto a nylon membrane, and the DNA fixed on the needles was spotted onto the membrane. Denaturation of the spotted DNA and immobilization of the DNA on the nylon membrane were carried out according to conventional methods (Sambrook et al., Molecular Cloning, A laboratory manual, 2nd edition, Cold Spring Harbor Laboratory Press, 1989).  
         [0176]    1 st strand cDNA labeled with radioisotope was used as the hybridization probe. The 1 st strand cDNA was synthesized by using Thermoscript ™  RT-PCR System (GIBCO). More specifically, the 1st strand cDNA was synthesized by using 1.5 μg mRNAs from various human tissues (Clontech), 1 μl 50 μM Oligo(dT)20, and 50 μCi [α 33 P]dATP according to the attached protocol. Purification of the probe was carried out by using ProbeQuant™ G-50 micro column (Amersham-Pharmacia Biotech) according to the attached protocol. In the next step, 2 units of  E. coli  RNaseH were added to the reaction mixture. The mixture was incubated at room temperature for 10 minutes, and then 100 μg of human COT-1 DNA (GIBCO) was added thereto. The mixture was incubated at 97° C. for 10 minutes, and then was allowed to stand on ice to give the hybridization probe.  
         [0177]    Hybridization of the radioisotope-labeled probe to the DNA array was performed in a usual manner (Sambrook et al., Molecular Cloning, A laboratory manual, 2nd edition, Cold Spring Harbor Laboratory Press, 1989). The membrane was washed as follows: the nylon membrane was washed three times by incubating in the Washing solution 1 (2× SSC, 1% SDS) at room temperature (about 26° C.) for 20 minutes; then the membrane was washed 3 times by incubating it in the Washing solution 2 (0.1× SSC, 1% SDS) at 65° C. for 20 minutes. Autoradiography was performed by using an image plate for BAS2000 (Fuji Photo Film Co., Ltd.). Specifically, the nylon membrane used for the hybridization was wrapped with a piece of Saran Wrap, and was contacted with the light-sensitive surface of the image plate. The membrane with the image plate was placed in an imaging cassette for radioisotope and was allowed to stand in dark for 4 hours. The radioactivity recorded on the image plate was analyzed by BAS2000 (Fuji Photo Film Co., Ltd.) and was recorded as an image file of the autoradiogram by electronic conversion. The signal intensity of each DNA spot was analyzed by using Visage High Density Grid Analysis Systems (Genomic Solutions Inc.). The signal intensity was converted into numerical data. The data were taken by duplicated measurements. The reproducibility was assessed by comparing the signal intensities of the corresponding spots on the duplicated DNA filters that were hybridized to a single DNA probe. The ratio between the corresponding spots falls within a range of 2-folds or less in 95% of entire spots, and the correlation coefficient was r=0.97. Thus, the reproducibility was assumed to be satisfactory.  
         [0178]    The detection sensitivity in gene expression analysis was estimated by examining increases in the signal intensity of the probe concentration-dependent spot of the hybridization using a probe complementary to the DNA spotted on the nylon membrane. PLACE1008092 (the same DNA as that deposited in GenBank Accession No. AF107253) was used as the DNA. The DNA array with the DNA of PLACE1008092 was prepared according to the above-mentioned method. The probe was prepared as follows: mRNA was synthesized in vitro from the clone, PLACE1008092; using this mRNA as the template, radioisotope-labeled 1st strand cDNA was synthesized in the same manner as the probe preparation method described above; and the cDNA was used as the probe. The cDNA PLACE1008092 was inserted into pBluescript SK(−), so that the 5′-end of the PLACE1008092 is ligated to the T7 promoter of the pBluescript SK(−) to give a recombinant plasmid for in vitro synthesis of the mRNA from PLACE1008092. Specifically, the PLACE1008092 inserted at the DraIII site of the pME18SFL3 was cut out by XhoI digestion. The resulting PLACE1008092 fragment was ligated to XhoI-predigested pBluescript SK(−) by using the DNA ligation kit ver.2 (Takara). The in-vitro mRNA synthesis from PLACE1008092 inserted in pBluescript SK(−) was carried out by using the Ampliscribe™ T7 high yield transcription kit (Epicentre technologies). The hybridization and analysis of signal intensity of each DNA spot were conducted using the same methods described above. When the probe concentration was 1×10 7  μg/ml or less, there was no increase of signal intensity proportional to the probe concentration. Therefore it was assumed to be difficult to compare the signals with one another in this concentration range. Thus, spots with a intensity of 40 or less were indiscriminately taken as low-level signals. Within a concentration of the probe ranging from 1×10 7  μg/ml to 0.1 μg/ml, signals were found to increase in a probe concentration-dependent manner. The detection sensitivity is 1:100,000 in a ratio of mRNA expression level in a sample.  
         [0179]    Table 2 shows the expression of each cDNA in human normal tissues (heart, lung, pituitary gland, thymus, brain, kidney, liver and spleen). The expression levels are indicated by numerical values of 0 to 10,000. Each of the “C-NT2RP3001938” and “C-OVARC1000945” was expressed in at least one tissue.  
                                                                                     TABLE 2                                   Pituitary                           Clone name   Heart   Lung   gland   Thymus   Brain   Kidney   Liver   Spleen                                GAPDH   38.210   32.670   23.820   13.580   11.230   21.120   24.910   22.440       β-actin   279.280   368.870   111.100   117.500   92.880   114.650   82.990   256.790       NT2RP3001938   40.274   25.723   28.062   7.496   13.890   31.768   21.367   10.885       OVARC1000945   72.670   66.756   35.734   31.061   28.439   44.288   57.299   34.609                  
 
       EXAMPLE 6  
     Analysis of Disease-Associated Genes  
       [0180]    Non-enzymic protein glycation reaction is believed to be a cause of a variety of chronic diabetic complications. Accordingly, genes of which expression is elevated or decreased in a glycated protein-specific manner are associated with diabetic complications caused by glycated proteins. Vascular endothelial cells are affected with glycated proteins present in blood.  
         [0181]    Reaction products of non-enzymic protein glycation include amadori compound (glycated protein) as a mildly glycated protein and advanced glycation endproduct as a heavily glycated protein. Hence, whether or not the expression of the KP genes of this invention was varied depending on the presence of these proteins in endothelial cells was examined.  
         [0182]    The mRNAs were extracted from endothelial cells that were cultured in the presence or absence of glycated protein. The mRNAs were converted into radiolabeled first strand cDNAs for preparing probes. The probes were hybridized to the above-mentioned DNA array. Signal of each DNA spot was detected by BAS2000 and analyzed by ArrayGauge (Fuji Photo Film Co., Ltd.).  
         [0183]    Advanced glycation endproduct of bovine serum albumin was prepared as follows: bovine serum albumin (BSA; Sigma) was incubated in a phosphate buffer solution containing 50 mM glucose at 37° C. for 8 weeks; and the resulting brownish BSA was dialyzed against a phosphate buffer solution.  
         [0184]    Human normal pulmonary arterial endothelial cells (Cell Applications) were cultured in an Endothelial Cell Growth Medium (Cell Applications). The culture dish (Falcon) with the cells was incubated in a CO 2  incubator (37° C., 5% CO 2 , in a humid atmosphere). When the cells were grown to be confluent in the dish, 250 μg/ml of bovine serum albumin (sigma), glycated bovine serum albumin (Sigma) or advanced glycation endproduct of serum albumin was added thereto and the cells were incubated for 33 hours. The mRNA was extracted from the cells by using a FastTrack ™  2.0 kit (Invitrogen). The labeling of hybridization probe was carried out by using the mRNA according to the same procedure as described above.  
         [0185]    Table 3 shows the expression level of each cDNA in human pulmonary arterial endothelial cells cultured in a medium containing bovine serum albumin, glycated bovine serum albumin or advanced glycation endproduct of bovine serum albumin. The expression of “C-NT2RP3001938” was detected in the endothelial cell.  
                                                             TABLE 3                                   Advanced   Glycated   Advanced glycation                   glycation   bovine albumin   endproduct of bovine                   endproduct of   addition/   serum albumin/           Bovine serum   Glycated   bovine serum   Bovine serum   Bovine serum       Clone name   albumin   bovine albumin   albumin   albumin ratio   albumin ratio                                GAPDH(Cr1)   100.81   134.21   115.16   1.33   1.14       βactin(Cr2)   1101.9   1092.57   997.36   0.99   0.91       NT2RP3001938   44.42   42.62   38.19   0.96   0.9                   
 
       Example 7  
     Analysis of Ultraviolet Radiation Damage-Associated Genes  
       [0186]    It is known that ultraviolet rays give considerably adverse influence on health. In recent years, the risks of tissue damage by ultraviolet rays has been increased due to the destruction of the ozone layer, and ultraviolet radiation has been recognized as a risk factor for diseases such as skin cancers (United States Environmental Protection Agency: Ozone Depletion Home Page, http://www.epa.gov/ozone/). Genes whose expression levels change with exposure of the skin epidermal cells to ultraviolet rays are considered to be associated with skin damage caused by ultraviolet radiation. Culturing primary cultured skin fibroblast cells irradiated with ultraviolet ray, it was examined whether the expression of KP genes of this invention varies depending on the irradiation of ultraviolet ray. First, after culturing to confluence in a culture dish, the primary cultured skin fibroblast cells (Cell Applications) were exposed to 10,000 PJ/cm 2  of 254-nm ultraviolet light. Thereafter, messenger RNAs were extracted by using a FastTrack™ 2.0 mRNA Isolation kit (Invitrogen) from the unexposed cells and from the cells that were exposed to the ultraviolet light and then cultured for 4 or 24 hours. The labeling of the hybridization probe was carried out by using 1.5 μg of each mRNA in the same manner as described above. The data were obtained in triplicate (n=3). The hybridization signals were compared between the cells exposed to the ultraviolet light and the unexposed cells. The comparison was preformed by statistical treatment with two-sample t-test. Clones with significant differences in the signal distribution were selected under the condition of p&lt;0.05. According to the analysis, the difference in the signal values can be also detected statistically even when the signal values are low. Accordingly, clones with signal value of 40 or lower were also assessed.  
         [0187]    Table 4 shows the expression of each cDNA in skin-derived fibroblast cells exposed and unexposed to ultraviolet light.  
         [0188]    Averaged signal values (M 1 , M 2 ) and sample variances (s 1   2 , s 2   2 ) were calculated for each gene in each of the cells, and then, pooled sample variances s were obtained from the sample variances of the two types of cells to be compared. The t values were determined according to the following formula: t=(M 1 −M 2 )/s/(1/3+1/3) 1/2 . When the determined t-value was greater than a t-value at P, probability of significance level, of 0.05 or 0.01 in the t-distribution table with 4 degrees of freedom, it was judged that a difference exists in the expression level of the gene between the two types of cells at P&lt;0.05 or P&lt;0.01, respectively. The table also includes the information of an increase (+) or decrease (−) in the average expression level of a signal in the clones compared with that of undifferentiated cells.  
         [0189]    The results showed that the expression level of “C-OVARC1000945” was reduced 4 hours or 24 hours after ultraviolet ray irradiation, suggesting that it is a clone associated with ultraviolet ray disorders.  
                                                                                                                                                               TABLE 4                                       UV_0 h   UV_4 h   UV_24 h   t test   4 h   24 h            Clone   Exp. 1   Exp. 2   Exp. 3   Exp. 1   Exp. 2   Exp. 3   Exp. 1   Exp. 2   Exp. 3   0/4   0/24   +/−   +/−                    GAPDH(Cr1)   0   1.29   0.1   0.9   0.06   1.18   1.49   0.47   0                       βactin(Cr2)   256.82   283.53   414.29   388.38   117.29   329.8   189.18   190.26   157.87       *       −       OVARC1000945   15   14.98   13.39   5.71   5.62   7.78   3.1   4.11   2.76   **   **   −   −                  
 
       INDUSTRIAL APPLICABILITY  
       [0190]    The present invention provides novel human protein kinase and protein phosphatase proteins, as well as genes encoding the proteins. The regulation of the phosphorylation state of proteins by kinase and/or phosphatase plays central roles in normal differentiation and/or proliferation of cells, as well as in physiological functions at the cellular level. The novel kinases and phosphatases of the present invention can be assumed to be closely associated with intracellular physiological functions, and thus, the inventive proteins are useful as target molecules of agents in the development of pharmaceuticals. Furthermore, agents acting on the inventive proteins are expected to be effective pharmaceuticals which can control intracellular physiological functions more precisely than agents represented by previous receptor agonists and antagonists.  
     
       
       
         1 
         
           
             43  
           
           
             1  
             2174  
             DNA  
             Homo sapiens  
             
               CDS  
               (366)..(1619)  
             
           
            1 

ccccgccttc tcgctgccca gccccgggga gggaggcggg gccgcgaccc cggcgcgggt     60 

ggggcgaatg cgttcccagc gggtagcctg gggctggtgc agagttccaa gcccacggcc    120 

ccggtcgcgg cctcgccgcc ctcccgcgcc ccgcgccggg agcgggccta gagcgctcgc    180 

ctcgcccctc cgcgagcagg gctctggcgc ccgcccctgt ccgcaccgct ggcagcctga    240 

agagagtcgc tggccgtggt cgccgctagg taggatatat ctgcatcttg aaaggaagat    300 

aaaacaaaag ccttctttgg aatagatgga tttttgtcac tttctgtgtg aactaaagtg    360 

attca atg tct ctt ttg gat tgc ttc tgc act tca aga aca caa gtt gaa    410 
      Met Ser Leu Leu Asp Cys Phe Cys Thr Ser Arg Thr Gln Val Glu 
        1               5                  10                  15 

tca ctc aga cct gaa aaa cag tct gaa acc agt atc cat caa tac ttg      458 
Ser Leu Arg Pro Glu Lys Gln Ser Glu Thr Ser Ile His Gln Tyr Leu 
                 20                  25                  30 

gtt gat gag cca acc ctt tcc tgg tca cgt cca tcc act aga gcc agt      506 
Val Asp Glu Pro Thr Leu Ser Trp Ser Arg Pro Ser Thr Arg Ala Ser 
             35                  40                  45 

gaa gta cta tgt tcc acc aac gtt tct cac tat gag ctc caa gta gaa      554 
Glu Val Leu Cys Ser Thr Asn Val Ser His Tyr Glu Leu Gln Val Glu 
         50                  55                  60 

ata gga aga gga ttt gac aac ttg act tct gtc cat ctt gca cgg cat      602 
Ile Gly Arg Gly Phe Asp Asn Leu Thr Ser Val His Leu Ala Arg His 
     65                  70                  75 

act ccc aca gga aca ctg gta act ata aaa att aca aat ctg gaa aac      650 
Thr Pro Thr Gly Thr Leu Val Thr Ile Lys Ile Thr Asn Leu Glu Asn 
 80                  85                  90                  95 

tgc aat gaa gaa cgc ctg aaa gct tta cag aaa gcc gtg att cta tcc      698 
Cys Asn Glu Glu Arg Leu Lys Ala Leu Gln Lys Ala Val Ile Leu Ser 
                100                 105                 110 

cac ttt ttc cgg cat ccc aat att aca act tat tgg aca gtt ttc act      746 
His Phe Phe Arg His Pro Asn Ile Thr Thr Tyr Trp Thr Val Phe Thr 
            115                 120                 125 

gtt ggc agc tgg ctt tgg gtt att tct cca ttt atg gcc tat ggt tca      794 
Val Gly Ser Trp Leu Trp Val Ile Ser Pro Phe Met Ala Tyr Gly Ser 
        130                 135                 140 

gca agt caa ctc ttg agg acc tat ttt cct gaa gga atg agt gaa act      842 
Ala Ser Gln Leu Leu Arg Thr Tyr Phe Pro Glu Gly Met Ser Glu Thr 
    145                 150                 155 

tta ata aga aac att ctc ttt gga gcc gtg aga ggg ttg aac tat ctg      890 
Leu Ile Arg Asn Ile Leu Phe Gly Ala Val Arg Gly Leu Asn Tyr Leu 
160                 165                 170                 175 

cac caa aat ggc tgt att cac agg agt att aaa gcc agc cat atc ctc      938 
His Gln Asn Gly Cys Ile His Arg Ser Ile Lys Ala Ser His Ile Leu 
                180                 185                 190 

att tct ggt gat ggc cta gtg acc ctc tct ggc ctg tcc cat ctg cat      986 
Ile Ser Gly Asp Gly Leu Val Thr Leu Ser Gly Leu Ser His Leu His 
            195                 200                 205 

agt ttg gtt aag cat gga cag agg cat agg gct gtg tat gat ttc cca     1034 
Ser Leu Val Lys His Gly Gln Arg His Arg Ala Val Tyr Asp Phe Pro 
        210                 215                 220 

cag ttc agc aca tca gtg cag ccg tgg ctg agt cca gaa cta ctg aga     1082 
Gln Phe Ser Thr Ser Val Gln Pro Trp Leu Ser Pro Glu Leu Leu Arg 
    225                 230                 235 

cag gat tta cat ggg tat aat gtg aag tca gat att tac agt gtt ggg     1130 
Gln Asp Leu His Gly Tyr Asn Val Lys Ser Asp Ile Tyr Ser Val Gly 
240                 245                 250                 255 

att aca gca tgt gaa tta gcc agt ggg cag gtg cct ttc cag gac atg     1178 
Ile Thr Ala Cys Glu Leu Ala Ser Gly Gln Val Pro Phe Gln Asp Met 
                260                 265                 270 

cat aga act cag atg ctg tta cag aaa ctg aaa ggt cct cct tat agc     1226 
His Arg Thr Gln Met Leu Leu Gln Lys Leu Lys Gly Pro Pro Tyr Ser 
            275                 280                 285 

cca ttg gat atc agt att ttc cct caa tca gaa tcc aga atg aaa aat     1274 
Pro Leu Asp Ile Ser Ile Phe Pro Gln Ser Glu Ser Arg Met Lys Asn 
        290                 295                 300 

tcc cag tca ggt gta gac tct ggg att gga gaa agt gtg ctt gtc tcc     1322 
Ser Gln Ser Gly Val Asp Ser Gly Ile Gly Glu Ser Val Leu Val Ser 
    305                 310                 315 

agt gga act cac aca gta aat agt gac cga tta cac aca cca tcc tca     1370 
Ser Gly Thr His Thr Val Asn Ser Asp Arg Leu His Thr Pro Ser Ser 
320                 325                 330                 335 

aaa act ttc tct cct gcc ttc ttt agc ttg gta cag ctc tgt ttg caa     1418 
Lys Thr Phe Ser Pro Ala Phe Phe Ser Leu Val Gln Leu Cys Leu Gln 
                340                 345                 350 

caa gat cct gag aaa agg cca tca gca agc agt tta ttg tcc cat gtt     1466 
Gln Asp Pro Glu Lys Arg Pro Ser Ala Ser Ser Leu Leu Ser His Val 
            355                 360                 365 

ttc ttc aaa cag atg aaa gaa gaa agc cag gat tca ata ctt tca ctg     1514 
Phe Phe Lys Gln Met Lys Glu Glu Ser Gln Asp Ser Ile Leu Ser Leu 
        370                 375                 380 

ttg cct cct gct tat aac aag cca tca ata tca ttg cct cca gtg tta     1562 
Leu Pro Pro Ala Tyr Asn Lys Pro Ser Ile Ser Leu Pro Pro Val Leu 
    385                 390                 395 

cct tgg act gag cca gaa tgt gat ttt cct gat gaa aaa gac tca tac     1610 
Pro Trp Thr Glu Pro Glu Cys Asp Phe Pro Asp Glu Lys Asp Ser Tyr 
400                 405                 410                 415 

tgg gaa ttc tagggctgcc aaatcatttt atgtcctata tacttgacac             1659 
Trp Glu Phe 

tttctccttg ctgctttttc ttctgtattt ctaggtacaa ataccagaat tatacttgaa   1719 

aatacagttg gtgcactgga gaatctatta tttaaaacca ctctgttcaa aggggcacca   1779 

gtttgtagtc cctctgtttc gcacagagta ctatgacaag gaaacatcag aattactaat   1839 

ctagctagtg tcatttattc tggaattttt ttctaagctg tgactaactc tttttatctc   1899 

tcaatataat ttttgagcca gttaattttt ttcagtattt tgctgtccct tgggaatggg   1959 

ccctcagagg acagtgcttc caagtacatc ttctcccaga ttctctggcc tttttaatga   2019 

gctattgtta aaccaacagg ctagtttatc ttacatcaga cccttttctg gtagagggaa   2079 

aatgtttgtg ctttcccttt ttcttctgtt aatacttatg gtaacaccta actgagcctc   2139 

actcacatta aatgattcac ttgaaatata tacag                              2174 

 
           
             2  
             418  
             PRT  
             Homo sapiens  
           
            2 

Met Ser Leu Leu Asp Cys Phe Cys Thr Ser Arg Thr Gln Val Glu Ser 
  1               5                  10                  15 

Leu Arg Pro Glu Lys Gln Ser Glu Thr Ser Ile His Gln Tyr Leu Val 
             20                  25                  30 

Asp Glu Pro Thr Leu Ser Trp Ser Arg Pro Ser Thr Arg Ala Ser Glu 
         35                  40                  45 

Val Leu Cys Ser Thr Asn Val Ser His Tyr Glu Leu Gln Val Glu Ile 
     50                  55                  60 

Gly Arg Gly Phe Asp Asn Leu Thr Ser Val His Leu Ala Arg His Thr 
 65                  70                  75                  80 

Pro Thr Gly Thr Leu Val Thr Ile Lys Ile Thr Asn Leu Glu Asn Cys 
                 85                  90                  95 

Asn Glu Glu Arg Leu Lys Ala Leu Gln Lys Ala Val Ile Leu Ser His 
            100                 105                 110 

Phe Phe Arg His Pro Asn Ile Thr Thr Tyr Trp Thr Val Phe Thr Val 
        115                 120                 125 

Gly Ser Trp Leu Trp Val Ile Ser Pro Phe Met Ala Tyr Gly Ser Ala 
    130                 135                 140 

Ser Gln Leu Leu Arg Thr Tyr Phe Pro Glu Gly Met Ser Glu Thr Leu 
145                 150                 155                 160 

Ile Arg Asn Ile Leu Phe Gly Ala Val Arg Gly Leu Asn Tyr Leu His 
                165                 170                 175 

Gln Asn Gly Cys Ile His Arg Ser Ile Lys Ala Ser His Ile Leu Ile 
            180                 185                 190 

Ser Gly Asp Gly Leu Val Thr Leu Ser Gly Leu Ser His Leu His Ser 
        195                 200                 205 

Leu Val Lys His Gly Gln Arg His Arg Ala Val Tyr Asp Phe Pro Gln 
    210                 215                 220 

Phe Ser Thr Ser Val Gln Pro Trp Leu Ser Pro Glu Leu Leu Arg Gln 
225                 230                 235                 240 

Asp Leu His Gly Tyr Asn Val Lys Ser Asp Ile Tyr Ser Val Gly Ile 
                245                 250                 255 

Thr Ala Cys Glu Leu Ala Ser Gly Gln Val Pro Phe Gln Asp Met His 
            260                 265                 270 

Arg Thr Gln Met Leu Leu Gln Lys Leu Lys Gly Pro Pro Tyr Ser Pro 
        275                 280                 285 

Leu Asp Ile Ser Ile Phe Pro Gln Ser Glu Ser Arg Met Lys Asn Ser 
    290                 295                 300 

Gln Ser Gly Val Asp Ser Gly Ile Gly Glu Ser Val Leu Val Ser Ser 
305                 310                 315                 320 

Gly Thr His Thr Val Asn Ser Asp Arg Leu His Thr Pro Ser Ser Lys 
                325                 330                 335 

Thr Phe Ser Pro Ala Phe Phe Ser Leu Val Gln Leu Cys Leu Gln Gln 
            340                 345                 350 

Asp Pro Glu Lys Arg Pro Ser Ala Ser Ser Leu Leu Ser His Val Phe 
        355                 360                 365 

Phe Lys Gln Met Lys Glu Glu Ser Gln Asp Ser Ile Leu Ser Leu Leu 
    370                 375                 380 

Pro Pro Ala Tyr Asn Lys Pro Ser Ile Ser Leu Pro Pro Val Leu Pro 
385                 390                 395                 400 

Trp Thr Glu Pro Glu Cys Asp Phe Pro Asp Glu Lys Asp Ser Tyr Trp 
                405                 410                 415 

Glu Phe 

 
           
             3  
             2718  
             DNA  
             Homo sapiens  
             
               CDS  
               (33)..(2627)  
             
           
            3 

ttgaggtcac accttcagtc cttcgagcaa at atg cct ctt cat gtt cga cgc       53 
                                    Met Pro Leu His Val Arg Arg 
                                      1               5 

agt agt gac cca gct cta att ggc ctc tcc act tct gtc agt gat agt      101 
Ser Ser Asp Pro Ala Leu Ile Gly Leu Ser Thr Ser Val Ser Asp Ser 
         10                  15                  20 

aat ttt tcc tct gaa gag cct tca agg aaa aat ccc aca cgc tgg tca      149 
Asn Phe Ser Ser Glu Glu Pro Ser Arg Lys Asn Pro Thr Arg Trp Ser 
     25                  30                  35 

aca aca gct ggc ttc ctc aag cag aac act gct ggg agt cct aaa gcc      197 
Thr Thr Ala Gly Phe Leu Lys Gln Asn Thr Ala Gly Ser Pro Lys Ala 
 40                  45                  50                  55 

tgc gac agg aag aaa gat gaa aac tac aga agc ctc ccg cgg gat act      245 
Cys Asp Arg Lys Lys Asp Glu Asn Tyr Arg Ser Leu Pro Arg Asp Thr 
                 60                  65                  70 

agt aac tgg tct aac caa ttt cag aga gac aat gct cgc tcg tct ctg      293 
Ser Asn Trp Ser Asn Gln Phe Gln Arg Asp Asn Ala Arg Ser Ser Leu 
             75                  80                  85 

agt gcc agt cac cca atg gtg ggc aag tgg cag gag aaa caa gaa cag      341 
Ser Ala Ser His Pro Met Val Gly Lys Trp Gln Glu Lys Gln Glu Gln 
         90                  95                 100 

gat gag gat ggg aca gaa gag gat aac agt cgt gtt gaa cct gtt gga      389 
Asp Glu Asp Gly Thr Glu Glu Asp Asn Ser Arg Val Glu Pro Val Gly 
    105                 110                 115 

cat gct gac acg ggt ttg gag cat ata ccc aac ttt tct ctg gat gat      437 
His Ala Asp Thr Gly Leu Glu His Ile Pro Asn Phe Ser Leu Asp Asp 
120                 125                 130                 135 

atg gta aag ctc gta gaa gtc ccc aac gat gga ggg cct ctg gga atc      485 
Met Val Lys Leu Val Glu Val Pro Asn Asp Gly Gly Pro Leu Gly Ile 
                140                 145                 150 

cat gta gtg cct ttc agt gct cga ggc ggc aga acc ctg ggg tta tta      533 
His Val Val Pro Phe Ser Ala Arg Gly Gly Arg Thr Leu Gly Leu Leu 
            155                 160                 165 

gta aaa cga ttg gag aaa ggt ggt aaa gct gaa cat gaa aat ctt ttt      581 
Val Lys Arg Leu Glu Lys Gly Gly Lys Ala Glu His Glu Asn Leu Phe 
        170                 175                 180 

cgt gag aat gat tgc att gtc agg att aat gat ggc gac ctt cga aat      629 
Arg Glu Asn Asp Cys Ile Val Arg Ile Asn Asp Gly Asp Leu Arg Asn 
    185                 190                 195 

aga aga ttt gaa caa gca caa cat atg ttt cgc caa gcc atg cgt aca      677 
Arg Arg Phe Glu Gln Ala Gln His Met Phe Arg Gln Ala Met Arg Thr 
200                 205                 210                 215 

ccc atc att tgg ttc cat gtg gtt cct gca gca aat aaa gag cag tat      725 
Pro Ile Ile Trp Phe His Val Val Pro Ala Ala Asn Lys Glu Gln Tyr 
                220                 225                 230 

gaa caa cta tcc caa agt gag aag aac aat tac tat tca agc cgt ttt      773 
Glu Gln Leu Ser Gln Ser Glu Lys Asn Asn Tyr Tyr Ser Ser Arg Phe 
            235                 240                 245 

agc cct gac agc cag tat att gac aac agg agt gtg aac agt gca ggg      821 
Ser Pro Asp Ser Gln Tyr Ile Asp Asn Arg Ser Val Asn Ser Ala Gly 
        250                 255                 260 

ctt cac acg gtg cag aga gca ccc cga ctg aac cac ccg cct gag cag      869 
Leu His Thr Val Gln Arg Ala Pro Arg Leu Asn His Pro Pro Glu Gln 
    265                 270                 275 

ata gac tct cac tca aga cta cct cat agc gca cac ccc tcg gga aaa      917 
Ile Asp Ser His Ser Arg Leu Pro His Ser Ala His Pro Ser Gly Lys 
280                 285                 290                 295 

cca cca tcc gct cca gcc tcg gca cct cag aat gta ttt agt acg act      965 
Pro Pro Ser Ala Pro Ala Ser Ala Pro Gln Asn Val Phe Ser Thr Thr 
                300                 305                 310 

gta agc agt ggt tat aac acc aaa aaa ata ggc aag agg ctt aat atc     1013 
Val Ser Ser Gly Tyr Asn Thr Lys Lys Ile Gly Lys Arg Leu Asn Ile 
            315                 320                 325 

cag ctt aag aaa ggt aca gaa ggt ttg gga ttc agc atc act tcc aga     1061 
Gln Leu Lys Lys Gly Thr Glu Gly Leu Gly Phe Ser Ile Thr Ser Arg 
        330                 335                 340 

gat gta aca ata ggt ggc tca gct cca atc tat gtg aaa aac att ctc     1109 
Asp Val Thr Ile Gly Gly Ser Ala Pro Ile Tyr Val Lys Asn Ile Leu 
    345                 350                 355 

ccc cgg ggg gcg gcc att cag gat ggc cga ctt aag gca gga gac aga     1157 
Pro Arg Gly Ala Ala Ile Gln Asp Gly Arg Leu Lys Ala Gly Asp Arg 
360                 365                 370                 375 

ctt ata gag gta aat gga gta gat tta gtg ggc aaa tcc caa gag gaa     1205 
Leu Ile Glu Val Asn Gly Val Asp Leu Val Gly Lys Ser Gln Glu Glu 
                380                 385                 390 

gtt gtt tcg ctg ttg aga agc acc aag atg gaa gga act gtg agc ctt     1253 
Val Val Ser Leu Leu Arg Ser Thr Lys Met Glu Gly Thr Val Ser Leu 
            395                 400                 405 

ctg gtc ttt cgc cag gaa gac gcc ttc cac cca agg gaa ctg aat gca     1301 
Leu Val Phe Arg Gln Glu Asp Ala Phe His Pro Arg Glu Leu Asn Ala 
        410                 415                 420 

gag cca agc cag atg cag att cca aaa gaa acg aaa gca gaa gat gag     1349 
Glu Pro Ser Gln Met Gln Ile Pro Lys Glu Thr Lys Ala Glu Asp Glu 
    425                 430                 435 

gat att gtt ctt aca cct gat ggc acc agg gaa ttt ctg aca ttt gaa     1397 
Asp Ile Val Leu Thr Pro Asp Gly Thr Arg Glu Phe Leu Thr Phe Glu 
440                 445                 450                 455 

gtc cca ctt agt gat tca gga tct gca ggc ctt ggt gtc agt gtc aaa     1445 
Val Pro Leu Ser Asp Ser Gly Ser Ala Gly Leu Gly Val Ser Val Lys 
                460                 465                 470 

ggt aac cgg tca aaa gag aac cac gca gat ttg gga atc ttt gtc aag     1493 
Gly Asn Arg Ser Lys Glu Asn His Ala Asp Leu Gly Ile Phe Val Lys 
            475                 480                 485 

tcc att att aat gga gga gca gca tct aaa gat gga agg ctt cgg gtg     1541 
Ser Ile Ile Asn Gly Gly Ala Ala Ser Lys Asp Gly Arg Leu Arg Val 
        490                 495                 500 

aat gat caa ctg ata gca gta aat gga gaa tcc ctg ttg ggc aag aca     1589 
Asn Asp Gln Leu Ile Ala Val Asn Gly Glu Ser Leu Leu Gly Lys Thr 
    505                 510                 515 

aac caa gat gcc atg gaa acc cta aga agg tct atg tct act gaa ggc     1637 
Asn Gln Asp Ala Met Glu Thr Leu Arg Arg Ser Met Ser Thr Glu Gly 
520                 525                 530                 535 

aat aaa cga gga atg atc cag ctt att gtt gca agg aga ata agc aag     1685 
Asn Lys Arg Gly Met Ile Gln Leu Ile Val Ala Arg Arg Ile Ser Lys 
                540                 545                 550 

tgc aat gag ctg aag tca cct ggg agc ccc cct gga cct gag ctg ccc     1733 
Cys Asn Glu Leu Lys Ser Pro Gly Ser Pro Pro Gly Pro Glu Leu Pro 
            555                 560                 565 

att gaa aca gcg ttg gat gat aga gaa cga aga att tcc cat tcc ctc     1781 
Ile Glu Thr Ala Leu Asp Asp Arg Glu Arg Arg Ile Ser His Ser Leu 
        570                 575                 580 

tac agt ggg att gag ggg ctt gat gaa tcg ccc agc aga aat gct gcc     1829 
Tyr Ser Gly Ile Glu Gly Leu Asp Glu Ser Pro Ser Arg Asn Ala Ala 
    585                 590                 595 

ctc agt agg ata atg ggt aaa tac cag ctg tcc cct aca gtg aat atg     1877 
Leu Ser Arg Ile Met Gly Lys Tyr Gln Leu Ser Pro Thr Val Asn Met 
600                 605                 610                 615 

ccc caa gat gac act gtc att ata gaa gat gac agg ttg cca gtg ctt     1925 
Pro Gln Asp Asp Thr Val Ile Ile Glu Asp Asp Arg Leu Pro Val Leu 
                620                 625                 630 

cct cca cat ctc tct gac cag tcc tct tcc agc tcc cat gat gat gtg     1973 
Pro Pro His Leu Ser Asp Gln Ser Ser Ser Ser Ser His Asp Asp Val 
            635                 640                 645 

ggg ttt gtg acg gca gat gct ggt act tgg gcc aag gct gca atc agt     2021 
Gly Phe Val Thr Ala Asp Ala Gly Thr Trp Ala Lys Ala Ala Ile Ser 
        650                 655                 660 

gat tca gcc gac tgc tct ttg agt cca gat gtt gat cca gtt ctt gct     2069 
Asp Ser Ala Asp Cys Ser Leu Ser Pro Asp Val Asp Pro Val Leu Ala 
    665                 670                 675 

ttt caa cga gaa gga ttt gga cgt cag act gac gag act aaa ctc aat     2117 
Phe Gln Arg Glu Gly Phe Gly Arg Gln Thr Asp Glu Thr Lys Leu Asn 
680                 685                 690                 695 

aca gtg gat gac cag aaa gca ggt tct ccc agc aga gat gtg ggt cct     2165 
Thr Val Asp Asp Gln Lys Ala Gly Ser Pro Ser Arg Asp Val Gly Pro 
                700                 705                 710 

tcc ctg ggt ctg aag aag tca agc tca ttg gag agt ctg cag acc gca     2213 
Ser Leu Gly Leu Lys Lys Ser Ser Ser Leu Glu Ser Leu Gln Thr Ala 
            715                 720                 725 

gtt gcc gag gtg act ttg aat ggg gat att cct ttc cat cgt cca cgg     2261 
Val Ala Glu Val Thr Leu Asn Gly Asp Ile Pro Phe His Arg Pro Arg 
        730                 735                 740 

ccg cgg ata atc aga ggc agg gga tgc aat gag agc ttc aga gct gcc     2309 
Pro Arg Ile Ile Arg Gly Arg Gly Cys Asn Glu Ser Phe Arg Ala Ala 
    745                 750                 755 

atc gac aaa tct tat gat aaa ccc gcg gta gat gat gat gat gaa ggc     2357 
Ile Asp Lys Ser Tyr Asp Lys Pro Ala Val Asp Asp Asp Asp Glu Gly 
760                 765                 770                 775 

atg gag acc ttg gaa gaa gac aca gaa gaa agt tca aga tca ggg aga     2405 
Met Glu Thr Leu Glu Glu Asp Thr Glu Glu Ser Ser Arg Ser Gly Arg 
                780                 785                 790 

gag tct gta tcc aca gcc agt gat cag cct tcc cac tct ctg gag aga     2453 
Glu Ser Val Ser Thr Ala Ser Asp Gln Pro Ser His Ser Leu Glu Arg 
            795                 800                 805 

caa atg aat gga aac caa gag aaa ggt gat aag act gat aga aaa aag     2501 
Gln Met Asn Gly Asn Gln Glu Lys Gly Asp Lys Thr Asp Arg Lys Lys 
        810                 815                 820 

gat aaa act gga aaa gaa aag aag aaa gat aga gat aag gag aag gat     2549 
Asp Lys Thr Gly Lys Glu Lys Lys Lys Asp Arg Asp Lys Glu Lys Asp 
    825                 830                 835 

aaa atg aaa gcc aag aag gga atg ctg aag ggc ttg gga gac atg ttc     2597 
Lys Met Lys Ala Lys Lys Gly Met Leu Lys Gly Leu Gly Asp Met Phe 
840                 845                 850                 855 

agc ctt gcc aaa ctg aag ccc gag aag aga tgaacaacaa agcgattcaa       2647 
Ser Leu Ala Lys Leu Lys Pro Glu Lys Arg 
                860                 865 

aacatgtctt gaacagcaca tattgcacag ttgttgtttt ttttaaacaa acaataaatt   2707 

tacttttaat g                                                        2718 

 
           
             4  
             865  
             PRT  
             Homo sapiens  
           
            4 

Met Pro Leu His Val Arg Arg Ser Ser Asp Pro Ala Leu Ile Gly Leu 
  1               5                  10                  15 

Ser Thr Ser Val Ser Asp Ser Asn Phe Ser Ser Glu Glu Pro Ser Arg 
             20                  25                  30 

Lys Asn Pro Thr Arg Trp Ser Thr Thr Ala Gly Phe Leu Lys Gln Asn 
         35                  40                  45 

Thr Ala Gly Ser Pro Lys Ala Cys Asp Arg Lys Lys Asp Glu Asn Tyr 
     50                  55                  60 

Arg Ser Leu Pro Arg Asp Thr Ser Asn Trp Ser Asn Gln Phe Gln Arg 
 65                  70                  75                  80 

Asp Asn Ala Arg Ser Ser Leu Ser Ala Ser His Pro Met Val Gly Lys 
                 85                  90                  95 

Trp Gln Glu Lys Gln Glu Gln Asp Glu Asp Gly Thr Glu Glu Asp Asn 
            100                 105                 110 

Ser Arg Val Glu Pro Val Gly His Ala Asp Thr Gly Leu Glu His Ile 
        115                 120                 125 

Pro Asn Phe Ser Leu Asp Asp Met Val Lys Leu Val Glu Val Pro Asn 
    130                 135                 140 

Asp Gly Gly Pro Leu Gly Ile His Val Val Pro Phe Ser Ala Arg Gly 
145                 150                 155                 160 

Gly Arg Thr Leu Gly Leu Leu Val Lys Arg Leu Glu Lys Gly Gly Lys 
                165                 170                 175 

Ala Glu His Glu Asn Leu Phe Arg Glu Asn Asp Cys Ile Val Arg Ile 
            180                 185                 190 

Asn Asp Gly Asp Leu Arg Asn Arg Arg Phe Glu Gln Ala Gln His Met 
        195                 200                 205 

Phe Arg Gln Ala Met Arg Thr Pro Ile Ile Trp Phe His Val Val Pro 
    210                 215                 220 

Ala Ala Asn Lys Glu Gln Tyr Glu Gln Leu Ser Gln Ser Glu Lys Asn 
225                 230                 235                 240 

Asn Tyr Tyr Ser Ser Arg Phe Ser Pro Asp Ser Gln Tyr Ile Asp Asn 
                245                 250                 255 

Arg Ser Val Asn Ser Ala Gly Leu His Thr Val Gln Arg Ala Pro Arg 
            260                 265                 270 

Leu Asn His Pro Pro Glu Gln Ile Asp Ser His Ser Arg Leu Pro His 
        275                 280                 285 

Ser Ala His Pro Ser Gly Lys Pro Pro Ser Ala Pro Ala Ser Ala Pro 
    290                 295                 300 

Gln Asn Val Phe Ser Thr Thr Val Ser Ser Gly Tyr Asn Thr Lys Lys 
305                 310                 315                 320 

Ile Gly Lys Arg Leu Asn Ile Gln Leu Lys Lys Gly Thr Glu Gly Leu 
                325                 330                 335 

Gly Phe Ser Ile Thr Ser Arg Asp Val Thr Ile Gly Gly Ser Ala Pro 
            340                 345                 350 

Ile Tyr Val Lys Asn Ile Leu Pro Arg Gly Ala Ala Ile Gln Asp Gly 
        355                 360                 365 

Arg Leu Lys Ala Gly Asp Arg Leu Ile Glu Val Asn Gly Val Asp Leu 
    370                 375                 380 

Val Gly Lys Ser Gln Glu Glu Val Val Ser Leu Leu Arg Ser Thr Lys 
385                 390                 395                 400 

Met Glu Gly Thr Val Ser Leu Leu Val Phe Arg Gln Glu Asp Ala Phe 
                405                 410                 415 

His Pro Arg Glu Leu Asn Ala Glu Pro Ser Gln Met Gln Ile Pro Lys 
            420                 425                 430 

Glu Thr Lys Ala Glu Asp Glu Asp Ile Val Leu Thr Pro Asp Gly Thr 
        435                 440                 445 

Arg Glu Phe Leu Thr Phe Glu Val Pro Leu Ser Asp Ser Gly Ser Ala 
    450                 455                 460 

Gly Leu Gly Val Ser Val Lys Gly Asn Arg Ser Lys Glu Asn His Ala 
465                 470                 475                 480 

Asp Leu Gly Ile Phe Val Lys Ser Ile Ile Asn Gly Gly Ala Ala Ser 
                485                 490                 495 

Lys Asp Gly Arg Leu Arg Val Asn Asp Gln Leu Ile Ala Val Asn Gly 
            500                 505                 510 

Glu Ser Leu Leu Gly Lys Thr Asn Gln Asp Ala Met Glu Thr Leu Arg 
        515                 520                 525 

Arg Ser Met Ser Thr Glu Gly Asn Lys Arg Gly Met Ile Gln Leu Ile 
    530                 535                 540 

Val Ala Arg Arg Ile Ser Lys Cys Asn Glu Leu Lys Ser Pro Gly Ser 
545                 550                 555                 560 

Pro Pro Gly Pro Glu Leu Pro Ile Glu Thr Ala Leu Asp Asp Arg Glu 
                565                 570                 575 

Arg Arg Ile Ser His Ser Leu Tyr Ser Gly Ile Glu Gly Leu Asp Glu 
            580                 585                 590 

Ser Pro Ser Arg Asn Ala Ala Leu Ser Arg Ile Met Gly Lys Tyr Gln 
        595                 600                 605 

Leu Ser Pro Thr Val Asn Met Pro Gln Asp Asp Thr Val Ile Ile Glu 
    610                 615                 620 

Asp Asp Arg Leu Pro Val Leu Pro Pro His Leu Ser Asp Gln Ser Ser 
625                 630                 635                 640 

Ser Ser Ser His Asp Asp Val Gly Phe Val Thr Ala Asp Ala Gly Thr 
                645                 650                 655 

Trp Ala Lys Ala Ala Ile Ser Asp Ser Ala Asp Cys Ser Leu Ser Pro 
            660                 665                 670 

Asp Val Asp Pro Val Leu Ala Phe Gln Arg Glu Gly Phe Gly Arg Gln 
        675                 680                 685 

Thr Asp Glu Thr Lys Leu Asn Thr Val Asp Asp Gln Lys Ala Gly Ser 
    690                 695                 700 

Pro Ser Arg Asp Val Gly Pro Ser Leu Gly Leu Lys Lys Ser Ser Ser 
705                 710                 715                 720 

Leu Glu Ser Leu Gln Thr Ala Val Ala Glu Val Thr Leu Asn Gly Asp 
                725                 730                 735 

Ile Pro Phe His Arg Pro Arg Pro Arg Ile Ile Arg Gly Arg Gly Cys 
            740                 745                 750 

Asn Glu Ser Phe Arg Ala Ala Ile Asp Lys Ser Tyr Asp Lys Pro Ala 
        755                 760                 765 

Val Asp Asp Asp Asp Glu Gly Met Glu Thr Leu Glu Glu Asp Thr Glu 
    770                 775                 780 

Glu Ser Ser Arg Ser Gly Arg Glu Ser Val Ser Thr Ala Ser Asp Gln 
785                 790                 795                 800 

Pro Ser His Ser Leu Glu Arg Gln Met Asn Gly Asn Gln Glu Lys Gly 
                805                 810                 815 

Asp Lys Thr Asp Arg Lys Lys Asp Lys Thr Gly Lys Glu Lys Lys Lys 
            820                 825                 830 

Asp Arg Asp Lys Glu Lys Asp Lys Met Lys Ala Lys Lys Gly Met Leu 
        835                 840                 845 

Lys Gly Leu Gly Asp Met Phe Ser Leu Ala Lys Leu Lys Pro Glu Lys 
    850                 855                 860 

Arg 
865 

 
           
             5  
             30  
             RNA  
             Artificial Sequence  
             
               Artificially Synthesized Sequence  
             
           
            5 

agcaucgagu cggccuuguu ggccuacugg                                      30 

 
           
             6  
             42  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            6 

gcggctgaag acggcctatg tggccttttt tttttttttt tt                        42 

 
           
             7  
             21  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            7 

agcatcgagt cggccttgtt g                                               21 

 
           
             8  
             21  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            8 

gcggctgaag acggcctatg t                                               21 

 
           
             9  
             433  
             PRT  
             Homo sapiens  
           
            9 

Met Glu Val Val Asp Pro Gln Gln Leu Gly Met Phe Thr Glu Gly Glu 
  1               5                  10                  15 

Leu Met Ser Val Gly Met Asp Thr Phe Ile His Arg Ile Asp Ser Thr 
             20                  25                  30 

Glu Val Ile Tyr Gln Pro Arg Arg Lys Arg Ala Lys Leu Ile Gly Lys 
         35                  40                  45 

Tyr Leu Met Gly Asp Leu Leu Gly Glu Gly Ser Tyr Gly Lys Val Lys 
     50                  55                  60 

Glu Val Leu Asp Ser Glu Thr Leu Cys Arg Arg Ala Val Lys Ile Leu 
 65                  70                  75                  80 

Lys Lys Lys Lys Leu Arg Arg Ile Pro Asn Gly Glu Ala Asn Val Lys 
                 85                  90                  95 

Lys Glu Ile Gln Leu Leu Arg Arg Leu Arg His Lys Asn Val Ile Gln 
            100                 105                 110 

Leu Val Asp Val Leu Tyr Asn Glu Glu Lys Gln Lys Met Tyr Met Val 
        115                 120                 125 

Met Glu Tyr Cys Val Cys Gly Met Gln Glu Met Leu Asp Ser Val Pro 
    130                 135                 140 

Glu Lys Arg Phe Pro Val Cys Gln Ala His Gly Tyr Phe Cys Gln Leu 
145                 150                 155                 160 

Ile Asp Gly Leu Glu Tyr Leu His Ser Gln Gly Ile Val His Lys Asp 
                165                 170                 175 

Ile Lys Pro Gly Asn Leu Leu Leu Thr Thr Gly Gly Thr Leu Lys Ile 
            180                 185                 190 

Ser Asp Leu Gly Val Ala Glu Ala Leu His Pro Phe Ala Ala Asp Asp 
        195                 200                 205 

Thr Cys Arg Thr Ser Gln Gly Ser Pro Ala Phe Gln Pro Pro Glu Ile 
    210                 215                 220 

Ala Asn Gly Leu Asp Thr Phe Ser Gly Phe Lys Val Asp Ile Trp Ser 
225                 230                 235                 240 

Ala Gly Val Thr Leu Tyr Asn Ile Thr Thr Gly Leu Tyr Pro Phe Glu 
                245                 250                 255 

Gly Asp Asn Ile Tyr Lys Leu Phe Glu Asn Ile Gly Lys Gly Ser Tyr 
            260                 265                 270 

Ala Ile Pro Gly Asp Cys Gly Pro Pro Leu Ser Asp Leu Leu Lys Gly 
        275                 280                 285 

Met Leu Glu Tyr Glu Pro Ala Lys Arg Phe Ser Ile Arg Gln Ile Arg 
    290                 295                 300 

Gln His Ser Trp Phe Arg Lys Lys His Pro Pro Ala Glu Ala Pro Val 
305                 310                 315                 320 

Pro Ile Pro Pro Ser Pro Asp Thr Lys Asp Arg Trp Arg Ser Met Thr 
                325                 330                 335 

Val Val Pro Tyr Leu Glu Asp Leu His Gly Ala Asp Glu Asp Glu Asp 
            340                 345                 350 

Leu Phe Asp Ile Glu Asp Asp Ile Ile Tyr Thr Gln Asp Phe Thr Val 
        355                 360                 365 

Pro Gly Gln Val Pro Glu Glu Glu Ala Ser His Asn Gly Gln Arg Arg 
    370                 375                 380 

Gly Leu Pro Lys Ala Val Cys Met Asn Gly Thr Glu Ala Ala Gln Leu 
385                 390                 395                 400 

Ser Thr Lys Ser Arg Ala Glu Gly Arg Ala Pro Asn Pro Ala Arg Lys 
                405                 410                 415 

Ala Cys Ser Ala Ser Ser Lys Ile Arg Arg Leu Ser Ala Cys Lys Gln 
            420                 425                 430 

Gln 

 
           
             10  
             396  
             PRT  
             Homo sapiens  
           
            10 

Met Pro Arg Val Lys Ala Ala Gln Ala Gly Arg Gln Ser Ser Ala Lys 
  1               5                  10                  15 

Arg His Leu Ala Glu Gln Phe Ala Val Gly Glu Ile Ile Thr Asp Met 
             20                  25                  30 

Ala Lys Lys Glu Trp Lys Val Gly Leu Pro Ile Gly Gln Gly Gly Phe 
         35                  40                  45 

Gly Cys Ile Tyr Leu Ala Asp Met Asn Ser Ser Glu Ser Val Gly Ser 
     50                  55                  60 

Asp Ala Pro Cys Val Val Lys Val Glu Pro Ser Asp Asn Gly Pro Leu 
 65                  70                  75                  80 

Phe Thr Glu Leu Lys Phe Tyr Gln Arg Ala Ala Lys Pro Glu Gln Ile 
                 85                  90                  95 

Gln Lys Trp Ile Arg Thr Arg Lys Leu Lys Tyr Leu Gly Val Pro Lys 
            100                 105                 110 

Tyr Trp Gly Ser Gly Leu His Asp Lys Asn Gly Lys Ser Tyr Arg Phe 
        115                 120                 125 

Met Ile Met Asp Arg Phe Gly Ser Asp Leu Gln Lys Ile Tyr Glu Ala 
    130                 135                 140 

Asn Ala Lys Arg Phe Ser Arg Lys Thr Val Leu Gln Leu Ser Leu Arg 
145                 150                 155                 160 

Ile Leu Asp Ile Leu Glu Tyr Ile His Glu His Glu Tyr Val His Gly 
                165                 170                 175 

Asp Ile Lys Ala Ser Asn Leu Leu Leu Asn Tyr Lys Asn Pro Asp Gln 
            180                 185                 190 

Val Tyr Leu Val Asp Tyr Gly Leu Ala Tyr Arg Tyr Cys Pro Glu Gly 
        195                 200                 205 

Val His Lys Glu Tyr Lys Glu Asp Pro Lys Arg Cys His Asp Gly Thr 
    210                 215                 220 

Ile Glu Phe Thr Ser Ile Asp Ala His Asn Gly Val Ala Pro Ser Arg 
225                 230                 235                 240 

Arg Gly Asp Leu Glu Ile Leu Gly Tyr Cys Met Ile Gln Trp Leu Thr 
                245                 250                 255 

Gly His Leu Pro Trp Glu Asp Asn Leu Lys Asp Pro Lys Tyr Val Arg 
            260                 265                 270 

Asp Ser Lys Ile Arg Tyr Arg Glu Asn Ile Ala Ser Leu Met Asp Lys 
        275                 280                 285 

Cys Phe Pro Glu Lys Asn Lys Pro Gly Glu Ile Ala Lys Tyr Met Glu 
    290                 295                 300 

Thr Val Lys Leu Leu Asp Tyr Thr Glu Lys Pro Leu Tyr Glu Asn Leu 
305                 310                 315                 320 

Arg Asp Ile Leu Leu Gln Gly Leu Lys Ala Ile Gly Ser Lys Asp Asp 
                325                 330                 335 

Gly Lys Leu Asp Leu Ser Val Val Glu Asn Gly Gly Leu Lys Ala Lys 
            340                 345                 350 

Thr Ile Thr Lys Lys Arg Lys Lys Glu Ile Glu Glu Ser Lys Glu Pro 
        355                 360                 365 

Gly Val Glu Asp Thr Glu Trp Ser Asn Thr Gln Thr Glu Glu Ala Ile 
    370                 375                 380 

Gln Thr Arg Ser Arg Thr Arg Lys Arg Val Gln Lys 
385                 390                 395 

 
           
             11  
             297  
             PRT  
             Homo sapiens  
           
            11 

Met Glu Asp Tyr Thr Lys Ile Glu Lys Ile Gly Glu Gly Thr Tyr Gly 
  1               5                  10                  15 

Val Val Tyr Lys Gly Arg His Lys Thr Thr Gly Gln Val Val Ala Met 
             20                  25                  30 

Lys Lys Ile Arg Leu Glu Ser Glu Glu Glu Gly Val Pro Ser Thr Ala 
         35                  40                  45 

Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Arg His Pro Asn Ile Val 
     50                  55                  60 

Ser Leu Gln Asp Val Leu Met Gln Asp Ser Arg Leu Tyr Leu Ile Phe 
 65                  70                  75                  80 

Glu Phe Leu Ser Met Asp Leu Lys Lys Tyr Leu Asp Ser Ile Pro Pro 
                 85                  90                  95 

Gly Gln Tyr Met Asp Ser Ser Leu Val Lys Ser Tyr Leu Tyr Gln Ile 
            100                 105                 110 

Leu Gln Gly Ile Val Phe Cys His Ser Arg Arg Val Leu His Arg Asp 
        115                 120                 125 

Leu Lys Pro Gln Asn Leu Leu Ile Asp Asp Lys Gly Thr Ile Lys Leu 
    130                 135                 140 

Ala Asp Phe Gly Leu Ala Arg Ala Phe Gly Ile Pro Ile Arg Val Tyr 
145                 150                 155                 160 

Thr His Glu Val Val Thr Leu Trp Tyr Arg Ser Pro Glu Val Leu Leu 
                165                 170                 175 

Gly Ser Ala Arg Tyr Ser Thr Pro Val Asp Ile Trp Ser Ile Gly Thr 
            180                 185                 190 

Ile Phe Ala Glu Leu Ala Thr Lys Lys Pro Leu Phe His Gly Asp Ser 
        195                 200                 205 

Glu Ile Asp Gln Leu Phe Arg Ile Phe Arg Ala Leu Gly Thr Pro Asn 
    210                 215                 220 

Asn Glu Val Trp Pro Glu Val Glu Ser Leu Gln Asp Tyr Lys Asn Thr 
225                 230                 235                 240 

Phe Pro Lys Trp Lys Pro Gly Ser Leu Ala Ser His Val Lys Asn Leu 
                245                 250                 255 

Asp Glu Asn Gly Leu Asp Leu Leu Ser Lys Met Leu Ile Tyr Asp Pro 
            260                 265                 270 

Ala Lys Arg Ile Ser Gly Lys Met Ala Leu Asn His Pro Tyr Phe Asn 
        275                 280                 285 

Asp Leu Asp Asn Gln Ile Lys Lys Met 
    290                 295 

 
           
             12  
             403  
             PRT  
             Homo sapiens  
           
            12 

Met Asp Arg Ser Lys Glu Asn Cys Ile Ser Gly Pro Val Lys Ala Thr 
  1               5                  10                  15 

Ala Pro Val Gly Gly Pro Lys Arg Val Leu Val Thr Gln Gln Phe Pro 
             20                  25                  30 

Cys Gln Asn Pro Leu Pro Val Asn Ser Gly Gln Ala Gln Arg Val Leu 
         35                  40                  45 

Cys Pro Ser Asn Ser Ser Gln Arg Ile Pro Leu Gln Ala Gln Lys Leu 
     50                  55                  60 

Val Ser Ser His Lys Pro Val Gln Asn Gln Lys Gln Lys Gln Leu Gln 
 65                  70                  75                  80 

Ala Thr Ser Val Pro His Pro Val Ser Arg Pro Leu Asn Asn Thr Gln 
                 85                  90                  95 

Lys Ser Lys Gln Pro Leu Pro Ser Ala Pro Glu Asn Asn Pro Glu Glu 
            100                 105                 110 

Glu Leu Ala Ser Lys Gln Lys Asn Glu Glu Ser Lys Lys Arg Gln Trp 
        115                 120                 125 

Ala Leu Glu Asp Phe Glu Ile Gly Arg Pro Leu Gly Lys Gly Lys Phe 
    130                 135                 140 

Gly Asn Val Tyr Leu Ala Arg Glu Lys Gln Ser Lys Phe Ile Leu Ala 
145                 150                 155                 160 

Leu Lys Val Leu Phe Lys Ala Gln Leu Glu Lys Ala Gly Val Glu His 
                165                 170                 175 

Gln Leu Arg Arg Glu Val Glu Ile Gln Ser His Leu Arg His Pro Asn 
            180                 185                 190 

Ile Leu Arg Leu Tyr Gly Tyr Phe His Asp Ala Thr Arg Val Tyr Leu 
        195                 200                 205 

Ile Leu Glu Tyr Ala Pro Leu Gly Thr Val Tyr Arg Glu Leu Gln Lys 
    210                 215                 220 

Leu Ser Lys Phe Asp Glu Gln Arg Thr Ala Thr Tyr Ile Thr Glu Leu 
225                 230                 235                 240 

Ala Asn Ala Leu Ser Tyr Cys His Ser Lys Arg Val Ile His Arg Asp 
                245                 250                 255 

Ile Lys Pro Glu Asn Leu Leu Leu Gly Ser Ala Gly Glu Leu Lys Ile 
            260                 265                 270 

Ala Asp Phe Gly Trp Ser Val His Ala Pro Ser Ser Arg Arg Thr Thr 
        275                 280                 285 

Leu Cys Gly Thr Leu Asp Tyr Leu Pro Pro Glu Met Ile Glu Gly Arg 
    290                 295                 300 

Met His Asp Glu Lys Val Asp Leu Trp Ser Leu Gly Val Leu Cys Tyr 
305                 310                 315                 320 

Glu Phe Leu Val Gly Lys Pro Pro Phe Glu Ala Asn Thr Tyr Gln Glu 
                325                 330                 335 

Thr Tyr Lys Arg Ile Ser Arg Val Glu Phe Thr Phe Pro Asp Phe Val 
            340                 345                 350 

Thr Glu Gly Ala Arg Asp Leu Ile Ser Arg Leu Leu Lys His Asn Pro 
        355                 360                 365 

Ser Gln Arg Pro Met Leu Arg Glu Val Leu Glu His Pro Trp Ile Thr 
    370                 375                 380 

Ala Asn Ser Ser Lys Pro Ser Asn Cys Gln Asn Lys Glu Ser Ala Ser 
385                 390                 395                 400 

Lys Gln Ser 

 
           
             13  
             344  
             PRT  
             Homo sapiens  
           
            13 

Met Ala Gln Lys Glu Asn Ser Tyr Pro Trp Pro Tyr Gly Arg Gln Thr 
  1               5                  10                  15 

Ala Pro Ser Gly Leu Ser Thr Leu Pro Gln Arg Val Leu Arg Lys Glu 
             20                  25                  30 

Pro Val Thr Pro Ser Ala Leu Val Leu Met Ser Arg Ser Asn Val Gln 
         35                  40                  45 

Pro Thr Ala Ala Pro Gly Gln Lys Val Met Glu Asn Ser Ser Gly Thr 
     50                  55                  60 

Pro Asp Ile Leu Thr Arg His Phe Thr Ile Asp Asp Phe Glu Ile Gly 
 65                  70                  75                  80 

Arg Pro Leu Gly Lys Gly Lys Phe Gly Asn Val Tyr Leu Ala Arg Glu 
                 85                  90                  95 

Lys Lys Ser His Phe Ile Val Ala Leu Lys Val Leu Phe Lys Ser Gln 
            100                 105                 110 

Ile Glu Lys Glu Gly Val Glu His Gln Leu Arg Arg Glu Ile Glu Ile 
        115                 120                 125 

Gln Ala His Leu His His Pro Asn Ile Leu Arg Leu Tyr Asn Tyr Phe 
    130                 135                 140 

Tyr Asp Arg Arg Arg Ile Tyr Leu Ile Leu Glu Tyr Ala Pro Arg Gly 
145                 150                 155                 160 

Glu Leu Tyr Lys Glu Leu Gln Lys Ser Cys Thr Phe Asp Glu Gln Arg 
                165                 170                 175 

Thr Ala Thr Ile Met Glu Glu Leu Ala Asp Ala Leu Met Tyr Cys His 
            180                 185                 190 

Gly Lys Lys Val Ile His Arg Asp Ile Lys Pro Glu Asn Leu Leu Leu 
        195                 200                 205 

Gly Leu Lys Gly Glu Leu Lys Ile Ala Asp Phe Gly Trp Ser Val His 
    210                 215                 220 

Ala Pro Ser Leu Arg Arg Lys Thr Met Cys Gly Thr Leu Asp Tyr Leu 
225                 230                 235                 240 

Pro Pro Glu Met Ile Glu Gly Arg Met His Asn Glu Lys Val Asp Leu 
                245                 250                 255 

Trp Cys Ile Gly Val Leu Cys Tyr Glu Leu Leu Val Gly Asn Pro Pro 
            260                 265                 270 

Phe Glu Ser Ala Ser His Asn Glu Thr Tyr Arg Arg Ile Val Lys Val 
        275                 280                 285 

Asp Leu Lys Phe Pro Ala Ser Val Pro Thr Gly Ala Gln Asp Leu Ile 
    290                 295                 300 

Ser Lys Leu Leu Arg His Asn Pro Ser Glu Arg Leu Pro Leu Ala Gln 
305                 310                 315                 320 

Val Ser Ala His Pro Trp Val Arg Ala Asn Ser Arg Arg Val Leu Pro 
                325                 330                 335 

Pro Ser Ala Leu Gln Ser Val Ala 
            340 

 
           
             14  
             745  
             PRT  
             Homo sapiens  
           
            14 

Met Glu Arg Pro Pro Gly Leu Arg Pro Gly Ala Gly Gly Pro Trp Glu 
  1               5                  10                  15 

Met Arg Glu Arg Leu Gly Thr Gly Gly Phe Gly Asn Val Cys Leu Tyr 
             20                  25                  30 

Gln His Arg Glu Leu Asp Leu Lys Ile Ala Ile Lys Ser Cys Arg Leu 
         35                  40                  45 

Glu Leu Ser Thr Lys Asn Arg Glu Arg Trp Cys His Glu Ile Gln Ile 
     50                  55                  60 

Met Lys Lys Leu Asn His Ala Asn Val Val Lys Ala Cys Asp Val Pro 
 65                  70                  75                  80 

Glu Glu Leu Asn Ile Leu Ile His Asp Val Pro Leu Leu Ala Met Glu 
                 85                  90                  95 

Tyr Cys Ser Gly Gly Asp Leu Arg Lys Leu Leu Asn Lys Pro Glu Asn 
            100                 105                 110 

Cys Cys Gly Leu Lys Glu Ser Gln Ile Leu Ser Leu Leu Ser Asp Ile 
        115                 120                 125 

Gly Ser Gly Ile Arg Tyr Leu His Glu Asn Lys Ile Ile His Arg Asp 
    130                 135                 140 

Leu Lys Pro Glu Asn Ile Val Leu Gln Asp Val Gly Gly Lys Ile Ile 
145                 150                 155                 160 

His Lys Ile Ile Asp Leu Gly Tyr Ala Lys Asp Val Asp Gln Gly Ser 
                165                 170                 175 

Leu Cys Thr Ser Phe Val Gly Thr Leu Gln Tyr Leu Ala Pro Glu Leu 
            180                 185                 190 

Phe Glu Asn Lys Pro Tyr Thr Ala Thr Val Asp Tyr Trp Ser Phe Gly 
        195                 200                 205 

Thr Met Val Phe Glu Cys Ile Ala Gly Tyr Arg Pro Phe Leu His His 
    210                 215                 220 

Leu Gln Pro Phe Thr Trp His Glu Lys Ile Lys Lys Lys Asp Pro Lys 
225                 230                 235                 240 

Cys Ile Phe Ala Cys Glu Glu Met Ser Gly Glu Val Arg Phe Ser Ser 
                245                 250                 255 

His Leu Pro Gln Pro Asn Ser Leu Cys Ser Leu Ile Val Glu Pro Met 
            260                 265                 270 

Glu Asn Trp Leu Gln Leu Met Leu Asn Trp Asp Pro Gln Gln Arg Gly 
        275                 280                 285 

Gly Pro Val Asp Leu Thr Leu Lys Gln Pro Arg Cys Phe Val Leu Met 
    290                 295                 300 

Asp His Ile Leu Asn Leu Lys Ile Val His Ile Leu Asn Met Thr Ser 
305                 310                 315                 320 

Ala Lys Ile Ile Ser Phe Leu Leu Pro Pro Asp Glu Ser Leu His Ser 
                325                 330                 335 

Leu Gln Ser Arg Ile Glu Arg Glu Thr Gly Ile Asn Thr Gly Ser Gln 
            340                 345                 350 

Glu Leu Leu Ser Glu Thr Gly Ile Ser Leu Asp Pro Arg Lys Pro Ala 
        355                 360                 365 

Ser Gln Cys Val Leu Asp Gly Val Arg Gly Cys Asp Ser Tyr Met Val 
    370                 375                 380 

Tyr Leu Phe Asp Lys Ser Lys Thr Val Tyr Glu Gly Pro Phe Ala Ser 
385                 390                 395                 400 

Arg Ser Leu Ser Asp Cys Val Asn Tyr Ile Val Gln Asp Ser Lys Ile 
                405                 410                 415 

Gln Leu Pro Ile Ile Gln Leu Arg Lys Val Trp Ala Glu Ala Val His 
            420                 425                 430 

Tyr Val Ser Gly Leu Lys Glu Asp Tyr Ser Arg Leu Phe Gln Gly Gln 
        435                 440                 445 

Arg Ala Ala Met Leu Ser Leu Leu Arg Tyr Asn Ala Asn Leu Thr Lys 
    450                 455                 460 

Met Lys Asn Thr Leu Ile Ser Ala Ser Gln Gln Leu Lys Ala Lys Leu 
465                 470                 475                 480 

Glu Phe Phe His Lys Ser Ile Gln Leu Asp Leu Glu Arg Tyr Ser Glu 
                485                 490                 495 

Gln Met Thr Tyr Gly Ile Ser Ser Glu Lys Met Leu Lys Ala Trp Lys 
            500                 505                 510 

Glu Met Glu Glu Lys Ala Ile His Tyr Ala Glu Val Gly Val Ile Gly 
        515                 520                 525 

Tyr Leu Glu Asp Gln Ile Met Ser Leu His Ala Glu Ile Met Glu Leu 
    530                 535                 540 

Gln Lys Ser Pro Tyr Gly Arg Arg Gln Gly Asp Leu Met Glu Ser Leu 
545                 550                 555                 560 

Glu Gln Arg Ala Ile Asp Leu Tyr Lys Gln Leu Lys His Arg Pro Ser 
                565                 570                 575 

Asp His Ser Tyr Ser Asp Ser Thr Glu Met Val Lys Ile Ile Val His 
            580                 585                 590 

Thr Val Gln Ser Gln Asp Arg Val Leu Lys Glu Leu Phe Gly His Leu 
        595                 600                 605 

Ser Lys Leu Leu Gly Cys Lys Gln Lys Ile Ile Asp Leu Leu Pro Lys 
    610                 615                 620 

Val Glu Val Ala Leu Ser Asn Ile Lys Glu Ala Asp Asn Thr Val Met 
625                 630                 635                 640 

Phe Met Gln Gly Lys Arg Gln Lys Glu Ile Trp His Leu Leu Lys Ile 
                645                 650                 655 

Ala Cys Thr Gln Ser Ser Ala Arg Ser Leu Val Gly Ser Ser Leu Glu 
            660                 665                 670 

Gly Ala Val Thr Pro Gln Thr Ser Ala Trp Leu Pro Pro Thr Ser Ala 
        675                 680                 685 

Glu His Asp His Ser Leu Ser Cys Val Val Thr Pro Gln Asp Gly Glu 
    690                 695                 700 

Thr Ser Ala Gln Met Ile Glu Glu Asn Leu Asn Cys Leu Gly His Leu 
705                 710                 715                 720 

Ser Thr Ile Ile His Glu Ala Asn Glu Glu Gln Gly Asn Ser Met Met 
                725                 730                 735 

Asn Leu Asp Trp Ser Trp Leu Thr Glu 
            740                 745 

 
           
             15  
             318  
             PRT  
             Homo sapiens  
           
            15 

Met Ser Lys Pro Pro Ala Pro Asn Pro Thr Pro Pro Arg Asn Leu Asp 
  1               5                  10                  15 

Ser Arg Thr Phe Ile Thr Ile Gly Asp Arg Asn Phe Glu Val Glu Ala 
             20                  25                  30 

Asp Asp Leu Val Thr Ile Ser Glu Leu Gly Arg Gly Ala Tyr Gly Val 
         35                  40                  45 

Val Glu Lys Val Arg His Ala Gln Ser Gly Thr Ile Met Ala Val Lys 
     50                  55                  60 

Arg Ile Arg Ala Thr Val Asn Ser Gln Glu Gln Lys Arg Leu Leu Met 
 65                  70                  75                  80 

Asp Leu Asp Ile Asn Met Arg Thr Val Asp Cys Phe Tyr Thr Val Thr 
                 85                  90                  95 

Phe Tyr Gly Ala Leu Phe Arg Glu Gly Asp Val Trp Ile Cys Met Glu 
            100                 105                 110 

Leu Met Asp Thr Ser Leu Asp Lys Phe Tyr Arg Lys Val Leu Asp Lys 
        115                 120                 125 

Asn Met Thr Ile Pro Glu Asp Ile Leu Gly Glu Ile Ala Val Ser Ile 
    130                 135                 140 

Val Arg Ala Leu Glu His Leu His Ser Lys Leu Ser Val Ile His Arg 
145                 150                 155                 160 

Asp Val Lys Pro Ser Asn Val Leu Ile Asn Lys Glu Gly His Val Lys 
                165                 170                 175 

Met Cys Asp Phe Gly Ile Ser Gly Tyr Leu Val Asp Ser Val Ala Lys 
            180                 185                 190 

Thr Met Asp Ala Gly Cys Lys Pro Tyr Met Ala Pro Glu Arg Ile Asn 
        195                 200                 205 

Pro Glu Leu Asn Gln Lys Gly Tyr Asn Val Lys Ser Asp Val Trp Ser 
    210                 215                 220 

Leu Gly Ile Thr Met Ile Glu Met Ala Ile Leu Arg Phe Pro Tyr Glu 
225                 230                 235                 240 

Ser Trp Gly Thr Pro Phe Gln Gln Leu Lys Gln Val Val Glu Glu Pro 
                245                 250                 255 

Ser Pro Gln Leu Pro Ala Asp Arg Phe Ser Pro Glu Phe Val Asp Phe 
            260                 265                 270 

Thr Ala Gln Cys Leu Arg Lys Asn Pro Ala Glu Arg Met Ser Tyr Leu 
        275                 280                 285 

Glu Leu Met Glu His Pro Phe Phe Thr Leu His Lys Thr Lys Lys Thr 
    290                 295                 300 

Asp Ile Ala Ala Phe Val Lys Lys Ile Leu Gly Glu Asp Ser 
305                 310                 315 

 
           
             16  
             379  
             PRT  
             Homo sapiens  
           
            16 

Met Ala Ala Ala Ala Ala Gln Gly Gly Gly Gly Gly Glu Pro Arg Arg 
  1               5                  10                  15 

Thr Glu Gly Val Gly Pro Gly Val Pro Gly Glu Val Glu Met Val Lys 
             20                  25                  30 

Gly Gln Pro Phe Asp Val Gly Pro Arg Tyr Thr Gln Leu Gln Tyr Ile 
         35                  40                  45 

Gly Glu Gly Ala Tyr Gly Met Val Ser Ser Ala Tyr Asp His Val Arg 
     50                  55                  60 

Lys Thr Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr 
 65                  70                  75                  80 

Tyr Cys Gln Arg Thr Leu Arg Glu Ile Gln Ile Leu Leu Arg Phe Arg 
                 85                  90                  95 

His Glu Asn Val Ile Gly Ile Arg Asp Ile Leu Arg Ala Ser Thr Leu 
            100                 105                 110 

Glu Ala Met Arg Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp 
        115                 120                 125 

Leu Tyr Lys Leu Leu Lys Ser Gln Gln Leu Ser Asn Asp His Ile Cys 
    130                 135                 140 

Tyr Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 
145                 150                 155                 160 

Asn Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Ser Asn Thr 
                165                 170                 175 

Thr Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Ile Ala Asp 
            180                 185                 190 

Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg 
        195                 200                 205 

Trp Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys 
    210                 215                 220 

Ser Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser 
225                 230                 235                 240 

Asn Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His 
                245                 250                 255 

Ile Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile 
            260                 265                 270 

Ile Asn Met Lys Ala Arg Asn Tyr Leu Gln Ser Leu Pro Ser Lys Thr 
        275                 280                 285 

Lys Val Ala Trp Ala Lys Leu Phe Pro Lys Ser Asp Ser Lys Ala Leu 
    290                 295                 300 

Asp Leu Leu Asp Arg Met Leu Thr Phe Asn Pro Asn Lys Arg Ile Thr 
305                 310                 315                 320 

Val Glu Glu Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro 
                325                 330                 335 

Thr Asp Glu Pro Val Ala Glu Glu Pro Phe Thr Phe Ala Met Glu Leu 
            340                 345                 350 

Asp Asp Leu Pro Lys Glu Arg Leu Lys Glu Leu Ile Phe Gln Glu Thr 
        355                 360                 365 

Ala Arg Phe Gln Pro Gly Val Leu Glu Ala Pro 
    370                 375 

 
           
             17  
             648  
             PRT  
             Homo sapiens  
           
            17 

Met Glu His Ile Gln Gly Ala Trp Lys Thr Ile Ser Asn Gly Phe Gly 
  1               5                  10                  15 

Phe Lys Asp Ala Val Phe Asp Gly Ser Ser Cys Ile Ser Pro Thr Ile 
             20                  25                  30 

Val Gln Gln Phe Gly Tyr Gln Arg Arg Ala Ser Asp Asp Gly Lys Leu 
         35                  40                  45 

Thr Asp Pro Ser Lys Thr Ser Asn Thr Ile Arg Val Phe Leu Pro Asn 
     50                  55                  60 

Lys Gln Arg Thr Val Val Asn Val Arg Asn Gly Met Ser Leu His Asp 
 65                  70                  75                  80 

Cys Leu Met Lys Ala Leu Lys Val Arg Gly Leu Gln Pro Glu Cys Cys 
                 85                  90                  95 

Ala Val Phe Arg Leu Leu His Glu His Lys Gly Lys Lys Ala Arg Leu 
            100                 105                 110 

Asp Trp Asn Thr Asp Ala Ala Ser Leu Ile Gly Glu Glu Leu Gln Val 
        115                 120                 125 

Asp Phe Leu Asp His Val Pro Leu Thr Thr His Asn Phe Ala Arg Lys 
    130                 135                 140 

Thr Phe Leu Lys Leu Ala Phe Cys Asp Ile Cys Gln Lys Phe Leu Leu 
145                 150                 155                 160 

Asn Gly Phe Arg Cys Gln Thr Cys Gly Tyr Lys Phe His Glu His Cys 
                165                 170                 175 

Ser Thr Lys Val Pro Thr Met Cys Val Asp Trp Ser Asn Ile Arg Gln 
            180                 185                 190 

Leu Leu Leu Phe Pro Asn Ser Thr Ile Gly Asp Ser Gly Val Pro Ala 
        195                 200                 205 

Leu Pro Ser Leu Thr Met Arg Arg Met Arg Glu Ser Val Ser Arg Met 
    210                 215                 220 

Pro Val Ser Ser Gln His Arg Tyr Ser Thr Pro His Ala Phe Thr Phe 
225                 230                 235                 240 

Asn Thr Ser Ser Pro Ser Ser Glu Gly Ser Leu Ser Gln Arg Gln Arg 
                245                 250                 255 

Ser Thr Ser Thr Pro Asn Val His Met Val Ser Thr Thr Leu Pro Val 
            260                 265                 270 

Asp Ser Arg Met Ile Glu Asp Ala Ile Arg Ser His Ser Glu Ser Ala 
        275                 280                 285 

Ser Pro Ser Ala Leu Ser Ser Ser Pro Asn Asn Leu Ser Pro Thr Gly 
    290                 295                 300 

Trp Ser Gln Pro Lys Thr Pro Val Pro Ala Gln Arg Glu Arg Ala Pro 
305                 310                 315                 320 

Val Ser Gly Thr Gln Glu Lys Asn Lys Ile Arg Pro Arg Gly Gln Arg 
                325                 330                 335 

Asp Ser Ser Tyr Tyr Trp Glu Ile Glu Ala Ser Glu Val Met Leu Ser 
            340                 345                 350 

Thr Arg Ile Gly Ser Gly Ser Phe Gly Thr Val Tyr Lys Gly Lys Trp 
        355                 360                 365 

His Gly Asp Val Ala Val Lys Ile Leu Lys Val Val Asp Pro Thr Pro 
    370                 375                 380 

Glu Gln Phe Gln Ala Phe Arg Asn Glu Val Ala Val Leu Arg Lys Thr 
385                 390                 395                 400 

Arg His Val Asn Ile Leu Leu Phe Met Gly Tyr Met Thr Lys Asp Asn 
                405                 410                 415 

Leu Ala Ile Val Thr Gln Trp Cys Glu Gly Ser Ser Leu Tyr Lys His 
            420                 425                 430 

Leu His Val Gln Glu Thr Lys Phe Gln Met Phe Gln Leu Ile Asp Ile 
        435                 440                 445 

Ala Arg Gln Thr Ala Gln Gly Met Asp Tyr Leu His Ala Lys Asn Ile 
    450                 455                 460 

Ile His Arg Asp Met Lys Ser Asn Asn Ile Phe Leu His Glu Gly Leu 
465                 470                 475                 480 

Thr Val Lys Ile Gly Asp Phe Gly Leu Ala Thr Val Lys Ser Arg Trp 
                485                 490                 495 

Ser Gly Ser Gln Gln Val Glu Gln Pro Thr Gly Ser Val Leu Trp Met 
            500                 505                 510 

Ala Pro Glu Val Ile Arg Met Gln Asp Asn Asn Pro Phe Ser Phe Gln 
        515                 520                 525 

Ser Asp Val Tyr Ser Tyr Gly Ile Val Leu Tyr Glu Leu Met Thr Gly 
    530                 535                 540 

Glu Leu Pro Tyr Ser His Ile Asn Asn Arg Asp Gln Ile Ile Phe Met 
545                 550                 555                 560 

Val Gly Arg Gly Tyr Ala Ser Pro Asp Leu Ser Lys Leu Tyr Lys Asn 
                565                 570                 575 

Cys Pro Lys Ala Met Lys Arg Leu Val Ala Asp Cys Val Lys Lys Val 
            580                 585                 590 

Lys Glu Glu Arg Pro Leu Phe Pro Gln Ile Leu Ser Ser Ile Glu Leu 
        595                 600                 605 

Leu Gln His Ser Leu Pro Lys Ile Asn Arg Ser Ala Ser Glu Pro Ser 
    610                 615                 620 

Leu His Arg Ala Ala His Thr Glu Asp Ile Asn Ala Cys Thr Leu Thr 
625                 630                 635                 640 

Thr Ser Pro Arg Leu Pro Val Phe 
                645 

 
           
             18  
             480  
             PRT  
             Homo sapiens  
           
            18 

Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly 
  1               5                  10                  15 

Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp 
             20                  25                  30 

Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg 
         35                  40                  45 

Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys 
     50                  55                  60 

Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp 
 65                  70                  75                  80 

Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg 
                 85                  90                  95 

Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys 
            100                 105                 110 

Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn 
        115                 120                 125 

Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg 
    130                 135                 140 

Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr 
145                 150                 155                 160 

Phe Gly Lys Val Ile Leu Val Lys Glu Lys Ala Thr Gly Arg Tyr Tyr 
                165                 170                 175 

Ala Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val 
            180                 185                 190 

Ala His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro 
        195                 200                 205 

Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys 
    210                 215                 220 

Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser 
225                 230                 235                 240 

Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu 
                245                 250                 255 

Ile Val Ser Ala Leu Asp Tyr Leu His Ser Glu Lys Asn Val Val Tyr 
            260                 265                 270 

Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile 
        275                 280                 285 

Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala 
    290                 295                 300 

Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val 
305                 310                 315                 320 

Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly 
                325                 330                 335 

Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln 
            340                 345                 350 

Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe 
        355                 360                 365 

Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu 
    370                 375                 380 

Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys 
385                 390                 395                 400 

Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val 
                405                 410                 415 

Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu 
            420                 425                 430 

Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr 
        435                 440                 445 

Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu 
    450                 455                 460 

Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Ser Thr Ala 
465                 470                 475                 480 

 
           
             19  
             724  
             PRT  
             Homo sapiens  
           
            19 

Met Ser Ala Glu Gly Tyr Gln Tyr Arg Ala Leu Tyr Asp Tyr Lys Lys 
  1               5                  10                  15 

Glu Arg Glu Glu Asp Ile Asp Leu His Leu Gly Asp Ile Leu Thr Val 
             20                  25                  30 

Asn Lys Gly Ser Leu Val Ala Leu Gly Phe Ser Asp Gly Gln Glu Ala 
         35                  40                  45 

Arg Pro Glu Glu Ile Gly Trp Leu Asn Gly Tyr Asn Glu Thr Thr Gly 
     50                  55                  60 

Glu Arg Gly Asp Phe Pro Gly Thr Tyr Val Glu Tyr Ile Gly Arg Lys 
 65                  70                  75                  80 

Lys Ile Ser Pro Pro Thr Pro Lys Pro Arg Pro Pro Arg Pro Leu Pro 
                 85                  90                  95 

Val Ala Pro Gly Ser Ser Lys Thr Glu Ala Asp Val Glu Gln Gln Ala 
            100                 105                 110 

Leu Thr Leu Pro Asp Leu Ala Glu Gln Phe Ala Pro Pro Asp Ile Ala 
        115                 120                 125 

Pro Pro Leu Leu Ile Lys Leu Val Glu Ala Ile Glu Lys Lys Gly Leu 
    130                 135                 140 

Glu Cys Ser Thr Leu Tyr Arg Thr Gln Ser Ser Ser Asn Leu Ala Glu 
145                 150                 155                 160 

Leu Arg Gln Leu Leu Asp Cys Asp Thr Pro Ser Val Asp Leu Glu Met 
                165                 170                 175 

Ile Asp Val His Val Leu Ala Asp Ala Phe Lys Arg Tyr Leu Leu Asp 
            180                 185                 190 

Leu Pro Asn Pro Val Ile Pro Ala Ala Val Tyr Ser Glu Met Ile Ser 
        195                 200                 205 

Leu Ala Pro Glu Val Gln Ser Ser Glu Glu Tyr Ile Gln Leu Leu Lys 
    210                 215                 220 

Lys Leu Ile Arg Ser Pro Ser Ile Pro His Gln Tyr Trp Leu Thr Leu 
225                 230                 235                 240 

Gln Tyr Leu Leu Lys His Phe Phe Lys Leu Ser Gln Thr Ser Ser Lys 
                245                 250                 255 

Asn Leu Leu Asn Ala Arg Val Leu Ser Glu Ile Phe Ser Pro Met Leu 
            260                 265                 270 

Phe Arg Phe Ser Ala Ala Ser Ser Asp Asn Thr Glu Asn Leu Ile Lys 
        275                 280                 285 

Val Ile Glu Ile Leu Ile Ser Thr Glu Trp Asn Glu Arg Gln Pro Ala 
    290                 295                 300 

Pro Ala Leu Pro Pro Lys Pro Pro Lys Pro Thr Thr Val Ala Asn Asn 
305                 310                 315                 320 

Gly Met Asn Asn Asn Met Ser Leu Gln Asn Ala Glu Trp Tyr Trp Gly 
                325                 330                 335 

Asp Ile Ser Arg Glu Glu Val Asn Glu Lys Leu Arg Asp Thr Ala Asp 
            340                 345                 350 

Gly Thr Phe Leu Val Arg Asp Ala Ser Thr Lys Met His Gly Asp Tyr 
        355                 360                 365 

Thr Leu Thr Leu Arg Lys Gly Gly Asn Asn Lys Leu Ile Lys Ile Phe 
    370                 375                 380 

His Arg Asp Gly Lys Tyr Gly Phe Ser Asp Pro Leu Thr Phe Ser Ser 
385                 390                 395                 400 

Val Val Glu Leu Ile Asn His Tyr Arg Asn Glu Ser Leu Ala Gln Tyr 
                405                 410                 415 

Asn Pro Lys Leu Asp Val Lys Leu Leu Tyr Pro Val Ser Lys Tyr Gln 

            420                 425                 430 
Gln Asp Gln Val Val Lys Glu Asp Asn Ile Glu Ala Val Gly Lys Lys 

        435                 440                 445 
Leu His Glu Tyr Asn Thr Gln Phe Gln Glu Lys Ser Arg Glu Tyr Asp 

    450                 455                 460 
Arg Leu Tyr Glu Glu Tyr Thr Arg Thr Ser Gln Glu Ile Gln Met Lys 

465                 470                 475                 480 
Arg Thr Ala Ile Glu Ala Phe Asn Glu Thr Ile Lys Ile Phe Glu Glu 

                485                 490                 495 
Gln Cys Gln Thr Gln Glu Arg Tyr Ser Lys Glu Tyr Ile Glu Lys Phe 

            500                 505                 510 
Lys Arg Glu Gly Asn Glu Lys Glu Ile Gln Arg Ile Met His Asn Tyr 

        515                 520                 525 
Asp Lys Leu Lys Ser Arg Ile Ser Glu Ile Ile Asp Ser Arg Arg Arg 

    530                 535                 540 
Leu Glu Glu Asp Leu Lys Lys Gln Ala Ala Glu Tyr Arg Glu Ile Asp 

545                 550                 555                 560 
Lys Arg Met Asn Ser Ile Lys Pro Asp Leu Ile Gln Leu Arg Lys Thr 

                565                 570                 575 
Arg Asp Gln Tyr Leu Met Trp Leu Thr Gln Lys Gly Val Arg Gln Lys 

            580                 585                 590 
Lys Leu Asn Glu Trp Leu Gly Asn Glu Asn Thr Glu Asp Gln Tyr Ser 

        595                 600                 605 
Leu Val Glu Asp Asp Glu Asp Leu Pro His His Asp Glu Lys Thr Trp 

    610                 615                 620 
Asn Val Gly Ser Ser Asn Arg Asn Lys Ala Glu Asn Leu Leu Arg Gly 

625                 630                 635                 640 
Lys Arg Asp Gly Thr Phe Leu Val Arg Glu Ser Ser Lys Gln Gly Cys 

                645                 650                 655 
Tyr Ala Cys Ser Val Val Val Asp Gly Glu Val Lys His Cys Val Ile 

            660                 665                 670 
Asn Lys Thr Ala Thr Gly Tyr Gly Phe Ala Glu Pro Tyr Asn Leu Tyr 

        675                 680                 685 
Ser Ser Leu Lys Glu Leu Val Leu His Tyr Gln His Thr Ser Leu Val 

    690                 695                 700 
Gln His Asn Asp Ser Leu Asn Val Thr Leu Ala Tyr Pro Val Tyr Ala 

705                 710                 715                 720 
Gln Gln Arg Arg 

 
           
             20  
             3056  
             PRT  
             Homo sapiens  
           
            20 

Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg Gln Leu Glu 
  1               5                  10                  15 

His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys Phe Lys Arg 
             20                  25                  30 

Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg His Ser Asp 
         35                  40                  45 

Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val Phe Arg Phe Leu 
     50                  55                  60 

Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu Arg Ile Ala Lys Pro 
 65                  70                  75                  80 

Asn Val Ser Ala Ser Thr Gln Ala Ser Arg Gln Lys Lys Met Gln Glu 
                 85                  90                  95 

Ile Ser Ser Leu Val Lys Tyr Phe Ile Lys Cys Ala Asn Arg Arg Ala 
            100                 105                 110 

Pro Arg Leu Lys Cys Gln Glu Leu Leu Asn Tyr Ile Met Asp Thr Val 
        115                 120                 125 

Lys Asp Ser Ser Asn Gly Ala Ile Tyr Gly Ala Asp Cys Ser Asn Ile 
    130                 135                 140 

Leu Leu Lys Asp Ile Leu Ser Val Arg Lys Tyr Trp Cys Glu Ile Ser 
145                 150                 155                 160 

Gln Gln Gln Trp Leu Glu Leu Phe Ser Val Tyr Phe Arg Leu Tyr Leu 
                165                 170                 175 

Lys Pro Ser Gln Asp Val His Arg Val Leu Val Ala Arg Ile Ile His 
            180                 185                 190 

Ala Val Thr Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu Asn Ser Lys 
        195                 200                 205 

Phe Leu Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg Gln Glu Lys 
    210                 215                 220 

Ser Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr Ile Phe Leu 
225                 230                 235                 240 

Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu Leu Gly Asp 
                245                 250                 255 

Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His Arg Leu Asn 
            260                 265                 270 

Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu Gln Ile Tyr 
        275                 280                 285 

Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys Gly Ala Tyr Glu 
    290                 295                 300 

Ser Thr Lys Trp Arg Ser Ile Leu Tyr Asn Leu Tyr Asp Leu Leu Val 
305                 310                 315                 320 

Asn Glu Ile Ser His Ile Gly Ser Arg Gly Lys Tyr Ser Ser Gly Phe 
                325                 330                 335 

Arg Asn Ile Ala Val Lys Glu Asn Leu Ile Glu Leu Met Ala Asp Ile 
            340                 345                 350 

Cys His Gln Val Phe Asn Glu Asp Thr Arg Ser Leu Glu Ile Ser Gln 
        355                 360                 365 

Ser Tyr Thr Thr Thr Gln Arg Glu Ser Ser Asp Tyr Ser Val Pro Cys 
    370                 375                 380 

Lys Arg Lys Lys Ile Glu Leu Gly Trp Glu Val Ile Lys Asp His Leu 
385                 390                 395                 400 

Gln Lys Ser Gln Asn Asp Phe Asp Leu Val Pro Trp Leu Gln Ile Ala 
                405                 410                 415 

Thr Gln Leu Ile Ser Lys Tyr Pro Ala Ser Leu Pro Asn Cys Glu Leu 
            420                 425                 430 

Ser Pro Leu Leu Met Ile Leu Ser Gln Leu Leu Pro Gln Gln Arg His 
        435                 440                 445 

Gly Glu Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu Val Ala Leu 
    450                 455                 460 

Cys Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys Ser Asp Leu 
465                 470                 475                 480 

Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg Gly Ile Ser 
                485                 490                 495 

Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly Ala Ile Ile 
            500                 505                 510 

Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys Leu Phe Thr 
        515                 520                 525 

Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys Cys Leu Thr Leu 
    530                 535                 540 

Ala Leu Thr Thr Ser Ile Val Pro Gly Ala Val Lys Met Gly Ile Glu 
545                 550                 555                 560 

Gln Asn Met Cys Glu Val Asn Arg Ser Phe Ser Leu Lys Glu Ser Ile 
                565                 570                 575 

Met Lys Trp Leu Leu Phe Tyr Gln Leu Glu Gly Asp Leu Glu Asn Ser 
            580                 585                 590 

Thr Glu Val Pro Pro Ile Leu His Ser Asn Phe Pro His Leu Val Leu 
        595                 600                 605 

Glu Lys Ile Leu Val Ser Leu Thr Met Lys Asn Cys Lys Ala Ala Met 
    610                 615                 620 

Asn Phe Phe Gln Ser Val Pro Glu Cys Glu His His Gln Lys Asp Lys 
625                 630                 635                 640 

Glu Glu Leu Ser Phe Ser Glu Val Glu Glu Leu Phe Leu Gln Thr Thr 
                645                 650                 655 

Phe Asp Lys Met Asp Phe Leu Thr Ile Val Arg Glu Cys Gly Ile Glu 
            660                 665                 670 

Lys His Gln Ser Ser Ile Gly Phe Ser Val His Gln Asn Leu Lys Glu 
        675                 680                 685 

Ser Leu Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu Leu Asn Asn 
    690                 695                 700 

Tyr Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg Cys Ser Arg 
705                 710                 715                 720 

Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly Val Ile Ala 
                725                 730                 735 

Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala Asn Ser Leu 
            740                 745                 750 

Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn Lys Thr Asn 
        755                 760                 765 

Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met Gln Leu Cys Thr 
    770                 775                 780 

Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro Asn Lys Ile Ala Ser 
785                 790                 795                 800 

Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys Leu Met Asn Asp Ile Ala 
                805                 810                 815 

Asp Ile Cys Lys Ser Leu Ala Ser Phe Ile Lys Lys Pro Phe Asp Arg 
            820                 825                 830 

Gly Glu Val Glu Ser Met Glu Asp Asp Thr Asn Gly Asn Leu Met Glu 
        835                 840                 845 

Val Glu Asp Gln Ser Ser Met Asn Leu Phe Asn Asp Tyr Pro Asp Ser 
    850                 855                 860 

Ser Val Ser Asp Ala Asn Glu Pro Gly Glu Ser Gln Ser Thr Ile Gly 
865                 870                 875                 880 

Ala Ile Asn Pro Leu Ala Glu Glu Tyr Leu Ser Lys Gln Asp Leu Leu 
                885                 890                 895 

Phe Leu Asp Met Leu Lys Phe Leu Cys Leu Cys Val Thr Thr Ala Gln 
            900                 905                 910 

Thr Asn Thr Val Ser Phe Arg Ala Ala Asp Ile Arg Arg Lys Leu Leu 
        915                 920                 925 

Met Leu Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser Leu His Leu 
    930                 935                 940 

His Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu Glu Tyr Pro 
945                 950                 955                 960 

Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu Ser Asn Val 
                965                 970                 975 

Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr Ile Leu Asn 
            980                 985                 990 

His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn Met Asp Ser 
        995                1000                1005 

Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr Val Ile Gly Ala 
   1010                1015                1020 

Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Phe Ser Val Arg Met 
1025               1030                1035                1040 

Ala Leu Val Asn Cys Leu Lys Thr Leu Leu Glu Ala Asp Pro Tyr Ser 
               1045                1050                1055 

Lys Trp Ala Ile Leu Asn Val Met Gly Lys Asp Phe Pro Val Asn Glu 
           1060                1065                1070 

Val Phe Thr Gln Phe Leu Ala Asp Asn His His Gln Val Arg Met Leu 
       1075                1080                1085 

Ala Ala Glu Ser Ile Asn Arg Leu Phe Gln Asp Thr Lys Gly Asp Ser 
   1090                1095                1100 

Ser Arg Leu Leu Lys Ala Leu Pro Leu Lys Leu Gln Gln Thr Ala Phe 
1105               1110                1115                1120 

Glu Asn Ala Tyr Leu Lys Ala Gln Glu Gly Met Arg Glu Met Ser His 
               1125                1130                1135 

Ser Ala Glu Asn Pro Glu Thr Leu Asp Glu Ile Tyr Asn Arg Lys Ser 
           1140                1145                1150 

Val Leu Leu Thr Leu Ile Ala Val Val Leu Ser Cys Ser Pro Ile Cys 
       1155                1160                1165 

Glu Lys Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys Glu Asn Gly 
   1170                1175                1180 

Leu Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val Ser Glu Thr 
1185               1190                1195                1200 

Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His Leu Asp Tyr 
               1205                1210                1215 

Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr Asn Leu Ser 
           1220                1225                1230 

Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu Asp Phe Tyr 
       1235                1240                1245 

Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val Ile Arg Ser His 
   1250                1255                1260 

Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile Gln Glu Asp Trp Lys 
1265               1270                1275                1280 

Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile Leu Val Asn Ile Leu Pro 
               1285                1290                1295 

Tyr Phe Ala Tyr Glu Gly Thr Arg Asp Ser Gly Met Ala Gln Gln Arg 
           1300                1305                1310 

Glu Thr Ala Thr Lys Val Tyr Asp Met Leu Lys Ser Glu Asn Leu Leu 
       1315                1320                1325 

Gly Lys Gln Ile Asp His Leu Phe Ile Ser Asn Leu Pro Glu Ile Val 
   1330                1335                1340 

Val Glu Leu Leu Met Thr Leu His Glu Pro Ala Asn Ser Ser Ala Ser 
1345               1350                1355                1360 

Gln Ser Thr Asp Leu Cys Asp Phe Ser Gly Asp Leu Asp Pro Ala Pro 
               1365                1370                1375 

Asn Pro Pro His Phe Pro Ser His Val Ile Lys Ala Thr Phe Ala Tyr 
           1380                1385                1390 

Ile Ser Asn Cys His Lys Thr Lys Leu Lys Ser Ile Leu Glu Ile Leu 
       1395                1400                1405 

Ser Lys Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala Ile Cys Glu 
   1410                1415                1420 

Gln Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg Ile Leu Lys 
1425               1430                1435                1440 

Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile Lys Ser Gly 
               1445                1450                1455 

Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile Tyr Thr Leu 
           1460                1465                1470 

Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp Val Ser Leu 
       1475                1480                1485 

Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln Val Cys Gln Thr 
   1490                1495                1500 

Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn His Leu His Val Ile 
1505               1510                1515                1520 

Val Gly Thr Leu Ile Pro Leu Val Tyr Glu Gln Val Glu Val Gln Lys 
               1525                1530                1535 

Gln Val Leu Asp Leu Leu Lys Tyr Leu Val Ile Asp Asn Lys Asp Asn 
           1540                1545                1550 

Glu Asn Leu Tyr Ile Thr Ile Lys Leu Leu Asp Pro Phe Pro Asp His 
       1555                1560                1565 

Val Val Phe Lys Asp Leu Arg Ile Thr Gln Gln Lys Ile Lys Tyr Ser 
   1570                1575                1580 

Arg Gly Pro Phe Ser Leu Leu Glu Glu Ile Asn His Phe Leu Ser Val 
1585               1590                1595                1600 

Ser Val Tyr Asp Ala Leu Pro Leu Thr Arg Leu Glu Gly Leu Lys Asp 
               1605                1610                1615 

Leu Arg Arg Gln Leu Glu Leu His Lys Asp Gln Met Val Asp Ile Met 
           1620                1625                1630 

Arg Ala Ser Gln Asp Asn Pro Gln Asp Gly Ile Met Val Lys Leu Val 
       1635                1640                1645 

Val Asn Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His Thr Gly Glu 
   1650                1655                1660 

Lys Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu Val Gly Pro 
1665               1670                1675                1680 

Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp Ala Ser Tyr 
               1685                1690                1695 

Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln Trp Thr Phe 
           1700                1705                1710 

Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp Cys Val Lys 
       1715                1720                1725 

Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile Leu Ala Thr Lys 
   1730                1735                1740 

Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met Thr Thr Asp Pro Met 
1745               1750                1755                1760 

Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser Arg Lys Lys Phe Leu Glu 
               1765                1770                1775 

Val Pro Arg Phe Asp Lys Glu Asn Pro Phe Glu Gly Leu Asp Asp Ile 
           1780                1785                1790 

Asn Leu Trp Ile Pro Leu Ser Glu Asn His Asp Ile Trp Ile Lys Thr 
       1795                1800                1805 

Leu Thr Cys Ala Phe Leu Asp Ser Gly Gly Thr Lys Cys Glu Ile Leu 
   1810                1815                1820 

Gln Leu Leu Lys Pro Met Cys Glu Val Lys Thr Asp Phe Cys Gln Thr 
1825               1830                1835                1840 

Val Leu Pro Tyr Leu Ile His Asp Ile Leu Leu Gln Asp Thr Asn Glu 
               1845                1850                1855 

Ser Trp Arg Asn Leu Leu Ser Thr His Val Gln Gly Phe Phe Thr Ser 
           1860                1865                1870 

Cys Leu Arg His Phe Ser Gln Thr Ser Arg Ser Thr Thr Pro Ala Asn 
       1875                1880                1885 

Leu Asp Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu Asp Lys Lys 
   1890                1895                1900 

Ser Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg Arg Gln Lys 
1905               1910                1915                1920 

Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp Leu Asp Leu 
               1925                1930                1935 

Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala Ala His Phe 
           1940                1945                1950 

Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys Ser Met Asp 
       1955                1960                1965 

Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly Ser Gln Ser Thr 
   1970                1975                1980 

Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu Glu Thr Gly Ile Ser 
1985               1990                1995                2000 

Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg Ser Ile Gly Glu Pro Asp 
               2005                2010                2015 

Ser Leu Tyr Gly Cys Gly Gly Gly Lys Met Leu Gln Pro Ile Thr Arg 
           2020                2025                2030 

Leu Arg Thr Tyr Glu His Glu Ala Met Trp Gly Lys Ala Leu Val Thr 
       2035                2040                2045 

Tyr Asp Leu Glu Thr Ala Ile Pro Ser Ser Thr Arg Gln Ala Gly Ile 
   2050                2055                2060 

Ile Gln Ala Leu Gln Asn Leu Gly Leu Cys His Ile Leu Ser Val Tyr 
2065               2070                2075                2080 

Leu Lys Gly Leu Asp Tyr Glu Asn Lys Asp Trp Cys Pro Glu Leu Glu 
               2085                2090                2095 

Glu Leu His Tyr Gln Ala Ala Trp Arg Asn Met Gln Trp Asp His Cys 
           2100                2105                2110 

Thr Ser Val Ser Lys Glu Val Glu Gly Thr Ser Tyr His Glu Ser Leu 
       2115                2120                2125 

Tyr Asn Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser Thr Phe Tyr 
   2130                2135                2140 

Glu Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu Met Cys Lys 
2145               2150                2155                2160 

Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu Ser Arg Leu 
               2165                2170                2175 

Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe Ser Arg Ser 
           2180                2185                2190 

Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp Gln Lys His 
       2195                2200                2205 

Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln Glu Pro Ile Met 
   2210                2215                2220 

Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met Glu Lys Glu Met Asp 
2225               2230                2235                2240 

Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile Leu Thr Lys His Leu Val 
               2245                2250                2255 

Glu Leu Ser Ile Leu Ala Arg Thr Phe Lys Asn Thr Gln Leu Pro Glu 
           2260                2265                2270 

Arg Ala Ile Phe Gln Ile Lys Gln Tyr Asn Ser Val Ser Cys Gly Val 
       2275                2280                2285 

Ser Glu Trp Gln Leu Glu Glu Ala Gln Val Phe Trp Ala Lys Lys Glu 
   2290                2295                2300 

Gln Ser Leu Ala Leu Ser Ile Leu Lys Gln Met Ile Lys Lys Leu Asp 
2305               2310                2315                2320 

Ala Ser Cys Ala Ala Asn Asn Pro Ser Leu Lys Leu Thr Tyr Thr Glu 
               2325                2330                2335 

Cys Leu Arg Val Cys Gly Asn Trp Leu Ala Glu Thr Cys Leu Glu Asn 
           2340                2345                2350 

Pro Ala Val Ile Met Gln Thr Tyr Leu Glu Lys Ala Val Glu Val Ala 
       2355                2360                2365 

Gly Asn Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn Gly Lys Met 
   2370                2375                2380 

Lys Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln Tyr Gln Arg 
2385               2390                2395                2400 

Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys Gln Ala Leu 
               2405                2410                2415 

Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu His Lys Ile 
           2420                2425                2430 

Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu Glu Leu Asp 
       2435                2440                2445 

Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg Lys Arg Phe Leu Cys 
   2450                2455                2460 

Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu Ser Gly Glu Glu His 
2465               2470                2475                2480 

Asp Met Trp Val Phe Arg Leu Cys Ser Leu Trp Leu Glu Asn Ser Gly 
               2485                2490                2495 

Val Ser Glu Val Asn Gly Met Met Lys Arg Asp Gly Met Lys Ile Pro 
           2500                2505                2510 

Thr Tyr Lys Phe Leu Pro Leu Met Tyr Gln Leu Ala Ala Arg Met Gly 
       2515                2520                2525 

Thr Lys Met Met Gly Gly Leu Gly Phe His Glu Val Leu Asn Asn Leu 
   2530                2535                2540 

Ile Ser Arg Ile Ser Met Asp His Pro His His Thr Leu Phe Ile Ile 
2545               2550                2555                2560 

Leu Ala Leu Ala Asn Ala Asn Arg Asp Glu Phe Leu Thr Lys Pro Glu 
               2565                2570                2575 

Val Ala Arg Arg Ser Arg Ile Thr Lys Asn Val Pro Lys Gln Ser Ser 
           2580                2585                2590 

Gln Leu Asp Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile Ile Cys Thr 
       2595                2600                2605 

Ile Arg Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu Ala Leu Cys 
   2610                2615                2620 

Asp Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln Trp Lys Thr 
2625               2630                2635                2640 

Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile Thr Lys Leu 
               2645                2650                2655 

Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile Lys Val Asp 
           2660                2665                2670 

His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser Phe Lys Ala 
       2675                2680                2685 

Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys Ile Ile Asp Cys 
   2690                2695                2700 

Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu Val Lys Gly Arg Asp 
2705               2710                2715                2720 

Asp Leu Arg Gln Asp Ala Val Met Gln Gln Val Phe Gln Met Cys Asn 
               2725                2730                2735 

Thr Leu Leu Gln Arg Asn Thr Glu Thr Arg Lys Arg Lys Leu Thr Ile 
           2740                2745                2750 

Cys Thr Tyr Lys Val Val Pro Leu Ser Gln Arg Ser Gly Val Leu Glu 
       2755                2760                2765 

Trp Cys Thr Gly Thr Val Pro Ile Gly Glu Phe Leu Val Asn Asn Glu 
   2770                2775                2780 

Asp Gly Ala His Lys Arg Tyr Arg Pro Asn Asp Phe Ser Ala Phe Gln 
2785               2790                2795                2800 

Cys Gln Lys Lys Met Met Glu Val Gln Lys Lys Ser Phe Glu Glu Lys 
               2805                2810                2815 

Tyr Glu Val Phe Met Asp Val Cys Gln Asn Phe Gln Pro Val Phe Arg 
           2820                2825                2830 

Tyr Phe Cys Met Glu Lys Phe Leu Asp Pro Ala Ile Trp Phe Glu Lys 
       2835                2840                2845 

Arg Leu Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile Val Gly Tyr 
   2850                2855                2860 

Ile Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu Ile Asn Glu 
2865               2870                2875                2880 

Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala Phe Glu Gln 
               2885                2890                2895 

Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg Leu Thr Arg 
           2900                2905                2910 

Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly Val Phe Arg 
       2915                2920                2925 

Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn Ser Gln Glu Thr 
   2930                2935                2940 

Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp Pro Leu Phe Asp Trp 
2945               2950                2955                2960 

Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu Gln Gln Arg Pro Glu Asp 
               2965                2970                2975 

Glu Thr Glu Leu His Pro Thr Leu Asn Ala Asp Asp Gln Glu Cys Lys 
           2980                2985                2990 

Arg Asn Leu Ser Asp Ile Asp Gln Ser Phe Asp Lys Val Ala Glu Arg 
       2995                3000                3005 

Val Leu Met Arg Leu Gln Glu Lys Leu Lys Gly Val Glu Glu Gly Thr 
   3010                3015                3020 

Val Leu Ser Val Gly Gly Gln Val Asn Leu Leu Ile Gln Gln Ala Ile 
3025               3030                3035                3040 

Asp Pro Lys Asn Leu Ser Arg Leu Phe Pro Gly Trp Lys Ala Trp Val 
               3045                3050                3055 

 
           
             21  
             450  
             PRT  
             Homo sapiens  
           
            21 

Met Ser Ala Ile Gln Ala Ala Trp Pro Ser Gly Thr Glu Cys Ile Ala 
  1               5                  10                  15 

Lys Tyr Asn Phe His Gly Thr Ala Glu Gln Asp Leu Pro Phe Cys Lys 
             20                  25                  30 

Gly Asp Val Leu Thr Ile Val Ala Val Thr Lys Asp Pro Asn Trp Tyr 
         35                  40                  45 

Lys Ala Lys Asn Lys Val Gly Arg Glu Gly Ile Ile Pro Ala Asn Tyr 
     50                  55                  60 

Val Gln Lys Arg Glu Gly Val Lys Ala Gly Thr Lys Leu Ser Leu Met 
 65                  70                  75                  80 

Pro Trp Phe His Gly Lys Ile Thr Arg Glu Gln Ala Glu Arg Leu Leu 
                 85                  90                  95 

Tyr Pro Pro Glu Thr Gly Leu Phe Leu Val Arg Glu Ser Thr Asn Tyr 
            100                 105                 110 

Pro Gly Asp Tyr Thr Leu Cys Val Ser Cys Asp Gly Lys Val Glu His 
        115                 120                 125 

Tyr Arg Ile Met Tyr His Ala Ser Lys Leu Ser Ile Asp Glu Glu Val 
    130                 135                 140 

Tyr Phe Glu Asn Leu Met Gln Leu Val Glu His Tyr Thr Ser Asp Ala 
145                 150                 155                 160 

Asp Gly Leu Cys Thr Arg Leu Ile Lys Pro Lys Val Met Glu Gly Thr 
                165                 170                 175 

Val Ala Ala Gln Asp Glu Phe Tyr Arg Ser Gly Trp Ala Leu Asn Met 
            180                 185                 190 

Lys Glu Leu Lys Leu Leu Gln Thr Ile Gly Lys Gly Glu Phe Gly Asp 
        195                 200                 205 

Val Met Leu Gly Asp Tyr Arg Gly Asn Lys Val Ala Val Lys Cys Ile 
    210                 215                 220 

Lys Asn Asp Ala Thr Ala Gln Ala Phe Leu Ala Glu Ala Ser Val Met 
225                 230                 235                 240 

Thr Gln Leu Arg His Ser Asn Leu Val Gln Leu Leu Gly Val Ile Val 
                245                 250                 255 

Glu Glu Lys Gly Gly Leu Tyr Ile Val Thr Glu Tyr Met Ala Lys Gly 
            260                 265                 270 

Ser Leu Val Asp Tyr Leu Arg Ser Arg Gly Arg Ser Val Leu Gly Gly 
        275                 280                 285 

Asp Cys Leu Leu Lys Phe Ser Leu Asp Val Cys Glu Ala Met Glu Tyr 
    290                 295                 300 

Leu Glu Gly Asn Asn Phe Val His Arg Asp Leu Ala Ala Arg Asn Val 
305                 310                 315                 320 

Leu Val Ser Glu Asp Asn Val Ala Lys Val Ser Asp Phe Gly Leu Thr 
                325                 330                 335 

Lys Glu Ala Ser Ser Thr Gln Asp Thr Gly Lys Leu Pro Val Lys Trp 
            340                 345                 350 

Thr Ala Pro Glu Ala Leu Arg Glu Lys Lys Phe Ser Thr Lys Ser Asp 
        355                 360                 365 

Val Trp Ser Phe Gly Ile Leu Leu Trp Glu Ile Tyr Ser Phe Gly Arg 
    370                 375                 380 

Val Pro Tyr Pro Arg Ile Pro Leu Lys Asp Val Val Pro Arg Val Glu 
385                 390                 395                 400 

Lys Gly Tyr Lys Met Asp Ala Pro Asp Gly Cys Pro Pro Ala Val Tyr 
                405                 410                 415 

Glu Val Met Lys Asn Cys Trp His Leu Asp Ala Ala Met Arg Pro Ser 
            420                 425                 430 

Phe Leu Gln Leu Arg Glu Gln Leu Glu His Ile Lys Thr His Glu Leu 
        435                 440                 445 

His Leu 
    450 

 
           
             22  
             1142  
             PRT  
             Homo sapiens  
           
            22 

Met Ala Phe Cys Ala Lys Met Arg Ser Ser Lys Lys Thr Glu Val Asn 
  1               5                  10                  15 

Leu Glu Ala Pro Glu Pro Gly Val Glu Val Ile Phe Tyr Leu Ser Asp 
             20                  25                  30 

Arg Glu Pro Leu Arg Leu Gly Ser Gly Glu Tyr Thr Ala Glu Glu Leu 
         35                  40                  45 

Cys Ile Arg Ala Ala Gln Ala Cys Arg Ile Ser Pro Leu Cys His Asn 
     50                  55                  60 

Leu Phe Ala Leu Tyr Asp Glu Asn Thr Lys Leu Trp Tyr Ala Pro Asn 
 65                  70                  75                  80 

Arg Thr Ile Thr Val Asp Asp Lys Met Ser Leu Arg Leu His Tyr Arg 
                 85                  90                  95 

Met Arg Phe Tyr Phe Thr Asn Trp His Gly Thr Asn Asp Asn Glu Gln 
            100                 105                 110 

Ser Val Trp Arg His Ser Pro Lys Lys Gln Lys Asn Gly Tyr Glu Lys 
        115                 120                 125 

Lys Lys Ile Pro Asp Ala Thr Pro Leu Leu Asp Ala Ser Ser Leu Glu 
    130                 135                 140 

Tyr Leu Phe Ala Gln Gly Gln Tyr Asp Leu Val Lys Cys Leu Ala Pro 
145                 150                 155                 160 

Ile Arg Asp Pro Lys Thr Glu Gln Asp Gly His Asp Ile Glu Asn Glu 
                165                 170                 175 

Cys Leu Gly Met Ala Val Leu Ala Ile Ser His Tyr Ala Met Met Lys 
            180                 185                 190 

Lys Met Gln Leu Pro Glu Leu Pro Lys Asp Ile Ser Tyr Lys Arg Tyr 
        195                 200                 205 

Ile Pro Glu Thr Leu Asn Lys Ser Ile Arg Gln Arg Asn Leu Leu Thr 
    210                 215                 220 

Arg Met Arg Ile Asn Asn Val Phe Lys Asp Phe Leu Lys Glu Phe Asn 
225                 230                 235                 240 

Asn Lys Thr Ile Cys Asp Ser Ser Val Ser Thr His Asp Leu Lys Val 
                245                 250                 255 

Lys Tyr Leu Ala Thr Leu Glu Thr Leu Thr Lys His Tyr Gly Ala Glu 
            260                 265                 270 

Ile Phe Glu Thr Ser Met Leu Leu Ile Ser Ser Glu Asn Glu Met Asn 
        275                 280                 285 

Trp Phe His Ser Asn Asp Gly Gly Asn Val Leu Tyr Tyr Glu Val Met 
    290                 295                 300 

Val Thr Gly Asn Leu Gly Ile Gln Trp Arg His Lys Pro Asn Val Val 
305                 310                 315                 320 

Ser Val Glu Lys Glu Lys Asn Lys Leu Lys Arg Lys Lys Leu Glu Asn 
                325                 330                 335 

Lys Asp Lys Lys Asp Glu Glu Lys Asn Lys Ile Arg Glu Glu Trp Asn 
            340                 345                 350 

Asn Phe Ser Phe Phe Pro Glu Ile Thr His Ile Val Ile Lys Glu Ser 
        355                 360                 365 

Val Val Ser Ile Asn Lys Gln Asp Asn Lys Lys Met Glu Leu Lys Leu 
    370                 375                 380 

Ser Ser His Glu Glu Ala Leu Ser Phe Val Ser Leu Val Asp Gly Tyr 
385                 390                 395                 400 

Phe Arg Leu Thr Ala Asp Ala His His Tyr Leu Cys Thr Asp Val Ala 
                405                 410                 415 

Pro Pro Leu Ile Val His Asn Ile Gln Asn Gly Cys His Gly Pro Ile 
            420                 425                 430 

Cys Thr Glu Tyr Ala Ile Asn Lys Leu Arg Gln Glu Gly Ser Glu Glu 
        435                 440                 445 

Gly Met Tyr Val Leu Arg Trp Ser Cys Thr Asp Phe Asp Asn Ile Leu 
    450                 455                 460 

Met Thr Val Thr Cys Phe Glu Lys Ser Glu Gln Val Gln Gly Ala Gln 
465                 470                 475                 480 

Lys Gln Phe Lys Asn Phe Gln Ile Glu Val Gln Lys Gly Arg Tyr Ser 
                485                 490                 495 

Leu His Gly Ser Asp Arg Ser Phe Pro Ser Leu Gly Asp Leu Met Ser 
            500                 505                 510 

His Leu Lys Lys Gln Ile Leu Arg Thr Asp Asn Ile Ser Phe Met Leu 
        515                 520                 525 

Lys Arg Cys Cys Gln Pro Lys Pro Arg Glu Ile Ser Asn Leu Leu Val 
    530                 535                 540 

Ala Thr Lys Lys Ala Gln Glu Trp Gln Pro Val Tyr Pro Met Ser Gln 
545                 550                 555                 560 

Leu Ser Phe Asp Arg Ile Leu Lys Lys Asp Leu Val Gln Gly Glu His 
                565                 570                 575 

Leu Gly Arg Gly Thr Arg Thr His Ile Tyr Ser Gly Thr Leu Met Asp 
            580                 585                 590 

Tyr Lys Asp Asp Glu Gly Thr Ser Glu Glu Lys Lys Ile Lys Val Ile 
        595                 600                 605 

Leu Lys Val Leu Asp Pro Ser His Arg Asp Ile Ser Leu Ala Phe Phe 
    610                 615                 620 

Glu Ala Ala Ser Met Met Arg Gln Val Ser His Lys His Ile Val Tyr 
625                 630                 635                 640 

Leu Tyr Gly Val Cys Val Arg Asp Val Glu Asn Ile Met Val Glu Glu 
                645                 650                 655 

Phe Val Glu Gly Gly Pro Leu Asp Leu Phe Met His Arg Lys Ser Asp 
            660                 665                 670 

Val Leu Thr Thr Pro Trp Lys Phe Lys Val Ala Lys Gln Leu Ala Ser 
        675                 680                 685 

Ala Leu Ser Tyr Leu Glu Asp Lys Asp Leu Val His Gly Asn Val Cys 
    690                 695                 700 

Thr Lys Asn Leu Leu Leu Ala Arg Glu Gly Ile Asp Ser Glu Cys Gly 
705                 710                 715                 720 

Pro Phe Ile Lys Leu Ser Asp Pro Gly Ile Pro Ile Thr Val Leu Ser 
                725                 730                 735 

Arg Gln Glu Cys Ile Glu Arg Ile Pro Trp Ile Ala Pro Glu Cys Val 
            740                 745                 750 

Glu Asp Ser Lys Asn Leu Ser Val Ala Ala Asp Lys Trp Ser Phe Gly 
        755                 760                 765 

Thr Thr Leu Trp Glu Ile Cys Tyr Asn Gly Glu Ile Pro Leu Lys Asp 
    770                 775                 780 

Lys Thr Leu Ile Glu Lys Glu Arg Phe Tyr Glu Ser Arg Cys Arg Pro 
785                 790                 795                 800 

Val Thr Pro Ser Cys Lys Glu Leu Ala Asp Leu Met Thr Arg Cys Met 
                805                 810                 815 

Asn Tyr Asp Pro Asn Gln Arg Pro Phe Phe Arg Ala Ile Met Arg Asp 
            820                 825                 830 

Ile Asn Lys Leu Glu Glu Gln Asn Pro Asp Ile Val Ser Arg Lys Lys 
        835                 840                 845 

Asn Gln Pro Thr Glu Val Asp Pro Thr His Phe Glu Lys Arg Phe Leu 
    850                 855                 860 

Lys Arg Ile Arg Asp Leu Gly Glu Gly His Phe Gly Lys Val Glu Leu 
865                 870                 875                 880 

Cys Arg Tyr Asp Pro Glu Asp Asn Thr Gly Glu Gln Val Ala Val Lys 
                885                 890                 895 

Ser Leu Lys Pro Glu Ser Gly Gly Asn His Ile Ala Asp Leu Lys Lys 
            900                 905                 910 

Glu Ile Glu Ile Leu Arg Asn Leu Tyr His Glu Asn Ile Val Lys Tyr 
        915                 920                 925 

Lys Gly Ile Cys Thr Glu Asp Gly Gly Asn Gly Ile Lys Leu Ile Met 
    930                 935                 940 

Glu Phe Leu Pro Ser Gly Ser Leu Lys Glu Tyr Leu Pro Lys Asn Lys 
945                 950                 955                 960 

Asn Lys Ile Asn Leu Lys Gln Gln Leu Lys Tyr Ala Val Gln Ile Cys 
                965                 970                 975 

Lys Gly Met Asp Tyr Leu Gly Ser Arg Gln Tyr Val His Arg Asp Leu 
            980                 985                 990 

Ala Ala Arg Asn Val Leu Val Glu Ser Glu His Gln Val Lys Ile Gly 
        995                1000                1005 

Asp Phe Gly Leu Thr Lys Ala Ile Glu Thr Asp Lys Glu Tyr Tyr Thr 
   1010                1015                1020 

Val Lys Asp Asp Arg Asp Ser Pro Val Phe Trp Tyr Ala Pro Glu Cys 
1025               1030                1035                1040 

Leu Met Gln Ser Lys Phe Tyr Ile Ala Ser Asp Val Trp Ser Phe Gly 
               1045                1050                1055 

Val Thr Leu His Glu Leu Leu Thr Tyr Cys Asp Ser Asp Ser Ser Pro 
           1060                1065                1070 

Met Ala Leu Phe Leu Lys Met Ile Gly Pro Thr His Gly Gln Met Thr 
       1075                1080                1085 

Val Thr Arg Leu Val Asn Thr Leu Lys Glu Gly Lys Arg Leu Pro Cys 
   1090                1095                1100 

Pro Pro Asn Cys Pro Asp Glu Val Tyr Gln Leu Met Arg Lys Cys Trp 
1105               1110                1115                1120 

Glu Phe Gln Pro Ser Asn Arg Thr Ser Phe Gln Asn Leu Ile Glu Gly 
               1125                1130                1135 

Phe Glu Ala Leu Leu Lys 
           1140 

 
           
             23  
             1338  
             PRT  
             Homo sapiens  
           
            23 

Met Val Ser Tyr Trp Asp Thr Gly Val Leu Leu Cys Ala Leu Leu Ser 
  1               5                  10                  15 

Cys Leu Leu Leu Thr Gly Ser Ser Ser Gly Ser Lys Leu Lys Asp Pro 
             20                  25                  30 

Glu Leu Ser Leu Lys Gly Thr Gln His Ile Met Gln Ala Gly Gln Thr 
         35                  40                  45 

Leu His Leu Gln Cys Arg Gly Glu Ala Ala His Lys Trp Ser Leu Pro 
     50                  55                  60 

Glu Met Val Ser Lys Glu Ser Glu Arg Leu Ser Ile Thr Lys Ser Ala 
 65                  70                  75                  80 

Cys Gly Arg Asn Gly Lys Gln Phe Cys Ser Thr Leu Thr Leu Asn Thr 
                 85                  90                  95 

Ala Gln Ala Asn His Thr Gly Phe Tyr Ser Cys Lys Tyr Leu Ala Val 
            100                 105                 110 

Pro Thr Ser Lys Lys Lys Glu Thr Glu Ser Ala Ile Tyr Ile Phe Ile 
        115                 120                 125 

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
    130                 135                 140 

Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
145                 150                 155                 160 

Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
                165                 170                 175 

Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
            180                 185                 190 

Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
        195                 200                 205 

Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg 
    210                 215                 220 

Gln Thr Asn Thr Ile Ile Asp Val Gln Ile Ser Thr Pro Arg Pro Val 
225                 230                 235                 240 

Lys Leu Leu Arg Gly His Thr Leu Val Leu Asn Cys Thr Ala Thr Thr 
                245                 250                 255 

Pro Leu Asn Thr Arg Val Gln Met Thr Trp Ser Tyr Pro Asp Glu Lys 
            260                 265                 270 

Asn Lys Arg Ala Ser Val Arg Arg Arg Ile Asp Gln Ser Asn Ser His 
        275                 280                 285 

Ala Asn Ile Phe Tyr Ser Val Leu Thr Ile Asp Lys Met Gln Asn Lys 
    290                 295                 300 

Asp Lys Gly Leu Tyr Thr Cys Arg Val Arg Ser Gly Pro Ser Phe Lys 
305                 310                 315                 320 

Ser Val Asn Thr Ser Val His Ile Tyr Asp Lys Ala Phe Ile Thr Val 
                325                 330                 335 

Lys His Arg Lys Gln Gln Val Leu Glu Thr Val Ala Gly Lys Arg Ser 
            340                 345                 350 

Tyr Arg Leu Ser Met Lys Val Lys Ala Phe Pro Ser Pro Glu Val Val 
        355                 360                 365 

Trp Leu Lys Asp Gly Leu Pro Ala Thr Glu Lys Ser Ala Arg Tyr Leu 
    370                 375                 380 

Thr Arg Gly Tyr Ser Leu Ile Ile Lys Asp Val Thr Glu Glu Asp Ala 
385                 390                 395                 400 

Gly Asn Tyr Thr Ile Leu Leu Ser Ile Lys Gln Ser Asn Val Phe Lys 
                405                 410                 415 

Asn Leu Thr Ala Thr Leu Ile Val Asn Val Lys Pro Gln Ile Tyr Glu 
            420                 425                 430 

Lys Ala Val Ser Ser Phe Pro Asp Pro Ala Leu Tyr Pro Leu Gly Ser 
        435                 440                 445 

Arg Gln Ile Leu Thr Cys Thr Ala Tyr Gly Ile Pro Gln Pro Thr Ile 
    450                 455                 460 

Lys Trp Phe Trp His Pro Cys Asn His Asn His Ser Glu Ala Arg Cys 
465                 470                 475                 480 

Asp Phe Cys Ser Asn Asn Glu Glu Ser Phe Ile Leu Asp Ala Asp Ser 
                485                 490                 495 

Asn Met Gly Asn Arg Ile Glu Ser Ile Thr Gln Arg Met Ala Ile Ile 
            500                 505                 510 

Glu Gly Lys Asn Lys Met Ala Ser Thr Leu Val Val Ala Asp Ser Arg 
        515                 520                 525 

Ile Ser Gly Ile Tyr Ile Cys Ile Ala Ser Asn Lys Val Gly Thr Val 
    530                 535                 540 

Gly Arg Asn Ile Ser Phe Tyr Ile Thr Asp Val Pro Asn Gly Phe His 
545                 550                 555                 560 

Val Asn Leu Glu Lys Met Pro Thr Glu Gly Glu Asp Leu Lys Leu Ser 
                565                 570                 575 

Cys Thr Val Asn Lys Phe Leu Tyr Arg Asp Val Thr Trp Ile Leu Leu 
            580                 585                 590 

Arg Thr Val Asn Asn Arg Thr Met His Tyr Ser Ile Ser Lys Gln Lys 
        595                 600                 605 

Met Ala Ile Thr Lys Glu His Ser Ile Thr Leu Asn Leu Thr Ile Met 
    610                 615                 620 

Asn Val Ser Leu Gln Asp Ser Gly Thr Tyr Ala Cys Arg Ala Arg Asn 
625                 630                 635                 640 

Val Tyr Thr Gly Glu Glu Ile Leu Gln Lys Lys Glu Ile Thr Ile Arg 
                645                 650                 655 

Asp Gln Glu Ala Pro Tyr Leu Leu Arg Asn Leu Ser Asp His Thr Val 
            660                 665                 670 

Ala Ile Ser Ser Ser Thr Thr Leu Asp Cys His Ala Asn Gly Val Pro 
        675                 680                 685 

Glu Pro Gln Ile Thr Trp Phe Lys Asn Asn His Lys Ile Gln Gln Glu 
    690                 695                 700 

Pro Gly Ile Ile Leu Gly Pro Gly Ser Ser Thr Leu Phe Ile Glu Arg 
705                 710                 715                 720 

Val Thr Glu Glu Asp Glu Gly Val Tyr His Cys Lys Ala Thr Asn Gln 
                725                 730                 735 

Lys Gly Ser Val Glu Ser Ser Ala Tyr Leu Thr Val Gln Gly Thr Ser 
            740                 745                 750 

Asp Lys Ser Asn Leu Glu Leu Ile Thr Leu Thr Cys Thr Cys Val Ala 
        755                 760                 765 

Ala Thr Leu Phe Trp Leu Leu Leu Thr Leu Leu Ile Arg Lys Met Lys 
    770                 775                 780 

Arg Ser Ser Ser Glu Ile Lys Thr Asp Tyr Leu Ser Ile Ile Met Asp 
785                 790                 795                 800 

Pro Asp Glu Val Pro Leu Asp Glu Gln Cys Glu Arg Leu Pro Tyr Asp 
                805                 810                 815 

Ala Ser Lys Trp Glu Phe Ala Arg Glu Arg Leu Lys Leu Gly Lys Ser 
            820                 825                 830 

Leu Gly Arg Gly Ala Phe Gly Lys Val Val Gln Ala Ser Ala Phe Gly 
        835                 840                 845 

Ile Lys Lys Ser Pro Thr Cys Arg Thr Val Ala Val Lys Met Leu Lys 
    850                 855                 860 

Glu Gly Ala Thr Ala Ser Glu Tyr Lys Ala Leu Met Thr Glu Leu Lys 
865                 870                 875                 880 

Ile Leu Thr His Ile Gly His His Leu Asn Val Val Asn Leu Leu Gly 
                885                 890                 895 

Ala Cys Thr Lys Gln Gly Gly Pro Leu Met Val Ile Val Glu Tyr Cys 
            900                 905                 910 

Lys Tyr Gly Asn Leu Ser Asn Tyr Leu Lys Ser Lys Arg Asp Leu Phe 
        915                 920                 925 

Phe Leu Asn Lys Asp Ala Ala Leu His Met Glu Pro Lys Lys Glu Lys 
    930                 935                 940 

Met Glu Pro Gly Leu Glu Gln Gly Lys Lys Pro Arg Leu Asp Ser Val 
945                 950                 955                 960 

Thr Ser Ser Glu Ser Phe Ala Ser Ser Gly Phe Gln Glu Asp Lys Ser 
                965                 970                 975 

Leu Ser Asp Val Glu Glu Glu Glu Asp Ser Asp Gly Phe Tyr Lys Glu 
            980                 985                 990 

Pro Ile Thr Met Glu Asp Leu Ile Ser Tyr Ser Phe Gln Val Ala Arg 
        995                1000                1005 

Gly Met Glu Phe Leu Ser Ser Arg Lys Cys Ile His Arg Asp Leu Ala 
   1010                1015                1020 

Ala Arg Asn Ile Leu Leu Ser Glu Asn Asn Val Val Lys Ile Cys Asp 
1025               1030                1035                1040 

Phe Gly Leu Ala Arg Asp Ile Tyr Lys Asn Pro Asp Tyr Val Arg Lys 
               1045                1050                1055 

Gly Asp Thr Arg Leu Pro Leu Lys Trp Met Ala Pro Glu Ser Ile Phe 
           1060                1065                1070 

Asp Lys Ile Tyr Ser Thr Lys Ser Asp Val Trp Ser Tyr Gly Val Leu 
       1075                1080                1085 

Leu Trp Glu Ile Phe Ser Leu Gly Gly Ser Pro Tyr Pro Gly Val Gln 
   1090                1095                1100 

Met Asp Glu Asp Phe Cys Ser Arg Leu Arg Glu Gly Met Arg Met Arg 
1105               1110                1115                1120 

Ala Pro Glu Tyr Ser Thr Pro Glu Ile Tyr Gln Ile Met Leu Asp Cys 
               1125                1130                1135 

Trp His Arg Asp Pro Lys Glu Arg Pro Arg Phe Ala Glu Leu Val Glu 
           1140                1145                1150 

Lys Leu Gly Asp Leu Leu Gln Ala Asn Val Gln Gln Asp Gly Lys Asp 
       1155                1160                1165 

Tyr Ile Pro Ile Asn Ala Ile Leu Thr Gly Asn Ser Gly Phe Thr Tyr 
   1170                1175                1180 

Ser Thr Pro Ala Phe Ser Glu Asp Phe Phe Lys Glu Ser Ile Ser Ala 
1185               1190                1195                1200 

Pro Lys Phe Asn Ser Gly Ser Ser Asp Asp Val Arg Tyr Val Asn Ala 
               1205                1210                1215 

Phe Lys Phe Met Ser Leu Glu Arg Ile Lys Thr Phe Glu Glu Leu Leu 
           1220                1225                1230 

Pro Asn Ala Thr Ser Met Phe Asp Asp Tyr Gln Gly Asp Ser Ser Thr 
       1235                1240                1245 

Leu Leu Ala Ser Pro Met Leu Lys Arg Phe Thr Trp Thr Asp Ser Lys 
   1250                1255                1260 

Pro Lys Ala Ser Leu Lys Ile Asp Leu Arg Val Thr Ser Lys Ser Lys 
1265               1270                1275                1280 

Glu Ser Gly Leu Ser Asp Val Ser Arg Pro Ser Phe Cys His Ser Ser 
               1285                1290                1295 

Cys Gly His Val Ser Glu Gly Lys Arg Arg Phe Thr Tyr Asp His Ala 
           1300                1305                1310 

Glu Leu Glu Arg Lys Ile Ala Cys Cys Ser Pro Pro Pro Asp Tyr Asn 
       1315                1320                1325 

Ser Val Val Leu Tyr Ser Thr Pro Pro Ile 
   1330                1335 

 
           
             24  
             309  
             PRT  
             Homo sapiens  
           
            24 

Met Asp Glu Lys Val Phe Thr Lys Glu Leu Asp Gln Trp Ile Glu Gln 
  1               5                  10                  15 

Leu Asn Glu Cys Lys Gln Leu Ser Glu Ser Gln Val Lys Ser Leu Cys 
             20                  25                  30 

Glu Lys Ala Lys Glu Ile Leu Thr Lys Glu Ser Asn Val Gln Glu Val 
         35                  40                  45 

Arg Cys Pro Val Thr Val Cys Gly Asp Val His Gly Gln Phe His Asp 
     50                  55                  60 

Leu Met Glu Leu Phe Arg Ile Gly Gly Lys Ser Pro Asp Thr Asn Tyr 
 65                  70                  75                  80 

Leu Phe Met Gly Asp Tyr Val Asp Arg Gly Tyr Tyr Ser Val Glu Thr 
                 85                  90                  95 

Val Thr Leu Leu Val Ala Leu Lys Val Arg Tyr Arg Glu Arg Ile Thr 
            100                 105                 110 

Ile Leu Arg Gly Asn His Glu Ser Arg Gln Ile Thr Gln Val Tyr Gly 
        115                 120                 125 

Phe Tyr Asp Glu Cys Leu Arg Lys Tyr Gly Asn Ala Asn Val Trp Lys 
    130                 135                 140 

Tyr Phe Thr Asp Leu Phe Asp Tyr Leu Pro Leu Thr Ala Leu Val Asp 
145                 150                 155                 160 

Gly Gln Ile Phe Cys Leu His Gly Gly Leu Ser Pro Ser Ile Asp Thr 
                165                 170                 175 

Leu Asp His Ile Arg Ala Leu Asp Arg Leu Gln Glu Val Pro His Glu 
            180                 185                 190 

Gly Pro Met Cys Asp Leu Leu Trp Ser Asp Pro Asp Asp Arg Gly Gly 
        195                 200                 205 

Trp Gly Ile Ser Pro Arg Gly Ala Gly Tyr Thr Phe Gly Gln Asp Ile 
    210                 215                 220 

Ser Glu Thr Phe Asn His Ala Asn Gly Leu Thr Leu Val Ser Arg Ala 
225                 230                 235                 240 

His Gln Leu Val Met Glu Gly Tyr Asn Trp Cys His Asp Arg Asn Val 
                245                 250                 255 

Val Thr Ile Phe Ser Ala Pro Asn Tyr Cys Tyr Arg Cys Gly Asn Gln 
            260                 265                 270 

Ala Ala Ile Met Glu Leu Asp Asp Thr Leu Lys Tyr Ser Phe Leu Gln 
        275                 280                 285 

Phe Asp Pro Ala Pro Arg Arg Gly Glu Pro His Val Thr Arg Arg Thr 
    290                 295                 300 

Pro Asp Tyr Phe Leu 
305 

 
           
             25  
             394  
             PRT  
             Homo sapiens  
           
            25 

Met Val Thr Met Glu Glu Leu Arg Glu Met Asp Cys Ser Val Leu Lys 
  1               5                  10                  15 

Arg Leu Met Asn Arg Asp Glu Asn Gly Gly Gly Ala Gly Gly Ser Gly 
             20                  25                  30 

Ser His Gly Thr Leu Gly Leu Pro Ser Gly Gly Lys Cys Leu Leu Leu 
         35                  40                  45 

Asp Cys Arg Pro Phe Leu Ala His Ser Ala Gly Tyr Ile Leu Gly Ser 
     50                  55                  60 

Val Asn Val Arg Cys Asn Thr Ile Val Arg Arg Arg Ala Lys Gly Ser 
 65                  70                  75                  80 

Val Ser Leu Glu Gln Ile Leu Pro Ala Glu Glu Glu Val Arg Ala Arg 
                 85                  90                  95 

Leu Arg Ser Gly Leu Tyr Ser Ala Val Ile Val Tyr Asp Glu Gly Ser 
            100                 105                 110 

Pro Arg Ala Glu Ser Leu Arg Glu Asp Ser Thr Val Ser Leu Val Val 
        115                 120                 125 

Gln Ala Leu Arg Arg Asn Ala Glu Arg Thr Asp Ile Cys Leu Leu Lys 
    130                 135                 140 

Gly Gly Tyr Glu Arg Phe Ser Ser Glu Tyr Pro Glu Phe Cys Ser Lys 
145                 150                 155                 160 

Thr Lys Ala Leu Ala Ala Ile Pro Pro Pro Val Pro Pro Ser Ala Thr 
                165                 170                 175 

Glu Pro Leu Asp Leu Gly Cys Ser Ser Cys Gly Thr Pro Leu His Asp 
            180                 185                 190 

Gln Gly Gly Pro Val Glu Ile Leu Pro Phe Leu Tyr Leu Gly Ser Ala 
        195                 200                 205 

Tyr His Ala Ala Arg Arg Asp Met Leu Asp Ala Leu Gly Ile Thr Ala 
    210                 215                 220 

Leu Leu Asn Val Ser Ser Asp Cys Pro Asn His Phe Glu Gly His Tyr 
225                 230                 235                 240 

Gln Tyr Lys Cys Ile Pro Val Glu Asp Asn His Lys Ala Asp Ile Ser 
                245                 250                 255 

Ser Trp Phe Met Glu Ala Ile Glu Tyr Ile Asp Ala Val Lys Asp Cys 
            260                 265                 270 

Arg Gly Arg Val Leu Val His Cys Gln Ala Gly Ile Ser Arg Ser Ala 
        275                 280                 285 

Thr Ile Cys Leu Ala Tyr Leu Met Met Lys Lys Arg Val Arg Leu Glu 
    290                 295                 300 

Glu Ala Phe Glu Phe Val Lys Gln Arg Arg Ser Ile Ile Ser Pro Asn 
305                 310                 315                 320 

Phe Ser Phe Met Gly Gln Leu Leu Gln Phe Glu Ser Gln Val Leu Ala 
                325                 330                 335 

Thr Ser Cys Ala Ala Glu Ala Ala Ser Pro Ser Gly Pro Leu Arg Glu 
            340                 345                 350 

Arg Gly Lys Thr Pro Ala Thr Pro Thr Ser Gln Phe Val Phe Ser Phe 
        355                 360                 365 

Pro Val Ser Val Gly Val His Ser Ala Pro Ser Ser Leu Pro Tyr Leu 
    370                 375                 380 

His Ser Pro Ile Thr Thr Ser Pro Ser Cys 
385                 390 

 
           
             26  
             185  
             PRT  
             Homo sapiens  
           
            26 

Met Ser Gly Ser Phe Glu Leu Ser Val Gln Asp Leu Asn Asp Leu Leu 
  1               5                  10                  15 

Ser Asp Gly Ser Gly Cys Tyr Ser Leu Pro Ser Gln Pro Cys Asn Glu 
             20                  25                  30 

Val Thr Pro Arg Ile Tyr Val Gly Asn Ala Ser Val Ala Gln Asp Ile 
         35                  40                  45 

Pro Lys Leu Gln Lys Leu Gly Ile Thr His Val Leu Asn Ala Ala Glu 
     50                  55                  60 

Gly Arg Ser Phe Met His Val Asn Thr Asn Ala Asn Phe Tyr Lys Asp 
 65                  70                  75                  80 

Ser Gly Ile Thr Tyr Leu Gly Ile Lys Ala Asn Asp Thr Gln Glu Phe 
                 85                  90                  95 

Asn Leu Ser Ala Tyr Phe Glu Arg Ala Ala Asp Phe Ile Asp Gln Ala 
            100                 105                 110 

Leu Ala Gln Lys Asn Gly Arg Val Leu Val His Cys Arg Glu Gly Tyr 
        115                 120                 125 

Ser Arg Ser Pro Thr Leu Val Ile Ala Tyr Leu Met Met Arg Gln Lys 
    130                 135                 140 

Met Asp Val Lys Ser Ala Leu Ser Ile Val Arg Gln Asn Arg Glu Ile 
145                 150                 155                 160 

Gly Pro Asn Asp Gly Phe Leu Ala Gln Leu Cys Gln Leu Asn Asp Arg 
                165                 170                 175 

Leu Ala Lys Glu Gly Lys Leu Lys Pro 
            180                 185 

 
           
             27  
             657  
             PRT  
             Homo sapiens  
           
            27 

Met Arg Arg Ala Val Cys Phe Pro Ala Leu Cys Leu Leu Leu Asn Leu 
  1               5                  10                  15 

His Ala Ala Gly Cys Phe Ser Gly Asn Asn Asp His Phe Leu Ala Ile 
             20                  25                  30 

Asn Gln Lys Lys Ser Gly Lys Pro Val Phe Ile Tyr Lys His Ser Gln 
         35                  40                  45 

Asp Ile Glu Lys Ser Leu Asp Ile Ala Pro Gln Lys Ile Tyr Arg His 
     50                  55                  60 

Ser Tyr His Ser Ser Ser Glu Ala Gln Val Ser Lys Arg His Gln Ile 
 65                  70                  75                  80 

Val Asn Ser Ala Phe Pro Arg Pro Ala Tyr Asp Pro Ser Leu Asn Leu 
                 85                  90                  95 

Leu Ala Met Asp Gly Gln Asp Leu Glu Val Glu Asn Leu Pro Ile Pro 
            100                 105                 110 

Ala Ala Asn Val Ile Val Val Thr Leu Gln Met Asp Val Asn Lys Leu 
        115                 120                 125 

Asn Ile Thr Leu Leu Arg Ile Phe Arg Gln Gly Val Ala Ala Ala Leu 
    130                 135                 140 

Gly Leu Leu Pro Gln Gln Val His Ile Asn Arg Leu Ile Gly Lys Lys 
145                 150                 155                 160 

Asn Ser Ile Glu Leu Phe Val Ser Pro Ile Asn Arg Lys Thr Gly Ile 
                165                 170                 175 

Ser Asp Ala Leu Pro Ser Glu Glu Val Leu Arg Ser Leu Asn Ile Asn 
            180                 185                 190 

Val Leu His Gln Ser Leu Ser Gln Phe Gly Ile Thr Glu Val Ser Pro 
        195                 200                 205 

Glu Lys Asn Val Leu Gln Gly Gln His Glu Ala Asp Lys Ile Trp Ser 
    210                 215                 220 

Lys Glu Gly Phe Tyr Ala Val Val Ile Phe Leu Ser Ile Phe Val Ile 
225                 230                 235                 240 

Ile Val Thr Cys Leu Met Ile Leu Tyr Arg Leu Lys Glu Arg Phe Gln 
                245                 250                 255 

Leu Ser Leu Arg Gln Asp Lys Glu Lys Asn Gln Glu Ile His Leu Ser 
            260                 265                 270 

Pro Ile Thr Leu Gln Pro Ala Leu Ser Glu Ala Lys Thr Val His Ser 
        275                 280                 285 

Met Val Gln Pro Glu Gln Ala Pro Lys Val Leu Asn Val Val Val Asp 
    290                 295                 300 

Pro Gln Gly Arg Gly Ala Pro Glu Ile Arg Ala Thr Thr Ala Thr Ser 
305                 310                 315                 320 

Val Cys Pro Ser Pro Phe Lys Met Lys Pro Ile Gly Leu Gln Glu Arg 
                325                 330                 335 

Arg Gly Ser Asn Val Ser Leu Thr Leu Asp Met Ser Ser Leu Gly Asn 
            340                 345                 350 

Ile Glu Pro Phe Val Ser Ile Pro Thr Pro Arg Glu Lys Val Ala Met 
        355                 360                 365 

Glu Tyr Leu Gln Ser Ala Ser Arg Ile Leu Thr Arg Ser Gln Leu Arg 
    370                 375                 380 

Asp Val Val Ala Ser Ser His Leu Leu Gln Ser Glu Phe Met Glu Ile 
385                 390                 395                 400 

Pro Met Asn Phe Val Asp Pro Lys Glu Ile Asp Ile Pro Arg His Gly 
                405                 410                 415 

Thr Lys Asn Arg Tyr Lys Thr Ile Leu Pro Asn Pro Leu Ser Arg Val 
            420                 425                 430 

Cys Leu Arg Pro Lys Asn Val Thr Asp Ser Leu Ser Thr Tyr Ile Asn 
        435                 440                 445 

Ala Asn Tyr Ile Arg Gly Tyr Ser Gly Lys Glu Lys Ala Phe Ile Ala 
    450                 455                 460 

Thr Gln Gly Pro Met Ile Asn Thr Val Asp Asp Phe Trp Gln Met Val 
465                 470                 475                 480 

Trp Gln Glu Asp Ser Pro Val Ile Val Met Ile Thr Lys Leu Lys Glu 
                485                 490                 495 

Lys Asn Glu Lys Cys Val Leu Tyr Trp Pro Glu Lys Arg Gly Ile Tyr 
            500                 505                 510 

Gly Lys Val Glu Val Leu Val Ile Ser Val Asn Glu Cys Asp Asn Tyr 
        515                 520                 525 

Thr Ile Arg Asn Leu Val Leu Lys Gln Gly Ser His Thr Gln His Val 
    530                 535                 540 

Lys His Tyr Trp Tyr Thr Ser Trp Pro Asp His Lys Thr Pro Asp Ser 
545                 550                 555                 560 

Ala Gln Pro Leu Leu Gln Leu Met Leu Asp Val Glu Glu Asp Arg Leu 
                565                 570                 575 

Ala Ser Gln Gly Arg Gly Pro Val Val Val His Cys Ser Ala Gly Ile 
            580                 585                 590 

Gly Arg Thr Gly Cys Phe Ile Ala Thr Ser Ile Gly Cys Gln Gln Leu 
        595                 600                 605 

Lys Glu Glu Gly Val Val Asp Ala Leu Ser Ile Val Cys Gln Leu Arg 
    610                 615                 620 

Met Asp Arg Gly Gly Met Val Gln Thr Ser Glu Gln Tyr Glu Phe Val 
625                 630                 635                 640 

His His Ala Leu Cys Leu Tyr Glu Ser Arg Leu Ser Ala Glu Thr Val 
                645                 650                 655 

Gln 

 
           
             28  
             537  
             PRT  
             Homo sapiens  
           
            28 

Glu Arg Leu Leu Gly Arg Pro Gln Pro Ile Val Met Glu Ala Leu Asp 
  1               5                  10                  15 

Glu Ala Glu Gly Leu Gln Asp Ser Gln Arg Glu Met Pro Pro Pro Pro 
             20                  25                  30 

Pro Pro Ser Pro Pro Ser Asp Pro Ala Gln Lys Pro Pro Pro Arg Gly 
         35                  40                  45 

Ala Gly Ser His Ser Leu Thr Val Arg Ser Ser Leu Cys Leu Phe Ala 
     50                  55                  60 

Ala Ser Gln Phe Leu Leu Ala Cys Gly Val Leu Trp Phe Ser Gly Tyr 
 65                  70                  75                  80 

Gly His Met Trp Ser Gln Asn Ala Thr Asn Leu Val Ser Ser Leu Leu 
                 85                  90                  95 

Thr Leu Leu Lys Gln Leu Glu Pro Thr Ser Trp Leu Asp Ser Gly Thr 
            100                 105                 110 

Trp Gly Val Pro Gly Leu Leu Leu Val Phe Leu Ser Val Gly Leu Val 
        115                 120                 125 

Leu Val Thr Thr Leu Val Trp His Leu Leu Arg Thr Pro Pro Glu Pro 
    130                 135                 140 

Pro Thr Pro Leu Pro Pro Glu Asp Arg Arg Gln Ser Val Ser Arg Gln 
145                 150                 155                 160 

Pro Ser Phe Thr Tyr Ser Glu Trp Met Glu Glu Lys Ile Glu Asp Asp 
                165                 170                 175 

Phe Leu Asp Leu Asp Pro Val Pro Glu Thr Pro Val Phe Asp Cys Val 
            180                 185                 190 

Met Asp Ile Lys Pro Glu Ala Asp Pro Thr Ser Leu Thr Val Lys Ser 
        195                 200                 205 

Met Gly Leu Gln Glu Arg Arg Gly Ser Asn Val Ser Leu Thr Leu Asp 
    210                 215                 220 

Met Cys Thr Pro Gly Cys Asn Glu Glu Gly Phe Gly Tyr Leu Met Ser 
225                 230                 235                 240 

Pro Arg Glu Glu Ser Ala Arg Glu Tyr Leu Leu Ser Ala Ser Arg Val 
                245                 250                 255 

Leu Gln Ala Glu Glu Leu His Glu Lys Ala Leu Asp Pro Phe Leu Leu 
            260                 265                 270 

Gln Ala Glu Phe Phe Glu Ile Pro Met Asn Phe Val Val Pro Lys Glu 
        275                 280                 285 

Tyr Asp Ile Pro Gly Arg Cys Arg Lys Asn Arg Tyr Lys Thr Ile Leu 
    290                 295                 300 

Pro Asn Pro His Ser Arg Val Cys Leu Thr Ser Pro Asp Pro Asp Asp 
305                 310                 315                 320 

Pro Leu Ser Ser Tyr Ile Asn Ala Asn Tyr Ile Arg Gly Tyr Gly Gly 
                325                 330                 335 

Glu Glu Lys Val Tyr Ile Ala Thr Gln Gly Pro Ile Val Ser Thr Val 
            340                 345                 350 

Ala Asp Phe Trp Arg Met Val Trp Gln Glu His Thr Pro Ile Ile Val 
        355                 360                 365 

Met Ile Thr Asn Ile Glu Glu Met Asn Glu Lys Cys Thr Glu Tyr Trp 
    370                 375                 380 

Pro Glu Glu Gln Val Ala Tyr Asp Gly Val Glu Ile Thr Val Gln Lys 
385                 390                 395                 400 

Val Ile His Thr Glu Asp Tyr Arg Leu Arg Leu Ile Ser Leu Lys Ser 
                405                 410                 415 

Gly Thr Glu Glu Arg Gly Leu Lys His Tyr Trp Phe Thr Ser Trp Pro 
            420                 425                 430 

Asp Gln Lys Thr Pro Asp Arg Ala Pro Pro Leu Leu His Leu Val Arg 
        435                 440                 445 

Glu Val Glu Glu Ala Ala Gln Gln Glu Gly Pro His Cys Ala Pro Ile 
    450                 455                 460 

Ile Val His Cys Ser Ala Gly Ile Gly Arg Thr Gly Cys Phe Ile Ala 
465                 470                 475                 480 

Thr Ser Ile Cys Cys Gln Gln Leu Arg Gln Glu Gly Val Val Asp Ile 
                485                 490                 495 

Leu Lys Thr Thr Cys Gln Leu Arg Gln Asp Arg Gly Gly Met Ile Gln 
            500                 505                 510 

His Cys Glu Gln Tyr Gln Phe Val His His Val Met Ser Leu Tyr Glu 
        515                 520                 525 

Lys Gln Leu Ser His Gln Ser Pro Glu 
    530                 535 

 
           
             29  
             403  
             PRT  
             Homo sapiens  
           
            29 

Met Thr Ala Ile Ile Lys Glu Ile Val Ser Arg Asn Lys Arg Arg Tyr 
  1               5                  10                  15 

Gln Glu Asp Gly Phe Asp Leu Asp Leu Thr Tyr Ile Tyr Pro Asn Ile 
             20                  25                  30 

Ile Ala Met Gly Phe Pro Ala Glu Arg Leu Glu Gly Val Tyr Arg Asn 
         35                  40                  45 

Asn Ile Asp Asp Val Val Arg Phe Leu Asp Ser Lys His Lys Asn His 
     50                  55                  60 

Tyr Lys Ile Tyr Asn Leu Cys Ala Glu Arg His Tyr Asp Thr Ala Lys 
 65                  70                  75                  80 

Phe Asn Cys Arg Val Ala Gln Tyr Pro Phe Glu Asp His Asn Pro Pro 
                 85                  90                  95 

Gln Leu Glu Leu Ile Lys Pro Phe Cys Glu Asp Leu Asp Gln Trp Leu 
            100                 105                 110 

Ser Glu Asp Asp Asn His Val Ala Ala Ile His Cys Lys Ala Gly Lys 
        115                 120                 125 

Gly Arg Thr Gly Val Met Ile Cys Ala Tyr Leu Leu His Arg Gly Lys 
    130                 135                 140 

Phe Leu Lys Ala Gln Glu Ala Leu Asp Phe Tyr Gly Glu Val Arg Thr 
145                 150                 155                 160 

Arg Asp Lys Lys Gly Val Thr Ile Pro Ser Gln Arg Arg Tyr Val Tyr 
                165                 170                 175 

Tyr Tyr Ser Tyr Leu Leu Lys Asn His Leu Asp Tyr Arg Pro Val Ala 
            180                 185                 190 

Leu Leu Phe His Lys Met Met Phe Glu Thr Ile Pro Met Phe Ser Gly 
        195                 200                 205 

Gly Thr Cys Asn Pro Gln Phe Val Val Cys Gln Leu Lys Val Lys Ile 
    210                 215                 220 

Tyr Ser Ser Asn Ser Gly Pro Thr Arg Arg Glu Asp Lys Phe Met Tyr 
225                 230                 235                 240 

Phe Glu Phe Pro Gln Pro Leu Pro Val Cys Gly Asp Ile Lys Val Glu 
                245                 250                 255 

Phe Phe His Lys Gln Asn Lys Met Leu Lys Lys Asp Lys Met Phe His 
            260                 265                 270 

Phe Trp Val Asn Thr Phe Phe Ile Pro Gly Pro Glu Glu Thr Ser Glu 
        275                 280                 285 

Lys Val Glu Asn Gly Ser Leu Cys Asp Gln Glu Ile Asp Ser Ile Cys 
    290                 295                 300 

Ser Ile Glu Arg Ala Asp Asn Asp Lys Glu Tyr Leu Val Leu Thr Leu 
305                 310                 315                 320 

Thr Lys Asn Asp Leu Asp Lys Ala Asn Lys Asp Lys Ala Asn Arg Tyr 
                325                 330                 335 

Phe Ser Pro Asn Phe Lys Val Lys Leu Tyr Phe Thr Lys Thr Val Glu 
            340                 345                 350 

Glu Pro Ser Asn Pro Glu Ala Ser Ser Ser Thr Ser Val Thr Pro Asp 
        355                 360                 365 

Val Ser Asp Asn Glu Pro Asp His Tyr Arg Tyr Ser Asp Thr Thr Asp 
    370                 375                 380 

Ser Asp Pro Glu Asn Glu Pro Phe Asp Glu Asp Gln His Thr Gln Ile 
385                 390                 395                 400 

Thr Lys Val 

 
           
             30  
             447  
             PRT  
             Homo sapiens  
           
            30 

Met Arg Ser Ser Thr Leu Gln Asp Pro Arg Arg Arg Asp Pro Gln Asp 
  1               5                  10                  15 

Asp Val Tyr Val Asp Ile Thr Asp Arg Leu Arg Phe Ala Ile Leu Tyr 
             20                  25                  30 

Ser Arg Pro Lys Ser Ala Ser Asn Val His Tyr Phe Ser Ile Asp Asn 
         35                  40                  45 

Glu Leu Glu Tyr Glu Asn Phe Ser Glu Asp Phe Gly Pro Leu Asn Leu 
     50                  55                  60 

Ala Met Val Tyr Arg Tyr Cys Cys Lys Ile Asn Lys Lys Leu Lys Ser 
 65                  70                  75                  80 

Ile Thr Met Leu Arg Lys Lys Ile Val His Phe Thr Gly Ser Asp Gln 
                 85                  90                  95 

Arg Lys Gln Ala Asn Ala Ala Phe Leu Val Gly Cys Tyr Met Val Ile 
            100                 105                 110 

Tyr Leu Gly Arg Thr Pro Glu Ala Ala Tyr Arg Ile Leu Ile Phe Gly 
        115                 120                 125 

Asp Thr Pro Tyr Ile Pro Phe Arg Asp Ala Ala Tyr Gly Ser Cys Asn 
    130                 135                 140 

Phe Tyr Ile Thr Leu Leu Asp Cys Phe His Ala Val Lys Lys Ala Met 
145                 150                 155                 160 

Gln Tyr Gly Phe Leu Asn Phe Asn Ser Phe Asn Leu Asp Glu Tyr Glu 
                165                 170                 175 

His Tyr Glu Lys Ala Glu Asn Gly Asp Leu Asn Trp Ile Ile Pro Asp 
            180                 185                 190 

Arg Phe Ile Ala Phe Cys Gly Pro His Ser Arg Ala Arg Leu Glu Ser 
        195                 200                 205 

Gly Tyr His Gln His Ser Pro Glu Thr Tyr Ile Gln Tyr Phe Lys Asn 
    210                 215                 220 

His Asn Val Thr Thr Ile Ile Arg Leu Asn Lys Arg Met Tyr Asp Ala 
225                 230                 235                 240 

Lys Arg Phe Thr Asp Ala Gly Phe Asp His His Asp Leu Phe Phe Ala 
                245                 250                 255 

Asp Gly Ser Thr Pro Thr Asp Ala Ile Val Lys Arg Phe Leu Asp Ile 
            260                 265                 270 

Cys Glu Asn Ala Glu Gly Ala Ile Ala Val His Cys Lys Ala Gly Leu 
        275                 280                 285 

Gly Arg Thr Gly Thr Leu Ile Ala Cys Tyr Ile Met Lys His Tyr Arg 
    290                 295                 300 

Met Thr Ala Ala Glu Thr Ile Ala Trp Val Arg Ile Cys Arg Pro Gly 
305                 310                 315                 320 

Leu Val Ile Gly Pro Gln Gln Gln Phe Leu Val Met Lys Gln Thr Ser 
                325                 330                 335 

Leu Trp Leu Glu Gly Asp Tyr Phe Arg Gln Arg Leu Lys Gly Gln Glu 
            340                 345                 350 

Asn Gly Gln His Arg Ala Ala Phe Ser Lys Leu Leu Ser Gly Val Asp 
        355                 360                 365 

Asp Ile Ser Ile Asn Gly Val Glu Asn Gln Asp Gln Gln Glu Pro Lys 
    370                 375                 380 

Pro Tyr Ser Asp Asp Asp Glu Ile Asn Gly Val Thr Gln Gly Asp Arg 
385                 390                 395                 400 

Ser Arg Ala Leu Lys Arg Arg Arg Gln Ser Lys Thr Asn Asp Ile Leu 
                405                 410                 415 

Leu Pro Ser Pro Leu Ala Val Leu Thr Phe Thr Leu Cys Ser Val Val 
            420                 425                 430 

Ile Trp Trp Ile Val Cys Asp Tyr Ile Leu Pro Ile Leu Leu Phe 
        435                 440                 445 

 
           
             31  
             340  
             PRT  
             Homo sapiens  
           
            31 

Met Leu Glu Ala Pro Gly Pro Ser Asp Gly Cys Glu Leu Ser Asn Pro 
  1               5                  10                  15 

Ser Ala Ser Arg Val Ser Cys Ala Gly Gln Met Leu Glu Val Gln Pro 
             20                  25                  30 

Gly Leu Tyr Phe Gly Gly Ala Ala Ala Val Ala Glu Pro Asp His Leu 
         35                  40                  45 

Arg Glu Ala Gly Ile Thr Ala Val Leu Thr Val Asp Ser Glu Glu Pro 
     50                  55                  60 

Ser Phe Lys Ala Gly Pro Gly Val Glu Asp Leu Trp Arg Leu Phe Val 
 65                  70                  75                  80 

Pro Ala Leu Asp Lys Pro Glu Thr Asp Leu Leu Ser His Leu Asp Arg 
                 85                  90                  95 

Cys Val Ala Phe Ile Gly Gln Ala Arg Ala Glu Gly Arg Ala Val Leu 
            100                 105                 110 

Val His Cys His Ala Gly Val Ser Arg Ser Val Ala Ile Ile Thr Ala 
        115                 120                 125 

Phe Leu Met Lys Thr Asp Gln Leu Pro Phe Glu Lys Ala Tyr Glu Lys 
    130                 135                 140 

Leu Gln Ile Leu Lys Pro Glu Ala Lys Met Asn Glu Gly Phe Glu Trp 
145                 150                 155                 160 

Gln Leu Lys Leu Tyr Gln Ala Met Gly Tyr Glu Val Asp Thr Ser Ser 
                165                 170                 175 

Ala Ile Tyr Lys Gln Tyr Arg Leu Gln Lys Val Thr Glu Lys Tyr Pro 
            180                 185                 190 

Glu Leu Gln Asn Leu Pro Gln Glu Leu Phe Ala Val Asp Pro Thr Thr 
        195                 200                 205 

Val Ser Gln Gly Leu Lys Asp Glu Val Leu Tyr Lys Cys Arg Lys Cys 
    210                 215                 220 

Arg Arg Ser Leu Phe Arg Ser Ser Ser Ile Leu Asp His Arg Glu Gly 
225                 230                 235                 240 

Ser Gly Pro Ile Ala Phe Ala His Lys Arg Met Thr Pro Ser Ser Met 
                245                 250                 255 

Leu Thr Thr Gly Arg Gln Ala Gln Cys Thr Ser Tyr Phe Ile Glu Pro 
            260                 265                 270 

Val Gln Trp Met Glu Ser Ala Leu Leu Gly Val Met Asp Gly Gln Leu 
        275                 280                 285 

Leu Cys Pro Lys Cys Ser Ala Lys Leu Gly Ser Phe Asn Trp Tyr Gly 
    290                 295                 300 

Glu Gln Cys Ser Cys Gly Arg Trp Ile Thr Pro Ala Phe Gln Ile His 
305                 310                 315                 320 

Lys Asn Arg Val Asp Glu Met Lys Ile Leu Pro Val Leu Gly Ser Gln 
                325                 330                 335 

Thr Gly Lys Ile 
            340 

 
           
             32  
             150  
             PRT  
             Homo sapiens  
           
            32 

Met Gly Val Gln Pro Pro Asn Phe Ser Trp Val Leu Pro Gly Arg Leu 
  1               5                  10                  15 

Ala Gly Leu Ala Leu Pro Arg Leu Pro Ala His Tyr Gln Phe Leu Leu 
             20                  25                  30 

Asp Leu Gly Val Arg His Leu Val Ser Leu Thr Glu Arg Gly Pro Pro 
         35                  40                  45 

His Ser Asp Ser Cys Pro Gly Leu Thr Leu His Arg Leu Arg Ile Pro 
     50                  55                  60 

Asp Phe Cys Pro Pro Ala Pro Asp Gln Ile Asp Arg Phe Val Gln Ile 
 65                  70                  75                  80 

Val Asp Glu Ala Asn Ala Arg Gly Glu Ala Val Gly Val His Cys Ala 
                 85                  90                  95 

Leu Gly Phe Gly Arg Thr Gly Thr Met Leu Ala Cys Tyr Leu Val Lys 
            100                 105                 110 

Glu Arg Gly Leu Ala Ala Gly Asp Ala Ile Ala Glu Ile Arg Arg Leu 
        115                 120                 125 

Arg Pro Gly Pro Ile Glu Thr Tyr Glu Gln Glu Lys Ala Val Phe Gln 
    130                 135                 140 

Phe Tyr Gln Arg Thr Lys 
145                 150 

 
           
             33  
             322  
             PRT  
             Homo sapiens  
           
            33 

Gly Leu Met Leu Arg Arg Leu Arg Lys Gly Asn Leu Pro Ile Arg Ser 
  1               5                  10                  15 

Ile Ile Pro Asn His Ala Asp Lys Glu Arg Phe Ala Thr Arg Cys Lys 
             20                  25                  30 

Ala Ala Thr Val Leu Leu Tyr Asp Glu Ala Thr Ala Glu Trp Gln Pro 
         35                  40                  45 

Glu Pro Gly Ala Pro Ala Ser Val Leu Gly Leu Leu Leu Gln Lys Leu 
     50                  55                  60 

Arg Asp Asp Gly Cys Gln Ala Tyr Tyr Leu Gln Gly Gly Phe Asn Lys 
 65                  70                  75                  80 

Phe Gln Thr Glu Tyr Ser Glu His Cys Glu Thr Asn Val Asp Ser Ser 
                 85                  90                  95 

Ser Ser Pro Ser Ser Ser Pro Pro Thr Ser Val Leu Gly Leu Gly Gly 
            100                 105                 110 

Leu Arg Ile Ser Ser Asp Cys Ser Asp Gly Glu Ser Asp Arg Glu Leu 
        115                 120                 125 

Pro Ser Ser Ala Thr Glu Ser Asp Gly Ser Pro Val Pro Ser Ser Gln 
    130                 135                 140 

Pro Ala Phe Pro Val Gln Ile Leu Pro Tyr Leu Tyr Leu Gly Cys Ala 
145                 150                 155                 160 

Lys Asp Ser Thr Asn Leu Asp Val Leu Gly Lys Tyr Gly Ile Lys Tyr 
                165                 170                 175 

Ile Leu Asn Val Thr Pro Asn Leu Pro Asn Ala Phe Glu His Gly Gly 
            180                 185                 190 

Glu Phe Thr Tyr Lys Gln Ile Pro Ile Ser Asp His Trp Ser Gln Asn 
        195                 200                 205 

Leu Ser Gln Phe Phe Pro Glu Ala Ile Ser Phe Ile Asp Glu Ala Arg 
    210                 215                 220 

Ser Lys Lys Cys Gly Val Leu Val His Cys Leu Ala Gly Ile Ser Arg 
225                 230                 235                 240 

Ser Val Thr Val Thr Val Ala Tyr Leu Met Gln Lys Met Asn Leu Ser 
                245                 250                 255 

Leu Asn Asp Ala Tyr Asp Phe Val Lys Arg Lys Lys Ser Asn Ile Ser 
            260                 265                 270 

Pro Asn Phe Asn Phe Met Gly Gln Leu Leu Asp Phe Glu Arg Thr Leu 
        275                 280                 285 

Gly Leu Ser Ser Pro Cys Asp Asn His Ala Ser Ser Glu Gln Leu Tyr 
    290                 295                 300 

Phe Ser Thr Pro Thr Asn His Asn Leu Phe Pro Leu Asn Thr Leu Glu 
305                 310                 315                 320 

Ser Thr 

 
           
             34  
             521  
             PRT  
             Homo sapiens  
           
            34 

Met Ser Glu Pro Lys Ala Ile Asp Pro Lys Leu Ser Thr Thr Asp Arg 
  1               5                  10                  15 

Val Val Lys Ala Val Pro Phe Pro Pro Ser His Arg Leu Thr Ala Lys 
             20                  25                  30 

Glu Val Phe Asp Asn Asp Gly Lys Pro Arg Val Asp Ile Leu Lys Ala 
         35                  40                  45 

His Leu Met Lys Glu Gly Arg Leu Glu Glu Ser Val Ala Leu Arg Ile 
     50                  55                  60 

Ile Thr Glu Gly Ala Ser Ile Leu Arg Gln Glu Lys Asn Leu Leu Asp 
 65                  70                  75                  80 

Ile Asp Ala Pro Val Thr Val Cys Gly Asp Ile His Gly Gln Phe Phe 
                 85                  90                  95 

Asp Leu Met Lys Leu Phe Glu Val Gly Gly Ser Pro Ala Asn Thr Arg 
            100                 105                 110 

Tyr Leu Phe Leu Gly Asp Tyr Val Asp Arg Gly Tyr Phe Ser Ile Glu 
        115                 120                 125 

Cys Val Leu Tyr Leu Trp Ala Leu Lys Ile Leu Tyr Pro Lys Thr Leu 
    130                 135                 140 

Phe Leu Leu Arg Gly Asn His Glu Cys Arg His Leu Thr Glu Tyr Phe 
145                 150                 155                 160 

Thr Phe Lys Gln Glu Cys Lys Ile Lys Tyr Ser Glu Arg Val Tyr Asp 
                165                 170                 175 

Ala Cys Met Asp Ala Phe Asp Cys Leu Pro Leu Ala Ala Leu Met Asn 
            180                 185                 190 

Gln Gln Phe Leu Cys Val His Gly Gly Leu Ser Pro Glu Ile Asn Thr 
        195                 200                 205 

Leu Asp Asp Ile Arg Lys Leu Asp Arg Phe Lys Glu Pro Pro Ala Tyr 
    210                 215                 220 

Gly Pro Met Cys Asp Ile Leu Trp Ser Asp Pro Leu Glu Asp Phe Gly 
225                 230                 235                 240 

Asn Glu Lys Thr Gln Glu His Phe Thr His Asn Thr Val Arg Gly Cys 
                245                 250                 255 

Ser Tyr Phe Tyr Ser Tyr Pro Ala Val Cys Glu Phe Leu Gln His Asn 
            260                 265                 270 

Asn Leu Leu Ser Ile Leu Arg Ala His Glu Ala Gln Asp Ala Gly Tyr 
        275                 280                 285 

Arg Met Tyr Arg Lys Ser Gln Thr Thr Gly Phe Pro Ser Leu Ile Thr 
    290                 295                 300 

Ile Phe Ser Ala Pro Asn Tyr Leu Asp Val Tyr Asn Asn Lys Ala Ala 
305                 310                 315                 320 

Val Leu Lys Tyr Glu Asn Asn Val Met Asn Ile Arg Gln Phe Asn Cys 
                325                 330                 335 

Ser Pro His Pro Tyr Trp Leu Pro Asn Phe Met Asp Val Phe Thr Trp 
            340                 345                 350 

Ser Leu Pro Phe Val Gly Glu Lys Val Thr Glu Met Leu Val Asn Val 
        355                 360                 365 

Leu Asn Ile Cys Ser Asp Asp Glu Leu Gly Ser Glu Glu Asp Gly Phe 
    370                 375                 380 

Asp Gly Ala Thr Ala Ala Ala Arg Lys Glu Val Ile Arg Asn Lys Ile 
385                 390                 395                 400 

Arg Ala Ile Gly Lys Met Ala Arg Val Phe Ser Val Leu Arg Glu Glu 
                405                 410                 415 

Ser Glu Ser Val Leu Thr Leu Lys Gly Leu Thr Pro Thr Gly Met Leu 
            420                 425                 430 

Pro Ser Gly Val Leu Ser Gly Gly Lys Gln Thr Leu Gln Ser Ala Thr 
        435                 440                 445 

Val Glu Ala Ile Glu Ala Asp Glu Ala Ile Lys Gly Phe Ser Pro Gln 
    450                 455                 460 

His Lys Ile Thr Ser Phe Glu Glu Ala Lys Gly Leu Asp Arg Ile Asn 
465                 470                 475                 480 

Glu Arg Met Pro Pro Arg Arg Asp Ala Met Pro Ser Asp Ala Asn Leu 
                485                 490                 495 

Asn Ser Ile Asn Lys Ala Leu Thr Ser Glu Thr Asn Gly Thr Asp Ser 
            500                 505                 510 

Asn Gly Ser Asn Ser Ser Asn Ile Gln 
        515                 520 

 
           
             35  
             1267  
             PRT  
             Homo sapiens  
           
            35 

Asp Leu Ser Arg Ser His Cys His Val Tyr Leu Ala His Leu Glu Asn 
  1               5                  10                  15 

Ser Phe Gly Pro Ser Gly Ala Arg Glu Gly Ser Leu Ser Ser Gln Asp 
             20                  25                  30 

Ser Arg Thr Glu Ser Ala Ser Leu Ser Gln Ser Gln Val Asn Gly Phe 
         35                  40                  45 

Phe Ala Ser His Leu Gly Asp Gln Thr Trp Gln Glu Ser Gln His Gly 
     50                  55                  60 

Ser Pro Ser Pro Ser Val Ile Ser Lys Ala Thr Glu Lys Glu Thr Phe 
 65                  70                  75                  80 

Thr Asp Ser Asn Gln Ser Lys Thr Lys Lys Pro Gly Ile Ser Asp Val 
                 85                  90                  95 

Thr Asp Tyr Ser Asp Arg Gly Asp Ser Asp Met Asp Glu Ala Thr Tyr 
            100                 105                 110 

Ser Ser Ser Gln Asp His Gln Thr Pro Lys Gln Glu Ser Ser Ser Ser 
        115                 120                 125 

Val Asn Thr Ser Asn Lys Met Asn Phe Lys Thr Phe Pro Ser Ser Pro 
    130                 135                 140 

Pro Arg Ser Gly Asp Ile Phe Glu Val Glu Leu Ala Lys Asn Asp Asn 
145                 150                 155                 160 

Ser Leu Gly Ile Ser Val Thr Gly Gly Val Asn Thr Ser Val Arg His 
                165                 170                 175 

Gly Gly Ile Tyr Val Lys Ala Val Ile Pro Gln Gly Ala Ala Glu Ser 
            180                 185                 190 

Asp Gly Arg Ile His Lys Gly Asp Arg Val Leu Ala Val Asn Gly Val 
        195                 200                 205 

Ser Leu Glu Gly Ala Thr His Lys Gln Ala Val Glu Thr Leu Arg Asn 
    210                 215                 220 

Thr Gly Gln Val Val His Leu Leu Leu Glu Lys Gly Gln Ser Pro Thr 
225                 230                 235                 240 

Ser Lys Glu His Val Pro Val Thr Pro Gln Cys Thr Leu Ser Asp Gln 
                245                 250                 255 

Asn Ala Gln Gly Gln Gly Pro Glu Lys Val Lys Lys Thr Thr Gln Val 
            260                 265                 270 

Lys Asp Tyr Ser Phe Val Thr Glu Glu Asn Thr Phe Glu Val Lys Leu 
        275                 280                 285 

Phe Lys Asn Ser Ser Gly Leu Gly Phe Ser Phe Ser Arg Glu Asp Asn 
    290                 295                 300 

Leu Ile Pro Glu Gln Ile Asn Ala Ser Ile Val Arg Val Lys Lys Leu 
305                 310                 315                 320 

Phe Pro Gly Gln Pro Ala Ala Glu Ser Gly Lys Ile Asp Val Gly Asp 
                325                 330                 335 

Val Ile Leu Lys Val Asn Gly Ala Ser Leu Lys Gly Leu Ser Gln Gln 
            340                 345                 350 

Glu Val Ile Ser Ala Leu Arg Gly Thr Ala Pro Glu Val Phe Leu Leu 
        355                 360                 365 

Leu Cys Arg Pro Pro Pro Gly Val Leu Pro Glu Ile Asp Thr Ala Leu 
    370                 375                 380 

Leu Thr Pro Leu Gln Ser Pro Ala Gln Val Leu Pro Asn Ser Ser Lys 
385                 390                 395                 400 

Asp Ser Ser Gln Pro Ser Cys Val Glu Gln Ser Thr Ser Ser Asp Glu 
                405                 410                 415 

Asn Glu Met Ser Asp Lys Ser Lys Lys Gln Cys Lys Ser Pro Ser Arg 
            420                 425                 430 

Lys Asp Ser Tyr Ser Asp Ser Ser Gly Ser Gly Glu Asp Asp Leu Val 
        435                 440                 445 

Thr Ala Pro Ala Asn Ile Ser Asn Ser Thr Trp Ser Ser Ala Leu His 
    450                 455                 460 

Gln Thr Leu Ser Asn Met Val Ser Gln Ala Gln Ser His His Glu Ala 
465                 470                 475                 480 

Pro Arg Val Lys Lys Ile Pro Phe Val Pro Cys Phe Thr Ile Leu Arg 
                485                 490                 495 

Lys Arg Pro Asn Lys Pro Glu Phe Glu Asp Ser Asn Pro Ser Pro Leu 
            500                 505                 510 

Pro Pro Asp Met Ala Pro Gly Gln Ser Tyr Gln Pro Gln Ser Glu Ser 
        515                 520                 525 

Ala Ser Ser Ser Ser Met Asp Lys Tyr His Ile His His Ile Ser Glu 
    530                 535                 540 

Pro Thr Arg Gln Glu Asn Trp Thr Pro Leu Lys Asn Asp Leu Glu Asn 
545                 550                 555                 560 

His Leu Glu Asp Phe Glu Leu Glu Val Glu Leu Leu Ile Thr Leu Ile 
                565                 570                 575 

Lys Ser Glu Lys Gly Ser Leu Gly Phe Thr Val Thr Lys Gly Asn Gln 
            580                 585                 590 

Arg Ile Gly Cys Tyr Val His Asp Val Ile Gln Asp Pro Ala Lys Ser 
        595                 600                 605 

Asp Gly Arg Leu Lys Pro Gly Asp Arg Leu Ile Lys Val Asn Asp Thr 
    610                 615                 620 

Asp Val Thr Asn Met Thr His Thr Asp Ala Val Asn Leu Leu Arg Gly 
625                 630                 635                 640 

Ser Lys Thr Val Arg Leu Val Ile Gly Arg Val Leu Glu Leu Pro Arg 
                645                 650                 655 

Ile Pro Met Leu Pro His Leu Leu Pro Asp Ile Thr Leu Thr Cys Asn 
            660                 665                 670 

Lys Glu Glu Leu Gly Phe Ser Leu Cys Gly Gly His Asp Ser Leu Tyr 
        675                 680                 685 

Gln Val Val Tyr Ile Ser Asp Ile Asn Pro Arg Ser Val Ala Ala Ile 
    690                 695                 700 

Glu Gly Asn Leu Gln Leu Leu Asp Val Ile His Tyr Val Asn Gly Val 
705                 710                 715                 720 

Ser Thr Gln Gly Met Thr Leu Glu Glu Val Asn Arg Ala Leu Asp Met 
                725                 730                 735 

Ser Leu Pro Ser Leu Val Leu Lys Ala Thr Arg Asn Asp Leu Pro Val 
            740                 745                 750 

Val Pro Ser Ser Lys Arg Ser Ala Val Ser Ala Pro Lys Ser Thr Lys 
        755                 760                 765 

Gly Asn Gly Ser Tyr Ser Val Gly Ser Cys Ser Gln Pro Ala Leu Thr 
    770                 775                 780 

Pro Asn Asp Ser Phe Ser Thr Val Ala Gly Glu Glu Ile Asn Glu Ile 
785                 790                 795                 800 

Ser Tyr Pro Lys Gly Lys Cys Ser Thr Tyr Gln Ile Lys Gly Ser Pro 
                805                 810                 815 

Asn Leu Thr Leu Pro Lys Glu Ser Tyr Ile Gln Glu Asp Asp Ile Tyr 
            820                 825                 830 

Asp Asp Ser Gln Glu Ala Glu Val Ile Gln Ser Leu Leu Asp Val Val 
        835                 840                 845 

Asp Glu Glu Ser Gln Asn Leu Leu Asn Glu Asn Asn Ala Ala Gly Tyr 
    850                 855                 860 

Ser Cys Gly Pro Gly Thr Leu Lys Met Asn Gly Lys Leu Ser Glu Glu 
865                 870                 875                 880 

Arg Thr Glu Asp Thr Asp Cys Asp Gly Ser Pro Leu Pro Glu Tyr Phe 
                885                 890                 895 

Thr Glu Ala Thr Lys Met Asn Gly Cys Glu Glu Tyr Cys Glu Glu Lys 
            900                 905                 910 

Val Lys Ser Glu Ser Leu Ile Gln Lys Pro Gln Glu Lys Lys Thr Asp 
        915                 920                 925 

Asp Asp Glu Ile Thr Trp Gly Asn Asp Glu Leu Pro Ile Glu Arg Thr 
    930                 935                 940 

Asn His Glu Asp Ser Asp Lys Asp His Ser Phe Leu Thr Asn Asp Glu 
945                 950                 955                 960 

Leu Ala Val Leu Pro Val Val Lys Val Leu Pro Ser Gly Lys Tyr Thr 
                965                 970                 975 

Gly Ala Asn Leu Lys Ser Val Ile Arg Val Leu Arg Val Ala Arg Ser 
            980                 985                 990 

Gly Ile Pro Ser Lys Glu Leu Glu Asn Leu Gln Glu Leu Lys Pro Leu 
        995                1000                1005 

Asp Gln Cys Leu Ile Gly Gln Thr Lys Glu Asn Arg Arg Lys Asn Arg 
   1010                1015                1020 

Tyr Lys Asn Ile Leu Pro Tyr Asp Ala Thr Arg Val Pro Leu Gly Asp 
1025               1030                1035                1040 

Glu Gly Gly Tyr Ile Asn Ala Ser Phe Ile Lys Ile Pro Val Gly Lys 
               1045                1050                1055 

Glu Glu Phe Val Tyr Ile Ala Cys Gln Gly Pro Leu Pro Thr Thr Val 
           1060                1065                1070 

Gly Asp Phe Trp Gln Met Ile Trp Glu Gln Lys Ser Thr Val Ile Ala 
       1075                1080                1085 

Met Met Thr Gln Glu Val Glu Gly Glu Lys Ile Lys Cys Gln Arg Tyr 
   1090                1095                1100 

Trp Pro Asn Ile Leu Gly Lys Thr Thr Met Val Ser Asn Arg Leu Arg 
1105               1110                1115                1120 

Leu Ala Leu Val Arg Met Gln Gln Leu Lys Gly Phe Val Val Arg Ala 
               1125                1130                1135 

Met Thr Leu Glu Asp Ile Gln Thr Arg Glu Val Arg His Ile Ser His 
           1140                1145                1150 

Leu Asn Phe Thr Ala Trp Pro Asp His Asp Thr Pro Ser Gln Pro Asp 
       1155                1160                1165 

Asp Leu Leu Thr Phe Ile Ser Tyr Met Arg His Ile His Arg Ser Gly 
   1170                1175                1180 

Pro Ile Ile Thr His Cys Ser Ala Gly Ile Gly Arg Ser Gly Thr Leu 
1185               1190                1195                1200 

Ile Cys Ile Asp Val Val Leu Gly Leu Ile Ser Gln Asp Leu Asp Phe 
               1205                1210                1215 

Asp Ile Ser Asp Leu Val Arg Cys Met Arg Leu Gln Arg His Gly Met 
           1220                1225                1230 

Val Gln Thr Glu Asp Gln Tyr Ile Phe Cys Tyr Gln Val Ile Leu Tyr 
       1235                1240                1245 

Val Leu Thr Arg Leu Gln Ala Glu Glu Glu Gln Lys Gln Gln Pro Gln 
   1250                1255                1260 

Leu Leu Lys 
1265 

 
           
             36  
             551  
             PRT  
             Homo sapiens  
           
            36 

Met Asn Glu Ser Pro Asp Pro Thr Asp Leu Ala Gly Val Ile Ile Glu 
  1               5                  10                  15 

Leu Gly Pro Asn Asp Ser Pro Gln Thr Ser Glu Phe Lys Gly Ala Thr 
             20                  25                  30 

Glu Glu Ala Pro Ala Lys Glu Ser Pro His Thr Ser Glu Phe Lys Gly 
         35                  40                  45 

Ala Ala Arg Val Ser Pro Ile Ser Glu Ser Val Leu Ala Arg Leu Ser 
     50                  55                  60 

Lys Phe Glu Val Glu Asp Ala Glu Asn Val Ala Ser Tyr Asp Ser Lys 
 65                  70                  75                  80 

Ile Lys Lys Ile Val His Ser Ile Val Ser Ser Phe Ala Phe Gly Leu 
                 85                  90                  95 

Phe Gly Val Phe Leu Val Leu Leu Asp Val Thr Leu Ile Leu Ala Asp 
            100                 105                 110 

Leu Ile Phe Thr Asp Ser Lys Leu Tyr Ile Pro Leu Glu Tyr Arg Ser 
        115                 120                 125 

Ile Ser Leu Ala Ile Ala Leu Phe Phe Leu Met Asp Val Leu Leu Arg 
    130                 135                 140 

Val Phe Val Glu Arg Arg Gln Gln Tyr Phe Ser Asp Leu Phe Asn Ile 
145                 150                 155                 160 

Leu Asp Thr Ala Ile Ile Val Ile Leu Leu Leu Val Asp Val Val Tyr 
                165                 170                 175 

Ile Phe Phe Asp Ile Lys Leu Leu Arg Asn Ile Pro Arg Trp Thr His 
            180                 185                 190 

Leu Leu Arg Leu Leu Arg Leu Ile Ile Leu Leu Arg Ile Phe His Leu 
        195                 200                 205 

Phe His Gln Lys Arg Gln Leu Glu Lys Leu Ile Arg Arg Arg Val Ser 
    210                 215                 220 

Glu Asn Lys Arg Arg Tyr Thr Arg Asp Gly Phe Asp Leu Asp Leu Thr 
225                 230                 235                 240 

Tyr Val Thr Glu Arg Ile Ile Ala Met Ser Phe Pro Ser Ser Gly Arg 
                245                 250                 255 

Gln Ser Phe Tyr Arg Asn Pro Ile Lys Glu Val Val Arg Phe Leu Asp 
            260                 265                 270 

Lys Lys His Arg Asn His Tyr Arg Val Tyr Asn Leu Cys Ser Glu Arg 
        275                 280                 285 

Ala Tyr Asp Pro Lys His Phe His Asn Arg Val Val Arg Ile Met Ile 
    290                 295                 300 

Asp Asp His Asn Val Pro Thr Leu His Gln Met Val Val Phe Thr Lys 
305                 310                 315                 320 

Glu Val Asn Glu Trp Met Ala Gln Asp Leu Glu Asn Ile Val Ala Ile 
                325                 330                 335 

His Cys Lys Gly Gly Thr Asp Arg Thr Gly Thr Met Val Cys Ala Phe 
            340                 345                 350 

Leu Ile Ala Ser Glu Ile Cys Ser Thr Ala Lys Glu Ser Leu Tyr Tyr 
        355                 360                 365 

Phe Gly Glu Arg Arg Thr Asp Lys Thr His Ser Glu Lys Phe Gln Gly 
    370                 375                 380 

Val Glu Thr Pro Ser Gln Lys Arg Tyr Val Ala Tyr Phe Ala Gln Val 
385                 390                 395                 400 

Lys His Leu Tyr Asn Trp Asn Leu Pro Pro Arg Arg Ile Leu Phe Ile 
                405                 410                 415 

Lys His Phe Ile Ile Tyr Ser Ile Pro Arg Tyr Val Arg Asp Leu Lys 
            420                 425                 430 

Ile Gln Ile Glu Met Glu Lys Lys Val Val Phe Ser Thr Ile Ser Leu 
        435                 440                 445 

Gly Lys Cys Ser Val Leu Asp Asn Ile Thr Thr Asp Lys Ile Leu Ile 
    450                 455                 460 

Asp Val Phe Asp Gly Pro Pro Leu Tyr Asp Asp Val Lys Val Gln Phe 
465                 470                 475                 480 

Phe Tyr Ser Asn Leu Pro Thr Tyr Tyr Asp Asn Cys Ser Phe Tyr Phe 
                485                 490                 495 

Trp Leu His Thr Ser Phe Ile Glu Asn Asn Arg Leu Tyr Leu Pro Lys 
            500                 505                 510 

Asn Glu Leu Asp Asn Leu His Lys Gln Lys Ala Arg Arg Ile Tyr Pro 
        515                 520                 525 

Ser Asp Phe Ala Val Glu Ile Leu Phe Gly Glu Lys Met Thr Ser Ser 
    530                 535                 540 

Asp Val Val Ala Gly Ser Asp 
545                 550 

 
           
             37  
             323  
             PRT  
             Homo sapiens  
           
            37 

Met Ala Asp Leu Asp Lys Leu Asn Ile Asp Ser Ile Ile Gln Arg Leu 
  1               5                  10                  15 

Leu Glu Val Arg Gly Ser Lys Pro Gly Lys Asn Val Gln Leu Gln Glu 
             20                  25                  30 

Asn Glu Ile Arg Gly Leu Cys Leu Lys Ser Arg Glu Ile Phe Leu Ser 
         35                  40                  45 

Gln Pro Ile Leu Leu Glu Leu Glu Ala Pro Leu Lys Ile Cys Gly Asp 
     50                  55                  60 

Ile His Gly Gln Tyr Tyr Asp Leu Leu Arg Leu Phe Glu Tyr Gly Gly 
 65                  70                  75                  80 

Phe Pro Pro Glu Ser Asn Tyr Leu Phe Leu Gly Asp Tyr Val Asp Arg 
                 85                  90                  95 

Gly Lys Gln Ser Leu Glu Thr Ile Cys Leu Leu Leu Ala Tyr Lys Ile 
            100                 105                 110 

Lys Tyr Pro Glu Asn Phe Phe Leu Leu Arg Gly Asn His Glu Cys Ala 
        115                 120                 125 

Ser Ile Asn Arg Ile Tyr Gly Phe Tyr Asp Glu Cys Lys Arg Arg Tyr 
    130                 135                 140 

Asn Ile Lys Leu Trp Lys Thr Phe Thr Asp Cys Phe Asn Cys Leu Pro 
145                 150                 155                 160 

Ile Ala Ala Ile Val Asp Glu Lys Ile Phe Cys Cys His Gly Gly Leu 
                165                 170                 175 

Ser Pro Asp Leu Gln Ser Met Glu Gln Ile Arg Arg Ile Met Arg Pro 
            180                 185                 190 

Thr Asp Val Pro Asp Gln Gly Leu Leu Cys Asp Leu Leu Trp Ser Asp 
        195                 200                 205 

Pro Asp Lys Asp Val Leu Gly Trp Gly Glu Asn Asp Arg Gly Val Ser 
    210                 215                 220 

Phe Thr Phe Gly Ala Glu Val Val Ala Lys Phe Leu His Lys His Asp 
225                 230                 235                 240 

Leu Asp Leu Ile Cys Arg Ala His Gln Val Val Glu Asp Gly Tyr Glu 
                245                 250                 255 

Phe Phe Ala Lys Arg Gln Leu Val Thr Leu Phe Ser Ala Pro Asn Tyr 
            260                 265                 270 

Cys Gly Glu Phe Asp Asn Ala Gly Ala Met Met Ser Val Asp Glu Thr 
        275                 280                 285 

Leu Met Cys Ser Phe Gln Ile Leu Lys Pro Ala Glu Lys Lys Lys Pro 
    290                 295                 300 

Asn Ala Thr Arg Pro Val Thr Pro Pro Arg Gly Met Ile Thr Lys Gln 
305                 310                 315                 320 

Ala Lys Lys 

 
           
             38  
             319  
             PRT  
             Homo sapiens  
           
            38 

Asp Lys Leu Asn Ile Asp Ser Ile Ile Gln Arg Leu Leu Glu Val Arg 
  1               5                  10                  15 

Gly Ser Lys Pro Gly Lys Asn Val Gln Leu Gln Glu Asn Glu Ile Arg 
             20                  25                  30 

Gly Leu Cys Leu Lys Ser Arg Glu Ile Phe Leu Ser Gln Pro Ile Leu 
         35                  40                  45 

Leu Glu Leu Glu Ala Pro Leu Lys Ile Cys Gly Asp Ile His Gly Gln 
     50                  55                  60 

Tyr Tyr Asp Leu Leu Arg Leu Phe Glu Tyr Gly Gly Phe Pro Pro Glu 
 65                  70                  75                  80 

Ser Asn Tyr Leu Phe Leu Gly Asp Tyr Val Asp Arg Gly Lys Gln Ser 
                 85                  90                  95 

Leu Glu Thr Ile Cys Leu Leu Leu Ala Tyr Lys Ile Lys Tyr Pro Glu 
            100                 105                 110 

Asn Phe Phe Leu Leu Arg Gly Asn His Glu Cys Ala Ser Ile Asn Arg 
        115                 120                 125 

Ile Tyr Gly Phe Tyr Asp Glu Cys Lys Arg Arg Tyr Asn Ile Lys Leu 
    130                 135                 140 

Trp Lys Thr Phe Thr Asp Cys Phe Asn Cys Leu Pro Ile Ala Ala Ile 
145                 150                 155                 160 

Val Asp Glu Lys Ile Phe Cys Cys His Gly Gly Leu Ser Pro Asp Leu 
                165                 170                 175 

Gln Ser Met Glu Gln Ile Arg Arg Ile Met Arg Pro Thr Asp Val Pro 
            180                 185                 190 

Asp Gln Gly Leu Leu Cys Asp Leu Leu Trp Ser Asp Pro Asp Lys Asp 
        195                 200                 205 

Val Leu Gly Trp Gly Glu Asn Asp Arg Gly Val Ser Phe Thr Phe Gly 
    210                 215                 220 

Ala Glu Val Val Ala Lys Phe Leu His Lys His Asp Leu Asp Leu Ile 
225                 230                 235                 240 

Cys Arg Ala His Gln Val Val Glu Asp Gly Tyr Glu Phe Phe Ala Lys 
                245                 250                 255 

Arg Gln Leu Val Thr Leu Phe Ser Ala Pro Asn Tyr Cys Gly Glu Phe 
            260                 265                 270 

Asp Asn Ala Gly Ala Met Met Ser Val Asp Glu Thr Leu Met Cys Ser 
        275                 280                 285 

Phe Gln Ile Leu Lys Pro Ala Glu Lys Lys Lys Pro Asn Ala Thr Arg 
    290                 295                 300 

Pro Val Thr Pro Pro Arg Gly Met Ile Thr Lys Gln Ala Lys Lys 
305                 310                 315 

 
           
             39  
             309  
             PRT  
             Homo sapiens  
           
            39 

Met Asp Glu Lys Val Phe Thr Lys Glu Leu Asp Gln Trp Ile Glu Gln 
  1               5                  10                  15 

Leu Asn Glu Cys Lys Gln Leu Ser Glu Ser Gln Val Lys Ser Leu Cys 
             20                  25                  30 

Glu Lys Ala Lys Glu Ile Leu Thr Lys Glu Ser Asn Val Gln Glu Val 
         35                  40                  45 

Arg Cys Pro Val Thr Val Cys Gly Asp Val His Gly Gln Phe His Asp 
     50                  55                  60 

Leu Met Glu Leu Phe Arg Ile Gly Gly Lys Ser Pro Asp Thr Asn Tyr 
 65                  70                  75                  80 

Leu Phe Met Gly Asp Tyr Val Asp Arg Gly Tyr Tyr Ser Val Glu Thr 
                 85                  90                  95 

Val Thr Leu Leu Val Ala Leu Lys Val Arg Tyr Arg Glu Arg Ile Thr 
            100                 105                 110 

Ile Leu Arg Gly Asn His Glu Ser Arg Gln Ile Thr Gln Val Tyr Gly 
        115                 120                 125 

Phe Tyr Asp Glu Cys Leu Arg Lys Tyr Gly Asn Ala Asn Val Trp Lys 
    130                 135                 140 

Tyr Phe Thr Asp Leu Phe Asp Tyr Leu Pro Leu Thr Ala Leu Val Asp 
145                 150                 155                 160 

Gly Gln Ile Phe Cys Leu His Gly Gly Leu Ser Pro Ser Ile Asp Thr 
                165                 170                 175 

Leu Asp His Ile Arg Ala Leu Asp Arg Leu Gln Glu Val Pro His Glu 
            180                 185                 190 

Gly Pro Met Cys Asp Leu Leu Trp Ser Asp Pro Asp Asp Arg Gly Gly 
        195                 200                 205 

Trp Gly Ile Ser Pro Arg Gly Ala Gly Tyr Thr Phe Gly Gln Asp Ile 
    210                 215                 220 

Ser Glu Thr Phe Asn His Ala Asn Gly Leu Thr Leu Val Ser Arg Ala 
225                 230                 235                 240 

His Gln Leu Val Met Glu Gly Tyr Asn Trp Cys His Asp Arg Asn Val 
                245                 250                 255 

Val Thr Ile Phe Ser Ala Pro Asn Tyr Cys Tyr Arg Cys Gly Asn Gln 
            260                 265                 270 

Ala Ala Ile Met Glu Leu Asp Asp Thr Leu Lys Tyr Ser Phe Leu Gln 
        275                 280                 285 

Phe Asp Pro Ala Pro Arg Arg Gly Glu Pro His Val Thr Arg Arg Thr 
    290                 295                 300 

Pro Asp Tyr Phe Leu 
305 

 
           
             40  
             20  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            40 

tacggaagtg ttacttctgc                                                 20 

 
           
             41  
             20  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            41 

tgtgggaggt tttttctcta                                                 20 

 
           
             42  
             17  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            42 

gttttcccag tcacgac                                                    17 

 
           
             43  
             17  
             DNA  
             Artificial Sequence  
             
               Artificially Synthesized Primer Sequence  
             
           
            43 

caggaaacag ctatgac                                                    17

Technology Classification (CPC): 0