CN101300274A - Immunomodulatory compositions and uses therefor - Google Patents

Abstract

The poxvirus proteins designated A41L and 130L bind to three receptor-like protein tyrosine phosphatases (RPTP), leukocyte common antigen related protein (LAR), RPTP d, and RPTP-s, that are present on the cell surface of immune cells. When a host is infected with the poxvirus, binding of A41L to cell surface proteins on the host cells results in suppression of the immune response. The present invention provides agents such as antibodies, and antigen-binding fragments thereof, small molecules, aptamers, small interfering RNAs, and peptide-IgFc fusion polypeptides that interact with one or more of LAR, RPTP-d, and RPTP-s expressed by immune cells or interact with a polynucleotide encoding the RPTP. Also provided are RPTP Ig domain oligomers and Fc fusion polypeptides. Such agents are useful for treating an immunological disorder in a subject according to the methods described herein.

Description

Immune regulation composite and application thereof

Statement about the sequence table submitted to CD-ROM

The sequence table relevant with the application substitutes paper spare copy with CD-ROM and provides, and therefore is combined in the specification sheets by reference.3 CD-ROMs are provided, and it comprises the sequence table of identical version: CD-ROM No.1 is the version 1 of mark, comprises 0.76MB's and the file seq_930118_401.app.txt that generates on September 29th, 2006; CD-ROM No.2 is the version 2 of mark, comprises 0.76MB's and the file seq_930118_401.app.txt that generates on September 29th, 2006; CD-ROM No.3 is the CRF (computer-reader form) of mark, comprises 0.76MB's and the file seq_930118_401.app.txt that generates on September 29th, 2006.

Cross reference to related application

The application requires the U.S. Provisional Application submitted on September 29th, 2005 number 60/721,876; The U.S. Provisional Application of submitting on March 22nd, 2006 number 60/784,710; With the interests of the U.S. Provisional Application of submitting on May 19th, 2006 number 60/801,992, described application all is incorporated into this by reference fully.

Background of invention

Invention field

The invention provides to influence the three kinds of receptor-like protein tyrosine phosphatases (RPTP) that on the cell surface of immunocyte, exist: leukocyte common antigen (LCA) associated protein (LAR), the reagent of the function of one or more among RPTP-δ and the RPTP-σ with poxvirus albumen such as A41L and the same or analogous mode of 130L.Described reagent is effective to change the immunoreactivity of immunocyte, and is used for the treatment of the Immunological diseases among the experimenter.

Description of Related Art

Poxvirus forms one group and duplicate and be adapted at the double-stranded DNA virus that duplicates among many different hosts in the tenuigenin of cell.A kind of adaptation mechanism of many poxvirus comprises the acquisition of host gene, and it allows virus to escape host's immunity system and/or promotes virus replication (Bugert and Darai, VirusGenes (virogene) 21:111 (2000); Alcami etc., Semin.Virol. (virological investigation meeting) 8:419 (1998); McFadden and Barry, Semin.Virol. (virological investigation meeting) 8:429 (1998)).This effect is by the big relatively size of poxvirus genome group and complicacy and promote.Vaccinia virus, a kind of prototype poxvirus that is widely used as antismallpox vaccine has the genome of about 190kb, and it can be encoded potentially greater than 200 kinds of protein (Goebel etc., Virology (virusology) 179:247 (1990)).Even the whole genome of vaccinia virus all checks order, but the function of many potential open reading frame (ORFs) and thus the existence maintenance of encoded polypeptides be unknown.

Some poxvirus polypeptide helps the virulence of virus.The ORF that is appointed as A41L is present in some different poxvirus, comprises vaccinia virus (CPV), vaccinia virus (strain Copenhagen, Ankara, Tian Tan and WR) and variola virus (comprising strain Harvey, India-1967 and Garcia-1966).A kind of glycoprotein of A41L genes encoding (this paper is called the A41L polypeptide), it is a kind of virus virulence factor, its emiocytosis by the infection poxvirus (referring to, for example, U.S. Patent number 6,852,486; International application published WO 98/37217; Ng etc., J.Gen.Virol. (hereditary Journal of Virology) 82:2095-105 (2001)).A41L is the partial action inhibition immune response special to described virus at least in the host who infects poxvirus.

The evaluation of other virus virulence factor and express by immunocyte and with the evaluation of the interactional cell polypeptide of A41L, for the treatment Immunological diseases is useful and useful, described Immunological diseases are such as for example, inflammatory disease and autoimmune disorders, comprise the multiple sclerosis disease, rheumatoid arthritis, and system lupus erythematosus (SLE).There is the demand of identifying and developing the composition that can be used for described Immunological diseases and treatment of conditions and prevention.

The invention summary

Embodiments more as herein described relate to composition and the method that is used to prevent and treat Immunological diseases and illness.In one embodiment, a kind of isolated antibody or its antigen-binding fragment are provided, (a) its in conjunction with at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide, described receptor-like protein tyrosine phosphatase (RPTP) polypeptide is selected from (i) leukocyte common antigen (LCA) associated protein (LAR) specifically; (ii) RPTP-σ; (iii) RPTP-δ; (b) its competitive inhibition poxvirus polypeptide and described at least two kinds of RPTP polypeptide combines.In another embodiment, a kind of isolated antibody, or its antigen-binding fragment, be combined at least a receptor-like protein tyrosine phosphatase (RPTP) of the cell surface existence of immunocyte specifically, wherein said at least a RPTP is RPTP-σ or RPTP-δ, and the RPTP on wherein said antibody or its antigen-binding fragment and the cell surface that is present in immunocyte combine the immunoreactivity that suppresses immunocyte.In a special embodiment, described antibody is polyclonal antibody or monoclonal antibody.In other some special embodiment, described antigen-binding fragment is to be selected from F (ab ') ₂, Fab ', Fab, Fd, Fv and strand Fv (scFv).In another embodiment, described poxvirus polypeptide is A41L or tanapox virus 130L.This paper also provides the composition that comprises any antibody or its Fab and pharmaceutical excipient.Also be provided in another embodiment and suppress immunoreactive method among the experimenter, it comprises to described experimenter's applying said compositions.In another embodiment, provide treatment among the experimenter Immunological diseases or the method for illness, it comprises to described experimenter's applying said compositions.In another embodiment, be provided for producing described preparation of compositions method.

The present invention also provides a kind of bi-specific antibody, and it comprises first antigen-bound fraction that (a) can specificity bind receptor sample Protein-tyrosine-phosphatase (RPTP), and wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) can specificity in conjunction with second antigen-bound fraction of RPTP, wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ, wherein said first antigen-bound fraction is different with second antigen-bound fraction, and wherein said bi-specific antibody suppresses the immunoreactivity of immunocyte.The present invention also provides the composition that comprises described bi-specific antibody and medicinal suitable vehicle.The method that suppresses the immunne response among the experimenter also is provided in another embodiment, and it comprises to described experimenter's applying said compositions.In another embodiment, provide treatment among the experimenter Immunological diseases or the method for illness, it comprises to described experimenter's applying said compositions.In another embodiment, be provided for producing the preparation method of described bi-specific antibody.

In another embodiment, provide a kind of fusion polypeptide, it comprises immunoglobulin like domain 2 polypeptide of (a) the first receptor-like protein tyrosine phosphatase (RPTP); (b) immunoglobulin like domain 3 polypeptide of the 2nd RPTP; (c) immunoglobulin Fc polypeptide or its mutain, each of a wherein said RPTP and described the 2nd RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ, and wherein said first and second RPTP are identical or different.In a specific embodiment, a described RPTP is identical with the 2nd RPTP.In another specific embodiment, a described RPTP is RPTP-σ, and described the 2nd RPTP is RPTP-σ, and wherein said fusion polypeptide also comprises immunoglobulin like domain 1 polypeptide of RPTP-σ.In another embodiment, a RPTP is RPTP-δ, and the 2nd RPTP is RPTP-δ, and wherein said fusion rotein also comprises immunoglobulin like domain 1 polypeptide of RPTP-δ.The present invention also provides the composition that comprises described fusion polypeptide and pharmaceutical excipient.The method that suppresses the immunne response among the experimenter is provided in another embodiment, and it comprises to described experimenter's applying said compositions.In another embodiment, provide treatment among the experimenter Immunological diseases or the method for illness, it comprises to described experimenter's applying said compositions.In another embodiment, be provided for producing the preparation method of described polypeptide.

The present invention also provides composite inhibiting, it comprises immunoglobulin like domain 2 polypeptide of (a) at least a first receptor-like protein tyrosine phosphatase (RPTP) and (b) immunoglobulin like domain 3 polypeptide of at least a the 2nd RPTP, wherein said first and second RPTP are identical or different, and are selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.In a special embodiment, a described RPTP is identical with the 2nd RPTP, and in another special embodiment, a described RPTP is different with the 2nd RPTP.In a special embodiment, a described RPTP is RPTP-σ, and described the 2nd RPTP is RPTP-σ, and wherein said composition also comprises immunoglobulin like domain 1 polypeptide of RPTP-σ.In another special embodiment, a RPTP is RPTP-δ, and the 2nd RPTP is RPTP-δ, and wherein said composition also comprises immunoglobulin like domain 1 polypeptide of RPTP-δ.

The present invention also provides the composition that comprises polypeptide dimer, and wherein said dimer comprises (a) first monomer, and it comprises immunoglobulin like domain 2 polypeptide and immunoglobulin like domain 3 polypeptide of the first receptor-like protein tyrosine phosphatase (RPTP); (b) second monomer, it comprises immunoglobulin like domain 2 polypeptide and immunoglobulin like domain 3 polypeptide of the 2nd RPTP, wherein said first and second RPTP are identical or different, and are selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.In a special embodiment, a described RPTP is different with the 2nd RPTP.In another special embodiment, a described RPTP is identical with the 2nd RPTP.In a special embodiment, described first monomer also comprises the immunoglobulin like domain 1 of a RPTP, and described second monomer also comprises the immunoglobulin like domain 1 of the 2nd RPTP.In another special embodiment, described first monomer and immunoglobulin Fc polypeptide merge, and described second monomer and the fusion of immunoglobulin Fc polypeptide.

In other special embodiment, each composition as herein described also comprises medicinal suitable vehicle.The method that suppresses the immunne response among the experimenter also is provided in another embodiment, and it comprises to described experimenter's applying said compositions.In another embodiment, provide treatment among the experimenter Immunological diseases or the method for illness, it comprises to described experimenter's applying said compositions.In another embodiment, be provided for producing described preparation of compositions method.

In another embodiment, the fusion polypeptide that comprises the poxvirus polypeptide that merges with mutain Fc polypeptide is provided, wherein said mutain Fc polypeptide comprises the aminoacid sequence of the Fc part of the human IgG1's immunoglobulin (Ig) that contains at least one sudden change, wherein said at least one sudden change is the cysteine residues that replaces or lack hinge area, the wherein said cysteine residues that is substituted or lacks is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin Fc part hinge area, and wherein said poxvirus polypeptide can be in conjunction with being selected from following receptor-like protein tyrosine phosphatase (RPTP): (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.In a special embodiment, described mutain Fc polypeptide comprises at least one second sudden change, wherein said at least one second sudden change is at least one amino acid that is substituted in the CH2 structural domain, and consequently described fusion polypeptide is reduced in conjunction with the ability of IgG Fc acceptor.

The present invention also provides the composition that comprises any described fusion polypeptide and comprise medicinal suitable vehicle.Also provide and comprise (a) antibody mentioned above or its antigen-binding fragment and (b) composition of medicinal suitable vehicle.In another embodiment, provide the method that suppresses the immunne response among the experimenter, it comprises to described experimenter's applying said compositions.In another embodiment, provide treatment among the experimenter Immunological diseases or the method for illness, it comprises to described experimenter's applying said compositions.In another embodiment, be provided for producing the preparation method of described fusion polypeptide.

In one embodiment, a kind of isolated antibody is provided, or its antigen-binding fragment, its (a) is specifically in conjunction with being selected from following at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) competitive inhibition A41L and described at least two kinds of RPTP polypeptide combines.In special embodiment, described antibodies specific is in conjunction with LAR and RPTP-σ; Described antibodies specific is in conjunction with LAR and RPTP-δ; Perhaps described antibodies specific is in conjunction with RPTP-σ and RPTP-δ.In another special embodiment, described antibodies specific is in conjunction with LAR, RPTP-σ and RPTP-δ.

In another embodiment, any one or two kinds of isolated antibody of specificity bind receptor sample Protein-tyrosine-phosphatase-σ (RPTP-σ) or receptor-like protein tyrosine phosphatase-δ (RPTP-δ) is provided, or its antigen-binding fragment, wherein antibody or its antigen-binding fragment in conjunction with suppressing combining of A41L and RPTP-σ, RPTP-δ or the two.

In another embodiment, a kind of isolated antibody is provided, or its Fab, its (a) is specifically in conjunction with being selected from following at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) immunoreactivity of the immunocyte of at least a RPTP polypeptide is expressed in inhibition.In special embodiment, described antibodies specific ground is in conjunction with LAR and RPTP-σ; Described antibodies specific is in conjunction with LAR and RPTP-δ; Perhaps described antibodies specific is in conjunction with RPTP-σ and RPTP-δ.In another special embodiment, described antibodies specific is in conjunction with LAR, RPTP-σ and RPTP-δ.

In another embodiment, a kind of isolated antibody, or its antigen-binding fragment are (a) specifically in conjunction with being selected from following at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) suppress A41L and expression (i) LAR; (ii) RPTP-σ; The (iii) at least a immunocyte combination among the RPTP-δ.In special embodiment, described antibodies specific is in conjunction with LAR and RPTP-σ; Described antibodies specific is in conjunction with LAR and RPTP-δ; Perhaps described antibodies specific is in conjunction with RPTP-σ and RPTP-δ.In another special embodiment, described antibodies specific is in conjunction with LAR, RPTP-σ and RPTP-δ.

In one embodiment, the isolated antibody of specificity bind receptor sample Protein-tyrosine-phosphatase-σ (RPTP-σ) is provided, or its antigen-binding fragment, the RPTP-σ on wherein said antibody or its antigen-binding fragment and the cell surface that is present in immunocyte combines the immunoreactivity that suppresses described immunocyte.In another embodiment, the isolated antibody of specificity bind receptor sample Protein-tyrosine-phosphatase-δ (RPTP-δ) is provided, or its antigen-binding fragment, the combining of the RPTP-δ on wherein said antibody or its antigen-binding fragment and the cell surface that is present in immunocyte suppresses to express the immunoreactivity of the immunocyte of RPTP-δ.In another embodiment, any or the RPTP-σ of specificity bind receptor sample Protein-tyrosine-phosphatase-σ (RPTP-σ) or receptor-like protein tyrosine phosphatase-δ (RPTP-δ) and RPTP-δ are provided the two isolated antibody, or its antigen-binding fragment, RPTP-σ on wherein said antibody or its antigen-binding fragment and the cell surface that is present in immunocyte or RPTP-δ any or RPTP-σ and RPTP-δ the two combine the immunoreactivity that suppresses described immunocyte.

In certain embodiments, any about in the above-mentioned antibody, described antibody is polyclonal antibody.In other some embodiment, described antibody is monoclonal antibody.In another special embodiment, described monoclonal antibody is selected from mouse monoclonal antibody, human monoclonal antibodies, rat monoclonal antibody and hamster monoclonal antibody.The present invention also provides the host cell of expressing described monoclonal antibody; And in some special embodiment, described host cell is a hybridoma.In another special embodiment, described antibody is humanized antibody or chimeric antibody.In another embodiment, provide the host cell of expressing humanized antibody or chimeric antibody.

In another special embodiment, provide the composition that comprises any and medicinal suitable carrier in the above-mentioned antibody (or its antigen-binding fragment).Also be provided for producing the antibody that any preamble mentions or the preparation method of its antigen-binding fragment in another embodiment.

In other special embodiments, about in the antigen-binding fragment of any antibody mentioned above any, described antigen-binding fragment is selected from F (ab ') ₂, Fab ', Fab, Fd, and Fv.In another special embodiment, described antigen-binding fragment is people, mouse, chicken or rabbit source.In another special embodiment, described Fab is strand Fv (scFv).In another special embodiment, provide the composition of any and medicinal suitable carrier in the antigen-binding fragment that comprises any antibody mentioned above.

A kind of isolated antibody that comprises antiidiotypic antibody or its antigen-binding fragment also is provided in another embodiment, and its specificity is in conjunction with any antibody mentioned above or its Fab.In certain embodiments, described antiidiotypic antibody is a polyclonal antibody.In other some embodiment, described antiidiotypic antibody is a monoclonal antibody.The present invention also provides the host cell of expressing described antiidiotypic antibody.In some special embodiment, described host cell is a hybridoma.In another special embodiment, provide the composition that comprises described antiidiotypic antibody or its antigen-binding fragment and medicinal suitable carrier.

In one embodiment, also provide bi-specific antibody, its comprise (a) can specificity in conjunction with first antigen-bound fraction of RPTP, wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) can specificity in conjunction with second antigen-bound fraction of RPTP, wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ, wherein said bi-specific antibody suppresses the immunoreactivity of immunocyte.In a special embodiment, described first antigen-bound fraction can specificity in conjunction with LAR, and described second antigen-bound fraction can specificity in conjunction with RPTP-σ.In another special embodiment, described first antigen-bound fraction can specificity in conjunction with LAR, and described second antigen-bound fraction can specificity in conjunction with RPTP-δ.In another special embodiment, described first antigen-bound fraction can specificity in conjunction with RPTP-σ, and described second antigen-bound fraction can specificity in conjunction with RPTP-δ.In another special embodiment, provide the composition that comprises described bi-specific antibody and medicinal suitable carrier.

In another embodiment, provide a kind of fusion polypeptide, it comprises the immunoglobulin like domain of at least a RPTP that merges with at least a constant region for immunoglobulin structural domain, and described RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.In a special embodiment, the immunoglobulin like domain of described at least a RPTP and immunoglobulin Fc polypeptide merge.In a special embodiment, described Fc polypeptide derives from human IgG1's immunoglobulin (Ig).In another special embodiment, described RPTP is LAR, and described fusion polypeptide suppresses the immunoreactivity of immunocyte.In a special embodiment, described Fc polypeptide is included in the replacement of cysteine residues of hinge area or the mutain Fc polypeptide of disappearance, and the cysteine residues of wherein said replacement or disappearance is near the N-terminal cysteine residues of wild-type IgG1 immunoglobulin Fc part hinge area.In another special embodiment, described Fc polypeptide is to comprise the mutain Fc polypeptide that at least one amino-acid residue replaces in the CH2 structural domain of sudden change Fc polypeptide, thereby makes this fusion polypeptide be reduced in conjunction with the ability of IgG Fc acceptor.In another special embodiment, described mutain Fc polypeptide also is included in the replacement or the disappearance of the cysteine residues of hinge area, is near the N-terminal cysteine residues of wild-type IgG1 immunoglobulin Fc part hinge area by the cysteine residues of described replacement or disappearance wherein.In another special embodiment, described RPTP is RPTP-σ, and described fusion polypeptide suppresses the immunoreactivity of immunocyte.Particularly in the embodiment, described RPTP is RPTP-δ, and wherein said fusion rotein suppresses the immunoreactivity of immunocyte at another.In another special embodiment, provide the composition that comprises described fusion polypeptide and medicinal suitable carrier.

In one embodiment, provide a kind of reagent, its (a) is specifically in conjunction with being selected from following at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) weaken among A41L and LAR, RPTP-σ and the RPTP-δ combining of any.In specific embodiment, described reagent slackens among LAR, RPTP-σ on A41L and the cell surface that is present in immunocyte and the RPTP-δ combining of any.In other special embodiments, described reagent is selected from antibody or its Fab; Small molecules; Fit; And peptide-IgFc fusion polypeptide.In another special embodiment, provide the composition that comprises described reagent and medicinal suitable carrier.

Also provide specificity to weaken in one embodiment and be selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) reagent of at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide expression among the RPTP-δ.In a special embodiment, described reagent comprises antisense polynucleotides, and in another special embodiment, described reagent comprises short RNA interfering (siRNA).In another special embodiment, provide the composition that comprises described reagent and medicinal suitable carrier.

In another embodiment, provide the immunoreactive compositions and methods that identify to suppress immunocyte, it comprises: (a) fully allowing between at least a RPTP polypeptide and the A41L interactional condition and under the time, making (1) candidate agent; (2) expression is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) immunocyte of at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide of RPTP-δ; (3) A41L contact; And (b) determine A41L and immunocyte bonded level in the presence of described candidate agent, and compare A41L and immunocyte bonded level when not having described candidate agent, wherein A41L represents that with the decline of the level that combines of immunocyte described candidate agent suppresses the immunoreactivity of immunocyte in the presence of described candidate agent.In a special embodiment, described immunocyte is expressed and is selected from (i) LAR; (ii) RPTP-σ; (iii) at least two kinds of RPTP polypeptide of RPTP-δ.

The present invention also provides and identifies inhibition A41L and at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide bonded compositions and methods, it comprises: (a) fully allowing between two kinds of RPTP polypeptide and the A41L interactional condition at least and under the time, with following contact: (1) candidate agent; (2) comprise and be selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological sample of at least two kinds of RPTP polypeptide of RPTP-δ; (3) A41L; And (b) determine A41L and described at least two kinds of RPTP polypeptide bonded levels in the presence of described candidate agent, and relatively A41L and described at least two kinds of RPTP polypeptide bonded levels when not having described candidate agent, wherein combining of described candidate agent inhibition A41L and described at least two kinds of RPTP polypeptide represented in A41L and the decline of the level that combines of described at least two kinds of RPTP polypeptide in the presence of described candidate agent.

In another embodiment, the method that suppresses the immunne response among the experimenter is provided, it comprises uses the composition that comprises medicinal suitable carrier and antibody or its antigen-binding fragment, described antibody or its antigen-binding fragment specificity bind receptor sample Protein-tyrosine-phosphatase (RPTP)-σ.In one embodiment, the method that suppresses the immunne response among the experimenter is provided, it comprises uses the composition that comprises medicinal suitable carrier and antibody or its antigen-binding fragment, described antibody or its antigen-binding fragment specificity bind receptor sample Protein-tyrosine-phosphatase (RPTP)-δ.In another embodiment, the method of the immunne response that suppresses the experimenter is provided, it comprises uses the composition that comprises medicinal suitable carrier and antibody or its antigen-binding fragment, and described antibody or its antigen-binding fragment (a) specificity are in conjunction with being selected from following at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.

In one embodiment, treatment experimenter's the Immunological diseases or the method for illness are provided, it comprises to described experimenter uses medicinal suitable carrier and a kind of reagent, described reagent (a) changes the biological activity of at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide, and wherein said RPTP is RPTP-σ or RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In a special embodiment, described Immunological diseases or illness are autoimmune disorders or inflammatory disease.In specific embodiment, described autoimmunity or inflammatory disease are the multiple sclerosis diseases, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.In another special embodiment, described reagent is selected from antibody or its antigen-binding fragment; Small molecules; Fit; Antisense polynucleotides; Little RNA interfering (siRNA); And peptide-IgFc fusion polypeptide.

In one embodiment, be provided for treating among the experimenter with cell migration, cell proliferation and cytodifferentiation at least a change diseases associated or the method for illness, it comprises to described experimenter uses medicinal suitable carrier and a kind of reagent, and described reagent (a) changes the biological activity of at least a receptor-like protein tyrosine phosphatase (RPTP)-σ or RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In certain embodiments, described disease or illness are Immunological diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness, or hyperplasia or illness.In a special embodiment, described Immunological diseases or illness are autoimmune disorders or inflammatory disease.In another specific embodiment, described Immunological diseases or illness are the multiple sclerosis diseases, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.In another special embodiment, described cardiovascular disorder or illness are atherosclerosis, endocarditis, hypertension or periphery ischemic disease.In another special embodiment, described reagent is selected from antibody or its antigen-binding fragment; Small molecules; Fit; Antisense polynucleotides; Little RNA interfering (siRNA); And peptide-IgFc fusion polypeptide.

In another embodiment, be provided for producing the preparation method of the immunoreactive reagent that suppresses immunocyte, it comprises: (a) identify the immunoreactive reagent that suppresses immunocyte, wherein said authentication step comprises: (1) is fully allowing between at least a RPTP polypeptide and the A41L interactional condition and under the time, with following contact: (i) candidate agent; (ii) express and be selected from leukocyte common antigen (LCA) associated protein (LAR); RPTP-σ; Immunocyte with at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide of RPTP-δ; (iii) A41L; And (2) determine A41L and immunocyte bonded level in the presence of described candidate agent, and compare A41L and immunocyte bonded level when not having described candidate agent, wherein A41L represents that with the decline of the level that combines of immunocyte described candidate agent suppresses the immunoreactivity of immunocyte in the presence of described candidate agent; (b) produce the reagent of in step (a), identifying.In certain embodiments, described reagent is selected from antibody or its antigen-binding fragment; Small molecules; Fit; Antisense polynucleotides; Little RNA interfering (siRNA); And peptide-IgFc fusion polypeptide.In another specific embodiment, described reagent is antibody or its antigen-binding fragment.

In one embodiment, fusion polypeptide comprises with mutain Fc polypeptide and meets the A41L polypeptide that frame ground merges, wherein said mutain Fc polypeptide comprises the aminoacid sequence of human IgG1's immunoglobulin Fc part, wherein said mutain Fc polypeptide is different with wild-type human IgG1 immunoglobulin Fc part to be to comprise at least two sudden changes, wherein first sudden change in described mutain Fc polypeptide is included at least one the amino acid whose replacement in the CH2 structural domain, so that described fusion polypeptide reduces in conjunction with the ability of IgG Fc acceptor, and wherein second sudden change in described mutain Fc polypeptide is replacement or the disappearance at the cysteine residues of hinge area, and wherein said cysteine residues is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin hinge region.In a special embodiment, described mutain Fc polypeptide is included at least two amino acid whose replacements in the CH2 structural domain.In another special embodiment, described mutain Fc polypeptide is included at least three amino acid whose replacements in the CH2 structural domain.In another special embodiment, the described amino acid that replaces in the CH2 structural domain is arranged in and human IgG immunoglobulin (Ig) CH2 structural domain EU Position Number 235 corresponding positions.In another special embodiment, substituted first amino acid is arranged in the CH2 structural domain EU Position Number 234 corresponding positions with the human IgG immunoglobulin (Ig), and substituted second amino acid is arranged in the CH2 structural domain EU Position Number 235 corresponding positions with the human IgG immunoglobulin (Ig).In another special embodiment, substituted first amino acid is arranged in the CH2 structural domain EU Position Number 234 corresponding positions with the human IgG immunoglobulin (Ig), substituted second amino acid is arranged in the CH2 structural domain EU Position Number 235 corresponding positions with the human IgG immunoglobulin (Ig), and substituted the 3rd amino acid is arranged in the CH2 structural domain EU Position Number 237 corresponding positions with the human IgG immunoglobulin (Ig).In certain special embodiment, the leucine residue that is arranged in the CH2 structural domain EU Position Number 235 corresponding positions of human IgG immunoglobulin (Ig) is replaced by glutaminic acid residue or alanine residue.In another special embodiment, the leucine residue that is arranged in the EU Position Number 234 corresponding positions of the CH2 structural domain of human IgG immunoglobulin (Ig) is replaced by alanine residue.In another special embodiment, the glycine residue that is arranged in the EU Position Number 237 corresponding positions of the CH2 structural domain of human IgG immunoglobulin (Ig) is replaced by alanine residue.In another special embodiment, described mutain Fc polypeptide also is included in the replacement or the disappearance of at least one non-cysteine residues of hinge area.In another special embodiment, described mutain Fc polypeptide is included in the disappearance of at least two amino-acid residues of hinge area, wherein said at least two amino-acid residues comprise cysteine residues and contiguous C end residue, and wherein said cysteine residues is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin hinge region.In a special embodiment, described fusion polypeptide is included in the aminoacid sequence of describing among the SEQ ID NO:73.

The present invention also provides the method that suppresses the immunne response among the experimenter, and it comprises uses the composition that comprises medicinal suitable carrier and described fusion polypeptide, and described fusion polypeptide comprises with mutain Fc polypeptide mentioned above and meets the A41L polypeptide that frame ground merges.In a special embodiment, described fusion polypeptide (a) changes at least a biological activity among receptor-like protein tyrosine phosphatase (RPTP)-σ and the RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.

In another embodiment, be provided for treating the Immunological diseases among the experimenter or the method for illness, it comprises to described experimenter uses medicinal suitable carrier and described fusion polypeptide, and described fusion polypeptide comprises with mutain Fc polypeptide mentioned above and meets the A41L polypeptide that frame ground merges.In a special embodiment, described fusion polypeptide (a) changes at least a biological activity among receptor-like protein tyrosine phosphatase (RPTP)-σ and the RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In another special embodiment, described Immunological diseases or illness are autoimmune disorders or inflammatory disease, wherein in certain embodiments, described autoimmune disorders or inflammatory disease are the multiple sclerosis diseases, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.

In one embodiment, be provided for treating in the experimenter with cell migration, cell proliferation and cytodifferentiation at least a change diseases associated or the method for illness, it comprises to described experimenter uses medicinal suitable carrier and described fusion polypeptide, and described fusion polypeptide comprises with mutain Fc polypeptide mentioned above and meets the A41L polypeptide that frame ground merges.In a special embodiment, described fusion polypeptide (a) changes at least a biological activity among receptor-like protein tyrosine phosphatase (RPTP)-σ or the RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In another embodiment, described disease or illness are Immunological diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness, or hyperplasia or illness.In a special embodiment, described Immunological diseases or illness are autoimmune disorders or inflammatory disease.In another specific embodiment, described Immunological diseases or illness are the multiple sclerosis diseases, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.In another special embodiment, described cardiovascular disorder or illness are atherosclerosis, endocarditis, hypertension or periphery ischemic disease.In another embodiment, be provided for producing and comprise the preparation method who meets the fusion polypeptide of the A41L polypeptide that merges on frame ground with mutain Fc polypeptide mentioned above.

In another embodiment, a kind of isolated antibody or its antigen-binding fragment are provided, and its (a) is specifically in conjunction with being selected from following at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) combining of competitive inhibition 130L polypeptide and described at least a RPTP polypeptide, wherein said 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%.In a special embodiment, the 130L polypeptid specificity is incorporated into and is selected from (i) LAR; (ii) RPTP-σ; (iii) at least two kinds of RPTP polypeptide of RPTP-δ, and in another special embodiment, the 130L polypeptid specificity is in conjunction with (i) LAR; (ii) RPTP-σ; (iii) RPTP-δ.In some special embodiment, described antibody or its antigen-binding fragment, specificity is in conjunction with LAR and RPTP-σ.In another special embodiment, described antibody or its antigen-binding fragment, specificity is in conjunction with LAR and RPTP-δ.In another special embodiment, described antibody or its antigen-binding fragment, specificity is in conjunction with RPTP-σ and RPTP-δ.In another embodiment, described antibody or antigen-binding fragment changes the immunoreactivity of the immunocyte of expressing at least a RPTP polypeptide.In a special embodiment, the immunoreactivity that changes immunocyte is to suppress the immunoreactivity of immunocyte.

In another embodiment, a kind of isolated antibody is provided, or its Fab, its (a) is specifically in conjunction with being selected from following at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) suppress 130L polypeptide and expression (i) LAR; (ii) RPTP-σ; The (iii) combination of at least a immunocyte among the RPTP-δ, wherein said 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%.In a special embodiment, 130L amino acid sequence of polypeptide (a) is included in the aminoacid sequence of describing among SEQ ID NO:85 or the SEQ ID NO:150; (b) identical with SEQ ID NO:85 or SEQ IDNO:150 at least 95%; (c) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 90%; Or it is (d) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 85%.In some special embodiment, described antibody or its antigen-binding fragment specificity are in conjunction with LAR and RPTP-σ.In another special embodiment, described antibody or its antigen-binding fragment, specificity is in conjunction with LAR and RPTP-δ.In another special embodiment, described antibody or its antigen-binding fragment, specificity is in conjunction with RPTP-σ and RPTP-δ.In another special embodiment, described antibody or its antigen-binding fragment specificity are in conjunction with LAR, RPTP-σ and RPTP-δ.

The present invention also provides specificity bind receptor sample Protein-tyrosine-phosphatase-σ (RPTP-σ) or receptor-like protein tyrosine phosphatase-δ (RPTP-δ) or the isolated antibody of the two or its antigen-binding fragment, and the combination of wherein said antibody or its antigen-binding fragment changes the immunoreactivity of expressing the immunocyte that is selected from following RPTP: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.In certain embodiments, the immunoreactivity of change immunocyte is to suppress the immunoreactivity of immunocyte.

In some special embodiment, be polyclonal antibody above with any antibody described herein.In another special embodiment, described antibody is monoclonal antibody.In a specific embodiment, described monoclonal antibody is selected from mouse monoclonal antibody, human monoclonal antibodies, rat monoclonal antibody and hamster monoclonal antibody.The present invention also provides the host cell of expressing such antibody, and in special embodiment, described host cell is a hybridoma.In other embodiments, be humanized antibody or chimeric antibody above with any antibody described herein.The present invention also provides the host cell of expressing humanized antibody or chimeric antibody.In other special embodiment, described antigen-binding fragment is to be selected from F (ab ') ₂, Fab ', Fab, Fd, and Fv.In a special embodiment, described antigen-binding fragment is people, mouse, chicken or rabbit source.In another special embodiment, described antigen-binding fragment is strand Fv (scFv).A kind of isolated antibody or its antigen-binding fragment that comprises antiidiotypic antibody, its specificity in conjunction with above with any antibody described herein.In a special embodiment, described antiidiotypic antibody is a polyclonal antibody.In another special embodiment, described antiidiotypic antibody is a monoclonal antibody.In another embodiment, be a kind of composition, it comprises antiidiotypic antibody or its antigen-binding fragment and medicinal suitable carrier.

In another embodiment, the present invention also provides the composition that comprises any described antibody or its antigen-binding fragment and medicinal suitable carrier.The present invention also is provided for producing above and any antibody described herein or the preparation method of its antigen-binding fragment.

The present invention also provides a kind of reagent, and its (a) is specifically in conjunction with being selected from following at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide: (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; (b) slacken any combining among 130L polypeptide and LAR, RPTP-σ and the RPTP-δ, wherein said 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%.In certain embodiments, described 130 amino acid sequence of polypeptide (a) are included in the aminoacid sequence of describing among SEQ ID NO:85 or the SEQ ID NO:150; (b) identical with SEQ ID NO:85 or SEQ IDNO:150 at least 95%; (c) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 90%; Or it is (d) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 85%.In a special embodiment, described reagent specificity is in conjunction with being selected from (i) LAR; (ii) RPTP-σ; (iii) at least two kinds of RPTP polypeptide of RPTP-δ.In another special embodiment, described reagent slacken the 130L polypeptide and express LAR, RPTP-σ and RPTP-δ in any the combining of immunocyte.In a special embodiment, described reagent is to be selected from antibody or its Fab; Small molecules; Fit; And peptide-IgFc fusion polypeptide.

The present invention also provides and comprises above and any reagent described herein and the composition of medicinal suitable carrier.

In another embodiment, provide and identify the immunoreactive compositions and methods that suppresses immunocyte, it comprises: (a) fully allowing between at least a RPTP polypeptide and the 130L polypeptide interactional condition and under the time, with following contact: (1) candidate agent; (2) expression is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) immunocyte of at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide of RPTP-δ; (3) 130L polypeptide, wherein the 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%; And (b) determine 130L polypeptide and described immunocyte bonded level in the presence of described candidate agent, and compare 130L polypeptide and described immunocyte bonded level when not having described candidate agent, wherein the 130L polypeptide represents that with the decline of the level that combines of described immunocyte described candidate agent suppresses the immunoreactivity of immunocyte in the presence of described candidate agent.In certain embodiments, 130L amino acid sequence of polypeptide (a) is included in the aminoacid sequence of describing among SEQ IDNO:85 or the SEQ ID NO:150; (b) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 95%; (c) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 90%; Or it is (d) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 85%.In a special embodiment, described immunocyte is expressed and is selected from (i) LAR; (ii) RPTP-σ; (iii) at least two kinds of RPTP polypeptide of RPTP-δ.

In another embodiment, the present invention also provides and identifies the bonded compositions and methods that suppresses 130L polypeptide and at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide, it comprises: (a) fully allowing between RPTP polypeptide and the 130L polypeptide interactional condition and under the time, with following contact: (1) candidate agent; (2) comprise and be selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological sample of the RPTP polypeptide of RPTP-δ; (3) 130L polypeptide, wherein the 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%; And (b) determine 130L polypeptide and RPTP polypeptide bonded level in the presence of described candidate agent, and relatively 130L polypeptide and RPTP polypeptide bonded level when not having described candidate agent, wherein combining of described candidate agent inhibition 130L polypeptide and RPTP polypeptide represented in 130L polypeptide and the decline of the level that combines of RPTP polypeptide in the presence of described candidate agent.In certain embodiments, 130L amino acid sequence of polypeptide (a) is included in the aminoacid sequence of describing among SEQ ID NO:85 or the SEQ ID NO:150; (b) identical with SEQ IDNO:85 or SEQ ID NO:150 at least 95%; (c) identical with SEQ ID NO:85 or SEQ IDNO:150 at least 90%; Or it is (d) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 85%.

The present invention also is provided for producing the preparation method of the immunoreactive reagent that suppresses immunocyte, it comprises: (a) identify the immunoreactive reagent that suppresses immunocyte, wherein said authentication step comprises: (1) is fully allowing between at least a RPTP polypeptide and the 130L polypeptide interactional condition and under the time, with following contact: (i) candidate agent; (ii) express and be selected from leukocyte common antigen (LCA) associated protein (LAR); RPTP-σ; Immunocyte with at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide of RPTP-δ; (iii) 130L polypeptide, wherein the 130L amino acid sequence of polypeptide is identical with the aminoacid sequence of describing in SEQ ID NO:85 or SEQ ID NO:150 at least 80%; And (2) determine 130L polypeptide and immunocyte bonded level in the presence of described candidate agent, and compare 130L polypeptide and immunocyte bonded level when not having described candidate agent, wherein the 130L polypeptide represents that with the decline of the level that combines of immunocyte described candidate agent suppresses the immunoreactivity of immunocyte in the presence of described candidate agent; (b) produce the reagent of in step (a), identifying.In certain embodiments, 130L amino acid sequence of polypeptide (a) is included in the aminoacid sequence of describing among SEQ ID NO:85 or the SEQ ID NO:150; (b) identical with SEQ IDNO:85 or SEQ ID NO:150 at least 95%; (c) identical with SEQ ID NO:85 or SEQ IDNO:150 at least 90%; Or it is (d) identical with SEQ ID NO:85 or SEQ ID NO:150 at least 85%.In a special embodiment, described reagent is to be selected from antibody or its antigen-binding fragment; Small molecules; Fit; Antisense polynucleotides; Little RNA interfering (siRNA); And peptide-IgFc fusion polypeptide.In another specific embodiment, described reagent is antibody or its antigen-binding fragment.

In another embodiment, provide the fusion polypeptide that comprises the 130L polypeptide that merges with the Fc polypeptide.In a special embodiment, described Fc polypeptide is a human IgG1 Fc polypeptide.In a special embodiment, described human IgG1 Fc polypeptide is a mutain Fc polypeptide, wherein said mutain Fc polypeptide comprises the aminoacid sequence of human IgG1's immunoglobulin Fc part, wherein said mutain Fc polypeptide is different with the Fc part of wild-type human IgG1 immunoglobulin (Ig), difference is that it comprises at least two sudden changes, wherein first sudden change in described mutain Fc polypeptide is included at least one aminoacid replacement in the CH2 structural domain, so that described fusion polypeptide reduces in conjunction with the ability of IgG Fc acceptor, and wherein second sudden change in described mutain Fc polypeptide is replacement or the disappearance at the cysteine residues of hinge area, and wherein said cysteine residues is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin hinge region.In another special embodiment, described mutain Fc polypeptide is included at least two amino acid whose replacements in the CH2 structural domain.In another special embodiment, described mutain Fc polypeptide is included at least three aminoacid replacement in the CH2 structural domain.In certain embodiments, substituted amino acid is arranged in and human IgG immunoglobulin (Ig) CH2 structural domain EU Position Number 235 corresponding positions.

In other some embodiment, substituted first amino acid is arranged in the CH2 structural domain EU Position Number 234 corresponding positions with the human IgG immunoglobulin (Ig), and substituted second amino acid is arranged in the CH2 structural domain EU Position Number 235 corresponding positions with the human IgG immunoglobulin (Ig).In another specific embodiment, substituted first amino acid is arranged in the CH2 structural domain EU Position Number 234 corresponding positions with the human IgG immunoglobulin (Ig), substituted second amino acid is arranged in the CH2 structural domain EU Position Number 235 corresponding positions with the human IgG immunoglobulin (Ig), and substituted the 3rd amino acid is arranged in the CH2 structural domain EU Position Number 237 corresponding positions with the human IgG immunoglobulin (Ig).In a special embodiment, the leucine residue that is arranged in the CH2 structural domain EU Position Number 235 corresponding positions of human IgG immunoglobulin (Ig) is replaced by glutaminic acid residue or alanine residue.In another special embodiment, the leucine residue that is arranged in the EU Position Number 234 corresponding positions of the CH2 structural domain of human IgG immunoglobulin (Ig) is replaced by alanine residue.In another special embodiment, the glycine residue that is arranged in the EU Position Number 237 corresponding positions of the CH2 structural domain of human IgG immunoglobulin (Ig) is replaced by alanine residue.In another special embodiment, described mutain Fc polypeptide also is included in the replacement or the disappearance of at least one non-cysteine residues of hinge area.In a special embodiment, described mutain Fc polypeptide is included in the disappearance of at least two amino-acid residues of hinge area, wherein said at least two amino-acid residues comprise cysteine residues and contiguous C end residue, and wherein said cysteine residues is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin hinge region.In a special embodiment, described fusion polypeptide is included in the aminoacid sequence of describing among the SEQ ID NO:149.

In another embodiment, the method that suppresses the immunne response among the experimenter is provided, wherein said method comprises uses the composition that comprises medicinal suitable carrier and described fusion polypeptide, and described fusion polypeptide comprises and reaches the 130L polypeptide that merges with the Fc polypeptide described herein as mentioned.In a special embodiment, described fusion polypeptide (a) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least a receptor-like protein tyrosine phosphatase (RPTP) among the RPTP-δ; Perhaps (b) change is selected from (i) LAR; (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In another embodiment, provide treatment experimenter's the Immunological diseases or the method for illness, it comprises that using medicinal suitable carrier to described experimenter reaches fusion polypeptide described herein and the 130L polypeptide that the Fc polypeptide merges as mentioned with comprising.In a special embodiment, described fusion polypeptide (a) changes at least a biological activity among receptor-like protein tyrosine phosphatase (RPTP)-σ and the RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In certain embodiments, described Immunological diseases or illness are autoimmune disorders or inflammatory disease.In special embodiment, described autoimmune disorders or inflammatory disease are the multiple sclerosis diseases, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.

In another embodiment, be provided for treating in the experimenter with cell migration, cell proliferation and cytodifferentiation at least a change diseases associated or the method for illness, it comprises to described experimenter uses medicinal suitable carrier and described fusion polypeptide, and described fusion polypeptide comprises and reaches the 130L polypeptide that merges with mutain Fc polypeptide described herein as mentioned.In a special embodiment, described fusion polypeptide (a) changes at least a biological activity among receptor-like protein tyrosine phosphatase (RPTP)-σ or the RPTP-δ; Perhaps (b) change is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; The (iii) biological activity of at least two kinds of RPTP polypeptide among the RPTP-δ.In another special embodiment, described disease or illness are Immunological diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness, or hyperplasia or illness.In another special embodiment, described Immunological diseases or illness are autoimmune disorders or inflammatory disease.In certain embodiments, described Immunological diseases or illness are multiple sclerosis disease, rheumatoid arthritis, system lupus erythematosus, graft versus host disease, Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic perfusion again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.In some other embodiment, described cardiovascular disorder or illness are atherosclerosis, endocarditis, hypertension or periphery ischemic disease.The present invention also is provided for producing the preparation method who comprises the fusion polypeptide that reaches the 130L polypeptide that described herein and Fc polypeptide merge as mentioned.

Mention and/or in the request for data list, list all United States Patent (USP)s, U.S. Patent Application Publication, U.S. Patent application, foreign patent, foreign patent application and the announcement of non-patent in this manual and all be incorporated into this by reference fully.

The accompanying drawing summary

Figure 1A-1F provides RPTP-σ (SEQ ID NO:29), RPTP-δ (SEQ ID NO:37), and the comparison of the aminoacid sequence of LAR (SEQ ID NO:25).The leader peptide sequences of every kind of RPTP, an immunoglobulin like domain (Ig structural domain; The 2nd Ig structural domain, the 3rd Ig structural domain); Fibronectin III iteron (FNIII); Stride film district (TM district); (D1 and D2) marks in described sequence alignment with the Phosphoric acid esterase structural domain.First amino acid in each zone is represented with bold.Protease cracking site in every kind of Phosphoric acid esterase is represented by underscore.Amino acid in same area is represented with " * ", represents with point at the amino acid of similar area.Sequence alignment uses CLUSTALW program (Thompson etc., Nucleic Acids Res. (nucleic acids research) 22:4673-80 (1991)) and " GeneDoc " (Nicholas etc., EMBNEWNews (EMBNEW news) 4:14 (1991)) to generate.

Fig. 2 shows that wherein said recombinant expression construct body (A41LCRFC) is expressed the fusion polypeptide that is used for tandem affinity purification (TAP) by the synoptic diagram of the A41L fusion polypeptide of recombinant expression construct body (A41LCRFC) coding.Coded fusion polypeptide comprises the sophisticated A41L from vaccinia virus, and it is with the carboxyl terminal of its aminoterminal fusion at human growth hormone leading peptide (GH is leading).Series connection affinity labelling (CRFC) merges the carboxyl terminal at A41L, and comprise and meet protein C-TAG (EDQVDPRLIDGK (SEQ ID NO:68), be derived from the heavy chain of human protein C) human influenza virus's hemagglutinin (HA) epi-position (YPYDVDYA, SEQ ID NO:67) of frame; ERC group virus HRV3C protease site (HRV3C cracking site) (LEVLFQGP (SEQ ID NO:69)); Mutain derivative (mutain FC) with human IgG immunoglobulin Fc part.

Fig. 3 represents to identify the synoptic diagram with the TAP step of A41L bonded cell polypeptide.

Fig. 4 illustrates by LAR, RPTP-δ that identifies with A41L tandem affinity purification (TAP) and the peptide of RPTP-σ.Fig. 4 A illustrates the sequence (bold) of the peptide of LAR (SEQID NO:70) inside of identifying with LC/MS/MS behind TAP.Fig. 4 B illustrates the sequence (bold) of the peptide of RPTP-σ (the SEQ ID NO:71) inside of identifying with LC/MS/MS behind TAP.Fig. 4 C illustrates the sequence (bold) of the peptide of RPTP-δ (the SEQ ID NO:72) inside of identifying with LC/MS/MS behind TAP.

Fig. 5 is illustrated in (i) and comprises the A41L signal peptide sequence, a kind of A41L polypeptide, with the A41L/Fc fusion polypeptide (A41L/Fc) (SEQ ID NO:74) of human IgG1 Fc polypeptide with (ii) comprise the human growth hormone signal peptide sequence, a kind of A41L polypeptide variants, and the comparison of the aminoacid sequence between the A41L/ mutain Fc fusion polypeptide (A41L/ mutain Fc) (SEQ ID NO:73) of mutain Fc polypeptide.Also shown consensus sequence (SEQ ID NO:75).Vertical dotted line is represented the aminoterminal and the C-terminal of A41L polypeptide.

Fig. 6 provides from the 130L polypeptide of tanapox virus (YLDV) (GenBank registration number CAC21368.1) (SEQ ID NO:85) with from the sequence alignment of the aminoacid sequence of the A41L (SEQ ID NO:87) (GenBank registration number AAM13618) of vaccinia virus.

Fig. 7 illustrates LAR, RPTP-δ and the RPTP-σ peptide of identifying by with the tandem affinity purification (TAP) of tanapox virus 130L.Fig. 7 A illustrates the sequence (bold and underscore) of the peptide of LAR (the SEQ ID NO:155) inside of identifying by LC/MS/MS behind TAP.Fig. 7 B illustrates the sequence (bold and underscore) of the peptide of RPTP-σ (the SEQ ID NO:156) inside of identifying with LC/MS/MS behind TAP.Fig. 7 C illustrates the sequence (bold and underscore) of the peptide of RPTP-δ (the SEQ ID NO:157) inside of identifying with LC/MS/MS behind TAP.

Fig. 8 A illustrates in the presence of leukocyte common antigen (LCA) associated protein-people Fc conjugate (Lar-hFc), the production of interferon-(IFN-γ) in non-adhesive peripheral blood lymphocytes (PBMCs).Fig. 8 B and 8C are illustrated in Lar-hFc and have down the IFN-γ production level in blended lymphocyte reaction (MLR).Will be from donor Do476 (Fig. 8 B) with from the dendritic cell (10 of the cells of monocytic origin of the second donor Do495 (Fig. 8 C) ⁴) stick the PBMCs combination with the Lar-hFc that adds various concentration non-.The production of IFN-γ is determined by ELISA.Add human IgG in contrast with the concentration that shows.

Fig. 9 represents to be applied to the elution mode of the LAR Ig-1-Ig-2-Ig-3-Fc fusion polypeptide on the gel-filtration HPLC post.

Figure 10 represents the immunoblotting of the LAR-Ig structural domain construct that merges with human IgG Fc, and described construct combines with A41L.Mixture is by separating with the a-protein immunoprecipitation.Use the Fc part (Figure 10 A) of anti--Fc antibody test LAR-Ig-Fc construct, and the existence of A41L is by determining (Figure 10 B) with the immunoblotting of anti--A41L antibody.

Detailed Description Of The Invention

The present invention relates to such discovery, that is, and three kinds of receptor-like protein tyrosine phosphatases (RPTPs): LCA GAP-associated protein GAP (LAR), receptor protein tyrosine phosphatase-δ (RPTP-δ), With receptor protein tyrosine phosphatase-σ (RPTP-σ), show immunoloregulation function. Immunocyte Express LAR, RPTP-δ and RPTP-σ be tested and appraised expressed by immunocyte with the poxvirus polypeptide A41L and from the interactional polypeptide of 130L of tanapox virus (YLDV) and find.

LAR is on the cell surface of immunocyte (for example, macrophage, THP-1 clone) Existence be tested and appraised and express with the cell of the interactional polypeptide of poxvirus polypeptide A 41L and show (for example, referring to, U.S. Patent number 6,852,486). Unexpectedly, as described herein, RPTP-δ Also be to be expressed by immunocyte with RPTP-σ, and with A41L and another kind of poxvirus polypeptide The 130L combination. Previous studies show that RPTP-δ and RPTP-σ are mainly in brain and neural system tissue The middle expression (referring to, for example, Pulido etc., Proc.Natl.Acad.Sci USA (American National science Institute's journal) 92:11686-90 (1995)). Nearer LAR, RPTP-δ and the RPTP-σ of studies show that In the adjusting axon guidance of fruit bat (Drosophila) (referring to, for example, Johnson etc., Physiol. Rev. (ginseng (physiology summary) 83:1-21 (2003)) with in the growth of excitatory synapse and in keeping See, for example, Dunah etc., Nat.Neurosci. (Nature Neuroscience) 8:458-67 (2005)) rise Effect.

With LAR, RPTP-δ and RPTP-σ specific binding and/or interactional virus polypeptide 130L and A41L be homology (participation Fig. 6) not. Tanapox virus (YLDV) belongs to the subfamily poxvirus The inferior tower poxvirus (Yatapoxvirus) of notochord subfamily (Chrodopoxvirinae) belongs to. This accessory Three members are arranged: that poxvirus of tower (tanapox virus), yaba monkey tumour virus and YLDV. In spirit In the long class, YLDV cause the febris acuta disease of typically following local skin damage (referring to, for example, Knight etc., Virology (virology) 172:116-24 (1989)). The YLDV base that is called 130L Because of coding have the estimation molecular weight of about 21Kd secretory protein (referring to, for example, Lee etc., Virology (virology) 281:170-92 (2001)).

The poxvirus polypeptide such as A41L and 130L, is done among the host at least partially in poxvirus infection With, to suppress the immune response special to described virus. Immune response in the host of virus infections Inhibition produce virus and can continue therein the environment that copies and infect. As described herein, identify the place Chief cell and interactional such as A41L and 130L with the poxvirus polypeptide as described in the composition of host cell, Comprise polypeptide, can cause researching and developing the treatment molecule that changes immune response. Described poxvirus polypeptide is passable By suppressing or block the merit of host's factor such as interferon, complement, cell factor and/or chemokines Can, perhaps by suppress, blocking-up or change inflammation and the fever effect work (also referring to, for example, U.S. Patent number 6,852,486). For example, the polypeptide in the LAR-source is (that is, many with human IgG Fc The immunoglobulin like domain 1,2 and 3 of the LAR that peptide merges) under the existence, peripheral blood mononuclear Cell is stimulated to produce interferon gamma (IFN-γ). Do not wish to be subjected to the restriction of any theory, because IFN-γ By stimulating and inducing the aspect of some immune responses to participate in the elimination of pathogen, so A41L can Suppressing LAR with the ability that stimulates IFN-γ production by suppressing LAR helps for the acne of invading The ability of the performance of the immune response of virus. The IFN-γ that increases production is also exempted from immunological diseases with from body Epidemic is sick relevant such as system lupus erythematosus (SLE). Therefore, A41L, 130L or simulation A41L Or the interactional reagent between 130L and the LAR, big molecule or compound, for example, can be Effective immunodepressant. The poxvirus polypeptide, such as A41L and 130L, or poxvirus is many as described Peptide equally acts on immunoreactive other reagent, polypeptide, molecule or the compound of Immunosuppression cell, Can be used for treating or epidemic prevention disease or illness.

The invention provides the composition and the method that are used for the treatment of disease and illness, described disease and illness bag Draw together inflammatory disease and autoimmune disease, described method is passed through immunocyte and and LAR, RPTP-δ Contact with molecule, compound or the composition of one or more effects among the RPTP-σ, (subtract suppressing Eliminate less,, suppress or prevent) immunoreactivity of described immunocyte. Such compound or group Compound can also be used for the treatment of angiocardiopathy as herein described or metabolic disease. Alternatively, with LAR, One or more effects among RPTP-δ and the RPTP-σ and be used for the treatment of inflammatory or the autoimmunity disease Molecule, compound or the composition of sick, cardiovascular or metabolic disease can strengthen immune exempting from The epidemic disease reactivity.

The invention provides and be used for the treatment of or prevent, suppress, slow down autoimmune disease or illness, painstaking effort The development of pipe disease or illness, metabolic disease or illness or hyperplasia or illness or alleviate with described Composition and the method for the symptom that disease or illness are relevant. Immune disorders comprise inflammatory disease or illness and Autoimmune disease or illness. Although inflammation or inflammatory reaction are that the host is for the normal and guarantor of damage The reaction of protecting property, but inflammation can cause unwanted damage. For example, atherosclerotic, extremely Small part is the pathological reaction for arterial injury and consequential inflammatory cascade. Can use and this One or more combinations among literary composition described LAR, RPTP-δ and the RPTP-σ or interactional anti-The example of immune disorders of body or its antigen-binding fragment (or other reagent) treatment comprises but not Be limited to, multiple sclerosis, rheumatoid arthritis, system lupus erythematosus (SLE), graft resist Host disease (GVHD), pyemia, diabetes, psoriasis, atherosclerotic, Si Yegelun Syndrome, expansionary system hardening illness, chorionitis, acute coronary syndrome, ischemic Again perfusion, regional enteritis, mullerianosis, glomerulonephritis, myasthenia gravis, congenital Property lung fibrosis, asthma, ARDS (ARDS), vasculitis or inflammatory are from body Immunity myositis and other inflammatory and muscle deterioration disease (for example, dermatomyositis, polymyositis, blue or green few Year dermatomyositis, inclusion body myositis). Treatable angiocardiopathy or illness, it can comprise also Can be considered to disease and the illness of immunological diseases/illness, comprise, for example, atherosclerotic, Endocarditis, hypertension or periphery ischaemic disease. Treatable metabolic disease or illness, it also Can comprise disease and the illness that can also be considered to autoimmune disease/illness, comprise, for example, Diabetes, obesity and the disease relevant with mitochondrial function unusual or that change.

When being used for this paper, term " separation " mean material from its initial environment (for example, if It is naturally occurring, is natural surroundings so) shift out. For example, be present in sky in the animal alive Right nucleic acid or the polypeptide that exists do not separate, still with natural system in some or all coexistence Identical identical nucleic acid or the polypeptide of separating substances separate. Such nucleic acid can be one of carrier Part, and/or such nucleic acid or polypeptide can be the part of composition, and remain separation , reason is that described carrier or composition are not ones of natural surroundings of described nucleic acid or polypeptide Divide. Term " gene " means the dna fragmentation that participates in producing polypeptide chain; It is included in the code area it Before and zone afterwards " leading and afterbody " and between between the single encoded fragment (extron) Insert sequence (introne).

When being used for this paper and being used in the claim of enclosing, singulative " one, " " is a kind of, " and " described " comprises plural indicant, unless clearly in addition indication of context. Therefore, for example, " one Kind of reagent (an agent) " formulation comprise multiple described reagent, and " described cell (the cell) " Formulation comprise the formulation of one or more cells and equivalent known to those skilled in the art, Etc.. Term " comprises (comprising) ", and (and relevant term is as " comprising (comprise) " or " comprise (comprises) " or " have (having) " or " comprise (including) ") unexpectedly Wish is got rid of, for example, and in other some embodiment, any composition of material as herein described, The embodiment of composition, method or technology etc. can by described feature " form " or " substantially " by Described feature " composition ".

The A41L polypeptide

A41L refers to the locus in poxvirus family member's the virus, and described poxvirus family comprises, For example, smallpox, myxoma, rabbit fibroma virus, camel acne, monkeypox, ecromelia, cowpox and Vaccinia virus. A kind of glycoprotein of A41L gene code (this paper is called the A41L polypeptide), it is a kind of The virus virulence factor, its by the cell that infects poxvirus secreted (referring to, for example, the international monopoly Shen Please announce WO 98/37217; Ng etc., J.Gen.Virol. (hereditary Journal of Virology) 82:2095-105 (2001)). Poxvirus, its genome is double-stranded DNA, by obtaining to allow described virus to escape Keep away host's immune system and/or promote the host gene of virus replication and be adapted at various host species In copy (referring to, for example .Virus Genes (viral gene) 21:111-33 (2000) such as Bugert; Alcami etc., Immunol.Today (immunology today) 21:447-55 (2000); McFadden etc., J.Leukoc.Biol. (leucocyte biology magazine) 57:731-38 (1995)). By various poxvirus The polypeptide of genome encoding can by suppress or blocking-up host's factor such as interferon, complement, cell because of The function of son or/or chemokines is perhaps by suppressing, block or change the effect of inflammation and fever And affect immune response. For example, the recombinant expressed A41L polypeptide chemistry of inducing in conjunction with IFN-γ because of Son, as Mig and IP-10 (referring to, for example, international application published WO 98/37217), and And A41L in conjunction with LAR (referring to, for example, U.S. Patent number 6,852,486).

When being used for this paper, the A41L polypeptide refers to by any the genome institute in many poxvirus (it can not be called by nomenclature in many A41L polypeptide of coding any in the art A41L), described poxvirus includes but not limited to, smallpox, myxoma, rabbit fibroma virus (rabbit fibre The dimension tumor virus), camel acne (camelpox), monkeypox, ecromelia, cowpox and vaccinia virus (referring to GenBank registration number NC_001559; NC_001611; Y16780; X69198; NC_003310; NC_005337; AY603355; NC_003391; AF438165; U94848; AY243312; AF380138; L22579; M35027; NC_003663; X94355; AF482758; NC_001132; AF170726; NC_001266; AF170722; The reality of the genome sequence of F36852 (just polypeptide) Example (it comprises the nucleotide sequence of coding A41L polypeptide)). The A41L polypeptide can comprise this paper public affairs The variant of any amino acid sequence that open or known in the art or such amino acid sequence (comprising straight homologues). The representative amino acid sequence of A41L polypeptide is at SEQ ID NOs:1-8 In and at GenBank registration number NP_063835 (SEQ ID NO:10); NP_042191 (SEQ ID NO:11); CAA49088 (SEQ ID NO:12); NP_536578 (SEQ ID NO:13); P33854 (SEQ ID NO:14); P24766 (SEQ ID NO:15); P21 064 (SEQ ID NO: 16); AA50551 (SEQ ID NO:17); NP_570550 (SEQ ID NO:18); NP-570548 (SEQ ID NO:19); AAL73 867 (SEQ ID NO:20); AAL73865 (SEQ ID NO:21) In list.

The A41L polypeptide can also comprise the A41L polypeptide variants, and it is included at least one amino acid The amino acid sequence different from A41L peptide sequence as herein described or known in the art. Described The A41L polypeptide variants can owing to insert, lack, add and/or replace at least one amino acid and with Wild-type amino acid sequence difference, and can be owing to inserting, lack, add and/or replacing at least Two, three, four, five, six, seven, eight, nine or ten amino acid and difference, Arbitrary amino acid number that perhaps can be between 10 and 45 amino acid and difference. The A41L polypeptide Variant comprises that for example, naturally occurring polymorphism (that is, is compiled by the genome of different poxvirus strains The straight homologues of A41L polypeptide of code) or the A41L polypeptide variants of reorganization operation or transformation.

In certain embodiments, the variant of A41L polypeptide keeps wild type A41L polypeptide at least A kind of function or biologically active, and in other some embodiment, the A41L polypeptide variants keeps At least a, and in certain embodiments, keep wild type A41L polypeptide repertoire or life The thing activity. The function of A41L polypeptide or its variant or biologically active can be according to as herein described and bases The known method in field determines that its function or activity comprise (1) and acceptor PTPs:LAR, RPTP-δ With at least a or at least two kinds or whole three kinds of combinations or the interactional energy among the RPTP-σ Power; The ability of (2) being combined with the antibody of specific binding wild type A41L polypeptide; (3) suppress Express the ability of the immune response of at least a cell among LAR, RPTP-δ and the RPTP-σ. The function or the bioactive A41L polypeptide variants that keep wild type A41L polypeptide show with described The function that wild type A41L polypeptide shows or bioactive function of being on close level or activity Level (that is, not with statistically significant mode difference).

The polynucleotides of A41L polypeptide variants and these variants of coding can reflect by the sequence comparison Fixed. When being used for this paper, if when with maximum correspondence comparison, the amino of two seed amino acid sequences The acid residue is identical, and this two seed amino acids sequence has 100% amino acid sequence homogeny so. Similarly, if when with maximum correspondence comparison, the nucleotide residue of two kinds of sequences is identical, These two kinds of polynucleotides have 100% nucleotide sequence homogeny so. Sequence relatively can be used and appoint Where method is carried out, and comprises computer algorithm known to a person of ordinary skill in the art. Such fortune Algorithm comprise the comparison or the BLAST algorithm (referring to, for example, Altschul, J.Mol.Biol. (molecular biology magazine) 219:555-565,1991; Henikoff and Henikoff, Proc.Natl. Acad.Sci.USA (NAS's journal) 89:10915-10919,1992), it is at NCBI Available on the network address (referring to [online] Internet:＜URL: Http:// www/ncbi.nlm.nih.gov/cgi-bin/BLAST). Can use the parameter of acquiescence. In addition, The standard software program is available, as LASERGENE bioinformatics calculating group (DNASTAR, Company, Madison, WI) in comprise those; CLUSTALW program (Thompson etc., Nucleic Acids Res. (nucleic acids research) 22:4673-80 (1991)); With " GeneDoc " (Nicholas etc., EMBNEW News (EMBNEW news) 4:14 (1991)). By determining the optimal sequence comparison And other method that compares two kinds of nucleotides or amino acid sequence is implemented (ginseng by those skilled in the art See, for example, Peruski and Peruski, The Internet and the New Biology:Tools for Genomic and Molecular Research (Internet and neontology: genome and molecule The instrument of research) (ASM publishing company, 1997); Wu etc. (eds.), " Information Superhighway and Computer Databases of Nucleic Acids and Proteins (nucleic acid Information ultrahigh speed road and Computer Database with protein), " at Methods in Gene Among the Biotechnology (Genetic Biotechnologies method), 123-151 page or leaf (CRC publishing company, 1997); And Bishop (ed.), Guide to Human Genome Computing (guidance that human genome calculates), The 2nd edition. (Academic publishing company, 1998)).

In certain embodiments, the amino acid sequence of A41L polypeptide variants and corresponding A41L Wild type peptide or A41L polypeptide as herein described and/or well known in the art (referring to, for example, SEQ ID NOs:1-21) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 98% Identical. The nuclear of the polynucleotides that alternatively, the A41L polypeptide variants can be by the described variant of will encoding Nucleotide sequence compares and identifies with the polynucleotides of coding A41L polypeptide. In special enforcement side In the case, nucleotide sequence and the coding as herein described of the polynucleotides of coding A41L polypeptide variants One or more polynucleotide sequences at least 70%, 75%, 80%, 85%, 90% of A41L polypeptide, or 95% is identical. The polynucleotides variant also comprises because the degeneracy of genetic code is same at nucleotide sequence The property on different but coding to have an A41L of disclosed herein or amino acid sequence known in the art many The polynucleotides of peptide.

As described herein, the A41L polypeptide, it comprises A41L polypeptide variants and sheet as described herein Section and fused polypeptide (among itself and LAR, RPTP-δ and the RPTP-σ at least a, two kinds or Three kinds interact or combination, perhaps among itself and LAR, RPTP-δ and the RPTP-σ at least a, Two or three interacts or combination), it is present on the cell surface, can be used for changing (example As, suppress or strengthen) immunoreactivity of immunocyte.

In one embodiment, A41L as described herein or its variant or A41L fused polypeptide Can be used for the treatment of the patient who shows acute immune response. For example, A41L polypeptide, its variant or The immunity that fragment is can inhibition relevant with disease or the patient's condition such as ARDS (ARDS) should Answer. ARDS, it can be suffered from adult and children, usually along damage vesicle-capillary list The direct lung of position or system invade (for example, pyemia, pneumonia, suction). Some cell factors Relevant with described syndromic development, described cell factor comprises, for example, and tumor necrosis factor-alpha (TNF-α), interleukin-β (IL-β), IL-10 and soluble intercellular adhesion molecule 1 (sICAM-1). The level of the increase of these factors and cell factor or minimizing can in biological sample With by as herein described and usually implement with monitoring acute state and monitor therapy in the art The method of effect and mensuration and easily determine.

In order to reduce or to minimize possibility or degree to the special immune response of A41L, can with A41L, A41L variant, or derivatives thereof or fragment are used with the dosage of limited quantity, can be to change The glycosylated mode of change A41L is produced or is derived, can be at the antigen that reduces or minimize A41L Use under the condition of property. For example, A41L can reply, particularly using Immunosuppression to the host To before special second composition of replying of A41L, simultaneously or use afterwards. In addition, originally The pharmacokinetic characteristic that the technical staff in field is familiar with improving the half-life of polypeptide and/or improves polypeptide Method, such as by polypeptide Pegylation (pegylating) is carried out.

In some other embodiment, it is anti-that the A41L polypeptide fragment can change the immunity of immunocyte Answering property. Such A41L fragment and acceptor PTPs, among LAR, RPTP-δ and the RPTP-σ at least A kind of, at least two or all three kinds interaction or combination. Described fragment can comprise at least 6,7, 8,9,10,11,12,13,14, or 15 continuous amino acid. In certain embodiments, described The A41L fragment comprises at least any between 20 and 50 of the A41L polypeptide continuous amino acid The amino acid of number, and in other embodiments, described A41L fragment is included in A41L at least The amino acid of any number between 50 and 100 continuous amino acid of polypeptide. The A41L fragment also The truncate that comprises the A41L polypeptide. The A41L polypeptide of brachymemma can be from the ammonia of total length A41L polypeptide Base end or c-terminus or lack at least 1 from aminoterminal and c-terminus two ends, 2-10,11-20,21-30, 31-40, or 50 amino acid. In certain embodiments, described A41L fragment lacks total length A41L The whole aminoterminal part (half) of polypeptide or c-terminus part (half). In other embodiments, institute Stating A41L polypeptide fragment (fragment that comprises brachymemma) can be conjugated to, is fused to or is connected in addition Not on the part of A41L polypeptide or fragment. For example, the A41L polypeptide fragment can connect and can change Become the another kind of the immunoreactivity (for example, the immunoreactivity of Immunosuppression cell) of immunocyte Molecule, described immunocyte can be same cell, same type cell or with by described A41L The different cell of cell of polypeptide or fragment impact.

The example of A41L-fused polypeptide comprises that meeting frame ground with immunoglobulin (Ig) (Ig) Fc polypeptide melts A41L polypeptide as described herein, its variant or the fragment of closing. The Fc polypeptide bag of immunoglobulin (Ig) Draw together heavy chain CH2 domain and CH3 domain, and the part between CH1 and CH2 or Complete hinge area. On the origin history, the Fc fragment derives from the papain of immunoglobulin (Ig) Digest, and comprise the hinge area of immunoglobulin (Ig). The Fc district can pass through covalency (for example, spy Not disulfide bond) and non-covalent association and connect into the monomer polypeptide of dimer or polymer form. Fc The number of the intermolecular disulfide bond between the monomer subunit of polypeptide depends on described immunoglobulin (Ig) kind (for example, IgG, IgA, IgE) or subclass (for example, the human IgG1, IgG2, IgG3, IgG4, IgA1, IgA2) and different.

Can also use the fragment of Fc polypeptide, such as at the Fc polypeptide of the terminal brachymemma of C (that is, Remove or disappearance at least 1,2,3,4,5,10,15,20 or more amino acid). In some embodiment In, Fc polypeptide as herein described comprises a plurality of cysteine residues, at least one such as at hinge area A little or whole cysteine residues is with what allow at the A41L/Fc of two separation fused protein Form interchain disulfide bond between the Fc polypeptide portion, therefore form A41L/Fc fused polypeptide dimer. In other embodiments, if need to keep the cytotoxicity (ADCC) of antibody dependent cellular mediation With complement fixation (and relevant cytotoxicity (the associated complement of relevant complement Associated cytotoxicity, CDC)), so described Fc polypeptide is included in half Guang ammonia of hinge area Replacement or the disappearance of acid residue, thus the Fc polypeptide amalgamation protein is monomer, and can not form two Aggressiveness (referring to, for example, U.S. Patent Application Publication No. 2005/0175614).

Some effector function of the Fc part mediated immunity globulin of immunoglobulin (Ig). With the Fc zone Relevant three major types effector function comprises the activation of (1) classical complement cascade, (2) and effector cell Interaction and the compartmentation of (3) immunoglobulin (Ig). At present, very familiar according to the technical staff The recombinant molecule biology techniques, can easily prepare Fc polypeptide and any one or multiple perseverance Decide the plot structure territory and comprise the fusion of at least one constant region for immunoglobulin domain.

A41L polypeptide or its variant or fragment can meet frame ground with the immunoglobulin Fc polypeptide and merge (A41L-Fc fused polypeptide), its use derive from and are intended to use described A41L-Fc fused polypeptide The nucleotides of animal species and the amino acid sequence of coding are prepared. According to as herein described and ability The method of territory conventional practice, the technical staff of biology field can easily prepare such melting Close polypeptide. In one embodiment, described Fc polypeptide is the people source, and can come from and appoint A kind of immunoglobulin (Ig) kind, such as the human IgG1, IgG2, IgG3, IgG4, or IgA. Specific at one Embodiment in, described Fc polypeptide derive from human IgG1's immunoglobulin (Ig) (referring to, Kabat etc., As previously mentioned). In another embodiment, described A41L-Fc fused polypeptide comprises from inhuman Animal is such as, but not limited to, the Fc polypeptide of mouse, rat, rabbit or hamster. Derive from A41L-Fc The amino acid sequence of the Fc polypeptide of the immunoglobulin (Ig) of the host species that fused polypeptide can be used may Than the Fc polypeptide that comes from non-syngenic host still less immunity or disimmune. As described herein, each The immunoglobulin sequences of kind of species is in the art available, for example, at Kabat etc. (at Sequences Among of Proteins of Immunological Interest (sequence of immune destination protein), the 4th edition, (U.S. State HHS (U.S.Dept.of Health and Human Services), U.S.'s political affairs Mansion printing place (U.S.Government Printing Office), 1991)).

As described herein, with the Fc polypeptide meet the A41L polypeptide that merges on frame ground (or its variant or Fragment) can comprise any A41L polypeptide disclosed herein or known in the art. For example, tool Have by the amino acid sequence of the A41L polypeptide of the genome encoding of cowpox Brighton Red strain The A41L polypeptide can meet frame ground with immunoglobulin fc region and merge. Also as described herein, merge The Fc part of polypeptide can derive from people or non-human immunoglobulin. By way of example, The Fc of A41L-Fc fused polypeptide part can comprise human immunoglobulin(HIg) such as IgG1 hinge area, The all or part of amino acid sequence of CH2 domain and CH3 domain. Exemplary melting like this Closing polypeptide shows in Fig. 5. The A41L-Fc fused polypeptide can further comprise signal peptide sequence, institute After stating signal peptide sequence and promoting the translation of described polypeptide in expressing the host cell of described fused polypeptide Transhipment. Described signal peptide sequence can derive from by the poxvirus genome group that obtains the A41L sequence and be compiled The A41L signal peptide sequence of code. Alternatively, described signal peptide sequence can comprise derive from uncorrelated Polypeptide such as the amino acid sequence of human growth hormone (HGH).

Fc polypeptide as described herein also comprises the Fc polypeptide variants. A kind of such Fc polypeptide variants So that form interchain disulfide bond one or more cysteine residues (such as one of hinge area or A plurality of cysteine residues) replaced by another kind of amino acid such as serine, can form to reduce The number of the interchain disulfide bond that forms between two CH polypeptide of Fc polypeptide. In addition, or The person alternatively forms the hinge of disulfide bond with constant region of light chain in complete immunoglobulin molecules The aminoterminal cysteine residues in district can be substituted, and for example, replaces with serine residue. Alternative Ground, one or more cysteine residues can be from the wild type hinge area disappearance of Fc polypeptide. Fc is many Another example of peptide variant is so that relate to one or more amino acid of effector function and be substituted Or the variant of disappearance, so that described Fc polypeptide has the effector function level of minimizing. For example, exist The amino acid in Fc zone can be substituted, with the combination (ginseng of the composition that reduces or eliminates complement cascade See, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995)), perhaps reduce or eliminate the combination of Fc polypeptide The ability of the IgG Fc acceptor of being expressed by immunocyte (Wines etc., (immunology is assorted for J Immunol. Will) 164:5313-18 (2000); Chappel etc., Proc.Natl.Acad.Sci USA (American National Academy of sciences's journal) 88:9036 (1991); Canfield etc., J.Exp.Med. (The Journal of Experimental Medicine) 173:1483 (1991); Duncan etc., as previously mentioned); Perhaps change the thin of antibody-dependent cell Cellular toxicity. The such Fc polypeptide variants different from wild type Fc polypeptide also are called sudden change in this article Albumen Fc polypeptide.

In one embodiment, A41L polypeptide (or its fragment or variant) and Fc polypeptide meet and read Frame ground merges, and described Fc polypeptide is included in and helps the Fc polypeptide in the polypeptide of wild type Fc zone or exempt from The epidemic disease globulin is residual with one or more IgG Fc receptors bind of expressing at specific immunocyte At least a replacement of base. Such mutain Fc polypeptide is included in described mutain Fc polypeptide The CH2 domain at least a replacement of amino acid residue so that described fused polypeptide combination IgG Fc acceptor reduces such as the ability of the IgG Fc acceptor that exists on the immunocyte surface.

By the mode of background technology, express three kinds of dissimilar Fc IgG-the HL and be subjected to Body, it can and pass through antigenic structure and distinguish by the 26S Proteasome Structure and Function characteristics, and its difference is passed through CD Monoclonal antibody specific and detecting. Described IgG Fc acceptor is designated as Fc γ RI (CD64), Fc γ RII (CD32) and Fc γ RIII (CD 16), and differential expression is on overlapping leucocyte subset.

Fc γ RI (CD64) is at monocyte, macrophage, neutrophil cell, myelocyte precursor With the high-affinity receptor of expressing on the dendritic cells, comprise isotype Ia and Ib. Fc γ RII (CD32), Comprise isotype IIa, IIb1, IIb2, IIb3 and IIc are the people Fc γ R types of the most extensive distribution Low-affinity receptor; It on the blood leucocyte of most of type and Langerhans cell, Express on dendritic cells and the blood platelet. Fc γ RIII (CD 16) has two kinds of isotypes, and the two can both Be combined with human IgG1 and IgG3. The FcyRIIIa isotype has the medium affinity to IgG, and Express in macrophage, monocyte, NK (NK) cell and T cell subset. Fc γ RIIIb Be the low-affinity receptor of IgG, and optionally express at neutrophil cell.

Aminoterminal residue partly at the CH2 domain that helps IgG Fc receptors bind is included in The residue of position Leu234-Ser239 (Leu-Leu-Gly-Gly-Pro-Ser (SEQ ID NO:80) (EU Numbering system, Kabat etc., as previously mentioned) (referring to, for example, Morgan etc., Immunology (exempts from Epidemiology) 86:319-24 (1995) and the list of references wherein quoted). These positions and human IgG1 Fc The position 15-20 of the amino acid sequence of polypeptide (SEQ ID NO:79) is corresponding. In the CH2 domain In these 6 positions one or more (that is, one, two, three, four, five or all Six) 49-Phe ,82-Ser,115-Arg,144-Met,145-Asn ,161-Arg,169-Met Human Connective tissue growth factor of position cause described Fc polypeptide in conjunction with one or more IgG Fc acceptors (or The minimizing of ability its isotype) (referring to, for example, Burton etc., Adv.Immunol. is (senior Immunology) 51:1 (1992); Hulett etc., Adv.Immunol. (senior immunology) 57:1 (1994); Jefferis etc., Immunol.Rev. (immunology research) 163:59 (1998); Lund etc., J Immunol. (Journal of Immunology) 147:2657 (1991); Sarmay etc., Mol.Immunol. (molecular immunology) 29:633 (1992); Lund etc., Mol.Immunol. (molecular immunology) 29:53 (1992); Morgan Deng, as previously mentioned). Except the one or more amino acid that are substituted in EU position 234-239, (the carboxyl terminal side of close position 239, the perhaps close position that can also replace contiguous this zone 234 amino terminal side) one, two or three or more amino acid.

By way of example, (it is right to be substituted in position 235 with glutaminic acid residue or alanine residue Answer the position 16 of SEQ ID NO:79) leucine residue eliminate respectively or reduce immunoglobulin (Ig) (such as human IgG 3) to the affinity of Fc γ RI (Lund etc., 1991, as previously mentioned; Canfield etc., as Front described; Morgan etc., as previously mentioned). As another example, for example, will be in the position 234 Leucine residue alanine with 235 (positions 15 and 16 of its corresponding SEQ ID NO:79) Residue substitutes, eliminated immunoglobulin (Ig) and Fc γ RIIa combination (referring to, for example, Wines etc., As previously mentioned). Alternatively, 234 (positions 15 of its corresponding SEQ ID NO:79) in the position Leucine, in the position leucine of 235 (positions 16 of its corresponding SEQ ID NO:79) and The glycine of position 237 (position 18 of its corresponding SEQ ID NO:79), each can be used not With 49-Phe ,82-Ser,115-Arg,144-Met,145-Asn ,161-Arg,169-Met Human Connective tissue growth factor, such as 234 leucine can replace with alanine residue in the position (L234A), can replace (L235A) with alanine residue or use glutaminic acid residue at 235 leucine Replace (L235E), and 237 glycine residue can be used another kind of 49-Phe ,82-Ser,115-Arg,144-Met,145-Asn ,161-Arg,169-Met Human Connective tissue growth factor in the position, For example replace (G237A) with alanine residue.

In one embodiment, meeting frame ground with virus polypeptide (or its variant or fragment) merges Mutain Fc polypeptide be included in one, two, three of SEQ ID NO:79 position 15-20, Four, five or six sudden changes, the position 15-20 of SEQ ID NO:79 and people as described herein The position 234-239 of IgG1 CH2 domain (EU numbering system) is corresponding. A kind of exemplary prominent The white Fc polypeptide of a kink of preserved egg has the amino acid sequence of listing in SEQ ID NO:77, wherein with (L234A), (L235E), the replacement corresponding with (G237A) can be in the position of SEQ ID NO:77 13,14 and 16 find.

In another embodiment, mutain Fc polypeptide is included in the hinge area of Fc polypeptide The sudden change of cysteine residues. In one embodiment, near the ammonia of the hinge area of Fc polypeptide The cysteine residues of cardinal extremity (for example, for example, near the Fc of wild type IgG1 immunoglobulin (Ig) The N-terminal cysteine residues of hinge area of part) lacked or by another kind of 49-Phe ,82-Ser,115-Arg,144-Met,145-Asn ,161-Arg,169-Met Human Connective tissue growth factor. That is, the mode that illustrates by way of example, the cysteine residues in SEQ ID NO:79 position 1 is lacked Lose, the another kind of amino acid that perhaps 1 cysteine residues can not be formed disulfide bond in the position is got In generation, for example replace with serine residue. In another embodiment, mutain Fc polypeptide bag Contain disappearance or replacement near the N-terminal cysteine residues of the hinge area of Fc polypeptide, also bag Draw together disappearance or the replacement of contiguous C terminal amino acid. In a specific embodiment, this half Guang Propylhomoserin residue and contiguous C end residue are all lacked by the hinge area from mutain Fc polypeptide. One In the individual special embodiment, at the cysteine residues of SEQ ID NO:79 position 1 with at SEQ The aspartic acid of ID NO:79 position 2 is lacked. Be included in these cysteines and the sky of hinge area The Fc polypeptide of the disappearance of winter propylhomoserin residue can be expressed in host cell effectively, and at some In the situation, can be than the Fc polypeptide that keeps wild type cysteine and asparagicacid residue more effectively At cells.

In a special embodiment, mutain Fc polypeptide is included in SEQ ID NO:77 In the amino acid sequence listed, they are different from wild type Fc polypeptide (SEQ ID NO:79), wherein exist The cysteine residues of SEQ ID NO:79 position 1 is lacked, and in SEQ ID NO:79 position 2 aspartic acid is lacked, and at leucine residue third ammonia of SEQ ID NO:79 position 15 The acid residue replaces, and 16 leucine residue replaces with glutaminic acid residue in the position, and in the position 18 Glycine replace (also referring to Fig. 5) with alanine residue. Therefore, exemplary mutain Fc Polypeptide partly comprises amino acid sequence KTHTCPPCPAPEAEGAPS (SEQ ID at its aminoterminal NO:81) (referring to SEQ ID NO:77, a kind of exemplary Fc mutain sequence).

Other Fc variant comprises the similar amino acid sequence of known Fc peptide sequence, and it has little Little change, for example, the mode of explanation rather than restriction by way of example, covalent chemical modify, insert, Disappearance and/or replacement, it can further comprise conservative the replacement. Similar amino acid sequence can each other To enjoy the fundamental region of sequence homology. Similarly, the nucleotide sequence of coding Fc variant can wrap Draw together basically similar nucleotide sequences, and only have small variation, for example, say by way of example Bright rather than limit mode, covalent chemical are modified, insert, are lacked and/or replace, owing to heredity The degeneracy of password, it can further comprise silent mutation. Similar nucleotide sequences can each other Enjoy the fundamental region of sequence homology.

When merging with purpose peptide or polypeptide, Fc polypeptide or at least one constant region for immunoglobulin or Its part, at least part of excipient or carrier part of acting as, its prevent described peptide degraded and/or Increase the half-life, reduce toxicity, reduce immunogenicity, and/or increase biologically active, such as passing through Formation dimer or other polymer (referring to, for example, U.S. Patent number 6,018,026; 6,291,646; 6,323,323; 6,300,099; 5,843,725). (also referring to, for example, U.S. Patent number 5,428,130; Beautiful State's patent No. 6,660,843; U.S. Patent Application Publication No. 2003/064480; 2001/053539; 2004/087778; 2004/077022; 2004/071712; 2004/057953/2004/053845/ 2004/044188; 2004/001853; 2004/082039).

Meeting frame ground with Fc polypeptide or Fc polypeptide variants (for example, mutain Fc polypeptide) melts The A41L polypeptide that closes (or its variant or fragment) can wrap between A41L polypeptide and Fc polypeptide Contain peptide linker. Described joint can be single amino acids (such as for example glycine residue), or can Two, three, four, five, six, seven, eight, nine or ten amino acid, Maybe can be the amino acid of any number between 10 and 20 amino acid. By way of example the explanation and Be not the mode of restriction, joint can comprise by the nucleotide sequence as the Restriction Enzyme recognition site to be compiled At least two amino acid of code. The example of such Restriction Enzyme recognition site comprises, for example, and BamHI, ClaI, EcoRI, HindIII, KpnI, NcoI, NheI, PmlI, PstI, SalI, and XhoI.

Meet A41L polypeptide, its fragment or its variant that frame ground merges with mutain Fc polypeptide, When suitable according to the known method of the practitioner of as herein described and field of medicaments and pharmacy or physiology When the carrier that closes or excipient are used together, can be used for suppressing the immune response among the experimenter. Like this Fused polypeptide can change RPTP polypeptide as herein described (that is, LAR, RPTP-σ, RPTP-δ) In at least a, the biologically active of at least two kinds of RPTP polypeptide or whole three kinds of RPTP polypeptide. In certain embodiments, with mutain Fc polypeptide meet the A41L polypeptide that merges on frame ground, Its fragment or its variant are used for the treatment of immunological diseases or illness and (comprise autoimmune disease or inflammatory Sick), it is described in detail in this article. As described herein, described A41L/ mutain Fc polypeptide Can also be used to treat disease or the disease relevant with the change of cell migration, cell proliferation or Cell Differentiation Disease, it includes but not limited to immunological diseases or illness, angiocardiopathy or illness, metabolic disease or disease Disease or hyperplasia or illness.

The A41L polypeptide fragment comprises A41L polypeptide variants fragment. The A41L polypeptide fragment also comprises having The A41L fragment of the amino acid sequence different from the total length A41L in described fragment source, that is, described The part of A41L polypeptide fragment variant and total length A41L polypeptide has at least 99%, 98%, and 97%, 95%, 90%, 87%, 85%, or 80% amino acid sequence homogeny. Having change (suppresses or increases By force) variant of the A41L polypeptide fragment of the immunoreactive ability of immunocyte keeps the change immunity The immunoreactive suitable ability of cell.

The A41L polypeptide variants and the A41L that keep the immunoreactive ability that changes immunocyte are many The fragments of peptides variant comprises and contains the variant that conserved amino acid replaces. Known to those skilled in the art Whether various rule indications are (or similar) of guarding at the amino acid of the ad-hoc location of peptide or polypeptide. For example, similar amino acid or conservative 49-Phe ,82-Ser,115-Arg,144-Met,145-Asn ,161-Arg,169-Met Human Connective tissue growth factor are so a kind of, that is, wherein amino acid is residual Base substitutes with the amino acid residue with similar side chain, such as the amino acid with following side chain: alkalescence Side chain (for example, lysine, arginine, histidine); Acid side-chain (for example, aspartic acid, paddy Propylhomoserin); Uncharged polar side chain (for example, glycine, asparagine, glutamine, silk ammonia Acid, threonine, tyrosine, cysteine, histidine); Non-polar sidechain (for example, alanine, figured silk fabrics Propylhomoserin, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan); β-side chain Side chain (for example, threonine, valine, isoleucine), and aromatic side chain (for example, tyrosine, benzene Alanine, tryptophan). Proline, it is considered to more be difficult to classification, enjoys the ammonia with aliphatic side chains The characteristics of base acid (for example, leucine, valine, isoleucine and alanine). In some situation In, glutamine replaces glutamic acid or asparagine replacement aspartic acid can be thought similar getting In generation, reason is that glutamine and asparagine are respectively that the acid amides of glutamic acid and aspartic acid is derived Thing. As understanding in the art, " similitude " between two peptide species is by with described The amino acid sequence of polypeptide and its conserved amino acid replace and the sequence of second polypeptide (for example, compares Use GENEWORKS, Align, or BLAST algorithm, as described herein) and determine. By way of example, A41L variant as herein described has in the position 50 of SEQ ID NO:82 With lysine residue replace arginine residues conservative replacement (GenBank registration number AAM13618, On May 20th, 2003), thus provide SEQ ID NO:83 (also referring to, for example, Hu etc., Virology (virology) 181:716-20 (1991); Hu etc., Virology (virology) 204:343-56 (1994)). This A41L variant keeps function and the characteristic of wild type A41L polypeptide.

The A41L polypeptide variants also comprises and unique one or both (that is, LAR and RPTP-δ, LAR With RPTP-σ, or RPTP-δ and RPTP-σ) rather than whole three kinds of LAR, RPTP-δ and The variant of RPTP-σ interaction or combination. Compare such variant with wild type A41L polypeptide Comprise at least 1,2,3,4,5,6,7,8,9,10,11-15,16-25,26-35, or 36-45 amino acid Replace, lack or insert. The combination of A41L and every kind of RPTPs can be according to as herein described and basis The method of field practice is determined. The source that is used for the polypeptide of binding comprises, for example, separates A41L and RPTPs, or its fragment, or can recombinant expressed A41L, LAR, RPTP-δ and A kind of individual cells system among the RPTP-σ.

The variant of A41L full-length polypeptide or A41L fragment can be given birth to by heredity processing and recombinant molecule Thing method and technology easily prepare. The firsts and seconds amino acid sequence analysis of A41L polypeptide and Analyzing the computer model of the tertiary structure of described polypeptide can assistant identification can be substituted and do not change Therefore become described structure and do not change potentially the special amino acid of function of described A41L polypeptide residual Base. The modification of the DNA of coding A41L polypeptide or fragment can be undertaken by the whole bag of tricks, comprises The locus specificity of DNA or site-directed mutagenesis, described method comprise that the DNA that uses primer expands Increase, in dna profiling, to introduce and the amplification change, such as the PCR by overlapping extension (SOE) Montage. Sudden change can be by the synthetic restriction site side that comprises by the fragment that can connect native sequences The oligonucleotides of the mutant nucleotide sequence that connects and introducing at ad-hoc location. After the connection, the order of the reconstruct that obtains The row coding has the variant (or derivative) of the amino acid insertion, replacement or the disappearance that need.

Phage vector such as the M13 with strand and double chain form typically used in site-directed mutagenesis Phage vector and realize that described phage vector is known and commercially available. Can use and comprise Other suitable carrier of single stranded phage origin of replication (referring to, for example, Veira etc., Meth. Enzymol. (Enzymology method) 15:3 (1987)). Usually, site-directed mutagenesis is by preparation coding order Albumen single-stranded vector and carry out. Will with single-stranded vector in the zone of dna homology in comprise The Oligonucleolide primers of the sudden change that needs and the annealing of described carrier add archaeal dna polymerase then, and is all Such as Escherichia coli (E.coli) dna polymerase i (Ke Lienuo (Klenow) fragment), its use Double-stranded region is as primer, generates heteroduplex, sequence that chain encoding changes wherein, another Bar chain encoding original series. For example, can be at (Meth.Enzymol. (Enzymology method) such as Kunkel 154:367 (1987)) and find in the U.S. Patent number 4,518,584 and 4,737,462 about the site fixed Other disclosure to mutagenesis. Described heteroduplex is incorporated in the suitable bacterial cell, and And selection comprises the clone of the sudden change of needs. The dna molecular of the change that obtains can be in suitable place Recombinant expressed in the chief cell, to generate described variant, the albumen of modification.

Can use locus specificity (or fragments specific) method of mutagenesis that oligonucleotides instructs, with Provide replacement, disappearance or the insertion that has as required and the change of the specific codon that changes many Nucleotides. The disappearance of protein or brachymemma derivative can also be by using the normal of the contiguous disappearance that needs Rule restriction endonuclease site and making up. Behind restriction enzyme digestion, jag can be filled also And DNA reconnects. Prepare the illustrative methods of above-mentioned change by (Molecular such as Sambrook Cloning:A Laboratory Manual (molecular cloning: laboratory manual), the 3rd edition, Cold Spring Harbor Laboratory Press (publishing house of cold spring harbor laboratory), New York 2001) open. Alternatively, the random mutagenesis technology, such as alanine subregion mutagenesis, error-prone PCR lures The mutagenesis that change and oligonucleotides instruct can be used for preparing A41L polypeptide variants and fragment variant (ginseng See, for example, Sambrook etc., as previously mentioned).

Whether be folded into the survey of the conformation suitable with non-variant polypeptide or fragment for assessment of described variant Surely comprise, for example, described albumen with to monoclonal natural or not folding epitope specificity or many The ability of clonal antibody reaction, the reservation of part-binding function and described mutain are to protease The sensitiveness of digestion or resistance (referring to, Sambrook etc., as previously mentioned). As described herein The A41L variant can be implemented usually according to these methods as herein described or those skilled in the art Other method known in the art is identified, characteristic is described and/or preparation.

The sudden change of preparation or evaluation preferably keeps code sequence in the nucleic acid molecules of coding A41L polypeptide The reading frame of row. In addition, described sudden change preferably will not produce complementary district, and described complementary district is transcribing The time can hybridize to produce the secondary mRNA structure of the translation that adversely affects mRNA, such as ring or send out Folder. Although the mutational site can pre-determine, the character of sudden change itself does not need to pre-determine. For example, in order to be chosen in the best features to the sudden change of anchor point, can the target codon carry out with Machine mutagenesis, and for bioactive acquisition or lose or keep and screen expressed mutant.

The A41L polynucleotides are coding A41L polypeptide or the part of A41L polypeptide (or fragment) at least Or any polynucleotides of its variant, or with any polynucleotides of described polynucleotides complementation. For example, the nucleotide sequence of the polynucleotides of coding A41L or its straight homologues can be about this Find in the genome sequence of the poxvirus that provides in the GenBank record of the registration number that literary composition provides, At GenBank registration number NC_001559; NC_001611; Y16780; X69198; NC_003310; NC_005337; AY603355; NC_003391; AF438165; U94848; AY243312; AF380138; L22579; M35027; NC_003663; X94355; AF482758; NC_001132; AF170726; NC_001266; AF170722 and can deriving from amino acid sequence disclosed herein The sequence that goes out (for example, SEQ ID NOs:1-21). Polynucleotides comprise at least 15 continuous nucleosides Acid or at least 30,35,40,50,55 or 60 continuous nucleotides, in certain embodiments, at least 70,75,80,90,100,110,120,125, or 130 continuous nucleotides, and in other enforcement side In the case, at least 135,140,145,150,155,160, or 170 continuous nucleotides, and at it In its embodiment, at least 180,190,200,225,250,275,300,325,350,375,400, 405,410,420,425,445,450,475,500,525,530,545,550,575,600,625,650, Or 660 continuous nucleotides, described continuous nucleotide comprise coding A41L polypeptide sequence or and this The nucleotide sequence of the sequence complementation of sample. Some multinuclear of coding A41L polypeptide or its variant or fragment Thuja acid can also be used as RNA interfering (siRNA) or the ASON of probe, primer, weak point, As described herein. Polynucleotides can be single stranded DNA or RNA (coding or antisense) or two Chain RNA (for example, genome or synthetic) or DNA (for example, cDNA or synthetic).

The polynucleotide variant can also be identified by hybridizing method.Suitable medium stringent condition comprises, for example, at 5X SSC, 0.5%SDS, prewashing in 1.0mM EDTA (pH 8.0) solution; At 50 ℃-70 ℃, 5X SSC hybridization 1-16 hour; Then 22-65 ℃ with every kind of 2X that contains 0.05-0.1%SDS, one or more washings among 0.5X and the 0.2X SSC reach 20-40 minute once or twice.For extra severity, condition can be included among 0.1X SSC and the 0.1%SDS 50-60 ℃ of washing 15 minutes.Will be understood by those skilled in the art that the variation of hybridization conditions severity can obtain by change time, temperature and/or the concentration that is used for the solution of prehybridization, hybridization and washing step.Suitable condition can also depend in part on the specific nucleotide sequence (that is, for example, guanine adds cytosine(Cyt) (G/C) and adds thymus pyrimidine (A/T) content with respect to VITAMIN B4) of used probe.Therefore, it should be appreciated by those skilled in the art, when the selectivity of the needs of identifying probe, can need not unsuitable experiment and easily select suitable stringency.

The 130L polypeptide

As described herein, a kind of glycoprotein of 130L genes encoding (this paper is called the 130L polypeptide), it may be a kind of virus virulence factor, and it is by the emiocytosis of infecting YLDV.Similar to other poxvirus, the genome of YLDV is a double-stranded DNA, and described virus allows described virus to escape host's immunity system by acquisition and/or promote the host gene of virus replication to be adapted at duplicating in the various host species (referring to, for example, Najarro etc., J Gen.Virol. (hereditary Journal of Virology) 84:3325-36 (2003)).Can be by suppressing or the function of blocking-up host's factor such as Interferon, rabbit, complement, cytokine and/or chemokine by the polypeptide of the genome encodings of many poxvirus, perhaps by suppress, blocking-up or the effect that changes inflammation and fever influence immunne response.

When being used for this paper, the 130L polypeptide is meant by any (referring to the example (it comprises the nucleotide sequence of coding 130L polypeptide) about the genome sequence of tanapox virus, GenBank registration number AJ293568.1 and NC_002642.1) in many 130L polypeptide of the genome encoding of inferior tower poxvirus tanapox virus.The 130L polypeptide can comprise the variant (comprising directly to homologue) of any aminoacid sequence disclosed herein or known in the art or such aminoacid sequence.The representative aminoacid sequence of 130L polypeptide is in SEQ ID NO:85 (referring to, GenBank registration number CAC21368.1) and list in GenBank registration number NP_073515.1 (SEQ ID NO:144).

The 130L polypeptide can also comprise the 130L polypeptide variants, and it is included at least one amino acid and the different aminoacid sequence of 130L peptide sequence as herein described or known in the art.Described 130L polypeptide variants can be owing to inserting, lack, add and/or replacing at least one amino acid and different with the wild-type amino acid sequence, and can be owing to inserting, disappearance, adding and/or replace at least two, three, four, five, six, seven, eight, nine or ten amino acid and difference, perhaps can be and difference at the arbitrary amino acid number between 10 and 45 amino acid.The 130L polypeptide variants comprises, for example, and the 130L polypeptide variants of naturally occurring polymorphism (that is, by the 130L polypeptide of the genome encoding of the inferior tower poxvirus of difference strain directly to homologue) or reorganization operation or processing.

In certain embodiments, the 130L variant polypeptides keeps at least a function or the biological activity of wild-type 130L polypeptide, and in other some embodiment, the 130L polypeptide variants keeps at least a, and in certain embodiments, keep wild-type 130L polypeptide repertoire or biological activity.The function of 130L polypeptide or its variant or biological activity can be determined according to as herein described and methods known in the art, its function or activity comprise (1) and acceptor PTPs, at least a or at least two kinds or whole three kinds of combinations or interactional ability among LAR, RPTP-δ and the RPTP-σ; (2) combine the ability of the antibodies of wild-type 130L polypeptide with specificity; (3) ability of the immunne response of at least a cell among LAR, RPTP-δ and the RPTP-σ is expressed in inhibition.The function or the bioactive 130L polypeptide variants that keep wild-type 130L polypeptide show function or bioactive function of being on close level or the active level (that is, not having with statistics the remarkable or remarkable mode difference of biology) that is shown with described wild-type 130L polypeptide.

The polynucleotide of 130L polypeptide variants and these variants of coding can be identified by the sequence comparison.When being used for this paper, if when comparing with maximum correspondence, the amino-acid residue of two seed amino acid sequences is identical, and this two seed amino acids sequence has 100% aminoacid sequence homogeny so.Similarly, if when comparing with maximum correspondence, the nucleotide residue of two kinds of sequences is identical, and these two kinds of polynucleotide have 100% nucleotide sequence homogeny so.Sequence relatively can use any method to carry out, and comprises using computer algorithm known to a person of ordinary skill in the art.Such algorithm comprise the comparison or the BLAST algorithm (referring to, for example, Altschul, J.Mol.Biol. (molecular biology magazine) 219:555-565,1991; Henikoff and Henikoff, Proc.Natl.Acad.Sci.USA (NAS's journal) 89:10915-10919,1992), it is available on the NCBI network address (referring to [online] Internet:＜URL:http: //www/ncbi.nlm.nih.gov/cgi-bin/BLAST).Can use the parameter of acquiescence.In addition, the standard software program is an available, as at LASERGENE information biology calculating group (DNASTAR, company, Madison, those that comprise in WI); CLUSTALW program (Thompson etc., NucleicAcids Res. (nucleic acids research) 22:4673-80 (1991)); With " GeneDoc " (Nicholas etc., EMBNEW News (EMBNEW news) 4:14 (1991)).By determine other method that optimal sequence compares two kinds of Nucleotide or aminoacid sequence by those skilled in the art's enforcement (referring to, for example, Peruski and Peruski, The Internet and the New Biology:Tools forGenomic and Molecular Research (Internet and neontology: the instrument of genome and molecular studies) (ASM publishing company, 1997); Wu etc. (eds.), " InformationSuperhighway and Computer Databases of Nucleic Acids and Proteins (nucleic acid and proteinic information ultra-high speed road and Computer Database); " in Methods in GeneBiotechnology (gene biological technological method), 123-151 page or leaf (CRC publishing company, 1997); And Bishop (ed.), Guide to Human Genome Computing (guidance that the people's gene batch total is calculated), the 2nd edition. (Academic publishing company, 1998)).

In certain embodiments, the aminoacid sequence of 130L polypeptide variants and corresponding 130L wild type peptide or 130L polypeptide as herein described and/or well known in the art (referring to, for example, SEQID NO:85 (it has signal peptide sequence (SEQ ID NO:151)) or SEQ ID NO:150 (sophisticated 130L polypeptide)) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 98% is identical.Alternatively, the polynucleotide of the nucleotide sequence of the polynucleotide that the 130L polypeptide variants can be by the described variant of will encoding and coding 130L polypeptide compare and identify.In special embodiment, the nucleotide sequence of the polynucleotide of coding 130L polypeptide variants and one or more polynucleotide sequences at least 70%, 75%, 80%, 85%, 90% of the 130L polypeptide of encoding as herein described, or 95% is identical.The polynucleotide variant also comprises because the degeneracy of genetic code different still codings on nucleotide sequence homology have the polynucleotide of the 130L polypeptide of disclosed herein or aminoacid sequence known in the art.

As described herein, the 130L polypeptide, it comprise 130L polypeptide variants as described herein and fragment and fusion polypeptide (its with LAR, RPTP-δ and RPTP-σ at least a, two or three interact or combine), it is present on the cell surface, can be used for changing the immunoreactivity of (for example, suppressing or enhancing) immunocyte.In one embodiment, 130L polypeptide as described herein or its variant or 130L fusion polypeptide can be used for the treatment of the patient who shows acute immunne response.For example, 130L polypeptide, its variant or fragment can inhibition and disease or the patient's condition such as the relevant immunne response of adult respiratory distress syndrome (ARDS).ARDS, it can be suffered from grownup and children, and direct lung or the system along damage vesicle-kapillary unit invades (for example, Sepsis, pneumonia, suction) usually.Some cytokines are relevant with described syndromic development, and described cytokine comprises, for example, and tumor necrosis factor-alpha (TNF-α), interleukin-β (IL-β), IL-10 and soluble iuntercellular adhesion molecule 1 (sICAM-1).The level of the increase of these factors and cytokine or minimizing can be by as herein described and usually implement in the art easily to determine with the method for monitoring acute state and monitoring therapeuticing effect and mensuration in biological sample.

In order to reduce or to minimize possibility or degree to the special immunne response of 130L, can or comprise its fusion rotein with 130L polypeptide, 130L variant, or derivatives thereof or fragment, dosage with limited quantity is used, can produce or derive in the glycosylated mode that changes 130L, and/or can use reducing or minimize under antigenic condition of 130L.For example, 130L can use to the host suppress immunne response, particularly to 130L before special second composition of replying, simultaneously or use afterwards.

In some other embodiment, the 130L polypeptide fragment can change the immunoreactivity of immunocyte.Such 130L fragment and acceptor PTPs, at least a, two or all three kinds interaction or combination at least among LAR, RPTP-δ and the RPTP-σ.Described fragment can comprise at least 6,7,8,9,10,11,12,13,14, or 15 successive amino acid.In certain embodiments, described 130L fragment comprises the amino acid of any number between 20 and 50 successive amino acid of 130L polypeptide at least, and in other embodiments, described 130L fragment is included in the amino acid of any number between 50 and 100 successive amino acid of 130L polypeptide at least.The 130L fragment also comprises the truncate of 130L polypeptide.The 130L polypeptide of brachymemma can lack at least 1,2-10,11-20,21-30,31-40, or 50 amino acid from the N-terminal of total length 130L polypeptide or carboxyl terminal or from aminoterminal and carboxyl terminal two ends.In certain embodiments, described 130L fragment lacks the whole aminoterminal part or the carboxyl terminal part of total length 130L polypeptide.In other embodiments, described 130L polypeptide fragment (fragment that comprises brachymemma) can be conjugated to, be fused to or be connected in addition and not be on 130L polypeptide or the segmental part.For example, the 130L polypeptide fragment can connect can change immunocyte immunoreactivity (for example, the immunoreactivity that suppresses immunocyte) another kind of molecule, described immunocyte can be same cell, same type cell or with the different cell of cell by described 130L polypeptide or fragment influence.In addition, those skilled in the art are afamiliar with the method that is used to improve the transformation period of polypeptide and/or improves the pharmacokinetics feature, such as by described polypeptide Pegylation is carried out.

The example of 130L-fusion polypeptide comprises 130L polypeptide as described herein, its variant or the fragment that meets the fusion of frame ground with immunoglobulin (Ig) (Ig) Fc polypeptide.The Fc polypeptide of immunoglobulin (Ig) comprises heavy chain CH2 structural domain and CH3 structural domain, and the partial or complete hinge area between CH1 and CH2.On the origin history, the Fc fragment derives from the papain digestion of immunoglobulin (Ig), and comprises the hinge area of immunoglobulin (Ig).The Fc district can pass through covalency (for example, particularly disulfide linkage) or non-covalent association and the monomer polypeptide that connects into dimer or polymer form.The number of the intermolecular disulfide bond between the monomer subunit of Fc polypeptide depend on described immunoglobulin (Ig) kind (for example, IgG.IgA, IgE) or subclass (for example, the human IgG1, IgG2, IgG3, IgG4, IgA1, IgA2) and different.

Can also use the fragment of Fc polypeptide, such as at the Fc of C-terminal brachymemma polypeptide (that is, removed or lacked at least 1,2,3,4,5,10,15,20 or more a plurality of amino acid).In certain embodiments, Fc polypeptide as herein described comprises a plurality of cysteine residues, such as at least some of hinge area or whole cysteine residues, to allow between the Fc of two isolating 130L/Fc fused proteins polypeptide portion, forming interchain disulfide bond, therefore form 130L/Fc fusion polypeptide dimer.In other embodiments, the cytotoxicity (ADCC) and complement fixation(CF) (and the relevant cytotoxicity (CDC) of relevant complement) that keep the antibody dependent cellular mediation if desired, so described Fc polypeptide is included in the replacement or the disappearance of the cysteine residues of hinge area, so that the Fc polypeptide amalgamation protein is monomeric, and can not form dimer (referring to, for example, U.S. Patent Application Publication No. 2005/0175614).

The Fc of immunoglobulin (Ig) partly mediates some effector function of immunoglobulin (Ig).The three major types effector function relevant with the Fc zone comprises the activation of (1) classical complement cascade, (2) and the interaction of effector cell and the compartmentation of (3) immunoglobulin (Ig).At present, according to the recombinant molecule biology techniques that the technician is familiar with very much, can easily prepare Fc polypeptide and any one or multiple constant region structural domain and comprise the fusion rotein of at least one constant region for immunoglobulin structural domain.

130L polypeptide or its variant or fragment can meet frame ground with the immunoglobulin Fc polypeptide and merge (130L-Fc fusion polypeptide), and described immunoglobulin Fc polypeptide uses the Nucleotide and the amino acid sequence coded that derive from the animal species that is intended to use described 130L-IgFc fusion polypeptide to be prepared.According to as herein described and method this area conventional practice, the technician of biology field can easily prepare such fusion polypeptide.In one embodiment, described Fc polypeptide is the people source, and can come from any immunoglobulin (Ig) kind and subclass, as the human IgG1, and IgG2, IgG3, IgG4, or IgA.In a specific embodiment, described Fc polypeptide derives from human IgG1's immunoglobulin (Ig) (referring to, Kabat etc., as previously mentioned).In another embodiment, described 130L-Fc fusion polypeptide comprises from the non-human animal, for example, but is not limited to the Fc polypeptide of mouse, rat, rabbit or hamster.The Fc amino acid sequence of polypeptide that derives from the immunoglobulin (Ig) of the host species that the 130L-Fc fusion polypeptide can use may be than the Fc polypeptide that comes from non-syngenic host still less immunity or disimmune.As described herein, the immunoglobulin sequences of various species is available in the art, for example, at Kabat etc. (in Sequences of Proteins of Immunological Interest (sequence of immune target protein), the 4th edition, (U.S. HHS (U.S.Dept.of Health andHuman Services), United States Government's printing place (U.S.Government Printing Office), 1991)).

As described herein, meet the 130L polypeptide (or its variant or fragment) that merges on frame ground with the Fc polypeptide and can comprise any 130L polypeptide disclosed herein or known in the art.For example, have by the 130L amino acid sequence of polypeptide of the genome encoding of tanapox virus (referring to, for example, GenBank registration number AJ293568.1 and NC_002642) the 130L polypeptide can with immunoglobulin fc region (for example, referring to, SEQ ID NO:154) meet frame ground and merge.Also as described herein, the Fc part of fusion polypeptide can derive from people or non-human immunoglobulin.By way of example, the Fc of 130L-Fc fusion polypeptide part can comprise all or part of aminoacid sequence of hinge area, CH2 structural domain and the CH3 structural domain of human normal immunoglobulin such as IgG1.The 130L-Fc fusion polypeptide can further comprise signal peptide sequence, and described signal peptide sequence promotes the post-translational transport of described polypeptide in the host cell of expressing described fusion polypeptide.Described signal peptide sequence can derive from by the coded 130L signal peptide sequence of poxvirus genome group that obtains the 130L sequence.Alternatively, described signal peptide sequence can comprise the aminoacid sequence that derives from incoherent polypeptide such as human growth hormone.

Fc polypeptide as described herein also comprises the Fc polypeptide variants.A kind of such Fc polypeptide variants makes the one or more cysteine residues (such as the one or more cysteine residues at hinge area) that form interchain disulfide bond be replaced by another kind of amino acid such as Serine, to reduce the number of the interchain disulfide bond that can form between two CH polypeptide that form the Fc polypeptide.In addition, perhaps alternatively, the aminoterminal cysteine residues that forms the hinge area of disulfide linkage with constant region of light chain in complete immunoglobulin molecules can be substituted, and for example, replaces with serine residue.Alternatively, one or more cysteine residues can be from the wild-type hinge area disappearance of Fc polypeptide.Another example of Fc polypeptide variants is the variant that the feasible one or more amino acid that participate in effector function are substituted or lack, so that described Fc polypeptide has the effector function level of minimizing.For example, the amino acid in the Fc zone can be substituted, with the combination of the composition that reduces or eliminates complement cascade (referring to, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995)), perhaps reduce or eliminate the Fc polypeptide in conjunction with the ability of the IgG Fc acceptor of expressing by immunocyte (Wines etc., J Immunol. (Journal of Immunology) 164:5313-18 (2000); Chappel etc., Proc.Natl.Acad.Sci USA (NAS's journal) 88:9036 (1991); Canfield etc., J.Exp.Med. (The Journal of Experimental Medicine) 173:1483 (1991); Duncan etc., as previously mentioned); Perhaps change the cytotoxicity of antibody-dependent cell.The such Fc polypeptide variants different with wild-type Fc polypeptide also are called mutain Fc polypeptide in this article.

In one embodiment, 130L polypeptide (or its fragment or variant) and Fc polypeptide merge, and described Fc polypeptide is included at least a replacement of the residue of the one or more IgG Fc receptors bind that help Fc polypeptide or immunoglobulin (Ig) in the polypeptide of wild-type Fc zone and express on specific immunocyte.Such mutain Fc polypeptide is included at least a replacement of the amino-acid residue in the CH2 structural domain of described mutain Fc polypeptide, so that described fusion polypeptide reduces in conjunction with the ability of IgG Fc acceptor as the IgG Fc acceptor that exists on the immunocyte surface.

Discuss as this paper, be included in residue (Leu-Leu-Gly-Gly-Pro-Ser (SEQ ID NO:152) (the EU numbering system of position Leu234-Ser239 at the aminoterminal residue partly of the CH2 structural domain that helps IgG Fc receptors bind, Kabat etc., as previously mentioned) (referring to, for example, Morgan etc., Immunology (immunology) 86:319-24 (1995) and the reference of wherein quoting).In the CH2 structural domain in these 6 positions one or more (promptly, one, two, three, four, five or whole six) aminoacid replacement of position cause described Fc polypeptide in conjunction with the minimizing of the ability of one or more IgG Fc acceptors (or its isotype) (referring to, for example, Burton etc., Adv.Immunol. (senior immunology) 51:1 (1992); Hulett etc., Adv.Immunol. (senior immunology) 57:1 (1994); Jefferis etc., Immunol.Rev. (immunology research) 163:59 (1998); Lund etc., J Immunol. (Journal of Immunology) 147:2657 (1991); Sarmay etc., Mol.Immunol. (molecular immunology) 29:633 (1992); Lund etc., Mol.Immunol. (molecular immunology) 29:53 (1992); Morgan etc., as previously mentioned).Except the one or more amino acid that are substituted in EU position 234-239, can also replace (the C-terminal side of close position 239, perhaps the N-terminal side of close position 234) one, two or three or more amino acid in contiguous this zone.

By way of example, the leucine residue that is substituted in position 235 with glutaminic acid residue or alanine residue eliminate respectively or reduce immunoglobulin (Ig) (as human IgG 3) to the avidity of Fc γ RI (Lund etc., 1991, as previously mentioned; Canfield etc., as previously mentioned; Morgan etc., as previously mentioned).As another example, for example, will be in the position 234 and 235 leucine residue substitute with alanine residue, eliminate the combining of immunoglobulin (Ig) and Fc γ RIIa (referring to, for example, Wines etc., as previously mentioned).Alternatively, 234 the leucine in the position, 235 the leucine in the position, with 237 glycine in the position, each can be with different aminoacid replacement, and such as 234 leucine can replace (L234A) with alanine residue in the position, the leucine 235 can replace (L235A) with alanine residue or replace (L235E) with glutaminic acid residue, and 237 glycine residue can be used another kind of aminoacid replacement in the position, for example replaces (G237A) with alanine residue.

In one embodiment, and 130L polypeptide (or its variant or fragment) meets the mutain Fc polypeptide that merges on frame ground and comprises, two, three, four, five or six sudden changes (with the replacement of EU234,235 and 237 corresponding positions) that are located between the SEQ ID NO:145 position 15-20 or between SEQ ID NO:146 position 13-18, and described position is corresponding with the position 234-239 (EU numbering system) of human IgG1 CH2 structural domain as described herein.

In another embodiment, mutain Fc polypeptide is included in the sudden change of the cysteine residues in the hinge area of Fc polypeptide.In one embodiment, (the most for example near the N-terminal cysteine residues of the hinge area of Fc polypeptide, for example, near the N-terminal cysteine residues of the hinge area of the Fc part of wild-type IgG1 immunoglobulin (Ig)) lacked or by another kind of aminoacid replacement.That is, Shuo Ming mode by way of example, the cysteine residues in SEQ ID NO:145 position 1 is lacked, and perhaps 1 cysteine residues can not be formed the another kind of aminoacid replacement of disulfide linkage in the position, for example replaces with serine residue.In another embodiment, mutain Fc polypeptide comprises disappearance or the replacement near the N-terminal cysteine residues of the hinge area of Fc polypeptide, also comprises the disappearance or the replacement of contiguous C terminal amino acid.In a specific embodiment, this cysteine residues and contiguous C end residue are all lacked by the hinge area from mutain Fc polypeptide.In a special embodiment, cysteine residues and the aspartic acid in SEQID NO:145 position 2 in SEQ ID NO:145 position 1 are lacked.The Fc polypeptide of disappearance that is included in the aminoterminal cysteine residues of hinge area is more effectively expressed in the host cell of the recombinant expression construct body that comprises the such Fc polypeptide of coding.

In a special embodiment, mutain Fc polypeptide is included in the aminoacid sequence of listing among the SEQ ID NO:146, they are different with wild-type Fc polypeptide (SEQ ID NO:145), wherein lacked at the N-terminal cysteine residues near the hinge area of Fc polypeptide, and lacked at the contiguous aspartic acid of C end, and the leucine residue corresponding with EU234 replaces with alanine residue, the leucine residue corresponding with EU235 replaces with glutaminic acid residue, and the glycine corresponding with EU237 replaces (referring to SEQ ID NO:146) with alanine residue.Therefore, exemplary mutain Fc polypeptide has aminoacid sequence KTHTCPPCPAPEAEGAPS (SEQ ID NO:148) (the position 1-18 of SEQ ID NO:146) at its N-terminal.

Other Fc variant comprises the similar aminoacid sequence of known Fc peptide sequence, it has small change, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, and it can further comprise conservative the replacement.Similar each other aminoacid sequence can be enjoyed the elementary zone of sequence homology.Similarly, the nucleotide sequence of coding Fc variant can comprise similar basically nucleotide sequence, and only has small variation, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, because the degeneracy of genetic code, it can further comprise silent mutation.Similar each other nucleotide sequence can be enjoyed the elementary zone of sequence homology.

When merging with purpose peptide or polypeptide, Fc polypeptide or at least one constant region for immunoglobulin or its part, partial action is vehicle or carrier part at least, it prevents the degraded of described peptide and/or increases the transformation period, reduce toxicity, reduce immunogenicity, and/or increase biological activity, such as by form dimer or other polymer (referring to, for example, U.S. Patent number 6,018,026; 6,291,646; 6,323,323; 6,300,099; 5,843,725).(also referring to, for example, U.S. Patent number 5,428,130; U.S. Patent number 6,660,843; U.S. Patent Application Publication No. 2003/064480; 2001/053539; 2004/087778; 2004/077022; 2004/071712; 2004/057953/2004/053845/2004/044188; 2004/001853; 2004/082039).

Meet the 130L polypeptide (or its variant or fragment) that merges on frame ground with Fc polypeptide or Fc polypeptide variants (for example, mutain Fc polypeptide) and can between 130L polypeptide and Fc polypeptide, comprise peptide linker.Described joint can be single amino acids (such as a for example glycine residue), maybe can be two, three, four, five, six, seven, eight, nine or ten amino acid, maybe can be the amino acid of any number between 10 and 20 amino acid.By way of example the explanation rather than the restriction mode, joint can comprise by two the nucleotide sequence coded amino acid as the Restriction Enzyme recognition site at least.The example of such Restriction Enzyme recognition site comprises, for example, and BamHI, ClaI, EcoRI, HindIII, KpnI, NcoI, NheI, PmlI, PstI, SalI, and XhoI.

Meet 130L polypeptide, its fragment or its variant that frame ground merges with mutain Fc polypeptide, when the carrier that is fit to pharmacy or physiology according to the known method of the practitioner of as herein described and field of medicaments or vehicle are used, can be used for suppressing the immunne response among the experimenter.Such fusion polypeptide can change at least a in the RPTP polypeptide as herein described (that is, LAR, RPTP-σ, RPTP-δ), the biological activity of at least two kinds of RPTP polypeptide or whole three kinds of RPTP polypeptide.In certain embodiments, meet 130L polypeptide, its fragment or its variant that frame ground merges with mutain Fc polypeptide, be used for the treatment of Immunological diseases or illness (comprising autoimmune disorders or inflammatory disease), it is described in detail in this article.As described herein, described 130L/ mutain Fc polypeptide can also be used to treating disease or the illness relevant with the change of cell migration, cell proliferation or cytodifferentiation, and it includes but not limited to Immunological diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness or hyperplasia or illness.

The 130L polypeptide fragment comprises 130L polypeptide variants fragment.The 130L polypeptide fragment also comprises the 130L fragment with aminoacid sequence different with the total length 130L in described fragment source, promptly, the part of described 130L polypeptide fragment variant and total length 130L polypeptide has at least 99%, 98%, 97%, 95%, 90%, 87%, 85%, or 80% aminoacid sequence homogeny.The variant of 130L polypeptide fragment with immunoreactive ability of change (suppress or strengthen) immunocyte keeps the immunoreactive suitable ability that changes immunocyte.

The 130L polypeptide variants and the 130L polypeptide fragment variant that keep the immunoreactive ability that changes immunocyte comprise and contain the variant that conserved amino acid replaces.Whether various rule indication known to those skilled in the art is (or similar) of guarding at the amino acid of the specific position of peptide or polypeptide.For example, it is a kind of like this that similar amino acid or conserved amino acid replace, that is, wherein amino-acid residue substitutes with the amino-acid residue with similar side chain, such as the amino acid with following side chain: basic side chain (for example, Methionin, arginine, Histidine); Acid side-chain (for example, aspartic acid, L-glutamic acid); Uncharged polar side chain (for example, glycine, l-asparagine, glutamine, Serine, Threonine, tyrosine, halfcystine, Histidine); Non-polar sidechain (for example, L-Ala, Xie Ansuan, leucine, Isoleucine, proline(Pro), phenylalanine, methionine(Met), tryptophane); β-side chain side chain (for example, Threonine, Xie Ansuan, Isoleucine), and aromatic side chain (for example, tyrosine, phenylalanine, tryptophane).Proline(Pro), it is considered to more be difficult to classification, enjoys the characteristics of the amino acid (for example, leucine, Xie Ansuan, Isoleucine and L-Ala) with aliphatic side chains.In some cases, glutamine replaces L-glutamic acid or l-asparagine replacement aspartic acid can be considered to similar replacement, and reason is that glutamine and l-asparagine are respectively the amide derivatives of L-glutamic acid and aspartic acid.As understanding in the art, " similarity " between two peptide species is by described amino acid sequence of polypeptide and the replacement of its conserved amino acid relatively (for example, are used GENEWORKS, Align with the sequence of second peptide species, or the BLAST algorithm, as described herein) and determine.

The 130L polypeptide variants also comprises and unique one or both (that is, LAR and RPTP-δ, LAR and RPTP-σ, or RPTP-δ and RPTP-σ) rather than whole three kinds of LAR, RPTP-δ and RPTP-σ interaction or bonded variant.Compare with wild-type 130L polypeptide, such variant comprises at least 1,2, and 3,4,5,6,7,8,9,10,11-15,16-25,26-35, or 36-45 aminoacid replacement, disappearance or insertion.130L can determine according to method as herein described and this area practice with combining of every kind of RPTPs.Be used for comprising in conjunction with the source of polypeptide of research, for example, isolating 130L and RPTPs, or its fragment, or can recombinant expressed 130L, LAR, a kind of individual cells system among RPTP-δ and the RPTP-σ.

The segmental variant of 130L full-length polypeptide or 130L can easily prepare by heredity processing and recombinant molecule biological method and technology.The firsts and seconds amino acid sequence analysis of 130L polypeptide and analyze the computer model of the tertiary structure of described polypeptide and can assistant identification can be substituted and do not change described structure and therefore do not change the special amino-acid residue of the function of described 130L polypeptide potentially.The modification of coding 130L polypeptide or segmental DNA can be undertaken by the whole bag of tricks, comprise locus specificity or the site-directed mutagenesis of DNA, described method comprises the DNA cloning of using primer, to introduce in dna profiling and the amplification change, such as the PCR montage by overlapping extension (SOE).Sudden change can be introduced at specific position by synthetic comprising by the oligonucleotide of the segmental restriction site side mutant nucleotide sequence even that can connect native sequences.After the connection, the variant (or derivative) that the reconstruction sequence coding that obtains has the aminoacid insertion, replacement or the disappearance that need.

Site-directed mutagenesis is typically used phage vector with strand and double chain form such as M13 phage vector and is realized that described phage vector is known and commercially available.Can use other appropriate carriers of comprising the single stranded phage replication orgin (referring to, for example, Veira etc., Meth.Enzymol. (Enzymology method) 15:3 (1987)).Usually, site-directed mutagenesis is undertaken by the single-stranded vector of preparation coding target protein.Will with single-stranded vector in the zone of dna homology in comprise the Oligonucleolide primers and the annealing of described carrier of the sudden change of needs, add archaeal dna polymerase then, such as e. coli dna polymerase I (Ke Lienuo (Klenow) fragment), it uses double-stranded region as primer, generate heteroduplex, the sequence that changes of chain encoding wherein, another chain encoding original series.For example, can be in (Meth.Enzymol. (Enzymology method) 154:367 (1987)) and U.S. Patent number 4,518,584 and 4,737 such as Kunkel, find other disclosure in 462 about site-directed mutagenesis.Described heteroduplex is incorporated in the suitable bacterial cell, and selection comprises the clone of the sudden change of needs.The dna molecular of the change that obtains can be recombinant expressed in appropriate host cell, to generate described variant, the albumen of modification.

Can use locus specificity (or fragments specific) mutafacient system that oligonucleotide instructs, the polynucleotide of the change of the specific codon that changes so that replacement, disappearance or the insertion that has as required to be provided.Proteinic disappearance or brachymemma derivative can also make up by the site of restriction endonuclease easily of using the contiguous disappearance that needs.Behind restriction enzyme digestion, overhang can be filled and DNA reconnects.The illustrative methods for preparing above-mentioned change is by (Molecular Cloning:A Laboratory Manual (molecular clonings: laboratory manual) such as Sambrook, the 3rd edition, Cold Spring Harbor Laboratory Press (press of cold spring harbor laboratory), New York 2001) open.Alternatively, the random mutagenesis technology, such as L-Ala subregion mutagenesis, the mutagenesis that error-prone PCR mutagenesis and oligonucleotide instruct can be used for preparing 130L polypeptide variants and fragment variant (referring to, for example, Sambrook etc., as previously mentioned).

Being used to assess the mensuration whether described variant be folded into the conformation suitable with non-variant polypeptide or fragment comprises, for example, described albumen and ability to mono-clonal natural or not folding epitope specificity or polyclonal antibody reaction, the reservation of part-combined function, with described mutain to the susceptibility of protease digestion or resistance (referring to, Sambrook etc., as previously mentioned).130L variant as described herein can be identified according to other method known in the art that these methods as herein described or those skilled in the art implement usually, characteristic is described and/or preparation.

The sudden change of preparation or evaluation preferably keeps the reading frame of encoding sequence in the nucleic acid molecule of coding 130L polypeptide.In addition, described sudden change preferably will not produce complementary district, thereby the secondary mRNA structure that produces the translation that influences mRNA unfriendly can be hybridized in described complementary district when transcribing, as ring or hair clip.Although the mutational site can pre-determine, the character of sudden change itself does not need to pre-determine.For example,, can carry out random mutagenesis at the target codon in order to be chosen in the best features of given site mutation, and at bioactive acquisition or lose or keep and screen expressed mutant.

The 130L polynucleotide are coding 130L polypeptide or any polynucleotide of the part of 130L polypeptide (or fragment) or its variant at least, or with any polynucleotide of described polynucleotide complementary.For example, coding 130L or its directly find in the genome sequence of the inferior tower poxvirus that the nucleotide sequence of the polynucleotide of homologue can provide in the GenBank record about registration number provided herein, in GenBank registration number AJ293568 and NC_002642 and the sequence (for example, SEQ ID NO:85 and SEQ ID NO:150) that can derive from aminoacid sequence disclosed herein.Polynucleotide comprise at least 15 continuous nucleotides or at least 30,35,40,50,55 or 60 continuous nucleotides, in certain embodiments, at least 70,75,80,90,100,110,120,125, or 130 continuous nucleotides, and in other embodiments, at least 135,140,145,150,155,160, or 170 continuous nucleotides, and in other embodiments, at least 180,190,200,225,250,275,300,325,350,375,400,405,410,420,425,445,450,475,500,525,530,545,550,575,600,625,650, or 660 continuous nucleotides, described continuous nucleotide comprise coding 130L polypeptide sequence or with such sequence complementary nucleotide sequence.Coding 130L polypeptide, its variant or its segmental some polynucleotide can also be used as the RNA interfering (siRNA) or the antisense oligonucleotide of probe, primer, weak point, and are as described herein.Polynucleotide can be single stranded DNA or RNA (coding or antisense) or double-stranded RNA (for example, genome or synthetic) or DNA (for example, cDNA or synthetic).

The polynucleotide variant can also be identified by hybridizing method.Suitable medium stringent condition comprises, for example, at 5X SSC, 0.5%SDS, prewashing in 1.0mM EDTA (pH 8.0) solution; At 50 ℃-70 ℃, 5X SSC hybridization 1-16 hour; Then 22-65 ℃ with every kind of 2X that contains 0.05-0.1%SDS, one or more washings among 0.5X and the 0.2X SSC reach 20-40 minute once or twice.For extra severity, condition can be included among 0.1X SSC and the 0.1%SDS 50-60 ℃ of washing 15 minutes.Will be understood by those skilled in the art that the variation of hybridization conditions severity can obtain by change time, temperature and/or the concentration that is used for the solution of prehybridization, hybridization and washing step.Suitable condition can also depend in part on the specific nucleotide sequence (that is, for example, guanine adds cytosine(Cyt) (G/C) and adds thymus pyrimidine (A/T) content with respect to VITAMIN B4) of used probe.Therefore, it should be appreciated by those skilled in the art, when the selectivity of the needs of identifying probe, can need not undo experimentation and easily select suitable stringency.

Receptor protein tyrosine phosphatase (RPTP): LAR, RPTP-δ and RPTP-σ

Leukocyte common antigen (LCA) associated protein (LAR), receptor-like protein tyrosine phosphatase-δ (RPTP-δ) and RPTP-σ are the members of acceptor sample II type Protein-tyrosine-phosphatase (PTPs).These RPTPs (being also referred to as Protein-tyrosine-phosphatase (PTP) or receptor protein tyrosine phosphatase in this article) have three immunoglobulin-likes (Ig-sample) structural domain, a series of fibronectin III type sample motifs in extracellular domain, potential proteolysis processing site, stride membrane element and two series connection tenuigenin Phosphoric acid esterase structural domain D1 and D2 (referring to, for example, Alonso etc., Cell (cell) 117:699-711 (2004) is referring to Fig. 2 wherein; Streuli etc., J Exp.Med. (The Journal of Experimental Medicine) 168:1523 (1988); Charbonneau etc., Annu.Rev.Cell Biol. (cytobiology summary annual) 8:463-93 (1992); Pan etc., J.Biol.Chem. (biological The Chemicals) 268:19284-91 (1993); Walton etc., Neuron (neuroscience) 11:387-400 (1993); Yan etc., J Biol.Chem. (biological The Chemicals) 268:24880-86 (1993); Zhang etc., Biochem.J. (journal of biological chemistry) 302:39-47 (1994); Pulido etc., J.Biol.Chem. (biological The Chemicals) 270:6722-28 (1995)).

Identified the variant of some alternative splicings of LAR, and it is believed that it is (O ' Grady etc., J.Biol.Chem. (biological The Chemicals) 269:25193 (1994) that is grown adjusting; Zhang and Longo, J Cell.Biol. (cytobiology magazine) 128:415 (1995); Honkaniemi etc., Mol.Brain.Res. (research of molecule cerebrology) 61:1 (1998)).The multiple isotype of RPTP-δ and RPTP-σ and LAR as if by the tissue specificity alternative splicing produce (referring to, for example, Pulido etc., Proc.Natl.Acad.Sci USA (NAS's journal) 92:11686-90 (1995)).In the people, the LAR assignment of genes gene mapping is at karyomit(e) 1p32, a zone (Jirik etc., Cytogenet.Cell Genet. (genetics of cytogenetics and cell) 61:266 (1992)) that lacks in the tumour of neuroectodermal origin usually.

Protein-tyrosine-phosphatase such as LAR, RPTP-δ and RPTP-σ will be as the tyrosyl phosphorprotein dephosphorylations of cell signaling pathway components.The phosphorylation of the adjusting of the tyrosine residues of substrate and dephosphorylation are the major control mechanism of cell processes such as cell growth, cell proliferation, metabolism, differentiation and motion.Therefore, the activity of the Protein-tyrosine-phosphatase of adjusting reversible tyrosine phosphorylation effect and protein tyrosine kinase must combination and regulation and control in cell.Unusual adjusting causes the performance of some diseases and illness.(referring to, for example, Tonks and Neel, Curr.Opin.Cell Biol. (the modern viewpoint of cytobiology) 13:182-95 (2001)).Do not wish to be bound by any theory, the biological specificity of acceptor PTPs (RPTPs) can be released from their similar part.The result of gene knockout zooscopy has pointed out some different biological function of LAR, RPTP-δ and RPTP-σ.Because the trichopore (alveoli) that weakens in conceived process breaks up latter stage, the interruption of LAR genetic expression causes defective mammogenesis (Schaapveid etc., Dev.Biol. (developmental biology) 188:134-46 (1996)); Some defectives (Yeo etc., JNeurosci.Res. (neurobiology research magazine) 47:348-60 (1997)) that cause forebrain size and hippocampal tissue; And the defective (Ren etc., Diabetes (diabetes) 47:493-97 (1998)) that causes possibly, glucose metabolism.On the contrary, the disappearance of RPTP-δ influences enhancing of hippocampus long term and study (Ren etc., EMBO J. (fetology magazine) 19:2775-85 (2000)), and RPTP-σ deficient mice shows the defective in brain development, (Elchebly etc., Nat.Genet. (natural genetics) 21:330-33 (1999) of reducing that comprises hypothalamus, olfactory bulb and pituitary gland size; Wallace etc., Nat.Genet. (natural genetics) 21:334-38 (1999)).

The result of many researchs has shown many biological actions of LAR: the ability of change cell proliferation (referring to, for example, Yang etc., Carcinogenesis (oncogenesis) 21:125; Tisi etc., JNeurobiol. (neurobiology magazine) 42:477 (2000)); Suppress growth of tumour cell (Zhai etc., Mol.Carcinogen. (molecule carcinogenesis) 14:103 (1995)); Make insulin receptor dephosphorylation and affecting glucose running balance (Ahmad and Goldstein, J Biol.Chem. (biological The Chemicals) 272:448 (1997); Ren etc., Diabetes (diabetes) 47:493 (1998)); The interaction of adjusting cell-matrix (Pulido etc., as previously mentioned); Adjusting cynapse form generation and function (referring to, for example, Dunah etc., Nat.Neurosci. (natural neuroscience) 8:458-67 (2005); And influence immune cell function (U.S. Patent number 6,852,486).Although research has shown that RPTP-δ and RPTP-σ can also influence cell adhesion (Pulido etc., as previously mentioned) and the cynapse form takes place and function (referring to, for example, Dunah etc., as previously mentioned), still not studies show that still these two kinds of Phosphoric acid esterases can also influence immune cell function.Therefore, embodiment as herein described relates to so unexpected discovery, that is, all three kinds of Phosphoric acid esterases, LAR, RPTP-δ and RPTP-σ are expressed by immunocyte.

LAR, RPTP-δ and RPTP-σ are the cell target spots of viral protein A41L and 130L.Any combine and to influence immune cell function of these viral proteins and these Phosphoric acid esterases.Especially, A41L or 130L can suppress immunne response, and act as the inhibitor of host immune system.A41L and 130L can in conjunction with and the exemplary isotype that changes the LAR of its function comprise the LAR:GenBank registration number NP_002832 (SEQ ID NO:22) (by polynucleotide encoding) that contains the aminoacid sequence that in following, proposes with nucleotide sequence of proposition among NM_002840 (SEQ ID NO:23); SEQ ID NO:24 (AAH48768) (by polynucleotide encoding) with the nucleotide sequence that in BCO48768 (SEQ ID NO:65), proposes; CAI14894 (SEQID NO:25); GenBank NP_569707 (SEQ ID NO:26) (by polynucleotide encoding) with the nucleotide sequence that in NM_130440 (SEQ ID NO:27), proposes; And CAI14895 (SEQ ID NO:28).A41L or 130L can in conjunction with and the exemplary isotype that changes the RPTP-σ of its function comprise the RPTP-σ that contains the aminoacid sequence that in following, proposes: GenBank NP_002841 (SEQ ID NO:29) (by polynucleotide encoding) with nucleotide sequence of proposition among NM_002850 (SEQ IDNO:30); NP_570924 (SEQ ID NO:31) (by polynucleotide encoding) with the nucleotide sequence that in NM_130854 (SEQ ID NO:32), proposes; GenBank NP_570923 (SEQ ID NO:33) (by polynucleotide encoding) with the nucleotide sequence that in NM_130853 (SEQID NO:34), proposes; And NP_570925 (SEQ IDNO:35) (by polynucleotide encoding) with the nucleotide sequence that in NM_130855 (SEQ ID NO:36), proposes; And Q13332 (SEQ ID NO:64)).Viral protein can in conjunction with and the exemplary isotype that changes the RPTP-δ of its function comprise the RPTP-δ that contains the aminoacid sequence that in following, proposes: GenBank NP_002830 (SEQ ID NO:37) (by polynucleotide encoding) with nucleotide sequence of proposition among NM_002839 (SEQ ID NO:38); NP_569075 (SEQID NO:39) (by polynucleotide encoding) with the nucleotide sequence that in NM_120391 (SEQ ID NO:40), proposes; NP_569076 (SEQ ID NO:41) (by polynucleotide encoding) with the nucleotide sequence that in NM_130392 (SEQID NO:42), proposes; And NP_569077 (SEQ IDNO:43) (by polynucleotide encoding) with the nucleotide sequence that in NM_130393 (SEQ ID NO:44), proposes.

LAR as herein described, RPTP-δ and RPTP-σ polypeptide also comprise variant or every kind of RPTP separately, and it has the aminoacid sequence similar to aminoacid sequence disclosed herein.Variant comprises, for example, and the RPTP polypeptide variants of naturally occurring polymorphism (for example, such as allele variant) or reorganization operation or processing.RPTP variant and wild-type RPTP have at least 70%, 75%, and 80%, 85%, 90%, 95%, or 98% homogeny or similarity.Whether various rule indication known to those skilled in the art is that guard or similar at the amino acid of the specific position of peptide or polypeptide.For example, similar amino acid or conservative aminoacid replacement are a kind of like this, that is, wherein amino-acid residue substitutes with the amino-acid residue with similar side chain, such as the amino acid with following side chain: basic side chain (for example, Methionin, arginine, Histidine); Acid side-chain (for example, aspartic acid, L-glutamic acid); Uncharged polar side chain (for example, glycine, l-asparagine, glutamine, Serine, Threonine, tyrosine, halfcystine, Histidine); Non-polar sidechain (for example, L-Ala, Xie Ansuan, leucine, Isoleucine, proline(Pro), phenylalanine, methionine(Met), tryptophane); β-side chain side chain (for example, Threonine, Xie Ansuan, Isoleucine) and aromatic series side chain (for example, tyrosine, phenylalanine, tryptophane).Proline(Pro), it is considered to more be difficult to classification, enjoys the characteristics of the amino acid (for example, leucine, Xie Ansuan, Isoleucine and L-Ala) with aliphatic side chains.In some cases, glutamine replaces L-glutamic acid or l-asparagine replacement aspartic acid can be thought similar replacement, and reason is that glutamine and l-asparagine are respectively the amide derivatives of L-glutamic acid and aspartic acid.Can be (for example at the homogeny or the similarity percentage ratio that have between two kinds of RPTPs of aminoacid sequence by the sequence alignment method, use GENEWORKS, Align or BLAST algorithm) and determine that easily described method is also described in this article and is that those of ordinary skill in the art is familiar with.

The RPTP variant can also easily prepare by heredity processing and recombinant molecule biological method and the technology about the A41L polypeptide variants as herein described.In brief, the firsts and seconds amino acid sequence analysis of RPTP and analyze the computer model of the tertiary structure of described polypeptide can assistant identification can substituted special amino-acid residue.The modification of coding RPTP polypeptide or segmental DNA can be undertaken by the whole bag of tricks, comprise locus specificity or the site-directed mutagenesis of DNA, described method comprises the DNA cloning of using primer, to introduce in dna profiling and the amplification change, such as the PCR montage by overlapping extension (SOE).Sudden change can be introduced at specific position by synthetic comprising by the oligonucleotide of the segmental restriction site side mutant nucleotide sequence even that can connect native sequences.After the connection, the variant (or derivative) that the reconstruction sequence coding that obtains has the aminoacid insertion, replacement or the disappearance that need.

As described herein, site-directed mutagenesis is typically used phage vector with strand and double chain form such as M13 phage vector and is realized, described phage vector be known and commercially available (referring to, for example, Veira etc., Meth.Enzymol. (Enzymology method) 15:3 (1987); Kunkel etc., MethEnzymol. (Enzymology method) 154:367 (1987) and at U.S. Patent number 4,518 is in 584 and 4,737,462).Can use locus specificity (or fragments specific) mutafacient system that oligonucleotide instructs, the polynucleotide of the change of the special codon that changes so that replacement, disappearance or the insertion that has according to described needs to be provided.Proteinic disappearance or brachymemma derivative can also make up by the site of restriction endonuclease easily of using the contiguous disappearance that needs.The illustrative methods for preparing above-mentioned change is by (Molecular Cloning:A Laboratory Manual (molecular clonings: laboratory manual) such as Sambrook, the 3rd edition, Cold Spring Harbor Laboratory Press (press of cold spring harbor laboratory), New York 2001) open.Alternatively, the random mutagenesis technology, such as the mutagenesis of L-Ala subregion, error-prone PCR mutagenesis and oligonucleotide instruct mutagenesis can be used for preparing RPTP polypeptide variants and fragment variant (referring to, for example, Sambrook etc., as previously mentioned).Being used to assess the mensuration whether described variant be folded into the conformation suitable with non-variant polypeptide or fragment comprises, for example, described albumen and ability to mono-clonal natural or not folding epitope specificity or polyclonal antibody reaction, the reservation of part-combined function, with described mutain to the susceptibility of protease digestion or resistance (referring to, Sambrook etc., as previously mentioned).RPTP variant as described herein can be identified according to other method known in the art that these methods as herein described or those skilled in the art implement usually, characteristic is described and/or preparation.

The sudden change of preparation or evaluation preferably keeps the reading frame of encoding sequence in the nucleic acid molecule of coding RPTP polypeptide.In addition, described sudden change preferably will not produce complementary district, thereby the secondary mRNA structure that produces the translation that influences mRNA unfriendly can be hybridized in described complementary district when transcribing, as ring or hair clip.Although the mutational site can pre-determine, the character of sudden change itself does not need to pre-determine.For example,, can carry out random mutagenesis at the target codon in order to be chosen in the best features of given site mutation, and at bioactive acquisition or lose or keep and screen expressed mutant.

The RPTP variant keep at least a biological activity of wild-type RPTP or function (for example, phosphatase activity, regulation and control or the initial signal relevant with wild-type RPTP conduct incident, combine with at least a cognate ligand, and as in this article further in detail as described in).Preferably, described RPTP keeps with its cognate ligand interaction with the dephosphorylized ability of the substrate of tyrosine phosphorylation.

The polynucleotide variant can also be identified by hybridizing method.Suitable medium stringent condition comprises, for example, at 5X SSC, 0.5%SDS, prewashing in 1.0mM EDTA (pH 8.0) solution; At 50 ℃-70 ℃, 5X SSC hybridization 1-16 hour; Then 22-65 ℃ with every kind of 2X that contains 0.05-0.1%SDS, one or more washings among 0.5X and the 0.2X SSC reach 20-40 minute once or twice.For extra severity, condition can be included among 0.1X SSC and the 0.1%SDS 50-60 ℃ of washing 15 minutes.Will be understood by those skilled in the art that the variation of hybridization conditions severity can obtain by change time, temperature and/or the concentration that is used for the solution of prehybridization, hybridization and washing step.Suitable condition can also depend in part on the specific nucleotide sequence (that is, for example, guanine adds cytosine(Cyt) (G/C) and adds thymus pyrimidine (A/T) content with respect to VITAMIN B4) of used probe.Therefore, it should be appreciated by those skilled in the art, when the selectivity of the needs of identifying probe, can need not undo experimentation and easily select suitable stringency.

Every kind of RPTPs N-terminal have about 20-30 amino acid whose signal peptide sequence (referring to, for example, Pulido etc., (also referring to, for example, GenBank database report) as previously mentioned).Because signal peptide is cut in proteic transposition process or signal peptide keeps being anchored on (such peptide also is called the signal anchor stator) on the outside cytolemma, so signal peptide be not exposed on the cell surface of excretory or transmembrane protein (referring to, for example, Nielsen etc., Protein Engineering (protein processing) 10:1-6 (1997); Nielsen etc. at J.Glasgow etc., compile, and Proc.Sixth Int.Conf.onIntelligent Systems for Molecular Biology (the 6th international conference journal of molecular biology intelligence system) is among the 122-30 (AAAI publishes 1998)).Therefore, the signal peptide sequence of RPTP may not be in conjunction with the antibody of the extracellular part of RPTP or its antigen-binding fragment part with the binding site on the part of bonded RPTP extracellular in part such as A41L or specificity.

As described herein, be exposed to the extracellular part of the RPTP on cell (as the immunocyte) outside surface, it does not comprise signal peptide (yet being called ripe RPTP herein), comprises three immunoglobulin like domain.Described immunoglobulin domains (or immunoglobulin like domain) is referred to herein as first, second and the 3rd immunoglobulin domains (alternatively, be called Ig-1, Ig-2, Ig-3 or be called immunoglobulin like domain 1, immunoglobulin like domain 2 and immunoglobulin like domain 3), wherein first immunoglobulin domains is near the structural domain (see figure 1) of the N end of RPTP.The carboxyl terminal (see figure 1) of first immunoglobulin domains next-door neighbour signal peptide.Therefore, when being used for this paper, first immunoglobulin like domain of RPTP is near the N-terminal immunoglobulin like domain of RPTP; Second immunoglobulin like domain of RPTP is at first immunoglobulin like domain of RPTP and the immunoglobulin like domain between the 3rd immunoglobulin like domain; And the 3rd immunoglobulin like domain of RPTP is near the immunoglobulin like domain of the carboxyl terminal of RPTP.

Technician in the protein field should be appreciated that, the accurate amino acid position in unnecessary correspondence in the end of structural domain or border such as the example primary sequence as shown in FIG. 1.Therefore, for example, immunoglobulin domains, fibronectin III tumor-necrosis factor glycoproteins and catalyst structure domain can comprise one, two, three, four, five, six, seven, eight or more a plurality of amino acid at the N-terminal of contiguous each structural domain and/or the position of C-terminal.Use sequence provided herein and accompanying drawing and sequence known in the art (amino acid and coding nucleotide sequence), those skilled in the art can easily determine each Ig spline structure territory of the corresponding RPTP in that position of RPTP.For example, but non-limiting, the amino acid position 31-125 of the corresponding SEQ ID of the Ig-1 structural domain of LAR NO:25; The corresponding amino acid position 111-227 of the Ig-2 structural domain of LAR; And the corresponding amino acid position 228-316 of the Ig-3 structural domain of LAR.For RPTP-σ, the corresponding amino acid position 31-125 of Ig-1 structural domain; The corresponding amino acid position 127-240 of Ig-2 structural domain; And the corresponding amino acid position 241-329 of Ig-3 structural domain.For RPTP-δ, the corresponding amino acid position 22-116 of Ig-1 structural domain; The corresponding amino acid position 118-231 of Ig-2 structural domain; And the corresponding amino acid position 232-320 of Ig-3 structural domain.When being used for this paper, can depend on special RPTP or its variant (such as allele variant, cell type variant etc.) and difference at each terminal amino acid of structural domain, the Ig domain variants comprises the Ig structural domain of LAR, RPTP-δ or RPTP-σ, and the sequence of every kind of immunoglobulin like domain of itself and every kind of RPTP as herein described has 99%, 98%, 97%, 96%, 95%, or 90%, 85%, or 80% homogeny.

In one embodiment, the extracellular part of LAR, RPTP-δ or RPTP-σ can be used for changing the immunoreactivity of (strengthen or suppress with statistics or the significant mode of biology) immunocyte.In another embodiment, comprise at least a, the two or all three kinds immunoglobulin like domain of LAR, RPTP-δ or RPTP-σ and do not comprise the extracellular part of the RPTP (also being called soluble LAR, RPTP-δ or RPTP-σ) of any one or more fibronectin structural domain of RPTP, can be used for changing the immunoreactivity of immunocyte at this paper.For ease of reference, latter's polypeptide (promptly, comprise RPTP (LAR, RPTP-δ or RPTP-σ) at least a, the two or all three kinds immunoglobulin like domain, as monomer as described herein or oligomer) be referred to herein as RPTP Ig-spline structure domain polypeptide.

In certain embodiments, the immunoreactivity of enhancing immunity cell.Extracellular part or the fragment of RPTP, all at least a as described, two or all three kinds immunoglobulin like domain, can be administered to host or experimenter, so that combine with the RPTP fragment of at least a part of RPTP bonded of on immunocyte, expressing and external source interpolation.Described part can be soluble, and perhaps described part can be expressed on the cell surface of the cell identical with the immunocyte of expressing RPTP, and perhaps described part can be the cell surface protein by another kind of cell expressing.Therefore, soluble LAR, RPTP-δ or RPTP-σ can with described ligand interaction, and reduce the amount that can be used for the RPTP bonded part of on immunocyte, expressing, promptly, block combining of described part and the RPTP that on cell, expresses, suppress, prevent, dwindle, reduce or eliminate the function relevant with combining of RPTP, activity (for example, phosphatase activity) or signal conduction incident again with part.

In another embodiment, any extracellular part (for example, at least a, two or all three kinds immunoglobulin like domain) can suppress the immune response immunne response among LAR, RPTP-δ or the RPTP-σ.Part, it can be a soluble part or as the part of cell surface protein, can interact with the RPTP on the cell surface of immunocyte, and this interaction can be induced Inflammatory response, perhaps can the inducing cell factor (for example, but be not limited to cytokine as herein described, comprise IFN-γ) expression or generation, described cytokine induction or aggravation inflammatory or autoimmunity are replied.The interaction of one or more LAR that express on immunocyte, RPTP-δ and RPTP-σ and such part (soluble or cell surface protein) can at first be suppressed, be prevented or be blocked with described ligand interaction or the soluble RPTP of bonded.

In a specific embodiment, at least a or at least two kinds or whole three kinds of immunoglobulin like domain partly are connected (that is, adhere to or merge) with non-RPTP.Described part can be connected on the RPTP fragment by described part and described segmental covalently or non-covalently adhering to, for example, by using conjugation methods, it depends on the character of described part and difference (such as, whether described part is carbohydrate or polypeptide or small molecules), and the technician of specific area is familiar with described method.Alternatively, when described non-RPTP partly was peptide or polypeptide, the connection of can recombinating of described part was to form RPTP fragment fusion polypeptide.For example, the recombinant expression construct body that can prepare the polynucleotide that comprise the fusion polypeptide of encoding, described fusion polypeptide comprises, for example, at least a, the two or all three kinds immunoglobulin like domain (or its part) at least of the RPTP that merges with at least one immunoglobulin (Ig) (Ig) constant region structural domain of immunoglobulin Fc polypeptide or at least two Ig constant region structural domains.

In one embodiment, LAR, RPTP-δ's or RPTP-σ's the second and the 3rd immunoglobulin like domain and immunoglobulin Fc polypeptide merge; And in another embodiment, LAR, RPTP-δ's or RPTP-σ's first, second and the 3rd immunoglobulin like domain and immunoglobulin Fc polypeptide merge.In certain embodiments, first immunoglobulin like domain of LAR, RPTP-δ or RPTP-σ and immunoglobulin Fc polypeptide merge.In another embodiment, second immunoglobulin like domain of LAR, RPTP-δ or RPTP-σ and immunoglobulin Fc polypeptide merge; In another embodiment, the 3rd immunoglobulin like domain of LAR, RPTP-δ or RPTP-σ and immunoglobulin Fc polypeptide merge.In other embodiments, LAR, RPTP-δ's or RPTP-σ's first and second immunoglobulin like domain and immunoglobulin Fc polypeptide merge; In other embodiments, LAR, RPTP-δ's or RPTP-σ's the first and the 3rd immunoglobulin like domain and immunoglobulin Fc polypeptide merge.In some cases, use first immunoglobulin like domain (promptly separately, do not have the second and/or the 3rd immunoglobulin like domain) or polypeptide with first immunoglobulin like domain that merges with the Fc polypeptide and second immunoglobulin like domain is (promptly, do not have the 3rd Ig-spline structure territory), can more suppress immunne response among immunocyte or the host in the lowland with the mode efficient similar to A41L.Do not wish to be subjected to the constraint of any concrete theory, and it is as described herein, because A41L does not combine with independent first immunoglobulin like domain when not having the second and the 3rd Ig-spline structure territory, so only with the described first structural domain bonded RPTP Ig-spline structure territory can efficient more lowland and part or cell surface polypeptide interact, thereby realize inhibition in the mode identical to immunne response with A41L.

In other embodiments, soluble RPTP (promptly, RPTP Ig-spline structure domain polypeptide) can comprise a kind of, two or three immunoglobulin like domain with above-mentioned various combinations, described immunoglobulin like domain is not attached to or is fused on the non-RPTP part.For example, all structural domain polypeptide of RPTP Ig-can comprise first, second and the 3rd Ig-spline structure territory (LAR, RPTP-δ or RPTP-σ) of RPTP; The second and the 3rd Ig-spline structure territory of RPTP.In some alternate embodiment, RPTP Ig-spline structure domain polypeptide can comprise the first and second or first and the 3rd Ig-spline structure territory of RPTP; Or each independent Ig-spline structure territory.

Soluble RPTP Ig-spline structure domain polypeptide can also exist with polymer such as dimer and tripolymer.Described polymer can (it comprises physiological condition) forms by noncovalent interaction under so interactional condition helping, and perhaps can form by the combination of covalency and noncovalent interaction.Alternatively, polymer can be by forming at least two monomer RPTP Ig-spline structure domain polypeptide chemistry or reorganization connection.Described polymer can comprise, for example, and homodimer or heterodimer.For example, homodimer can comprise first monomer of at least a, two or three immunoglobulin like domain of (1) RPTP, with second monomer of same at least a, two or three immunoglobulin like domain of (2) identical RPTP.In some special embodiment, for example, homodimer can comprise comprise respectively LAR the second and the 3rd (perhaps, alternatively, first, second and the 3rd) first and second monomers of immunoglobulin like domain.In another embodiment, each monomer of homodimer (for example, the second and the 3rd immunoglobulin like domain or first, second and the 3rd immunoglobulin like domain) derive from RPTP-δ, and in another embodiment, each monomer derives from RPTP-σ.

Alternatively, oligomer such as dimer, can be a heterodimer, and each monomer derives from different RPTP (that is, LAR, RPTP-δ or RPTP-σ).In a specific embodiment, heterodimer can comprise first monomer, its comprise LAR the second and the 3rd (perhaps, alternatively, first, second and the 3rd) immunoglobulin like domain and second monomer, its comprise RPTP-δ or RPTP-σ the second and the 3rd (perhaps, alternatively, first, second and the 3rd) immunoglobulin like domain.In another embodiment, first monomer of heterodimer comprise RPTP-δ the second and the 3rd (perhaps, alternatively, first, second and the 3rd) immunoglobulin like domain, and second monomer of described heterodimer comprises the immunoglobulin like domain of corresponding RPTP-σ.

In some other embodiment, homodimer or heterodimer comprise first and second monomers, and each monomer comprises the unique immunoglobulin like domain from RPTP.In other embodiments, each monomer of homodimer or heterodimer comprises the first and the 3rd immunoglobulin like domain of RPTP; And in some other embodiment, each monomer comprises first and second immunoglobulin like domain of RPTP.Therefore, homodimer can comprise two monomers, and each is made up of first and second immunoglobulin like domain of LAR, and perhaps each monomer can be made up of the first and the 3rd immunoglobulin like domain of LAR.For RPTP-δ and RPTP-σ each, can make up homodimer similarly.Heterodimer can be by different first and second monomers preparations, for example, first monomer can comprise first and second immunoglobulin like domain or the first and the 3rd immunoglobulin like domain of LAR, and second monomer can comprise first and second immunoglobulin like domain or the first and the 3rd immunoglobulin like domain of RPTP-δ or RPTP-σ respectively.In other embodiments, heterodimer can comprise first and second immunoglobulin like domain that contain RPTP-δ or first monomer of the first and the 3rd immunoglobulin like domain, and second monomer can comprise first and second immunoglobulin like domain or the first and the 3rd immunoglobulin like domain of RPTP-σ respectively.

In other embodiments, can be fused on the immunoglobulin domains from different RPTP from the immunoglobulin like domain of a kind of RPTP.For example, first immunoglobulin like domain of RPTP-δ or RPTP-σ can be fused on the second and the 3rd immunoglobulin like domain of LAR.Can expect many combinations of the immunoglobulin like domain of each among three kinds of RPTPs as herein described, so that the soluble RPTP molecule that comprises two or three immunoglobulin like domain altogether to be provided.As described herein, soluble RPTP Ig structural domain polypeptide can use Protocols in Molecular Biology reorganization preparation, perhaps can non-covalent combination or with or need not one or more connections or amino acid and covalency fusion at interval.

Can be fused to the Fc polypeptide of the immunoglobulin (Ig) on the RPTP Ig-spline structure domain polypeptide, at length discuss as mentioned, comprise heavy chain CH2 structural domain and CH3 structural domain, and the partial or complete hinge area between CH1 and CH2.On the origin history, the Fc fragment derives from the papain digestion of immunoglobulin (Ig), and comprises the hinge area of immunoglobulin (Ig).The Fc district can pass through covalency (for example, particularly disulfide linkage) and non-covalent association and the monomer polypeptide that connects into dimer or polymer form.The number of the intermolecular disulfide bond between the monomer subunit of Fc polypeptide depend on described immunoglobulin (Ig) kind (for example, IgG, IgA, IgE) or subclass (for example, the human IgG1, IgG2, IgG3, IgG4, IgA1, IgA2) and different.

Can also use the fragment of Fc polypeptide, such as at the Fc of C-terminal brachymemma polypeptide (that is, removed or lacked at least 1,2,3,4,5,10,15,20 or more a plurality of amino acid).In certain embodiments, Fc polypeptide as herein described comprises a plurality of cysteine residues, such as at least some of hinge area or whole cysteine residues, to allow between the Fc polypeptide portion of two isolating RPTP structural domain/Fc fused proteins, forming interchain disulfide bond, therefore form RPTP structural domain/Fc fusion polypeptide dimer.In other embodiments, the cytotoxicity (ADCC) and complement fixation(CF) (and the relevant cytotoxicity (CDC) of relevant complement) that keep the antibody dependent cellular mediation if desired, so described Fc polypeptide is included in the replacement or the disappearance of the cysteine residues of hinge area, so that the Fc polypeptide amalgamation protein is monomeric, and can not form dimer (referring to, for example, U.S. Patent Application Publication No. 2005/0175614).

The Fc of immunoglobulin (Ig) partly mediates some effector function of immunoglobulin (Ig).The three major types effector function relevant with the Fc zone comprises the activation of (1) classical complement cascade, (2) and the interaction of effector cell and the compartmentation of (3) immunoglobulin (Ig).At present, according to the recombinant molecule biology techniques that the technician is familiar with very much, can easily prepare Fc polypeptide and any one or multiple constant region structural domain and comprise the fusion rotein of at least one constant region for immunoglobulin structural domain.

The Fc polypeptide preferably uses the nucleotide sequence and the amino acid sequence coded that derive from the animal species that is intended to use described peptide-Ig Fc fusion polypeptide to be prepared.In one embodiment, described Fc polypeptide is the people source, and can come from any immunoglobulin (Ig) kind, as human IgG1 and IgG2.

Fc polypeptide as described herein also comprises the Fc polypeptide variants.A kind of such Fc polypeptide variants makes and one or more cysteine residues (such as the one or more cysteine residues at hinge area) of another Fc polypeptide formation disulfide linkage are replaced by another kind of amino acid such as Serine, to reduce the number of the disulfide linkage that forms between two Fc polypeptide.Alternatively, one or more cysteine residues can be from the wild-type hinge area disappearance of Fc polypeptide.

Another example of Fc polypeptide variants is the variant that the feasible one or more amino acid that participate in effector function are substituted or lack, so that described Fc polypeptide has the effector function level of minimizing.For example, the amino acid in the Fc zone can be substituted, with the combination of the composition that reduces or eliminates complement cascade (referring to, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995)), perhaps reduce or eliminate the Fc polypeptide in conjunction with the ability of the IgG Fc acceptor of expressing by immunocyte (Wines etc., J Immunol. (Journal of Immunology) 164:5313-18 (2000); Chappel etc., Proc.Natl.Acad.Sci USA (NAS's journal) 88:9036 (1991); Canfield etc., J.Exp.Med. (The Journal of Experimental Medicine) 173:1483 (1991); Duncan etc., as previously mentioned); Perhaps change the cytotoxicity of antibody-dependent cell.The such Fc polypeptide variants different with wild-type Fc polypeptide also are called mutain Fc polypeptide in this article.

In one embodiment, at least one immunoglobulin like domain of RPTP (LAR, RPTP-δ, RPTP-σ or its variant) and Fc polypeptide meet frame ground and merge, and described Fc polypeptide is included at least a replacement of the residue of the one or more IgG Fc receptors bind that help Fc polypeptide or immunoglobulin (Ig) in the polypeptide of wild-type Fc zone and express on specific immunocyte.Such mutain Fc polypeptide is included at least a replacement of the amino-acid residue in the CH2 structural domain of described mutain Fc polypeptide, so that described fusion polypeptide reduces in conjunction with the ability of IgG Fc acceptor as the IgG Fc acceptor that exists on the immunocyte surface.In the type that has above described the Fc IgG acceptor of on human leukocyte, expressing in detail.

As this paper in detail as described in, be included in residue (Leu-Leu-Gly-Gly-Pro-Ser (SEQ ID NO:80) (the EU numbering system of position Leu234-Ser239 at the aminoterminal residue partly of the CH2 structural domain that helps IgG Fc receptors bind, Kabat etc., as previously mentioned) (referring to, for example, Morgan etc., Immunology (immunology) 86:319-24 (1995) and the reference of wherein quoting).These positions are corresponding with the position 15-20 of human IgG1 Fc amino acid sequence of polypeptide (SEQ ID NO:79).In the CH2 structural domain in these 6 positions one or more (promptly, one, two, three, four, five or whole six) aminoacid replacement of position cause described Fc polypeptide in conjunction with the minimizing of the ability of one or more IgG Fc acceptors (or its isotype) (referring to, for example, Burton etc., Adv.Immunol. (senior immunology) 51:1 (1992); Hulett etc., Adv.Immunol. (senior immunology) 57:1 (1994); Jefferis etc., Immunol.Rev. (immunology research) 163:59 (1998); Lund etc., J Immunol. (Journal of Immunology) 147:2657 (1991); Sarmay etc., Mol.Immunol. (molecular immunology) 29:633 (1992); Lund etc., Mol.Immunol. (molecular immunology) 29:53 (1992); Morgan etc., as previously mentioned).Except the one or more amino acid that are substituted in EU position 234-239, can also replace (the C-terminal side of close position 239, perhaps the N-terminal side of close position 234) one, two or three or more amino acid in contiguous this zone.

By way of example, the leucine residue that is substituted in position 235 (position 16 of its corresponding SEQ ID NO:79) with glutaminic acid residue or alanine residue is eliminated respectively or is reduced the avidity (Lund etc. of immunoglobulin (Ig) (as human IgG 3) to Fc γ RI, 1991, as previously mentioned; Canfield etc., as previously mentioned; Morgan etc., as previously mentioned).As another example, for example, will be in the position leucine residue of 234 and 235 (positions 15 and 16 of its corresponding SEQ ID NO:79) substitute with alanine residue, eliminated the combining of immunoglobulin (Ig) and Fc γ RIIa (referring to, for example, Wines etc., as previously mentioned).Alternatively, the leucine of 234 (positions 15 of its corresponding SEQ ID NO:79) in the position, the leucine of 235 (positions 16 of its corresponding SEQ ID NO:79) in the position, with the glycine of 237 (positions 18 of its corresponding SEQ ID NO:79) in the position, each can be with different aminoacid replacement, such as 234 leucine can replace (L234A) with alanine residue in the position, leucine 235 can replace (L235A) with alanine residue or replace (L235E) with glutaminic acid residue, and 237 glycine residue can be used another kind of aminoacid replacement in the position, for example replaces (G237A) with alanine residue.

In one embodiment, meet, two, three, four, five or six sudden changes that the mutain Fc polypeptide that merges on frame ground is included in SEQ ID NO:79 position 15-20 with viral polypeptide (or its variant or fragment), the position 15-20 of SEQ ID NO:79 is corresponding with the position 234-239 (EU numbering system) of human IgG1 CH2 structural domain as described herein.A kind of exemplary mutain Fc polypeptide has the aminoacid sequence of listing in SEQ ID NO:77, wherein with (L234A), (L235E) and (G237A) corresponding replacement can be found in the position 13,14 and 16 of SEQ ID NO:77.

In another embodiment, mutain Fc polypeptide is included in the sudden change of the cysteine residues in the hinge area of Fc polypeptide.In one embodiment, (the most for example near the N-terminal cysteine residues of the hinge area of Fc polypeptide, for example, near the N-terminal cysteine residues of the hinge area of the Fc part of wild-type IgG1 immunoglobulin (Ig)) lacked or by another kind of aminoacid replacement.That is, Shuo Ming mode by way of example, the cysteine residues in SEQ ID NO:79 position 1 is lacked, and perhaps 1 cysteine residues can not be formed the another kind of aminoacid replacement of disulfide linkage in the position, for example replaces with serine residue.In another embodiment, mutain Fc polypeptide comprises disappearance or the replacement near the N-terminal cysteine residues of the hinge area of Fc polypeptide, also comprises the disappearance or the replacement of contiguous C terminal amino acid.In a specific embodiment, this cysteine residues and contiguous C end residue are all lacked by the hinge area from mutain Fc polypeptide.In a special embodiment, cysteine residues and the aspartic acid in SEQ ID NO:79 position 2 in SEQ ID NO:79 position 1 are lacked.The Fc polypeptide that is included in the disappearance of these halfcystines of hinge area and asparagicacid residue can be expressed in host cell effectively, and can more effectively in cell, express in some cases, than the Fc polypeptide that keeps wild-type halfcystine and asparagicacid residue.

In a special embodiment, mutain Fc polypeptide is included in the aminoacid sequence of listing among the SEQ ID NO:77, they are different with wild-type Fc polypeptide (SEQ ID NO:79), wherein the cysteine residues in SEQ ID NO:79 position 1 is lacked, and the aspartic acid in SEQ ID NO:79 position 2 is lacked, and in the SEQ of correspondence position EU234 ID NO:79 position 15, leucine residue is replaced with alanine residue, the leucine residue of 16 (its corresponding EU235) replaces with glutaminic acid residue in the position, and replaces (also referring to Fig. 5) at the glycine of the position 18 of corresponding EU237 with alanine residue.Therefore, exemplary mutain Fc polypeptide partly comprises aminoacid sequence KTHTCPPCPAPEAEGAPS (SEQ ID NO:81) (referring to SEQID NO:77, a kind of exemplary Fc mutain sequence) at its aminoterminal.

Other Fc variant comprises the similar aminoacid sequence of known Fc peptide sequence, it has small change, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, and it can further comprise conservative the replacement.Similar each other aminoacid sequence can be enjoyed the elementary zone of sequence homology.Similarly, the nucleotide sequence of coding Fc variant can comprise similar basically nucleotide sequence, and only has small variation, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, because the degeneracy of genetic code, it can further comprise silent mutation.Similar each other nucleotide sequence can be enjoyed the elementary zone of sequence homology.

When merging with purpose peptide or polypeptide, Fc polypeptide or at least one constant region for immunoglobulin or its part, partial action is vehicle or carrier part at least, it prevents the degraded of described peptide and/or increases its transformation period, reduce its toxicity, reduce its immunogenicity, and/or increase its biological activity, such as by form dimer or other polymer (referring to, for example, U.S. Patent number 6,018,026; 6,291,646; 6,323,323; 6,300,099; 5,843,725).(also referring to, for example, U.S. Patent number 5,428,130; U.S. Patent number 6,660,843; U.S. Patent Application Publication No. 2003/064480; 2001/053539; 2004/087778; 2004/077022; 2004/071712; 2004/057953/2004/053845/2004/044188; 2004/001853; 2004/082039).The alternative part that can be connected to or be fused to constant region for immunoglobulin such as the Fc polypeptide on the immunoreactive peptide that changes immunocyte comprises, for example, and linear polymer (for example, polyoxyethylene glycol, polylysine, dextran etc.; Referring to, for example, U.S. Patent number 4,289,872; International application published WO93/21259); Lipid; Cholesterol group (as steroid); Carbohydrate or oligosaccharides.

Coding is known from different types of Fc polypeptide with from the nucleotide sequence of the isotype of the immunoglobulin (Ig) of different plant species, and can be at the GenBank database with at Kabat (Kabat etc., in Sequences of Proteins of Immunological Interest (sequence of immunology target protein matter), the 4th edition, (U.S. HHS, United States Government's printing place, 1991), also referring to the renewal of online Kabat database) in obtain, any sequence wherein can be used to prepare recombinant precursor according to the conventional molecular biology method of implementing of those skilled in the art.For described Fc polypeptide is reduced to minimum host that can use RPTP fragment fusion polypeptide or the immunogenicity among the experimenter, the sequence of described Fc polypeptide typically is selected from the immunoglobulin (Ig) of same species, promptly, for example, people Fc peptide sequence is fused to is administered on people experimenter or host's the RPTP fragment.

Described hereinly be used to identify with poxvirus polypeptide such as A41L or 130L interacts and/or the method for bonded cell surface molecule such as RPTPS, can also be used to identifying with RPTPs as herein described (that is, LAR, RPTP-δ and/or RPTP-σ) interact, be its part, form mixture or the interior molecule of cell associating in addition with it with it.Do not wish to be bound by theory, molecule according to the interaction between poxvirus polypeptide and the RPTP and in one or more the interactional cells among evaluation and LAR, RPTP-δ and the RPTP-σ, can identify special approach (and composition), described approach participates in or causes the performance of disease or illness when interrupting or activate.Associate with one or more RPTPs and (for example participate in such cell of one or more signal transduction paths molecule, by identifying with the TAP-TAG method of A41L at least and the interactional plakoglobin of LAR and LIP related protein-1-β), can be to be used for the treatment of Immunological diseases as herein described or the reagent of illness, cardiovascular disorder or illness or metabolic trouble or illness and the target spot of composition.Alternatively, reagent as herein described, one or more interactions among itself and LAR, RPTP-δ and the RPTP-σ, and the immunoreactivity that is used for the treatment of disease or illness and/or change immunocyte, can influence the interaction between the molecule in RPTP and the cell, and therefore can change one or more biological activitys of described cell.

Reagent

Poxvirus polypeptide such as A41L or 130L and LAR, RPTP-δ and/or RPTP-σ combine at least a biological function that changes these Phosphoric acid esterases, and it is as described herein, can change the immunoreactivity of (for example, suppressing or enhancing) described cell at the LAR, the RPTP-δ that express on A41L or 130L and the cell surface and/or the interaction between the RPTP-σ at immunocyte.The immunoreactive change of immunocyte can also realize in the mode similar to the poxvirus polypeptide by biologically active agent (compound or molecule).Biologically active agent comprises, for example, and small molecules, nucleic acid (as fit, siRNAs, antisense nucleic acid), antibody and fragment thereof and fusion rotein (as peptide-Fc fusion rotein and RPTP Ig zone-Fc fusion rotein).The position that reagent is can be on RPTP identical with A41L or 130L bonded position or near at least a interaction among the position of described same position and LAR, RPTP-δ and the RPTP-σ with combine.Alternatively, by reagent with the similar mode of A41L (or 130L) effect change immunoreactivity can by described reagent and RPTP away from the position of poxvirus polypeptide bonded position combine or interaction causes.In conjunction with research, comprise competitive binding assay, and functional examination, the immunoreactive level of its indicator cells, the method that can implement according to as herein described and this area and carrying out, with determine and relatively reagent in conjunction with and influence the immunoreactive ability and the level of immunocyte.

This paper is provided for identify changing the immunoreactive reagent of (for example, suppress with statistics or the significant mode of biology or strengthens) immunocyte and in case is used for after identifying that characteristic is described and the inhibition of definite such reagent or the method for enhanced level.Such method, it discusses in more detail and those skilled in the art are afamiliar with at this paper, and it includes but not limited to, in conjunction with measuring, such as immunoassay (for example, ELISA, radioimmunoassay, immunoblotting etc.), competitive binding assay and surface plasmon resonance.These methods are included between at least a RPTP polypeptide of abundant permission and the described poxvirus polypeptide interactional condition and under the time, with following contact (mix, combination or to allow interactional certain mode): (1) candidate agent; (2) at least a immunocyte among expression LAR, RPTP-σ and the RPTP-δ; (3) poxvirus polypeptide is as A41L or 130L.The condition that is used for specific mensuration comprises temperature, damping fluid (comprising salt, positively charged ion, medium) and keeps other composition of cell, reagent and poxvirus polypeptide integrity, its be those skilled in the art are afamiliar with and/or its can easily determine.In the presence of candidate agent, A41L (or 130L) can easily determine with the interaction of immunocyte or the level that combines, and when not having described reagent the comparing of A41L (or 130L) and described cell in conjunction with level.In the presence of candidate agent, A41L (or 130L) shows that with the minimizing of immunocyte bonded level described candidate agent suppresses the immunoreactivity of immunocyte.

In another embodiment, the immunoreactive compositions and methods that is used for evaluation change (suppressing or enhancing) immunocyte comprises to be determined in the presence of reagent, expresses the immunoreactive level of at least a immunocyte among LAR, RPTP-σ and the RPTP-δ.In some special embodiment, identified a kind of immunoreactive reagent that suppresses immunocyte.Immunoreactivity can be determined according to the method that implement this area, such as the level of measuring cytokine, propagation and stimulation.The immunoreactivity of immunocyte can also determine that described cell protein includes but not limited to cytoskeletal protein and influences other protein of cell adhesion and migration by the variation in assessment cell adhesion and the cell migration and by check cell protein tyrosine phosphorylation pattern.

Those skilled in the art implements many mensuration and technology, to determine interaction or the combination between biomolecules and the cognate ligand.Therefore, interaction between in poxvirus polypeptide such as A41L or 130L and LAR, RPTP-σ and RPTP-δ any one or more, be included in when having described reagent biologically active agent to this interaction and/or bonded effect, can be by this paper described such mensuration and technology and easily determine in detail.

Small molecules

Biologically active agent can also comprise natural and synthetic molecule, for example, small molecules, itself and poxvirus polypeptide are (for example, A41L or 130L), or with LAR, RPTP-σ and RPTP-δ in one or more, and/or with poxvirus polypeptide (for example, A41L or 130L) and LAR, RPTP-σ and RPTP-δ in any between the mixture combination.Being used for screening changes the immunoreactivity of (suppressing or enhancing) immunocyte and/or (for example suppresses described poxvirus polypeptide, A41L or 130L) with LAR, RPTP-σ and RPTP-δ in bonded compositions and methods at least a, two or all three kinds at least in candidate agent, can be used as " library " of compound, composition or molecule or set and provide.

Such molecule typically comprises the compound that is known in the industry as " small molecules ", and has less than 10 ⁵Dalton, less than 10 ⁴Dalton or less than 10 ³Daltonian molecular weight.For example, the library member of test compounds can be imposed on multiple sample, every duplicate samples comprises at least a tyrosine phosphatase enzyme polypeptide provided herein, strengthen at their then or suppress LAR, RPTP-σ and/or RPTP-δ-mediation the substrate dephosphorylation or with the bonded ability of substrate; Suppress or enhancing Phosphoric acid esterase and poxvirus polypeptide (for example, A41L or 130L) bonded ability; And/or the immunoreactive ability of test compounds adjusting immunocyte, and detect described sample.The compound that is accredited as at least a function that can influence poxvirus polypeptide LAR, RPTP-σ and/or RPTP-δ like this is valuable for treatment and/or diagnostic purpose, and reason is that they allow treatment and/or detection and LAR, RPTP-σ and/or the active relevant disease of RPTP-δ.Such compound also is valuable at any one or more the research of molecular signal transmission mechanism that relates among LAR, RPTP-σ and/or the RPTP-δ.

Candidate agent can also provide as the member of combinatorial library, and it preferably includes the synthetic agent for preparing according to a plurality of predetermined chemical reaction that carries out in a plurality of reaction vessels.For example, according to one or more solid phase synthesis, recording blending means and allow given component to experience the recording schizokinesis technology of the combination of multiple variation and/or reaction conditions at random traceablely, can prepare various initial compounds.The product that obtains comprises can be by repeating to select the library with the synthetic method screening, such as the synthetic combinatorial libraries of peptide (referring to, for example, international patent application no PCT/US91/08694 and PCT/US91/04666) maybe can comprise micromolecular other composition provided herein synthetic combinatorial libraries (referring to, for example, international patent application no PCT/US94/08542, the EP patent No. 0774464, U.S. Patent number 5,798,035, U.S. Patent number 5,789,172, U.S. Patent number 5,751,629, they are incorporated into this by reference fully).Will be understood by those skilled in the art that the difference classification in such library can prepare according to fixed method, and detects according to present disclosure.

The example that is used for molecular library synthetic method can find in the art, for example, and at DeWitt etc., Proc.Natl.Acad.Sci.U.S.A. (NAS's journal) 90:6909 (1993); Erb etc., Proc.Natl.Acad.Sci USA (NAS's journal) 91:11422 (1994); Zuckermann etc., J Med.Chem. (journal of medicinal chemistry) 37:2678 (1994); Cho etc., Science (science) 261:1303 (1993); Carrell etc., Angew.Chem.Int.Ed.Engl. (the international version of England Angewandte chemistry) 33:2059 (1994); Carell etc. are among Angew.Chem.Int.Ed.Engl. (the international version of England Angewandte chemistry) 33:2061 (1994); With at Gallop etc., among J Med.Chem. (journal of medicinal chemistry) 37:1233 (1994).The library of compound may reside in (for example, Houghten, Biotechniques (biotechnology) 13:412-21 (1992)) in the solution, or on the pearl (Lam, Nature (nature) 354:82-84 (1991)); Chip (Fodor, Nature (nature) 364:555-56 (1993)); Bacterium (Ladner, U.S. Patent number 5,223,409); Spore (Ladner, as previously mentioned); Plasmid (Cull etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 89:1865-69 (1992)); Or (Scott and Smith, Science (science) 249:386-390 (1990) on the phage; Devlin, Science (science) 249:404-406 (1990); Cwirla etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 87:6378-82 (1990); Felici, J.Mol.Biol. (molecular biology magazine) 222:301-10 (1991); Ladner, as previously mentioned).

Peptide-immunoglobulin-constant region fusion polypeptide

In one embodiment, the biologically active agent that is used to change the immunoreactivity of immunocyte and can be used for the treatment of Immunological diseases or illness is peptide-immunoglobulin-(Ig) constant region fusion polypeptide, and it comprises peptide-IgFc fusion polypeptide.Described peptide can be the molecule of any naturally occurring or reorganization preparation.A kind of peptide-Ig constant region fusion polypeptide, such as peptide-IgFc fusion polypeptide (be also referred to as in the art peptide body (peptibody) (referring to, for example, U.S. Patent number 6,660,843)), comprise and to change active biologically active peptides or the polypeptide of target protein matter as the RPTP (LAR, RPTP-σ and/or RPTP-δ) that expresses by immunocyte, the part of itself and immunoglobulin (Ig), at least one constant region structural domain are (for example, CH1, CH2, CH3, and/or CH4) or Fc polypeptide (CH2-CH3) fusion.Described Fc polypeptide also is called Fc part or Fc zone at this paper.

In one embodiment, the peptide moiety of fusion polypeptide can with LAR, RPTP-σ and RPTP-δ at least a, two or all three kinds interact or combine at least, and when it combines with at least a RPTPs, with the poxvirus polypeptide (for example, A41L or 130L) equally realize identical biological activity therefore suppressing the immunoreactivity that (reduce, prevent, reduce or eliminate) expresses the immunocyte of RPTP.The invention provides the method that is used for identifying the immunoreactive peptide to change (for example, suppressing) the immunocyte peptide of A41L or 130L stand-in (that is, as).For example, such peptide can be identified by determining its inhibition or blocking-up A41L (or 130L) and the bonded ability of the cell of expressing at least a RPTPs.Alternatively, can allow candidate's peptide contact or interacts, and can measure the immunoreactive ability of described candidate's peptide inhibition or enhancing immunity cell according to the method for implementing with this area as herein described with the immunocyte of expressing at least a RPTPs.Candidate's peptide can be used as the member of combinatorial library and provides, and described combinatorial library comprises the synthetic peptide for preparing according to a plurality of predetermined chemical reaction that carries out in a plurality of reaction vessels.For example, the standard peptide synthetic technology of being familiar with according to the technician can prepare various initial peptides.

Change immunocyte immunoreactive peptide can from combinatorial library (referring to, for example, international patent application no PCT/US91/08694 and PCT/US91/04666) and the phage display peptide library (referring to, for example, Scott etc., Science (science) 249:386 (1990); Devlin et al., Science249:404 (1990); Cwirla etc., Science (science) 276:1696-99 (1997); U.S. Patent number 5,223,409; U.S. Patent number 5,733,731; U.S. Patent number 5,498,530; U.S. Patent number 5,432,018; U.S. Patent number 5,338,665; 1994; U.S. Patent number 5,922,545; International application published WO 96/40987 and WO 98/15833) in identify and separate.In the phage display peptide library, peptide sequence at random is fused on the bacteriophage coat protein, so that described peptide is illustrated on the filobactivirus particulate outside surface.Typically, the peptide of showing is contacted with purpose part or binding molecule,, remove unconjugated phage to allow the interaction between described peptide and described part or the binding molecule, and the bonded phage is eluted, and take turns affinity purification and breed and enrichment again by continuously several subsequently.Can be with the peptide sequencing that has at the avidity of described part or binding molecule or purpose target molecule (for example, RPTPs as herein described) maximum, to identify Key residues, this can identify the peptide in the peptide family of one or more structurally associateds.The comparison of peptide sequence can also show which residue can be replaced by mutagenesis or lack safely in described peptide.Then, these peptides can be incorporated into can be screened other peptide library in, and can identify peptide with best avidity.

Be used to identify the immunoreactivity that can change immunocyte and therefore can be used for the treatment of and/or other method of the peptide of epidemic prevention disease or illness comprises, but be not limited to, (1) structural analysis of protein-protein interaction, as analyze the RPTP target spot crystalline structure (referring to, for example, Jia, Biochem.Cell Biol (biological chemistry cytobiology) 75:17-26 (1997)), with identify and the important residue of definite RPTP towards, this will be used for designed peptide (referring to, for example, Takasaki etc., Nature Biotech. (Nature Biotechnol) 15:1266-70 (1997)); (2) peptide library, it comprises and is fused on peptidoglycan-bonded lipoprotein and is illustrated in peptide on bacterium such as the colibacillary outside surface; (3) produce the library that RNA-bonded peptide produces peptide by the translation of interrupting polypeptide; (4) by producing peptide with one or more protease digestion polypeptide.(also referring to, for example, U.S. Patent number 6,660,843; 5,773,569; 5,869,451; 5,932,946; 5,608,035; 5,786,331; 5,880,096).Peptide can be included between 3 and 75 amino acid, between 3 and 60 amino acid, and between 3 and 50 amino acid, between 3 and 40 amino acid, between 3 and 30 amino acid, between 3 and 20 amino acid, or the amino acid of the arbitrary number between 3 and 10 amino acid.Have change immunocyte immunoreactivity (for example, in certain embodiments, the immunoreactivity that suppresses immunocyte, and in some other embodiment, the peptide of the ability immunoreactivity of enhancing immunity cell) can also further be derived, and is used to make up the amino acid (all catenation sequences in this way or the amino acid of intervening sequence) of peptide-Ig constant region fusion proteins with interpolation or insertion.

The peptide that can be used for making up peptide-Ig constant region fusion polypeptide (comprising peptide-Ig Fc fusion polypeptide) can derive from the poxvirus polypeptide, such as A41L polypeptide or 130L polypeptide.A41L or 130L peptide can by use various proteolytic enzyme any one or more proteolytic digestion and produce at random, separate, and analyze the immunoreactive ability that their change immunocyte then.Such peptide can also use recombination method as herein described and that implement this area to produce.The peptide of Chan Shenging can also be used to preparation as described peptide combinatorial library or phage library in this paper and this area at random.Alternatively, the part that the aminoacid sequence of the part of A41L or 130L and LAR, RPTP-σ and/or RPTP-delta mutual action can be by described Phosphoric acid esterase or described Phosphoric acid esterase for example determine by the computer model and/or the X-radiocrystallgraphy (it can comprise the crystalline preparation of single Phosphoric acid esterase or Phosphoric acid esterase-viral polypeptide complex body and analyze) of extracellular part or Ig structural domain.

Described in detail as mentioned, the Fc polypeptide of immunoglobulin (Ig) comprises heavy chain CH2 structural domain and CH3 structural domain and part between CH1 and CH2 or whole hinge area.The Fc district can pass through covalency (for example, particularly disulfide linkage) and non-covalent association and the monomer polypeptide that connects into dimer or polymer form.The number of the intermolecular disulfide bond between the monomer subunit of Fc polypeptide depend on described immunoglobulin (Ig) kind (for example, IgG, IgA, IgE) or subclass (for example, the human IgG1, IgG2, IgG3, IgG4, IgA1, IgA2) and different.At present, according to the recombinant molecule biology techniques that the technician is familiar with very much, the fusion rotein that can easily prepare Fc polypeptide and any one or more constant region structural domain and comprise at least one immunoglobulin (Ig) (Ig) constant region structural domain.

Described Fc polypeptide preferably uses the Nucleotide and the amino acid sequence coded that derive from the animal species that is intended to use described peptide-IgFc fusion polypeptide to be prepared.In one embodiment, described Fc polypeptide is the people source, and can come from any immunoglobulin (Ig) kind, as human IgG1 and IgG2.

Fc polypeptide as herein described also comprises the Fc polypeptide variants.A kind of such Fc polypeptide variants makes and one or more cysteine residues (such as the one or more cysteine residues at hinge area) of another Fc polypeptide formation disulfide linkage are replaced by another kind of amino acid such as Serine, to reduce the number of the disulfide linkage that forms between two Fc polypeptide.Alternatively, one or more cysteine residues can be from the wild-type hinge area disappearance of Fc polypeptide.

Another example of Fc polypeptide variants is the variant that the feasible one or more amino acid that participate in effector function are substituted or lack, so that described Fc polypeptide has the effector function level of minimizing.For example, the amino acid in the Fc zone can be substituted, with the combination of the composition that reduces or eliminates complement cascade (referring to, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995)), perhaps reduce or eliminate the Fc polypeptide in conjunction with the ability of the IgG Fc acceptor of expressing by immunocyte (Wines etc., J Immunol. (Journal of Immunology) 164:5313-18 (2000); Chappel etc., Proc.Natl.Acad.Sci USA (NAS's journal) 88:9036 (1991); Canfield etc., J.Exp.Med. (The Journal of Experimental Medicine) 173:1483 (1991); Duncan etc., as previously mentioned); Perhaps change the cytotoxicity of antibody-dependent cell.The such Fc polypeptide variants different with wild-type Fc polypeptide also are called mutain Fc polypeptide in this article.

In one embodiment, peptide as herein described and Fc polypeptide meet frame ground and merge, and described Fc polypeptide is included at least a replacement of the residue of the one or more IgG Fc receptors bind that help Fc polypeptide or immunoglobulin (Ig) in the polypeptide of wild-type Fc zone and express on specific immunocyte.Such mutain Fc polypeptide is included at least a replacement of the amino-acid residue in the CH2 structural domain of described mutain Fc polypeptide, so that described fusion polypeptide reduces in conjunction with the ability of IgG Fc acceptor as the IgG Fc acceptor that exists on the immunocyte surface.In above detailed description the type of the Fc IgG acceptor of on human leukocyte, expressing.

Be included in residue (Leu-Leu-Gly-Gly-Pro-Ser (SEQ ID NO:80) (the EU numbering system of position Leu234-Ser239 at the aminoterminal residue partly of the CH2 structural domain that helps IgG Fc receptors bind, Kabat etc., as previously mentioned) (referring to, for example, Morgan etc., Immunology (immunology) 86:319-24 (1995) and the reference of wherein quoting).These positions are corresponding with the position 15-20 of human IgG1 Fc amino acid sequence of polypeptide (SEQ ID NO:79).In the CH2 structural domain in these 6 positions one or more (promptly, one, two, three, four, five or whole six) aminoacid replacement of position cause described Fc polypeptide in conjunction with the minimizing of the ability of one or more IgG Fc acceptors (or its isotype) (referring to, for example, Burton etc., Adv.Immunol. (senior immunology) 51:1 (1992); Hulett etc., Adv.Immunol. (senior immunology) 57:1 (1994); Jefferis etc., Immunol.Rev. (immunology research) 163:59 (1998); Lund etc., J Immunol. (Journal of Immunology) 147:2657 (1991); Sarmay etc., Mol.Immunol. (molecular immunology) 29:633 (1992); Lund etc., Mol.Immunol. (molecular immunology) 29:53 (1992); Morgan etc., as previously mentioned).Except the one or more amino acid that are substituted in EU position 234-239, can also replace (the C-terminal side of close position 239, perhaps the N-terminal side of close position 234) one, two or three or more amino acid in contiguous this zone.

By way of example, the leucine residue that is substituted in position 235 (position 16 of its corresponding SEQ ID NO:79) with glutaminic acid residue or alanine residue is eliminated respectively or is reduced the avidity (Lund etc. of immunoglobulin (Ig) (as human IgG 3) to Fc γ RI, 1991, as previously mentioned; Canfield etc., as previously mentioned; Morgan etc., as previously mentioned).As another example, for example, will be in the position leucine residue of 234 and 235 (positions 15 and 16 of its corresponding SEQ ID NO:79) substitute with alanine residue, eliminated the combining of immunoglobulin (Ig) and Fc γ RIIa (referring to, for example, Wines etc., as previously mentioned).Alternatively, the leucine of 234 (positions 15 of its corresponding SEQ ID NO:79) in the position, the leucine of 235 (positions 16 of its corresponding SEQ ID NO:79) in the position, with the glycine of 237 (positions 18 of its corresponding SEQ ID NO:79) in the position, each can be with different aminoacid replacement, such as 234 leucine can replace (L234A) with alanine residue in the position, leucine 235 can replace (L235A) with alanine residue or replace (L235E) with glutaminic acid residue, and 237 glycine residue can be used another kind of aminoacid replacement in the position, for example replaces (G237A) with alanine residue.

In one embodiment, meet, two, three, four, five or six sudden changes that the mutain Fc polypeptide that merges on frame ground is included in SEQ ID NO:79 position 15-20 with viral polypeptide (or its variant or fragment), the position 15-20 of SEQ ID NO:79 is corresponding with the position 234-239 (EU numbering system) of human IgG1 CH2 structural domain as described herein.A kind of exemplary mutain Fc polypeptide has the aminoacid sequence of listing in SEQ ID NO:77, wherein with (L234A), (L235E) and (G237A) corresponding replacement can be found in the position 13,14 and 16 of SEQ ID NO:77.

In another embodiment, mutain Fc polypeptide is included in the sudden change of the cysteine residues in the hinge area of Fc polypeptide.In one embodiment, (the most for example near the N-terminal cysteine residues of the hinge area of Fc polypeptide, for example, near the N-terminal cysteine residues of the hinge area of the Fc part of wild-type IgG1 immunoglobulin (Ig)) lacked or by another kind of aminoacid replacement.That is, Shuo Ming mode by way of example, the cysteine residues in SEQ ID NO:79 position 1 is lacked, and perhaps 1 cysteine residues can not be formed the another kind of aminoacid replacement of disulfide linkage in the position, for example replaces with serine residue.In another embodiment, mutain Fc polypeptide comprises disappearance or the replacement near the N-terminal cysteine residues of the hinge area of Fc polypeptide, also comprises the disappearance or the replacement of contiguous C terminal amino acid.In a specific embodiment, this cysteine residues and contiguous C end residue are all lacked by the hinge area from mutain Fc polypeptide.In a special embodiment, cysteine residues and the aspartic acid in SEQ ID NO:79 position 2 in SEQ ID NO:79 position 1 are lacked.The Fc polypeptide that is included in the disappearance of these halfcystines of hinge area and asparagicacid residue can be expressed in host cell effectively, and can more effectively in cell, express in some cases, than the Fc polypeptide that keeps wild-type halfcystine and asparagicacid residue.

In a special embodiment, mutain Fc polypeptide is included in the aminoacid sequence of listing among the SEQ ID NO:77, they are different with wild-type Fc polypeptide (SEQ ID NO:79), wherein the cysteine residues in SEQ ID NO:79 position 1 lacks, and aspartic acid disappearance in SEQ ID NO:79 position 2, and the leucine residue in SEQ ID NO:79 position 15 replaces with alanine residue, 16 leucine residue replaces with glutaminic acid residue in the position, and 18 glycine replaces (also referring to Fig. 5) with alanine residue in the position.Therefore, exemplary mutain Fc polypeptide partly comprises aminoacid sequence KTHTCPPCPAPEAEGAPS (SEQ IDNO:81) (referring to SEQ ID NO:77, a kind of exemplary Fc mutain sequence) at its aminoterminal.

Other Fc variant comprises the similar aminoacid sequence of known Fc peptide sequence, it has small change, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, and it can further comprise conservative the replacement.Similar each other aminoacid sequence can be enjoyed the elementary zone of sequence homology.Similarly, the nucleotide sequence of coding Fc variant can comprise similar basically nucleotide sequence, and only has small variation, for example, by way of example the explanation rather than the restriction mode, covalent chemical is modified, inserts, is lacked and/or replaces, because the degeneracy of genetic code, it can further comprise silent mutation.Similar each other nucleotide sequence can be enjoyed the elementary zone of sequence homology.

When merging with purpose peptide or polypeptide, Fc polypeptide or at least one constant region for immunoglobulin or its part, partial action is vehicle or carrier part at least, it prevents the degraded of described peptide and/or increases its transformation period, reduce its toxicity, reduce its immunogenicity, and/or increase its biological activity, such as by form dimer or other polymer (referring to, for example, U.S. Patent number 6,018,026; 6,291,646; 6,323,323; 6,300,099; 5,843,725).(also referring to, for example, U.S. Patent number 5,428,130; U.S. Patent number 6,660,843; U.S. Patent Application Publication No. 2003/064480; 2001/053539; 2004/087778; 2004/077022; 2004/071712; 2004/057953/2004/053845/2004/044188; 2004/001853; 2004/082039).The alternative part that can be connected to or be fused to constant region for immunoglobulin such as the Fc polypeptide on the immunoreactive peptide that changes immunocyte comprises, for example, and linear polymer (for example, polyoxyethylene glycol, polylysine, dextran etc.; Referring to, for example, U.S. Patent number 4,289,872; International application published WO93/21259); Lipid; Cholesterol group (as steroid); Carbohydrate or oligosaccharides.

Nucleic acid molecule

In certain embodiments, such polynucleotide and oligonucleotide is provided, promptly, its with to the sequence complementation of the coding RPTP (LAR, RPTP-σ or RPTP-δ) of small part (for example, short interfere RNA, antisense polynucleotides, ribozyme or peptide nucleic acid(PNA)), and it can be used to change gene and/or protein expression.When being used for this paper, combine with the nucleic acid molecule specificity of coding RPTP (LAR, RPTP-σ or RPTP-δ) or these polynucleotide of hybridizing can use the provided herein and nucleotide sequence that can obtain in the art (for example, the encode SEQ ID NOS:23 and 27 of LAR; The SEQ ID NOS:30 of coding RPTP-σ, 32,34,36; With the SEQID NOS:38 of coding RPTP-δ, 40,42,44) and prepare.In another embodiment, not sequence-specific nucleic acid molecule such as fitly can be used to change gene and/or protein expression yet.

RNA disturbs (RNAi)

By the mode of background technology, RNA disturbs method (Zamore etc., Cell (cell), the 101:25-33 (2000) be meant in animal by gene silencing behind the sequence-specific transcriptional of short RNA interfering s (siRNAs) mediation; Fire etc., Nature (nature) 391:806 (1998); Hamilton etc., Science (science) 286:950-51 (1999); Lin etc., Nature (nature) 402:128-29 (1999); Sharp, Genes ﹠amp; Dev. (gene and growth) 13:139-41 (1999); And Strauss, Science (science) 286:886 (1999); Sandy etc., Biotechniques (biotechnology) 39:215-24 (2005); U.S. Patent number 6,506,559; 6,573,099; International application published WO 01/75164).Because the part that nucleotide sequence is selected from target spot gene (for example, expressing the gene of RPTP as herein described) to be producing inhibitory RNA, so to suppress be sequence-specific.Think that the method for PTGS is the cytophylaxis mechanism (Fire etc., Trends Genet. (genetics trend) 15:358 (1999)) that is used for preventing exogenous gene expression.Described method comprises having the nucleic acid molecule of double-stranded feature partially or completely, and normally RNA is incorporated in the cell.The existence of dsRNA in cell causes the RNAi reaction by the mechanism of characteristic description fully.As if this mechanism different with other mechanism that relates to double-stranded RNA-specific ribonucleic acid enzyme, described other mechanism such as the protein kinase PKR and 2 that mediates by dsRNA-', 5 '-activation of oligoadenylate synthetase and the ifn response that causes, described ifn response by ribonuclease l cause mRNA non-specific cracking (referring to, for example U.S. Patent number 6,107,094; 5,898,031; Clemens etc., J Interferon Cytokine Res. (Interferon, rabbit cytokine research magazine) 17:503-24 (1997); Adah etc., Curr.Med.Chem. (modern medicine chemistry) 8:1189 (2001)).

The existence of long dsRNAs in cell stimulates activity (Bass, Cell (cell) 101:235 (2000) that is called the rnase iii enzyme of cutting enzyme; Zamore etc., Cell (cell), 101:25-33 (2000); Hammond etc., Nature (nature) 404:293 (2000)).Cut the segmental process of dsRNA (Zamore etc., Cell (cell) 101:25-33 (2000) that enzyme participates in dsRNA is processed into the weak point that is called siRNAs; Bass, Cell (cell) 101:235 (2000); Berstein etc., Nature (nature) 409:363 (2001)).Derive from the RNA interfering s length of the weak point of cutting enzymic activity typically about 21 to about 23 Nucleotide, and the duplex that comprises about 19 base pairs (for example, comprise the duplex nuclear of 19 base pairs and the dsRNA molecule of growing at 21-22 Nucleotide of each 3 ' two unpaired Nucleotide holding) (Zamore etc., 2000, as previously mentioned; Elbashir etc., 2001, as previously mentioned; Dykxhoorn etc., Nat.Rev.Mol.Cell Biol. (natural molecular cytobiology summary) 4:457-67 (2003)).Cutting enzyme also participates in from participating in translating the precursor RNA excision 21-of the conserved structure of controlling and little interim RNAs (small temporal RNAs, stRNAs) (Hutvagner etc., Science (science) 293:834 (2001)) of 22-Nucleotide.RNAi reaction is a feature with the endonuclease combined enzyme agent that is called RNA-inductive silencing complex (RISC) usually also, and described endonuclease combined enzyme agent regulation and control have the cracking with the single stranded RNA of the antisense strand complementary sequence of described siRNA duplex.The cracking of target spot RNA occur in the middle part in the antisense strand complementary zone of described siRNA duplex (Elbashir etc., 2001, as previously mentioned).

Short RNA interfering s can be used for regulating (reducing or inhibition) LAR, RPTP-σ and/or RPTP-δ expression of gene.The RNA that the content of this paper relates to by using little nucleic acid molecule disturbs expression of gene and active compound, composition and the method that is used to regulate coding RPTPs, LAR, RPTP-σ and RPTP-δ.Especially, little nucleic acid molecule can be used for regulating the expression of LAR, RPTP-σ and/or RPTP-δ or their variant according to method as herein described such as short RNA interfering (siRNA), little-RNA (miRNA) and short hairpin RNA (shRNA) molecule.The siRNA polynucleotide preferably include double-stranded RNA (dsRNA), but can comprise single stranded RNA (referring to, for example, Martinez etc., Cell (cell) 110:563-74 (2002)).The siRNA polynucleotide can comprise that other is naturally occurring, reorganization or synthetic strand or double-stranded nucleotide polymer (ribonucleotide or deoxyribonucleotide or the combination of the two) and/or as that this paper provided and nucleotide analog known to those skilled in the art and application.

At least one chain of double-stranded siRNA polynucleotide has at arbitrary chain of described siRNA polynucleotide or preferably at least one and two Nucleotide preferably of 3 ' end " giving prominence to " of two chains (that is, with at relative chain not base pairing of complementary base).Typically, every chain of described siRNA polynucleotide duplex has the overhang of two Nucleotide at 3 ' end.The overhang of described two Nucleotide can be thymidine dinucleotides (TT), perhaps can comprise other base, for example, TC dinucleotides or TG dinucleotides, perhaps any other dinucleotides (referring to, for example, international application published WO 01/75164).Alternatively, described siRNA polynucleotide can have flush end, that is, each Nucleotide of a chain of described duplex preferably with the Nucleotide complementary (for example, passing through Watson-Crick base pairing) of relative chain.

SiRNA can use the DNA that comprises rna polymerase promoter as U6 promotor or H1 rna plymerase iii promotor (genomic, cDNA or synthetic) to transcribe as template, and perhaps siRNA can be synthetic RNA molecule of originating.The duplex structure of siRNA can be by the complementary RNA chain formation of single oneself, perhaps by two complementary RNA chain formation.The RNA duplex forms can be at cell interior or outside initial.RNA can give the amount of at least one copy or each cell at least 5,10,50,100,250,500 or 1000 copies and introduces with each cell delivery.Polynucleotide as the siRNA polynucleotide can derive from such strand polynucleotide, promptly, its oligonucleotide fragment that comprises strand (for example, about 15-30 Nucleotide, about 19-25 Nucleotide, or about 19-22 Nucleotide, should be appreciated that it comprises contains and any complete integer Nucleotide between 15 and 30) and opposite complement, typically separate by intervening sequence.According to some such embodiment, the cracking of transcribed spacer provides single stranded oligonucleotide fragment and opposite complement thereof, so that they can be annealed and form double-stranded siRNA polynucleotide.Randomly, extra procedure of processing can cause holding interpolation or removing one, two, three or more Nucleotide from the 3 ' end and/or 5 ' of arbitrary chain or two chains.In certain embodiments, described interval had before the transcribed spacer cracking and to allow described fragment and opposite complement annealing thereof and (for example to form duplex structure, as the hair clip polynucleotide) (and, randomly, can cause adding or removing one, two, the subsequent process steps of three or more Nucleotide from 3 ' end of each chain or two chains and/or 5 ' end) length.Therefore, intervening sequence can be any polynucleotide sequence between two complementary polynucleotide sequence zones, and described two complementary polynucleotide sequence zones comprise the siRNA polynucleotide when annealing forms double-strandednucleic acid.Intervening sequence can comprise at least 4 Nucleotide, although in certain embodiments, described interval can comprise 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21-25,26-30,31-40,41-50,51-70,71-90,91-110,111-150,151-200 or more Nucleotide.Example (for example, Brummelkamp etc., 2002 Science (science) 296:550 of the siRNA polynucleotide that derive from the single nucleotide chain that comprises two complementary nucleotide sequences that separated by the interval have been described; Paddison etc., 2002 GenesDevelop. (gene development) 16:948; Nat.Biotechnol. such as Paul (Nature Biotechnol) 20:505-508 (2002); Grabarek etc., Biotechniques (biotechnology) 34:734-44 (2003)).

Be applicable to that the carrier of expressing the siRNA polynucleotide can comprise such recombinant nucleic acid construct, promptly, it contains the promotor that the one or more RNA of being used for molecules are transcribed, for example, people U6 snRNA promotor (referring to, for example, Miyagishi etc., Nat.Biotechnol. (Nature Biotechnol) 20:497-500 (2002); Lee etc., Nat.Biotechnol. (Nature Biotechnol) 20:500-505 (2002); Paul etc., Nat.Biotechnol. (Nature Biotechnol) 20:505-508 (2002); Grabarek etc., BioTechniques (biotechnology) 34:73544 (2003); Also referring to Sui etc., Proc.Natl.Acad.Sci USA (NAS's journal) 99:5515-20 (2002)).Every chain of siRNA polynucleotide can separately be transcribed, and every chain is transcribed under the guiding of promotor independently, and can hybridize in cell then to form siRNA polynucleotide duplex.Every chain can also be transcribed from isolated vectors (referring to, Lee etc., as previously mentioned).Alternatively, there are justice and antisense sequences under the control of single promotor, to transcribe to RPTP (LAR, RPTP-σ and/or RPTP-δ) is sequence-specific, thus siRNA polynucleotide formation hair clip molecule (Paul etc., as previously mentioned).In this case, the complementary strand of siRNA specific sequence is by separating at interval, and described interval comprises at least 4 Nucleotide, but can comprise at least 5,6,7,8,9,10,11,12,13,14,15,16,17, or 18 Nucleotide or more Nucleotide, as described herein.In addition, form hair clip the siRNAs that under the control of U6 promotor, transcribes can 3 ' end have about 4 uridines that act as transcription termination signal fragment (Miyagishi etc., as previously mentioned; Paul etc., as previously mentioned).Shuo Ming mode by way of example, if target sequence is 19 Nucleotide, siRNA hair clip polynucleotide (5 ' end is initial) have thereafter the adopted sequence that has of 19 Nucleotide of (it has two uridine Nucleotide that 3 of adopted sequence ' end is arranged of contiguous described 19 Nucleotide) then at interval so, and described interval is connected on the antisense sequences of 19 Nucleotide following 4 uridine terminator sequences thereafter, and described 4 uridine terminator sequences form overhang.RNA interfering polynucleotide with weak point of such overhang disturb the target polypeptide expression (referring to, Miyagishi etc., as previously mentioned effectively; Paul etc., as previously mentioned).Recombinant precursor can also use another kind of rna plymerase iii promotor, H1 RNA promotor, and prepare, described promotor can be connected to operability on the special sequence of siRNA polynucleotide, described recombinant precursor can be used for transcribing the hairpin structure that comprises described siRNA specific sequence, perhaps separately transcribe siRNA duplex polynucleotide every chain (referring to, for example, Brummelkamp etc., Science (science) 296:550-53 (2002); Paddison etc., as previously mentioned).The dna vector that is used to insert the sequence of transcribing the siRNA polynucleotide comprise the pSUPER carrier (referring to, for example, Brummelkamp etc., as previously mentioned); Be derived from pCWRSVN the pAV carrier (referring to, for example, Paul etc., as previously mentioned); And pIND (referring to, for example, Lee etc., as previously mentioned), or the like.

The RPTP polypeptide can be expressed in mammalian cell, yeast, bacterium or other cell under suitable promotor control, therefore provide system, and described system can be used to identify with characteristic and describes the siRNA polynucleotide that can disturb as expression of polypeptides provided herein.Suitable clone and the expression vector used with protokaryon and eucaryon host have been described, for example, by Sambrook, Deng, Molecular Cloning:A Laboratory Manual (molecular cloning: laboratory manual), the 3rd edition, the cold spring port, New York, (2001).

These siRNA can be used for suppressing, reduce or eliminate one or more the expression in LAR, RPTP-σ and RPTP-δ or their variant, therefore change the immunoreactivity of immunocyte, and can be used for treating experimenter or the host who suffers from inflammatory or autoimmune disorders or the cardiovascular or metabolic trouble relevant with the expression of one or more RPTPs or overexpression.Use the siRNA molecule to disturb rat LAR, RPTP-σ and the RPTP-δ expression (Dunah etc., Nat.Neurosci. (Nature Neuroscience) 8:458-67 (2005)) in hippocampal neuron effectively.

In one embodiment, the siRNA molecule has influences the RNAi of LAR rna expression activity, and wherein said siRNA molecule comprises the sequence with the RNA complementary element of coding LAR polypeptide or its variant, and it includes but not limited to those sequences as herein described.In another embodiment, the siRNA molecule has the RNAi activity that influences RPTP-σ or RPTP-δ rna expression, wherein said siRNA molecule comprises the RNA complementary sequence with encode respectively RPTP-σ or coding RPTP-δ polypeptide or their variant, and it includes but not limited to those sequences as herein described.In some other embodiment, the siRNA molecule has the RNAi activity that influences at least two kinds expression among LAR RNA, RPTP-σ RNA and the RPTP-δ RNA.Suppress, implement to reduce or eliminate at least two kinds of codings RPTP (s) expression such siRNA identification, in conjunction with or hybridize in the part of the encoding sequence total and identical with at least two kinds of RPTP nucleotide sequences.In another embodiment, siRNA can suppress, implement to reduce or eliminate the expression of LAR RNA, RPTP-σ RNA and RPTP-δ RNA, and identification, in conjunction with or hybridization and whole three kinds of RPTP nucleotide sequences have and the part of identical encoding sequence.

As described herein, the nucleotides sequence of the every kind of LAR that encodes, RPTP-σ and RPTP-δ is listed on the specific position of described polynucleotide and enjoys the sequence homogeny.Such homology or identical sequence can for example, be used sequence alignment according to method known in the art and as herein described, identify.The siRNA molecule can be designed to the such homologous sequence of target, for example, uses complete complementary sequence or by in conjunction with nonstandard base pair, for example, mispairing and/or wobble base are right, its can provide other target sequence (referring to, for example, Application No. 2005/0137155).

The siRNA molecule comprises and has and coding LAR, RPTP-σ and/or the nucleotide sequence of RPTP-δ polypeptide or the antisense strand of its part complementary nucleotide sequence, and can comprise sense strand, wherein said sense strand comprises the nucleotide sequence of LAR, RPTP-σ and/or RPTP-δ gene or mRNA or their part.In one embodiment, the siRNA molecule comprises and has about 15,16,17,18,19,20, or the antisense strand of 21 Nucleotide, and about in another embodiment 19 to about 30 (for example, about 19,20,21,22,23,24,25,26,27,28,29, or 30) Nucleotide, the RNA sequence complementation of one or more among wherein said antisense strand and coding LAR, RPTP-σ and the RPTP-δ.In some other embodiment, described siRNA also comprise have about 16,17,18,19,20, or the sense strand of 21 Nucleotide, and about in another embodiment 19 to about 30 (for example, about 19,20,21,22,23,24,25,26,27,28,29, or 30) Nucleotide.Described sense strand is the different nucleotide sequence that has at least about 19 complementary nucleotides with antisense strand.The nucleotide sequence of described siRNA polynucleotide can be identical with the part of polynucleotide sequence of coding RPTP as herein described, and perhaps described nucleotide sequence can have one, two, three or four Nucleotide differences.Have been found that the simple point mutation with respect to target sequence is effective for suppressing.

Various algorithms can be used for determining the sequence of siRNA molecule.Usually, the zone of the target polynucleotide sequence that will avoid when design siRNA comprises: the zone in (1) 50-100 base pair in initiator codon or terminator codon; (2) intron zone; The fragment of (3) 4 or more a plurality of identical bases; (4) have and be lower than 30% or greater than the zone of 60% GC content; (5) multiple and low multiplexed sequence.A kind of algorithm that can be used for designing the siRNA of the expression that suppresses LAR, RPTP-σ and/or RPTP-δ gene or mRNA is called Tuschl rule (Elbashir etc., Nature (nature) 411:494-98 (2001); .EMBO J. such as Elbashir (fetology magazine) 20:6877-88 (2001); Elbashir etc., Methods (method) 26:199-213 (2002)).Be chosen in the target area of 50-100 the Nucleotide in initiator codon downstream, its sequence comprises (1) 23 nucleotide sequence motif AA (N with preferred order ₁₉); (2) 23 nucleotide sequence motif (NA (N ₂₁); To there be 3 of adopted siRNA ' end to change into TT; (3) NAR (N ₁₇) YNN, wherein R=A or G (purine); Y-T or C (pyrimidine), and any Nucleotide of N=.Described target sequence should have about 50% GC content.The method (Dharmacon, company) that another kind is called rational siRNA design for the feature of special sequence give point value (referring to, for example, Reynolds etc., Nat.Biotechnol. (Nature Biotechnol) 22:326-30 (2004)).In addition, some suppliers based on target sequence use proprietary algorithm design and preparation siRNA molecule (referring to, for example, Ambion, company, Austin, TX, the algorithm of Cenix bio-science (Cenix Bioscience) exploitation; Qiagen, company, Valencia, CA).

SiRNA does not modify or chemically modified, and can chemosynthesis, and from vector expression, perhaps enzymatic is synthetic.The application of the siRNA of chemically modified improves the numerous characteristics of natural siRNA molecule, for example, take in to the resistance of nucleic acid in vivo enzyme liberating and/or by the cell that improves and to improve by improving (referring to, for example, Application No. 2005/0137155).

The inhibition of genetic expression is meant the minimizing (or observable minimizing) of the level of the albumen of target gene of own coding LAR, RPTP-σ or RPTP-δ and/or mRNA product.Specificity is meant the ability that suppresses target gene and do not show the obvious effect of other gene of pair cell.The cell analysis (FACS) of characteristic that the result who suppresses can be by inspection cell or organism or genetic expression monitoring, antibodies, enzyme-linked immunosorbent assay (ELISA), western blotting, radioimmunoassay (RIA), other immunoassay and the fluorescence-activation by Measurement for Biochemistry such as RNA solution hybridization, nuclease protection, RNA hybridization, reverse transcription, use microarray confirms.For the inhibition of the mediation of RNA-in clone or whole organism, genetic expression detects by report or the drug resistant gene that uses its protein product to measure easily expediently.The example of reporter gene comprises acetohydroxy acid synthetase (AHAS), alkaline phosphatase (AP), beta galactosidase enzyme (LacZ), β glycuronidase (glucoronidase) (GUS), E.C. 2.3.1.28 (CAT), green fluorescent protein (GFP), horseradish peroxidase (HRP), luciferase (Luc), nopaline synthetic enzyme (NOS), octopine synthase (OCS), and their derivative.The multiple choices mark of giving penbritin, bleomycin, paraxin, gentamicin, Totomycin, kantlex, lincomycin, methotrexate, phosphinothricin, tetracycline and tetracyclin resistance is an available.

Antisense polynucleotides and ribozyme

Antisense polynucleotides combines with sequence-specific mode and nucleic acid such as mRNA or DNA.Identify that the DNA that is used for the gene that target spot sends as the oligonucleotide of antisense reagent and ribozyme and identification code comprises method well known in the art.For example, the characteristic of the needs of such oligonucleotide, length and further feature are known.Antisense technology can be used for by disturbing polysaccharase, transcription factor or other to regulate the combination of molecule controlling gene express (referring to, Gee etc., at Huber and Carr, among the Molecular and Immunologic Approaches (molecule and immunological method), Futura publishing company. (Mt.Kisco, NY; 1994)).Antisense polynucleotides can also change any the genetic expression among LAR, RPTP-σ and/or the RPTP-δ, its by specificity with do not translate and can be to regulate the encoding gene of sequence of sequence or the part hybridization of mRNA changes.Can design control area (for example, promotor, enhanser or the transcription initiation site) hybridization of such antisense molecule and RPTP gene, and block described gene transcription or block translation with ribosomal the combination by suppressing transcript.

When combining with mRNA with complementary sequence, antisense prevent described mRNA translation (referring to, for example, U.S. Patent number 5,168,053; U.S. Patent number 5,190,931; U.S. Patent number 5,135,917; U.S. Patent number 5,087,617; Clusel etc., Nucleic Acids Res. (nucleic acids research) 21:3405-3411 (1993), it has described reticent antisense oligonucleotide (dumbbell antisenseoligonucleotides)).The triplex molecule is meant the unique DNA chain in conjunction with duplex DNA, forms the triplex molecule of collinearity, prevent from thus to transcribe (referring to, for example, U.S. Patent number 5,176,996, it has described the method for preparing the synthetic oligonucleotide that is combined in the target spot site on the duplex DNA; Also referring to, for example, Helene, Anticancer Drug Des. (cancer therapy drug design) 6:569-84 (1991); Helene etc., Ann.N Y.Acad.Sci. (NYAS's annual) 660:27-36 (1992); Maher, Bioassays (biological assay) 14:807-15 (1992)).

Antisense polynucleotides comprises and the adopted polynucleotide complementary of having of proteins encoded nucleotide sequence, for example, with the coding strand of double-stranded cDNA molecule complementary or with the complementation of mRNA sequence.Therefore, antisense polynucleotides can with adopted polynucleotide hydrogen bonded is arranged.Described antisense polynucleotides can with complete RPTP coding strand or only with its part complementation.In one embodiment, the antisense polynucleotides molecule is to the coding region antisense of the polynucleotide of coding LAR, RPTP-σ or RPTP-δ.The part that described antisense polynucleotides can comprise the nucleotide sequence of LAR, RPTP-σ or RPTP-δ uniqueness is the sequence of antisense, and the part that perhaps can comprise the encoding sequence similar or identical with every kind of polynucleotide of coding LAR, RPTP-σ or RPTP-δ is the sequence of antisense.The term coding region is meant the zone of the nucleotide sequence that comprises the codon of translating into amino-acid residue.In another embodiment, described antisense nucleic acid molecule is to any " non-coding region " antisense of coding strand of nucleotide sequence among coding LAR, RPTP-σ or the RPTP-δ.Term " non-coding region " is meant that not translating into amino acid whose side connects 5 of coding region ' and 3 ' sequence (that is, also be called 5 ' and 3 ' untranslated region).

According to the disclosed herein and coding strand sequence of available coding RPTPs in the art, can be according to Wo Sen and Ke Like base pairing rules design antisense polynucleotides.Described antisense polynucleotides can with the whole coding region complementation of RPTP mRNA, for example, perhaps can be only to the oligonucleotide of the part antisense of the coding of RPTPmRNA or non-coding region.For example, described antisense oligonucleotide can with the regional complementarity around the translation initiation site of RPTP mRNA.Antisense oligonucleotide length can be, and is for example about 5,10,15,20,25,30,35,40,45 or 50 Nucleotide or more.Antisense nucleic acid is can applied chemistry synthetic and use the enzymatic ligation of methods known in the art and make up.For example, antisense nucleic acid (for example, antisense oligonucleotide) can use the Nucleotide of naturally occurring Nucleotide or different modifying and chemosynthesis, the Nucleotide of described different modifying is designed to improve the biologically stable of molecule or improves at antisense and the physical stability of the duplex that forms between the phosphorothioate odn is arranged, for example, the Nucleotide that can use thiophosphoric acid derivative and acridine to replace.

By using such connection as thiophosphatephosphorothioate, methyl phosphorodithioate, sulfone, sulfuric ester, ketyl, phosphorodithioate, phosphoramidate, phosphoric acid ester and the connection other, typically design antisense oligonucleotide with the degraded of anti-endogenous nucleic acid degrading enzyme (referring to, for example, Agrwal etc., Tetrahedron Lett. (tetrahedron communication) 28:3539-42 (1987); Miller etc., J.Am.Chem.Soc. (U.S. chemical institute magazine) 93:6657-65 (1971); Stec etc., Tetrahedron Lett. (tetrahedron communication) 26:2191-2194 (1985); Moody etc., Nucleic Acids Res. (nucleic acids research) 12:4769-82 (1989); Uznanski etc., Nucleic Acids Res. (nucleic acids research) 17:4863-71 (1989); Letsinger etc., Tetrahedron (tetrahedron) 40:137-43 (1984); Eckstein, Annu.Rev.Biochem. (biological chemistry summary annual) 54:367-402 (1985); Eckstein, Trends Biol.Sci (bio-science trend) 14:97-100 (1989); Stein: Oligodeoxynucleotides.Antisense Inhibitors of Gene Expression (oligodeoxynucleotide. the antisense inhibitor of genetic expression) in, Cohen compiles, and Macmillan publishes, London, 97-117 page or leaf (1989); Jager etc., Biochemistry (biological chemistry) 27:7237-46 (1988)).Can comprise 5 FU 5 fluorouracil with the example of the Nucleotide of the modification that generates antisense nucleic acid, 5-bromouracil, the 5-chlorouracil, 5-iodouracil, xanthoglobulin, xanthine (xantine), the 4-acetylcytosine, 5-(carboxyl hydroxymethyl) uridylic, 5-carboxyl methylamino methyl-2-thio uridine, 5-carboxyl methylamino 6-Methyl Uracil, dihydrouracil, β-D-galactosyl queosine, inosine, N6-isopentenyl gland purine, the 1-methyl guanine, the 1-methylinosine, 2, the 2-dimethylguanine, the 2-methyladenine, the 2-methyl guanine, 3-methylcystein, 5-methylcytosine, the N6-VITAMIN B4, the 7-methyl guanine, 5-methylamino 6-Methyl Uracil, 5-methoxyl group amino methyl-2-thiouracil, β-D-mannose group queosine, 5 '-methoxyl group carboxyl 6-Methyl Uracil, 5-methoxyuracil, 2-methylthio group-N6-isopentenyl gland purine, uridylic-the 5-oxyacetic acid (v), bosom fourth glycosides (wybutoxosine), pseudouracil, queosine, 2-sulfo-cytosine(Cyt), 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, methyl uracil, uridylic-5-oxyacetic acid methyl ester, uridylic-5-oxyacetic acid (v), 5 methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxyl propyl group) uridylic, (acp3) w, and 2,6-diaminopurine.Alternatively, described antisense polynucleotides (or oligonucleotide) can use wherein with antisense orientation (that is, the RNA from the transcribed nucleic acid that inserted should be the antisense orientation of purpose target polynucleotide) subclone the expression of nucleic acids carrier and biological the generation.

To typically be administered to experimenter or generation in position to the special antisense polynucleotides of one or more polynucleotide of coding LAR, RPTP-σ or RPTP-δ, so that cell mRNA and/or the genomic dna of coding RPTP are hybridized or be incorporated into to described antisense polynucleotides, with the expression of arrestin thus, for example, undertaken by suppressing to transcribe and/or to translate.Hybridization can be by the conventional Nucleotide complementarity that causes stable duplex to form, and perhaps, for example, when antisense polynucleotides during in conjunction with DNA duplex, described antisense polynucleotides is combined in the double-helical main chase groove by special interaction and carries out.

Antisense polynucleotides can be by being administered to host or experimenter at tissue site's direct injection.Alternatively, the cell of selecting with target, systemic application then can be modified or be processed to antisense polynucleotides.For example, for systemic application, antisense molecule can be modified, so that their specificitys are combined in the acceptor or the antigen of expressing on the selected cell surface, for example, by carrying out with described antisense nucleic acid molecule with cell surface receptor or antigen bonded peptide or antibodies.Antisense polynucleotides can also use the as herein described and used carrier in this area and be delivered to cell.In order to obtain the antisense molecule of enough ICs, can carrier construction, so that described antisense polynucleotides is under the control of strong pol II or pol III promotor.

In another embodiment, described antisense polynucleotides is a α-different nucleic acid molecule.α-different nucleic acid molecule and complementary RNA form special double-stranded hybrid, and be wherein opposite with the β-unit of routine, chain trend parallel to each other (Gaultier etc. (1987) Nucleic Acids.Res. (nucleic acids research) 15:6625-6641).Antisense nucleic acid molecule can also comprise 2 '-o-methyl ribonucleotides (Inoue etc., Nucleic Acids Res. (nucleic acids research) 15:6131-6148 (1987)) or chimeric RNA-DNA analogue (Inoue etc., FEBS Lett (FEBS communication) 215:327-330 (1987)).

In another embodiment, the immunoreactivity of immunocyte can contact with ribozyme and changes by expressing one or more cell among LAR, RPTP-σ or the RPTP-δ.Ribozyme is the catalysis RNA molecule with ribonuclease activity, and it is cracking single-chain nucleic acid such as mRNA specifically, and ribozyme has complementary district with it, causes the specificity of cellular gene expression to suppress or interference.The cracking of at least five kinds of known ribozyme kind participation RNA chains and/or connection (for example, hammerhead ribozyme, it is at Haselhoff and Gerlach (describing among Nature (nature) 334:585-591 (1988)).Ribozyme can any rna transcription thing of target, and can catalytic pyrolysis such transcript (referring to, for example, U.S. Patent number 5,272,262; U.S. Patent number 5,144,019; With U.S. Patent number 5,168,053,5,180,818,5,116,742 and 5,093,246).Therefore, based on as described herein and, can design the ribozyme special to the RPTP-coding nucleic acid at the nucleotide sequence of this area available RPTP.For example, can make up the derivative of thermophilas L-19 IVS RNA, wherein the nucleotide sequence of avtive spot with will cracked nucleotide sequence complementation in RPTP-encodes mRNA.(referring to, for example, Cech etc. U.S. Patent number 4,987,071; With Cech etc. U.S. Patent number 5,116,742).Alternatively, the mRNA molecule of coding RPTP can be used for from the set of RNA molecule selecting to have the catalytic RNA of specific ribonucleic acid enzymic activity (referring to, for example, Bartel etc., Science (science) 261:1411-18 (1993)).

Peptide nucleic acid(PNA)

In another embodiment, the deoxyribose phosphate main chain of polynucleotide (or its part) that can be by modifying coding any RPTPs as herein described prepare peptide nucleic acid(PNA) (PNAs) (referring to, for example, Hyrup B. etc., Bioorganic; Medicinal Chemistry (biological organic and medicinal chemistry) 4:5-23 (1996)).Term " peptide nucleic acid(PNA) " or " PNA " are meant nucleic acid mimics, for example, dna analog, wherein the deoxyribose phosphate main chain is replaced by false peptide main chain, wherein only keeps 4 natural nuclear bases.Show that the neutral main chain of PNA allows under low ionic strength and DNA and RNA specific hybrid.PNA oligomer synthetic can use the solid-phase peptide synthetic method of standard and carry out (referring to, for example, Hyrup B., as previously mentioned; Perry-O ' Keefe etc., Proc.Natl.Acad.Sci USA (NAS's journal) 93:14670-75 (1996)).Can be with antisense that acts on the sequence-specific regulate gene expression or inverted defined gene reagent to one or more the special pna molecules among LAR, RPTP-σ and the RPTP-δ, for example, stagnate or undertaken by suppressing to duplicate by inducible transcription or translation.

Fit

Fit is DNA or RNA molecule, strand normally, its be based on they in conjunction with the ability of other molecule from what select the hangar, described other molecule comprises nucleic acid, albumen, lipid etc.With different in conjunction with the polynucleotide of the sequence that comprises the desired polypeptides of encode and antisense polynucleotides that change is transcribed or translated, the RNA interfering (siRNA) or the ribozyme of lacking, fit can target and in conjunction with polypeptide.Fit can the selection from oligonucleotide library at random or unmodified in conjunction with the ability of special target spot by them, in this case, described special target spot be LAR, RPTP-δ and/or RPTP-σ (referring to, for example, U.S. Patent number 6,867,289; U.S. Patent number 5,567,588).Fit ability with the various 2 and 3 dimensional organizations of formation, and chemistry is multi-functional fully to have in their monomer available, with in fact any chemical compound, no matter be monomer or polymer, act as part (that is, form special combination to).The molecule or the composition of any size can be used as target spot.The method repeatedly of external selection can be used for enrichment has the kind of high-affinity to target spot library.This method comprises such recirculation: with the target spot incubation of described library with needs, from those of targeted integration the oligonucleotide of separated free, and amplification bonded oligonucleotide subclass is such as by using polymerase chain reaction (PCR).From the subpopulation of the selection of the sequence that target spot had high-affinity, subpopulation can carry out subclone, and special fit quilt checks in further detail, with identify the biological function that changes target spot fit (referring to, for example, U.S. Patent number 6,699,843).

The fit modification that can comprise any deoxyribonucleotide or ribonucleotide or these bases, such as deoxidation thiophosphatephosphorothioate (or thiophosphatephosphorothioate), its sulphur with replacement oxygen is as a kind of and disconnected part of phosphorus bonded.Monothio phosphoric acid ester α S has a sulphur atom, and is chirality around the phosphorus center therefore.Phosphorodithioate is substituted at two oxygen places, and is achirality therefore.Thiophosphoric acid Nucleotide can be purchased, and perhaps can synthesize by diverse ways more known in the art.

Antibody and antigen-binding fragment

The invention provides the antibody of specificity in conjunction with LAR, RPTP-δ or RPTP-σ; Specificity is in conjunction with the antibody of LAR and RPTP-δ; Specificity is in conjunction with the antibody of LAR and RPTP-σ; Specificity is in conjunction with the antibody of RPTP-δ and RPTP-σ; And specificity is in conjunction with the antibody of LAR, RPTP-δ and RPTP-σ and preparation and use the method for these antibody.These specific antibody can be polyclonal or monoclonal, separate described antibody subsequently by immune animal and prepare, and perhaps described antibody can be recombinant antibodies.Antibody as herein described is used for influencing the immunoreactivity of at least a immunocyte of expressing LAR, RPTP-δ and RPTP-σ.In certain embodiments, described antibody suppresses to express the immunoreactivity of at least a immunocyte among LAR, RPTP-δ and the RPTP-σ.Such antibody comprises immunocyte is shown those of the effect similar to poxvirus albumin A 41L or 130L.These antibody can competitive inhibition in conjunction with and/or weaken (that is, prevent, block, reduce) A41L (or alternatively, 130L) with the combining of immunocyte.In one embodiment, antibody or its antigen-binding fragment specificity is in conjunction with at least two kinds of RPTPs, and it can be among LAR, RPTP-δ and the RPTP-σ any two kinds, and the combining of competitive inhibition A41L (or 130L) and at least two kinds of RPTP polypeptide.In another embodiment, such antibody suppresses any the combining of immunocyte among A41L (or 130L) and expression LAR, RPTP-δ and the RPTP-σ.Therefore, the immunoreactivity of the immunocyte of any among described antibody or its antigen-binding fragment inhibition expression LAR, RPTP-δ and the RPTP-σ.In a special embodiment, antibody or its antigen-binding fragment, specificity is in conjunction with RPTP-δ and RPTP-σ, and suppress A41L or 130L and RPTP-δ or with RPTP-σ or with the two combine of RPTP-δ and RPTP-σ.In another embodiment, antibody or its antigen-binding fragment specificity are in conjunction with whole three kinds of LAR, RPTP-δ and RPTP-σ.

Antibody as herein described can be used for the treatment of or prevent, suppress, slow down the development relevant with Immunological diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness or hyperplasia or illness or reduce associated symptom.Immune disorders comprises inflammatory diseases or illness and autoimmune disorders or illness.Although inflammation or Inflammatory response are the reaction of host to the normal and protectiveness of damage, inflammation can cause unwanted infringement.For example, atherosclerosis to small part is the pathologic reaction to arterial injury and inflammatory cascade subsequently.Can be with the example of the immune disorders of antibody as herein described or its antigen-binding fragment treatment, include but not limited to, the multiple sclerosis disease, rheumatoid arthritis, system lupus erythematosus (SLE), graft versus host disease (GVHD), Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis and other inflammatory and muscle deterioration disease (for example, dermatomyositis, polymyositis, teenager's dermatomyositis, inclusion body myositis).Treatable cardiovascular disorder or illness, it can comprise disease and the illness that also is considered to Immunological diseases/illness, comprises, for example, atherosclerosis, endocarditis, hypertension or periphery local asphyxia disease.Metabolic trouble or illness comprise diabetes, obesity with relevant disease and the illness of mitochondrial function unusual or that change.

The method that any or multiple RPTPs as herein described can also be used for screening the sample that comprises antibody, described sample for example, the sample of antibody purified, antiserum(antisera) or cell culture supernatant maybe can contain any other biological sample to one or more special antibody of one or more described RPTPs.One or more described RPTPs can also be used for identifying and select the method for one or more B cells (for example, plaque forms to be measured, etc.) from biological sample, and described B cell produces the antibody of specificity in conjunction with one or more described RPTPs.Then, described B cell can be as the source of special antibody-coded polynucleotide, and described special antibody-coded polynucleotide can clone and/or modify by recombinant molecule biology techniques known in the art and as herein described.

When being used for this paper, if it preferably has more than or equal to about 10 with can detected level and one or more RPTPs reaction ⁴M ^-1, or more than or equal to about 10 ⁵M ^-1, more than or equal to about 10 ⁶M ^-1, more than or equal to about 10 ⁷M ^-1, or more than or equal to 10 ⁸M ^-1Affinity constant K _a, think antibody to one or more " immunologic opsonins " among LAR, RPTP-δ and the RPTP-σ, " specific " or with it " specificity in conjunction with " so.Antibody also is typically expressed as dissociation constant K to the avidity of its isogeneic _D, and if it is to be less than or equal to 10 ^-4M, be less than or equal to about 10 ^-5M, be less than or equal to about 10 ^-6M, be less than or equal to 10 ^-7M or be less than or equal to 10 ^-8The K of M _DIn conjunction with, so anti--RPTP antibodies specific is in conjunction with one or more RPTPs.

The avidity of binding partners or antibody can be used routine techniques and easily determine, for example, use Scatchard etc. (Ann.N.Y.Acad.Sci USA (USA New York academy of sciences annual) 51:660 (1949)) described those and by surperficial plasmon resonance (SPR; BIAcore ^TM, Biosensor (biosensor), Piscataway, NJ).For surperficial plasmon resonance, the target spot molecule is fixed on the solid phase, and is exposed at the part in the flow chamber mobile phase flows.If the generation part combines with the fixed target spot, the local refraction index changes so, causes the change at SPR angle, and it can the monitoring in real time by the variation of detection of reflected light intensity.Can analyze the velocity of variation of surperficial plasmon resonance signal, with the association of generation association reaction and the apparent speed constant of the state that dissociates.The ratio of these values provide apparent equilibrium constant (avidity) (referring to, for example, Wolff etc., CancerRes. (cancer research) 53:2560-2565 (1993)).

The binding characteristic of antibody and RPTP as herein described can use immunologic detection method to determine and measure usually, and described immunologic detection method comprises, for example, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, immunoblotting, counterimmunoelectrophoresis, radioimmunoassay, dot blotting is measured, suppress or competition assay, etc., its can easily carry out by those of ordinary skill in the art (referring to, for example, U.S. Patent number 4,376,110 and 4,486,530; Harlow etc., and Antibodies:A LaboratoryManual (antibody: laboratory manual), cold spring harbor laboratory (1988)).Method of immunity can comprise determine antibody whether specificity in conjunction with LAR, RPTP-δ and/or RPTP-σ and nonrecognition or with other Protein-tyrosine-phosphatase, the particularly contrast and the method for other receptor-like protein tyrosine phosphatase cross reaction.In addition, for detect reply be conjugated to that RPTP on the special carrier polypeptide produces host's immunity anti--RPTP (promptly, anti--LAR, anti--RPTP-δ and/or anti--RPTP-σ) antibody and the immunoassay carried out, can be used in combination be conjugated to be used for the immunity different carrier polypeptides on RPTP, to reduce or eliminate the antibody of the carrier polypeptide that detects the specificity binding immunoassay.Alternatively, the RPTP as herein described that does not put together with carrier molecule can be used for detecting the immunoassay of immunologic opsonin antibody.

In certain embodiments, antibody as herein described unique a kind of special among LAR, RPTP-δ and the RPTP-σ only.That is, for example, specificity does not combine with RPTP-δ or RPTP-σ specificity in conjunction with the antibody of LAR; Specificity does not combine with LAR or RPTP-σ specificity in conjunction with the antibody of RPTP-δ; And specificity does not combine with LAR or RPTP-δ specificity in conjunction with the antibody of RPTP-σ.As herein described specificity is in conjunction with the such epi-position of such antibodies of a kind of RPTP (antigenic determinant), promptly, described epi-position comprises not the aminoacid sequence with the same or analogous RPTP of aminoacid sequence that exists in another kind of RPTP, perhaps such antibodies specific is in conjunction with a conformational epitope that only exists on described antibodies specific bonded RPTP.Antibody for the specificity of special RPTP can use in this area available and the various immunoassay as herein described any and easily determine.

In other embodiments, antibody or its antigen-binding fragment are specifically in conjunction with at least two kinds among LAR, RPTP-δ and the RPTP-σ (that is, LAR and RPTP-δ; LAR and RPTP-σ, or RPTP-δ and RPTP-σ), and in other embodiments, antibody or its antigen-binding fragment specificity are in conjunction with whole three kinds of RPTPs as herein described.Specificity is present in epi-position (antigenic determinant) among every kind of RPTPs usually in conjunction with the antibody recognition of LAR, RPTP-δ and RPTP-σ.Can be included in at least two kinds of total antigenic determinants among LAR, RPTP-δ and the RPTP-σ or epi-position in each of described at least two kinds of RPTPs identical or or similar aminoacid sequence, perhaps can comprise the conformational epitope total at least two kinds of RPTPs, perhaps can comprise similar chemical structure, for example, the chemical structure that distributes and cause by the amino acid whose surface charge that described epi-position comprised.By way of example, the aminoacid sequence of listing in SEQ ID NO:54 (YSAPANLYV) is that among LAR, RPTP-δ and the RPTP-σ each is total.Therefore, incite somebody to action each that combine specifically among LAR, RPTP-δ and the RPTP-σ with such epi-position bonded antibody, described epi-position comprises this aminoacid sequence of second immunoglobulin like domain that is positioned at every kind of RPTP.

Antibody can be prepared by in the known various technology of those of ordinary skill in the art any usually.Referring to, for example, Harlow etc., Antibodies:A Laboratory Manual (antibody: laboratory manual), cold spring harbor laboratory (1988); Peterson, ILAR J. (ILAR magazine) 46:314-19 (2005)).RPTPs as herein described, or its peptide or segmental any, the cell of perhaps expressing one or more described RPTPs can be used to produce polyclonal antibody or monoclonal antibody as the immunogen of immune animal.Can comprise bigger fragment as the fragment of immunogenic every kind of RPTP, such as zone, extracellular (it comprises three immunoglobulin (Ig) (Ig) structural domains and fibronectin structural domain) and intracellular region territory (it comprises two phosphatase catalytic structural domain D1 and D2), or its littler fragment.

Immunogen can comprise the part in zone, extracellular, such as at least a Ig structural domain or its part or at least a fibronectin structural domain or its part.RPTP peptide and polypeptide immunogen can be used for producing and/or identify and can change immunoreactive antibody or its antigen-binding fragment of (with statistics remarkable or the significant mode of biology increase or reduces, preferably minimizing) immunocyte.Exemplary peptide based immunogens can comprise 6,7,8,9,10,11,12 of LAR provided herein, RPTP-δ or RPTP-σ (or its variant), 20-25,21-50,26-30,31-40,41-50,51-60,61-70, or 71-75 successive amino acid.For example, be derived from the peptide of Ig structural domain, such as the SEQ ID NO:53 (SGALQIEQSEESDQGK) of RPTP-δ; SEQ ID NO:54 (YSAPANLYV); SEQ ID NO:55 (WMLGAEDLTPEDDMPIGR); Can be used as immunogen with SEQ ID NO:56 (NVLELNDVR).The example of peptide that is derived from the fibronectin III tumor-necrosis factor glycoproteins of RPTP-δ comprises SEQ ID NO:57 (GPPSEPVLTQTSEQAPSSAPR); SEQID NO:58 (SPQGLGASTAEISAR); SEQ ID NO:59 (YTAVDGEDDKPHEILGIPSDTTK); SEQ ID NO:60 (VGFGEEMVK); With SEQ ID NO:61 (GPGPYSPSVQFR).The example of peptide that is derived from the fibronectin III tumor-necrosis factor glycoproteins of RPTP-σ comprises SEQ ID NO:45 (SIGQGPPSESVVTR); SEQ ID NO:46 (HNVDDSLLTTVGSLLEDETYVR); SEQ ID NO:47 (VLAFTSVGDGPLSDPIQVK); SEQ ID NO:48 (TEVGPGPESSPVVVR); SEQ ID NO:49 (WEPPAGTAEDQVLGYR); With SEQ ID NO:50 (TSVLLSWEFPDNYNSPTPYK).Specificity estimates not suppress competitively combining of (or slackening) poxvirus polypeptide such as A41L or 130L and RPTP in conjunction with the antibody that is present in the antigenic determinant (epi-position) on the intracellular portion of RPTP, and reason is that described viral polypeptide may change the immunne response of immunocyte by the extracellular part in conjunction with cell-surface antigens such as LAR, RPTP-δ and/or RPTP-σ.Specificity can be used in combination with immunoreactivity that changes immunocyte and the bonded antibody (or other reagent) of competitive inhibition A41L or 130L and at least a RPTP in conjunction with the antibody of the intracellular portion of RPTP.Therefore, comprise from cell intracellular domain catalyst structure domain particularly, the peptide of the aminoacid sequence of D1 or D2 and fragment also can be used as immunogen (for example, the SEQ ID NO:51 (TEVGPGPESSPVVVR) of RPTP-σ).

Comprise A41L or the 130L part of bonded RPTP with it as immunogenic RPTP peptide and fragment.Can identify by making up the RPTP extracellular domain polypeptide that wherein lacks one or more extracellular domains with A41L or the interactional RPTP structural domain of 130L.By way of example, for example, fusion polypeptide can be got rid of the fibronectin structural domain of RPTP, and therefore comprises unique one, two or three RPTP Ig-spline structure territories.Such RPTP Ig-spline structure domain polypeptide can be fused on immunoglobulin Fc polypeptide or its mutain, and comprise and be fused to following on the Fc polypeptide: first immunoglobulin like domain of RPTP, first and second immunoglobulin like domain, the first and the 3rd immunoglobulin like domain, the second or the 3rd immunoglobulin like domain, perhaps whole three kinds of immunoglobulin like domain.Such RPTP Ig-spline structure domain polypeptide can also be used to identify and definite poxvirus polypeptide in conjunction with or cell ligand in conjunction with the degree of RPTP immunoglobulin like domain.

A kind of definite LAR, RPTP-δ and RPTP-σ any poxvirus polypeptide binding site or the method for the aminoacid sequence of the part of binding site comprise the peptide mapping technology.For example, LAR, RPTP-δ or RPTP-σ peptide can carry out proteolytic digestion and produce at random by any one or more that uses various proteolytic enzyme, described peptide (is for example separated and/or separates, by gel electrophoresis, column chromatography), determine poxvirus polypeptide such as A41L or 130L then in conjunction with which kind of peptide, and the described peptide of sequential analysis then.The RPTP peptide can also use recombination method as herein described and that implement this area to produce.The peptide that produces at random by recombination method can also be used to preparing peptide combinatorial library or the phage library in described herein and this area.Alternatively, the aminoacid sequence of LAR, RPTP-σ and/or RPTP-δ and the interactional part of poxvirus polypeptide can be by the part of Phosphoric acid esterase or Phosphoric acid esterase, for example, the computer simulation of the extracellular part of Ig structural domain and determining, and/or X-ray crystallization process (it can comprise the crystalline preparation of having only Phosphoric acid esterase or Phosphoric acid esterase-viral polypeptide complex body and analyze) and determining.

The immunogen peptide of LAR, RPTP-δ or RPTP-σ can also be determined to determine the wetting ability collection of illustrative plates by the aminoacid sequence of Computer Analysis RPTP.The part of the accessible antibody of RPTP most likely contacts with aqueous environments and is hydrophilic described proteic part.Hydrophilic region can use those skilled in the art's available computer program to determine, and it be each amino acid appointment " hydrophilic index " in the albumen, and draws a diagram then.

Preparation is used for being expelled to the immunogen of animal, particularly polypeptide fragment or peptide, can comprise RPTP fragment or peptide (or its variant) covalent coupling to another kind of immunogen protein, for example, carrier proteins is such as keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) etc.Polypeptide or peptide based immunogens can comprise the one or more extra amino acid that promotes to put together step (for example, adding halfcystine to promote puting together of peptide and KLH) at N end or C end.Other amino-acid residue in polypeptide or peptide can be substituted, to prevent (for example puting together at described special amino acid position and carrier polypeptide, interior location at polypeptide/peptide replaces halfcystine with serine residue), perhaps can be substituted to promote solvability or to increase immunogenicity.

This paper relates to and the antibody described can belong to any immunoglobulin (Ig) kind, for example, and IgG, IgE, IgM, IgD, or IgA.It can available from or derive from animal, for example, poultry (for example, chicken) and Mammals, it includes but not limited to mouse, rat, hamster, rabbit or other rodent, ox, horse, sheep, goat, camel, people or other primates.Described antibody can be the antibody of internalization.In a kind of such technology, animal is carried out immunity with RPTP as herein described or its fragment as antigen, to produce polyclonal antiserum.Suitable animal comprises, for example, and rabbit, sheep, goat, pig, ox, and can comprise littler mammalian species, such as mouse, rat and hamster, or other species.

Specificity in conjunction with the polyclonal antibody of LAR, RPTP-δ and/or RPTP-σ can use method as herein described and that those skilled in the art implements be prepared (referring to, for example, Green etc., " Production of Polyclonal Antisera (production of polyclonal antiserum); " (Manson in Immunochemical Protocols (immuno-chemical method), ed.), 1-5 page or leaf (Humana press 1992); Harlow etc., and Antibodies:A Laboratory Manual (antibody: laboratory manual), cold spring harbor laboratory (1988); Williams etc., " Expression of foreignproteins in E.coli using plasmid vectors and purification of specific polyclonalantibodies (using plasmid vector at expression in escherichia coli foreign protein and purification specificity polyclonal antibody); " at DNA Cloning 2:Expression Systems (dna clone 2: expression system), the 2nd edition, Glover etc. (eds.), the 15th page (Oxford University Press (1995)).Although polyclonal antibody typically produces in animal such as rat, mouse, rabbit, goat, ox or sheep, anti--RPTP antibody can also obtain from the human primate in Asia.For example, at international application published WO 91/11465 (1991) with at Losman etc., Int.J.Cancer (international journal of cancer) 46:310 can find in 1990 and produce diagnosis and the treatment current techique with antibody in baboon (baboon).

In addition, LAR, RPTP-δ and/or RPTP-σ polypeptide, its fragment or peptide or express one or more these as the cell of immunogenic RPTPs, can emulsification in adjuvant.Referring to, for example, Harlow etc., Antibodies:A Laboratory Manual (antibody: laboratory manual), cold spring harbor laboratory (1988).The adjuvant that typically is used for immune non-human animal includes but not limited to Freund's complete adjuvant, Freund's incomplete adjuvant, montanide ISA, Ribi adjuvant system (RAS) (Corixa company, the Seattle, WA), and the antigen of soluble cotton-absorption.Immunogen can be expelled in the animal by any amount of different approach, comprises intraperitoneal, intravenously, intramuscular, intracutaneous, intraocular or subcutaneous.Usually, after injection for the first time, according to can be especially according to antigen, adjuvant (if there is) and/or animal species and different preferred arrangements of time especially, animals received one or many booster immunization.Immunne response can be by regularly taking a blood sample to animal, serum is separated from the blood of collecting, and serum is analyzed in immunoassay such as ELISA or slab gel bidirectional diffusion mensuration (Ouchterlonydiffusion assay) etc.,, and monitored with definite concrete antibody titers.In case determine enough antibody titerss, animal regularly can be taken a blood sample, to gather polyclonal antiserum.Then, can be from such antiserum(antisera) purification specificity in conjunction with the polyclonal antibody of LAR, RPTP-δ and/or RPTP-σ, for example, by use be fixed on a-protein on the suitable solid support or protein G affinity chromatography (referring to, for example, Coligan, as previously mentioned, 2.7.1-2.7.1 2; 2.9.1-2.9.3 page or leaf; Baines etc., Purification of Immunoglobulin G (IgG) (purifying of immunoglobulin G (IgG)), in Methods in Molecular Biology (molecular biology method), 10:9-104 (Humana press, company (1992)).Alternatively, affinity chromatography can be carried out like this, wherein is fixed on the suitable solid support with RPTP or to the special antibody of Ig constant region of animal species of immunity especially.

Can also prepare specificity in conjunction with LAR, the monoclonal antibody of RPTP-δ and/or RPTP-σ and hybridoma, described hybridoma is the example of infinite multiplication eukaryotic cell lines, its generation has the monoclonal antibody of the binding specificity that needs, for example, use the technology (Nature (nature) of Kohler and Milstein, 256:495-97 (1976), Eur.J.Immunol. (European Journal of Immunology) (6:511-19 (1975)) and improvement thereof (referring to, for example, Coligan etc. (eds.), Current Protocols inImmunology (Immunization Update method), 1: 2.5.1-2.6.7 (John Wiley ﹠amp; Sons 1991); U.S. Patent number 4,902,614,4,543,439 and 4,411,993; Monoclonal Antibodies, and Hybridomas:A New Dimension in Biological Analyses (monoclonal antibody, hybridoma: the new dimension of biological analysis), Plenum press, Kennett etc. (eds.) (1980); With Antibodies:A Laboratory Manual (antibody: laboratory manual), Harlow and Lane (eds.), press of cold spring harbor laboratory (1988); Also referring to, for example, Brand etc., Planta Med. (plant medical science) 70:986-92 (2004); Pasqualini etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 101:257-59 (2004)) be prepared.With animal, for example, rat, hamster or more common mouse are with the RPTP immunogen immune of preparation as indicated above.After initial injection back (injection can be used by about in some approach that produce polyclonal antibody any as herein described) and/or booster shots, can be by obtaining serum sample, and use in immunologic detection methods known in the art and more as herein described any and detect existence in conjunction with the antibody of LAR, RPTP-δ and/or RPTP-σ, and the existence that the monitoring specific antibody is produced.

Pipette lymphocyte from the animal that produces in conjunction with the antibody of LAR, RPTP-δ and/or RPTP-σ, from the modal cell of spleen or lymphoglandula, to obtain the B-lymphocyte, it is the lymphocyte as the cell that forms antibody.Described lymphocyte, splenocyte typically, can by with the myelomatosis of medicine sensitization (for example, plasmoma) the cytogamy mating partner merges and infinite multiplication, preferably with immune animal homology and the cell that randomly has other characteristic that needs (for example, can not express endogenous Ig gene product such as P3X63-Ag 8.653 (ATCC No.CRL 1580); NS0, SP20)).Described lymphocyte and myeloma cell can use film to merge promotor such as polyoxyethylene glycol or nonionic detergent in conjunction with several minutes, are coated on the selective medium of myeloma cell's growth of supporting hybridoma rather than not merging with low density then.Preferred selective medium is HAT (xanthoglobulin, aminopterinum, a thymidine).Behind grace time, common about one to two week, observe the bacterium colony of cell.It is active to the combination of LAR, RPTP-δ and/or RPTP-σ to detect the antibody that is produced by described cell.With described hybridoma clone (for example, separating), and select and cultivate the positive colony that produces the antibody of described antigen-specific by limited dilution cloning or by the soft agar plaque.The preferred hybridoma that LAR, RPTP-δ and/or RPTP-σ are had high-affinity and specific monoclonal antibody that produces.

Monoclonal antibody can be separated from the supernatant of hybridoma culture.The alternative approach of producing the mouse resource monoclonal antibody is that described hybridoma is expelled in the peritoneal cavity of homology mouse, for example, and in treated (for example, pristane-excite) mouse peritoneum chamber, with the formation of the ascites that promotes to contain monoclonal antibody.Pollutent can by routine techniques such as chromatography (for example, size exclusion, ion-exchange), gel-filtration, precipitation, extraction etc. (referring to, Coligan for example, as previously mentioned, 2.7.1-2.7.12; 2.9.1-2.9.3 page or leaf; Baines etc., Purification of Immunoglobulin G (IgG) (purifying of immunoglobulin G (IgG)), in Methods in Molecular Biology (molecular biology method), 10:9-104 (Humana press, company (1992)) and removal from the ascites of collecting subsequently (usually at 1-3 in week).For example, antibody can pass through affinitive layer purification, and it uses the suitable part that special character based on described monoclonal antibody (for example, heavy chain or light chain isotype, binding specificity, etc.) selects and carries out.The example that is fixed on the suitable part on the solid support comprises a-protein, protein G and anti--constant region (light chain or heavy chain) antibody, antiidiotypic antibody, LAR, RPTP-δ and/or RPTP-σ or its fragment.

Specificity can be a human monoclonal antibodies in conjunction with the antibody of LAR, RPTP-δ and/or RPTP-σ.Human monoclonal antibodies can produce by many technology that those of ordinary skill in the art should be familiar with.Such method includes but not limited to, the human peripheral blood cell (for example, comprise bone-marrow-derived lymphocyte) dust crust virus (EBV) transform, the external immunity of human B cell, fusion from the splenocyte of the transgenic mice of the human immunoglobulin gene's who carries insertion immunity, separate from human normal immunoglobulin V zone phage library, or known in the art and based on other method of this paper disclosure.

For example, human monoclonal antibodies can obtain from transgenic mice, and described transgenic mice is produced special people's antibody by transformation to reply antigenic stimulation.For example, Green etc., Nature Genet. (natural genetics) 7:13 (1994); Lonberg etc., Nature (nature) 368:856 (1994); Taylor etc., Int.Immun. (international immunology) 6:579 (1994); U.S. Patent number 5,877,397; Bruggemann etc., Curr.Opin.Biotechnol. (contemporary biotechnology viewpoint) 8:455-58 (1997); Jakobovits etc., Ann.N.Y.Acad.Sci. (NYAS's annual) 764:525-35 (1995) have described the method that obtains people's antibody from transgenic mice.In this technology, the element of people's heavy chain and light chain gene seat manually is incorporated in the mouse species that is derived from embryonic stem cell line by heredity processing, the target spot that described embryonic stem cell line contains endogenous murine source heavy chain and light chain gene seat destroys.(also referring to Bruggemann etc., Curr.Opin.Biotechnol. (contemporary biotechnology viewpoint) 8:455-58 (1997)).For example, the human normal immunoglobulin transgenosis can be the minigene construct, or the transgenosis seat on the yeast artificial chromosome, and its DNA that carries out the B cell-specific in the mouse lymph tissue resets and hypermutation.Human monoclonal antibodies can pass through the immune transgenic mouse, and transgenic mice can produce people's antibody of described antigen-specific and obtain then.According to method as herein described, the lymphocyte of the transgenic mice of immunity can be used for producing the hybridoma of secretion people antibody.The polyclonal serum that contains people's antibody can also obtain from the blood of immune animal.

The another kind of method that produces human antigen's monoclonal antibody specific comprises transforming by EBV makes human peripheral blood cell's infinite multiplication.Referring to, for example, U.S. Patent number 4,464,456.Producing specificity can be by immunologic detection method provided herein for example in conjunction with the B clone (or lymphoblastoid clone) of such infinite multiplication of the monoclonal antibody of LAR, RPTP-δ and/or RPTP-σ, ELISA, identify, separate by the standard clone technology then.Produce anti--LAR, RPTP-δ and/or RPTP-σ antibody lymphoblastoid clone stability can by according to methods known in the art with described cell transformed system and mouse source myelomatosis merge produce mouse-people's hybrid cell line improve (referring to, for example, Glasky etc., Hyhridoma (hybridoma) 8:377-89 (1989)).The another kind of method that produces human monoclonal antibodies is external immunity, and it comprises people's spleen B cell antigen stimulation, then B cell and the different heterozygosis fusion partner that excites is merged.Referring to, for example, Boerner etc., J Immunol. (Journal of Immunology) 147:86-95 (1991).

In certain embodiments, select to produce the B cell of anti--RPTP antibody, and foundation is known in the art, and (WO 92/02551; U.S. Patent number 5,627,052; Babcook etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 93:7843-48 (1996)) and Protocols in Molecular Biology as herein described, from described B cell clone light chain and variable region of heavy chain.By select producing the cell of specificity in conjunction with the antibody of LAR, RPTP-δ and/or RPTP-σ, and will be from the B cell of the animal of immunity from spleen, lymphoglandula or peripheral blood sample separation.The B cell can also separate from the people, for example, and from the peripheral blood sample separation.Detect to produce that the method for the single B cell with the specific antibody that needs is known in the art, for example, then detect special antibody etc. by plaque formation, the cell sorting of fluorescence-activation, stimulated in vitro.Select the method for the B cell of the special antibody of generation to comprise, for example, the unicellular suspension of preparation B cell in containing LAR, RPTP-δ and/or RPTP-σ or their segmental soft agar.The special antibody that is produced by described B cell causes forming mixture with antigenic the combination, and as seen it can be used as immunoprecipitate and.After having selected to produce the B cell of special antibody, described special antibody gene can be by separating according to method known in the art and as herein described and DNA amplification or mRNA clone.

Can also produce LAR, RPTP-δ and/or the special chimeric antibody of RPTP-σ, comprise humanized antibody.Chimeric antibody has at least one constant region structural domain of deriving from first kind of mammalian species and derives from second kind, at least one variable region structural domain of different mammalian species.Referring to, for example, Morrison etc., Proc.Natl.Acad.Sci USA (NAS's journal), 81:6851-55 (1984).In one embodiment, chimeric antibody can be by deriving from coding at least a variable region structural domain of non-human monoclonal antibodies, be cloned into such as the polynucleotide sequence of the variable region that derives from mouse source, rat or hamster monoclonal antibody in the carrier of the nucleotide sequence that contains at least a human constant region of encoding and make up (referring to, for example, Shin etc., Methods Enzymol. (Enzymology method) 178:459-76 (1989); Walls etc., Nucleic Acids Res. (nucleic acids research) 21:2921-29 (1993)).By way of example, the polynucleotide sequence of the variable region of light chain of coding mouse resource monoclonal antibody can be inserted in the carrier of the nucleotide sequence that contains coding human kappa light chain constant region sequence.In a kind of isolated vectors, the polynucleotide sequence of the variable region of heavy chain of the described monoclonal antibody of encoding can meet coding human IgG1 constant region sequence frame and clone.Selected special human constant region can depend on the needed effector function of special antibody (for example, complement fixation(CF), with combining of special Fc acceptor, etc.).The another kind of method that is used to produce chimeric antibody known in the art is homologous recombination (for example, U.S. Patent number 5,482,856).Preferably, with described carrier with transfection in eukaryotic cell, with the described chimeric antibody of stably express.

Inhuman/people's chimeric antibody further heredity is processed to produce " humanized " antibody.Humanized antibody like this can comprise a plurality of CDRs of the immunoglobulin (Ig) that derives from the non-human mammal species, the variable framework region of at least one individual and at least one human normal immunoglobulin constant region.In certain embodiments, for example, when obtaining the non-human monoclonal antibodies that LAR, RPTP-δ and/or RPTP-σ combine the variable region with as indicated above coming from, or the chimeric antibody with such V district and at least one individual C district is relatively the time, and humanization can provide the antibody that has the binding affinity of the minimizing of LAR, RPTP-δ and/or RPTP-σ.Therefore, the useful strategy of design humanized antibody can comprise, for example, explanation and unrestricted mode are by way of example identified and the variable framework region of homologous people of the inhuman framework region of described chimeric antibody.Do not wish to be bound by theory, such strategy can increase the possibility of described humanized antibody reservation to the specificity binding affinity of LAR, RPTP-δ and/or RPTP-σ, in some preferred embodiments, it can be the essentially identical avidity to LAR, RPTP-δ and/or RPTP-σ, and in some other embodiment, can be to LAR, RPTP-δ and/or RPTP-σ bigger avidity (referring to, for example, Jones etc., Nature (nature) 321:522-25 (1986); Riechmann etc., Nature (nature) 332:323-27 (1988)).

Therefore, the design humanized antibody can comprise CDR ring conformation and the structural determinant of determining inhuman variable region, for example, by computer simulation, then described CDR ring and determinant are compared with known people CDR ring structure and determinant (referring to, for example, Padlan etc., FASEB 9:133-39 (1995); Chothia etc., Nature (nature), 342:377-83 (1989)).Computer simulation can also be used to relatively people's stay in place form of selecting by sequence homology and inhuman variable region (referring to, for example, Bajorath etc., Ther.Immunol. (immunological therapy) 2:95-103 (1995); EP-0578515-A3).If the humanization of inhuman CDRs causes the minimizing of binding affinity, computer simulation can assistant identification can change and part, fully or the special amino-acid residue of supra-optimum ground (that is, bring up to greater than non-humanized antibody level) reservation avidity by site-directed or other induced-mutation technique so.Those of ordinary skill in the art is familiar with these technology, and should easily understand many changes and improvements of such layout strategy.

A kind of such method that is used to prepare humanized antibody is called edge and covers art (veneering).Edge cover framework (FR) residue and is meant that the FR residue selectivity of choosing substitutes the FR residue in rodents heavy chain freely or light chain V district, so that the heterologous molecule that comprises the antigen-binding site that keeps whole natural FR polypeptide pleated sheet structures basically to be provided.Edge covers the art technology and is based on such understanding, promptly, the part of antigen-binding site in conjunction with feature mainly by the structure of heavy chain in antigen-mating surface and light chain CDR group determine with relative arrangement (referring to, for example, Davies etc., Ann.Rev.Biochem. (biological chemistry summary annual) 59:439-73, (1990)).Therefore, when keep carefully the CDR structure, they each other interaction and during the interaction in they and all the other V plot structure territories, in humanized antibody, can keep antigen-binding specificity.Cover the art technology by using edge, with immunity system easily antagonism external (for example, solvent-can and) the FR residue residue of optionally choosing is alternative, so that the hybrid molecule that comprises weak immunogenicity or essentially no immunogenic edge cap surface to be provided.

Inlay the method for covering art and utilize Kabat etc., in Sequences of Proteins of ImmunologicalInterest (sequence of immune target protein matter), the 4th edition, (U.S. HHS, United States Government's printing place, 1991), editor's available sequence data about people's antibody variable territory, the renewal of Kabat database, and the database (nucleic acid and albumen) of other available U.S. and foreign country.The amino acid whose solvent accessibility in V district can be from deriving out about the known three-dimensional structure of people and mouse source antibody fragment.At first, with the FR aminoacid sequence of the variable domains of purpose antibody molecule with from the database of above-mentioned evaluation and the corresponding FR sequence of the people's variable domains that obtains announcing compare.Then will homologous people V district residue comparing to residue with corresponding mouse source amino acid.Use recombinant technology well known in the art, will be in the FR of mouse source different with the negative body of people residues is used in the residue that exists in people's part and substitutes.Residue exchange only uses (solvent can and the) part that exposes to small part to carry out, and pays close attention to substituting of the amino-acid residue that can have remarkable effect to the tertiary structure in V plot structure territory, as proline(Pro), glycine and charged amino acid.

By this way, " the edge lid " antigen-binding site that obtains is designed to keep the CDR residue of rodent, basically be close to the residue of CDRs, be accredited as embedding or most of embedding (solvent is untouchable) residue, it is believed that participate between heavy chain and the light chain structural domain non-covalent (for example, static and hydrophobicity) residue that contacts, and from the residue of the conservative structural region of the FRs that it is believed that " standard " tertiary structure that influences CDR ring (referring to, for example, Chothia etc., Nature (nature), 342:377-383 (1989)).Then, these standards are used for preparing the nucleotide sequence of reorganization, it is combined to the two CDRs of the heavy chain of antigen-binding site and light chain and can be used among the FRs of the mankind-appearance of transfection mammalian cell, shows people's antibody of reorganization of the antigen-specific of rodent antibody molecule with expression.

For special application, may need the antigen-binding site of antibody.Antibody fragment, F (ab ') ₂, Fab, Fab ', Fv, and Fd for example, can obtain by the proteolysis of antibody, for example, according to ordinary method with whole antibody with stomach en-or papain digestion and obtain.Explanation as an example, antibody fragment can be called F (ab ') to provide by with stomach en-the antibody enzymatic lysis being produced ₂Fragment.This fragment can further be used the thiol reductant cracking, to produce Fab ' unit price fragment.Randomly, scission reaction can be used for the blocking groups of the mercapto groups that is obtained by the disulfide linkage cracking and carry out.As alternatives, use papoid enzymatic lysis two unit price Fab fragments of antibody generation and Fc fragment (referring to, for example, U.S. Patent number 4,331,647; Nisonoff etc., Arch.Biochem.Biophys. (biological chemistry and biophysics archives) 89:230 (1960); Porter, Biochem.J. (journal of biological chemistry) 73:119 (1959); Edelman etc., in Methods inEnzymology (Enzymology method), 1:422 (press of institute 1967); Weir, Handbook ofExperimental Immunology (experiment immunization learns to do volume), Blackwell Scientific, Boston (1986)).Described Fab can separate with the Fc fragment by affinity chromatography, for example, uses fixed a-protein, protein G, the special antibody of Fc, or fixed RPTP polypeptide or its fragment.Can use other method of cracking antibody, such as separating heavy chain forming monovalent light chain-heavy chain fragment (Fd), segmental further cracking, perhaps other enzymatic, chemistry or genetic technique are as long as described fragment is in conjunction with the RPTP by complete antibody recognition.

Antibody fragment can also be the protein as any synthetic of synantibody effect or heredity processing, because it combines the formation complex body with special antigen.For example, antibody fragment comprises the isolating fragment of being made up of variable region of light chain, the Fv fragment of forming by the variable region of heavy chain and light chain, recombinant single chain peptide molecule that light chain and variable region of heavy chain are connected by peptide linker (scFv albumen) and the atom of forming by the amino-acid residue of the super variable region of simulation.Described antibody comprises at least one variable region structural domain.Described variable region structural domain can be that any size or amino acid are formed, and comprise usually and be responsible at least one super variable aminoacid sequence of antigen bonded, and described super variable aminoacid sequence is close to or meets the frame of one or more frame sequences.In generic term, variable (V) plot structure territory can be the heavy (V of immunoglobulin (Ig) _H) and/or light (V _L) any suitable arrangement of chain variable domains.Therefore, for example, described V plot structure territory can be a monomer, and is V _HOr V _LStructural domain, it can be with acceptable avidity conjugated antigen independently.Alternatively, described V plot structure territory can be dimeric, and comprises V _H-V _H, V _H-V _L, or V _L-V _LDimer.Preferably, described V district dimer comprises non-covalent associating (F hereinafter referred to as _v) at least one V _HWith at least one V _LChain.If desired, described chain can be direct, the disulfide linkage by between two variable domains for example, and perhaps by joint, peptide linker for example, and covalent coupling are to form the Fv (scF of strand _v).

Atom is the antibody fragment that comprises single complementary determining region (CDR).Such CDR peptide can be by making up coding purpose antibody the polynucleotide of CDR obtain.For example, described polynucleotide by use from the cellular segregation that produces antibody or be included in produce antibody intracellular mRNA as template, the method of implementing according to those skilled in the art (referring to, for example, Larrick etc., Methods:A Companion to Methods in Enzymology (method: the 2:106 Enzymology method guide), (1991); Courtenay-Luck, " Genetic Manipulation ofMonoclonal Antibodies (genetic manipulation of monoclonal antibody); " at MonoclonalAntibodies:Production, among the Engineering and Clinical Application (monoclonal antibody: production, processing and clinical application), Ritter etc. (eds.), the 166th page (Cambridge University Press 1995); With Ward etc., " Genetic Manipulation and Expression of Antibodies (genetic manipulation of antibody and expression); " in Monoclonal Antibodies:Principles and Applications (monoclonal antibody: principle and application), Birch etc., (eds.), the 137th page (Wiley-Liss, company 1995)), use the polymerase chain reaction synthetic variable region and prepare.Alternatively, such CDR peptide and other antibody fragment can use the automatic peptide synthesizer and synthesize.

According to some embodiment, inhuman, the people of any Ig molecule as herein described or humanized heavy chain and variable region of light chain can be constructed as scFv polypeptide fragment (single-chain antibody).Referring to, for example, Bird etc., Science (science) 242:423-426 (1988); Huston etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 85:5879-83 (1988).Multi-functional scFv fusion rotein can be by the scFv polypeptide of will encoding polynucleotide sequence and the many known effect proteins of coding in any at least a polynucleotide sequence meet frame ground and be connected and produce.These methods are as known in the art, and for example at EP-B1-0318554, U.S. Patent number 5,132,405, U.S. Patent number 5,091,513 and U.S. Patent number 5,476,786 in open.By way of example, effect protein can comprise the constant region for immunoglobulin sequence.Referring to, for example, Hollenbaugh etc., J.Immunol Methods (immunological method magazine) 188:1-7 (1995).Other example of effect protein is an enzyme.As limiting examples, such enzyme can be provided for therapeutic purpose biological activity (referring to, for example, Siemers etc., Bioconjug.Chem. (bioconjugates chemistry) 8:510-19 (1997)), perhaps can be provided for the detectable activity of diagnostic use, such as many known substrates are changed into detectable product with horseradish peroxidase enzyme catalytic.

In certain embodiments, scFv can be fused to and allow to detect on the specificity bonded peptide or polypeptide structure territory between fusion rotein and the antigen (for example, one or more RPTPs as herein described).For example, described fusion polypeptide structural domain can be the affinity marker polypeptide.Therefore, can use affine polypeptide or peptide-labeled, such as avidin, streptavidin or His (for example, polyhistidyl) mark, detect the combination of scFv fusion rotein and binding partners (for example, one or more RPTPs as herein described or their fragment) by in the various technology that those skilled in the art are afamiliar with any.Detection technique can also comprise, for example, avidin or streptavidin fusion rotein and vitamin H or with the combining of vitamin H simulated series (referring to, for example, Luo etc., J.Biotechnol. (biotechnology magazine) 65:225 (1998) and the reference wherein quoted), with detectable part (for example, the part of mark) direct covalent modification fusion rotein, fusion rotein combines with the non-covalent of reporter molecule of specific marker, fusion rotein by comprising the part with enzymic activity is perhaps fixed fusion rotein (covalently or non-covalently) on solid support to the enzymatically modifying of detectable substrate.Comprise RPTP-specific immunoglobulin source polypeptide the scFv fusion rotein can with another kind of polypeptide as the effector peptide fusion of avidity character with needs (referring to, for example, U.S. Patent number 5,100,788; WO 89/03422; U.S. Patent number 5,489,528; U.S. Patent number 5,672,691; WO 93/24631; U.S. Patent number 5,168,049; U.S. Patent number 5,272,254; EP 511,747).Provide as this paper, the scFv peptide sequence can be fused on the fusion polypeptide sequence, comprises the effect protein sequence, and it can comprise the fusion polypeptide of total length, and it alternatively comprises its variant or fragment.

Antibody can also from the human normal immunoglobulin phage library, from the rabbit immunoglobulin phage library, from the mouse immuning ball protein phage library and/or from chicken immune sphaeroprotein phage library identify with separate (referring to, for example, Winter etc., Annu.Rev.Immunol. (immunology summary annual) 12:433-55 (1994); Burton etc., Adv.Immunol. (senior immunology) 57:191-280 (1994); U.S. Patent number 5,223,409; Huse etc., Science (science) 246:1275-81 (1989); Schlebusch etc., Hybridoma (hybridoma) 16:47-52 (1997) and the reference of wherein quoting; Rader etc., J Biol.Chem. (biological The Chemicals) 275:13668-76 (2000); Popkov etc., J Mol.Biol. (molecular biology magazine) 325:325-35 (2003); Andris-Widhopf etc., J.Immunol.Methods (immunological method magazine) 242:159-31 (2000)).Can be from inhuman species or non-human immunoglobulin library isolated antibody according to as herein described and methods known in the art genetic modification, with described antibody or its fragment " humanization ".Can in phage vector, produce the immune globulin variable region gene combinatorial library, can screen to select Ig fragment (Fab, the Fv of specificity it in conjunction with RPTP as herein described, scFv, or their polymer) (referring to, for example, U.S. Patent number 5,223,409; Huse etc., Science (science) 246:1275-81 (1989); Sastry etc., Proc.Natl.Acad.Sci USA (NAS's journal) 86:5728-32 (1989); Alting-Mees etc., Strategies in Molecular Biology (molecular biological strategy) 3:1-9 (1990); Kang etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 88:4363-66 (1991); Hoogenboom etc., J Molec.Biol. (molecular biology magazine) 227:381-388 (1992); Schlebusch etc., Hybridoma (hybridoma) 16:47-52 (1997) and the reference of wherein quoting; U.S. Patent number 6,703,015).

For example, the library that comprises the segmental multiple polynucleotide sequence in coding Ig variable region can be inserted in the genome of filamentous bacterium phage such as M13 or its variant, meet the sequence of the bacteriophage coat protein of encoding such as the frame of gene III or gene VIII.Fusion rotein can be coat protein and variable region of light chain structural domain and/or with the fusion rotein of variable region of heavy chain structural domain.According to some embodiment, IgF ab fragment can also be illustrated on the phage particle (referring to, for example, U.S. Patent number 5,698,426).

Heavy chain and light chain immunoglobulin (Ig) cDNA expression library can also prepare in lambda particles phage, for example, use λ ImmunoZap ^TM(H) and λ ImmunoZap ^TM(L) carrier (Stratagene, La Jolla, California).In brief, mRNA is separated from the B cell colony, and be used for being created in heavy chain and light chain immunoglobulin (Ig) cDNA expression library in λ JmmunoZap (H) and λ JmmunoZap (L) carrier.These carriers can screen separately or co expression, to form Fab fragment or antibody (referring to Huse etc., as previously mentioned; Also referring to Sastry etc., as previously mentioned).Positive plaque can be subsequently converted to the not cracked plasmid of permission from intestinal bacteria high level expression monoclonal antibody fragment.

Displaying in conjunction with the Ig fragment of LAR, RPTP-δ and/or RPTP-σ (for example, Ig V-district or Fab) plaque can select like this: by described phage library and LAR, RPTP-δ and/or RPTP-σ or their fragment are mixed, perhaps by fully allowing the bonded condition and under the time, described phage library is contacted with such polypeptide or peptide molecule on being fixed on solid substrate.Unconjugated phage is removed by washing, and then, wash-out specificity bonded phage (promptly, comprise the segmental phage of RPTP specificity Ig) (referring to, for example, Messmer etc., Biotechniques (biotechnology) 30:798-802 (2001)).The phage of wash-out can breed in suitable host bacterium, and can repeat combination and the wash-out of several RPTP of wheel continuously usually, to increase the output of the phage of expressing the special immunoglobulin (Ig) of RPTP-.

Display technique of bacteriophage can also be used to selection and LAR, RPTP-δ and/or RPTP-σ bonded Ig fragment or single-chain antibody.For have the candidate nucleic acid molecule that can insert such antibody fragment of coding or relevant peptide (for example, the example of the appropriate carriers of multiple clone site DNA), referring to, McLafferty etc. for example, Gene (gene) 128:29-36 (1993); Scott etc., Science (science) 249:386-90 (1990); Smith etc., Meth.Enzymol. (Enzymology method) 217:228-57 (1993); Fisch etc., Proc.Natl.Acad.Sci USA (NAS's journal) 93:7761-66 (1996)).The dna molecular that is inserted can comprise the sequence that produces at random, and the specificity of maybe can encoding is in conjunction with the known peptide of LAR, RPTP-δ and/or RPTP-σ or the variant of polypeptide structure territory (such as A41L).Usually, described nucleic acid inset coding is 60 amino acid whose peptides nearly, 3 to 35 the amino acid whose peptides of perhaps can encoding, 6 to 20 the amino acid whose peptides of perhaps can encoding.Peptide by described insertion sequence coding is illustrated on the surface of bacteriophage.Can be based on fixed RPTP or its segmental specific combination and select to express the phage of the binding domains of RPTP.Known genetic recombination technology can be used for making up and comprise described segmental fusion rotein.For example, can produce the polypeptide of the serial array that comprises the RPTP binding peptide structural domain that two or more similar or dissimilar avidity select, with the binding affinity maximization of the product that will obtain for LAR, RPTP-δ and/or RPTP-σ.

Use the combinatorial mutagenesis strategy of phage library can also be used for inhuman variable region humanization (referring to, for example, Rosok etc., J Biol.Chem. (biological The Chemicals) 271:22611-18 (1996); Rader etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 95:8910-15 (1998)).Can select to have the humanized variable region of binding affinity that reduced by minimum or suitable with inhuman variable region, and the nucleotide sequence of the described humanization variable region of encoding can determine by standard technique (referring to, Sambrook etc., Molecular Cloning:A Laboratory Manual (molecular cloning: laboratory manual), cold spring port press (2001)).Then, the Ig-encoding sequence that avidity is selected can be cloned in the another kind of appropriate carriers,, perhaps randomly, can be cloned in the carrier that comprises the Ig constant region, with the immunoglobulin chain of The expressed to express described Ig fragment.

Similarly, can use conventional enzymatic digestion or recombinant DNA technology to make up the part or the fragment of the special antibody of RPTP, as Fab and Fv fragment, with in conjunction with the variable region of coding to the gene of the special antibody of LAR, RPTP-δ and/or RPTP-σ.In an embodiment, use nucleotide primer, the variable region of the gene of purpose monoclonal antibody is expressed in amplification in hybridoma.These primers can be by those of ordinary skill in the art's synthetic, perhaps can buy from commercial source (referring to, for example, Stratagene (La Jolla, California), its sale be used to increase primer of mouse and people variable region).Described primer can be used for heavy chain or the variable region of light chain of increasing, and it can be inserted into carrier such as ImmunoZAP respectively then ^TMH or ImmunoZAP ^TMAmong the L (Stratagene).Then, these carriers can be incorporated into intestinal bacteria, yeast or based in the mammiferous expression system.Use these methods, can produce and contain V in a large number _HAnd V _LThe single chain protein of the fusion of structural domain (referring to Bird etc., Science (science) 242:423-426 (1988)).In addition, such technology can be used for non-human antibody V district's humanization is not changed the binding specificity of described antibody.

In some other embodiment, the RPTP-specific antibody is the polymer antibody fragment.For example, usually at Hayden etc., useful method is described among Curr Opin.Immunol. (Immunization Update viewpoint) 9:201-12 (1997) and the Coloma etc., Nat.Biotechnol. (Nature Biotechnol) 15:159-63 (1997).For example, the polymer antibody fragment can produce by phage technology, to form miniantibody (miniantibody) (U.S. Patent number 5,910 573) or double antibody (Holliger etc., CancerImmunol.Immunother. (cancer immunity and immunotherapy) 45:128-30 (1997)).Can produce the polymer fragment, it is the polymer of RPTP-specificity Fv.

Polymer antibody comprises dual specific and bi-functional antibody, its comprise with the associating Fv of the 2nd Fv with different antigen-specifiies to certain antigen-specific (referring to, for example, Drakeman etc., Expert Opin.Investig.Drugs (expert's viewpoint of research medicine) 6:1169-78 (1997); Koelemij etc., J.Immunother. (immunotherapy magazine) 22:514-24 (1999); Marvin etc., Acta Pharmacol.Sin.26:649-58 (2005); Das etc., Methods Mol.Med. (molecular medicine method) 109:329-46 (2005)).For example, in one embodiment, bi-specific antibody comprises the Fv of specificity in conjunction with LAR, or other antigen-binding fragment as herein described, and comprises the Fv of specificity in conjunction with RPTP-σ, or other antigen-binding fragment.Similarly, in another embodiment, bi-specific antibody comprises the Fv of specificity in conjunction with LAR, or other antigen-binding fragment as herein described, and comprises the Fv of specificity in conjunction with RPTP-δ, or other antigen-binding fragment.In another embodiment, bi-specific antibody comprises the Fv of specificity in conjunction with RPTP-σ, or other antigen-binding fragment as herein described, and comprises the Fv of specificity in conjunction with RPTP-δ, or other antigen-binding fragment.In other some embodiment, multivalent antibody or bi-specific antibody comprise specificity in conjunction with at least a Fv among LAR, RPTP-δ and the RPTP-σ, or other antigen-binding fragment, and further comprise the special Fv of non-PTP polypeptide, or other antigen-binding fragment, such as for example, cell-surface antigens, when by specific antibody in conjunction with the time, described cell-surface antigens helps, promotes or can change the immunoreactivity of (suppress or strengthen) immunocyte.

Amino acid mutation is incorporated into can be to improving specificity or the avidity or useful to changing effector function to RPTP in the RPTP-binding domain-immunoglobulin molecule.The immunoglobulin (Ig) that has the higher avidity of LAR, RPTP-δ and/or RPTP-σ can produce by the site-directed mutagenesis of special residue.The simulation of computer assisted three-dimensional molecular can be used for identifying for improve the amino-acid residue that will change to the avidity of RPTP (referring to, for example, Mountain etc., Biotechnol.Genet.Eng.Rev. (biotechnology genetic engineering summary) 10:1-142 (1992)).Alternatively, the combinatorial library of CDRs can produce in the M13 phage, and the screening have raising avidity immunoglobulin fragment (referring to, for example, Glaser etc., J Immunol. (Journal of Immunology) 149:3903-13 (1992); Barbas etc., Proc.Natl.Acad.Sci USA (NAS's journal) 91:3809-13 (1994); U.S. Patent number 5,792,456).

In certain embodiments, described antibody can carry out heredity processing to have the effector function of change.For example, described antibody can have the ability (increase or reduce with biology or the remarkable mode of statistics) of the cytotoxicity (ADCC) of the mediation CDC (CDC) of change or antibody dependent cellular, or the Fc receptors bind effector cell's that exists on described effector cell of passing through of changing ability.Effector function can by the fixed point directed mutagenesis change (referring to, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995); Eghtedarzedeh-Kondri etc., Biotechniques (biotechnology) 23:830-34 (1997)).For example, the sudden change of the glycosylation site on the Fc of immunoglobulin (Ig) part can change the ability of described immunoglobulin (Ig) complement-fixing (referring to, for example, Wright etc., TrendsBiotechnol. (biotechnology trend) 15:26-32 (1997)).Other sudden change of constant region structural domain can change described immunoglobulin (Ig) complement-fixing or influence ADCC ability (referring to, for example, Duncan etc., Nature (nature) 332:563-64 (1988); Morgan etc., Immunology (immunology) 86:319-24 (1995); Sensel etc., Mol.Immunol (molecular immunology) 34:1019-29 (1997)).(also referring to, for example, U.S. Patent Publication number 2003/0118592; 2003/0133939).

The specificity as described herein of encoding is in conjunction with antibody or its segmental nucleic acid molecule of RPTP, can be according to breeding about in many known methods of nucleic acid excision, connection, conversion and transfection any and expressing.Therefore, in certain embodiments, the expression of antibody fragment can be preferably in prokaryotic host cell such as intestinal bacteria (Escherichia coli) (referring to, for example, Pluckthun etc., Methods Enzymol. (Enzymology method) 178:497-515 (1989)).In some other embodiment, the expression of antibody or its antigen-binding fragment can be preferably in eukaryotic host cell, it comprises that yeast (for example, yeast saccharomyces cerevisiae (Saccharomyces cerevisiae), schizosaccharomyces pombe (Schizosaccharomyces pombe), and pichia pastoris phaff (Pichia pastoris)); Zooblast (comprising mammalian cell); Or vegetable cell.The example of suitable zooblast includes, but not limited to myelomatosis, COS, CHO or hybridoma.The example of vegetable cell comprises tobacco, corn, soybean and rice cell.By the known method of those of ordinary skill in the art and based on this content, can design a kind of nucleic acid carrier that is used for expressing exogenous array, the polynucleotide sequence of the described RPTP binding antibody of coding (or its fragment) can be inserted then at special host system.Regulatory element will be different according to concrete host.

Can prepare the reproducible expression vector that one or more comprise the polynucleotide of encode variable and/or constant region, and be used for transforming suitable clone, for example, nonproductive myeloma cell line, such as mouse NSO system, or bacterium, such as intestinal bacteria, the production of antibody wherein will take place.In order to obtain effectively to transcribe and translate, the polynucleotide sequence in every kind of carrier is connected to promotor and the leader sequence on the variable domains sequence with should comprising suitable adjusting sequence, particularly operability.The special method that is used in this way producing antibody is normally known and conventional application.For example, by (Molecular Cloning, A Laboratory Manual (molecular cloning, laboratory manual), the 2nd edition, Cold Spring Harbor Laboratory (cold spring harbor laboratory), New York, 1989 such as Sambrook; Also referring to Sambrook etc., the 3rd edition, Cold Spring HarborLaboratory (cold spring harbor laboratory), New York, (2001)) molecular cloning method described.Dna sequencing can be according to described and carry out in the international plc order-checking handbook (Amersham International picsequencing handbook) of Sanger etc. (Proc.Natl.Acad.Sci.USA (NAS's journal) 74:5463 (1977)) and peace agate West Asia and the improvement that wherein comprises.

In many methods that the site-directed mutagenesis of immunoglobulin variable (V district), framework region and/or constant region can be implemented according to as herein described and this area any and carry out (Kramer etc., Nucleic Acids Res. (nucleic acids research) 12:9441 (1984); Kunkel Proc.Natl.Acad.Sci.USA (NAS's journal) 82:488-92 (1985); Kunkel etc., Methods Enzymol. (Enzymology method) 154:367-82 (1987)).Can also be according to conventional method (for example, the L-Ala subregion mutagenesis of implementing of those skilled in the art; Error-prone PCR mutagenesis; The mutagenesis of instructing with oligonucleotide (referring to, for example, Molecular Cloning:A LaboratoryManual such as Sambrook (molecular cloning: laboratory manual), the 3rd edition, Cold Spring Harbor LaboratoryPress (press of cold spring harbor laboratory), New York (2001))) carry out random mutagenesis methods, to identify for combining important residue with RPTP (LAR, RPTP-δ and/or RPTP-σ) or or not the bonded residue of antigen and antibody when the change.Alternatively, many published content have been described the technology that is applicable to preparation antibody, it is by operating DNA, producing expression vector and transform suitable cell and carry out (Mountain etc., (ed.Tombs, M P, 10 in Biotechnology and Genetic Engineering Reviews (biotechnology and genetic engineering summary), the 1st chapter, Intercept, Andover, Britain (1992)); International Patent Publication No. W WO 91/09967).

Specificity can also be as the reagent of immunochemical analyses, to detect one or more RPTPs existing in biological sample in conjunction with antibody and the antigen-binding fragment thereof of LAR, RPTP-δ and/or RPTP-σ.In certain embodiments, specificity can be used for detecting the expression of described at least a RPTP in conjunction with at least one the antibody among LAR, RPTP-δ and the RPTP-σ.In some special embodiment, a kind of antibody or one group of antibody can be exposed to the cell of expressing RPTP, and the expression of described RPTP can be determined by detecting, the special antibody of another kind of RPTP is used in described detection, its combination and the epi-position different epi-position of the initial permission of described one or more antibody with cell interaction.

For such purpose, RPTP-binding domain-immunoglobulin as herein described (or its fragment) can comprise detectable part or mark, such as enzyme, cytotoxic agent or other acceptor molecule, it comprises dyestuff, radionuclide, luminophore, fluorophor or vitamin H etc.Described RPTP-specific immunoglobulin or its fragment can be used for diagnosis or treatment application by radio-labeling.The technology of radiolabelled antibody be known in the art (referring to, for example, Adams, In Vivo (body in) 12:11-21 (1998); Hiltunen, Acta Oncol.32:831-9 (1993)).Effector molecule or reporter molecule can or be positioned at described anti-intravital carbohydrate functional group by any available amino acid side chain, end amino acid and be attached on the antibody, condition is described adheres to or attachment means does not influence binding characteristic unfriendly, so that the availability of described molecule is eliminated.Functional group comprises especially, for example, and any free amino, imino-, mercaptan, hydroxyl, carboxyl or aldehyde radical.Adhering to of antibody or its antigen-binding fragment and effector molecule and/or reporter molecule can realize by the suitable functional group in such group and described effector molecule or the acceptor molecule.Connection can be directly or by at interval or linking group and indirect.(referring to, for example, international application published WO93/06231, WO 92/22583, WO 90/091195 and WO 89/01476; Also referring to, for example, commercial supplier such as Pierce Biotechnology (Pierre's Si biotechnology), Rockford (Rockford), IL).

Provide and according to method well known in the art as this paper, polyclone and monoclonal antibody can be used for LAR, RPTP-δ and/or RPTP-σ and segmental affine separation the thereof (referring to, for example, Hermanson etc., Immobilized Affinity Ligand Techniques (fixed affinity ligand technology), Academic Press, Inc. (publishing company of institute) New York, (1992)).In brief, antibody (or its antigen-binding fragment) can be fixed on the solid support material, and its contact contains the sample of RPTP then.Fully allowing under the condition and time of RPTP and described fixed antibodies, described sample and fixed antibody interact; Remove the non-binding composition (that is, with incoherent those compositions of RPTP) of sample; And use suitable elute soln that RPTP is discharged from described fixed antibody then.

In certain embodiments, provide antiidiotypic antibody, its identification and specificity binding specificity be in conjunction with the antibody (or its antigen-binding fragment) of LAR, RPTP-δ and/or RPTP-σ, and the method for using these antiidiotypic antibodys is provided.Antiidiotypic antibody can use anti--LAR, anti--RPTP-δ or anti--RPTP-σ antibody (or its antigen-binding fragment) to produce as polyclonal antibody or as monoclonal antibody as immunogen by method as herein described.Antiidiotypic antibody or its fragment can also be selected to produce by genetic recombination remodeling method mentioned above or by phage display.According to the description that this paper provides in detail, can further transform antiidiotypic antibody, so that chimeric or humanized antiidiotypic antibody to be provided.Antiidiotypic antibody can specificity in conjunction with the antigen-binding site of anti--RPTP antibody so that described antibody is suppressed competitively with combining of RPTP.Alternatively, antiidiotypic antibody provided herein can noncompetitive ground suppresses anti--RPTP antibody and combines with RPTP's.

In one embodiment, antiidiotypic antibody can be used for changing the immunoreactivity of immunocyte.In certain embodiments, antiidiotypic antibody can be used for suppressing the immunoreactivity of immunocyte, and is used for treating Immunological diseases or illness.Antiidiotypic antibody combines the antibodies specific ground combination of LAR, RPTP-δ and/or RPTP-σ with specificity, and the epi-position of the antigen of described antiidiotypic antibody-binding site simulation RPTP, that is, described antiidiotypic antibody will be in conjunction with cognate ligand and the specificity antibody in conjunction with RPTP.Therefore, antiidiotypic antibody can be used to prevent, block or reduce the combination of cognate ligand, and when such part combined with RPTP, described cognate ligand stimulated, induces or the immunoreactivity of enhancing immunity cell.

Antiidiotypic antibody also is used for immunoassay, with existing of anti--RPTP antibody in definite biological sample.For example, immunoassay such as ELISA and other mensuration of being implemented by those skilled in the art described herein, can be used for determining the existence of inductive immunne response by use (immunity) RPTP polypeptide as herein described or its fragment to the host.

In certain embodiments, can be antibody or its antigen-binding fragment of expressing to LAR, RPTP-δ and/or the special antibody of RPTP-σ as intracellular protein.Such intrabody also is called intracellular antibody, and can comprise Fab fragment, Fv fragment, scFv molecule, scFv-Fc fusion antibody or bi-specific antibody, all these can be as described herein and the method implemented according to this area and prepare (referring to, for example, Lobato etc., Curr.Mol.Med. (contemporary molecular medicine) 4:519-28 (2004); Strube etc., Methods (method) 34:179-83 (2004); Lecerf etc., Proc.Natl.Acad.Sci USA (NAS's journal) 98:4764-49 (2001); (Weisbart etc., Int.J.Oncol (international oncology magazine) 25:1113-18 (2004)).Exist effective antibody to comprise the antibody of specificity as the intracellular antibody form in conjunction with the intracellular portion of RPTP.For example, be combined in the antibody of epi-position in the zone of intracellular portion of LAR, RPTP-δ and/or RPTP-σ, for example, it comprises catalyst structure domain D1 and D2 and the zone that comprises the peptide with sequence of listing in SEQ ID NO:51.

Can modify the framework region that side connects the CDR zone, with the expression level, stability and/or the solvability that improve intracellular antibody in the reducing environment in cell (referring to, for example, Auf der Maur etc., Methods (method) 34:215-24 (2004); Strube etc., as previously mentioned; Worn etc., J Biol.Chem. (biological The Chemicals) 275:2795-803 (2000)).Intracellular antibody can be at special cell position or cell organelle, for example, the carrier of polynucleotide sequence that comprises the variable region of the intracellular antibody of encoding by structure, described polynucleotide sequence can be fused to operability in the Codocyte on the special antigenic polynucleotide sequence of target spot (referring to, for example, Graus-Porta etc., Mol.CellBiol. (molecular cytobiology) 15:1182-91 (1995); Lener etc., Eur.J.Biochem. (european journal of biological chemistry) 267:1196-205 (2000); Popkov etc., Cancer Res. (cancer research) 65:972-81 (2005)).Various types of intracellular antibodies be studied as the treatment cancer (referring to, for example, Weisbart etc., as previously mentioned; Popkov etc. as previously mentioned; Krauss etc., Breast Dis. (galactophore disease) 11:113-24 (1999)) and treatment nerve degenerative diseases such as Parkinson's disease (Zhou etc., (molecular therapy) 10:1023-31 (2004)) and Huntington Chorea (Murphy etc., BrainRes.Mol.Brain Res. (brain research and molecule brain are studied) 121:141-45 (2004) Mol.Ther.; Colby etc., JMol.Biol. (molecular biology magazine) 342:901-12 (2004); Colby etc., Proc.Natl.Acad.Sci USA (NAS's journal) 101:17616-21 (2004), Erratum in Proc.Natl.Acad.Sci USA (correcting errors in printing in NAS's journal) 102:955 (2005)) therapeutical agent.Intracellular antibody can be incorporated in the cell by the various technology of those skilled in the art's available, comprises by gene therapy vector, lipid mixt (for example, by Imgenex company, the Provectin of California, San Diego supply ^TM), photochemistry internalization method, or other method known in the art.

A41L, 130L, the expression of RPTPs and polypeptide reagent

The A41L that comprises described herein, 130L, RPTPs (LAR, RPTP-δ and RPTP-σ) and fusion polypeptide (for example, peptide-IgFc fusion polypeptide, RPTP Ig structural domain-Fc fusion polypeptide) polypeptide can use the carrier and the construct of any polynucleotide that comprise the such polypeptide of coding, particularly the recombinant expression construct body is expressed.With host cell by recombinant technology with carrier and/or construct genetic modification, to produce these polypeptide and fusion rotein or its fragment or variant.Every peptide species as herein described and fusion polypeptide can expressed in mammalian cell, yeast, bacterium or other cell under the control of suitable promotor.Use derives from the RNAs of DNA construct, and not celliferous translation system also can be used for producing such protein.For example, Sambrook, etc., MolecularCloning:A Laboratory Manual (molecular cloning: laboratory manual), the 3rd edition, ColdSpring Harbor (cold spring port), suitable clone and the expression vector that is used for protokaryon and eucaryon host described in New York, (2001).

Usually, recombinant expression vector comprises replication orgin, allows the selective marker of the conversion of host cell, for example, the promotor that derives from cance high-expression gene of transcribing of colibacillary ampicillin resistance gene and yeast saccharomyces cerevisiae (S.cerevisiae) TRP1 gene and guiding downstream configurations sequence.Promotor can derive from the operon of coding glycolytic ferment such as glycerol 3-phosphate acid kinase (PGK), α-factor, acid Phosphoric acid esterase or heat shock protein(HSP) etc. especially.The suitable stage with allos structure sequence and translation initiation and terminator sequence assembling.

Randomly, heterologous sequence can encoding fusion protein, and described fusion rotein comprises the aminoterminal or the carboxyl terminal of the character of giving needs and identifies peptide or polypeptide, described character for example, the stable polypeptide that produces or simplify the character of the purifying of expressed recombinant products.Described evaluation peptide comprise polyhistidine tag (his mark) or

Position mark (DYKDDDDK, SEQ ID NO:62), beta-galactosidase enzymes (galactosidase), alkali formula Phosphoric acid esterase, GST, or XPRESS ^TMEpi-position mark (DLYDDDDK, SEQ ID NO:63; The Invitrogen life technology, Carlsbad, California) etc. (referring to, for example, U.S. Patent number 5,011,912; Hopp etc., (Bio/Technology (biotechnology) 6:1204 (1988)).Affine sequence can be provided by carrier, such as for example, and the six-histidine mark that in pBAD/His (Invitrogen), provides.Alternatively, affine sequence can be synthesized to add or be worked into and is used for reorganization and generates in the primer of nucleic acid coding sequence (for example, using the polymerase chain reaction).

The host cell that contains the recombinant expression construct body of needs can be processed (transduction, conversion or transfection) with carrier and/or expression construct (for example, cloning vector, shuttle vectors or expression construct) heredity.Described carrier or construct can be the forms of plasmid, virion, phage etc.The host cell of transforming can be to cultivate in the conventional nutritional medium that is suitable for activating promotor, selecting transformant or increase special gene or nucleotide sequence coding in improvement.Selecting and be kept for the culture condition of special host cell, such as temperature, pH etc., should be that those of ordinary skill in the art is conspicuous.Preferably, according to the method that this area is determined, host cell can be adapted at continuing in the culture propagation unchangeably, to produce clone.In certain embodiments, described clone is the clone of infinite multiplication, and it is meant after logarithmic phase growth and can repeats the clone that (at least 10 times, but maintenance viability) simultaneously go down to posterity in culture.In other embodiments, the host cell that is used for producing clone is the cell that can grow not modulatedly, such as cancer cells or cell transformed or malignant cell.

Be inserted into by the proteic structural DNA sequence that need will encode and suitable translation initiation and termination signal and make up effective bacterial expression construct in the expression vector about the mode of the exercisable read state of function on.Described construct can comprise one or more Phenotypic Selection marks and replication orgin, guaranteeing keeping of described vector construction body, and if desired, provides amplification in the host.The prokaryotic hosts that be fit to transform comprises intestinal bacteria, subtilis (Bacillussubtilis), Salmonella typhimurium (Salmonella typhimurium) and the various species in Rhodopseudomonas (Pseudomonas), streptomyces (Streptomyces) and Staphylococcus (Staphylococcus), but other also can be with the content that elects.Can use any other plasmid or carrier, as long as they are reproducible and survival in the host.Therefore, for example, nucleic acid provided herein can be included in any of various expression vector establishment bodies, as the recombinant expression construct body of express polypeptide.Such carrier and construct comprise karyomit(e), non-chromosome and synthetic dna sequence dna, for example, and bacterial plasmid; Phage DNA; Baculovirus; Yeast plasmid; Derive from the bonded carrier of plasmid and phage DNA; Viral DNA is such as bovine vaccine, adenovirus, fowlpox virus and pseudorabies.Yet any other carrier can be used for preparing the recombinant expression construct body, as long as it is reproducible and survival in the host.

Suitable dna sequence dna can be inserted in the carrier by the whole bag of tricks.Usually, dna sequence dna is inserted into suitable restriction endonuclease site by methods known in the art.Be used to clone, DNA separation, amplification and purifying, be used to comprise the standard technique of the enzymatic reaction of dna ligase, archaeal dna polymerase, restriction endonuclease etc., and various isolation technique is known to those skilled in the art and those of common application.For example, at (Current Protocolsin Molecular Biology (contemporary molecular biology method) (Greene Publ.Assoc. company and John Wiley ﹠amp such as Ausubel; Sons, company, 1993)); Sambrook etc. (Molecular Cloning:ALaboratory Manual (molecular cloning: laboratory manual), the 3rd edition, (Cold Spring HarborLaboratory (cold spring harbor laboratory) 2001)); Many standard techniques have been described in Maniatis etc. (Molecular Cloning (molecular cloning), (cold spring harbor laboratory 1982)) and other place.

Being connected to the dna sequence dna operability of coded polypeptide at least a suitable expression control sequenc (for example, the promotor of promotor or regulation and control) in expression vector goes up to instruct synthesizing of mRNA.The representative example of such expression control sequenc comprises LTR or SV40 promotor, intestinal bacteria lac or trp, phage P _LPromotor, and other promotor of the known expression of controlling gene in protokaryon or eukaryotic cell or in their virus.The carrier that can use CAT (CAT) carrier or other to have selective marker is selected promoter region from the gene of any needs.Concrete bacterium promotor comprises lacI, lacZ, T3, T5, T7, gpt, λ P _R, P _L, and trp.Eukaryotic promoter comprises the instant early promoter of CMV, the HSV thymidine kinase promoter, early stage and late period SV40 promotor, the LTRs promotor of retrovirus and mouse metallothionein(MT) I promotor.Select appropriate carriers and promotor, and preparation comprises the specific recombinant expression construct body of at least a promotor that is connected with nucleic acid operability as herein described ground or modulated promotor, within abundant one skilled in the relevant art's the level.

The design and the selection of the promotor of derivable, modulated promotor and/or tight regulation and control are known in the art, and depend on special host cell and expression system.PBAD expression system (Invitrogen life technology, Carlsbad, California) is to use intestinal bacteria arabinose operon (P _BADOr P _ARA) tight regulation and control expression system example (referring to, Guzman etc., J.Bacteriology (bacteriology magazine) 177:4121-30 (1995); Smith etc., J.Biol.Chem. (biological The Chemicals) 253:6931-33 (1978); Hirsh etc., Cell (cell) 11:545-50 (1977)), described arabinose operon control pectinose pathways metabolism.Many carriers of using this system can be purchased.Other example of the expression system of the promotor-promotion of tight regulation and control comprises can be from Stratagene (La Jolla, CA) pet sheet of Huo Deing reach system (referring to, U.S. Patent number 4.952,496) or expression system (Gossen etc., Proc.Natl.Acad.Sci.USA (NAS's journal) 89:5547-51 (1992) of tet-regulation and control; Gossen etc., Science (science) 268:1766-69 (1995)).(BD bio-science Clontech, Palo Alto is CA) with CLONTECH ' s Creator for design pLP-TRE2 acceptor carrier ^TMClone's test kit uses together, with the expression construct of quick generation tsiklomitsin regulation and control, be used to use that site-specific Cre-lox recombination system is closely controlled, inductively express goal gene (referring to, for example, Sauer, Methods (method) 14:381-92 (1998); Furth, J.Mamm.Gland Biol.Neoplas. (mammalian adenovirus biology and tumorigenesis magazine) 2:373 (1997)), its can also be used for the host cell infinite multiplication (referring to, for example, Cascio, Artig.Organs (artificial organ) 25:529 (2001)).

Described carrier can be a virus vector, such as retrovirus vector.For example, described retrovirus plasmid vector can include, but are not limited to from retrovirus wherein, Moloney murine leukemia poison, SNV, Rous sarcoma virus, Harvey sarcoma virus, avian leukosis viruses, gibbon (gibbon ape) leukosis virus, human immunodeficiency virus, adenovirus, myeloproliferative sarcoma virus, and mammary tumor virus.Virus vector also comprises one or more promotors.Operable suitable promotor includes, but not limited to retrovirus LTR; The SV40 promotor; With at Miller etc., human cytomegalic inclusion disease virus (CMV) promotor of describing among Biotechniques (biotechnology) 7:980-990 (1989), or any other promotor (for example, eukaryotic promotor, comprise, for example, histone, pol III and beta-actin promotor).Operable other viral promotors includes, but not limited to adenovirus promoter, thymidine kinase (TK) promotor and B19 parvovirus promotor.

Described retrovirus plasmid vector be used for transduceing package cell line (for example, PE501, PA317, ψ-2, ψ-AM, PA12, T19-14X, VT-19-17-H2, ψ CRE, ψ CRIP, GP+E-86, GP+envAm12, DAN; Also referring to, for example, Miller, Human Gene Therapy (human gene therapy), 1:5-14 (1990)) to form production clone.Described carrier can be by any way known in the art transduction packing cell, such as for example, electroporation, uses liposome and calcium phosphate precipitation.Described production clone produces the infectious retrovirus carrier granule of the nucleotide sequence that comprises coding polypeptide as herein described or fusion rotein.Then, such retroviral vector particles can be used for the eukaryotic cell of transduceing in external or body.The eukaryotic cell that can transduce comprises that for example, embryonic stem cell, embryo cells, hemopoietic stem cell, liver cell, inoblast, sarcoplast, keratinocyte, endotheliocyte, bronchial epithelial cell and other suitable cultured cells are.

As another example, can be produced by the host cell of the recombinant virus construct transduction of instructing polypeptide or Expression of Fusion Protein and to comprise the expressed polypeptide or the virion of fusion rotein, described expressed polypeptide or fusion rotein are derived from the sprout part of the bonded of virion described in process host cell membrane of virus.The nucleic acid encoding sequence can be cloned in the baculovirus shuttle vectors, then itself and baculovirus are recombinated, to produce the baculovirus expression construct of reorganization, for example, its be used for infecting the Sf9 host cell (referring to, for example, Baculovirus Expression Protocols, Methods in Molecular Biology (baculovirus expression method, molecular biology method) volume 39, Richardson, Ed. (human press 1995); Piwnica-Worms, " Expression ofProteins in Insect Cells Using Baculoviral Vectors (using baculovirus vector at expressed in insect cells albumen); " part ii, the 16th chapter, in Short Protocols in MolecularBiology (molecular biology weak point method), the 2nd edition, Ausubel etc., eds., (John Wiley and Sons 1992), 16-32 is to the 16-48 page or leaf).

Evaluation and characteristic are described the immunoreactive compositions and methods that changes immunocyte

The invention provides and be used for identifying or select to change the immunoreactive reagent of (the remarkable or significant mode of biology suppresses or strengthens preferred the inhibition with statistics) immunocyte or be used for determining the method for the immunoreactive ability of reagent change immunocyte as herein described.In one embodiment, be provided for identifying the immunoreactive compositions and methods that suppresses immunocyte, it comprises: fully allow between at least a RPTP and the poxvirus polypeptide interactional condition and under the time, with following contact (mix, combination or allow interactional mode) with certain: (1) candidate agent; (2) express RPTPs, at least a immunocyte among LAR, RPTP-δ and the RPTP-σ; (3) poxvirus polypeptide as A41L or 130L, and is determined in the existence of described candidate agent and the level that combines of described poxvirus polypeptide (that is, A41L or 130L) and described immunocyte not then.The poxvirus polypeptide represents that with the decline of the level that combines of immunocyte described candidate agent suppresses the immunoreactivity of immunocyte in the presence of described candidate agent.In certain embodiments, at least two kinds among immunocyte expression LAR, RPTP-δ and the RPTP-σ are (such as LAR and RPTP-δ; LAR and RPTP-σ; And RPTP-δ and RPTP-σ), and in some special embodiment, immunocyte is expressed all three kinds of RPTPs.Described immunocyte may reside in the biological sample as herein described or from wherein separating.For example, described immunocyte can obtain from former generation or secular cell culture, perhaps may reside in available from experimenter (people or non-human animal's) the biological sample or from wherein separating.

In another embodiment, be provided for identifying the bonded compositions and methods that suppresses poxvirus polypeptide such as A41L or 130L and at least two kinds of RPTPs (that is at least two kinds among LAR, RPTP-δ and the RPTP-σ).Described method comprises: fully allowing between two kinds of RPTP polypeptide and the poxvirus polypeptide interactional condition at least and under the time, with following contact (mix, combination or to allow interactional certain mode between it): (1) candidate agent; (2) comprise and be selected from (i) LAR; (ii) RPTP-σ; The (iii) biological sample of at least two kinds of RPTP polypeptide among the RPTP-δ; (3) poxvirus polypeptide.Determine the level that combines of described poxvirus polypeptide and described at least two kinds of RPTP polypeptide in the presence of described candidate agent then, and compare with each bonded level in poxvirus polypeptide when not having described candidate agent and the described at least two kinds of RPTP polypeptide.Poxvirus polypeptide and the decline of the level that combines of described at least two kinds of RPTP polypeptide represent that described candidate agent suppresses combining of poxvirus polypeptide and described at least two kinds of RPTP polypeptide in the presence of described candidate agent.In another embodiment, described candidate agent contacts with the biological sample of RPTP-δ with comprising LAR, RPTP-σ, and determines when existing and do not have described reagent the level that combines with every kind of Phosphoric acid esterase.

Allow the interactional suitable condition of reacted constituent to comprise according to this method and other method as herein described, for example, suitable concentration, temperature and the buffer reagent of reagent that those skilled in the art should be familiar with and composition (comprising poxvirus polypeptide and candidate agent and RPTPs).The concentration of reacted constituent, buffer reagent, temperature and fully allow the interactional time phase between the described reacted constituent to determine and/or adjust according to as herein described and method that those skilled in the art are afamiliar with.In order to implement method as herein described, those skilled in the art also should easily understand and understand when these methods of enforcement suitably to comprise which contrast.

Many mensuration and technology are implemented by those skilled in the art, to determine interaction or the combination between biomolecules and the cognate ligand.Therefore, interaction between among poxvirus polypeptide A 41L and/or 130L and LAR, RPTP-σ and the RPTP-δ any one or more, being included in described reagent exists following biologically active agent to this interaction and/or bonded effect, can determine by such mensuration and technology easily that it can comprise competitive assay format.Exemplary method includes but not limited to, FRET (fluorescence resonance energy transfer), fluorescence polarization, the time resolved fluorescence resonance energy shifts, get close to flicker detection (scintillation proximity assays), reporter gene is measured, the enzyme substrates of fluorescent quenching, luminous enzyme substrates and electrochemiluminescence, immunoassay are (such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, immunoblotting, immunohistochemistry etc.), surface plasmon resonance, mensuration based on cell, such as using those of reporter gene, and functional examination (for example, is measured LAR, among RPTP-σ and the RPTP-δ one or more are to mensuration and the measurement immunologic function and the immunoreactive mensuration of the dephosphorylation of the substrate of tyrosine phosphorylation).Many methods as herein described and known to those skilled in the art go for analyzing a large amount of biologically active agents such as the high flux screening from library of compounds, to determine that reagent is to poxvirus polypeptide and/or LAR, the combination of RPTP-σ and RPTP-δ, the influence of interaction or biological function, and reagent to the immunoreactive influence of immunocyte (referring to, for example, High Throughput Screening:The Discovery of Bioactive Substances (high flux screening: the discovery of biologically active substance), Devlin, compile, (Marcel Dekker New York, 1997)).

Described technology and mensuration form can also comprise second class grade chemical, and such as specific antibody, it is used for detecting and/or amplification indication mixture forms, such as the signal of the formation of the mixture between poxvirus polypeptide (for example, A41L or 130L) and RPTP.One or more measure composition or but second class grade chemical can be attached on the test section (or mark or reporter molecule), such as enzyme, cytotoxic agent or other reporter molecule, comprise dyestuff, radionuclide, luminophore, fluorophor or vitamin H etc.The technology that is used for radiolabelled antibody and other polypeptide in this area be known (referring to, for example, Adams, In Vivo (in the body) 12:11-21 (1998); Hiltunen, Acta Oncol.32:831-9 (1993)).Described detectable part (for example can be attached to polypeptide, antibody) on, such as by being positioned at any available amino acid side chain, end amino acid or the carbohydrate functional group of described polypeptide, condition is described adheres to or attachment means does not influence binding characteristic unfriendly, so that the purposes of described molecule is eliminated.Functional group comprises especially, for example, and any free amino, imino-, mercaptan, hydroxyl, carboxyl or aldehyde radical.But adhering to of polypeptide and test section can realize by such group and the suitable functional group in described detectable part.Connection can be directly or by at interval or linking group and indirect.(referring to, for example, international application published WO93/06231, WO 92/22583, WO 90/091195 and WO 89/01476; Also referring to, for example, commercial supplier such as Pierce Biotechnology (Pierre's Si biotechnology), Rockford (Rockford), IL).

When being used for this paper, " biological sample " is meant the sample that comprises at least a or poxvirus polypeptide or its variant among LAR, RPTP-σ and the RPTP-δ in certain embodiments.Biological sample can be blood sample (can prepare serum or blood plasma from it), the examination of living tissue sample, body fluid (for example, lung-douching fluid, ascites, mucous membrane washing lotion, synovia), marrow, lymphoglandula, tissue grafts, organ cultures or from any other the tissue or cellular preparations of experimenter or biogenetic derivation.Sample can also refer to complete form or interrupted tissue of physical condition or cellular preparations wherein, for example, by dissection, decomposition, dissolving, fractionation, homogenate, biochemistry or chemical extraction, pulverizing, freeze-drying, supersound process or any other the method that is used to process the sample that derives from experimenter or biogenetic derivation interrupt.Described experimenter or biogenetic derivation can be people or non-human animal, primary cell culture (for example, the cell of immunocyte, virus infection), or suitable cultured cells is, it includes but not limited to, but can comprise the clone of the genetic modification of the nucleotide sequence karyomit(e) combination or additional reorganization, clone infinite multiplication or infinite multiplication, somatocyte hybrid cell system, the clone that maybe can break up of breaking up, cell transformed system etc.

Candidate agent includes but not limited to, antibody as described herein or its antigen-binding fragment, and it can also comprise bi-specific antibody or bifunctional antibody, chimeric antibody, people or humanized antibody, scFv or double antibody etc.The immunoreactivity that is used to change immunocyte as herein described (in certain embodiments, the immunoreactivity that suppresses immunocyte) and other reagent that is used for the treatment of Immunological diseases or illness include but not limited to, small molecules, peptide-immunoglobulin-constant region fusion polypeptide such as peptide-IgFc fusion polypeptide, fit, siRNA polynucleotide, antisense nucleic acid, ribozyme and peptide nucleic acid(PNA).

Immunocyte and immunne response

Immunocyte is immune any cell, comprises lymphocyte and non-lymphocyte such as accessory cell.Lymphocyte is specific recognition and the cell of replying exotic antigen, but and accessory cell be or not those of the identification of specific participation immunne response and activation stage to specific antigen.For example, mononuclear phagocyte (scavenger cell), other white corpuscle (for example, granulocyte comprises neutrophilic granulocyte, eosinophilic granulocyte, basophilic granulocyte) and dendritic cell act as accessory cell in the inducing of immunne response.Exotic antigen causes acting as inducing or exciting of the described antigenic many effector mechanism of elimination to lymphocytic activation.The accessory cell of influence or participation effector mechanism such as mononuclear phagocyte, also is called the effector cell.

The lymphocyte of main kind comprises bone-marrow-derived lymphocyte (B cell), T lymphocyte (T cell) and NK cell (NK) cell, and it is big grain lymphocyte.The B cell can produce antibody.The T lymphocyte further is subdivided into helper cell (CD4+) and cytolysis or cytotoxic T cell (CD8+).The helper secretion promotes T cell and other cell, comprises the cytokine of B cell and macrophage proliferation and differentiation, and recovers and the activation inflammatory leukocytes.Another subgroup T cell is called modulating T cell or suppressor T cell, and it initiatively suppresses immune activation, and prevents that the pathologic oneself is reactive, that is, and and autoimmune disorders.The inhibitive ability of immunity cytokine, TGF-β and interleukin-10 (IL-10) also participate in the modulating T cell functioning.

Usually, immunne response can comprise humoral response, wherein by the bone-marrow-derived lymphocyte that the is called plasmacytic differentiation former special antibody that creates antagonism.Except humoral response or substitute it, immunne response can also comprise the reaction of cell regulate and control, and wherein various types of T lymphocytes are eliminated antigens by many machining functions.For example, can discern special antigenic helper cell and can react, participate in immunne response to convene immune other cell by discharging soluble adjusting control agent such as cytokine.In addition, can also discern special antigenic cytotoxic T cell can by in conjunction with and destroy or damage and carry antigenic cell or particle reacts.

Immunne response in host or experimenter can be determined by the many known immunological method that as herein described and those of ordinary skill in the art are easy to be familiar with.Such mensuration comprises, but be not necessarily limited to, interior or the external definite soluble antibodies of body, soluble medium such as cytokine (for example, IFN-γ, IL-2, IL-4, IL-10, IL-12, with TGF-β), lymphokine, chemokine, hormone, somatomedin etc., and other soluble little peptide, carbohydrate, Nucleotide and/or lipid medium; The cell-stimulating change of state that the function of the change by immune system cell or constitutional features are determined, for example, cell proliferation, the mobility of change induces special activity such as specific gene to express or the cytolysis behavior; The cytodifferentiation of immune system cell comprises the outbreak of the surface antigen expression characteristic or the apoptosis (apoptosis) (apoptosis (programmed cell death)) of change.For example, being used to carry out these and similar method for measuring can be at Lefkovits (Immunology Methods Manual:The Comprehensive Sourcebook ofTechniques (immunological method handbook: the technological synthesis data), find in 1998).Also referring to Current Protocols in Immunology (Immunization Update method); Weir, Handbook ofExperimental Immunology (experiment immunization learns to do volume), Blackwell Scientific, Boston, MA (1986); Mishell and Shigii (eds.) Selected Methods in CellularImmunology (cellular immunology method of selection), Freeman press, San Francisco, CA (1979); Green and Reed, Science (science) 281:1309 (1998) and the reference of wherein being quoted).

(for example, specificity is in conjunction with antibody or its antigen-binding fragment of LAR, RPTP-σ and/or RPTP-δ for poxvirus polypeptide such as A41L or 130L or its fragment or variant and reagent as herein described; Nucleic acid molecule (such as fit, siRNA, antisense polynucleotides); Peptide-IgFc fusion polypeptide) the immunoreactive ability of inhibition immunocyte, and the ability that therefore is used for the treatment of Immunological diseases or illness such as autoimmune disorders or inflammatory diseases or illness, cardiovascular disorder or illness, metabolic trouble or illness or hyperplasia or illness, determine in any that can be in the used many animal models of as herein described and those skilled in the art and assessment (referring to, for example, following summary: Taneja etc., Nat.Immunol. (natural immunity) 2:781-84 (2001); Lam-Tse etc., SpringerSemin.Immunopathol. (immunotherapy Springer symposial) 24:297-321 (2002)).For example, knock out three gene Tyro3, Mer of coding receptor tyrosine kinase and the mouse of Axl and show the symptom (Lu etc., Science (science) 293:228-29 (2001)) that some autoimmune disorderss comprise rheumatoid arthritis and SLE.With NZB/WF1 hybrid mouse described spontaneous lupoid acne disease the Muridae model (referring to, for example, Drake etc., Immunol.Rev. (immunology summary) 144:51-74 (1995)).The animal model about type i diabetes that avoids ill reagent and molecule that allows detection influence outbreak, regulates and/or watch for animals uses MHC transgenosis (Tg) mouse.To express the mouse and the hybridization of RIP (rat insulin promoter) .B7-1-Tg mouse of HLA-DQ8 transgenosis (HLA-DQ8 is the main ill gene in people's type i diabetes) and HLA-DQ6 transgenosis (it is the diabetes protections), with provide the HLA-DQ8 RIP.B7-1 transgenic mice of suffering from spontaneous diabetes (referring to, Wakeland etc., Curr.Opin.Immunol. (Immunization Update viewpoint) 11:701-707 (1999); Wen etc., J Exp.Med. (The Journal of Experimental Medicine) 191:97-104 (2000)).(also referring to Brondum etc., Horm.Metab.Res. (hormone metabolism research) 37 supplementary issue 1:56-60 (2005)).

Can be used for characteristic describe the animal model of the reagent be used for the treatment of rheumatoid arthritis comprise collagen protein-inductive arthritis model (referring to, for example, Kakimoto, Chin.Med.Sci.J. (Chinese medicine science magazine) 6:78-83 (1991); Myers etc., Life Sci. (life science) 61:1861-78 (1997)) and the former protein antibodies of anticol-inductive arthritis model (referring to, for example, Kakimoto, as previously mentioned).Other animal model that is suitable for that is used for Immunological diseases comprises experiment autoimmune type encephalomyelitis model (also being called experiment allergic encephalitis model), the sick animal model of multiple sclerosis; Psoriasis model, it uses AGR129 mouse (Zenz etc., Nature (nature) 437:369-75 (2005) of disappearance I type and II type Interferon Receptors and disappearance recombination activating gene 2; Boyman etc., JExp.Med. (The Journal of Experimental Medicine) 199:731-36 (2004); On February 23rd, 2004 is online open); With the TNBS that is used for inflammatory bowel (2,4, the 6-trinitro-benzene-sulfonic acid) mouse model.The many animal models that are used for cardiovascular disorder are available, and are included in van Vlijmen etc., J Clin.Invest. (Journal of Clinical Investigation) 93:1403-10 (1994); Kiriazis etc., Annu.Rev.Physiol. (physiology summary annual) 62:321-51 (2000); Babu etc., the model described in Methods Mol.Med. (molecular medicine method) 112:365-77 (2005).

Immune disorders and treatment of diseases

In another embodiment, be provided for treating and/or preventing the method for Immunological diseases as herein described and illness, particularly inflammatory diseases or illness, autoimmune disorders or illness, cardiovascular disorder or illness, metabolic trouble or illness or hyperplasia or illness disease.Needing the experimenter of such treatment can be the people, perhaps can be inhuman primates or other animal (that is, the animal doctor uses), and it suffers from the symptom of Immunological diseases or it is in the danger of suffering from Immunological diseases.The example of non-human primates and other animal includes but not limited to, farming animals, pet and zoo animal (for example, horse, cow, buffalo, yamma (llama), goat, rabbit, cat, dog, chimpanzee, orangutan, gorilla, monkey, elephant, bear, leopard (large cats) etc.).In certain embodiments, provide to comprise antibody as described herein or its antigen-binding fragment, bi-specific antibody, fusion polypeptide, RPTP Ig structural domain polypeptide (monomer or polymer), macromole, nucleic acid or other reagent, add the composition of pharmaceutical excipient.

As described in this article, be provided for (for example changing, suppress or strengthen) method of immunne response among the experimenter (host or patient), described experimenter suffers from or is in the danger of suffering from Immunological diseases or illness, and described method comprises medicinal suitable carrier and specificity and carries out in conjunction with the composition of at least a antibody among LAR, RPTP-σ and the RPTP-δ or its antigen-binding fragment by using.In special embodiment, described antibody or its antigen-binding fragment can suppress, prevent or compete combining of A41L or 130L and RPTP.In certain embodiments, described composition comprises antibody or its antigen-binding fragment of specificity in conjunction with RPTP-σ, and in another particular, described composition comprises antibody or its antigen-binding fragment of specificity in conjunction with RPTP-δ.Also be provided for (for example changing, suppress or strengthen) method of immunne response among the experimenter (host or patient), described experimenter suffers from or is in the danger of suffering from Immunological diseases or illness, described method comprises medicinal suitable carrier and specificity in conjunction with at least two kinds among LAR, RPTP-σ and the RPTP-δ (for example, LAR and RPTP-σ by using; LAR and RPTP-δ; RPTP-σ and RPTP-δ) antibody (that is, at least) or the composition of its antigen-binding fragment carry out.In a special embodiment, such method suppresses the immunne response among the experimenter.Alternatively, described composition comprises antibody or its antigen-binding fragment of specificity in conjunction with whole three kinds of RPTPs.In certain embodiments, described composition comprises the antibody of pharmaceutical carrier and the whole three kinds of LAR of at least a combination, RPTP-σ and RPTP-δ.In other embodiments, described composition comprises two or more antibody or its antigen-binding fragment arbitrarily as herein described.Therefore, the composition that is used for changing (suppress or strengthen) immunne response comprises at least a antibody in conjunction with LAR, at least a antibody and at least a antibody in conjunction with RPTP-δ in conjunction with RPTP-σ.In another embodiment, described composition comprises at least a antibody in conjunction with LAR and at least a in conjunction with the two antibody of RPTP-σ and RPTP-δ.The invention still further relates to and describe comprise at least a in conjunction with any two kinds first antibody among LAR, RPTP-σ and the RPTP-δ and at least a combination not by the composition of the second antibody of the RPTP of described at least a first antibody specific recognition.

In another embodiment, be provided for treating the method for Immunological diseases or illness, wherein said method comprises to its experimenter of needs to be used medicinal suitable carrier and changes at least a biological activity among LAR, RPTP-σ or the RPTP-δ or change the bioactive reagent of the two or all three kinds at least among LAR, RPTP-σ and the RPTP-δ.The reagent that is used for the treatment of Immunological diseases or illness as herein described (comprises antibody or its antigen-binding fragment; Small molecules; Fit; Antisense polynucleotides; SiRNA (siRNA); Peptide-IgFc fusion polypeptide or peptide Ig constant region structural domain fusion polypeptide; RPTP Ig-spline structure domain polypeptide (monomer or polymer), and RPTP Ig spline structure territory-Ig constant region structural domain fusion polypeptide, all these is described in detail in this article) can change at least a biological activity (function) of (with statistics significant or the significant mode of biology improve or reduce) at least a RPTP.In other embodiments, described reagent changes at least a biological function of at least a, the two or all three kinds among LAR, RPTP-σ and the RPTP-δ.As described herein, these Protein-tyrosine-phosphatase dephosphorylation tyrosyl phosphorproteins are regulated and control the reversible tyrosine phosphorylation effect with protein tyrosine kinase with the kinetics relation that is combined in the cell.The modulated phosphorylation of the tyrosine residues of substrate and dephosphorylation are the major control mechanism of cell processes such as cell growth, cell proliferation, metabolism, differentiation and motion in signal transduction pathway.Therefore, the reagent that is used for the treatment of Immunological diseases or illness can influence or change any one or more biological activity or the function of at least a, the two or all three kinds among LAR, RPTP-σ and the RPTP-δ, it comprises: (1) makes the dephosphorylized ability of the substrate of tyrosyl phosphorylation (that is, influencing catalytic activity); (2) influence the ability of cell proliferation; (3) influence the ability of cellular metabolism; (4) influence the ability of cytodifferentiation; (5) influence the ability of cell movement; (6) ability of the function of the another kind of composition of influence in same signal transduction pathway.

Reagent as herein described, composition, antibody or its fragment, fusion polypeptide, RPTP Ig structural domain polypeptide, molecule and method can be used for the treatment of (that is, cure, prevent, alleviate the symptom of Immunological diseases or illness or slow down, suppress or stop the development) Immunological diseases or illness.Special disease or illness can be treated by the special reagent of using significant quantity, and the special reagent of described significant quantity can easily be determined by the technician of medical field.The such disease and the illness that are autoimmune disorders or inflammatory diseases include but not limited to, the multiple sclerosis disease, rheumatoid arthritis, system lupus erythematosus (SLE), graft versus host disease (GVHD), Sepsis, diabetes, psoriatic, atherosclerosis, xerodermosteosis, expansionary system sclerosis, scleroderma, acute coronary syndrome, ischemic pours into again, regional ileitis, endometriosis, glomerulonephritis, myasthenia gravis, the idiopathic pulmonary fibrosis, asthma, adult respiratory distress syndrome (ARDS), vasculitis or inflammatory autoimmune myositis.Immune disorders or disease also comprise cardiovascular disorder or illness, metabolic trouble or illness or hyperplasia or illness.Comprise according to method as herein described and use treatable cardiovascular disorder of described reagent or illness, for example, atherosclerosis, endocarditis, hypertension or periphery local asphyxia disease.The metabolic trouble that also is Immunological diseases or illness comprises, diabetes, regional ileitis and inflammatory bowel.A kind of exemplary hyperplasia is a cancer.

When being used for this paper, patient (or experimenter) can be any Mammals, comprises the people, and it can suffer from or stand the torment of Immunological diseases or illness, and perhaps it can not suffer from detectable disease.Therefore, described treatment can be administered to the experimenter who suffers from already present disease, and perhaps described treatment can prophylactically be administered to the experimenter of the danger that is in the development disease or the patient's condition.

Pharmaceutical composition can be aseptic water-based or non-aqueous solution, suspension or milk sap, and it comprises the acceptable vehicle of physiology (vehicle that pharmacy is acceptable or suitable or carrier) (that is, not the active nontoxicity material of interferon activity composition) in addition.Such composition can be the form of solid, liquid or gas (aerosol).Alternatively, composition as herein described can be used as the lyophilized products preparation, perhaps can use technology known in the art that compound is encapsulated in the liposome.Pharmaceutical composition can also comprise other composition, and it can be bioactive or non-activity.Such composition comprises, but be not limited to, buffer reagent (for example, the salts solution of neutral buffered salts solution or phosphoric acid buffer), carbohydrate (for example, glucose, seminose, sucrose or dextran), N.F,USP MANNITOL, protein, polypeptide or amino acid such as glycine, antioxidant, sequestrant such as EDTA or gsh, stablizer, dyestuff, seasonings and suspensoid and/or sanitas.

Any appropriate excipients or carrier that those of ordinary skill in the art becomes known for pharmaceutical composition can be used for composition as herein described.The vehicle that treatment is used is known, and for example, at Remingtons Pharmaceutical Sciences (Lei Mingdun pharmaceutical science), describes in the Mack publishing company (A.R.Gennaro ed.1985).Usually, based on the type of the model selection vehicle of using.Pharmaceutical composition can be prepared and be used for any suitable method of application, comprise, for example, in local, oral, nose, the sheath, under the rectum, vagina, intraocular, conjunctiva, hypogloeeis or parenteral administration, it comprises in subcutaneous, intravenously, intramuscular, the breastbone in (intrasternal), the hole in (intracavernous), the road (intraurethral) or urethra is interior injects or infusion.For parenteral administration, described carrier preferably includes water, salt solution, alcohol, fat, paraffin or damping fluid.For Orally administered, can use any above-mentioned vehicle or solid excipient or carrier, such as N.F,USP MANNITOL, lactose, starch, Magnesium Stearate, soluble saccharin, talcum, Mierocrystalline cellulose, kaolin, glycerine, amylodextrin, sodiun alginate, carboxymethyl cellulose, ethyl cellulose, glucose, sucrose and/or magnesiumcarbonate.

Pharmaceutical composition (for example, be used for Orally administered or pass through injected delivery) can be a liquid form.Composition of liquid medicine can comprise, for example, and following one or more: sterile diluent that is used to inject such as water, salts solution, preferred physiology salt, Ringer's solution, isotonic sodium chloride can be used as the fixed oil of solvent or suspension medium, polyoxyethylene glycol, glycerine, propylene glycol or other solvent; Antibacterial agent; The antioxidant sequestrant; Regulate the buffer reagent and the reagent of opening property, such as sodium-chlor or dextrose.Parenteral administration can be packaged in ampoule, disposable syringe or the multiple dose vials of being made by glass or plastics.Preferred use physiological saline, and Injectable composition is preferably aseptic.

Reagent as herein described, it comprises that specificity is in conjunction with at least a antibody among LAR, RPTP-σ and the RPTP-δ and antigen-binding fragment and bi-specific antibody, small molecules, nucleic acid molecule, RPTP Ig spline structure domain polypeptide, and peptide and polypeptide amalgamation protein, can prepare and be used for continuing or discharge slowly.Such composition can be to use technique known preparation usually, and, for example, use by oral, rectum or subcutaneous transplantation or by transplanting in the target spot site of needs.Sustained release formulation can comprise and is dispersed in the carrier matrix and/or is included in by the reagent in the membrane-enclosed reservoir of rate-controlling.The vehicle that is used in the described preparation is biocompatible, and can be biodegradable; Preferably described preparation provides relative constant activeconstituents emission levels.The amount that is included in the active compound in the extended release preparation depends on the time length of the speed of the site of transplanting, release and expectation and the character of the patient's condition that will treat or prevent.

Be used for the treatment of the parameter that the dosage of the composition of Immunological diseases or illness can understand according to the technician of medical field and determine.Therefore, suitable dosage can depend on the patient () the patient's condition for example, the people, that is, the stage of disease, comprehensive health state, and age, sex and body weight, and the other factors be familiar with of the technician of medical field.

The mode of the disease of (or prevention) suitable to be treated that pharmaceutical composition can be determined with the technician by field of medicaments is used.Suitable dosage and suitable time length and frequency of administration will be determined by such factor: as patient's the patient's condition, and the type of patient disease and seriousness, the specific form of activeconstituents and the method for using.Usually, suitable dosage and treatment plan treat and/or prevent benefit (for example, the clinical effectiveness of improvement are such as more frequent elimination wholly or in part to be enough to provide, or more permanent anosis and/or total survival, or the seriousness of mitigation symptoms) amount provides described composition.For prophylactic applications, the outbreak of the disease that dosage should be enough to prevent, delay is relevant with Immunological diseases or illness or reduce its seriousness.

Optimal dose can use experimental model and/or clinical trial usually and determine.Optimal dose can depend on patient's body quality, weight or blood volume.Usually, polypeptide, such as antibody as herein described or its antigen-binding fragment or fusion polypeptide or RPTP Ig structural domain polypeptide, the amount that in dosage, exists or produce by the DNA original position that is present in the dosage, from about 0.01 μ g in about 1000 μ g/kg hosts' scope.Usually the preferred minimum dose that is enough to provide effective treatment that uses.Usually can use the mensuration that is applicable to the patient's condition of being treated or preventing and the treatment or the preventive effect of monitoring the patient, described mensuration is that those ordinarily skilled in the art are familiar with.Suitable dosage size should be different along with patient's size, but typically in the scope of experimenter from about 1ml to about 500ml for 10-60kg.

For the pharmaceutical composition that comprises as the reagent of nucleic acid molecule, that described nucleic acid molecule comprises is fit, siRNA, antisense or ribozyme or peptide-nucleic acid, described nucleic acid molecule may reside in any of the known various delivery systems of those of ordinary skill in the art, comprise nucleic acid, and bacterium, virus and mammalian expression system, such as for example, recombinant expression construct body provided herein.The technology that is used for DNA is combined in such expression system is that those ordinarily skilled in the art are known.Described DNA also can be " naked ", for example at Ulmer etc., and Science (science) 259:1745-49, described in 1993 and by Cohen, Science (science) 259:1691-1692,1993 are summarized.The picked-up of naked DNA can be by improving on the biodegradable pearl in the effective transporte to cells of described DNA bag quilt to quilt.

Nucleic acid molecule can according in the described certain methods in this area any and be delivered in the cell (referring to, for example, Akhtar etc., Trends Cell Bio. (cytobiology trend) 2:139 (1992); Delivery Strategies for Antisense Oligonucleotide Therapeutics (delivery strategies of antisense strategy), Akhtar compiles, 1995, Maurer etc., Mol.Membr.Biol. (molecular film biology) 16:129-40 (1999); Hofland and Huang, Handb.Exp.Pharmacol. (experimental drug learns to do volume) 137:165-92 (1999); Lee etc., ACS Symp.Ser.752:184-92 (2000); U.S. Patent number 6,395,713; International application published WO 94/02595); Selbo etc., Int.J.Cancer (international journal of cancer) 87:853-59 (2000); Selbo etc., Tumour Biol. (oncobiology) 23:103-12 (2002); U.S. Patent Application Publication No. 2001/0007666 and 2003/077829).Such delivering method known to those skilled in the art includes, but not limited to be encapsulated in the liposome, by iontophoresis, perhaps by being attached in other vehicle, in Biodegradable polymeric; Hydrogel; Cyclodextrin (referring to, for example, Gonzalez etc., Bioconjug.Chem. (biology is puted together chemistry) 10:1068-74 (1999); Wang etc., international application published WO 03/47518 and WO 03/46185); Poly-(lactic acid-altogether-oxyacetic acid) acid (PLGA) and PLCA microsphere (also being used to send peptide and polypeptide and other material) (referring to, for example, U.S. Patent number 6,447,796; U.S. Patent Application Publication No. 2002/130430); Biodegradable Nano capsule; With the microsphere of bioadhesive, perhaps by protein carrier (international application published WO00/53722).In another embodiment, be used for changing the immunne response of (suppress or strengthen) immunocyte and be used for the treatment of Immunological diseases or the nucleic acid molecule of illness can also with polymine and derivative thereof such as polymine-polyoxyethylene glycol-N-acetylgalactosamine (PEI-PEG-GAL) or the preparation of polymine-polyoxyethylene glycol-three-N-acetylgalactosamine (PEI-PEG-triGAL) derivative or compound (also referring to, for example, U.S. Patent Application Publication No. 2003/0077829).

The present invention also is provided for produce changing the immunoreactivity of (suppress or strengthen) immunocyte and is used for the treatment of the preparation method of reagent who suffers from or be in the experimenter of the danger of suffering from Immunological diseases or illness.In one embodiment, such preparation method comprises: (a) identify the immunoreactive reagent that suppresses immunocyte according to the method for implementing in as herein described and this area.For example, indentifying substance comprises: fully allowing between at least a RPTP polypeptide and poxvirus polypeptide such as A41L and the 130L interactional condition and under the time, with following contact: (i) candidate agent; (ii) express and be selected from leukocyte common antigen (LCA) associated protein (LAR); RPTP-σ; Immunocyte with at least a receptor-like protein tyrosine phosphatase (RPTP) polypeptide among the RPTP-δ; (iii) A41L.Determine combining of in the presence of candidate agent described poxvirus polypeptide and described immunocyte, and the poxvirus polypeptide is compared with the combination of immunocyte when not having described candidate agent, and wherein the bonded of described poxvirus polypeptide and described immunocyte reduces and shows that described candidate agent suppresses the immunoreactivity of immunocyte in the presence of candidate agent.Be used to produce described compositions and methods and produce described reagent according to known in the art then.

Described reagent can be any reagent as herein described, such as for example, and antibody or its antigen-binding fragment; Bi-specific antibody, small molecules; Fit; Antisense polynucleotides; SiRNA (siRNA); RPTP Ig-spline structure domain polypeptide (monomer or polymer) and peptide-IgFc fusion polypeptide.In a special embodiment, described reagent is antibody or its antigen-binding fragment, and it can be according to as herein described and be applicable to that the method for mass preparation produces.For example, production method comprises the cell batch cultivation, and its monitored and control is to keep suitable culture condition.The purifying of antibody or its antigen-binding fragment can according to as herein described and known in the art and meet the home and overseas regulating and controlling mechanism guidance method and carry out.

Provide the following examples to illustrate the present invention, but it is not considered to limitation of the scope of the invention.

Embodiment

Embodiment 1

Identify the RPTPs that on immunocyte, expresses with the A41L bonded

Present embodiment is described the method be used to identify with A41L bonded cell surface polypeptide.

Structure comprises the recombinant expression vector of the polynucleotide of coding cowpox A41L fusion polypeptide, with be used for tandem affinity purification (TAP) method (also being called the Tap marking method) (also referring to, for example, Rigaut etc., Nat.Biotech. (Nature Biotechnol) 17:1030-32 (1999); Puig etc., Methods (method) 24:218-29 (2001); Knuesel etc., Mol.Cell.Proteomics (molecular cell proteomics) 2:1225-33 (2003)).Preparation is called the construct of A41LCRFC, and expresses with method with the affinity purification technology and separate fusion polypeptide according to standard molecular biology.The synoptic diagram of construct provides in Fig. 2.Described A41LCRFC construct comprises the nucleotide sequence from the ripe A41L encoding sequence of vaccinia virus that coding is fused to human growth hormone leading peptide C end.CRFC series connection affinity labelling is fused to the C end of A41L.Described CRFC mark comprises human influenza virus's hemagglutinin peptide, HA epi-position, amino acid YPYDVDYA (SEQ ID NO:67), can be commercially available for its antibody, the expression that allows cell sorting (FACS) or immunoblotting by immuno-chemical method such as fluorescence-activation to detect fusion polypeptide.Be fused to the HA epi-position carboxyl terminal be the protein C mark, amino acid EDQVDPRLIDGK (SEQ ID NO:68), it derives from the heavy chain of human protein C.Carboxyl terminal at the protein C mark merges ERC group virus HRV3C protease site, amino acid LEVLFQGP (SEQ ID NO:69); And merge the mutain derivative of the Fc part of human IgG at the carboxyl terminal of HRV3C protease site.

The synoptic diagram that illustrates the TAP marking method is described in Fig. 3.With 10 μ g and a-protein bonded A41LCRFC fusion polypeptide with from 5 * 10 ⁶The cell lysate of individual monocyte preparation is incubation together.Many normal cells and tumor cell type can be used for identifying and combine or interactional cell polypeptide with A41L, comprise B cell and T cell (activated or unactivated), scavenger cell, epithelial cell, inoblast and clone such as Raji (B cell lymphoma), THP-1 (acute monocytic leukemia) and Jurkat (T chronic myeloid leukemia).

Wash A41LCRFC/ cell lysate mixture, and stand the division of HRV3C proteolytic enzyme then, it discharges A41L and associating albumen.Calcium chloride (1M) is joined in the A41L/ cell lysate mixture of release, use it for the affine resin of anti--protein C-mark then.Calcium chloride is that anti--C-mark and the interaction of C-mark epi-position are needed.Mixture on the affine resin of-protein C-mark anti-with being attached to washs in containing the damping fluid of calcium chloride, and uses EGTA to pass through the calcium chelating and wash-out then.With eluate tryptic digestion subsequently, and the A41L mixture of digestion carried out direct tandem mass spectrum to identify A41L and associating albumen thereof.

The sequence of the peptide of trypsinase-generation is identified by mass spectrum.Described peptide is accredited as the receptor-like protein tyrosine phosphatase, and the part of LAR, RPTP-σ and RPTP-δ is respectively as shown in Fig. 4 A, 4B and the 4C.

Embodiment 2

Preparation A41L-Fc fusion polypeptide

Present embodiment is described the preparation of the recombinant expression vector be used to express A41L-Fc fusion polypeptide and A41L-mutain Fc fusion polypeptide.

Recombinant expression vector is prepared according to the conventional method of implementing of the technician of biology field.The polynucleotide of the polynucleotide of coding A41L-Fc and coding A41L-mutain Fc are cloned in the multiple clone site of carrier pDC409 (referring to, for example, U.S. Patent number 6,512,095 and U.S. Patent number 6,680,840, and the reference of wherein being quoted).The A41L-Fc amino acid sequence of polypeptide is listed in SEQ ID NO:74, and A41L-mutain Fc amino acid sequence of polypeptide is listed (referring to Fig. 5) in SEQ ID NO:73.The nucleotides sequence of encoding mutant albumen Fc (human IgG1) polypeptide (SEQ ID NO:77) is listed among the SEQ ID NO:78 to be listed.With every kind of expression plasmid transfection of 10 to 20 μ g on the normal structure culture plate of 10cm diameter, growing to about 80% HEK293T cell that converges or COS-7 cell (American Type TissueCollection (American type culture collection, ATCC), the Manassas, VA) in.Lipofectamine is used in transfection ^TMPlus ^TM(Invitrogen company, Carlsbad CA) carries out.Cells transfected was cultivated 48 hours, then the supernatant of collecting cell culture.The A41L fusion rotein carries out purifying according to standard method by the a-protein agarose affinity chromatography.

Embodiment 3

The RPTPs that evaluation is expressed on the immunocyte in conjunction with tanapox virus 130L

Present embodiment is described the method that is used to identify in conjunction with the cell surface polypeptide of 130L.

As described in the embodiment 1, make up the recombinant expression vector of the polynucleotide that comprise coding 130L fusion polypeptide, be used for tandem affinity purification (TAP) method (also being called the Tap marking method).Prepare described construct, and express and separate described fusion polypeptide according to standard molecular biology and affinity purification technology and method.

Described 130L series connection affinity labelling construct comprises the nucleotide sequence of coding from the ripe 130L aminoacid sequence of YLDV, it is fused to coding human growth hormone signal peptide aminoacid sequence, and (nucleotides sequence of the C end of MATGSRTSLLLAFGLLCLPWLQEGSA (SEQ ID NO:153) lists (that is 3 ' the end that 5 ' end of the nucleotide sequence of the 130L that, encodes is fused to the nucleotide sequence of coded signal peptide).

Described series connection affinity labelling is fused to the C end of 130L.Described mark comprises human influenza virus's hemagglutinin peptide, HA epi-position, amino acid YPYDVDYA (SEQ ID NO:141), can be commercially available to its antibody, the expression that allows cell sorting (FACS) or immunoblotting by immuno-chemical method such as fluorescence-activation to detect fusion polypeptide.Be fused to the HA epi-position carboxyl terminal be the protein C mark, amino acid EDQVDPRLIDGK (SEQ ID NO:142), it derives from the heavy chain of human protein C.Carboxyl terminal at the protein C mark merges ERC group virus HRV3C protease site, amino acid LEVLFQGP (SEQ ID NO:143); And merge the mutain derivative (for example, SEQ ID NO:146) of the Fc part of human IgG at the carboxyl terminal of HRV3C protease site.

Allow the recombinant expressed 130L fusion polypeptide of 10 μ g to combine with the a-protein affinity matrix.Will be with a-protein bonded 130L fusion polypeptide and from 5 * 10 ⁶The cell lysate of individual monocyte preparation is incubation together.Many normal cells and tumor cell type can be used for identifying and combine or interactional cell polypeptide with 130L, comprise B cell and T cell (activated or unactivated), scavenger cell, epithelial cell, inoblast and clone such as Raji (B cell lymphoma), THP-1 (acute monocytic leukemia) and Jurkat (T chronic myeloid leukemia).

Wash 130L fusion polypeptide/cell lysate mixture, and stand the cracking of HRV3C proteolytic enzyme then, it discharges 130L and associating albumen.Calcium chloride (1M) is joined in the 130L/ cell lysate mixture of release, use it for the affine resin of anti--protein C-mark then.Calcium chloride is that anti--C-mark and the interaction of C-mark epi-position are needed.Mixture on the affine resin of-protein C-mark anti-with being attached to washs in containing the damping fluid of calcium chloride, and uses EGTA to pass through the calcium chelating and wash-out then.With eluate tryptic digestion subsequently, and the 130L mixture of digestion carried out direct tandem mass spectrum to identify 130L and associating albumen thereof.

The sequence of the peptide of trypsinase-generation is identified by mass spectrum.Described peptide is accredited as the receptor-like protein tyrosine phosphatase, and the part of LAR, RPTP-σ and RPTP-δ is respectively as shown in Fig. 7 A, 7B and the 7C.

Embodiment 4

In non-adherent PBMCs, induce IFN-γ by LAR (IG structural domain)-Fc fusion rotein

When being described in existence and not having the allos donorcells, in peripheral blood lymphocytes (PBMCs), produces present embodiment IFN-γ.

The recombinant expression vector that is used to express the LAR-Fc fusion rotein is prepared according to the conventional method of implementing of the technician of biology field.The nucleotide sequence of the nucleotide sequence of first immunoglobulin like domain (Ig-1), second immunoglobulin like domain (Ig-2) and the 3rd immunoglobulin like domain (Ig-3) of coding LAR and coding Fc mutain polypeptide is met the fusion of frame ground.Described Fc mutain polypeptide derives from human IgG1's immunoglobulin (Ig).Described expression construct transfection in cell, and is separated expressed fusion polypeptide by the a-protein affinity chromatography from cell conditioned medium.

According to the standard method of this area, separation of human PBMCs from the fresh whole blood of taking.Enrichment PBMCs, obtaining not adherent PBMC, its RPMI that contains 2% human serum by PBMCs being placed tissue culture flasks 2 hours shifts out gently then and contains the not cell culture supernatant of adherent cell.Then with described not adherent cell (2 * 10 ⁵) single culture, perhaps have 10 ⁴0.8,4, cultivate in 20 and 100 μ g/ml LAR-Fc or the human IgG in the blended lymphocyte reaction thing of the dendritic cell in the monocyte-source of individual each from two allos donors (Do476 and Do495).After 18 hours, by measuring the IFN-γ that determines by described not adherent PBMC production.The concentration of IFN-γ in cell conditioned medium is determined (DuoSet ELISA people IFN-γ, catalog number (Cat.No.) D6285, R﹠amp by ELISA; The D development system, Minneapolis (Minneapolis), MN).As shown in FIG. 8, in blended lymphocyte reaction thing, the LAR-Fc fusion rotein improves the not IFN-γ secretion (Fig. 8 B and 8C) of adherent PBMC.In addition, when not having antigenic stimulation, the not adherent PBMC that handles with LAR-Fc produces IFN-γ (Fig. 8 A).

Embodiment 5

The gel permeation chromatography of LAR (IG structural domain)-Fc fusion rotein

Present embodiment is described the size exclusion chromatography of LAR Ig1-Ig2-Ig3-Fc (LAR-Fc) fusion polypeptide.

The LAR-Fc fusion polypeptide is according to preparation described in the embodiment 4.Then described fusion polypeptide is analyzed by the HPLC that uses gel-filtration column, to obtain the estimation molecular weight of described fusion polypeptide.The wash-out collection of illustrative plates is described in Fig. 9.The apparent molecular weight of described polypeptide by with elution time (minute) relatively determine with the elution time of standardized molecular weight marker polypeptide.The molecular weight of estimating according to described gel-filtration method is about 260,000 dalton.Prediction LAR-Fc fusion polypeptide forms dimer according to the interaction between two Fc polypeptide, and the molecular weight that calculates is 140,000 dalton.These data show, if described fusion polypeptide dimer has globosity, it is big that the Stoke ' s radius ratio of so described fusion polypeptide is predicted.Do not wish to be bound by theory, the Ig structural domain of each of two kinds of LARFc fusion polypeptide can be interact with each other forming dimeric structure, it does not rely on and is different from interaction between the Fc part of two kinds of fusion polypeptide.

Embodiment 6

Interaction between A41L and the LARIG structural domain

Present embodiment is described the interaction between the immunoglobulin like domain of A41L and LAR.

Application standard Protocols in Molecular Biology and according to described in the embodiment 2, the recombinant expression vector that preparation is used to express the LAR-Fc fusion polypeptide.Described fusion polypeptide comprises the TAP-Fc fusion polypeptide: have the fusion polypeptide of first, second and the 3rd immunoglobulin like domain and TAP sequence, it comprises human IgG Fc peptide sequence (LAR Ig1-2-3-tapFC); The fusion polypeptide (LAR Ig1-tapFC) of first immunoglobulin like domain of the LAR that merges with TAP-Fc; Fusion polypeptide (LAR Ig1-Ig2-tapFC) with first and second immunoglobulin like domain that merge with TAP-Fc.Described TAP construct is expressed in the 293-T17 cell.Expression vector cells transfected with this coding LAR Ig1-Ig2-tapFC is not expressed fusion polypeptide.The LAR Ig1-Ig2-Ig3-Fc fusion polypeptide and the P35-FC polypeptide (non--RPTP, non--contrast of A41L polypeptide) that also comprise purifying.

Carry out immunoprecipitation.With the recombinant expression construct body transfection of cell with coding every kind of TAP-Fc fusion polypeptide mentioned above, cultivate, and the collecting cell supernatant liquor.With described supernatant liquor and the A41L polypeptide (monomer) that adds the purifying of the pearl that a-protein puts together combine.The P35-FC and the LAR Ig1-Ig2-Ig3-Fc fusion polypeptide that are included as contrast are the polypeptide of purifying, and with the A41L incubation of purifying.Then the polypeptide that merges is separated from immunoprecipitate, and carry out SDS-PAGE.Pass through immunoblotting assay with the existence of LAR fusion polypeptide bonded A41L.The result describes in Figure 10.A41L combines with the LAR fusion polypeptide that comprises whole three kinds of immunoglobulin like domain, and does not combine with LAR Ig1-tapFC fusion polypeptide.

Should be appreciated that from preamble,, can carry out the various improvement that do not deviate from the spirit and scope of the present invention although this paper has described special embodiment of the present invention for illustrational purpose.Those skilled in the art uses the experiment of no more than routine just to should be realized that or can determine many Equivalents of special embodiment of the present invention as herein described.Such Equivalent is intended to be contained by accompanying Claim.

Sequence table

＜110〉Viral Logic Systems Technology

Daniel Craig A Smith

The Shi Difen Willie

A Jiamaitekayikasi

In the Jia Lalewaji

Peter's Probst

＜120〉immune regulation composite and application thereof

<130>930118.401PC

<140>PCT

<141>2006-09-29

<150>US?60/801,992

<151>2006-05-19

<150>US?60/784,710

<151>2006-03-22

<160>157

<170>FastSEQ?for?Windows?Version?4.0

<210>1

<211>218

<212>PRT

＜213〉big variola virus, strain Harvey

<400>1

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>2

<211>218

<212>PRT

＜213〉variola virus, strain India-1967

<400>2

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Thr?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>3

<211>218

<212>PRT

＜213〉alastrim virus, strain Garcia-1966

<400>

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asn?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>4

<211>219

<212>PRT

＜213〉vaccinia virus, strain WR

<400>4

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Lys?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Thr?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>5

<211>219

<212>PRT

＜213〉vaccinia virus, strain Tian Tan

<400>5

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>6

<211>219

<212>PRT

＜213〉vaccinia virus, strain Ankara

<400>6

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?His?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>7

<211>219

<212>PRT

＜213〉vaccinia virus, strain Copenhagen

<400>7

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>8

<211>218

<212>PRT

＜213〉vaccinia virus, strain Brighton Red

<400>8

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr

85 90 95

Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly

130 135 140

Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn?Val

145 150 155 160

Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Ser?Cys

210 215

<210>9

<211>654

<212>DNA

＜213〉vaccinia virus, strain Brighton Red

<400>9

atgtactcat?tatttattat?tttgatgggt?ctaccattta?gttttcaaac?aagtgaacca?60

gcgtatgata?aatcggtatg?cgattctaac?aataaagaat?atatgggaat?agaagtttat?120

gtagaagcaa?cgctagacga?acccctcaga?caaacaacgt?gtgaatccga?aatccataaa?180

tatggtgcat?ctgtatcaaa?cggaggatta?aatatttctg?ttgatctatt?aaactgtttt?240

cttaattttc?atacagttgg?tgtatacact?aatcgcgata?ccgtatacgc?gaagtttgct?300

agtttggatc?catctacgga?acctataaat?tctatgaccc?atgacgatct?agtaaaatta?360

acagaagaat?gtatagtgga?catttattta?aaatgtgaag?tggataaaac?aaaggatttc?420

atgaaaaacg?gcaatagatt?aaaaccaaga?gactttaaaa?ctgttcctcc?ttctaatgta?480

ggaagtatga?tcgaactaca?gtctgactat?tgcgtagaag?atgtgactgc?atacgtcaaa?540

atatacgatg?agtgcggaaa?cattaaacag?cattccattc?caacactacg?agattatttt?600

accaccaaga?atggtcaacc?acgtaaaata?ttaaagaaaa?aatttgatag?ttgt 654

<210>10

<211>219

<212>PRT

＜213〉vaccinia virus

<400>10

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>11

<211>277

<212>PRT

＜213〉variola virus

<400>11

Met?Leu?Arg?Val?Arg?Ile?Leu?Leu?Ile?Tyr?Leu?Cys?Thr?Phe?Val?Val

1 5 10 15

Ile?Thr?Ser?Thr?Lys?Thr?Ile?Glu?Tyr?Thr?Ala?Cys?Asn?Asp?Thr?Ile

20 25 30

Ile?Ile?Pro?Cys?Thr?Ile?Asp?Asn?Pro?Thr?Lys?Tyr?Ile?Arg?Trp?Lys

35 40 45

Leu?Asp?Asn?His?Asn?Ile?Leu?Thr?Tyr?Asn?Lys?Thr?Ser?Lys?Thr?Ile

50 55 60

Ile?Leu?Ser?Lys?Trp?His?Thr?Ser?Ala?Lys?Leu?His?Ser?Leu?Ser?Asp

65 70 75 80

Asn?Asp?Val?Ser?Leu?Ile?Ile?Lys?Tyr?Lys?Asp?Ile?Leu?Pro?Gly?Thr

85 90 95

Tyr?Thr?Cys?Glu?Asp?Asn?Thr?Gly?Ile?Lys?Ser?Thr?Val?Lys?Leu?Val

100 105 110

Gln?Arg?His?Thr?Asn?Trp?Phe?Asn?Asp?His?His?Thr?Met?Leu?Met?Phe

115 120 125

Ile?Phe?Thr?Gly?Ile?Thr?Leu?Phe?Leu?Leu?Phe?Leu?Glu?Ile?Ala?Tyr

130 135 140

Thr?Ser?Ile?Ser?Val?Val?Phe?Ser?Thr?Asn?Leu?Gly?Ile?Leu?Gln?Val

145 150 155 160

Phe?Gly?Cys?Ile?Ile?Ala?Met?Ile?Glu?Leu?Cys?Gly?Ala?Phe?Leu?Phe

165 170 175

Tyr?Pro?Ser?Met?Phe?Thr?Leu?Arg?His?Ile?Ile?Gly?Leu?Leu?Met?Met

180 185 190

Thr?Leu?Pro?Ser?Ile?Phe?Leu?Ile?Ile?Thr?Lys?Val?Phe?Ser?Phe?Trp

195 200 205

Leu?Leu?Cys?Lys?Leu?Ser?Cys?Ala?Val?His?Leu?Ile?Ile?Tyr?Tyr?Gln

210 215 220

Leu?Ala?Gly?Tyr?Ile?Leu?Thr?Val?Leu?Gly?Leu?Gly?Leu?Ser?Leu?Lys

225 230 235 240

Glu?Cys?Val?Asp?Gly?Thr?Leu?Leu?Leu?Ser?Gly?Leu?Gly?Thr?Ile?Met

245 250 255

Val?Ser?Glu?His?Phe?Ser?Leu?Leu?Phe?Leu?Val?Cys?Phe?Pro?Ser?Thr

260 265 270

Gln?Arg?Asp?Tyr?Tyr

275

<210>12

<211>277

<212>PRT

＜213〉variola virus

<400>12

Met?Leu?Arg?Val?Arg?Ile?Leu?Leu?Ile?Tyr?Leu?Cys?Thr?Phe?Val?Val

1 5 10 15

Ile?Thr?Ser?Thr?Lys?Thr?Ile?Glu?Tyr?Thr?Ala?Cys?Asn?Asp?Thr?Ile

20 25 30

Ile?Ile?Pro?Cys?Thr?Ile?Asp?Asn?Pro?Thr?Lys?Tyr?Ile?Arg?Trp?Lys

35 40 45

Leu?Asp?Asn?His?Asn?Ile?Leu?Thr?Tyr?Asn?Lys?Thr?Ser?Lys?Thr?Ile

50 55 60

Ile?Leu?Ser?Lys?Trp?His?Thr?Ser?Ala?Lys?Leu?His?Ser?Leu?Ser?Asp

65 70 75 80

Asn?Asp?Val?Ser?Leu?Ile?Ile?Lys?Tyr?Lys?Asp?Ile?Leu?Pro?Gly?Thr

85 90 95

Tyr?Thr?Cys?Glu?Asp?Asn?Thr?Gly?Ile?Lys?Ser?Thr?Val?Lys?Leu?Val

100 105 110

Gln?Arg?His?Thr?Asn?Trp?Phe?Asn?Asp?His?His?Thr?Met?Leu?Met?Phe

115 120 125

Ile?Phe?Thr?Gly?Ile?Thr?Leu?Phe?Leu?Leu?Phe?Leu?Glu?Ile?Ala?Tyr

130 135 140

Thr?Ser?Ile?Ser?Val?Val?Phe?Ser?Thr?Asn?Leu?Gly?Ile?Leu?Gln?Val

145 150 155 160

Phe?Gly?Cys?Ile?Ile?Ala?Met?Ile?Glu?Leu?Cys?Gly?Ala?Phe?Leu?Phe

165 170 175

Tyr?Pro?Ser?Met?Phe?Thr?Leu?Arg?His?Ile?Ile?Gly?Leu?Leu?Met?Met

180 185 190

Thr?Leu?Pro?Ser?Ile?Phe?Leu?Ile?Ile?Thr?Lys?Val?Phe?Ser?Phe?Trp

195 200 205

Leu?Leu?Cys?Lys?Leu?Ser?Cys?Ala?Val?His?Leu?Ile?Ile?Tyr?Tyr?Gln

210 215 220

Leu?Ala?Gly?Tyr?Ile?Leu?Thr?Val?Leu?Gly?Leu?Gly?Leu?Ser?Leu?Lys

225 230 235 240

Glu?Cys?Val?Asp?Gly?Thr?Leu?Leu?Leu?Ser?Gly?Leu?Gly?Thr?Ile?Met

245 250 255

Val?Ser?Glu?His?Phe?Ser?Leu?Leu?Phe?Leu?Val?Cys?Phe?Pro?Ser?Thr

260 265 270

Gln?Arg?Asp?Tyr?Tyr

275

<210>13

<211>221

<212>PRT

＜213〉monkey pox virus

<400>13

Met?Tyr?Leu?Leu?Phe?Ile?Ile?Leu?Met?Tyr?Leu?Leu?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn

20 25 30

Lys?Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu

35 40 45

Pro?Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala

50 55 60

Ser?Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys

65 70 75 80

Phe?Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val

85 90 95

Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn

100 105 110

Ser?Met?Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val

115 120 125

Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys

130 135 140

Thr?Asn?Asp?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro

145 150 155 160

Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn

165 170 175

Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys

180 185 190

Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly

195 200 205

Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Ile?Asp?Asn?Cys

210 215 220

<210>14

<211>218

<212>PRT

＜213〉variola virus

<400>14

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Thr?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>15

<211>219

<212>PRT

＜213〉vaccinia virus (strain WR)

<400>15

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Lys?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Thr?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>16

<211>219

<212>PRT

＜213〉vaccinia virus (strain Copenhagen)

<400>16

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>17

<211>219

<212>PRT

＜213〉vaccinia virus

<400>17

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?His?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>18

<211>219

<212>PRT

＜213〉camelpox virus

<400>18

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asp?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Val

65 70 75 80

Asn?Leu?Asn?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn

145 150 155 160

Ile?Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Val?Tyr?Val?Lys?Ile?Tyr?Asp?Ala?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>19

<211>277

<212>PRT

＜213〉camelpox virus

<400>19

Met?Leu?Arg?Val?Arg?Ile?Leu?Leu?Ile?Tyr?Leu?Cys?Thr?Phe?Val?Val

1 5 10 15

Ile?Thr?Ala?Thr?Lys?Thr?Ile?Glu?Tyr?Met?Ala?Cys?Asn?Asp?Thr?Ile

20 25 30

Ile?Ile?Pro?Cys?Thr?Ile?Asp?Asn?Pro?Thr?Lys?Tyr?Ile?Arg?Trp?Lys

35 40 45

Leu?Asp?Asn?His?Asp?Ile?Leu?Thr?Tyr?Asn?Lys?Thr?Ser?Lys?Thr?Thr

50 55 60

Ile?Leu?Ser?Lys?Trp?His?Thr?Ser?Ala?Lys?Leu?His?Ser?Leu?Ser?Asp

65 70 75 80

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

85 90 95

Tyr?Thr?Cys?Glu?Asp?Asn?Thr?Gly?Ile?Lys?Ser?Thr?Val?Lys?Leu?Val

100 105 110

Gln?Arg?His?Thr?Asn?Trp?Phe?Asn?Asp?His?His?Thr?Met?Leu?Met?Phe

115 120 125

Ile?Phe?Thr?Gly?Ile?Thr?Leu?Phe?Leu?Leu?Phe?Leu?Glu?Ile?Ala?Tyr

130 135 140

Thr?Ser?Thr?Ser?Val?Val?Phe?Ser?Thr?Asn?Leu?Gly?Ile?Leu?Gln?Val

145 150 155 160

Phe?Gly?Cys?Ile?Ile?Ala?Met?Ile?Glu?Leu?Cys?Gly?Ala?Phe?Leu?Phe

165 170 175

Tyr?Pro?Ser?Met?Phe?Thr?Leu?Arg?His?Ile?Ile?Gly?Leu?Leu?Met?Met

180 185 190

Thr?Leu?Pro?Ser?Ile?Phe?Leu?Ile?Ile?Thr?Lys?Val?Phe?Ser?Phe?Trp

195 200 205

Leu?Leu?Cys?Lys?Leu?Ser?Cys?Ala?Val?His?Leu?Ile?Ile?Tyr?Tyr?Gln

210 215 220

Leu?Ala?Gly?Tyr?Ile?Leu?Thr?Val?Leu?Gly?Leu?Gly?Leu?Ser?Leu?Lys

225 230 235 240

Glu?Cys?Val?Asp?Gly?Thr?Leu?Leu?Leu?Ser?Gly?Leu?Gly?Thr?Ile?Met

245 250 255

Val?Ser?Glu?His?Phe?Ser?Leu?Leu?Phe?Leu?Val?Cys?Phe?Pro?Ser?Thr

260 265 270

Gln?Arg?Asp?Tyr?Tyr

275

<210>20

<211>219

<212>PRT

＜213〉camelpox virus M-96

<400>20

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asp?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Val

65 70 75 80

Asn?Leu?Asn?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn

145 150 155 160

Ile?Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Val?Tyr?Val?Lys?Ile?Tyr?Asp?Ala?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>21

<211>277

<212>PRT

＜213〉camelpox virus M-96

<400>21

Met?Leu?Arg?Val?Arg?Ile?Leu?Leu?Ile?Tyr?Leu?Cys?Thr?Phe?Val?Val

1 5 10 15

Ile?Thr?Ala?Thr?Lys?Thr?Ile?Glu?Tyr?Met?Ala?Cys?Asn?Asp?Thr?Ile

20 25 30

Ile?Ile?Pro?Cys?Thr?Ile?Asp?Asn?Pro?Thr?Lys?Tyr?Ile?Arg?Trp?Lys

35 40 45

Leu?Asp?Asn?His?Asp?Ile?Leu?Thr?Tyr?Asn?Lys?Thr?Ser?Lys?Thr?Thr

50 55 60

Ile?Leu?Ser?Lys?Trp?His?Thr?Ser?Ala?Lys?Leu?His?Ser?Leu?Ser?Asp

65 70 75 80

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

85 90 95

Tyr?Thr?Cys?Glu?Asp?Asn?Thr?Gly?Ile?Lys?Ser?Thr?Val?Lys?Leu?Val

100 105 110

Gln?Arg?His?Thr?Asn?Trp?Phe?Asn?Asp?His?His?Thr?Met?Leu?Met?Phe

115 120 125

Ile?Phe?Thr?Gly?Ile?Thr?Leu?Phe?Leu?Leu?Phe?Leu?Glu?Ile?Ala?Tyr

130 135 140

Thr?Ser?Thr?Ser?Val?Val?Phe?Ser?Thr?Asn?Leu?Gly?Ile?Leu?Gln?Val

1451 50 155 160

Phe?Gly?Cys?Ile?Ile?Ala?Met?Ile?Glu?Leu?Cys?Gly?Ala?Phe?Leu?Phe

165 170 175

Tyr?Pro?Ser?Met?Phe?Thr?Leu?Arg?His?Ile?Ile?Gly?Leu?Leu?Met?Met

180 185 190

Thr?Leu?Pro?Ser?Ile?Phe?Leu?Ile?Ile?Thr?Lys?Val?Phe?Ser?Phe?Trp

195 200 205

Leu?Leu?Cys?Lys?Leu?Ser?Cys?Ala?Val?His?Leu?Ile?Ile?Tyr?Tyr?Gln

210 215 220

Leu?Ala?Gly?Tyr?Ile?Leu?Thr?Val?Leu?Gly?Leu?Gly?Leu?Ser?Leu?Lys

225 230 235 240

Glu?Cys?Val?Asp?Gly?Thr?Leu?Leu?Leu?Ser?Gly?Leu?Gly?Thr?Ile?Met

245 250 255

Val?Ser?Glu?His?Phe?Ser?Leu?Leu?Phe?Leu?Val?Cys?Phe?Pro?Ser?Thr

260 265 270

Gln?Arg?Asp?Tyr?Tyr

275

<210>22

<211>1445

<212>PRT

＜213〉people (homo sapiens)

<400>22

Met?Arg?Arg?Leu?Leu?Glu?Pro?Cys?Trp?Trp?Ile?Leu?Phe?Leu?Lys?Ile

1 5 10 15

Thr?Ser?Ser?Val?Leu?His?Tyr?Val?Val?Cys?Phe?Pro?Ala?Leu?Thr?Glu

20 25 30

Gly?Tyr?Val?Gly?Ala?Leu?His?Glu?Asn?Arg?His?Gly?Ser?Ala?Val?Gln

35 40 45

Ile?Arg?Arg?Arg?Lys?Ala?Ser?Gly?Asp?Pro?Tyr?Trp?Ala?Tyr?Ser?Gly

50 55 60

Ala?Tyr?Gly?Pro?Glu?His?Trp?Val?Thr?Ser?Ser?Val?Ser?Cys?Gly?Ser

65 70 75 80

Arg?His?Gln?Ser?Pro?Ile?Asp?Ile?Leu?Asp?Gln?Tyr?Ala?Arg?Val?Gly

85 90 95

Glu?Glu?Tyr?Gln?Glu?Leu?Gln?Leu?Asp?Gly?Phe?Asp?Asn?Glu?Ser?Ser

100 105 110

Asn?Lys?Thr?Trp?Met?Lys?Asn?Thr?Gly?Lys?Thr?Val?Ala?Ile?Leu?Leu

115 120 125

Lys?Asp?Asp?Tyr?Phe?Val?Ser?Gly?Ala?Gly?Leu?Pro?Gly?Arg?Phe?Lys

130 135 140

Ala?Glu?Lys?Val?Glu?Phe?His?Trp?Gly?His?Ser?Asn?Gly?Ser?Ala?Gly

145 150 155 160

Ser?Glu?His?Ser?Ile?Asn?Gly?Arg?Arg?Phe?Pro?Val?Glu?Met?Gln?Ile

165 170 175

Phe?Phe?Tyr?Asn?Pro?Asp?Asp?Phe?Asp?Ser?Phe?Gln?Thr?Ala?Ile?Ser

180 185 190

Glu?Asn?Arg?Ile?Ile?Gly?Ala?Met?Ala?Ile?Phe?Phe?Gln?Val?Ser?Pro

195 200 205

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

210 215 220

Val?His?His?Glu?Lys?Glu?Thr?Phe?Leu?Asp?Pro?Phe?Val?Leu?Arg?Asp

225 230 235 240

Leu?Leu?Pro?Ala?Ser?Leu?Gly?Ser?Tyr?Tyr?Arg?Tyr?Thr?Gly?Ser?Leu

245 250 255

Thr?Thr?Pro?Pro?Cys?Ser?Glu?Ile?Val?Glu?Trp?Ile?Val?Phe?Arg?Arg

260 265 270

Pro?Val?Pro?Ile?Ser?Tyr?His?Gln?Leu?Glu?Ala?Phe?Tyr?Ser?Ile?Phe

275 280 285

Thr?Thr?Glu?Gln?Gln?Asp?His?Val?Lys?Ser?Val?Glu?Tyr?Leu?Arg?Asn

290 295 300

Asn?Phe?Arg?Pro?Gln?Gln?Arg?Leu?His?Asp?Arg?Val?Val?Ser?Lys?Ser

305 310 315 320

Ala?Val?Arg?Asp?Ser?Trp?Asn?His?Asp?Met?Thr?Asp?Phe?Leu?Glu?Asn

325 330 335

Pro?Leu?Gly?Thr?Glu?Ala?Ser?Lys?Val?Cys?Ser?Ser?Pro?Pro?Ile?His

340 345 350

Met?Lys?Val?Gln?Pro?Leu?Asn?Gln?Thr?Ala?Leu?Gln?Val?Ser?Trp?Ser

355 360 365

Gln?Pro?Glu?Thr?Ile?Tyr?His?Pro?Pro?Ile?Met?Asn?Tyr?Met?Ile?Ser

370 375 380

Tyr?Ser?Trp?Thr?Lys?Asn?Glu?Asp?Glu?Lys?Glu?Lys?Thr?Phe?Thr?Lys

385 390 395 400

Asp?Ser?Asp?Lys?Asp?Leu?Lys?Ala?Thr?Ile?Ser?His?Val?Ser?Pro?Asp

405 410 415

Ser?Leu?Tyr?Leu?Phe?Arg?Val?Gln?Ala?Val?Cys?Arg?Asn?Asp?Met?Arg

420 425 430

Ser?Asp?Phe?Ser?Gln?Thr?Met?Leu?Phe?Gln?Ala?Asn?Thr?Thr?Arg?Ile

435 440 445

Phe?Gln?Gly?Thr?Arg?Ile?Val?Lys?Thr?Gly?Val?Pro?Thr?Ala?Ser?Pro

450 455 460

Ala?Ser?Ser?Ala?Asp?Met?Ala?Pro?Ile?Ser?Ser?Gly?Ser?Ser?Thr?Trp

465 470 475 480

Thr?Ser?Ser?Gly?Ile?Pro?Phe?Ser?Phe?Val?Ser?Met?Ala?Thr?Gly?Met

485 490 495

Gly?Pro?Ser?Ser?Ser?Gly?Ser?Gln?Ala?Thr?Val?Ala?Ser?Val?Val?Thr

500 505 510

Ser?Thr?Leu?Leu?Ala?Gly?Leu?Gly?Phe?Gly?Gly?Gly?Gly?Ile?Ser?Ser

515 520 525

Phe?Pro?Ser?Thr?Val?Trp?Pro?Thr?Arg?Leu?Pro?Thr?Ala?Ala?Ser?Ala

530 535 540

Ser?Lys?Gln?Ala?Ala?Arg?Pro?Val?Leu?Ala?Thr?Thr?Glu?Ala?Leu?Ala

545 550 555 560

Ser?Pro?Gly?Pro?Asp?Gly?Asp?Ser?Ser?Pro?Thr?Lys?Asp?Gly?Glu?Gly

565 570 575

Thr?Glu?Glu?Gly?Glu?Lys?Asp?Glu?Lys?Ser?Glu?Ser?Glu?Asp?Gly?Glu

580 585 590

Arg?Glu?His?Glu?Glu?Asp?Gly?Glu?Lys?Asp?Ser?Glu?Lys?Lys?Glu?Lys

595 600 605

Ser?Gly?Val?Thr?His?Ala?Ala?Glu?Glu?Arg?Asn?Gln?Thr?Glu?Pro?Ser

610 615 620

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

625 630 635 640

Ile?Pro?Gly?His?Glu?Gln?Asp?His?Thr?Ala?Val?Pro?Thr?Asp?Gln?Thr

645 650 655

Gly?Gly?Arg?Arg?Asp?Ala?Gly?Pro?Gly?Leu?Asp?Pro?Asp?Met?Val?Thr

660 665 670

Ser?Thr?Gln?Val?Pro?Pro?Thr?Ala?Thr?Glu?Glu?Gln?Tyr?Ala?Gly?Ser

675 680 685

Asp?Pro?Lys?Arg?Pro?Glu?Met?Pro?Ser?Lys?Lys?Pro?Met?Ser?Arg?Gly

690 695 700

Asp?Arg?Phe?Ser?Glu?Asp?Ser?Arg?Phe?Ile?Thr?Val?Asn?Pro?Ala?Glu

705 710 715 720

Lys?Asn?Thr?Ser?Gly?Met?Ile?Ser?Arg?Pro?Ala?Pro?Gly?Arg?Met?Glu

725 730 735

Trp?Ile?Ile?Pro?Leu?Ile?Val?Val?Ser?Ala?Leu?Thr?Phe?Val?Cys?Leu

740 745 750

Ile?Leu?Leu?Ile?Ala?Val?Leu?Val?Tyr?Trp?Arg?Gly?Cys?Asn?Lys?Ile

755 760 765

Lys?Ser?Lys?Gly?Phe?Pro?Arg?Arg?Phe?Arg?Glu?Val?Pro?Ser?Ser?Gly

770 775 780

Glu?Arg?Gly?Glu?Lys?Gly?Ser?Arg?Lys?Cys?Phe?Gln?Thr?Ala?His?Phe

785 790 795 800

Tyr?Val?Glu?Asp?Ser?Ser?Ser?Pro?Arg?Val?Val?Pro?Asn?Glu?Ser?Ile

805 810 815

Pro?Ile?Ile?Pro?Ile?Pro?Asp?Asp?Met?Glu?Ala?Ile?Pro?Val?Lys?Gln

820 825 830

Phe?Val?Lys?His?Ile?Gly?Glu?Leu?Tyr?Ser?Asn?Asn?Gln?His?Gly?Phe

835 840 845

Ser?Glu?Asp?Phe?Glu?Glu?Val?Gln?Arg?Cys?Thr?Ala?Asp?Met?Asn?Ile

850 855 860

Thr?Ala?Glu?His?Ser?Asn?His?Pro?Glu?Asn?Lys?His?Lys?Asn?Arg?Tyr

865 870 875 880

Ile?Asn?Ile?Leu?Ala?Tyr?Asp?His?Ser?Arg?Val?Lys?Leu?Arg?Pro?Leu

885 890 895

Pro?Gly?Lys?Asp?Ser?Lys?His?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val

900 905 910

Asp?Gly?Tyr?Asn?Lys?Ala?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

915 920 925

Lys?Ser?Thr?Phe?Glu?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Asn?Thr

930 935 940

Gly?Ile?Ile?Val?Met?Ile?Thr?Asn?Leu?Val?Glu?Lys?Gly?Arg?Arg?Lys

945 950 955 960

Cys?Asp?Gln?Tyr?Trp?Pro?Thr?Glu?Asn?Ser?Glu?Glu?Tyr?Gly?Asn?Ile

965 970 975

Ile?Val?Thr?Leu?Lys?Ser?Thr?Lys?Ile?His?Ala?Cys?Tyr?Thr?Val?Arg

980 985 990

Arg?Phe?Ser?Ile?Arg?Asn?Thr?Lys?Val?Lys?Lys?Gly?Gln?Lys?Gly?Asn

995 1000 1005

Pro?Lys?Gly?Arg?Gln?Asn?Glu?Arg?Val?Val?Ile?Gln?Tyr?His?Tyr?Thr

1010 1015 1020

Gln?Trp?Pro?Asp?Met?Gly?Val?Pro?Glu?Tyr?Ala?Leu?Pro?Val?Leu?Thr

1025 1030 1035 1040

Phe?Val?Arg?Arg?Ser?Ser?Ala?Ala?Arg?Met?Pro?Glu?Thr?Gly?Pro?Val

1045 1050 1055

Leu?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Thr?Tyr?Ile?Val

1060 1065 1070

Ile?Asp?Ser?Met?Leu?Gln?Gln?Ile?Lys?Asp?Lys?Ser?Thr?Val?Asn?Val

1075 1080 1085

Leu?Gly?Phe?Leu?Lys?His?Ile?Arg?Thr?Gln?Arg?Asn?Tyr?Leu?Val?Gln

1090 1095 1100

Thr?Glu?Glu?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Ile

1105 1110 1115 1120

Leu?Gly?Lys?Glu?Thr?Glu?Val?Ser?Ser?Asn?Gln?Leu?His?Ser?Tyr?Val

1125 1130 1135

Asn?Ser?Ile?Leu?Ile?Pro?Gly?Val?Gly?Gly?Lys?Thr?Arg?Leu?Glu?Lys

1140 1145 1150

Gln?Phe?Lys?Leu?Val?Thr?Gln?Cys?Asn?Ala?Lys?Tyr?Val?Glu?Cys?Phe

1155 1160 1165

Ser?Ala?Gln?Lys?Glu?Cys?Asn?Lys?Glu?Lys?Asn?Arg?Asn?Ser?Ser?Val

1170 1175 1180

Val?Pro?Ser?Glu?Arg?Ala?Arg?Val?Gly?Leu?Ala?Pro?Leu?Pro?Gly?Met

1185 1190 1195 1200

Lys?Gly?Thr?Asp?Tyr?Ile?Asn?Ala?Ser?Tyr?Ile?Met?Gly?Tyr?Tyr?Arg

1205 1210 1215

Ser?Asn?Glu?Phe?Ile?Ile?Thr?Gln?His?Pro?Leu?Pro?His?Thr?Thr?Lys

1220 1225 1230

Asp?Phe?Trp?Arg?Met?Ile?Trp?Asp?His?Asn?Ala?Gln?Ile?Ile?Val?Met

1235 1240 1245

Leu?Pro?Asp?Asn?Gln?Ser?Leu?Ala?Glu?Asp?Glu?Phe?Val?Tyr?Trp?Pro

1250 1255 1260

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

1265 1270 1275 1280

Ser?Lys?Asp?Arg?Leu?Cys?Leu?Ser?Asn?Glu?Glu?Gln?Ile?Ile?Ile?His

1285 1290 1295

Asp?Phe?Ile?Leu?Glu?Ala?Thr?Gln?Asp?Asp?Tyr?Val?Leu?Glu?Val?Arg

1300 1305 1310

His?Phe?Gln?Cys?Pro?Lys?Trp?Pro?Asn?Pro?Asp?Ala?Pro?Ile?Ser?Ser

1315 1320 1325

Thr?Phe?Glu?Leu?Ile?Asn?Val?Ile?Lys?Glu?Glu?Ala?Leu?Thr?Arg?Asp

1330 1335 1340

Gly?Pro?Thr?Ile?Val?His?Asp?Glu?Tyr?Gly?Ala?Val?Ser?Ala?Gly?Met

1345 1350 1355 1360

Leu?Cys?Ala?Leu?Thr?Thr?Leu?Ser?Gln?Gln?Leu?Glu?Asn?Glu?Asn?Ala

1365 1370 1375

Val?Asp?Val?Phe?Gln?Val?Ala?Lys?Met?Ile?Asn?Leu?Met?Arg?Pro?Gly

1380 1385 1390

Val?Phe?Thr?Asp?Ile?Glu?Gln?Tyr?Gln?Phe?Ile?Tyr?Lys?Ala?Arg?Leu

1395 1400 1405

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

1410 1415 1420

Lys?Asn?Gly?Ala?Val?Leu?Ile?Ala?Asp?Glu?Ser?Asp?Pro?Ala?Glu?Ser

1425 1430 1435 1440

Met?Glu?Ser?Leu?Val

1445

<210>23

<211>7718

<212>DNA

＜213〉people (homo sapiens)

<400>23

cgggagcggc?gggagcggtg?gcggcggcag?aggcggcggc?tccagcttcg?gctccggctc?60

gggctcgggc?tccggctccg?gctccggctc?cggctccagc?tcgggtggcg?gtggcgggag?120

cgggaccagg?tggaggcggc?ggcggcagag?gagtgggagc?agcggcccta?gcggcttgcg?180

gggggacatg?cggaccgacg?gcccctggat?aggcggaagg?agtggaggcc?ctggtgcccg?240

gcccttggtg?ctgagtatcc?agcaagagtg?accggggtga?agaagcaaag?actcggttga?300

ttgtcctggg?ctgtggctgg?ctgtggagct?agagccctgg?atggcccctg?agccagcccc?360

agggaggacg?atggtgcccc?ttgtgcctgc?actggtgatg?cttggtttgg?tggcaggcgc?420

ccatggtgac?agcaaacctg?tcttcattaa?agtccctgag?gaccagactg?ggctgtcagg?480

aggggtagcc?tccttcgtgt?gccaagctac?aggagaaccc?aagccgcgca?tcacatggat?540

gaagaagggg?aagaaagtca?gctcccagcg?cttcgaggtc?attgagtttg?atgatggggc?600

agggtcagtg?cttcggatcc?agccattgcg?ggtgcagcga?gatgaagcca?tctatgagtg?660

tacagctact?aacagcctgg?gtgagatcaa?cactagtgcc?aagctctcag?tgctcgaaga?720

ggaacagctg?ccccctgggt?tcccttccat?cgacatgggg?cctcagctga?aggtggtgga?780

gaaggcacgc?acagccacca?tgctatgtgc?cgcaggcgga?aatccagacc?ctgagatttc?840

ttggttcaag?gacttccttc?ctgtagaccc?tgccacgagc?aacggccgca?tcaagcagct?900

gcgttcaggt?gccttgcaga?tagagagcag?tgaggaatcc?gaccaaggca?agtacgagtg?960

tgtggcgacc?aactcggcag?gcacacgtta?ctcagcccct?gcgaacctgt?atgtgcgagt?1020

gcgccgcgtg?gctcctcgtt?tctccatccc?tcccagcagc?caggaggtga?tgccaggcgg?1080

cagcgtgaac?ctgacatgcg?tggcagtggg?tgcacccatg?ccctacgtga?agtggatgat?1140

gggggccgag?gagctcacca?aggaggatga?gatgccagtt?ggccgcaacg?tcctggagct?1200

cagcaatgtc?gtacgctctg?ccaactacac?ctgtgtggcc?atctcctcgc?tgggcatgat?1260

cgaggccaca?gcccaggtca?cagtgaaagc?tcttccaaag?cctccgattg?atcttgtggt?1320

gacagagaca?actgccacca?gtgtcaccct?cacctgggac?tctgggaact?cggagcctgt?1380

aacctactat?ggcatccagt?accgcgcagc?gggcacggag?ggcccctttc?aggaggtgga?1440

tggtgtggcc?accacccgct?acagcattgg?cggcctcagc?cctttctcgg?aatatgcctt?1500

ccgcgtgctg?gcggtgaaca?gcatcgggcg?agggccgccc?agcgaggcag?tgcgggcacg?1560

cacgggagaa?caggcgccct?ccagcccacc?gcgccgcgtg?caggcacgca?tgctgagcgc?1620

cagcaccatg?ctggtgcagt?gggagcctcc?cgaggagccc?aacggcctgg?tgcggggata?1680

ccgcgtctac?tatactccgg?actcccgccg?ccccccgaac?gcctggcaca?agcacaacac?1740

cgacgcgggg?ctcctcacga?ccgtgggcag?cctgctgcct?ggcatcacct?acagcctgcg?1800

cgtgcttgcc?ttcaccgccg?tgggcgatgg?ccctcccagc?cccaccatcc?aggtcaagac?1860

gcagcaggga?gtgcctgccc?agcccgcgga?cttccaggcc?gaggtggagt?cggacaccag?1920

gatccagctc?tcgtggctgc?tgccccctca?ggagcggatc?atcatgtatg?aactggtgta?1980

ctgggcggca?gaggacgaag?accaacagca?caaggtcacc?ttcgacccaa?cctcctccta?2040

cacactagag?gacctgaagc?ctgacacact?ctaccgcttc?cagctggctg?cacgctcgga?2100

tatgggggtg?ggcgtcttca?cccccaccat?tgaggcccgc?acagcccagt?ccaccccctc?2160

cgcccctccc?cagaaggtga?tgtgtgtgag?catgggctcc?accacggtcc?gggtaagttg?2220

ggtcccgccg?cctgccgaca?gccgcaacgg?cgttatcacc?cagtactccg?tggcccacga?2280

ggcggtggac?ggcgaggacc?gcgggcggca?tgtggtggat?ggcatcagcc?gtgagcactc?2340

cagctgggac?ctggtgggcc?tggagaagtg?gacggagtac?cgggtgtggg?tgcgggcaca?2400

cacagacgtg?ggccccggcc?ccgagagcag?cccggtgctg?gtgcgcaccg?atgaggacgt?2460

gcccagcggg?cctccgcgga?aggtggaggt?ggagccactg?aactccactg?ctgtgcatgt?2520

ctactggaag?ctgcctgtcc?ccagcaagca?gcatggccag?atccgcggct?accaggtcac?2580

ctacgtgcgg?ctggagaatg?gcgagccccg?tggactcccc?atcatccaag?acgtcatgct?2640

agccgaggcc?cagtggcggc?cagaggagtc?cgaggactat?gaaaccacta?tcagcggcct?2700

gaccccggag?accacctact?ccgttactgt?tgctgcctat?accaccaagg?gggatggtgc?2760

ccgcagcaag?cccaaaattg?tcactacaac?aggtgcagtc?ccaggccggc?ccaccatgat?2820

gatcagcacc?acggccatga?acactgcgct?gctccagtgg?cacccaccca?aggaactgcc?2880

tggcgagctg?ctgggctacc?ggctgcagta?ctgccgggcc?gacgaggcgc?ggcccaacac?2940

catagatttc?ggcaaggatg?accagcactt?cacagtcacc?ggcctgcaca?aggggaccac?3000

ctacatcttc?cggcttgctg?ccaagaaccg?ggctggcttg?ggtgaggagt?tcgagaagga?3060

gatcaggacc?cccgaggacc?tgcccagcgg?cttcccccaa?aacctgcatg?tgacaggact?3120

gaccacgtct?accacagaac?tggcctggga?cccgccagtg?ctggcggaga?ggaacgggcg?3180

catcatcagc?tacaccgtgg?tgttccgaga?catcaacagc?caacaggagc?tgcagaacat?3240

cacgacagac?acccgcttta?cccttactgg?cctcaagcca?gacaccactt?acgacatcaa?3300

ggtccgcgca?tggaccagca?aaggctctgg?cccactcagc?cccagcatcc?agtcccggac?3360

catgccggtg?gagcaagtgt?ttgccaagaa?cttccgggtg?gcggctgcaa?tgaagacgtc?3420

tgtgctgctc?agctgggagg?ttcccgactc?ctataagtca?gctgtgccct?ttaagattct?3480

gtacaatggg?cagagtgtgg?aggtggacgg?gcactcgatg?cggaagctga?tcgcagacct?3540

gcagcccaac?acagagtact?cgtttgtgct?gatgaaccgt?ggcagcagcg?cagggggcct?3600

gcagcacctg?gtgtccatcc?gcacagcccc?cgacctcctg?cctcacaagc?cgctgcctgc?3660

ctctgcctac?atagaggacg?gccgcttcga?tctctccatg?ccccatgtgc?aagacccctc?3720

gcttgtcagg?tggttctaca?ttgttgtggt?acccattgac?cgtgtgggcg?ggagcatgct?3780

gacgccaagg?tggagcacac?ccgaggaact?ggagctggac?gagcttctag?aagccatcga?3840

gcaaggcgga?gaggagcagc?ggcggcggcg?gcggcaggca?gaacgtctga?agccatatgt?3900

ggctgctcaa?ctggatgtgc?tcccggagac?ctttaccttg?ggggacaaga?agaactaccg?3960

gggcttctac?aaccggcccc?tgtctccgga?cttgagctac?cagtgctttg?tgcttgcctc?4020

cttgaaggaa?cccatggacc?agaagcgcta?tgcctccagc?ccctactcgg?atgagatcgt?4080

ggtccaggtg?acaccagccc?agcagcagga?ggagccggag?atgctgtggg?tgacgggtcc?4140

cgtgctggca?gtcatcctca?tcatcctcat?tgtcatcgcc?atcctcttgt?tcaaaaggaa?4200

aaggacccac?tctccgtcct?ctaaggatga?gcagtcgatc?ggactgaagg?actccttgct?4260

ggcccactcc?tctgaccctg?tggagatgcg?gaggctcaac?taccagaccc?caggtatgcg?4320

agaccaccca?cccatcccca?tcaccgacct?ggcggacaac?atcgagcgcc?tcaaagccaa?4380

cgatggcctc?aagttctccc?aggagtatga?gtccatcgac?cctggacagc?agttcacgtg?4440

ggagaattca?aacctggagg?tgaacaagcc?caagaaccgc?tatgcgaatg?tcatcgccta?4500

cgaccactct?cgagtcatcc?ttacctctat?cgatggcgtc?cccgggagtg?actacatcaa?4560

tgccaactac?atcgatggct?accgcaagca?gaatgcctac?atcgccacgc?agggccccct?4620

gcccgagacc?atgggcgatt?tctggagaat?ggtgtgggaa?cagcgcacgg?ccactgtggt?4680

catgatgaca?cggctggagg?agaagtcccg?ggtaaaatgt?gatcagtact?ggccagcccg?4740

tggcaccgag?acctgtggcc?ttattcaggt?gaccctgttg?gacacagtgg?agctggccac?4800

atacactgtg?cgcaccttcg?cactccacaa?gagtggctcc?agtgagaagc?gtgagctgcg?4860

tcagtttcag?ttcatggcct?ggccagacca?tggagttcct?gagtacccaa?ctcccatcct?4920

ggccttccta?cgacgggtca?aggcctgcaa?ccccctagac?gcagggccca?tggtggtgca?4980

ctgcagcgcg?ggcgtgggcc?gcaccggctg?cttcatcgtg?attgatgcca?tgttggagcg?5040

gatgaagcac?gagaagacgg?tggacatcta?tggccacgtg?acctgcatgc?gatcacagag?5100

gaactacatg?gtgcagacgg?aggaccagta?cgtgttcatc?catgaggcgc?tgctggaggc?5160

tgccacgtgc?ggccacacag?aggtgcctgc?ccgcaacctg?tatgcccaca?tccagaagct?5220

gggccaagtg?cctccagggg?agagtgtgac?cgccatggag?ctcgagttca?agttgctggc?5280

cagctccaag?gcccacacgt?cccgcttcat?cagcgccaac?ctgccctgca?acaagttcaa?5340

gaaccggctg?gtgaacatca?tgccctacga?attgacccgt?gtgtgtctgc?agcccatccg?5400

tggtgtggag?ggctctgact?acatcaatgc?cagcttcctg?gatggttata?gacagcagaa?5460

ggcctacata?gctacacagg?ggcctctggc?agagagcacc?gaggacttct?ggcgcatgct?5520

atgggagcac?aattccacca?tcatcgtcat?gctgaccaag?cttcgggaga?tgggcaggga?5580

gaaatgccac?cagtactggc?cagcagagcg?ctctgctcgc?taccagtact?ttgttgttga?5640

cccgatggct?gagtacaaca?tgccccagta?tatcctgcgt?gagttcaagg?tcacggatgc?5700

ccgggatggg?cagtcaagga?caatccggca?gttccagttc?acagactggc?cagagcaggg?5760

cgtgcccaag?acaggcgagg?gattcattga?cttcatcggg?caggtgcata?agaccaagga?5820

gcagtttgga?caggatgggc?ctatcacggt?gcactgcagt?gctggcgtgg?gccgcaccgg?5880

ggtgttcatc?actctgagca?tcgtcctgga?gcgcatgcgc?tatgagggcg?tggtcgacat?5940

gtttcagacc?gtgaagaccc?tgcgtacaca?gcgtcctgcc?atggtgcaga?cagaggacca?6000

gtatcagctg?tgctaccgtg?cggccctgga?gtacctcggc?agctttgacc?actatgcaac?6060

gtaactaccg?ctcccctctc?ctccgccacc?cccgccgtgg?ggctccggag?gggacccagc?6120

tcctctgagc?cataccgacc?atcgtccagc?cctcctacgc?agatgctgtc?actggcagag?6180

cacagcccac?ggggatcaca?gcgtttcagg?aacgttgcca?caccaatcag?agagcctaga?6240

acatccctgg?gcaagtggat?ggcccagcag?gcaggcactg?tggcccttct?gtccaccaga?6300

cccacctgga?gcccgcttca?agctctctgt?tgcgctcccg?catttctcat?gcttcttctc?6360

atggggtggg?gttggggcaa?agcctccttt?ttaatacatt?aagtggggta?gactgaggga?6420

ttttagcctc?ttccctctga?tttttccttt?cgcgaatccg?tatctgcaga?atgggccact?6480

gtaggggttg?gggtttattt?tgttttgttt?tttttttttt?tttgtatgac?ttctgctgaa?6540

ggacagaaca?ttgccttcct?cgtgcagagc?tggggctgcc?agcctgagcg?gaggctcggc?6600

cgtgggccgg?gaggcagtgc?tgatccggct?gctcctccag?cccttcagac?gagatcctgt?6660

ttcagctaaa?tgcagggaaa?ctcaatgttt?ttttaagttt?tgttttccct?ttaaagcctt?6720

tttttaggcc?acattgacag?tggtgggcgg?ggagaagata?gggaacactc?atccctggtc?6780

gtctatccca?gtgtgtgttt?aacattcaca?gcccagaacc?acagatgtgt?ctgggagagc?6840

ctggcaaggc?attcctcatc?accatcgtgt?ttgcaaaggt?taaaacaaaa?acaaaaaacc?6900

acaaaaataa?aaaacaaaaa?aaacaaaaaa?cccaaaaaaa?aaaaaaaaaa?gagtcagccc?6960

ttggcttctg?cttcaaaccc?tcaagagggg?aagcaactcc?gtgtgcctgg?ggttcccgag?7020

ggagctgctg?gctgacctgg?gcccacagag?cctggctttg?gtccccagca?ttgcagtatg?7080

gtgtggtgtt?tgtaggctgt?ggggtctggc?tgtgtggcca?aggtgaatag?cacaggttag?7140

ggtgtgtgcc?acaccccatg?cacctcaggg?ccaagcgggg?gcgtggctgg?cctttcaggt?7200

ccaggccagt?gggcctggta?gcacatgtct?gtcctcagag?caggggccag?atgattttcc?7260

tccctggttt?gcagctgttt?tcaaagcccc?cgataatcgc?tcttttccac?tccaagatgc?7320

cctcataaac?caatgtggca?agactactgg?acttctatca?atggtactct?aatcagtcct?7380

tattatccca?gcttgctgag?gggcagggag?agcgcctctt?cctctgggca?gcgctatcta?7440

gataggtaag?tgggggcggg?gaagggtgca?tagctgtttt?agctgaggga?cgtggtgccg?7500

acgtccccaa?acctagctag?gctaagtcaa?gatcaacatt?ccagggttgg?taatgttgga?7560

tgatgaaaca?ttcattttta?ccttgtggat?gctagtgctg?tagagttcac?tgttgtacac?7620

agtctgtttt?ctatttgtta?agaaaaacta?cagcatcatt?gcataattct?tgatggtaat?7680

aaatttgaat?aatcagattt?cttacaaaaa?aaaaaaaa 7718

<210>24

<211>1898

<212>PRT

＜213〉people (homo sapiens)

<400>24

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser

785 790 795 800

Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 910

Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val

930 935 940

Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr

945 950 955 960

Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1010 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser

1125 1130 1135

Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Asn?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Thr?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu

1875 1880 1885

Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>25

<211>1907

<212>PRT

＜213〉people (homo sapiens)

<400>25

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?LeuLys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Trp?Arg?Pro?Glu?Glu?Ser?Glu?Asp?Tyr?Glu?Thr?Thr?Ile

770 775 780

Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr?Ser?Val?Thr?Val?Ala?Ala?Tyr

785 790 795 800

Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Ile?Val?Thr?Thr

805 810 815

Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr?Met?Met?Ile?Ser?Thr?Thr?Ala

820 825 830

Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His?Pro?Pro?Lys?Glu?Leu?Pro?Gly

835 840 845

Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr?Cys?Arg?Ala?Asp?Glu?Ala?Arg

850 855 860

Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp?Asp?Gln?His?Phe?Thr?Val?Thr

865 870 875 880

Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile?Phe?Arg?Leu?Ala?Ala?Lys?Asn

885 890 895

Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu?Lys?Glu?Ile?Arg?Thr?Pro?Glu

900 905 910

Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn?Leu?His?Val?Thr?Gly?Leu?Thr

915 920 925

Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp?Pro?Pro?Val?Leu?Ala?Glu?Arg

930 935 940

Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val?Val?Phe?Arg?Asp?Ile?Asn?Ser

945 950 955 960

Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr?Asp?Thr?Arg?Phe?Thr?Leu?Thr

965 970 975

Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp?Ile?Lys?Val?Arg?Ala?TrpThr

980 985 990

Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro?Ser?Ile?Gln?Ser?Arg?Thr?Met

995 1000 1005

Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn?Phe?Arg?Val?Ala?Ala?Ala?Met

1010 1015 1020

Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Val?Pro?Asp?Ser?Tyr?Lys?Ser

1025 1030 1035 1040

Ala?Val?Pro?Phe?Lys?Ile?Leu?Tyr?Asn?Gly?Gln?Ser?Val?Glu?Val?Asp

1045 1050 1055

Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala?Asp?Leu?Gln?Pro?Asn?Thr?Glu

1060 1065 1070

Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly?Ser?Ser?Ala?Gly?Gly?Leu?Gln

1075 1080 1085

His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro?Asp?Leu?Leu?Pro?His?Lys?Pro

1090 1095 1100

Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp?Gly?Arg?Phe?Asp?Leu?Ser?Met

1105 1110 1115 1120

Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val?Arg?Trp?Phe?Tyr?Ile?Val?Val

1125 1130 1135

Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser?Met?Leu?Thr?Pro?Arg?Trp?Ser

1140 1145 1150

Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu?Leu?Leu?Glu?Ala?Ile?Glu?Gln

1155 1160 1165

Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg?Arg?Gln?Ala?Glu?Arg?Leu?Lys

1170 1175 1180

Pro?Tyr?Val?Ala?Ala?Gln?Leu?Asp?Val?Leu?Pro?Glu?Thr?Phe?Thr?Leu

1185 1190 1195 1200

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

1205 1210 1215

Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu?Ala?Ser?Leu?Lys?Glu?Pro?Met

1220 1225 1230

Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro?Tyr?Ser?Asp?Glu?Ile?Val?Val

1235 1240 1245

Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu?Glu?Pro?Glu?Met?Leu?Trp?Val

1250 1255 1260

Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu?Ile?Ile?Leu?Ile?Val?Ile?Ala

1265 1270 1275 1280

Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr?His?Ser?Pro?Ser?Ser?Lys?Asp

1285 1290 1295

Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser?Leu?Leu?Ala?His?Ser?Ser?Asp

1300 1305 1310

Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr?Gln?Thr?Pro?Gly?Met?Arg?Asp

1315 1320 1325

His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu?Ala?Asp?Asn?Ile?Glu?Arg?Leu

1330 1335 1340

Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp

1345 1350 1355 1360

Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn?Ser?Asn?Leu?Glu?Val?Asn?Lys

1365 1370 1375

Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val

1380 1385 1390

Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro?Gly?Ser?Asp?Tyr?Ile?Asn?Ala

1395 1400 1405

Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln

1410 1415 1420

Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu

1425 1430 1435 1440

Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser

1445 1450 1455

Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ala?Arg?Gly?Thr?Glu?Thr?Cys

1460 1465 1470

Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr

1475 1480 1485

Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys?Ser?Gly?Ser?Ser?Glu?Lys?Arg

1490 1495 1500

Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala?Trp?Pro?Asp?His?Gly?Val?Pro

1505 1510 1515 1520

Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Ala?Cys

1525 1530 1535

Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val

1540 1545 1550

Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Met

1555 1560 1565

Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Cys?Met?Arg

1570 1575 1580

Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Val?Phe?Ile

1585 1590 1595 1600

His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr?Cys?Gly?His?Thr?Glu?Val?Pro

1605 1610 1615

Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln?Lys?Leu?Gly?Gln?Val?Pro?Pro

1620 1625 1630

Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu?Glu?Phe?Lys?Leu?Leu?Ala?Ser

1635 1640 1645

Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn

1650 1655 1660

Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Leu?Thr?Arg

1665 1670 1675 1680

Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn

1685 1690 1695

Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr

1700 1705 1710

Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp

1715 1720 1725

Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met

1730 1735 1740

Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg

1745 1750 1755 1760

Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln

1765 1770 1775

Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser

1780 1785 1790

Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val

1795 1800 1805

Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys

1810 1815 1820

Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Thr?Val?His?Cys?Ser

1825 1830 1835 1840

Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr?Leu?Ser?Ile?Val?Leu

1845 1850 1855

Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Met?Phe?Gln?Thr?Val?Lys

1860 1865 1870

Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr

1875 1880 1885

Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His

1890 1895 1900

Tyr?Ala?Thr

1905

<210>26

<211>1888

<212>PRT

＜213〉people (Homo Sapiens)

<400>26

Met?Val?Pro?Leu?Val?Pro?Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly

1 5 10 15

Ala?His?Gly?Asp?Ser?Lys?Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln

20 25 30

Thr?Gly?Leu?Ser?Gly?Gly?Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly

35 40 45

Glu?Pro?Lys?Pro?Arg?Ile?Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser

50 55 60

Ser?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val

65 70 75 80

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

85 90 95

Cys?Thr?Ala?Thr?Asn?Ser?Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu

100 105 110

Ser?Val?Leu?Glu?Glu?Glu?Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp

115 120 125

Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met

130 135 140

Leu?Cys?Ala?Ala?Gly?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys

145 150 155 160

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

165 170 175

Leu?Arg?Ser?Gly?Ala?Leu?Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln

180 185 190

Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser

195 200 205

Ala?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe

210 215 220

Ser?Ile?Pro?Pro?Ser?Ser?Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn

225 230 235 240

Leu?Thr?Cys?Val?Ala?Val?Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met

245 250 255

Met?Gly?Ala?Glu?Glu?Leu?Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg

260 265 270

Asn?Val?Leu?Glu?Leu?Ser?Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys

275 280 285

Val?Ala?Ile?Ser?Ser?Leu?Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr

290 295 300

Val?Lys?Ala?Leu?Pro?Lys?Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr

305 310 315 320

Thr?Ala?Thr?Ser?Val?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro

325 330 335

Val?Thr?Tyr?Tyr?Gly?Ile?Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro

340 345 350

Phe?Gln?Glu?Val?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly

355 360 365

Leu?Ser?Pro?Phe?Ser?Glu?Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser

370 375 380

Ile?Gly?Arg?Gly?Pro?Pro?Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu

385 390 395 400

Gln?Ala?Pro?Ser?Ser?Pro?Pro?Arg?Arg?Val?Gln?Ala?Arg?Met?Leu?Ser

405 410 415

Ala?Ser?Thr?Met?Leu?Val?Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly

420 425 430

Leu?Val?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro

435 440 445

Pro?Asn?Ala?Trp?His?Lys?His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr

450 455 460

Val?Gly?Ser?Leu?Leu?Pro?Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala

465 470 475 480

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

485 490 495

Thr?Gln?Gln?Gly?Val?Pro?Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val

500 505 510

Glu?Ser?Asp?Thr?Arg?Ile?Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu

515 520 525

Arg?Ile?Ile?Met?Tyr?Glu?Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp

530 535 540

Gln?Gln?His?Lys?Val?Thr?Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu

545 550 555 560

Asp?Leu?Lys?Pro?Asp?Thr?Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser

565 570 575

Asp?Met?Gly?Val?Gly?Val?Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala

580 585 590

Gln?Ser?Thr?Pro?Ser?Ala?Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met

595 600 605

Gly?Ser?Thr?Thr?Val?Arg?Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser

610 615 620

Arg?Asn?Gly?Val?Ile?Thr?Gln?Tyr?Ser?Val?Ala?His?Glu?Ala?Val?Asp

625 630 635 640

Gly?Glu?Asp?Arg?Gly?Arg?His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His

645 650 655

Ser?Ser?Trp?Asp?Leu?Val?Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val

660 665 670

Trp?Val?Arg?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro

675 680 685

Val?Leu?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys

690 695 700

Val?Glu?Val?Glu?Pro?Leu?Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys

705 710 715 720

Leu?Pro?Val?Pro?Ser?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val

725 730 735

Thr?Tyr?Val?Arg?Leu?Glu?Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile

740 745 750

Gln?Asp?Val?Met?Leu?Ala?Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu

755 760 765

Thr?Pro?Glu?Thr?Thr?Tyr?Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys

770 775 780

Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala

785 790 795 800

Val?Pro?Gly?Arg?Pro?Thr?Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr

805 810 815

Ala?Leu?Leu?Gln?Trp?His?Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu

820 825 830

Gly?Tyr?Arg?Leu?Gln?Tyr?Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr

835 840 845

Ile?Asp?Phe?Gly?Lys?Asp?Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His

850 855 860

Lys?Gly?Thr?Thr?Tyr?Ile?Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly

865 870 875 880

Leu?Gly?Glu?Glu?Phe?Glu?Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro

885 890 895

Ser?Gly?Phe?Pro?Gln?Asn?Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr

900 905 910

Thr?Glu?Leu?Ala?Trp?Asp?Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg

915 920 925

Ile?Ile?Ser?Tyr?Thr?Val?Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu

930 935 940

Leu?Gln?Asn?Ile?Thr?Thr?Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys

945 950 955 960

Pro?Asp?Thr?Thr?Tyr?Asp?Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly

965 970 975

Ser?Gly?Pro?Leu?Ser?Pro?Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu

980 985 990

Gln?Val?Phe?Ala?Lys?Asn?Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser

995 1000 1005

Val?Leu?Leu?Ser?Trp?Glu?Val?Pro?Asp?Ser?Tyr?Lys?Ser?Ala?Val?Pro

1010 1015 1020

Phe?Lys?Ile?Leu?Tyr?Asn?Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser

1025 1030 1035 1040

Met?Arg?Lys?Leu?Ile?Ala?Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe

1045 1050 1055

Val?Leu?Met?Asn?Arg?Gly?Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val

1060 1065 1070

Ser?Ile?Arg?Thr?Ala?Pro?Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala

1075 1080 1085

Ser?Ala?Tyr?Ile?Glu?Asp?Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val

1090 1095 1100

Gln?Asp?Pro?Ser?Leu?Val?Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile

1105 1110 1115 1120

Asp?Arg?Val?Gly?Gly?Ser?Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu

1125 1130 1135

Glu?Leu?Glu?Leu?Asp?Glu?Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu

1140 1145 1150

Glu?Gln?Arg?Arg?Arg?Arg?Arg?Gln?Ala?Glu?Arg?Leu?Lys?Pro?Tyr?Val

1155 1160 1165

Ala?Ala?Gln?Leu?Asp?Val?Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys

1170 1175 1180

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

1185 1190 1195 1200

Tyr?Gln?Cys?Phe?Val?Leu?Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys

1205 1210 1215

Arg?Tyr?Ala?Ser?Ser?Pro?Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr

1220 1225 1230

Pro?Ala?Gln?Gln?Gln?Glu?Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro

1235 1240 1245

Val?Leu?Ala?Val?Ile?Leu?Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu

1250 1255 1260

Phe?Lys?Arg?Lys?Arg?Thr?His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser

1265 1270 1275 1280

Ile?Gly?Leu?Lys?Asp?Ser?Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu

1285 1290 1295

Met?Arg?Arg?Leu?Asn?Tyr?Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro

1300 1305 1310

Ile?Pro?Ile?Thr?Asp?Leu?Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn

1315 1320 1325

Asp?Gly?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln

1330 1335 1340

Gln?Phe?Thr?Trp?Glu?Asn?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn

1345 1350 1355 1360

Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr

1365 1370 1375

Ser?Ile?Asp?Gly?Val?Pro?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile

1380 1385 1390

Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

1395 1400 1405

Pro?Glu?Thr?Met?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr

1410 1415 1420

Ala?Thr?Val?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys

1425 1430 1435 1440

Cys?Asp?Gln?Tyr?Trp?Pro?Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile

1445 1450 1455

Gln?Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg

1460 1465 1470

Thr?Phe?Ala?Leu?His?Lys?Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg

1475 1480 1485

Gln?Phe?Gln?Phe?Met?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro

1490 1495 1500

Thr?Pro?Ile?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu

1505 1510 1515 1520

Asp?Ala?Gly?Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1525 1530 1535

Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu

1540 1545 1550

Lys?Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg

1555 1560 1565

Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala

1570 1575 1580

Leu?Leu?Glu?Ala?Ala?Thr?Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn

1585 1590 1595 1600

Leu?Tyr?Ala?His?Ile?Gln?Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser

1605 1610 1615

Val?Thr?Ala?Met?Glu?Leu?Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala

1620 1625 1630

His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys

1635 1640 1645

Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu

1650 1655 1660

Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe

1665 1670 1675 1680

Leu?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro

1685 1690 1695

Leu?Ala?Glu?Ser?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn

1700 1705 1710

Ser?Thr?Ile?Ile?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu

1715 1720 1725

Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr

1730 1735 1740

Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu

1745 1750 1755 1760

Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile

1765 1770 1775

Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr

1780 1785 1790

Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu

1795 1800 1805

Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Thr?Val?His?Cys?Ser?Ala?Gly?Val

1810 1815 1820

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

1825 1830 1835 1840

Arg?Tyr?Glu?Gly?Val?Val?Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg

1845 1850 1855

Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys

1860 1865 1870

Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1875 1880 1885

<210>27

<211>7691

<212>DNA

＜213〉people (homo sapiens)

<400>27

cgggagcggc?gggagcggtg?gcggcggcag?aggcggcggc?tccagcttcg?gctccggctc?60

gggctcgggc?tccggctccg?gctccggctc?cggctccagc?tcgggtggcg?gtggcgggag?120

cgggaccagg?tggaggcggc?ggcggcagag?gagtgggagc?agcggcccta?gcggcttgcg?180

gggggacatg?cggaccgacg?gcccctggat?aggcggaagg?agtggaggcc?ctggtgcccg?240

gcccttggtg?ctgagtatcc?agcaagagtg?accggggtga?agaagcaaag?actcggttga?300

ttgtcctggg?ctgtggctgg?ctgtggagct?agagccctgg?atggcccctg?agccagcccc?360

agggaggacg?atggtgcccc?ttgtgcctgc?actggtgatg?cttggtttgg?tggcaggcgc?420

ccatggtgac?agcaaacctg?tcttcattaa?agtccctgag?gaccagactg?ggctgtcagg?480

aggggtagcc?tccttcgtgt?gccaagctac?aggagaaccc?aagccgcgca?tcacatggat?540

gaagaagggg?aagaaagtca?gctcccagcg?cttcgaggtc?attgagtttg?atgatggggc?600

agggtcagtg?cttcggatcc?agccattgcg?ggtgcagcga?gatgaagcca?tctatgagtg?660

tacagctact?aacagcctgg?gtgagatcaa?cactagtgcc?aagctctcag?tgctcgaaga?720

ggaacagctg?ccccctgggt?tcccttccat?cgacatgggg?cctcagctga?aggtggtgga?780

gaaggcacgc?acagccacca?tgctatgtgc?cgcaggcgga?aatccagacc?ctgagatttc?840

ttggttcaag?gacttccttc?ctgtagaccc?tgccacgagc?aacggccgca?tcaagcagct?900

gcgttcaggt?gccttgcaga?tagagagcag?tgaggaatcc?gaccaaggca?agtacgagtg?960

tgtggcgacc?aactcggcag?gcacacgtta?ctcagcccct?gcgaacctgt?atgtgcgagt?1020

gcgccgcgtg?gctcctcgtt?tctccatccc?tcccagcagc?caggaggtga?tgccaggcgg?1080

cagcgtgaac?ctgacatgcg?tggcagtggg?tgcacccatg?ccctacgtga?agtggatgat?1140

gggggccgag?gagctcacca?aggaggatga?gatgccagtt?ggccgcaacg?tcctggagct?1200

cagcaatgtc?gtacgctctg?ccaactacac?ctgtgtggcc?atctcctcgc?tgggcatgat?1260

cgaggccaca?gcccaggtca?cagtgaaagc?tcttccaaag?cctccgattg?atcttgtggt?1320

gacagagaca?actgccacca?gtgtcaccct?cacctgggac?tctgggaact?cggagcctgt?1380

aacctactat?ggcatccagt?accgcgcagc?gggcacggag?ggcccctttc?aggaggtgga?1440

tggtgtggcc?accacccgct?acagcattgg?cggcctcagc?cctttctcgg?aatatgcctt?1500

ccgcgtgctg?gcggtgaaca?gcatcgggcg?agggccgccc?agcgaggcag?tgcgggcacg?1560

cacgggagaa?caggcgccct?ccagcccacc?gcgccgcgtg?caggcacgca?tgctgagcgc?1620

cagcaccatg?ctggtgcagt?gggagcctcc?cgaggagccc?aacggcctgg?tgcggggata?1680

ccgcgtctac?tatactccgg?actcccgccg?ccccccgaac?gcctggcaca?agcacaacac?1740

cgacgcgggg?ctcctcacga?ccgtgggcag?cctgctgcct?ggcatcacct?acagcctgcg?1800

cgtgcttgcc?ttcaccgccg?tgggcgatgg?ccctcccagc?cccaccatcc?aggtcaagac?1860

gcagcaggga?gtgcctgccc?agcccgcgga?cttccaggcc?gaggtggagt?cggacaccag?1920

gatccagctc?tcgtggctgc?tgccccctca?ggagcggatc?atcatgtatg?aactggtgta?1980

ctgggcggca?gaggacgaag?accaacagca?caaggtcacc?ttcgacccaa?cctcctccta?2040

cacactagag?gacctgaagc?ctgacacact?ctaccgcttc?cagctggctg?cacgctcgga?2100

tatgggggtg?ggcgtcttca?cccccaccat?tgaggcccgc?acagcccagt?ccaccccctc?2160

cgcccctccc?cagaaggtga?tgtgtgtgag?catgggctcc?accacggtcc?gggtaagttg?2220

ggtcccgccg?cctgccgaca?gccgcaacgg?cgttatcacc?cagtactccg?tggcccacga?2280

ggcggtggac?ggcgaggacc?gcgggcggca?tgtggtggat?ggcatcagcc?gtgagcactc?2340

cagctgggac?ctggtgggcc?tggagaagtg?gacggagtac?cgggtgtggg?tgcgggcaca?2400

cacagacgtg?ggccccggcc?ccgagagcag?cccggtgctg?gtgcgcaccg?atgaggacgt?2460

gcccagcggg?cctccgcgga?aggtggaggt?ggagccactg?aactccactg?ctgtgcatgt?2520

ctactggaag?ctgcctgtcc?ccagcaagca?gcatggccag?atccgcggct?accaggtcac?2580

ctacgtgcgg?ctggagaatg?gcgagccccg?tggactcccc?atcatccaag?acgtcatgct?2640

agccgaggcc?caggaaacca?ctatcagcgg?cctgaccccg?gagaccacct?actccgttac?2700

tgttgctgcc?tataccacca?agggggatgg?tgcccgcagc?aagcccaaaa?ttgtcactac?2760

aacaggtgca?gtcccaggcc?ggcccaccat?gatgatcagc?accacggcca?tgaacactgc?2820

gctgctccag?tggcacccac?ccaaggaact?gcctggcgag?ctgctgggct?accggctgca?2880

gtactgccgg?gccgacgagg?cgcggcccaa?caccatagat?ttcggcaagg?atgaccagca?2940

cttcacagtc?accggcctgc?acaaggggac?cacctacatc?ttccggcttg?ctgccaagaa?3000

ccgggctggc?ttgggtgagg?agttcgagaa?ggagatcagg?acccccgagg?acctgcccag?3060

cggcttcccc?caaaacctgc?atgtgacagg?actgaccacg?tctaccacag?aactggcctg?3120

ggacccgcca?gtgctggcgg?agaggaacgg?gcgcatcatc?agctacaccg?tggtgttccg?3180

agacatcaac?agccaacagg?agctgcagaa?catcacgaca?gacacccgct?ttacccttac?3240

tggcctcaag?ccagacacca?cttacgacat?caaggtccgc?gcatggacca?gcaaaggctc?3300

tggcccactc?agccccagca?tccagtcccg?gaccatgccg?gtggagcaag?tgtttgccaa?3360

gaacttccgg?gtggcggctg?caatgaagac?gtctgtgctg?ctcagctggg?aggttcccga?3420

ctcctataag?tcagctgtgc?cctttaagat?tctgtacaat?gggcagagtg?tggaggtgga?3480

cgggcactcg?atgcggaagc?tgatcgcaga?cctgcagccc?aacacagagt?actcgtttgt?3540

gctgatgaac?cgtggcagca?gcgcaggggg?cctgcagcac?ctggtgtcca?tccgcacagc?3600

ccccgacctc?ctgcctcaca?agccgctgcc?tgcctctgcc?tacatagagg?acggccgctt?3660

cgatctctcc?atgccccatg?tgcaagaccc?ctcgcttgtc?aggtggttct?acattgttgt?3720

ggtacccatt?gaccgtgtgg?gcgggagcat?gctgacgcca?aggtggagca?cacccgagga?3780

actggagctg?gacgagcttc?tagaagccat?cgagcaaggc?ggagaggagc?agcggcggcg?3840

gcggcggcag?gcagaacgtc?tgaagccata?tgtggctgct?caactggatg?tgctcccgga?3900

gacctttacc?ttgggggaca?agaagaacta?ccggggcttc?tacaaccggc?ccctgtctcc?3960

ggacttgagc?taccagtgct?ttgtgcttgc?ctccttgaag?gaacccatgg?accagaagcg?4020

ctatgcctcc?agcccctact?cggatgagat?cgtggtccag?gtgacaccag?cccagcagca?4080

ggaggagccg?gagatgctgt?gggtgacggg?tcccgtgctg?gcagtcatcc?tcatcatcct?4140

cattgtcatc?gccatcctct?tgttcaaaag?gaaaaggacc?cactctccgt?cctctaagga?4200

tgagcagtcg?atcggactga?aggactcctt?gctggcccac?tcctctgacc?ctgtggagat?4260

gcggaggctc?aactaccaga?ccccaggtat?gcgagaccac?ccacccatcc?ccatcaccga?4320

cctggcggac?aacatcgagc?gcctcaaagc?caacgatggc?ctcaagttct?cccaggagta?4380

tgagtccatc?gaccctggac?agcagttcac?gtgggagaat?tcaaacctgg?aggtgaacaa?4440

gcccaagaac?cgctatgcga?atgtcatcgc?ctacgaccac?tctcgagtca?tccttacctc?4500

tatcgatggc?gtccccggga?gtgactacat?caatgccaac?tacatcgatg?gctaccgcaa?4560

gcagaatgcc?tacatcgcca?cgcagggccc?cctgcccgag?accatgggcg?atttctggag?4620

aatggtgtgg?gaacagcgca?cggccactgt?ggtcatgatg?acacggctgg?aggagaagtc?4680

ccgggtaaaa?tgtgatcagt?actggccagc?ccgtggcacc?gagacctgtg?gccttattca?4740

ggtgaccctg?ttggacacag?tggagctggc?cacatacact?gtgcgcacct?tcgcactcca?4800

caagagtggc?tccagtgaga?agcgtgagct?gcgtcagttt?cagttcatgg?cctggccaga?4860

ccatggagtt?cctgagtacc?caactcccat?cctggccttc?ctacgacggg?tcaaggcctg?4920

caacccccta?gacgcagggc?ccatggtggt?gcactgcagc?gcgggcgtgg?gccgcaccgg?4980

ctgcttcatc?gtgattgatg?ccatgttgga?gcggatgaag?cacgagaaga?cggtggacat?5040

ctatggccac?gtgacctgca?tgcgatcaca?gaggaactac?atggtgcaga?cggaggacca?5100

gtacgtgttc?atccatgagg?cgctgctgga?ggctgccacg?tgcggccaca?cagaggtgcc?5160

tgcccgcaac?ctgtatgccc?acatccagaa?gctgggccaa?gtgcctccag?gggagagtgt?5220

gaccgccatg?gagctcgagt?tcaagttgct?ggccagctcc?aaggcccaca?cgtcccgctt?5280

catcagcgcc?aacctgccct?gcaacaagtt?caagaaccgg?ctggtgaaca?tcatgcccta?5340

cgaattgacc?cgtgtgtgtc?tgcagcccat?ccgtggtgtg?gagggctctg?actacatcaa?5400

tgccagcttc?ctggatggtt?atagacagca?gaaggcctac?atagctacac?aggggcctct?5460

ggcagagagc?accgaggact?tctggcgcat?gctatgggag?cacaattcca?ccatcatcgt?5520

catgctgacc?aagcttcggg?agatgggcag?ggagaaatgc?caccagtact?ggccagcaga?5580

gcgctctgct?cgctaccagt?actttgttgt?tgacccgatg?gctgagtaca?acatgcccca?5640

gtatatcctg?cgtgagttca?aggtcacgga?tgcccgggat?gggcagtcaa?ggacaatccg?5700

gcagttccag?ttcacagact?ggccagagca?gggcgtgccc?aagacaggcg?agggattcat?5760

tgacttcatc?gggcaggtgc?ataagaccaa?ggagcagttt?ggacaggatg?ggcctatcac?5820

ggtgcactgc?agtgctggcg?tgggccgcac?cggggtgttc?atcactctga?gcatcgtcct?5880

ggagcgcatg?cgctatgagg?gcgtggtcga?catgtttcag?accgtgaaga?ccctgcgtac?5940

acagcgtcct?gccatggtgc?agacagagga?ccagtatcag?ctgtgctacc?gtgcggccct?6000

ggagtacctc?ggcagctttg?accactatgc?aacgtaacta?ccgctcccct?ctcctccgcc?6060

acccccgccg?tggggctccg?gaggggaccc?agctcctctg?agccataccg?accatcgtcc?6120

agccctccta?cgcagatgct?gtcactggca?gagcacagcc?cacggggatc?acagcgtttc?6180

aggaacgttg?ccacaccaat?cagagagcct?agaacatccc?tgggcaagtg?gatggcccag?6240

caggcaggca?ctgtggccct?tctgtccacc?agacccacct?ggagcccgct?tcaagctctc?6300

tgttgcgctc?ccgcatttct?catgcttctt?ctcatggggt?ggggttgggg?caaagcctcc?6360

tttttaatac?attaagtggg?gtagactgag?ggattttagc?ctcttccctc?tgatttttcc?6420

tttcgcgaat?ccgtatctgc?agaatgggcc?actgtagggg?ttggggttta?ttttgttttg?6480

tttttttttt?ttttttgtat?gacttctgct?gaaggacaga?acattgcctt?cctcgtgcag?6540

agctggggct?gccagcctga?gcggaggctc?ggccgtgggc?cgggaggcag?tgctgatccg?6600

gctgctcctc?cagcccttca?gacgagatcc?tgtttcagct?aaatgcaggg?aaactcaatg?6660

tttttttaag?ttttgttttc?cctttaaagc?ctttttttag?gccacattga?cagtggtggg?6720

cggggagaag?atagggaaca?ctcatccctg?gtcgtctatc?ccagtgtgtg?tttaacattc?6780

acagcccaga?accacagatg?tgtctgggag?agcctggcaa?ggcattcctc?atcaccatcg?6840

tgtttgcaaa?ggttaaaaca?aaaacaaaaa?accacaaaaa?taaaaaacaa?aaaaaacaaa?6900

aaacccaaaa?aaaaaaaaaa?aaagagtcag?cccttggctt?ctgcttcaaa?ccctcaagag?6960

gggaagcaac?tccgtgtgcc?tggggttccc?gagggagctg?ctggctgacc?tgggcccaca?7020

gagcctggct?ttggtcccca?gcattgcagt?atggtgtggt?gtttgtaggc?tgtggggtct?7080

ggctgtgtgg?ccaaggtgaa?tagcacaggt?tagggtgtgt?gccacacccc?atgcacctca?7140

gggccaagcg?ggggcgtggc?tggcctttca?ggtccaggcc?agtgggcctg?gtagcacatg?7200

tctgtcctca?gagcaggggc?cagatgattt?tcctccctgg?tttgcagctg?ttttcaaagc?7260

ccccgataat?cgctcttttc?cactccaaga?tgccctcata?aaccaatgtg?gcaagactac?7320

tggacttcta?tcaatggtac?tctaatcagt?ccttattatc?ccagcttgct?gaggggcagg?7380

gagagcgcct?cttcctctgg?gcagcgctat?ctagataggt?aagtgggggc?ggggaagggt?7440

gcatagctgt?tttagctgag?ggacgtggtg?ccgacgtccc?caaacctagc?taggctaagt?7500

caagatcaac?attccagggt?tggtaatgtt?ggatgatgaa?acattcattt?ttaccttgtg?7560

gatgctagtg?ctgtagagtt?cactgttgta?cacagtctgt?tttctatttg?ttaagaaaaa?7620

ctacagcatc?attgcataat?tcttgatggt?aataaatttg?aataatcaga?tttcttacaa?7680

aaaaaaaaaa?a 7691

<210>28

<211>1898

<212>PRT

＜213〉people (homo sapiens)

<400>28

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser

785 790 795 800

Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 910

Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val

930 935 940

Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr

945 950 955 960

Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1010 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser

1125 1130 1135

Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Asn?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu

1875 1880 1885

Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>29

<211>1948

<212>PRT

＜213〉people (homo sapiens)

<400>29

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

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

195 200 205

Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Val

210 215 220

Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Glu?Leu?Arg?Glu?Val

225 230 235 240

Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser?His?Glu?Ile

245 250 255

Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro

260 265 270

Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu

275 280 285

Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr?Asp?Val?Lys

290 295 300

Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu?Gly?Val?Ile

305 310 315 320

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

325 330 335

Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr?Ile?Thr?Trp

340 345 350

Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile?Glu?Tyr?Lys

355 360 365

Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp?Ile?Thr?Thr

370 375 380

Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu?Tyr?Glu?Ile

385 390 395 400

Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser

405 410 415

Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala?Pro?Arg?Asn

420 425 430

Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val?Gln?Trp?Glu

435 440 445

Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr

450 455 460

Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys?His?Asn?Val

465 470 475 480

Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Glu?Asp?Glu?Thr

485 490 495

Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu

500 505 510

Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro?Gly?Gln?Pro

515 520 525

Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile?Thr?Leu?Ser

530 535 540

Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu?Leu?Leu?Phe

545 550 555 560

Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe?Asp?Pro?Thr

565 570 575

Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu?Tyr?Ala?Phe

580 585 590

Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe?Thr?Pro?Val

595 600 605

Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp

610 615 620

Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val?Ser?Trp?Arg

625 630 635 640

Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly?Tyr?Ser?Val

645 650 655

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

660 665 670

Gly?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala?Leu?Glu?Lys

675 680 685

Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu?Val?Gly?Pro

690 695 700

Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro

705 710 715 720

Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn?Ala?Thr?Ala

725 730 735

Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln?His?Gly?Gln

740 745 750

Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly?Ala?Glu?Ala

755 760 765

Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp

770 775 780

Glu?Thr?Asp?Asp?Thr?Ala?Glu?Tyr?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln

785 790 795 800

Pro?Glu?Thr?Ala?Tyr?Ser?Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly

805 810 815

Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val

820 825 830

Leu?Gly?Arg?Pro?Thr?Leu?Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu

835 840 845

Leu?Ala?Arg?Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu

850 855 860

Gly?Tyr?Arg?Leu?Gln?Phe?Gly?Arg?Glu?Asp?Ser?Thr?Pro?Leu?Ala?Thr

865 870 875 880

Leu?Glu?Phe?Pro?Pro?Ser?Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His

885 890 895

Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly

900 905 910

Leu?Gly?Glu?Glu?Ala?Ala?Glu?Val?Leu?Ser?Ile?Pro?Glu?Asp?Thr?Pro

915 920 925

Arg?Gly?His?Pro?Gln?Ile?Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly

930 935 940

Thr?Val?Leu?Leu?Arg?Trp?Leu?Pro?Pro?Val?Pro?Ala?Glu?Arg?Asn?Gly

945 950 955 960

Ala?Ile?Val?Lys?Tyr?Thr?Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly

965 970 975

Pro?Ala?Arg?Glu?Thr?Glu?Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu

980 985 990

Asn?Ala?Leu?Thr?Leu?Gln?Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu

995 1000 1005

Gln?Val?Arg?Ala?His?Thr?Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro

1010 1015 1020

Val?Arg?Tyr?Arg?Thr?Phe?Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe

1025 1030 1035 1040

Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe

1045 1050 1055

Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly

1060 1065 1070

Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His

1075 1080 1085

Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser

1090 1095 1100

Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn

1105 1110 1115 1120

Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly

1125 1130 1135

Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln

1140 1145 1150

Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln

1155 1160 1165

Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu

1170 1175 1180

Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg

1185 1190 1195 1200

Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu

1205 1210 1215

Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp

1220 1225 1230

Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala

1235 1240 1245

Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp

1250 1255 1260

Pro?Phe?Gln?Leu?Asp?Asn?Pro?AsP?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu

1265 1270 1275 1280

Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1285 1290 1295

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser

1300 1305 1310

Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala

1315 1320 1325

Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile

1330 1335 1340

Asn?Phe?Gln?Thr?Pro?Asp?Ser?Gly?Leu?Arg?Ser?Pro?Leu?Arg?Glu?Pro

1345 1350 1355 1360

Gly?Phe?His?Phe?Glu?Ser?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala

1365 1370 1375

Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys

1380 1385 1390

Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp

1395 1400 1405

Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn

1410 1415 1420

Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly

1425 1430 1435 1440

Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg

1445 1450 1455

Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe

1460 1465 1470

Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val

1475 1480 1485

Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr

1490 1495 1500

Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu

1505 1510 1515 1520

Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu

1525 1530 1535

His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe

1540 1545 1550

Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu

1555 1560 1565

Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro

1570 1575 1580

Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile

1585 1590 1595 1600

Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp

1605 1610 1615

Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val

1620 1625 1630

Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala

1635 1640 1645

Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr

1650 1655 1660

Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met

1665 1670 1675 1680

Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg

1685 1690 1695

Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val

1700 1705 1710

Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg

1715 1720 1725

Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr

1730 1735 1740

Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr

1745 1750 1755 1760

Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val

1765 1770 1775

Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln

1780 1785 1790

Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp

1795 1800 1805

Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys

1810 1815 1820

Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln

1825 1830 1835 1840

Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe

1845 1850 1855

Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln

1860 1865 1870

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

1875 1880 1885

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

1890 1895 1900

Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro

1905 1910 1915 1920

Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala

1925 1930 1935

Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1940 1945

<210>30

<211>6500

<212>DNA

＜213〉people (homo sapiens)

<400>30

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcagaaac?ctttgaaagc?actccgattc?840

gaggagccct?gcagattgaa?agcagtgagg?aaaccgacca?gggcaaatat?gagtgtgtgg?900

ccaccaacag?cgccggcgtg?cgctactcct?cacctgccaa?cctctacgtg?cgagagcttc?960

gagaagtccg?ccgcgtggcc?ccgcgcttct?ccatcctgcc?catgagccac?gagatcatgc?1020

cagggggcaa?cgtgaacatc?acctgcgtgg?ccgtgggctc?gcccatgcca?tacgtgaagt?1080

ggatgcaggg?ggccgaggac?ctgacccccg?aggatgacat?gcccgtgggt?cggaacgtgc?1140

tggaactcac?agatgtcaag?gactcggcca?actacacctg?cgtggccatg?tccagcctgg?1200

gcgtcattga?ggcggttgct?cagatcacgg?tgaaatctct?ccccaaagct?cccgggactc?1260

ccatggtgac?tgagaacaca?gccaccagca?tcaccatcac?gtgggactcg?ggcaacccag?1320

atcctgtgtc?ctattacgtc?atcgaatata?aatccaagag?ccaagacggg?ccgtatcaga?1380

ttaaagagga?catcaccacc?acacgttaca?gcatcggcgg?cctgagcccc?aactcggagt?1440

acgagatctg?ggtgtcggcc?gtcaactcca?tcggccaggg?gccccccagc?gagtccgtgg?1500

tcacccgcac?aggcgagcag?gccccggcca?gcgcgccgcg?gaacgtgcaa?gcccggatgc?1560

tcagcgcgac?caccatgatt?gtgcagtggg?aggagccggt?ggagcccaac?ggcctgatcc?1620

gcggctaccg?cgtctactac?accatggaac?cggagcaccc?cgtgggcaac?tggcagaagc?1680

acaacgtgga?cgacagcctg?ctgaccaccg?tgggcagcct?gctggaggac?gagacctaca?1740

ccgtgcgggt?gctcgccttc?acctccgtcg?gcgacgggcc?cctctcggac?cccatccagg?1800

tcaagacgca?gcagggagtg?ccgggccagc?ccatgaacct?gcgggccgag?gccaggtcgg?1860

agaccagcat?cacgctgtcc?tggagccccc?cgcggcagga?gagtatcatc?aagtacgagc?1920

tcctcttccg?ggaaggcgac?catggccggg?aggtgggaag?gaccttcgac?ccgacgactt?1980

cctacgtggt?ggaggacctg?aagcccaaca?cggagtacgc?cttccgcctg?gcggcccgct?2040

cgccgcaggg?cctgggcgcc?ttcacccccg?tggtgcggca?gcgcacgctg?cagtccaaac?2100

cgtcagcccc?ccctcaagac?gttaaatgtg?tcagcgtgcg?ctccacggcc?attttggtaa?2160

gttggcgccc?gccgccgccg?gaaacgcaca?acggggccct?ggtgggctac?agcgtccgct?2220

accgaccgct?gggctcagag?gacccggaac?ccaaggaggt?gaacggcatc?cccccgacca?2280

ccactcagat?cctgctggag?gccttggaga?agtggaccca?gtaccgcatc?acgactgtcg?2340

ctcacacaga?ggtgggacca?gggcccgaga?gctcgcccgt?ggtcgtccgc?accgacgagg?2400

atgtgcccag?cgcgccgccg?cggaaggtgg?aggcggaggc?gctcaacgcc?acggccatcc?2460

gcgtgctgtg?gcgctcgccc?gcgcccggcc?ggcagcacgg?ccagatccgc?ggctaccagg?2520

tccactacgt?gcgcatggag?ggcgccgagg?cccgcgggcc?gccgcgcatc?aaggacgtca?2580

tgctggccga?tgcccagtgg?gagacggatg?acacggccga?atatgagatg?gtcatcacaa?2640

acttgcagcc?tgagaccgcg?tactccatca?cggtagccgc?ctacaccatg?aagggcgatg?2700

gcgctcgcag?caaacccaag?gtggttgtga?ccaagggagc?agtgctgggc?cgcccaaccc?2760

tgtcggtgca?gcagaccccc?gagggcagcc?tgctggcacg?ctgggagccc?ccggctggca?2820

ccgcggagga?ccaggtgctg?ggctaccgcc?tgcagtttgg?ccgtgaggac?tcgacgcccc?2880

tggccaccct?ggagttcccg?ccctccgagg?accgctacac?ggcatcaggc?gtgcacaagg?2940

gggccacgta?tgtgttccgg?cttgcggccc?ggagccgcgg?cggcctgggc?gaggaggcag?3000

ccgaggtcct?gagcatcccg?gaggacacgc?cccgtggcca?cccgcagatt?ctggaggcgg?3060

ccggcaacgc?ctcggccggg?accgtccttc?tccgctggct?gccacccgtg?cccgccgagc?3120

gcaacggggc?catcgtcaaa?tacacggtgg?ccgtgcggga?ggccggtgcc?ctgggccctg?3180

cccgagagac?tgagctgccg?gcagcggctg?agccgggcgc?ggagaacgcg?ctcacgctgc?3240

agggcctgaa?gcccgacacg?gcctatgacc?tccaagtgcg?agcccacacg?cgccggggcc?3300

ctggcccctt?cagccccccc?gtccgctacc?ggacgttcct?gcgggaccaa?gtctcgccca?3360

agaacttcaa?ggtgaaaatg?atcatgaaga?catcagttct?gctcagctgg?gagttccctg?3420

acaactacaa?ctcacccaca?ccctacaaga?tccagtacaa?tgggctcaca?ctggatgtgg?3480

atggccgtac?caccaagaag?ctcatcacgc?acctcaagcc?ccacaccttc?tacaactttg?3540

tgctgaccaa?tcgcggcagc?agcctgggcg?gcctccagca?gacggtcacc?gcctggactg?3600

ccttcaacct?gctcaacggc?aagcccagcg?tcgcccccaa?gcctgatgct?gacggcttca?3660

tcatggtgta?tcttcctgac?ggccagagcc?ccgtgcctgt?ccagagctat?ttcattgtga?3720

tggtgccact?gcgcaagtct?cgtggaggcc?aattcctgac?cccgctgggt?agcccagagg?3780

acatggatct?ggaagagctc?atccaggaca?tctcacggct?acagaggcgc?agcctgcggc?3840

actcgcgtca?gctggaggtg?ccccggccct?atattgcagc?tcgcttctct?gtgctgccac?3900

ccacgttcca?tcccggcgac?cagaagcagt?atggcggctt?cgataaccgg?ggcctggagc?3960

ccggccaccg?ctatgtcctc?ttcgtgcttg?ccgtgcttca?gaagagcgag?cctacctttg?4020

cagccagtcc?cttctcagac?cccttccagc?tggataaccc?ggacccccag?cccatcgtgg?4080

atggcgagga?ggggcttatc?tgggtgatcg?ggcctgtgct?ggccgtggtc?ttcataatct?4140

gcattgtcat?tgctatcctg?ctctacaaga?acaaacccga?cagtaaacgc?aaggactcag?4200

aaccccgcac?caaatgcctc?ctgaacaatg?ccgacctcgc?ccctcaccac?cccaaggacc?4260

ctgtggaaat?gagacgcatt?aacttccaga?ctccagattc?aggcctcagg?agccccctca?4320

gggagccggg?gtttcacttt?gaaagcatgc?ttagccaccc?gccaattccc?atcgcagaca?4380

tggcggagca?cacggagcgg?ctcaaggcca?acgacagcct?caagctctcc?caggagtatg?4440

agtccatcga?ccctggacag?cagttcacat?gggaacattc?caacctggaa?gtgaacaagc?4500

cgaagaaccg?ctatgccaac?gtcatcgcct?atgaccactc?ccgtgtcatc?ctccagccca?4560

ttgaaggcat?catgggcagt?gattacatca?atgccaacta?cgtggacggc?taccggcgtc?4620

agaacgcgta?cattgccacg?caggggccgc?tgcctgagac?ctttggggac?ttctggcgta?4680

tggtgtggga?gcagcggtcg?gcgaccatcg?tcatgatgac?gcggctggag?gagaagtcac?4740

ggatcaagtg?tgatcagtat?tggcccaaca?gaggcacgga?gacctacggc?ttcatccagg?4800

tcacgttgct?agataccatc?gagctggcca?cattctgcgt?caggacattc?tctctgcaca?4860

agaatggctc?cagtgagaaa?cgcgaggtcc?gccagttcca?gtttacggcg?tggccggacc?4920

atggcgtgcc?cgaataccca?acgcccttcc?tggctttcct?gcggagagtc?aagacctgca?4980

acccgccaga?tgccggcccc?atcgtggttc?actgcagtgc?cggtgtgggc?cgcacaggct?5040

gctttatcgt?catcgacgcc?atgcttgagc?ggatcaagcc?agagaagaca?gtcgatgtct?5100

atggccacgt?gacgctcatg?aggtcccagc?gcaactacat?ggtgcagacg?gaggaccagt?5160

acagcttcat?ccacgaggcc?ctgctggagg?ccgtgggctg?tggcaacaca?gaagtgcccg?5220

cacgcagcct?ctatgcctac?atccagaagc?tggcccaggt?ggagcctggc?gaacacgtca?5280

ctggcatgga?actcgagttc?aagcggctgg?ctaactccaa?ggcccacacg?tcacgcttca?5340

tcagtgccaa?tctgccttgt?aacaagttca?agaaccgcct?ggtgaacatc?atgccctatg?5400

agagcacacg?ggtctgtctg?caacccatcc?ggggtgtgga?gggctctgac?tacatcaacg?5460

ccagcttcat?tgatggctac?aggcagcaga?aggcctacat?cgcgacacag?gggccgctgg?5520

cggagaccac?ggaagacttc?tggcgcatgc?tgtgggagaa?caattcgacg?atcgtggtga?5580

tgctgaccaa?gctgcgggag?atgggccggg?agaagtgtca?ccagtactgg?ccggccgagc?5640

gctctgcccg?ctaccagtac?tttgtggtag?atccgatggc?agaatacaac?atgcctcagt?5700

atatcctgcg?agagttcaag?gtcacagatg?cccgggatgg?ccagtcccgg?actgtccggc?5760

agttccagtt?cacagactgg?ccggaacagg?gtgtgccaaa?gtcgggggag?ggcttcatcg?5820

acttcattgg?ccaagtgcat?aagactaagg?agcagtttgg?ccaggacggc?cccatctctg?5880

tccactgcag?tgccggcgtg?ggcaggacgg?gcgtcttcat?cacgcttagc?atcgtgctgg?5940

agcggatgcg?gtatgaaggc?gtggtggaca?tctttcagac?ggtgaagatg?ctacgaaccc?6000

agcggccggc?catggtgcag?acagaggatg?agtaccagtt?ctgttaccag?gcggcactgg?6060

agtacctcgg?aagctttgac?cactatgcaa?cctaaagcca?tggtcccccc?caggcccgac?6120

accactggcc?ccggatgcct?ctgcccctcc?cgggcggacc?tcctgaggcc?tggaccccca?6180

gtgggcaggg?caggaggtgg?cagcggcagc?agctgtgttt?ctgcaccatt?tccgaggacg?6240

acgcagcccc?tcgagccccc?ccaccggccc?cggccgcccc?agcgacctcc?ctggcacggc?6300

cgccgccttc?aaatacttgg?cacattcctc?ctttccttcc?aattccaaaa?ccagattccg?6360

gggtgggggg?tggggggatg?gtgagcaaat?aggagtgctc?cccagaacca?gaggagggtg?6420

gggcacagac?catagacgga?cccctcgtcc?tcccccagcg?gtggtagggg?gacccggggg?6480

gctcctcccc?gctctgcacc 6500

<210>31

<211>1910

<212>PRT

＜213〉people (homo sapiens)

<400>31

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser

225 230 235 240

His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu

260 265 270

Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr

275 280 285

Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu

290 295 300

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

305 310 315 320

Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr

325 330 335

Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile

340 345 350

Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp

355 360 365

Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu

370 375 380

Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala

405 410 415

Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val

420 425 430

Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys

450 455 460

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

465 470 475 480

Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp

485 490 495

Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Gly?Gln?Pro?Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile

515 520 525

Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu

530 535 540

Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe

545 550 555 560

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

565 570 575

Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe

580 585 590

Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro

595 600 605

Pro?Gln?Asp?Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val

610 615 620

Ser?Trp?Arg?Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly

625 630 635 640

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

645 650 655

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

660 665 670

Leu?Glu?Lys?Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu

675 680 685

Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu

690 695 700

Asp?Val?Pro?Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn

705 710 715 720

Ala?Thr?Ala?Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln

725 730 735

His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly

740 745 750

Ala?Glu?Ala?Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp

755 760 765

Ala?Gln?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln?Pro?Glu?Thr?Ala?Tyr?Ser

770 775 780

Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys

785 790 795 800

Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val?Leu?Gly?Arg?Pro?Thr?Leu

805 810 815

Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu?Leu?Ala?Arg?Trp?Glu?Pro

820 825 830

Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu?Gly?Tyr?Arg?Leu?Gln?Phe

835 840 845

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

850 855 860

Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His?Lys?Gly?Ala?Thr?Tyr?Val

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly?Leu?Gly?Glu?Glu?Ala?Ala

885 890 895

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

900 905 910

Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly?Thr?Val?Leu?Leu?Arg?Trp

915 920 925

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

930 935 940

Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly?Pro?Ala?Arg?Glu?Thr?Glu

945 950 955 960

Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu?Asn?Ala?Leu?Thr?Leu?Gln

965 970 975

Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu?Gln?Val?Arg?Ala?His?Thr

980 985 990

Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro?Val?Arg?Tyr?Arg?Thr?Phe

995 1000 1005

Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe?Lys?Val?Lys?Met?Ile?Met

1010 1015 1020

Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser

1025 1030 1035 1040

Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly?Leu?Thr?Leu?Asp?Val?Asp

1045 1050 1055

Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His?Leu?Lys?Pro?His?Thr?Phe

1060 1065 1070

Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser?Ser?Leu?Gly?Gly?Leu?Gln

1075 1080 1085

Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn?Leu?Leu?Asn?Gly?Lys?Pro

1090 1095 1100

Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly?Phe?Ile?Met?Val?Tyr?Leu

1105 1110 1115 1120

Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln?Ser?Tyr?Phe?Ile?Val?Met

1125 1130 1135

Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln?Phe?Leu?Thr?Pro?Leu?Gly

1140 1145 1150

Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu?Ile?Gln?Asp?Ile?Ser?Arg

1155 1160 1165

Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg?Gln?Leu?Glu?Val?Pro?Arg

1170 1175 1180

Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu?Pro?Pro?Thr?Phe?His?Pro

1185 1190 1195 1200

Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp?Asn?Arg?Gly?Leu?Glu?Pro

1205 1210 1215

Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala?Val?Leu?Gln?Lys?Ser?Glu

1220 1225 1230

Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp?Pro?Phe?Gln?Leu?Asp?Asn

1235 1240 1245

Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu?Glu?Gly?Leu?Ile?Trp?Val

1250 1255 1260

Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala

1265 1270 1275 1280

Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser?Lys?Arg?Lys?Asp?Ser?Glu

1285 1290 1295

Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala?Asp?Leu?Ala?Pro?His?His

1300 1305 1310

Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile?Asn?Phe?Gln?Thr?Pro?Gly

1315 1320 1325

Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala?Asp?Met?Ala?Glu?His?Thr

1330 1335 1340

Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys?Leu?Ser?Gln?Glu?Tyr?Glu

1345 1350 1355 1360

Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu

1365 1370 1375

Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His

1380 1385 1390

Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly?Ile?Met?Gly?Ser?Asp?Tyr

1395 1400 1405

Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg?Arg?Gln?Asn?Ala?Tyr?Ile

1410 1415 1420

Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met

1425 1430 1435 1440

Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val?Met?Met?Thr?Arg?Leu?Glu

1445 1450 1455

Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Asn?Arg?Gly?Thr

1460 1465 1470

Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Ile?Glu?Leu

1475 1480 1485

Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu?His?Lys?Asn?Gly?Ser?Ser

1490 1495 1500

Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His

1505 1510 1515 1520

Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val

1525 1530 1535

Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Ile?Val?Val?His?Cys?Ser

1540 1545 1550

Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu

1555 1560 1565

Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp?Val?Tyr?Gly?His?Val?Thr

1570 1575 1580

Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr

1585 1590 1595 1600

Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Val?Gly?Cys?Gly?Asn?Thr

1605 1610 1615

Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Ala?Gln

1620 1625 1630

Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg

1635 1640 1645

Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu

1650 1655 1660

Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu

1665 1670 1675 1680

Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp

1685 1690 1695

Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr

1700 1705 1710

Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg

1715 1720 1725

Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu

1730 1735 1740

Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg

1745 1750 1755 1760

Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn

1765 1770 1775

Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp

1780 1785 1790

Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu

1795 1800 1805

Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln

1810 1815 1820

Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val

1825 1830 1835 1840

His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr?Leu?Ser

1845 1850 1855

Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln

1860 1865 1870

Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu

1875 1880 1885

Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser

1890 1895 1900

Phe?Asp?His?Tyr?Ala?Thr

1905 1910

<210>32

<211>6386

<212>DNA

＜213〉people (homo sapiens)

<400>32

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagtcc?gccgcgtggc?cccgcgcttc?tccatcctgc?960

ccatgagcca?cgagatcatg?ccagggggca?acgtgaacat?cacctgcgtg?gccgtgggct?1020

cgcccatgcc?atacgtgaag?tggatgcagg?gggccgagga?cctgaccccc?gaggatgaca?1080

tgcccgtggg?tcggaacgtg?ctggaactca?cagatgtcaa?ggactcggcc?aactacacct?1140

gcgtggccat?gtccagcctg?ggcgtcattg?aggcggttgc?tcagatcacg?gtgaaatctc?1200

tccccaaagc?tcccgggact?cccatggtga?ctgagaacac?agccaccagc?atcaccatca?1260

cgtgggactc?gggcaaccca?gatcctgtgt?cctattacgt?catcgaatat?aaatccaaga?1320

gccaagacgg?gccgtatcag?attaaagagg?acatcaccac?cacacgttac?agcatcggcg?1380

gcctgagccc?caactcggag?tacgagatct?gggtgtcggc?cgtcaactcc?atcggccagg?1440

ggccccccag?cgagtccgtg?gtcacccgca?caggcgagca?ggccccggcc?agcgcgccgc?1500

ggaacgtgca?agcccggatg?ctcagcgcga?ccaccatgat?tgtgcagtgg?gaggagccgg?1560

tggagcccaa?cggcctgatc?cgcggctacc?gcgtctacta?caccatggaa?ccggagcacc?1620

ccgtgggcaa?ctggcagaag?cacaacgtgg?acgacagcct?gctgaccacc?gtgggcagcc?1680

tgctggagga?cgagacctac?accgtgcggg?tgctcgcctt?cacctccgtc?ggcgacgggc?1740

ccctctcgga?ccccatccag?gtcaagacgc?agcagggagt?gccgggccag?cccatgaacc?1800

tgcgggccga?ggccaggtcg?gagaccagca?tcacgctgtc?ctggagcccc?ccgcggcagg?1860

agagtatcat?caagtacgag?ctcctcttcc?gggaaggcga?ccatggccgg?gaggtgggaa?1920

ggaccttcga?cccgacgact?tcctacgtgg?tggaggacct?gaagcccaac?acggagtacg?1980

ccttccgcct?ggcggcccgc?tcgccgcagg?gcctgggcgc?cttcaccccc?gtggtgcggc?2040

agcgcacgct?gcagtccaaa?ccgtcagccc?cccctcaaga?cgttaaatgt?gtcagcgtgc?2100

gctccacggc?cattttggta?agttggcgcc?cgccgccgcc?ggaaacgcac?aacggggccc?2160

tggtgggcta?cagcgtccgc?taccgaccgc?tgggctcaga?ggacccggaa?cccaaggagg?2220

tgaacggcat?ccccccgacc?accactcaga?tcctgctgga?ggccttggag?aagtggaccc?2280

agtaccgcat?cacgactgtc?gctcacacag?aggtgggacc?agggcccgag?agctcgcccg?2340

tggtcgtccg?caccgacgag?gatgtgccca?gcgcgccgcc?gcggaaggtg?gaggcggagg?2400

cgctcaacgc?cacggccatc?cgcgtgctgt?ggcgctcgcc?cgcgcccggc?cggcagcacg?2460

gccagatccg?cggctaccag?gtccactacg?tgcgcatgga?gggcgccgag?gcccgcgggc?2520

cgccgcgcat?caaggacgtc?atgctggccg?atgcccagga?gatggtcatc?acaaacttgc?2580

agcctgagac?cgcgtactcc?atcacggtag?ccgcctacac?catgaagggc?gatggcgctc?2640

gcagcaaacc?caaggtggtt?gtgaccaagg?gagcagtgct?gggccgccca?accctgtcgg?2700

tgcagcagac?ccccgagggc?agcctgctgg?cacgctggga?gcccccggct?ggcaccgcgg?2760

aggaccaggt?gctgggctac?cgcctgcagt?ttggccgtga?ggactcgacg?cccctggcca?2820

ccctggagtt?cccgccctcc?gaggaccgct?acacggcatc?aggcgtgcac?aagggggcca?2880

cgtatgtgtt?ccggcttgcg?gcccggagcc?gcggcggcct?gggcgaggag?gcagccgagg?2940

tcctgagcat?cccggaggac?acgccccgtg?gccacccgca?gattctggag?gcggccggca?3000

acgcctcggc?cgggaccgtc?cttctccgct?ggctgccacc?cgtgcccgcc?gagcgcaacg?3060

gggccatcgt?caaatacacg?gtggccgtgc?gggaggccgg?tgccctgggc?cctgcccgag?3120

agactgagct?gccggcagcg?gctgagccgg?gcgcggagaa?cgcgctcacg?ctgcagggcc?3180

tgaagcccga?cacggcctat?gacctccaag?tgcgagccca?cacgcgccgg?ggccctggcc?3240

ccttcagccc?ccccgtccgc?taccggacgt?tcctgcggga?ccaagtctcg?cccaagaact?3300

tcaaggtgaa?aatgatcatg?aagacatcag?ttctgctcag?ctgggagttc?cctgacaact?3360

acaactcacc?cacaccctac?aagatccagt?acaatgggct?cacactggat?gtggatggcc?3420

gtaccaccaa?gaagctcatc?acgcacctca?agccccacac?cttctacaac?tttgtgctga?3480

ccaatcgcgg?cagcagcctg?ggcggcctcc?agcagacggt?caccgcctgg?actgccttca?3540

acctgctcaa?cggcaagccc?agcgtcgccc?ccaagcctga?tgctgacggc?ttcatcatgg?3600

tgtatcttcc?tgacggccag?agccccgtgc?ctgtccagag?ctatttcatt?gtgatggtgc?3660

cactgcgcaa?gtctcgtgga?ggccaattcc?tgaccccgct?gggtagccca?gaggacatgg?3720

atctggaaga?gctcatccag?gacatctcac?ggctacagag?gcgcagcctg?cggcactcgc?3780

gtcagctgga?ggtgccccgg?ccctatattg?cagctcgctt?ctctgtgctg?ccacccacgt?3840

tccatcccgg?cgaccagaag?cagtatggcg?gcttcgataa?ccggggcctg?gagcccggcc?3900

accgctatgt?cctcttcgtg?cttgccgtgc?ttcagaagag?cgagcctacc?tttgcagcca?3960

gtcccttctc?agaccccttc?cagctggata?acccggaccc?ccagcccatc?gtggatggcg?4020

aggaggggct?tatctgggtg?atcgggcctg?tgctggccgt?ggtcttcata?atctgcattg?4080

tcattgctat?cctgctctac?aagaacaaac?ccgacagtaa?acgcaaggac?tcagaacccc?4140

gcaccaaatg?cctcctgaac?aatgccgacc?tcgcccctca?ccaccccaag?gaccctgtgg?4200

aaatgagacg?cattaacttc?cagactccag?gcatgcttag?ccacccgcca?attcccatcg?4260

cagacatggc?ggagcacacg?gagcggctca?aggccaacga?cagcctcaag?ctctcccagg?4320

agtatgagtc?catcgaccct?ggacagcagt?tcacatggga?acattccaac?ctggaagtga?4380

acaagccgaa?gaaccgctat?gccaacgtca?tcgcctatga?ccactcccgt?gtcatcctcc?4440

agcccattga?aggcatcatg?ggcagtgatt?acatcaatgc?caactacgtg?gacggctacc?4500

ggcgtcagaa?cgcgtacatt?gccacgcagg?ggccgctgcc?tgagaccttt?ggggacttct?4560

ggcgtatggt?gtgggagcag?cggtcggcga?ccatcgtcat?gatgacgcgg?ctggaggaga?4620

agtcacggat?caagtgtgat?cagtattggc?ccaacagagg?cacggagacc?tacggcttca?4680

tccaggtcac?gttgctagat?accatcgagc?tggccacatt?ctgcgtcagg?acattctctc?4740

tgcacaagaa?tggctccagt?gagaaacgcg?aggtccgcca?gttccagttt?acggcgtggc?4800

cggaccatgg?cgtgcccgaa?tacccaacgc?ccttcctggc?tttcctgcgg?agagtcaaga?4860

cctgcaaccc?accagatgcc?ggccccatcg?tggttcactg?cagtgccggt?gtgggccgca?4920

caggctgctt?tatcgtcatc?gacgccatgc?ttgagcggat?caagccagag?aagacagtcg?4980

atgtctatgg?ccacgtgacg?ctcatgaggt?cccagcgcaa?ctacatggtg?cagacggagg?5040

accagtacag?cttcatccac?gaggccctgc?tggaggccgt?gggctgtggc?aacacagaag?5100

tgcccgcacg?cagcctctat?gcctacatcc?agaagctggc?ccaggtggag?cctggcgaac?5160

acgtcactgg?catggaactc?gagttcaagc?ggctggctaa?ctccaaggcc?cacacgtcac?5220

gcttcatcag?tgccaatctg?ccttgtaaca?agttcaagaa?ccgcctggtg?aacatcatgc?5280

cctatgagag?cacacgggtc?tgtctgcaac?ccatccgggg?tgtggagggc?tctgactaca?5340

tcaacgccag?cttcattgat?ggctacaggc?agcagaaggc?ctacatcgcg?acacaggggc?5400

cgctggcgga?gaccacggaa?gacttctggc?gcatgctgtg?ggagaacaat?tcgacgatcg?5460

tggtgatgct?gaccaagctg?cgggagatgg?gccgggagaa?gtgtcaccag?tactggccgg?5520

ccgagcgctc?tgcccgctac?cagtactttg?tggtagatcc?gatggcagaa?tacaacatgc?5580

ctcagtatat?cctgcgagag?ttcaaggtca?cagatgcccg?ggatggccag?tcccggactg?5640

tccggcagtt?ccagttcaca?gactggccgg?aacagggtgt?gccaaagtcg?ggggagggct?5700

tcatcgactt?cattggccaa?gtgcataaga?ctaaggagca?gtttggccag?gacggcccca?5760

tctctgtcca?ctgcagtgcc?ggcgtgggca?ggacgggcgt?cttcatcacg?cttagcatcg?5820

tgctggagcg?gatgcggtat?gaaggcgtgg?tggacatctt?tcagacggtg?aagatgctac?5880

gaacccagcg?gccggccatg?gtgcagacag?aggatgagta?ccagttctgt?taccaggcgg?5940

cactggagta?cctcggaagc?tttgaccact?atgcaaccta?aagccatggt?cccccccagg?6000

cccgacacca?ctggccccgg?atgcctctgc?ccctcccggg?cggacctcct?gaggcctgga?6060

cccccagtgg?gcagggcagg?aggtggcagc?ggcagcagct?gtgtttctgc?accatttccg?6120

aggacgacgc?agcccctcga?gcccccccac?cggccccggc?cgccccagcg?acctccctgg?6180

cacggccgcc?gccttcaaat?acttggcaca?ttcctccttt?ccttccaatt?ccaaaaccag?6240

attccggggt?ggggggtggg?gggatggtga?gcaaatagga?gtgctcccca?gaaccagagg?6300

agggtggggc?acagaccata?gacggacccc?tcgtcctccc?ccagcggtgg?tagggggacc?6360

cggggggctc?ctccccgctc tgcacc 6386

<210>33

<211>1501

<212>PRT

＜213〉people (homo sapiens)

<400>33

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser

225 230 235 240

His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu

260 265 270

Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr

275 280 285

Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu

290 295 300

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

305 310 315 320

Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr

325 330 335

Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile

340 345 350

Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp

355 360 365

Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu

370 375 380

Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala

405 410 415

Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val

420 425 430

Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys

450 455 460

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

465 470 475 480

Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp

485 490 495

Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Gly?Gln?Pro?Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile

515 520 525

Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu

530 535 540

Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe

545 550 555 560

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

565 570 575

Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe

580 585 590

Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Ile?Ser?Pro?Lys?Asn

595 600 605

Phe?Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

610 615 620

Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn

625 630 635 640

Gly?Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr

645 650 655

His?Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly

660 665 670

Ser?Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe

675 680 685

Asn?Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp

690 695 700

Gly?Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val

705 710 715 720

Gln?Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly

725 730 735

Gln?Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu

740 745 750

Leu?Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser

755 760 765

Arg?Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val

770 775 780

Leu?Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe

785 790 795 800

Asp?Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu

805 810 815

Ala?Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser

820 825 830

Asp?Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly

835 840 845

Glu?Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe

850 855 860

Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp

865 870 875 880

Ser?Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn

885 890 895

Ala?Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg

900 905 910

Ile?Asn?Phe?Gln?Thr?Pro?Gly?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile

915 920 925

Ala?Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu

930 935 940

Lys?Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr

945 950 955 960

Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala

965 970 975

Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu

980 985 990

Gly?Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr

995 1000 1005

Arg?Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr

1010 1015 1020

Phe?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile

1025 1030 1035 1040

Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln

1045 1050 1055

Tyr?Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr

1060 1065 1070

Leu?Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser

1075 1080 1085

Leu?His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln

1090 1095 1100

Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe

1105 1110 1115 1120

Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly

1125 1130 1135

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

1140 1145 1150

Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val

1155 1160 1165

Asp?Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met

1170 1175 1180

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu

1185 1190 1195 1200

Ala?Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala

1205 1210 1215

Tyr?Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly

1220 1225 1230

Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser

1235 1240 1245

Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu

1250 1255 1260

Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile

1265 1270 1275 1280

Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly

1285 1290 1295

Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu

1300 1305 1310

Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile

1315 1320 1325

Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His

1330 1335 1340

Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val

1345 1350 1355 1360

Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe

1365 1370 1375

Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe

1380 1385 1390

Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly

1395 1400 1405

Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly

1410 1415 1420

Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1425 1430 1435 1440

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

1445 1450 1455

Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg

1460 1465 1470

Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala

1475 1480 1485

Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1490 1495 1500

<210>34

<211>5159

<212>DNA

＜213〉people (homo sapiens)

<400>34

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagtcc?gccgcgtggc?cccgcgcttc?tccatcctgc?960

ccatgagcca?cgagatcatg?ccagggggca?acgtgaacat?cacctgcgtg?gccgtgggct?1020

cgcccatgcc?atacgtgaag?tggatgcagg?gggccgagga?cctgaccccc?gaggatgaca?1080

tgcccgtggg?tcggaacgtg?ctggaactca?cagatgtcaa?ggactcggcc?aactacacct?1140

gcgtggccat?gtccagcctg?ggcgtcattg?aggcggttgc?tcagatcacg?gtgaaatctc?1200

tccccaaagc?tcccgggact?cccatggtga?ctgagaacac?agccaccagc?atcaccatca?1260

cgtgggactc?gggcaaccca?gatcctgtgt?cctattacgt?catcgaatat?aaatccaaga?1320

gccaagacgg?gccgtatcag?attaaagagg?acatcaccac?cacacgttac?agcatcggcg?1380

gcctgagccc?caactcggag?tacgagatct?gggtgtcggc?cgtcaactcc?atcggccagg?1440

ggccccccag?cgagtccgtg?gtcacccgca?caggcgagca?ggccccggcc?agcgcgccgc?1500

ggaacgtgca?agcccggatg?ctcagcgcga?ccaccatgat?tgtgcagtgg?gaggagccgg?1560

tggagcccaa?cggcctgatc?cgcggctacc?gcgtctacta?caccatggaa?ccggagcacc?1620

ccgtgggcaa?ctggcagaag?cacaacgtgg?acgacagcct?gctgaccacc?gtgggcagcc?1680

tgctggagga?cgagacctac?accgtgcggg?tgctcgcctt?cacctccgtc?ggcgacgggc?1740

ccctctcgga?ccccatccag?gtcaagacgc?agcagggagt?gccgggccag?cccatgaacc?1800

tgcgggccga?ggccaggtcg?gagaccagca?tcacgctgtc?ctggagcccc?ccgcggcagg?1860

agagtatcat?caagtacgag?ctcctcttcc?gggaaggcga?ccatggccgg?gaggtgggaa?1920

ggaccttcga?cccgacgact?tcctacgtgg?tggaggacct?gaagcccaac?acggagtacg?1980

ccttccgcct?ggcggcccgc?tcgccgcagg?gcctgggcgc?cttcaccccc?gtggtgcggc?2040

agcgcacgct?gcagtccatc?tcgcccaaga?acttcaaggt?gaaaatgatc?atgaagacat?2100

cagttctgct?cagctgggag?ttccctgaca?actacaactc?acccacaccc?tacaagatcc?2160

agtacaatgg?gctcacactg?gatgtggatg?gccgtaccac?caagaagctc?atcacgcacc?2220

tcaagcccca?caccttctac?aactttgtgc?tgaccaatcg?cggcagcagc?ctgggcggcc?2280

tccagcagac?ggtcaccgcc?tggactgcct?tcaacctgct?caacggcaag?cccagcgtcg?2340

cccccaagcc?tgatgctgac?ggcttcatca?tggtgtatct?tcctgacggc?cagagccccg?2400

tgcctgtcca?gagctatttc?attgtgatgg?tgccactgcg?caagtctcgt?ggaggccaat?2460

tcctgacccc?gctgggtagc?ccagaggaca?tggatctgga?agagctcatc?caggacatct?2520

cacggctaca?gaggcgcagc?ctgcggcact?cgcgtcagct?ggaggtgccc?cggccctata?2580

ttgcagctcg?cttctctgtg?ctgccaccca?cgttccatcc?cggcgaccag?aagcagtatg?2640

gcggcttcga?taaccggggc?ctggagcccg?gccaccgcta?tgtcctcttc?gtgcttgccg?2700

tgcttcagaa?gagcgagcct?acctttgcag?ccagtccctt?ctcagacccc?ttccagctgg?2760

ataacccgga?cccccagccc?atcgtggatg?gcgaggaggg?gcttatctgg?gtgatcgggc?2820

ctgtgctggc?cgtggtcttc?ataatctgca?ttgtcattgc?tatcctgctc?tacaagaaca?2880

aacccgacag?taaacgcaag?gactcagaac?cccgcaccaa?atgcctcctg?aacaatgccg?2940

acctcgcccc?tcaccacccc?aaggaccctg?tggaaatgag?acgcattaac?ttccagactc?3000

caggcatgct?tagccacccg?ccaattccca?tcgcagacat?ggcggagcac?acggagcggc?3060

tcaaggccaa?cgacagcctc?aagctctccc?aggagtatga?gtccatcgac?cctggacagc?3120

agttcacatg?ggaacattcc?aacctggaag?tgaacaagcc?gaagaaccgc?tatgccaacg?3180

tcatcgccta?tgaccactcc?cgtgtcatcc?tccagcccat?tgaaggcatc?atgggcagtg?3240

attacatcaa?tgccaactac?gtggacggct?accggcgtca?gaacgcgtac?attgccacgc?3300

aggggccgct?gcctgagacc?tttggggact?tctggcgtat?ggtgtgggag?cagcggtcgg?3360

cgaccatcgt?catgatgacg?cggctggagg?agaagtcacg?gatcaagtgt?gatcagtatt?3420

ggcccaacag?aggcacggag?acctacggct?tcatccaggt?cacgttgcta?gataccatcg?3480

agctggccac?attctgcgtc?aggacattct?ctctgcacaa?gaatggctcc?agtgagaaac?3540

gcgaggtccg?ccagttccag?tttacggcgt?ggccggacca?tggcgtgccc?gaatacccaa?3600

cgcccttcct?ggctttcctg?cggagagtca?agacctgcaa?cccaccagat?gccggcccca?3660

tcgtggttca?ctgcagtgcc?ggtgtgggcc?gcacaggctg?ctttatcgtc?atcgacgcca?3720

tgcttgagcg?gatcaagcca?gagaagacag?tcgatgtcta?tggccacgtg?acgctcatga?3780

ggtcccagcg?caactacatg?gtgcagacgg?aggaccagta?cagcttcatc?cacgaggccc?3840

tgctggaggc?cgtgggctgt?ggcaacacag?aagtgcccgc?acgcagcctc?tatgcctaca?3900

tccagaagct?ggcccaggtg?gagcctggcg?aacacgtcac?tggcatggaa?ctcgagttca?3960

agcggctggc?taactccaag?gcccacacgt?cacgcttcat?cagtgccaat?ctgccttgta?4020

acaagttcaa?gaaccgcctg?gtgaacatca?tgccctatga?gagcacacgg?gtctgtctgc?4080

aacccatccg?gggtgtggag?ggctctgact?acatcaacgc?cagcttcatt?gatggctaca?4140

ggcagcagaa?ggcctacatc?gcgacacagg?ggccgctggc?ggagaccacg?gaagacttct?4200

ggcgcatgct?gtgggagaac?aattcgacga?tcgtggtgat?gctgaccaag?ctgcgggaga?4260

tgggccggga?gaagtgtcac?cagtactggc?cggccgagcg?ctctgcccgc?taccagtact?4320

ttgtggtaga?tccgatggca?gaatacaaca?tgcctcagta?tatcctgcga?gagttcaagg?4380

tcacagatgc?ccgggatggc?cagtcccgga?ctgtccggca?gttccagttc?acagactggc?4440

cggaacaggg?tgtgccaaag?tcgggggagg?gcttcatcga?cttcattggc?caagtgcata?4500

agactaagga?gcagtttggc?caggacggcc?ccatctctgt?ccactgcagt?gccggcgtgg?4560

gcaggacggg?cgtcttcatc?acgcttagca?tcgtgctgga?gcggatgcgg?tatgaaggcg?4620

tggtggacat?ctttcagacg?gtgaagatgc?tacgaaccca?gcggccggcc?atggtgcaga?4680

cagaggatga?gtaccagttc?tgttaccagg?cggcactgga?gtacctcgga?agctttgacc?4740

actatgcaac?ctaaagccat?ggtccccccc?aggcccgaca?ccactggccc?cggatgcctc?4800

tgcccctccc?gggcggacct?cctgaggcct?ggacccccag?tgggcagggc?aggaggtggc?4860

agcggcagca?gctgtgtttc?tgcaccattt?ccgaggacga?cgcagcccct?cgagcccccc?4920

caccggcccc?ggccgcccca?gcgacctccc?tggcacggcc?gccgccttca?aatacttggc?4980

acattcctcc?tttccttcca?attccaaaac?cagattccgg?ggtggggggt?ggggggatgg?5040

tgagcaaata?ggagtgctcc?ccagaaccag?aggagggtgg?ggcacagacc?atagacggac?5100

ccctcgtcct?cccccagcgg?tggtaggggg?acccgggggg?ctcctccccg?ctctgcacc 5159

<210>35

<211>1505

<212>PRT

＜213〉people (homo sapiens)

<400>35

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Leu?Pro?Met?Ser?His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Thr?Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Ser?Leu?Gly?Val?Ile?Glu?Ala?Val?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ser?Leu?Pro?Lys?Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser

340 345 350

Tyr?Tyr?Val?Ile?Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln

355 360 365

Ile?Lys?Glu?Asp?Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser

370 375 380

Pro?Asn?Ser?Glu?Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly

385 390 395 400

Gln?Gly?Pro?Pro?Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala

405 410 415

Pro?Ala?Ser?Ala?Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr

420 425 430

Thr?Met?Ile?Val?Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile

435 440 445

Arg?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly

450 455 460

Asn?Trp?Gln?Lys?His?Asn?Val?Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly

465 470 475 480

Ser?Leu?Leu?Glu?Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Val?Gly?Asp?Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln

500 505 510

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

515 520 525

Glu?Thr?Ser?Ile?Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile

530 535 540

Ile?Lys?Tyr?Glu?Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val

545 550 555 560

Gly?Arg?Thr?Phe?Asp?Pro?Thr?Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys

565 570 575

Pro?Asn?Thr?Glu?Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Phe?Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Ile

595 600 605

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

610 615 620

Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys

625 630 635 640

Ile?Gln?Tyr?Asn?Gly?Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys

645 650 655

Lys?Leu?Ile?Thr?His?Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu

660 665 670

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

675 680 685

Trp?Thr?Ala?Phe?Asn?Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys

690 695 700

Pro?Asp?Ala?Asp?Gly?Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser

705 710 715 720

Pro?Val?Pro?Val?Gln?Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys

725 730 735

Ser?Arg?Gly?Gly?Gln?Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met

740 745 750

Asp?Leu?Glu?Glu?Leu?Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser

755 760 765

Leu?Arg?His?Ser?Arg?Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala

770 775 780

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

785 790 795 800

Tyr?Gly?Gly?Phe?Asp?Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val

805 810 815

Leu?Phe?Val?Leu?Ala?Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala

820 825 830

Ser?Pro?Phe?Ser?Asp?Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro

835 840 845

Ile?Val?Asp?Gly?Glu?Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu

850 855 860

Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys

865 870 875 880

Asn?Lys?Pro?Asp?Ser?Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys Cys

885 890 895

Leu?Leu?Asn?Asn?Ala?Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val

900 905 910

Glu?Met?Arg?Arg?Ile?Asn?Phe?Gln?Thr?Pro?Gly?Met?Leu?Ser?His?Pro

915 920 925

Pro?Ile?Pro?Ile?Ala?Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala

930 935 940

Asn?Asp?Ser?Leu?Lys?Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly

945 950 955 960

Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys

965 970 975

Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu

980 985 990

Gln?Pro?Ile?Glu?Gly?Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr

995 1000 1005

Val?Asp?Gly?Tyr?Arg?Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro

1010 1015 1020

Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg

1025 1030 1035 1040

Ser?Ala?Thr?Ile?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile

1045 1050 1055

Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe

1060 1065 1070

Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val

1075 1080 1085

Arg?Thr?Phe?Ser?Leu?His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val

1090 1095 1100

Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr

1105 1110 1115 1120

Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro

1125 1130 1135

Pro?Asp?Ala?Gly?Pro?Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg

1140 1145 1150

Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro

1155 1160 1165

Glu?Lys?Thr?Val?Asp?Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln

1170 1175 1180

Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu

1185 1190 1195 1200

Ala?Leu?Leu?Glu?Ala?Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg

1205 1210 1215

Ser?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu

1220 1225 1230

His?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys

1235 1240 1245

Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe

1250 1255 1260

Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys

1265 1270 1275 1280

Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser

1285 1290 1295

Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly

1300 1305 1310

Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn

1315 1320 1325

Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg

1330 1335 1340

Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln

1345 1350 1355 1360

Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile

1365 1370 1375

Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr

1380 1385 1390

Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys

1395 1400 1405

Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys

1410 1415 1420

Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly

1425 1430 1435 1440

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

1445 1450 1455

Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu

1460 1465 1470

Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe

1475 1480 1485

Cys?Tyr?Gln?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala

1490 1495 1500

Thr

1505

<210>36

<211>5171

<212>DNA

＜213〉people (homo sapiens)

<400>36

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc 60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc 120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc 180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagagc?ttcgagaagt?ccgccgcgtg?gccccgcgct?960

tctccatcct?gcccatgagc?cacgagatca?tgccaggggg?caacgtgaac?atcacctgcg?1020

tggccgtggg?ctcgcccatg?ccatacgtga?agtggatgca?gggggccgag?gacctgaccc?1080

ccgaggatga?catgcccgtg?ggtcggaacg?tgctggaact?cacagatgtc?aaggactcgg?1140

ccaactacac?ctgcgtggcc?atgtccagcc?tgggcgtcat?tgaggcggtt?gctcagatca?1200

cggtgaaatc?tctccccaaa?gctcccggga?ctcccatggt?gactgagaac?acagccacca?1260

gcatcaccat?cacgtgggac?tcgggcaacc?cagatcctgt?gtcctattac?gtcatcgaat?1320

ataaatccaa?gagccaagac?gggccgtatc?agattaaaga?ggacatcacc?accacacgtt?1380

acagcatcgg?cggcctgagc?cccaactcgg?agtacgagat?ctgggtgtcg?gccgtcaact?1440

ccatcggcca?ggggcccccc?agcgagtccg?tggtcacccg?cacaggcgag?caggccccgg?1500

ccagcgcgcc?gcggaacgtg?caagcccgga?tgctcagcgc?gaccaccatg?attgtgcagt?1560

gggaggagcc?ggtggagccc?aacggcctga?tccgcggcta?ccgcgtctac?tacaccatgg?1620

aaccggagca?ccccgtgggc?aactggcaga?agcacaacgt?ggacgacagc?ctgctgacca?1680

ccgtgggcag?cctgctggag?gacgagacct?acaccgtgcg?ggtgctcgcc?ttcacctccg?1740

tcggcgacgg?gcccctctcg?gaccccatcc?aggtcaagac?gcagcaggga?gtgccgggcc?1800

agcccatgaa?cctgcgggcc?gaggccaggt?cggagaccag?catcacgctg?tcctggagcc?1860

ccccgcggca?ggagagtatc?atcaagtacg?agctcctctt?ccgggaaggc?gaccatggcc?1920

gggaggtggg?aaggaccttc?gacccgacga?cttcctacgt?ggtggaggac?ctgaagccca?1980

acacggagta?cgccttccgc?ctggcggccc?gctcgccgca?gggcctgggc?gccttcaccc?2040

ccgtggtgcg?gcagcgcacg?ctgcagtcca?tctcgcccaa?gaacttcaag?gtgaaaatga?2100

tcatgaagac?atcagttctg?ctcagctggg?agttccctga?caactacaac?tcacccacac?2160

cctacaagat?ccagtacaat?gggctcacac?tggatgtgga?tggccgtacc?accaagaagc?2220

tcatcacgca?cctcaagccc?cacaccttct?acaactttgt?gctgaccaat?cgcggcagca?2280

gcctgggcgg?cctccagcag?acggtcaccg?cctggactgc?cttcaacctg?ctcaacggca?2340

agcccagcgt?cgcccccaag?cctgatgctg?acggcttcat?catggtgtat?cttcctgacg?2400

gccagagccc?cgtgcctgtc?cagagctatt?tcattgtgat?ggtgccactg?cgcaagtctc?2460

gtggaggcca?attcctgacc?ccgctgggta?gcccagagga?catggatctg?gaagagctca?2520

tccaggacat?ctcacggcta?cagaggcgca?gcctgcggca?ctcgcgtcag?ctggaggtgc?2580

cccggcccta?tattgcagct?cgcttctctg?tgctgccacc?cacgttccat?cccggcgacc?2640

agaagcagta?tggcggcttc?gataaccggg?gcctggagcc?cggccaccgc?tatgtcctct?2700

tcgtgcttgc?cgtgcttcag?aagagcgagc?ctacctttgc?agccagtccc?ttctcagacc?2760

ccttccagct?ggataacccg?gacccccagc?ccatcgtgga?tggcgaggag?gggcttatct?2820

gggtgatcgg?gcctgtgctg?gccgtggtct?tcataatctg?cattgtcatt?gctatcctgc?2880

tctacaagaa?caaacccgac?agtaaacgca?aggactcaga?accccgcacc?aaatgcctcc?2940

tgaacaatgc?cgacctcgcc?cctcaccacc?ccaaggaccc?tgtggaaatg?agacgcatta?3000

acttccagac?tccaggcatg?cttagccacc?cgccaattcc?catcgcagac?atggcggagc?3060

acacggagcg?gctcaaggcc?aacgacagcc?tcaagctctc?ccaggagtat?gagtccatcg?3120

accctggaca?gcagttcaca?tgggaacatt?ccaacctgga?agtgaacaag?ccgaagaacc?3180

gctatgccaa?cgtcatcgcc?tatgaccact?cccgtgtcat?cctccagccc?attgaaggca?3240

tcatgggcag?tgattacatc?aatgccaact?acgtggacgg?ctaccggcgt?cagaacgcgt?3300

acattgccac?gcaggggccg?ctgcctgaga?cctttgggga?cttctggcgt?atggtgtggg?3360

agcagcggtc?ggcgaccatc?gtcatgatga?cgcggctgga?ggagaagtca?cggatcaagt?3420

gtgatcagta?ttggcccaac?agaggcacgg?agacctacgg?cttcatccag?gtcacgttgc?3480

tagataccat?cgagctggcc?acattctgcg?tcaggacatt?ctctctgcac?aagaatggct?3540

ccagtgagaa?acgcgaggtc?cgccagttcc?agtttacggc?gtggccggac?catggcgtgc?3600

ccgaataccc?aacgcccttc?ctggctttcc?tgcggagagt?caagacctgc?aacccaccag?3660

atgccggccc?catcgtggtt?cactgcagtg?ccggtgtggg?ccgcacaggc?tgctttatcg?3720

tcatcgacgc?catgcttgag?cggatcaagc?cagagaagac?agtcgatgtc?tatggccacg?3780

tgacgctcat?gaggtcccag?cgcaactaca?tggtgcagac?ggaggaccag?tacagcttca?38

tccacgaggc?cctgctggag?gccgtgggct?gtggcaacac?agaagtgccc?gcacgcagcc?39

tctatgccta?catccagaag?ctggcccagg?tggagcctgg?cgaacacgtc?actggcatgg?39

aactcgagtt?caagcggctg?gctaactcca?aggcccacac?gtcacgcttc?atcagtgcca?40

atctgccttg?taacaagttc?aagaaccgcc?tggtgaacat?catgccctat?gagagcacac?40

gggtctgtct?gcaacccatc?cggggtgtgg?agggctctga?ctacatcaac?gccagcttca?41

ttgatggcta?caggcagcag?aaggcctaca?tcgcgacaca?ggggccgctg?gcggagacca?42

cggaagactt?ctggcgcatg?ctgtgggaga?acaattcgac?gatcgtggtg?atgctgacca?42

agctgcggga?gatgggccgg?gagaagtgtc?accagtactg?gccggccgag?cgctctgccc?43

gctaccagta?ctttgtggta?gatccgatgg?cagaatacaa?catgcctcag?tatatcctgc?43

gagagttcaa?ggtcacagat?gcccgggatg?gccagtcccg?gactgtccgg?cagttccagt?44

tcacagactg?gccggaacag?ggtgtgccaa?agtcggggga?gggcttcatc?gacttcattg?45

gccaagtgca?taagactaag?gagcagtttg?gccaggacgg?ccccatctct?gtccactgca?45

gtgccggcgt?gggcaggacg?ggcgtcttca?tcacgcttag?catcgtgctg?gagcggatgc?46

ggtatgaagg?cgtggtggac?atctttcaga?cggtgaagat?gctacgaacc?cagcggccgg?46

ccatggtgca?gacagaggat?gagtaccagt?tctgttacca?ggcggcactg?gagtacctcg?47

gaagctttga?ccactatgca?acctaaagcc?atggtccccc?ccaggcccga?caccactggc?48

cccggatgcc?tctgcccctc?ccgggcggac?ctcctgaggc?ctggaccccc?agtgggcagg?48

gcaggaggtg?gcagcggcag?cagctgtgtt?tctgcaccat?ttccgaggac?gacgcagccc?49

ctcgagcccc?cccaccggcc?ccggccgccc?cagcgacctc?cctggcacgg?ccgccgcctt?49

caaatacttg?gcacattcct?cctttccttc?caattccaaa?accagattcc?ggggtggggg?50

gtggggggat?ggtgagcaaa?taggagtgct?ccccagaacc?agaggagggt?ggggcacaga?51

ccatagacgg?acccctcgtc?ctcccccagc?ggtggtaggg?ggacccgggg?ggctcctccc?51

cgctctgcac?c 51

<210>37

<211>1912

<212>PRT

＜213〉people (homo sapiens)

<400>37

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Lys

595 600 605

Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser?Thr

610 615 620

Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn?Gly

625 630 635 640

Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp

645 650 655

Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys?Tyr

660 665 670

Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val?Thr

675 680 685

Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu?Ile

690 695 700

Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu?Val

705 710 715 720

Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro?Val

725 730 735

Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val

740 745 750

Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp?Val

755 760 765

Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr?Glu?His?Asp

770 775 780

Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser?Leu?Thr?Val

785 790 795 800

Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?LysLeu

805 810 815

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

820 825 830

His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro?Pro?Val?Asp

835 840 845

Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly?Arg?Lys?Asp

850 855 860

Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu?Asp?His?Phe

865 870 875 880

Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe?Arg?Leu?Ser

885 890 895

Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys?Glu?Ile?Ser

900 905 910

Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu?His?Ser?Glu

915 920 925

Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro?Pro?Val?Leu

930 935 940

Ala?Glu?Arg?Asn?Gly?Ile?Ile?Thr?Lys?Tyr?Thr?Leu?Leu?Tyr?Arg?Asp

945 950 955 960

Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val?Pro?Ala?Asp

965 970 975

Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp?Val

980 985 990

Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr?Ser?Pro?Ser

995 1000 1005

Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp?Gln?Val?Phe?Ala?Lys?Asn?Phe

1010 1015 1020

His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Ile

1025 1030 1035 1040

Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu?Tyr?Asp?Asp

1045 1050 1055

Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln?Lys?Leu?Ile

1060 1065 1070

Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu?Thr?Asn?Arg

1075 1080 1085

Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala?Lys?Thr?Ala

1090 1095 1100

Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys?Thr?Asn?Leu

1105 1110 1115 1120

Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala?Asn?Glu?Asn

1125 1130 1135

Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys?Ser?Arg?Gly

1140 1145 1150

Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu?Leu?Asp?Glu

1155 1160 1165

Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg?Tyr?Gly?Arg

1170 1175 1180

Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp?Val?Leu?Pro

1185 1190 1195 1200

Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly?Phe?Thr?Asn

1205 1210 1215

Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val?Leu?Ala?Val

1220 1225 1230

Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro?Tyr?Ser?Asp

1235 1240 1245

Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr?Asp?Glu?Glu

1250 1255 1260

Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1265 1270 1275 1280

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys?Arg?Ala?Glu

1285 1290 1295

Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu?Ile?Pro?Ser

1300 1305 1310

His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn?Phe?Gln?Thr

1315 1320 1325

Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu?Leu?Ala?Asp

1330 1335 1340

His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe?Ser?Gln?Glu

1345 1350 1355 1360

Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn

1365 1370 1375

Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr

1380 1385 1390

Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile?Pro?Gly?Ser

1395 1400 1405

Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala

1410 1415 1420

Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp

1425 1430 1435 1440

Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met?Met?Thr?Lys

1445 1450 1455

Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ser?Arg

1460 1465 1470

Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu?Asp?Thr?Val

1475 1480 1485

Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr?Lys?Asn?Gly

1490 1495 1500

Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro

1505 1510 1515 1520

Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg

1525 1530 1535

Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met?Val?Val?His

1540 1545 1550

Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala

1555 1560 1565

Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly?His

1570 1575 1580

Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp

1585 1590 1595 1600

Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val?Thr?Cys?Gly

1605 1610 1615

Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu

1620 1625 1630

Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe

1635 1640 1645

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

1650 1655 1660

Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro

1665 1670 1675 1680

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

1685 1690 1695

Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys

1700 1705 1710

Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe

1715 1720 1725

Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr

1730 1735 1740

Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala

1745 1750 1755 1760

Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu

1765 1770 1775

Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala

1780 1785 1790

Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp

1795 1800 1805

Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile

1810 1815 1820

Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile

1825 1830 1835 1840

Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr

1845 1850 1855

Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile

1860 1865 1870

Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln

1875 1880 1885

Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu

1890 1895 1900

Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1905 1910

<210>38

<211>6263

<212>DNA

＜213〉people (homo sapiens)

<400>38

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaaagccg?1980

tcagctcctc?ctcaagacat?tagttgcacc?agcccaagtt?ccactagtat?tttggtaagt?2040

tggcaacctc?caccagtgga?aaaacagaat?ggcattatca?ctgaatactc?catcaagtac?2100

actgcagtgg?atggggaaga?tgacaagcct?cacgagattt?tgggaattcc?ttcggacact?2160

accaaatacc?ttttggaaca?gctggaaaaa?tggactgaat?accggatcac?tgtgacagcc?2220

catacagatg?tcggccctgg?ccctgagagc?ttgtccgtgt?tgattcgaac?caatgaagat?2280

gttcctagtg?gtcctcctcg?caaagtcgag?gtagaggctg?tcaactcaac?atctgttaaa?2340

gtctcatggc?gctcacccgt?gcccaataaa?cagcatggcc?agataagagg?atatcaggtg?2400

cattatgtga?ggatggaaaa?tggtgagccc?aagggccagc?ccatgctgaa?agatgtcatg?2460

ctggctgatg?cacagtggga?atttgatgat?actactgaac?atgacatgat?catttctggg?2520

ctccagcctg?aaacttccta?ctccctcacc?gtcacagcct?acacaaccaa?aggagatggt?2580

gctcgcagca?agcccaaact?ggtgtccacc?actggggcag?ttccagggaa?acctcggctt?2640

gtgattaacc?acactcagat?gaatactgct?cttattcagt?ggcaccctcc?ggtggacaca?2700

tttggacctc?ttcagggcta?ccgtctaaaa?tttggccgca?aggatatgga?gccacttact?2760

actcttgagt?tctctgaaaa?agaagatcac?tttacagcta?cagacatcca?caagggagca?2820

tcatacgtct?tcaggctctc?agccagaaac?aaagtgggct?ttggggagga?gatggtgaag?2880

gagatttcca?ttccagaaga?agtaccaact?ggattccctc?aaaaccttca?ctcagaaggc?2940

accacttcaa?cctccgtcca?gttatcttgg?caaccacctg?tcctggcaga?gagaaatggc?3000

attatcacca?agtataccct?tctttatagg?gatatcaaca?tcccccttct?cccgatggag?3060

cagcttattg?ttccagctga?caccactatg?acactcactg?gcttaaaacc?agataccaca?3120

tacgatgtaa?aagtacgtgc?tcatacgagc?aaagggcccg?ggccatatag?tcccagtgtc?3180

cagttcagga?cactgcctgt?ggatcaagtg?tttgcaaaaa?attttcatgt?caaagcagta?3240

atgaagactt?ccgtgttgct?gtcttgggag?attccagaga?attataactc?cgccatgcct?3300

ttcaaaattc?tttatgatga?tgggaaaatg?gtagaagaag?tggatggccg?agccacacag?3360

aagttaattg?tcaacctgaa?gcctgagaaa?tcatattcat?ttgtgctgac?aaatcgtgga?3420

aacagtgctg?gtgggctgca?gcacagggtc?acggcaaaga?ctgcaccaga?tgtattacgt?3480

accaagcctg?ccttcattgg?gaagaccaac?ttggatggca?tgattactgt?gcaactgcct?3540

gaagtacctg?caaatgagaa?tataaaaggt?tactacataa?taattgtgcc?tttgaagaaa?3600

tctcgcggga?aatttatcaa?gccatgggag?agtccagatg?aaatggaatt?agatgagctg?3660

cttaaggaga?tatctaggaa?gcgcagaagc?atccgttatg?ggagagaagt?tgaattaaag?3720

ccatatattg?ccgctcactt?tgatgtcctt?cccactgagt?tcaccctggg?ggatgacaag?3780

cattatggtg?gatttacaaa?caagcaactc?caaagtggtc?aagaatatgt?cttctttgtg?3840

ttagcagtaa?tggaacatgc?agagtctaag?atgtatgcaa?ccagccctta?ctccgacccc?3900

gtggtgtcaa?tggatctgga?tccgcagcca?atcacggatg?aagaagaagg?cttgatctgg?3960

gttgtaggtc?ctgtccttgc?agtggtcttt?atcatctgca?ttgtcattgc?tattcttctt?4020

tataaaagga?agagggcaga?gtccgactct?agaaaaagca?gcataccgaa?caataaggag?4080

atcccttcac?accacccaac?agaccctgta?gaactgaggc?gccttaactt?tcaaacaccg?4140

ggtatggcta?gccatcctcc?aatacccatc?ttggaacttg?cagaccacat?tgaaagattg?4200

aaagcaaatg?acaacttgaa?gttttcccag?gaatatgagt?caattgaccc?tggccagcag?4260

ttcacttggg?aacattcaaa?cttggaagta?aacaaaccaa?agaatagata?cgcgaatgta?4320

atcgcatatg?atcattcccg?ggttctccta?tcagctatag?aagggatccc?aggaagtgac?4380

tatgtgaatg?ccaactacat?agatgggtat?aggaagcaaa?atgcctatat?tgcaacacag?4440

ggatctctcc?ccgaaacatt?tggggacttt?tggagaatga?tatgggaaca?acggagtgcc?4500

acagttgtca?tgatgacaaa?actagaagaa?agatcaaggg?tgaagtgtga?ccagtattgg?4560

cctagcagag?gcacagaaac?ccacggactc?gttcaagtaa?cgctgcttga?tactgtggag?4620

ctggccacat?attgtgttcg?aacatttgca?ctttacaaga?atggttcaag?tgagaagaga?4680

gaagtgagac?aattccagtt?caccgcctgg?cctgatcatg?gtgttccaga?acaccctaca?4740

ccttttctag?ctttcttacg?tagagtcaaa?acctgtaacc?ctcccgatgc?tggtccgatg?4800

gttgtgcact?gcagtgcggg?agttggccgg?actggttgct?tcatcgtcat?agatgccatg?4860

ttagaaagaa?taaagcatga?aaaaactgta?gatatttatg?gccatgtaac?tttaatgaga?4920

gcccagagga?actatatggt?tcaaacagaa?gaccaataca?tctttatcca?tgatgcactg?4980

ttagaagcag?tgacttgtgg?aaataccgaa?gtgccagcta?gaaacttgta?tgcctacatt?5040

cagaagctga?cacaaataga?aacgggagag?aatgtcacag?gaatggagct?cgaatttaag?5100

cgtctagcca?gctcaaaagc?tcacacctca?aggtttatca?gtgccaatct?tccatgtaat?5160

aaattcaaaa?atcgccttgt?taatattatg?ccatatgaat?ccacaagggt?atgcctgcag?5220

cctatccgtg?gagtagaagg?atctgattac?atcaatgcca?gttttattga?tggatacaga?5280

caacagaaag?cctacatcgc?tacccagggg?cccttggcag?agaccactga?agacttctgg?5340

cggatgctct?gggaacacaa?ttccaccata?gttgtgatgc?tcaccaagct?gcgtgaaatg?5400

ggcagagaga?aatgtcacca?atactggcca?gcagaacggt?ctgcaagata?ccagtacttt?5460

gttgtagatc?ccatggctga?gtacaacatg?ccacagtata?tcctaaggga?attcaaggtc?5520

acagatgcca?gggacggcca?gtcccgaaca?gtaaggcagt?tccagttcac?tgactggcca?5580

gagcaaggag?tgccaaagtc?cggagaagga?tttattgact?tcatcggcca?agtccataaa?5640

acaaaagaac?agtttggcca?agatggaccc?atttcagtcc?attgcagcgc?gggcgttgga?5700

agaactggag?tcttcataac?gctaagcatt?gttttggaaa?gaatgagata?tgaaggagtt?5760

gtagatatct?tccagactgt?caaaatgtta?agaacacaac?gaccagctat?ggtacagaca?5820

gaggatcaat?atcagttttc?ctatcgtgcc?gcactagagt?acctgggcag?ctttgaccac?5880

tatgcaacgt?agaaacccct?gacccattct?ggatttttac?tacaggccct?tcaatatcca?5940

tggagtctct?tctgagccat?acagggcact?tgagaagtcc?ttcttaactt?ctagctaaca?6000

actacttagt?gggactatta?cacacaaaac?aaattaaaaa?caaattattc?caggtggacc?6060

aagaattctt?tgacatcgcc?ccttcccacc?atactgctca?taataacatt?ttaggggcca?6120

aggggaggga?atgtttaaaa?agaaagtcct?tgatttagtt?ttttagtatt?gtaaagatac?6180

tgctgacctg?tgcttcattt?ctaactgtgt?aaactttttt?ttaacaaaat?gtatcattcg?6240

ataaagtgaa?ttttaaaaaa?gtt 6263

<210>39

<211>1899

<212>PRT

＜213〉people (homo sapiens)

<400>39

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

Gln?Leu?Arg?Ser?Gly?Ala?Leu?Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp

180 185 190

Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr

195 200 205

Ser?Ala?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Val?Arg?Arg?Val?Pro?Pro?Arg

210 215 220

Phe?Ser?Ile?Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val

225 230 235 240

Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp

245 250 255

Met?Leu?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly

260 265 270

Arg?Asn?Val?Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr

275 280 285

Cys?Val?Ala?Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile

290 295 300

Thr?Val?Lys?Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu

305 310 315 320

Ser?Thr?Ala?Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu

325 330 335

Pro?Val?Ser?Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu

340 345 350

Leu?Tyr?Lys?Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala

355 360 365

Gly?Leu?Ser?Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn

370 375 380

Asn?Ile?Gly?Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser

385 390 395 400

Glu?Gln?Ala?Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu

405 410 415

Ser?Ser?Thr?Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn

420 425 430

Gly?Gln?Ile?Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln

435 440 445

His?Val?Asn?Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr

450 455 460

Thr?Ile?Gly?Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu

465 470 475 480

Ala?Phe?Thr?Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val

485 490 495

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

500 505 510

Pro?Glu?Ser?Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser

515 520 525

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

530 535 540

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

545 550 555 560

Gly?Leu?Lys?Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser

565 570 575

Pro?Gln?Gly?Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met

580 585 590

Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro

595 600 605

Ser?Ser?Thr?Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys

610 615 620

Gln?Asn?Gly?Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp

625 630 635 640

Gly?Glu?Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr

645 650 655

Thr?Lys?Tyr?Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile

660 665 670

Thr?Val?Thr?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser

675 680 685

Val?Leu?Ile?Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys

690 695 700

Val?Glu?Val?Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg

705 710 715 720

Ser?Pro?Val?Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val

725 730 735

His?Tyr?Val?Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu

740 745 750

Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr

755 760 765

Glu?His?Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser

770 775 780

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

785 790 795 800

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

805 810 815

Val?Ile?Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro

820 825 830

Pro?Val?Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly

835 840 845

Arg?Lys?Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu

850 855 860

Asp?His?Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe

865 870 875 880

Arg?Leu?Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys

885 890 895

Glu?Ile?Ser?Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu

900 905 910

His?Ser?Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro

915 920 925

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

930 935 940

Tyr?Arg?Asp?Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val

945 950 955 960

Pro?Ala?Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr

965 970 975

Tyr?Asp?Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr

980 985 990

Ser?Pro?Ser?Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp?Gln?Val?Phe?Ala

995 1000 1005

Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser

1010 1015 1020

Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu

1025 1030 1035 1040

Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln

1045 1050 1055

Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu

1060 1065 1070

Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala

1075 1080 1085

Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys

1090 1095 1100

Thr?Asn?Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala

1105 1110 1115 1120

Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys

1125 1130 1135

Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu

1140 1145 1150

Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg

1155 1160 1165

Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp

1170 1175 1180

Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly

1185 1190 1195 1200

Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val

1205 1210 1215

Leu?Ala?Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr

1235 1240 1245

Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val

1250 1255 1260

Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys

1265 1270 1275 1280

Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu

1285 1290 1295

Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn

1300 1305 1310

Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu

1315 1320 1325

Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe

1330 1335 1340

Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu

1345 1350 1355 1360

His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val

1365 1370 1375

Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile

1380 1385 1390

Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys

1395 1400 1405

Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly

1410 1415 1420

Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met

1425 1430 1435 1440

Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp

1445 1450 1455

Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu

1460 1465 1470

Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr

1475 1480 1485

Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr

1490 1495 1500

Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala

l505 1510 1515 1520

Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met

1525 1530 1535

Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val

1540 1545 1550

Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile

1555 1560 1565

Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln

1570 1575 1580

Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val

1585 1590 1595 1600

Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile

1605 1610 1615

Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu

1620 1625 1630

Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe

1635 1640 1645

Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn

1650 1655 1660

Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly

1665 1670 1675 1680

Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg

1685 1690 1695

Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr

1700 1705 1710

Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val

1715 1720 1725

Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr

1730 1735 1740

Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro

1745 1750 1755 1760

Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val

1765 1770 1775

Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe

1780 1785 1790

Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile

1795 1800 1805

Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp

1810 1815 1820

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

1825 1830 1835 1840

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

1845 1850 1855

Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala

1860 1865 1870

Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu

1875 1880 1885

Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>40

<211>246

<212>DNA

＜213〉people (homo sapiens)

<400>40

atgtatttta?cccctaaaga?tggtcatgag?ctctgccata?gccaccaatg?tcttttgata?60

tggttcactg?ttcgagatgt?agtcttgatt?ggcatgaaaa?tgagaggttg?gtccaggagc?120

agtaaagaca?aacataatgc?acgagctcct?tcatatatat?acaagccatt?gcattttgtg?180

gtctcaagat?tcttggactc?atgcagtctt?cggaggatgc?agctaaatct?gtcattgatg?240

atgtag 246

<210>41

<211>1903

<212>PRT

＜213〉people (homo sapiens)

<400>41

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Lys

595 600 605

Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser?Thr

610 615 620

Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn?Gly

625 630 635 640

Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp

645 650 655

Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys?Tyr

660 665 670

Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val?Thr

675 680 685

Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu?Ile

690 695 700

Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu?Val

705 710 715 720

Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro?Val

725 730 735

Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val

740 745 750

Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp?Val

755 760 765

Met?Leu?Ala?Asp?Ala?Gln?Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu

770 775 780

Thr?Ser?Tyr?Ser?Leu?Thr?Val?Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly

785 790 795 800

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

805 810 815

Lys?Pro?Arg?Leu?Val?Ile?Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile

820 825 830

Gln?Trp?His?Pro?Pro?Val?Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg

835 840 845

Leu?Lys?Phe?Gly?Arg?Lys?Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe

850 855 860

Ser?Glu?Lys?Glu?Asp?His?Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala

865 870 875 880

Ser?Tyr?Val?Phe?Arg?Leu?Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu

885 890 895

Glu?Met?Val?Lys?Glu?Ile?Ser?Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe

900 905 910

Pro?Gln?Asn?Leu?His?Ser?Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu

915 920 925

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

930 935 940

Tyr?Thr?Leu?Leu?Tyr?Arg?Asp?Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu

945 950 955 960

Gln?Leu?Ile?Val?Pro?Ala?Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys

965 970 975

Pro?Asp?Thr?Thr?Tyr?Asp?Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly

980 985 990

Pro?Gly?Pro?Tyr?Ser?Pro?Ser?Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp

995 1000 1005

Gln?Val?Phe?Ala?Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser

1010 1015 1020

Val?Leu?Leu?Ser?Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro

1025 1030 1035 1040

Phe?Lys?Ile?Leu?Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly

1045 1050 1055

Arg?Ala?Thr?Gln?Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr

1060 1065 1070

Ser?Phe?Val?Leu?Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His

1075 1080 1085

Arg?Val?Thr?Ala?Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala

1090 1095 1100

Phe?Ile?Gly?Lys?Thr?Asn?Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro

1105 1110 1115 1120

Glu?Val?Pro?Ala?Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val

1125 1130 1135

Pro?Leu?Lys?Lys?Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro

1140 1145 1150

Asp?Glu?Met?Glu?Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg

1155 1160 1165

Arg?Ser?Ile?Arg?Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala

1170 1175 1180

Ala?His?Phe?Asp?Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys

1185 1190 1195 1200

His?Tyr?Gly?Gly?Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr

1205 1210 1215

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

1220 1225 1230

Ala?Thr?Ser?Pro?Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro

1235 1240 1245

Gln?Pro?Ile?Thr?Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro

1250 1255 1260

Val?Leu?Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu

1265 1270 1275 1280

Tyr?Lys?Arg?Lys?Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro

1285 1290 1295

Asn?Asn?Lys?Glu?Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu

1300 1305 1310

Arg?Arg?Leu?Asn?Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile

1315 1320 1325

Pro?Ile?Leu?Glu?Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp

1330 1335 1340

Asn?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln

1345 1350 1355 1360

Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg

1365 1370 1375

Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala

1380 1385 1390

Ile?Glu?Gly?Ile?Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp

1395 1400 1405

Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro

1410 1415 1420

Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala

1425 1430 1435 1440

Thr?Val?Val?Met?Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys

1445 1450 1455

Asp?Gln?Tyr?Trp?Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln

1460 1465 1470

Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr

1475 1480 1485

Phe?Ala?Leu?Tyr?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln

1490 1495 1500

Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr

1505 1510 1515 1520

Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp

1525 1530 1535

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

1540 1545 1550

Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys

1555 1560 1565

Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn

1570 1575 1580

Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu

1585 1590 1595 1600

Leu?Glu?Ala?Val?Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu

1605 1610 1615

Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val

1620 1625 1630

Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His

1635 1640 1645

Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn

1650 1655 1660

Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln

1665 1670 1675 1680

Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile

1685 1690 1695

Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

1700 1705 1710

Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser

1715 1720 1725

Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys

1730 1735 1740

Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe

1745 1750 1755 1760

Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg

1765 1770 1775

Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg

1780 1785 1790

Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly

1795 1800 1805

Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln

1810 1815 1820

Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly

1825 1830 1835 1840

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

1845 1850 1855

Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr

1860 1865 1870

Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr

1875 1880 1885

Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895 1900

<210>42

<211>6236

<212>DNA

＜213〉people (homo sapiens)

<400>42

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaaagccg?1980

tcagctcctc?ctcaagacat?tagttgcacc?agcccaagtt?ccactagtat?tttggtaagt?2040

tggcaacctc?caccagtgga?aaaacagaat?ggcattatca?ctgaatactc?catcaagtac?2100

actgcagtgg?atggggaaga?tgacaagcct?cacgagattt?tgggaattcc?ttcggacact?2160

accaaatacc?ttttggaaca?gctggaaaaa?tggactgaat?accggatcac?tgtgacagcc?2220

catacagatg?tcggccctgg?ccctgagagc?ttgtccgtgt?tgattcgaac?caatgaagat?2280

gttcctagtg?gtcctcctcg?caaagtcgag?gtagaggctg?tcaactcaac?atctgttaaa?2340

gtctcatggc?gctcacccgt?gcccaataaa?cagcatggcc?agataagagg?atatcaggtg?2400

cattatgtga?ggatggaaaa?tggtgagccc?aagggccagc?ccatgctgaa?agatgtcatg?2460

ctggctgatg?cacaggacat?gatcatttct?gggctccagc?ctgaaacttc?ctactccctc?2520

accgtcacag?cctacacaac?caaaggagat?ggtgctcgca?gcaagcccaa?actggtgtcc?2580

accactgggg?cagttccagg?gaaacctcgg?cttgtgatta?accacactca?gatgaatact?2640

gctcttattc?agtggcaccc?tccggtggac?acatttggac?ctcttcaggg?ctaccgtcta?2700

aaatttggcc?gcaaggatat?ggagccactt?actactcttg?agttctctga?aaaagaagat?2760

cactttacag?ctacagacat?ccacaaggga?gcatcatacg?tcttcaggct?ctcagccaga?2820

aacaaagtgg?gctttgggga?ggagatggtg?aaggagattt?ccattccaga?agaagtacca?2880

actggattcc?ctcaaaacct?tcactcagaa?ggcaccactt?caacctccgt?ccagttatct?2940

tggcaaccac?ctgtcctggc?agagagaaat?ggcattatca?ccaagtatac?ccttctttat?3000

agggatatca?acatccccct?tctcccgatg?gagcagctta?ttgttccagc?tgacaccact?3060

atgacactca?ctggcttaaa?accagatacc?acatacgatg?taaaagtacg?tgctcatacg?3120

agcaaagggc?ccgggccata?tagtcccagt?gtccagttca?ggacactgcc?tgtggatcaa?3180

gtgtttgcaa?aaaattttca?tgtcaaagca?gtaatgaaga?cttccgtgtt?gctgtcttgg?3240

gagattccag?agaattataa?ctccgccatg?cctttcaaaa?ttctttatga?tgatgggaaa?3300

atggtagaag?aagtggatgg?ccgagccaca?cagaagttaa?ttgtcaacct?gaagcctgag?3360

aaatcatatt?catttgtgct?gacaaatcgt?ggaaacagtg?ctggtgggct?gcagcacagg?3420

gtcacggcaa?agactgcacc?agatgtatta?cgtaccaagc?ctgccttcat?tgggaagacc?3480

aacttggatg?gcatgattac?tgtgcaactg?cctgaagtac?ctgcaaatga?gaatataaaa?3540

ggttactaca?taataattgt?gcctttgaag?aaatctcgcg?ggaaatttat?caagccatgg?3600

gagagtccag?atgaaatgga?attagatgag?ctgcttaagg?agatatctag?gaagcgcaga?3660

agcatccgtt?atgggagaga?agttgaatta?aagccatata?ttgccgctca?ctttgatgtc?3720

cttcccactg?agttcaccct?gggggatgac?aagcattatg?gtggatttac?aaacaagcaa?3780

ctccaaagtg?gtcaagaata?tgtcttcttt?gtgttagcag?taatggaaca?tgcagagtct?3840

aagatgtatg?caaccagccc?ttactccgac?cccgtggtgt?caatggatct?ggatccgcag?3900

ccaatcacgg?atgaagaaga?aggcttgatc?tgggttgtag?gtcctgtcct?tgcagtggtc?3960

tttatcatct?gcattgtcat?tgctattctt?ctttataaaa?ggaagagggc?agagtccgaG?4020

tctagaaaaa?gcagcatacc?gaacaataag?gagatccctt?cacaccaccc?aacagaccct?4080

gtagaactga?ggcgccttaa?ctttcaaaca?ccgggtatgg?ctagccatcc?tccaataccc?4140

atcttggaac?ttgcagacca?cattgaaaga?ttgaaagcaa?atgacaactt?gaagttttcc?4200

caggaatatg?agtcaattga?ccctggccag?cagttcactt?gggaacattc?aaacttggaa?4260

gtaaacaaac?caaagaatag?atacgcgaat?gtaatcgcat?atgatcattc?ccgggttctc?4320

ctatcagcta?tagaagggat?cccaggaagt?gactatgtga?atgccaacta?catagatggg?4380

tataggaagc?aaaatgccta?tattgcaaca?cagggatctc?tccccgaaac?atttggggac?4440

ttttggagaa?tgatatggga?acaacggagt?gccacagttg?tcatgatgac?aaaactagaa?4500

gaaagatcaa?gggtgaagtg?tgaccagtat?tggcctagca?gaggcacaga?aacccacgga?4560

ctcgttcaag?taacgctgct?tgatactgtg?gagctggcca?catattgtgt?tcgaacattt?4620

gcactttaca?agaatggttc?aagtgagaag?agagaagtga?gacaattcca?gttcaccgcc?4680

tggcctgatc?atggtgttcc?agaacaccct?acaccttttc?tagctttctt?acgtagagtc?4740

aaaacctgta?accctcccga?tgctggtccg?atggttgtgc?actgcagtgc?gggagttggc?4800

cggactggtt?gcttcatcgt?catagatgcc?atgttagaaa?gaataaagca?tgaaaaaact?4860

gtagatattt?atggccatgt?aactttaatg?agagcccaga?ggaactatat?ggttcaaaca?4920

gaagaccaat?acatctttat?ccatgatgca?ctgttagaag?cagtgacttg?tggaaatacc?4980

gaagtgccag?ctagaaactt?gtatgcctac?attcagaagc?tgacacaaat?agaaacggga?5040

gagaatgtca?caggaatgga?gctcgaattt?aagcgtctag?ccagctcaaa?agctcacacc?5100

tcaaggttta?tcagtgccaa?tcttccatgt?aataaattca?aaaatcgcct?tgttaatatt?5160

atgccatatg?aatccacaag?ggtatgcctg?cagcctatcc?gtggagtaga?aggatctgat?5220

tacatcaatg?ccagttttat?tgatggatac?agacaacaga?aagcctacat?cgctacccag?5280

gggcccttgg?cagagaccac?tgaagacttc?tggcggatgc?tctgggaaca?caattccacc?5340

atagttgtga?tgctcaccaa?gctgcgtgaa?atgggcagag?agaaatgtca?ccaatactgg?5400

ccagcagaac?ggtctgcaag?ataccagtac?tttgttgtag?atcccatggc?tgagtacaac?5460

atgccacagt?atatcctaag?ggaattcaag?gtcacagatg?ccagggacgg?ccagtcccga?5520

acagtaaggc?agttccagtt?cactgactgg?ccagagcaag?gagtgccaaa?gtccggagaa?5580

ggatttattg?acttcatcgg?ccaagtccat?aaaacaaaag?aacagtttgg?ccaagatgga?5640

cccatttcag?tccattgcag?cgcgggcgtt?ggaagaactg?gagtcttcat?aacgctaagc?5700

attgttttgg?aaagaatgag?atatgaagga?gttgtagata?tcttccagac?tgtcaaaatg?5760

ttaagaacac?aacgaccagc?tatggtacag?acagaggatc?aatatcagtt?ttcctatcgt?5820

gccgcactag?agtacctggg?cagctttgac?cactatgcaa?cgtagaaacc?cctgacccat?5880

tctggatttt?tactacaggc?ccttcaatat?ccatggagtc?tcttctgagc?catacagggc?5940

acttgagaag?tccttcttaa?cttctagcta?acaactactt?agtgggacta?ttacacacaa?6000

aacaaattaa?aaacaaatta?ttccaggtgg?accaagaatt?ctttgacatc?gccccttccc?6060

accatactgc?tcataataac?attttagggg?ccaaggggag?ggaatgttta?aaaagaaagt?6120

ccttgattta?gttttttagt?attgtaaaga?tactgctgac?ctgtgcttca?tttctaactg?6180

tgtaaacttt?tttttaacaa?aatgtatcat?tcgataaagt?gaattttaaa?aaagtt 6236

<210>43

<211>1501

<212>PRT

＜213〉people (homo sapiens)

<400>43

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Met

595 600 605

Phe?Ala?Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu

610 615 620

Leu?Ser?Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys

625 630 635 640

Ile?Leu?Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala

645 650 655

Thr?Gln?Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys Ser?Tyr?Ser?Phe

660 665 670

Val?Leu?Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val

675 680 685

Thr?Ala?Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile

690 695 700

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

705 710 715 720

Pro?Ala?Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu

725 730 735

Lys?Lys?Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu

740 745 750

Met?Glu?Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser

755 760 765

Ile?Arg?Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His

770 775 780

Phe?Asp?Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr

785 790 795 800

Gly?Gly?Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe

805 810 815

Phe?Val?Leu?Ala?Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr

820 825 830

Ser?Pro?Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro

835 840 845

Ile?Thr?Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu

850 855 860

Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys

865 870 875 880

Arg?Lys?Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn

885 890 895

Lys?Glu?Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg

900 905 910

Leu?Asn?Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile

915 920 925

Leu?Glu?Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu

930 935 940

Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr

945 950 955 960

Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala

965 970 975

Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu

980 985 990

Gly?Ile?Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr

995 1000 1005

Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr

1010 1015 1020

Phe?Gly?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val

1025 1030 1035 1040

Val?Met?Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln

1045 1050 1055

Tyr?Trp?Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr

1060 1065 1070

Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala

1075 1080 1085

Leu?Tyr?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln

1090 1095 1100

Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe

1105 1110 1115 1120

Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly

1125 1130 1135

Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe

1140 1145 1150

Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val

1155 1160 1165

Asp?Ile?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met

1170 1175 1180

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu

1185 1190 1195 1200

Ala?Val?Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala

1205 1210 1215

Tyr?Ile?Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly

1220 1225 1230

Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser

12351 240 1245

Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu

1250 1255 1260

Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile

1265 1270 1275 1280

Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly

1285 1290 1295

Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu

1300 1305 1310

Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile

1315 1320 1325

Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His

1330 1335 1340

Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val

1345 1350 1355 1360

Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe

1365 1370 1375

Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe

1380 1385 1390

Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly

1395 1400 1405

Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly

1410 1415 1420

Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1425 1430 1435 1440

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

1445 1450 1455

Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg

1460 1465 1470

Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala

1475 1480 1485

Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1490 1495 1500

<210>44

<211>5030

<212>DNA

＜213〉people (homo sapiens)

<400>44

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaatgttt?1980

gcaaaaaatt?ttcatgtcaa?agcagtaatg?aagacttccg?tgttgctgtc?ttgggagatt?2040

ccagagaatt?ataactccgc?catgcctttc?aaaattcttt?atgatgatgg?gaaaatggta?2100

gaagaagtgg?atggccgagc?cacacagaag?ttaattgtca?acctgaagcc?tgagaaatca?2160

tattcatttg?tgctgacaaa?tcgtggaaac?agtgctggtg?ggctgcagca?cagggtcacg?2220

gcaaagactg?caccagatgt?attacgtacc?aagcctgcct?tcattgggaa?gaccaacttg?2280

gatggcatga?ttactgtgca?actgcctgaa?gtacctgcaa?atgagaatat?aaaaggttac?2340

tacataataa?ttgtgccttt?gaagaaatct?cgcgggaaat?ttatcaagcc?atgggagagt?2400

ccagatgaaa?tggaattaga?tgagctgctt?aaggagatat?ctaggaagcg?cagaagcatc?2460

cgttatggga?gagaagttga?attaaagcca?tatattgccg?ctcactttga?tgtccttccc?2520

actgagttca?ccctggggga?tgacaagcat?tatggtggat?ttacaaacaa?gcaactccaa?2580

agtggtcaag?aatatgtctt?ctttgtgtta?gcagtaatgg?aacatgcaga?gtctaagatg?2640

tatgcaacca?gcccttactc?cgaccccgtg?gtgtcaatgg?atctggatcc?gcagccaatc?2700

acggatgaag?aagaaggctt?gatctgggtt?gtaggtcctg?tccttgcagt?ggtctttatc?2760

atctgcattg?tcattgctat?tcttctttat?aaaaggaaga?gggcagagtc?cgactctaga?2820

aaaagcagca?taccgaacaa?taaggagatc?ccttcacacc?acccaacaga?ccctgtagaa?2880

ctgaggcgcc?ttaactttca?aacaccgggt?atggctagcc?atcctccaat?acccatcttg?2940

gaacttgcag?accacattga?aagattgaaa?gcaaatgaca?acttgaagtt?ttcccaggaa?3000

tatgagtcaa?ttgaccctgg?ccagcagttc?acttgggaac?attcaaactt?ggaagtaaac?3060

aaaccaaaga?atagatacgc?gaatgtaatc?gcatatgatc?attcccgggt?tctcctatca?3120

gctatagaag?ggatcccagg?aagtgactat?gtgaatgcca?actacataga?tgggtatagg?3180

aagcaaaatg?cctatattgc?aacacaggga?tctctccccg?aaacatttgg?ggacttttgg?3240

agaatgatat?gggaacaacg?gagtgccaca?gttgtcatga?tgacaaaact?agaagaaaga?3300

tcaagggtga?agtgtgacca?gtattggcct?agcagaggca?cagaaaccca?cggactcgtt?3360

caagtaacgc?tgcttgatac?tgtggagctg?gccacatatt?gtgttcgaac?atttgcactt?3420

tacaagaatg?gttcaagtga?gaagagagaa?gtgagacaat?tccagttcac?cgcctggcct?3480

gatcatggtg?ttccagaaca?ccctacacct?tttctagctt?tcttacgtag?agtcaaaacc?3540

tgtaaccctc?ccgatgctgg?tccgatggtt?gtgcactgca?gtgcgggagt?tggccggact?3600

ggttgcttca?tcgtcataga?tgccatgtta?gaaagaataa?agcatgaaaa?aactgtagat?3660

atttatggcc?atgtaacttt?aatgagagcc?cagaggaact?atatggttca?aacagaagac?3720

caatacatct?ttatccatga?tgcactgtta?gaagcagtga?cttgtggaaa?taccgaagtg?3780

ccagctagaa?acttgtatgc?ctacattcag?aagctgacac?aaatagaaac?gggagagaat?3840

gtcacaggaa?tggagctcga?atttaagcgt?ctagccagct?caaaagctca?cacctcaagg?3900

tttatcagtg?ccaatcttcc?atgtaataaa?ttcaaaaatc?gccttgttaa?tattatgcca?3960

tatgaatcca?caagggtatg?cctgcagcct?atccgtggag?tagaaggatc?tgattacatc?4020

aatgccagtt?ttattgatgg?atacagacaa?cagaaagcct?acatcgctac?ccaggggccc?4080

ttggcagaga?ccactgaaga?cttctggcgg?atgctctggg?aacacaattc?caccatagtt?4140

gtgatgctca?ccaagctgcg?tgaaatgggc?agagagaaat?gtcaccaata?ctggccagca?4200

gaacggtctg?caagatacca?gtactttgtt?gtagatccca?tggctgagta?caacatgcca?4260

cagtatatcc?taagggaatt?caaggtcaca?gatgccaggg?acggccagtc?ccgaacagta?4320

aggcagttcc?agttcactga?ctggccagag?caaggagtgc?caaagtccgg?agaaggattt?4380

attgacttca?tcggccaagt?ccataaaaca?aaagaacagt?ttggccaaga?tggacccatt?4440

tcagtccatt?gcagcgcggg?cgttggaaga?actggagtct?tcataacgct?aagcattgtt?4500

ttggaaagaa?tgagatatga?aggagttgta?gatatcttcc?agactgtcaa?aatgttaaga?4560

acacaacgac?cagctatggt?acagacagag?gatcaatatc?agttttccta?tcgtgccgca?4620

ctagagtacc?tgggcagctt?tgaccactat?gcaacgtaga?aacccctgac?ccattctgga?4680

tttttactac?aggcccttca?atatccatgg?agtctcttct?gagccataca?gggcacttga?4740

gaagtccttc?ttaacttcta?gctaacaact?acttagtggg?actattacac?acaaaacaaa?4800

ttaaaaacaa?attattccag?gtggaccaag?aattctttga?catcgcccct?tcccaccata?4860

ctgctcataa?taacatttta?ggggccaagg?ggagggaatg?tttaaaaaga?aagtccttga?4920

tttagttttt?tagtattgta?aagatactgc?tgacctgtgc?ttcatttcta?actgtgtaaa?4980

ctttttttta?acaaaatgta?tcattcgata?aagtgaattt?taaaaaagtt 5030

<210>45

<211>14

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>45

Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser?Val?Val?Thr?Arg

1 5 10

<210>46

<211>22

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>46

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

1 5 10 15

Asp?Glu?Thr?Tyr?Val?Arg

20

<210>47

<211>19

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>47

Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu?Ser?Asp?Pro?Ile

1 5 10 15

Gln?Val?Lys

<210>48

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>48

Thr?Glu?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg

1 5 10 15

<210>49

<211>16

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>49

Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu?Gly?Tyr?Arg

1 5 10 15

<210>50

<211>20

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>50

Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro

1 5 10 15

Thr?Pro?Tyr?Lys

20

<210>51

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>51

Thr?Glu?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg

1 5 10 15

<210>52

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>52

Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser?Val?Leu?Arg

1 5 10 15

<210>53

<211>16

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>53

Ser?Gly?Ala?Leu?Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys

1 5 10 15

<210>54

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>54

Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr?Val

1 5

<210>55

<211>18

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>55

Trp?Met?Leu?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile

1 5 10 15

Gly?Arg

<210>56

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>56

Asn?Val?Leu?Glu?Leu?Asn?Asp?Val?Arg

1 5

<210>57

<211>21

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>57

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

1 5 10 15

Ser?Ser?Ala?Pro?Arg

20

<210>58

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>58

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

1 5 10 15

<210>59

<211>23

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>59

Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly

1 5 10 15

Ile?Pro?Ser?Asp?Thr?Thr?Lys

20

<210>60

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>60

Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys

1 5

<210>61

<211>12

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>61

Gly?Pro?Gly?Pro?Tyr?Ser?Pro?Ser?Val?Gln?Phe?Arg

1 5 10

<210>62

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉FLAG flag sequence

<400>62

Asp?Tyr?Lys?Asp?Asp?Asp?Asp?Lys

1 5

<210>63

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉XPRESS epi-position mark

<400>63

Asp?Leu?Tyr?Asp?Asp?Asp?Asp?Lys

1 5

<210>64

<211>1948

<212>PRT

＜213〉people (homo sapiens)

<400>64

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

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

195 200 205

Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Val

210 215 220

Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Glu?Leu?Arg?Glu?Val

225 230 235 240

Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser?His?Glu?Ile

245 250 255

Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro

260 265 270

Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu

275 280 285

Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr?Asp?Val?Lys

290 295 300

Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu?Gly?Val?Ile

305 310 315 320

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

325 330 335

Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr?Ile?Thr?Trp

340 345 350

Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile?Glu?Tyr?Lys

355 360 365

Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp?Ile?Thr?Thr

370 375 380

Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu?Tyr?Glu?Ile

385 390 395 400

Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser

405 410 415

Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala?Pro?Arg?Asn

420 425 430

Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val?Gln?Trp?Glu

435 440 445

Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr

450 455 460

Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys?His?Asn?Val

465 470 475 480

Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Glu?Asp?Glu?Thr

485 490 495

Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu

500 505 510

Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro?Gly?Gln?Pro

515 520 525

Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile?Thr?Leu?Ser

530 535 540

Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu?Leu?Leu?Phe

545 550 555 560

Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe?Asp?Pro?Thr

565 570 575

Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu?Tyr?Ala?Phe

580 585 590

Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe?Thr?Pro?Val

595 600 605

Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp

610 615 620

Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val?Ser?Trp?Arg

625 630 635 640

Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly?Tyr?Ser?Val

645 650 655

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

660 665 670

Gly?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala?Leu?Glu?Lys

675 680 685

Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu?Val?Gly?Pro

690 695 700

Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro

705 710 715 720

Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn?Ala?Thr?Ala

725 730 735

Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln?His?Gly?Gln

740 745 750

Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly?Ala?Glu?Ala

755 760 765

Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp

770 775 780

Glu?Thr?Asp?Asp?Thr?Ala?Glu?Tyr?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln

785 790 795 800

Pro?Glu?Thr?Ala?Tyr?Ser?Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly

805 810 815

Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val

820 825 830

Leu?Gly?Arg?Pro?Thr?Leu?Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu

835 840 845

Leu?Ala?Arg?Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu

850 855 860

Gly?Tyr?Arg?Leu?Gln?Phe?Gly?Arg?Glu?Asp?Ser?Thr?Pro?Leu?Ala?Thr

865 870 875 880

Leu?Glu?Phe?Pro?Pro?Ser?Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His

885 890 895

Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly

900 905 910

Leu?Gly?Glu?Glu?Ala?Ala?Glu?Val?Leu?Ser?Ile?Pro?Glu?Asp?Thr?Pro

915 920 925

Arg?Gly?His?Pro?Gln?Ile?Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly

930 935 940

Thr?Val?Leu?Leu?Arg?Trp?Leu?Pro?Pro?Val?Pro?Ala?Glu?Arg?Asn?Gly

945 950 955 960

Ala?Ile?Val?Lys?Tyr?Thr?Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly

965 970 975

Pro?Ala?Arg?Glu?Thr?Glu?Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu

980 985 990

Asn?Ala?Leu?Thr?Leu?Gln?Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu

995 1000 1005

Gln?Val?Arg?Ala?His?Thr?Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro

1010 1015 1020

Val?Arg?Tyr?Arg?Thr?Phe?Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe

1025 1030 1035 1040

Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe

1045 1050 1055

Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly

1060 1065 1070

Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His

1075 1080 1085

Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser

1090 1095 1100

Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn

1105 1110 1115 1120

Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly

1125 1130 1135

Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln

1140 1145 1150

Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln

1155 1160 1165

Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu

1170 1175 1180

Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg

1185 1190 1195 1200

Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu

1205 1210 1215

Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp

1220 1225 1230

Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala

1235 1240 1245

Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp

1250 1255 1260

Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu

1265 1270 1275 1280

Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1285 1290 1295

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser

1300 1305 1310

Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala

1315 1320 1325

Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile

1330 1335 1340

Asn?Phe?Gln?Thr?Pro?Asp?Ser?Gly?Leu?Arg?Ser?Pro?Leu?Arg?Glu?Pro

1345 1350 1355 1360

Gly?Phe?His?Phe?Glu?Ser?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala

1365 1370 1375

Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys

1380 1385 1390

Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp

1395 1400 1405

Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn

1410 1415 1420

Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly

1425 1430 1435 1440

Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg

1445 1450 1455

Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe

1460 1465 1470

Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val

1475 1480 1485

Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr

1490 1495 1500

Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu

1505 1510 1515 1520

Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu

1525 1530 1535

His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe

1540 1545 1550

Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu

1555 1560 1565

Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro

1570 1575 1580

Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile

1585 1590 1595 1600

Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp

1605 1610 1615

Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val

1620 1625 1630

Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala

1635 1640 1645

Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr

1650 1655 1660

Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met

1665 1670 1675 1680

Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg

1685 1690 1695

Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val

1700 1705 1710

Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg

1715 1720 1725

Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr

1730 1735 1740

Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr

1745 1750 1755 1760

Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val

1765 1770 1775

Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln

1780 1785 1790

Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp

1795 1800 1805

Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Lau?Arg?Glu?Phe?Lys

1810 1815 1820

Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln

1825 1830 1835 1840

Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe

1845 1850 1855

Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln

1860 1865 1870

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

1875 1880 1885

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

1890 1895 1900

Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro

1905 1910 1915 1920

Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala

1925 1930 1935

Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1940 1945

<210>65

<211>6412

<212>DNA

＜213〉people (homo sapiens)

<400>65

gcggtggcgg?cggcagaggc?ggcggctcca?gcttcggctc?cggctcgggc?tcgggctccg?60

gctccggctc?cggctccggc?tccagctcgg?gtggcggtgg?cgggagcggg?accaggtgga?120

ggcggcggcg?gcagaggagt?gggagcagcg?gccctagcgg?cttgcggggg?gacatgcgga?180

ccgacggccc?ctggataggc?ggaaggagtg?gaggccctgg?tgcccggccc?ttggtgctga?240

gtatccagca?agagtgaccg?gggtgaagaa?gcaaagactc?ggttgattgt?cctgggctgt?300

ggctggctgt?ggagctagag?ccctggatgg?cccctgagcc?agccccaggg?aggacgatgg?360

tgccccttgt?gcctgcactg?gtgatgcttg?gtttggtggc?aggcgcccat?ggtgacagca?420

aacctgtctt?cattaaagtc?cctgaggacc?agactgggct?gtcaggaggg?gtagcctcct?480

tcgtgtgcca?agctacagga?gaacccaagc?cgcgcatcac?atggatgaag?aaggggaaga?540

aagtcagctc?ccagcgcttc?gaggtcattg?agtttgatga?tggggcaggg?tcagtgcttc?600

ggatccagcc?attgcgggtg?cagcgagatg?aagccatcta?tgagtgtaca?gctactaaca?660

gcctgggtga?gatcaacact?agtgccaagc?tctcagtgct?cgaagaggaa?cagctgcccc?720

ctgggttccc?ttccatcgac?atggggcctc?agctgaaggt?ggtggagaag?gcacgcacag?780

ccaccatgct?atgtgccgca?ggcggaaatc?cagaccctga?gatttcttgg?ttcaaggact?840

tccttcctgt?agaccctgcc?acgagcaacg?gccgcatcaa?gcagctgcgt?tcaggtgcct?900

tgcagataga?gagcagtgag?gaatccgacc?aaggcaagta?cgagtgtgtg?gcgaccaact?960

cggcaggcac?acgttactca?gcccctgcga?acctgtatgt?gcgagtgcgc?cgcgtggctc?1020

ctcgtttctc?catccctccc?agcagccagg?aggtgatgcc?aggcggcagc?gtgaacctga?1080

catgcgtggc?agtgggtgca?cccatgccct?acgtgaagtg?gatgatgggg?gccgaggagc?1140

tcaccaagga?ggatgagatg?ccagttggcc?gcaacgtcct?ggagctcagc?aatgtcgtac?1200

gctctgccaa?ctacacctgt?gtggccatct?cctcgctggg?catgatcgag?gccacagccc?1260

aggtcacagt?gaaagctctt?ccaaagcctc?cgattgatct?tgtggtgaca?gagacaactg?1320

ccaccagtgt?caccctcacc?tgggactctg?ggaactcgga?gcctgtaacc?tactatggca?1380

tccagtaccg?cgcagcgggc?acggagggcc?cctttcagga?ggtggatggt?gtggccacca?1440

cccgctacag?cattggcggc?ctcagccctt?tctcggaata?tgccttccgc?gtgctggcgg?1500

tgaacagcat?cgggcgaggg?ccgcccagcg?aggcagtgcg?ggcacgcacg?ggagaacagg?1560

cgccctccag?cccaccgcgc?cgcgtgcagg?cacgcatgct?gagcgccagc?accatgctgg?1620

tgcagtggga?gcctcccgag?gagcccaacg?gcctggtgcg?gggataccgc?gtctactata?1680

ctccggactc?ccgccgcccc?ccgaacgcct?ggcacaagca?caacaccgac?gcggggctcc?1740

tcacgaccgt?gggcagcctg?ctgcctggca?tcacctacag?cctgcgcgtg?cttgccttca?1800

ccgccgtggg?cgatggccct?cccagcccca?ccatccaggt?caagacgcag?cagggagtgc?1860

ctgcccagcc?cgcggacttc?caggccgagg?tggagtcgga?caccaggatc?cagctctcgt?1920

ggctgctgcc?ccctcaggag?cggatcatca?tgtatgaact?ggtgtactgg?gcggcagagg?1980

acgaagacca?acagcacaag?gtgaccttcg?acccaacctc?ctcctacaca?ctagaggacc?2040

tgaagcctga?cacactctac?cgcttccagc?tggctgcacg?ctcggatatg?ggggtgggcg?2100

tcttcacccc?caccattgag?gcccgcacag?cccagtccac?cccctccgcc?cctccccaga?2160

aggtgatgtg?tgtgagcatg?ggctccacca?cggtccgggt?aagttgggtc?ccgccgcctg?2220

ccgacagccg?caacggcgtt?atcacccagt?actccgtggc?ctacgaggcg?gtggacggcg?2280

aggaccgcgg?gcggcatgtg?gtggatggca?tcagccgtga?gcactccagc?tgggacctgg?2340

tgggcctgga?gaagtggacg?gagtaccggg?tgtgggtgcg?ggcacacaca?gacgtgggcc?2400

ccggccccga?gagcagcccg?gtgctggtgc?gcaccgatga?ggacgtgccc?agcgggcctc?2460

cgcggaaggt?ggaggtggag?ccactgaact?ccactgctgt?gcatgtctac?tggaagctgc?2520

ctgtccccag?caagcagcat?ggccagatcc?gcggctacca?ggtcacctac?gtgcggctgg?2580

agaatggcga?gccccgtgga?ctccccatca?tccaagacgt?catgctagcc?gaggcccagg?2640

aaaccactat?cagcggcctg?accccggaga?ccacctactc?cgttactgtt?gctgcctata?2700

ccaccaaggg?ggatggtgcc?cgcagcaagc?ccaaaattgt?cactacaaca?ggtgcagtcc?2760

caggccggcc?caccatgatg?atcagcacca?cggccatgaa?cactgcgctg?ctccagtggc?2820

acccacccaa?ggaactgcct?ggcgagctgc?tgggctaccg?gctgcagtac?tgccgggccg?2880

acgaggcgcg?gcccaacacc?atagatttcg?gcaaggatga?ccagcacttc?acagtcaccg?2940

gcctgcacaa?ggggaccacc?tacatcttcc?ggcttgctgc?caagaaccgg?gctggcttgg?3000

gtgaggagtt?cgagaaggag?atcaggaccc?ccgaggacct?gcccagcggc?ttcccccaaa?3060

acctgcatgt?gacaggactg?accacgtcta?ccacagaact?ggcctgggac?ccgccagtgc?3120

tggcggagag?gaacgggcgc?atcatcagct?acaccgtggt?gttccgagac?atcaacagcc?3180

aacaggagct?gcagaacatc?acgacagaca?cccgctttac?ccttactggc?ctcaagccag?3240

acaccactta?cgacatcaag?gtccgcgcat?ggaccagcaa?aggctctggc?ccactcagcc?3300

ccagcatcca?gtcccggacc?atgccggtgg?agcaagtgtt?tgccaagaac?ttccgggtgg?3360

cggctgcaat?gaagacgtct?gtgctgctca?gctgggaggt?tcccgactcc?tataagtcag?3420

ctgtgccctt?taagattctg?tacaatgggc?agagtgtgga?ggtggacggg?cactcgatgc?3480

ggaagctgat?cgcagacctg?cagcccaaca?cagagtactc?gtttgtgctg?atgaaccgtg?3540

gcagcagcgc?agggggcctg?cagcacctgg?tgtccatccg?cacagccccc?gacctcctgc?3600

ctcacaagcc?gctgcctgcc?tctgcctaca?tagaggacgg?ccgcttcgat?ctctccatgc?3660

cccatgtgca?agacccctcg?cttgtcaggt?ggttctacat?tgttgtggtg?cccattgacc?3720

gtgtgggcgg?gagcatgctg?acgccaaggt?ggagcacacc?cgaggaactg?gagctggacg?3780

agcttctaga?agccatcgag?caaggcggag?aggagcagcg?gcggcggcgg?cggcaggcag?3840

aacgtctgaa?gccatatgtg?gctgctcaac?tggatgtgct?cccggagacc?tttaccttgg?3900

gggacaagaa?gaactaccgg?ggcttctaca?accggcccct?gtctccggac?ttgagctacc?3960

agtgctttgt?gcttgcctcc?ttgaaggaac?ccatggacca?gaagcgctat?gcctccagcc?4020

cctactcgga?tgagatcgtg?gtccaggtga?caccagccca?gcagcaggag?gagccggaga?4080

tgctgtgggt?gacgggtccc?gtgctggcag?tcatcctcat?catcctcatt?gtcatcgcca?4140

tcctcttgtt?caaaaggaaa?aggacccact?ctccgtcctc?taaggatgag?cagtcgatcg?4200

gactgaagga?ctccttgctg?gcccactcct?ctgaccctgt?ggagatgcgg?aggctcaact?4260

accagacccc?aggtatgcga?gaccacccac?ccatccccat?caccgacctg?gcggacaaca?4320

tcgagcgcct?caaagccaac?gatggcctca?agttctccca?ggagtatgag?tccatcgacc?4380

ctggacagca?gttcacgtgg?gagaattcaa?acctggaggt?gaacaagccc?aagaaccgct?4440

atgcgaatgt?catcgcctac?gaccactctc?gagtcatcct?tacctctatc?gatggcgtcc?4500

ccgggagtga?ctacatcaat?gccaactaca?tcgatggcta?ccgcaagcag?aatgcctaca?4560

ccgccacgca?gggccccctg?cccgagacca?tgggtgattt?ctggaggatg?gtgtgggaac?4620

agcgcacggc?cactgtggtc?atgatgacac?ggctggagga?gaagtcccgg?gtaaaatgtg?4680

atcagtactg?gccagcccgt?ggcaccgaga?cctgtggcct?tattcaggtg?accctgttgg?4740

acacagtgga?gctggccaca?tacactgtgc?gcaccttcgc?actccacaag?agtggctcca?4800

gtgagaagcg?cgagctgcgt?cagtttcagt?tcatggcctg?gccagaccat?ggagttcctg?4860

agtacccaac?tcccatcctg?gccttcctac?gacgggtcaa?ggcctgcaac?cccctagacg?4920

cagggcccat?ggtggtgcac?tgcagcgcgg?gcgtgggccg?caccggctgc?ttcatcgtga?4980

ttgatgccat?gttggagcgg?atgaagcacg?agaagacggt?ggacatctat?ggccacgtga?5040

cctgcatgcg?atcacagagg?aactacatgg?tgcagacgga?ggaccagtac?gtgttcatcc?5100

atgaggcgct?gctggaggct?gccacgtgcg?gccacacaga?ggtgcctgcc?cgcaacctgt?5160

atgcccacat?ccagaagctg?ggccaagtgc?ctccagggga?gagtgtgacc?gccatggagc?5220

tcgagttcaa?gttgctggcc?agctccaagg?cccacacgtc?ccgcttcatc?agcgccaacc?5280

tgccctgcaa?caagttcaag?aaccggctgg?tgaacatcat?gccctacgaa?ttgacccgtg?5340

tgtgtctgca?gcccatccgt?ggtgtggagg?gctctgacta?catcaatgcc?agcttcctgg?5400

atggttatag?acagcagaag?gcctacatag?ctacacaggg?gcctctggca?gagagcaccg?5460

aggacttctg?gcgcatgcta?tgggagcaca?attccaccat?catcgtcatg?ctgaccaagc?5520

ttcgggagat?gggcagggag?aaatgccacc?agtactggcc?agcagagcgc?tctgctcgct?5580

accagtactt?tgttgttgac?ccgatggctg?agtacaacat?gccccagtat?atcctgcgtg?5640

agttcaaggt?cacggatgcc?cgggatgggc?agtcaaggac?aatccggcag?ttccagttca?5700

cagactggcc?agagcagggc?gtgcccaaga?caggcgaggg?attcattgac?ttcatcgggc?5760

aggtgcataa?gaccaaggag?cagtttggac?aggatgggcc?tatcacggtg?cactgcagtg?5820

ctggcgtggg?ccgcaccggg?gtgttcatca?ctctgagcat?cgtcctggag?cgcatgcgct?5880

acgagggcgt?ggtcgacatg?tttcagaccg?tgaagaccct?gcgtacacag?cgtcctgcca?5940

tggtgcagac?agaggaccag?tatcagctgt?gctaccgtgc?ggccctggag?tacctcggca?6000

gctttgacca?ctatgcaacg?taactaccgc?tcccctctcc?tccgccaccc?ccgccgtggg?6060

gctccggagg?ggacccagct?cctctgagcc?ataccgacca?tcgtccagcc?ctcctacgca?6120

gatgctgtca?ctggcagagc?acagcccacg?gggatcacag?cgtttcagga?acgttgccac?6180

accaatcaga?gagcctagaa?catccctggg?caagtggatg?gcccagcagg?caggcactgt?6240

ggcccttctg?tccaccagac?ccacctggag?cccgcttcaa?gctctctgtt?gcgctcccgc?6300

atttctcatg?cttcttctca?tggggtgggg?ttggggcaaa?gcctcctttt?taatacatta?6360

agtggggtag?actgaggaaa?aaaaaaaaaa?aaaaaaaaaa?aaaaaaaaaa?aa 6412

<210>66

<211>277

<212>PRT

＜213〉variola virus

<400>66

Met?Leu?Arg?Val?Arg?Ile?Leu?Leu?Ile?Tyr?Leu?Cys?Thr?Phe?Val?Val

1 5 10 15

Ile?Thr?Ser?Thr?Lys?Thr?Ile?Glu?Tyr?Thr?Ala?Cys?Asn?Asp?Thr?Ile

20 25 30

Ile?Ile?Pro?Cys?Thr?Ile?Asp?Asn?Pro?Thr?Lys?Tyr?Ile?Arg?Trp?Lys

35 40 45

Leu?Asp?Asn?His?Asn?Ile?Leu?Thr?Tyr?Asn?Lys?Thr?Ser?Lys?Thr?Ile

50 55 60

Ile?Leu?Ser?Lys?Trp?His?Thr?Ser?Ala?Lys?Leu?His?Ser?Leu?Ser?Asp

65 70 75 80

Asn?Asp?Val?Ser?Leu?Ile?Ile?Lys?Tyr?Lys?Asp?Ile?Leu?Pro?Gly?Thr

85 90 95

Tyr?Thr?Cys?Glu?Asp?Asn?Thr?Gly?Ile?Lys?Ser?Thr?Val?Lys?Leu?Val

100 105 110

Gln?Arg?His?Thr?Asn?Trp?Phe?Asn?Asp?His?His?Thr?Met?Leu?Met?Phe

115 120 125

Ile?Phe?Thr?Gly?Ile?Thr?Leu?Phe?Leu?Leu?Phe?Leu?Glu?Ile?Ala?Tyr

130 135 140

Thr?Ser?Ile?Ser?Val?Val?Phe?Ser?Thr?Asn?Leu?Gly?Ile?Leu?Gln?Val

145 150 155 160

Phe?Gly?Cys?Ile?Ile?Ala?Met?Ile?Glu?Leu?Cys?Gly?Ala?Phe?Leu?Phe

165 170 175

Tyr?Pro?Ser?Met?Phe?Thr?Leu?Arg?His?Ile?Ile?Gly?Leu?Leu?Met?Met

180 185 190

Thr?Leu?Pro?Ser?Ile?Phe?Leu?Ile?Ile?Thr?Lys?Val?Phe?Ser?Phe?Trp

195 200 205

Leu?Leu?Cys?Lys?Leu?Ser?Cys?Ala?Val?His?Leu?Ile?Ile?Tyr?Tyr?Gln

210 215 220

Leu?Ala?Gly?Tyr?Ile?Leu?Thr?Val?Leu?Gly?Leu?Gly?Leu?Ser?Leu?Lys

225 230 235 240

Glu?Cys?Val?Asp?Gly?Thr?Leu?Leu?Leu?Ser?Gly?Leu?Gly?Thr?Ile?Met

245 250 255

Val?Ser?Glu?His?Phe?Ser?Leu?Leu?Phe?Leu?Val?Cys?Phe?Pro?Ser?Thr

260 265 270

Gln?Arg?Asp?Tyr?Tyr

275

<210>67

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉HA epi-position

<400>67

Tyr?Pro?Tyr?Asp?Val?Asp?Tyr?Ala

1 5

<210>68

<211>12

<212>PRT

＜213〉artificial sequence

<220>

＜223〉protein C mark

<400>68

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

1 5 10

<210>69

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉HRV3C protease site

<400>69

Leu?Glu?Val?Leu?Phe?Gln?Gly?Pro

1 5

<210>70

<211>1897

<212>PRT

＜213〉people (homo sapiens)

<400>70

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser

785 790 795 800

Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 910

Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val

930 935 940

Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr

945 950 955 960

Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1010 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser

1125 1130 1135

Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Asn?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Cys?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr

1875 1880 1885

Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>71

<211>1948

<212>PRT

＜213〉people (homo sapiens)

<400>71

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ser?Ala?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Asp?Gln?Ala

180 185 190

Phe?Ser?His?Leu?Pro?Thr?Gly?Ala?Leu?Gln?Ile?Glu?Ser?Ser?Glu?Glu

195 200 205

Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Val

210 215 220

Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Ala?Leu?Leu?Lys?Leu

225 230 235 240

Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser?His?Glu?Ile

245 250 255

Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro

260 265 270

Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu

275 280 285

Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr?Asp?Val?Lys

290 295 300

Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu?Gly?Val?Ile

305 310 315 320

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

325 330 335

Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr?Ile?Thr?Trp

340 345 350

Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile?Glu?Tyr?Lys

355 360 365

Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp?Ile?Thr?Thr

370 375 380

Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu?Tyr?Glu?Ile

385 390 395 400

Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser

405 410 415

Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala?Pro?Arg?Asn

420 425 430

Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val?Gln?Trp?Glu

435 440 445

Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr

450 455 460

Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys?His?Asn?Val

465 470 475 480

Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Glu?Asp?Glu?Thr

485 490 495

Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu

500 505 510

Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro?Gly?Gln?Pro

515 520 525

Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile?Thr?Leu?Ser

530 535 540

Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu?Leu?Leu?Phe

545 550 555 560

Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe?Asp?Pro?Thr

565 570 575

Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu?Tyr?Ala?Phe

580 585 590

Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe?Thr?Pro?Val

595 600 605

Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp

610 615 620

Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val?Ser?Trp?Arg

625 630 635 640

Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly?Tyr?Ser?Val

645 650 655

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

660 665 670

Gly?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala?Leu?Glu?Lys

675 680 685

Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu?Val?Gly?Pro

690 695 700

Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro

705 710 715 720

Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn?Ala?Thr?Ala

725 730 735

Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln?His?Gly?Gln

740 745 750

Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly?Ala?Glu?Ala

755 760 765

Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp

770 775 780

Glu?Thr?Asp?Asp?Thr?Ala?Glu?Tyr?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln

785 790 795 800

Pro?Glu?Thr?Ala?Tyr?Ser?Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly

805 810 815

Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val

820 825 830

Leu?Gly?Arg?Pro?Thr?Leu?Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu

835 840 845

Leu?Ala?Arg?Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu

850 855 860

Gly?Tyr?Arg?Leu?Gln?Phe?Gly?Arg?Glu?Asp?Ser?Thr?Pro?Leu?Ala?Thr

865 870 875 880

Leu?Glu?Phe?Pro?Pro?Ser?Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His

885 890 895

Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly

900 905 910

Leu?Gly?Glu?Glu?Ala?Ala?Glu?Val?Leu?Ser?Ile?Pro?Glu?Asp?Thr?Pro

915 920 925

Arg?Gly?His?Pro?Gln?Ile?Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly

930 935 940

Thr?Val?Leu?Leu?Arg?Trp?Leu?Pro?Pro?Val?Pro?Ala?Glu?Arg?Asn?Gly

945 950 955 960

Ala?Ile?Val?Lys?Tyr?Thr?Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly

965 970 975

Pro?Ala?Arg?Glu?Thr?Glu?Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu

980 985 990

Asn?Ala?Leu?Thr?Leu?Gln?Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu

995 1000 1005

Gln?Val?Arg?Ala?His?Thr?Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro

1010 1015 1020

Val?Arg?Tyr?Arg?Thr?Phe?Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe

1025 1030 1035 1040

Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe

1045 1050 1055

Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly

1060 1065 1070

Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His

1075 1080 1085

Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser

1090 1095 1100

Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn

1105 1110 1115 1120

Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly

1125 1130 1135

Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln

1140 1145 1150

Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln

1155 1160 1165

Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu

1170 1175 1180

Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg

1185 1190 1195 1200

Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu

1205 1210 1215

Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp

1220 1225 1230

Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala

1235 1240 1245

Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp

1250 1255 1260

Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu

1265 1270 1275 1280

Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1285 1290 1295

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser

1300 1305 1310

Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala

1315 1320 1325

Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile

1330 1335 1340

Asn?Phe?Gln?Thr?Pro?Asp?Ser?Gly?Leu?Arg?Ser?Pro?Leu?Arg?Glu?Pro

1345 1350 1355 1360

Gly?Phe?His?Phe?Glu?Ser?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala

1365 1370 1375

Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys

1380 1385 1390

Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp

1395 1400 1405

Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn

1410 1415 1420

Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly

1425 1430 1435 1440

Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg

1445 1450 1455

Cys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe

1460 1465 1470

Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val

1475 1480 1485

Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr

1490 1495 1500

Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu

1505 1510 1515 1520

Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu

1525 1530 1535

His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe

1540 1545 1550

Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu

1555 1560 1565

Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro

1570 1575 1580

Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile

1585 1590 1595 1600

Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp

1605 1610 1615

Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val

1620 1625 1630

Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala

1635 1640 1645

Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr

1650 1655 1660

Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met

1665 1670 1675 1680

Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg

1685 1690 1695

Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val

1700 1705 1710

Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg

1715 1720 1725

Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr

1730 1735 1740

Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr

1745 1750 1755 1760

Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val

1765 1770 1775

Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln

1780 1785 1790

Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp

1795 1800 1805

Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys

1810 1815 1820

Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln

1825 1830 1835 1840

Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe

1845 1850 1855

Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln

1860 1865 1870

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

1875 1880 1885

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

1890 1895 1900

Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro

1905 1910 1915 1920

Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala

1925 1930 1935

Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1940 1945

<210>72

<211>1913

<212>PRT

＜213〉people (homo sapiens)

<400>72

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

Gln?Leu?Arg?Ser?Gly?Arg?Val?Phe?Lys?Arg?Leu?Asn?Arg?Arg?Ala?Leu

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Glu?Thr?Pro?Gln?Val?Arg?Arg?Val?Pro?Pro?Arg?Phe?Ser

225 230 235 240

Ile?Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile

245 250 255

Thr?Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu

260 265 270

Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn

275 280 285

Val?Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val

290 295 300

Ala?Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val

305 310 315 320

Lys?Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr

325 330 335

Ala?Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val

340 345 350

Ser?Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr

355 360 365

Lys?Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu

370 375 380

Ser?Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile

385 390 395 400

Gly?Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln

405 410 415

Ala?Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser

420 425 430

Thr?Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln

435 440 445

Ile?Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val

450 455 460

Asn?Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile

465 470 475 480

Gly?Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe

485 490 495

Thr?Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr

500 505 510

Gln?Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu

515 520 525

Ser?Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr

530 535 540

Ile?Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu

545 550 555 560

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

565 570 575

Lys?Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln

580 585 590

Gly?Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser

595 600 605

Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser

610 615 620

Thr?Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn

625 630 635 640

Gly?Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu

645 650 655

Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys

660 665 670

Tyr?Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val

675 680 685

Thr?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu

690 695 700

Ile?Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu

705 710 715 720

Val?Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro

725 730 735

Val?Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr

740 745 750

Val?Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp

755 760 765

Val?Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr?Glu?His

770 775 780

Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser?Leu?Thr

785 790 795 800

Val?Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys

805 810 815

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

820 825 830

Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro?Pro?Val

835 840 845

Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly?Arg?Lys

850 855 860

Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu?Asp?His

865 870 875 880

Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe?Arg?Leu

885 890 895

Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys?Glu?Ile

900 905 910

Ser?Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu?His?Ser

915 920 925

Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro?Pro?Val

930 935 940

Leu?Ala?Glu?Arg?Asn?Gly?Ile?Ile?Thr?Lys?Tyr?Thr?Leu?Leu?Tyr?Arg

945 950 955 960

Asp?Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val?Pro?Ala

965 970 975

Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

980 985 990

Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr?Ser?Pro

995 1000 1005

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

1010 1015 1020

Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1025 1030 1035 1040

Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu?Tyr?Asp

1045 1050 1055

Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln?Lys?Leu

1060 1065 1070

Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu?Thr?Asn

1075 1080 1085

Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala?Lys?Thr

1090 1095 1100

Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys?Thr?Asn

1105 1110 1115 1120

Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala?Asn?Glu

1125 1130 1135

Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys?Ser?Arg

1140 1145 1150

Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu?Leu?Asp

1155 1160 1165

Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg?Tyr?Gly

1170 1175 1180

Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp?Val?Leu

1185 1190 1195 1200

Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly?Phe?Thr

1205 1210 1215

Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val?Leu?Ala

1220 1225 1230

Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro?Tyr?Ser

1235 1240 1245

Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr?Asp?Glu

1250 1255 1260

Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val?Val?Phe

1265 1270 1275 1280

Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys?Arg?Ala

1285 1290 1295

Glu?Ser?Asp?Ser?Arg?Lys Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu?Ile?Pro

1300 1305 1310

Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn?Phe?Gln

1315 1320 1325

Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu?Leu?Ala

1330 1335 1340

Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe?Ser?Gln

1345 1350 1355 1360

Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser

1365 1370 1375

Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala

1380 1385 1390

Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile?Pro?Gly

1395 1400 1405

Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn

1410 1415 1420

Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe

1425 1430 1435 1440

Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met?Met?Thr

1445 1450 1455

Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ser

1460 1465 1470

Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu?Asp?Thr

1475 1480 1485

Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr?Lys?Asn

1490 1495 1500

Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp

1505 1510 1515 1520

Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu

1525 1530 1535

Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met?Val?Val

1540 1545 1550

His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp

1555 1560 1565

Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly

1570 1575 1580

His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu

1585 1590 1595 1600

Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val?Thr?Cys

1605 1610 1615

Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys

1620 1625 1630

Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu?Leu?Glu

1635 1640 1645

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

1650 1655 1660

Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met

1665 1670 1675 1680

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

1685 1690 1695

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln

1700 1705 1710

Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp

1715 1720 1725

Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val?Met?Leu

1730 1735 1740

Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro

1745 1750 1755 1760

Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala

1765 1770 1775

Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp

1780 1785 1790

Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp

1795 1800 1805

Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe

1810 1815 1820

Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro

1825 1830 1835 1840

Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile

1845 1850 1855

Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp

1860 1865 1870

Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val

1875 1880 1885

Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr

1890 1895 1900

Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1905 1910

<210>73

<211>468

<212>PRT

＜213〉artificial sequence

<220>

＜223〉viral polypeptide that merges with the human sequence of sudden change

<400>73

Met?Ala?Thr?Gly?Ser?Arg?Thr?Ser?Leu?Leu?Leu?Ala?Phe?Gly?Leu?Leu

1 5 10 15

Cys?Leu?Pro?Trp?Leu?Gln?Glu?Gly?Ser?Ala?Thr?Ser?Gly?Thr?Thr?Ser

20 25 30

Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys?Glu?Tyr

35 40 45

Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu?Lys

50 55 60

Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val?Ser

65 70 75 80

Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu?Asn

85 90 95

Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Gly?Val?Tyr?Thr

100 105 110

Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Ser?Thr

115 120 125

Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu

130 135 140

Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys

145 150 155 160

Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr

165 170 175

Val?Pro?Pro?Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr

180 185 190

Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly

195 200 205

Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr

210 215 220

Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Ser?Cys

225 230 235 240

Gly?Ser?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Ala?Glu

245 250 255

Gly?Ala?Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu

260 265 270

Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val?Val?Asp?Val?Ser

275 280 285

His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu

290 295 300

Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr

305 310 315 320

Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln?Asp?Trp?Leu?Asn

325 330 335

Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro

340 345 350

Ile?Glu?Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln

355 360 365

Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val

370 375 380

Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val

385 390 395 400

Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr?Lys?Thr?Thr?Pro

405 410 415

Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr

420 425 430

Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe?Ser?Cys?Ser?Val

435 440 445

Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu

450 455 460

Ser?Pro?Gly?Lys

465

<210>74

<211>456

<212>PRT

＜213〉artificial sequence

<220>

＜223〉viral polypeptide that merges with the human sequence of sudden change

<400>74

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Gly?Val

85 90 95

Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro

100 105 110

Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp?Asp?Leu?Val?Lys?Leu

115 120 125

Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys

130 135 140

Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe

145 150 155 160

Lys?Thr?Val?Pro?Pro?Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser

165 170 175

Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu

180 185 190

Cys?Gly?Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe

195 200 205

Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp

210 215 220

Ser?Cys?Gly?Ser?Cys?Asp?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala

225 230 235 240

Pro?Glu?Leu?Leu?Gly?Gly?Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro

245 250 255

Lys?Asp?Thr?Leu?Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val

260 265 270

Val?Asp?Val?Ser?His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val

275 280 285

Asp?Gly?Val?Glu?Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln

290 295 300

Tyr?Asn?Ser?Thr?Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln

305 310 315 320

Asp?Trp?Leu?Asn?Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala

325 330 335

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

340 345 350

Arg?Glu?Pro?Gln?Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr

355 360 365

Lys?Asn?Gln?Val?Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser

370 375 380

Asp?Ile?Ala?Val?Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr

385 390 395 400

Lys?Thr?Thr?Pro?Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr

405 410 415

Ser?Lys?Leu?Thr?Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe

420 425 430

Ser?Cys?Ser?Val?Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys

435 440 445

Ser?Leu?Ser?Leu?Ser?Pro?Gly?Lys

450 455

<210>75

<211>440

<212>PRT

＜213〉the unknown

<220>

＜223〉consensus sequence

<400>75

Leu?Leu?Ile?Gly?Ser?Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys

1 5 10 15

Asp?Ser?Asn?Asn?Lys?Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala

20 25 30

Thr?Leu?Asp?Glu?Pro?Leu?Lys?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His

35 40 45

Lys?Tyr?Gly?Ala?Ser?Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp

50 55 60

Leu?Leu?Asn?Cys?Phe?Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn

65 70 75 80

Arg?Asp?Thr?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe

85 90 95

Ala?Ser?Leu?Asp?Pro?Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp

100 105 110

Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys

115 120 125

Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu

130 135 140

Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?ProPro?Ser?Asn?Val?Gly?Ser?Met

145 150 155 160

Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val

165 170 175

Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr

180 185 190

Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu

195 200 205

Lys?Lys?Lys?Phe?Asp?Ser?Cys?Gly?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys

210 215 220

Pro?Ala?Pro?Glu?Gly?Ala?Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro

225 230 235 240

Lys?Asp?Thr?Leu?Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val

245 250 255

Val?Asp?Val?Ser?His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val

260 265 270

Asp?Gly?Val?Glu?Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln

275 280 285

Tyr?Asn?Ser?Thr?Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln

290 295 300

Asp?Trp?Leu?Asn?Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala

305 310 315 320

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

325 330 335

Arg?Glu?Pro?Gln?Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr

340 345 350

Lys?Asn?Gln?Val?Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser

355 360 365

Asp?Ile?Ala?Val?Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr

370 375 380

Lys?Thr?Thr?Pro?Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr

385 390 395 400

Ser?Lys?Leu?Thr?Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val Phe

405 410 415

Ser?Cys?Ser?Val?Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys

420 425 430

Ser?Leu?Ser?Leu?Ser?Pro?Gly?Lys

435 440

<210>76

<211>210

<212>PRT

＜213〉poxvirus

<400>76

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

1 5 10 15

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

20 25 30

Leu?Lys?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

35 40 45

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

50 55 60

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Gly?Val

65 70 75 80

Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro

85 90 95

Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp?Asp?Leu?Val?Lys?Leu

100 105 110

Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys

115 120 125

Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe

130 135 140

Lys?Thr?Val?Pro?Pro?Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser

145 150 155 160

Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu

165 170 175

Cys?Gly?Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe

180 185 190

Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp

195 200 205

Ser?Cys

210

<210>77

<211>226

<212>PRT

＜213〉artificial sequence

<220>

＜223〉Tu Bian human sequence

<400>77

Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Ala?Glu?Gly?Ala

1 5 10 15

Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu?Met?Ile

20 25 30

Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val?Val?Asp?Val?Ser?His?Glu

35 40 45

Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu?Val?His

50 55 60

Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr?Tyr?Arg

65 70 75 80

Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln?Asp?Trp?Leu?Asn?Gly?Lys

85 90 95

Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro?Ile?Glu

100 105 110

Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln?Val?Tyr

115 120 125

Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val?Ser?Leu

130 135 140

Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val?Glu?Trp

145 150 155 160

Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr?Lys?Thr?Thr?Pro?Pro?Val

165 170 175

Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr?Val?Asp

180 185 190

Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe?Ser?Cys?Ser?Val?Met?His

195 200 205

Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu?Ser?Pro

210 215 220

Gly?Lys

225

<210>78

<211>678

<212>DNA

＜213〉artificial sequence

<220>

＜223〉Tu Bian human sequence

<400>78

aaaactcaca?catgcccacc?gtgcccagca?cctgaagccg?agggcgcgcc?gtcagtcttc?60

ctcttccccc?caaaacccaa?ggacaccctc?atgatctccc?ggacccctga?ggtcacatgc?120

gtggtggtgg?acgtgagcca?cgaagaccct?gaggtcaagt?tcaactggta?cgtggacggc?180

gtggaggtgc?ataatgccaa?gacaaagccg?cgggaggagc?agtacaacag?cacgtaccgt?240

gtggtcagcg?tcctcaccgt?cctgcaccag?gactggctga?atggcaagga?gtacaagtgc?300

aaggtctcca?acaaagccct?cccagccccc?atcgagaaaa?ccatctccaa?agccaaaggg?360

cagccccgag?aaccacaggt?gtacaccctg?cccccatccc?gggatgagct?gaccaagaac?420

caggtcagcc?tgacctgcct?ggtcaaaggc?ttctatccca?gcgacatcgc?cgtggagtgg?480

gagagcaatg?ggcagccgga?gaacaactac?aagaccacgc?ctcccgtgct?ggactccgac?540

ggctccttct?tcctctatag?caagctcacc?gtggacaaga?gcaggtggca?gcaggggaac?600

gtcttctcat?gctccgtgat?gcatgaggct?ctgcacaacc?actacacgca?gaagagcctc?660

tccctgtctc?cgggtaaa 678

<210>79

<211>228

<212>PRT

＜213〉people (homo sapiens)

<400>79

Cys?Asp?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Leu?Leu

1 5 10 15

Gly?Gly?Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu

20 25 30

Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val?Val?Asp?Val?Ser

35 40 45

His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu

50 55 60

Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr

65 70 75 80

Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln?Asp?Trp?Leu?Asn

85 90 95

Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro

100 105 110

Ile?Glu?Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln

115 120 125

Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val

130 135 140

Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val

145 150 155 160

Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr?Lys?Thr?Thr?Pro

165 170 175

Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr

180 185 190

Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe?Ser?Cys?Ser?Val

195 200 205

Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu

210 215 220

Ser?Pro?Gly?Lys

225

<210>80

<211>6

<212>PRT

＜213〉people (homo sapiens)

<400>80

Leu?Leu?Gly?Gly?Pro?Ser

1 5

<210>81

<211>18

<212>PRT

＜213〉artificial sequence

<220>

＜223〉Tu Bian human sequence

<400>81

Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Ala?Glu?Gly?Ala

1 5 10 15

Pro?Ser

<210>82

<211>218

<212>PRT

＜213〉vaccinia virus

<400>82

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr

85 90 95

Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly

130 135 140

Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn?Val

145 150 155 160

Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Ser?Cys

210 215

<210>83

<211>210

<212>PRT

＜213〉poxvirus

<400>83

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

1 5 10 15

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

20 25 30

Leu?Lys?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

35 40 45

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

50 55 60

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Gly?Val

65 70 75 80

Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro

85 90 95

Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp?Asp?Leu?Val?Lys?Leu

100 105 110

Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys

115 120 125

Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe

130 135 140

Lys?Thr?Val?Pro?Pro?Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser

145 150 155 160

Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu

165 170 175

Cys?Gly?Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe

180 185 190

Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp

195 200 205

Ser?Cys

210

<210>84

<211>226

<212>PRT

＜213〉poxvirus

<400>84

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Lys?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Gly?Val

85 90 95

Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro

100 105 110

Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met?Thr?His?Asp?Asp?Leu?Val?Lys?Leu

115 120 125

Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile?Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys

130 135 140

Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe

145 150 155 160

Lys?Thr?Val?Pro?Pro?Ser?Asn?Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser

165 170 175

Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu

180 185 190

Cys?Gly?Asn?Ile?Lys?Gln?His?Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe

195 200 205

Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp

210 215 220

Ser?Cys

225

<210>85

<211>186

<212>PRT

＜213〉tanapox virus

<400>85

Met?Ile?Leu?Leu?Ile?Phe?Leu?Cys?Val?Val?Ile?Thr?Asn?Leu?Ser?Pro

1 5 10 15

Ser?Tyr?Cys?Asn?Glu?Tyr?Ile?Asn?Ser?Thr?Ile?Leu?Val?Asn?Ile?Lys

20 25 30

Leu?Gly?Lys?Lys?Thr?Cys?Cys?Asn?Gly?Phe?Thr?Tyr?Leu?Leu?Asp?Asn

35 40 45

Asn?Leu?Glu?Phe?Tyr?Asn?Ile?Met?Tyr?Ser?Asn?Val?Asn?Val?Ser?Ile

50 55 60

Asn?Ile?Glu?Asn?Cys?Tyr?Phe?Asn?Asn?Ser?Ile?Phe?Lys?Asn?Thr?Lys

65 70 75 80

His?Lys?Asn?Ile?Ser?Ile?Leu?Leu?Thr?Ser?Lys?Ser?Asn?Ile?Gln?Lys

85 90 95

Asn?Ile?Ala?Ile?Ile?Pro?Ile?Thr?Cys?Lys?Ile?Thr?Ile?Asp?Ile?Thr

100 105 110

Cys?Thr?Lys?Asn?Gly?Lys?Lys?Lys?Cys?Leu?Ala?Gln?Glu?Lys?Leu?Pro

115 120 125

Lys?Thr?Pro?Asn?Leu?Ile?Tyr?Lys?Thr?Ala?Glu?His?Val?Asn?Gly?Ile

130 135 140

Ile?Asp?Leu?Asn?Ile?Tyr?Gly?Ser?Cys?Val?Lys?Tyr?Val?Tyr?Thr?Arg

145 150 155 160

Val?Asn?Ile?Tyr?Glu?Ile?Ser?Asn?Gly?Asn?Leu?Ile?Tyr?Asp?Gln?Leu

165 170 175

Asp?Ser?Asn?Phe?Leu?Lys?Leu?Asn?Thr?Lys

180 185

<210>86

<211>58

<212>PRT

＜213〉the unknown

<220>

＜223〉consensus sequence

<400>86

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

1 5 10 15

Asn?Ile?Ser?Ile?Ile?Asn?Cys?Phe?Asn?Lys?Ala?Ser?Ile?Ile?Cys?Ile

20 25 30

Ile?Ile?Cys?Lys?Leu?Asn?Lys?Val?Ile?Ile?Asp?Leu?Asn?Cys?Val?Val

35 40 45

Val?Ile?Tyr?Asp?Asn?Ile?Ile?Ser?Thr?Lys

50 55

<210>87

<211>218

<212>PRT

＜213〉vaccinia virus

<400>87

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr

85 90 95

Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly

130 135 140

Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn?Val

145 150 155 160

Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Ser?Cys

210 215

<210>88

<211>218

<212>PRT

＜213〉big variola virus, strain Harvey

<400>88

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>89

<211>218

<212>PRT

＜213〉variola virus, strain India-1967

<400>89

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Thr?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>90

<211>218

<212>PRT

＜213〉alastrim virus, strain Garcia-1966

<400>90

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Met?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?Tyr?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Ile?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Asn?Val

145 150 155 160

Gly?Ser?Ile?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asn?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Thr?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>91

<211>219

<212>PRT

＜213〉vaccinia virus, strain WR

<400>91

Met?Tyr?Ser?Leu?Val?Phe?Val?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Lys?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Thr?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>92

<211>219

<212>PRT

＜213〉vaccinia virus, strain Tian Tan

<400>92

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?As Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>93

<211>219

<212>PRT

＜213〉vaccinia virus, strain Ankara

<400>93

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?His?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>94

<211>219

<212>PRT

＜213〉vaccinia virus, strain Copenhagen

<400>94

Met?Tyr?Ser?Leu?Leu?Phe?Ile?Ile?Leu?Met?Cys?Ile?Pro?Phe?Ser?Phe

1 5 10 15

Gln?Thr?Val?Tyr?Asp?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asp?Asn?Lys?Glu

20 25 30

Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro?Leu

35 40 45

Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser?Val

50 55 60

Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe?Leu

65 70 75 80

Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr?Ala

85 90 95

Lys?Phe?Ala?Ser?Leu?Asp?Pro?Trp?Thr?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Thr?Asn

130 135 140

Gly?Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asp

145 150 155 160

Val?Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Asn?Asp?Val

165 170 175

Thr?Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His

180 185 190

Ser?Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro

195 200 205

Arg?Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Asn?Cys

210 215

<210>95

<211>218

<212>PRT

＜213〉vaccinia virus, strain BrIGhton Red

<400>95

Met?Tyr?Ser?Leu?Phe?Ile?Ile?Leu?Met?Gly?Leu?Pro?Phe?Ser?Phe?Gln

1 5 10 15

Thr?Ser?Glu?Pro?Ala?Tyr?Asp?Lys?Ser?Val?Cys?Asp?Ser?Asn?Asn?Lys

20 25 30

Glu?Tyr?Met?Gly?Ile?Glu?Val?Tyr?Val?Glu?Ala?Thr?Leu?Asp?Glu?Pro

35 40 45

Leu?Arg?Gln?Thr?Thr?Cys?Glu?Ser?Glu?Ile?His?Lys?Tyr?Gly?Ala?Ser

50 55 60

Val?Ser?Asn?Gly?Gly?Leu?Asn?Ile?Ser?Val?Asp?Leu?Leu?Asn?Cys?Phe

65 70 75 80

Leu?Asn?Phe?His?Thr?Val?Gly?Val?Tyr?Thr?Asn?Arg?Asp?Thr?Val?Tyr

85 90 95

Ala?Lys?Phe?Ala?Ser?Leu?Asp?Pro?Ser?Thr?Glu?Pro?Ile?Asn?Ser?Met

100 105 110

Thr?His?Asp?Asp?Leu?Val?Lys?Leu?Thr?Glu?Glu?Cys?Ile?Val?Asp?Ile

115 120 125

Tyr?Leu?Lys?Cys?Glu?Val?Asp?Lys?Thr?Lys?Asp?Phe?Met?Lys?Asn?Gly

130 135 140

Asn?Arg?Leu?Lys?Pro?Arg?Asp?Phe?Lys?Thr?Val?Pro?Pro?Ser?Asn?Val

145 150 155 160

Gly?Ser?Met?Ile?Glu?Leu?Gln?Ser?Asp?Tyr?Cys?Val?Glu?Asp?Val?Thr

165 170 175

Ala?Tyr?Val?Lys?Ile?Tyr?Asp?Glu?Cys?Gly?Asn?Ile?Lys?Gln?His?Ser

180 185 190

Ile?Pro?Thr?Leu?Arg?Asp?Tyr?Phe?Thr?Thr?Lys?Asn?Gly?Gln?Pro?Arg

195 200 205

Lys?Ile?Leu?Lys?Lys?Lys?Phe?Asp?Ser?Cys

210 215

<210>96

<211>654

<212>DNA

＜213〉vaccinia virus, strain Brighton Red

<400>96

atgtactcat?tatttattat?tttgatgggt?ctaccattta?gttttcaaac?aagtgaacca?60

gcgtatgata?aatcggtatg?cgattctaac?aataaagaat?atatgggaat?agaagtttat?120

gtagaagcaa?cgctagacga?acccctcaga?caaacaacgt?gtgaatccga?aatccataaa?180

tatggtgcat?ctgtatcaaa?cggaggatta?aatatttctg?ttgatctatt?aaactgtttt?240

cttaattttc?atacagttgg?tgtatacact?aatcgcgata?ccgtatacgc?gaagtttgct?300

agtttggatc?catctacgga?acctataaat?tctatgaccc?atgacgatct?agtaaaatta?360

acagaagaat?gtatagtgga?catttattta?aaatgtgaag?tggataaaac?aaaggatttc?420

atgaaaaacg?gcaatagatt?aaaaccaaga?gactttaaaa?ctgttcctcc?ttctaatgta?480

ggaagtatga?tcgaactaca?gtctgactat?tgcgtagaag?atgtgactgc?atacgtcaaa?540

atatacgatg?agtgcggaaa?cattaaacag?cattccattc?caacactacg?agattatttt?600

accaccaaga?atggtcaacc?acgtaaaata?ttaaagaaaa?aatttgatag?ttgt 654

<210>97

<211>1445

<212>PRT

＜213〉people (homo sapiens)

<400>97

Met?Arg?Arg?Leu?Leu?Glu?Pro?Cys?Trp?Trp?Ile?Leu?Phe?Leu?Lys?Ile

1 5 10 15

Thr?Ser?Ser?Val?Leu?His?Tyr?Val?Val?Cys?Phe?Pro?Ala?Leu?Thr?Glu

20 25 30

Gly?Tyr?Val?Gly?Ala?Leu?His?Glu?Asn?Arg?His?Gly?Ser?Ala?Val?Gln

35 40 45

Ile?Arg?Arg?Arg?Lys?Ala?Ser?Gly?Asp?Pro?Tyr?Trp?Ala?Tyr?Ser?Gly

50 55 60

Ala?Tyr?Gly?Pro?Glu?His?Trp?Val?Thr?Ser?Ser?Val?Ser?Cys?Gly?Ser

65 70 75 80

Arg?His?Gln?Ser?Pro?Ile?Asp?Ile?Leu?Asp?Gln?Tyr?Ala?Arg?Val?Gly

85 90 95

Glu?Glu?Tyr?Gln?Glu?Leu?Gln?Leu?Asp?Gly?Phe?Asp?Asn?Glu?Ser?Ser

100 105 110

Asn?Lys?Thr?Trp?Met?Lys?Asn?Thr?Gly?Lys?Thr?Val?Ala?Ile?Leu?Leu

115 120 125

Lys?Asp?Asp?Tyr?Phe?Val?Ser?Gly?Ala?Gly?Leu?Pro?Gly?Arg?Phe?Lys

130 135 140

Ala?Glu?Lys?Val?Glu?Phe?His?Trp?Gly?His?Ser?Asn?Gly?Ser?Ala?Gly

145 150 155 160

Ser?Glu?His?Ser?Ile?Asn?Gly?Arg?Arg?Phe?Pro?Val?Glu?Met?Gln?Ile

165 170 175

Phe?Phe?Tyr?Asn?Pro?Asp?Asp?Phe?Asp?Ser?Phe?Gln?Thr?Ala?Ile?Ser

180 185 190

Glu?Asn?Arg?Ile?Ile?Gly?Ala?Met?Ala?Ile?Phe?Phe?Gln?Val?Ser?Pro

195 200 205

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

210 215 220

Val?His?His?Glu?Lys?Glu?Thr?Phe?Leu?Asp?Pro?Phe?Val?Leu?Arg?Asp

225 230 235 240

Leu?Leu?Pro?Ala?Ser?Leu?Gly?Ser?Tyr?Tyr?Arg?Tyr?Thr?Gly?Ser?Leu

245 250 255

Thr?Thr?Pro?Pro?Cys?Ser?Glu?Ile?Val?Glu?Trp?Ile?Val?Phe?Arg?Arg

260 265 270

Pro?Val?Pro?Ile?Ser?Tyr?His?Gln?Leu?Glu?Ala?Phe?Tyr?Ser?Ile?Phe

275 280 285

Thr?Thr?Glu?Gln?Gln?Asp?His?Val?Lys?Ser?Val?Glu?Tyr?Leu?Arg?Asn

290 295 300

Asn?Phe?Arg?Pro?Gln?Gln?Arg?Leu?His?Asp?Arg?Val?Val?Ser?Lys?Ser

305 310 315 320

Ala?Val?Arg?Asp?Ser?Trp?Asn?His?Asp?Met?Thr?Asp?Phe?Leu?Glu?Asn

325 330 335

Pro?Leu?Gly?Thr?Glu?Ala?Ser?Lys?Val?Cys?Ser?Ser?Pro?Pro?Ile?His

340 345 350

Met?Lys?Val?Gln?Pro?Leu?Asn?Gln?Thr?Ala?Leu?Gln?Val?Ser?Trp?Ser

355 360 365

Gln?Pro?Glu?Thr?Ile?Tyr?His?Pro?Pro?Ile?Met?Asn?Tyr?Met?Ile?Ser

370 375 380

Tyr?Ser?Trp?Thr?Lys?Asn?Glu?Asp?Glu?Lys?Glu?Lys?Thr?Phe?Thr?Lys

385 390 395 400

Asp?Ser?Asp?Lys?Asp?Leu?Lys?Ala?Thr?Ile?Ser?His?Val?Ser?Pro?Asp

405 410 415

Ser?Leu?Tyr?Leu?Phe?Arg?Val?Gln?Ala?Val?Cys?Arg?Asn?Asp?Met?Arg

420 425 430

Ser?Asp?Phe?Ser?Gln?Thr?Met?Leu?Phe?Gln?Ala?Asn?Thr?Thr?Arg?Ile

435 440 445

Phe?Gln?Gly?Thr?Arg?Ile?Val?Lys?Thr?Gly?Val?Pro?Thr?Ala?Ser?Pro

450 455 460

Ala?Ser?Ser?Ala?Asp?Met?Ala?Pro?Ile?Ser?Ser?Gly?Ser?Ser?Thr?Trp

465 470 475 480

Thr?Ser?Ser?Gly?Ile?Pro?Phe?Ser?Phe?Val?Ser?Met?Ala?Thr?Gly?Met

485 490 495

Gly?Pro?Ser?Ser?Ser?Gly?Ser?Gln?Ala?Thr?Val?Ala?Ser?Val?Val?Thr

500 505 510

Ser?Thr?Leu?Leu?Ala?Gly?Leu?Gly?Phe?Gly?Gly?Gly?Gly?Ile?Ser?Ser

515 520 525

Phe?Pro?Ser?Thr?Val?Trp?Pro?Thr?Arg?Leu?Pro?Thr?Ala?Ala?Ser?Ala

530 535 540

Ser?Lys?Gln?Ala?Ala?Arg?Pro?Val?Leu?Ala?Thr?Thr?Glu?Ala?Leu?Ala

545 550 555 560

Ser?Pro?Gly?Pro?Asp?Gly?Asp?Ser?Ser?Pro?Thr?Lys?Asp?Gly?Glu?Gly

565 570 575

Thr?Glu?Glu?Gly?Glu?Lys?Asp?Glu?Lys?Ser?Glu?Ser?Glu?Asp?Gly?Glu

580 585 590

Arg?Glu?His?Glu?Glu?Asp?Gly?Glu?Lys?Asp?Ser?Glu?Lys?Lys?Glu?Lys

595 600 605

Ser?Gly?Val?Thr?His?Ala?Ala?Glu?Glu?Arg?Asn?Gln?Thr?Glu?Pro?Ser

610 615 620

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

625 630 635 640

Ile?Pro?Gly?His?Glu?Gln?Asp?His?Thr?Ala?Val?Pro?Thr?Asp?Gln?Thr

645 650 655

Gly?Gly?Arg?Arg?Asp?Ala?Gly?Pro?Gly?Leu?Asp?Pro?Asp?Met?Val?Thr

660 665 670

Ser?Thr?Gln?Val?Pro?Pro?Thr?Ala?Thr?Glu?Glu?Gln?Tyr?Ala?Gly?Ser

675 680 685

Asp?Pro?Lys?Arg?Pro?Glu?Met?Pro?Ser?Lys?Lys?Pro?Met?Ser?Arg?Gly

690 695 700

Asp?Arg?Phe?Ser?Glu?Asp?Ser?Arg?Phe?Ile?Thr?Val?Asn?Pro?Ala?Glu

705 710 715 720

Lys?Asn?Thr?Ser?Gly?Met?Ile?Ser?Arg?Pro?Ala?Pro?Gly?Arg?Met?Glu

725 730 735

Trp?Ile?Ile?Pro?Leu?Ile?Val?Val?Ser?Ala?Leu?Thr?Phe?Val?Cys?Leu

740 745 750

Ile?Leu?Leu?Ile?Ala?Val?Leu?Val?Tyr?Trp?Arg?Gly?Cys?Asn?Lys?Ile

755 760 765

Lys?Ser?Lys?Gly?Phe?Pro?Arg?Arg?Phe?Arg?Glu?Val?Pro?Ser?Ser?Gly

770 775 780

Glu?Arg?Gly?Glu?Lys?Gly?Ser?Arg?Lys?Cys?Phe?Gln?Thr?Ala?His?Phe

785 790 795 800

Tyr?Val?Glu?Asp?Ser?Ser?Ser?Pro?Arg?Val?Val?Pro?Asn?Glu?Ser?Ile

805 810 815

Pro?Ile?Ile?Pro?Ile?Pro?Asp?Asp?Met?Glu?Ala?Ile?Pro?Val?Lys?Gln

820 825 830

Phe?Val?Lys?His?Ile?Gly?Glu?Leu?Tyr?Ser?Asn?Asn?Gln?His?Gly?Phe

835 840 845

Ser?Glu?Asp?Phe?Glu?Glu?Val?Gln?Arg?Cys?Thr?Ala?Asp?Met?Asn?Ile

850 855 860

Thr?Ala?Glu?His?Ser?Asn?His?Pro?Glu?Asn?Lys?His?Lys?Asn?Arg?Tyr

865 870 875 880

Ile?Asn?Ile?Leu?Ala?Tyr?Asp?His?Ser?Arg?Val?Lys?Leu?Arg?Pro?Leu

885 890 895

Pro?Gly?Lys?Asp?Ser?Lys?His?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val

900 905 910

Asp?Gly?Tyr?Asn?Lys?Ala?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

915 920 925

Lys?Ser?Thr?Phe?Glu?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Asn?Thr

930 935 940

Gly?Ile?Ile?Val?Met?Ile?Thr?Asn?Leu?Val?Glu?Lys?Gly?Arg?Arg?Lys

945 950 955 960

Cys?Asp?Gln?Tyr?Trp?Pro?Thr?Glu?Asn?Ser?Glu?Glu?Tyr?Gly?Asn?Ile

965 970 975

Ile?Val?Thr?Leu?Lys?Ser?Thr?Lys?Ile?His?Ala?Cys?Tyr?Thr?Val?Arg

980 985 990

Arg?Phe?Ser?Ile?Arg?Asn?Thr?Lys?Val?Lys?Lys?Gly?Gln?Lys?Gly?Asn

995 1000 1005

Pro?Lys?Gly?Arg?Gln?Asn?Glu?Arg?Val?Val?Ile?Gln?Tyr?His?Tyr?Thr

1010 1015 1020

Gln?Trp?Pro?Asp?Met?Gly?Val?Pro?Glu?Tyr?Ala?Leu?Pro?Val?Leu?Thr

1025 1030 1035 1040

Phe?Val?Arg?Arg?Ser?Ser?Ala?Ala?Arg?Met?Pro?Glu?Thr?Gly?Pro?Val

1045 1050 1055

Leu?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Thr?Tyr?Ile?Val

1060 1065 1070

Ile?Asp?Ser?Met?Leu?Gln?Gln?Ile?Lys?Asp?Lys?Ser?Thr?Val?Asn?Val

1075 1080 1085

Leu?Gly?Phe?Leu?Lys?His?Ile?Arg?Thr?Gln?Arg?Asn?Tyr?Leu?Val?Gln

1090 1095 1100

Thr?Glu?Glu?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Ile

1105 1110 1115 1120

Leu?Gly?Lys?Glu?Thr?Glu?Val?Ser?Ser?Asn?Gln?Leu?His?Ser?Tyr?Val

1125 1130 1135

Asn?Ser?Ile?Leu?Ile?Pro?Gly?Val?Gly?Gly?Lys?Thr?Arg?Leu?Glu?Lys

1140 1145 1150

Gln?Phe?Lys?Leu?Val?Thr?Gln?Cys?Asn?Ala?Lys?Tyr?Val?Glu?Cys?Phe

1155 1160 1165

Ser?Ala?Gln?Lys?Glu?Cys?Asn?Lys?Glu?Lys?Asn?Arg?Asn?Ser?Ser?Val

1170 1175 1180

Val?Pro?Ser?Glu?Arg?Ala?Arg?Val?Gly?Leu?Ala?Pro?Leu?Pro?Gly?Met

1185 1190 1195 1200

Lys?Gly?Thr?Asp?Tyr?Ile?Asn?Ala?Ser?Tyr?Ile?Met?Gly?Tyr?Tyr?Arg

1205 1210 1215

Ser?Asn?Glu?Phe?Ile?Ile?Thr?Gln?His?Pro?Leu?Pro?His?Thr?Thr?Lys

1220 1225 1230

Asp?Phe?Trp?Arg?Met?Ile?Trp?Asp?His?Asn?Ala?Gln?Ile?Ile?Val?Met

1235 1240 1245

Leu?Pro?Asp?Asn?Gln?Ser?Leu?Ala?Glu?Asp?Glu?Phe?Val?Tyr?Trp?Pro

1250 1255 1260

Ser?Arg?Glu?Glu?Ser?Met?Asn?Cys?Glu?Ala?Phe?Thr?Val?Thr?LeuIle

1265 1270 1275 1280

Ser?Lys?Asp?Arg?Leu?Cys?Leu?Ser?Asn?Glu?Glu?Gln?Ile?Ile?Ile?His

1285 1290 1295

Asp?Phe?Ile?Leu?Glu?Ala?Thr?Gln?Asp?Asp?Tyr?Val?Leu?Glu?Val?Arg

1300 1305 1310

His?Phe?Gln?Cys?Pro?Lys?Trp?Pro?Asn?Pro?Asp?Ala?Pro?Ile?Ser?Ser

1315 1320 1325

Thr?Phe?Glu?Leu?Ile?Asn?Val?Ile?Lys?Glu?Glu?Ala?Leu?Thr?Arg?Asp

1330 1335 1340

Gly?Pro?Thr?Ile?Val?His?Asp?Glu?Tyr?Gly?Ala?Val?Ser?Ala?Gly?Met

1345 1350 1355 1360

Leu?Cys?Ala?Leu?Thr?Thr?Leu?Ser?Gln?Gln?Leu?Glu?Asn?Glu?Asn?Ala

1365 1370 1375

Val?Asp?Val?Phe?Gln?Val?Ala?Lys?Met?Ile?Asn?Leu?Met?Arg?Pro?Gly

1380 1385 1390

Val?Phe?Thr?Asp?Ile?Glu?Gln?Tyr?Gln?Phe?Ile?Tyr?Lys?Ala?Arg?Leu

1395 1400 1405

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

1410 1415 1420

Lys?Asn?Gly?Ala?Val?Leu?Ile?Ala?Asp?Glu?Ser?Asp?Pro?Ala?Glu?Ser

1425 1430 1435 1440

Met?Glu?Ser?Leu?Val

1445

<210>98

<211>7718

<212>DNA

＜213〉people (homo sapiens)

<400>98

cgggagcggc?gggagcggtg?gcggcggcag?aggcggcggc?tccagcttcg?gctccggctc?60

gggctcgggc?tccggctccg?gctccggctc?cggctccagc?tcgggtggcg?gtggcgggag?120

cgggaccagg?tggaggcggc?ggcggcagag?gagtgggagc?agcggcccta?gcggcttgcg?180

gggggacatg?cggaccgacg?gcccctggat?aggcggaagg?agtggaggcc?ctggtgcccg?240

gcccttggtg?ctgagtatcc?agcaagagtg?accggggtga?agaagcaaag?actcggttga?300

ttgtcctggg?ctgtggctgg?ctgtggagct?agagccctgg?atggcccctg?agccagcccc?360

agggaggacg?atggtgcccc?ttgtgcctgc?actggtgatg?cttggtttgg?tggcaggcgc?420

ccatggtgac?agcaaacctg?tcttcattaa?agtccctgag?gaccagactg?ggctgtcagg?480

aggggtagcc?tccttcgtgt?gccaagctac?aggagaaccc?aagccgcgca?tcacatggat?540

gaagaagggg?aagaaagtca?gctcccagcg?cttcgaggtc?attgagtttg?atgatggggc?600

agggtcagtg?cttcggatcc?agccattgcg?ggtgcagcga?gatgaagcca?tctatgagtg?660

tacagctact?aacagcctgg?gtgagatcaa?cactagtgcc?aagctctcag?tgctcgaaga?720

ggaacagctg?ccccctgggt?tcccttccat?cgacatgggg?cctcagctga?aggtggtgga?780

gaaggcacgc?acagccacca?tgctatgtgc?cgcaggcgga?aatccagacc?ctgagatttc?840

ttggttcaag?gacttccttc?ctgtagaccc?tgccacgagc?aacggccgca?tcaagcagct?900

gcgttcaggt?gccttgcaga?tagagagcag?tgaggaatcc?gaccaaggca?agtacgagtg?960

tgtggcgacc?aactcggcag?gcacacgtta?ctcagcccct?gcgaacctgt?atgtgcgagt?1020

gcgccgcgtg?gctcctcgtt?tctccatccc?tcccagcagc?caggaggtga?tgccaggcgg?1080

cagcgtgaac?ctgacatgcg?tggcagtggg?tgcacccatg?ccctacgtga?agtggatgat?1140

gggggccgag?gagctcacca?aggaggatga?gatgccagtt?ggccgcaacg?tcctggagct?1200

cagcaatgtc?gtacgctctg?ccaactacac?ctgtgtggcc?atctcctcgc?tgggcatgat?1260

cgaggccaca?gcccaggtca?cagtgaaagc?tcttccaaag?cctccgattg?atcttgtggt?1320

gacagagaca?actgccacca?gtgtcaccct?cacctgggac?tctgggaact?cggagcctgt?1380

aacctactat?ggcatccagt?accgcgcagc?gggcacggag?ggcccctttc?aggaggtgga?1440

tggtgtggcc?accacccgct?acagcattgg?cggcctcagc?cctttctcgg?aatatgcctt?1500

ccgcgtgctg?gcggtgaaca?gcatcgggcg?agggccgccc?agcgaggcag?tgcgggcacg?1560

cacgggagaa?caggcgccct?ccagcccacc?gcgccgcgtg?caggcacgca?tgctgagcgc?1620

cagcaccatg?ctggtgcagt?gggagcctcc?cgaggagccc?aacggcctgg?tgcggggata?1680

ccgcgtctac?tatactccgg?actcccgccg?ccccccgaac?gcctggcaca?agcacaacac?1740

cgacgcgggg?ctcctcacga?ccgtgggcag?cctgctgcct?ggcatcacct?acagcctgcg?1800

cgtgcttgcc?ttcaccgccg?tgggcgatgg?ccctcccagc?cccaccatcc?aggtcaagac?1860

gcagcaggga?gtgcctgccc?agcccgcgga?cttccaggcc?gaggtggagt?cggacaccag?1920

gatccagctc?tcgtggctgc?tgccccctca?ggagcggatc?atcatgtatg?aactggtgta?1980

ctgggcggca?gaggacgaag?accaacagca?caaggtcacc?ttcgacccaa?cctcctccta?2040

cacactagag?gacctgaagc?ctgacacact?ctaccgcttc?cagctggctg?cacgctcgga?2100

tatgggggtg?ggcgtcttca?cccccaccat?tgaggcccgc?acagcccagt?ccaccccctc?2160

cgcccctccc?cagaaggtga?tgtgtgtgag?catgggctcc?accacggtcc?gggtaagttg?2220

ggtcccgccg?cctgccgaca?gccgcaacgg?cgttatcacc?cagtactccg?tggcccacga?2280

ggcggtggac?ggcgaggacc?gcgggcggca?tgtggtggat?ggcatcagcc?gtgagcactc?2340

cagctgggac?ctggtgggcc?tggagaagtg?gacggagtac?cgggtgtggg?tgcgggcaca?2400

cacagacgtg?ggccccggcc?ccgagagcag?cccggtgctg?gtgcgcaccg?atgaggacgt?2460

gcccagcggg?cctccgcgga?aggtggaggt?ggagccactg?aactccactg?ctgtgcatgt?2520

ctactggaag?ctgcctgtcc?ccagcaagca?gcatggccag?atccgcggct?accaggtcac?2580

ctacgtgcgg?ctggagaatg?gcgagccccg?tggactcccc?atcatccaag?acgtcatgct?2640

agccgaggcc?cagtggcggc?cagaggagtc?cgaggactat?gaaaccacta?tcagcggcct?2700

gaccccggag?accacctact?ccgttactgt?tgctgcctat?accaccaagg?gggatggtgc?2760

ccgcagcaag?cccaaaattg?tcactacaac?aggtgcagtc?ccaggccggc?ccaccatgat?2820

gatcagcacc?acggccatga?acactgcgct?gctccagtgg?cacccaccca?aggaactgcc?2880

tggcgagctg?ctgggctacc?ggctgcagta?ctgccgggcc?gacgaggcgc?ggcccaacac?2940

catagatttc?ggcaaggatg?accagcactt?cacagtcacc?ggcctgcaca?aggggaccac?3000

ctacatcttc?cggcttgctg?ccaagaaccg?ggctggcttg?ggtgaggagt?tcgagaagga?3060

gatcaggacc?cccgaggacc?tgcccagcgg?cttcccccaa?aacctgcatg?tgacaggact?3120

gaccacgtct?accacagaac?tggcctggga?cccgccagtg?ctggcggaga?ggaacgggcg?318u

catcatcagc?tacaccgtgg?tgttccgaga?catcaacagc?caacaggagc?tgcagaacat?3240

cacgacagac?acccgcttta?cccttactgg?cctcaagcca?gacaccactt?acgacatcaa?3300

ggtccgcgca?tggaccagca?aaggctctgg?cccactcagc?cccagcatcc?agtcccggac?3360

catgccggtg?gagcaagtgt?ttgccaagaa?cttccgggtg?gcggctgcaa?tgaagacgtc?3420

tgtgctgctc?agctgggagg?ttcccgactc?ctataagtca?gctgtgccct?ttaagattct?3480

gtacaatggg?cagagtgtgg?aggtggacgg?gcactcgatg?cggaagctga?tcgcagacct?3540

gcagcccaac?acagagtact?cgtttgtgct?gatgaaccgt?ggcagcagcg?cagggggcct?3600

gcagcacctg?gtgtccatcc?gcacagcccc?cgacctcctg?cctcacaagc?cgctgcctgc?3660

ctctgcctac?atagaggacg?gccgcttcga?tctctccatg?ccccatgtgc?aagacccctc?3720

gcttgtcagg?tggttctaca?ttgttgtggt?acccattgac?cgtgtgggcg?ggagcatgct?3780

gacgccaagg?tggagcacac?ccgaggaact?ggagctggac?gagcttctag?aagccatcga?3840

gcaaggcgga?gaggagcagc?ggcggcggcg?gcggcaggca?gaacgtctga?agccatatgt?3900

ggctgctcaa?ctggatgtgc?tcccggagac?ctttaccttg?ggggacaaga?agaactaccg?3960

gggcttctac?aaccggcccc?tgtctccgga?cttgagctac?cagtgctttg?tgcttgcctc?4020

cttgaaggaa?cccatggacc?agaagcgcta?tgcctccagc?ccctactcgg?atgagatcgt?4080

ggtccaggtg?acaccagccc?agcagcagga?ggagccggag?atgctgtggg?tgacgggtcc?4140

cgtgctggca?gtcatcctca?tcatcctcat?tgtcatcgcc?atcctcttgt?tcaaaaggaa?4200

aaggacccac?tctccgtcct?ctaaggatga?gcagtcgatc?ggactgaagg?actccttgct?4260

ggcccactcc?tctgaccctg?tggagatgcg?gaggctcaac?taccagaccc?caggtatgcg?4320

agaccaccca?cccatcccca?tcaccgacct?ggcggacaac?atcgagcgcc?tcaaagccaa?4380

cgatggcctc?aagttctccc?aggagtatga?gtccatcgac?cctggacagc?agttcacgtg?4440

ggagaattca?aacctggagg?tgaacaagcc?caagaaccgc?tatgcgaatg?tcatcgccta?4500

cgaccactct?cgagtcatcc?ttacctctat?cgatggcgtc?cccgggagtg?actacatcaa?4560

tgccaactac?atcgatggct?accgcaagca?gaatgcctac?atcgccacgc?agggccccct?4620

gcccgagacc?atgggcgatt?tctggagaat?ggtgtgggaa?cagcgcacgg?ccactgtggt?4680

catgatgaca?cggctggagg?agaagtcccg?ggtaaaatgt?gatcagtact?ggccagcccg?4740

tggcaccgag?acctgtggcc?ttattcaggt?gaccctgttg?gacacagtgg?agctggccac?4800

atacactgtg?cgcaccttcg?cactccacaa?gagtggctcc?agtgagaagc?gtgagctgcg?4860

tcagtttcag?ttcatggcct?ggccagacca?tggagttcct?gagtacccaa?ctcccatcct?4920

ggccttccta?cgacgggtca?aggcctgcaa?ccccctagac?gcagggccca?tggtggtgca?4980

ctgcagcgcg?ggcgtgggcc?gcaccggctg?cttcatcgtg?attgatgcca?tgttggagcg?5040

gatgaagcac?gagaagacgg?tggacatcta?tggccacgtg?acctgcatgc?gatcacagag?5100

gaactacatg?gtgcagacgg?aggaccagta?cgtgttcatc?catgaggcgc?tgctggaggc?5160

tgccacgtgc?ggccacacag?aggtgcctgc?ccgcaacctg?tatgcccaca?tccagaagct?5220

gggccaagtg?cctccagggg?agagtgtgac?cgccatggag?ctcgagttca?agttgctggc?5280

cagctccaag?gcccacacgt?cccgcttcat?cagcgccaac?ctgccctgca?acaagttcaa?5340

gaaccggctg?gtgaacatca?tgccctacga?attgacccgt?gtgtgtctgc?agcccatccg?5400

tggtgtggag?ggctctgact?acatcaatgc?cagcttcctg?gatggttata?gacagcagaa?5460

ggcctacata?gctacacagg?ggcctctggc?agagagcacc?gaggacttct?ggcgcatgct?5520

atgggagcac?aattccacca?tcatcgtcat?gctgaccaag?cttcgggaga?tgggcaggga?5580

gaaatgccac?cagtactggc?cagcagagcg?ctctgctcgc?taccagtact?ttgttgttga?5640

cccgatggct?gagtacaaca?tgccccagta?tatcctgcgt?gagttcaagg?tcacggatgc?5700

ccgggatggg?cagtcaagga?caatccggca?gttccagttc?acagactggc?cagagcaggg?5760

cgtgcccaag?acaggcgagg?gattcattga?cttcatcggg?caggtgcata?agaccaagga?5820

gcagtttgga?caggatgggc?ctatcacggt?gcactgcagt?gctggcgtgg?gccgcaccgg?5880

ggtgttcatc?actctgagca?tcgtcctgga?gcgcatgcgc?tatgagggcg?tggtcgacat?5940

gtttcagacc?gtgaagaccc?tgcgtacaca?gcgtcctgcc?atggtgcaga?cagaggacca?6000

gtatcagctg?tgctaccgtg?cggccctgga?gtacctcggc?agctttgacc?actatgcaac?6060

gtaactaccg?ctcccctctc?ctccgccacc?cccgccgtgg?ggctccggag?gggacccagc?6120

tcctctgagc?cataccgacc?atcgtccagc?cctcctacgc?agatgctgtc?actggcagag?6180

cacagcccac?ggggatcaca?gcgtttcagg?aacgttgcca?caccaatcag?agagcctaga?6240

acatccctgg?gcaagtggat?ggcccagcag?gcaggcactg?tggcccttct?gtccaccaga?6300

cccacctgga?gcccgcttca?agctctctgt?tgcgctcccg?catttctcat?gcttcttctc?6360

atggggtggg?gttggggcaa?agcctccttt?ttaatacatt?aagtggggta?gactgaggga?6420

ttttagcctc?ttccctctga?tttttccttt?cgcgaatccg?tatctgcaga?atgggccact?6480

gtaggggttg?gggtttattt?tgttttgttt?tttttttttt?tttgtatgac?ttctgctgaa?6540

ggacagaaca?ttgccttcct?cgtgcagagc?tggggctgcc?agcctgagcg?gaggctcggc?6600

cgtgggccgg?gaggcagtgc?tgatccggct?gctcctccag?cccttcagac?gagatcctgt?6660

ttcagctaaa?tgcagggaaa?ctcaatgttt?ttttaagttt?tgttttccct?ttaaagcctt?6720

tttttaggcc?acattgacag?tggtgggcgg?ggagaagata?gggaacactc?atccctggtc?6780

gtctatccca?gtgtgtgttt?aacattcaca?gcccagaacc?acagatgtgt?ctgggagagc?6840

ctggcaaggc?attcctcatc?accatcgtgt?ttgcaaaggt?taaaacaaaa?acaaaaaacc?6900

acaaaaataa?aaaacaaaaa?aaacaaaaaa?cccaaaaaaa?aaaaaaaaaa?gagtcagccc?6960

ttggcttctg?cttcaaaccc?tcaagagggg?aagcaactcc?gtgtgcctgg?ggttcccgag?7020

ggagctgctg?gctgacctgg?gcccacagag?cctggctttg?gtccccagca?ttgcagtatg?7080

gtgtggtgtt?tgtaggctgt?ggggtctggc?tgtgtggcca?aggtgaatag?cacaggttag?7140

ggtgtgtgcc?acaccccatg?cacctcaggg?ccaagcgggg?gcgtggctgg?cctttcaggt?7200

ccaggccagt?gggcctggta?gcacatgtct?gtcctcagag?caggggccag?atgattttcc?7260

tccctggttt?gcagctgttt?tcaaagcccc?cgataatcgc?tcttttccac?tccaagatgc?7320

cctcataaac?caatgtggca?agactactgg?acttctatca?atggtactct?aatcagtcct?7380

tattatccca?gcttgctgag?gggcagggag?agcgcctctt?cctctgggca?gcgctatcta?7440

gataggtaag?tgggggcggg?gaagggtgca?tagctgtttt?agctgaggga?cgtggtgccg?7500

acgtccccaa?acctagctag?gctaagtcaa?gatcaacatt?ccagggttgg?taatgttgga?7560

tgatgaaaca?ttcattttta?ccttgtggat?gctagtgctg?tagagttcac?tgttgtacac?7620

agtctgtttt?ctatttgtta?agaaaaacta?cagcatcatt?gcataattct?tgatggtaat?7680

aaatttgaat?aatcagattt?cttacaaaaa?aaaaaaaa 7718

<210>99

<211>1898

<212>PRT

＜213〉people (homo sapiens)

<400>99

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser

785 790 795 800

Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 910

Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val

930 935 940

Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr

945 950 955 960

Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1010 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser

1125 1130 1135

Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Asn?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Thr?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu

1875 1880 1885

Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>100

<211>1907

<212>PRT

＜213〉people (homo sapiens)

<400>100

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Trp?Arg?Pro?Glu?Glu?Ser?Glu?Asp?Tyr?Glu?Thr?Thr?Ile

770 775 780

Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr?Ser?Val?Thr?Val?Ala?Ala?Tyr

785 790 795 800

Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Ile?Val?Thr?Thr

805 810 815

Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr?Met?Met?Ile?Ser?Thr?Thr?Ala

820 825 830

Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His?Pro?Pro?Lys?Glu?Leu?Pro?Gly

835 840 845

Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr?Cys?Arg?Ala?Asp?Glu?Ala?Arg

850 855 860

Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp?Asp?Gln?His?Phe?Thr?Val?Thr

865 870 875 880

Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile?Phe?Arg?Leu?Ala?Ala?Lys?Asn

885 890 895

Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu?Lys?Glu?Ile?Arg?Thr?Pro?Glu

900 905 910

Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn?Leu?His?Val?Thr?Gly?Leu?Thr

915 920 925

Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp?Pro?Pro?Val?Leu?Ala?Glu?Arg

930 935 940

Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val?Val?Phe?Arg?Asp?Ile?Asn?Ser

945 950 955 960

Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr?Asp?Thr?Arg?Phe?Thr?Leu?Thr

965 970 975

Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp?Ile?Lys?Val?Arg?Ala?Trp?Thr

980 985 990

Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro?Ser?Ile?Gln?Ser?Arg?Thr?Met

995 1000 1005

Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn?Phe?Arg?Val?Ala?Ala?Ala?Met

1010 1015 1020

Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Val?Pro?Asp?Ser?Tyr?Lys?Ser

1025 1030 1035 1040

Ala?Val?Pro?Phe?Lys?Ile?Leu?Tyr?Asn?Gly?Gln?Ser?Val?Glu?Val?Asp

1045 1050 1055

Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala?Asp?Leu?Gln?Pro?Asn?Thr?Glu

1060 1065 1070

Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly?Ser?Ser?Ala?Gly?Gly?Leu?Gln

1075 1080 1085

His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro?Asp?Leu?Leu?Pro?His?Lys?Pro

1090 1095 1100

Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp?Gly?Arg?Phe?Asp?Leu?Ser?Met

1105 1110 1115 1120

Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val?Arg?Trp?Phe?Tyr?Ile?Val?Val

1125 1130 1135

Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser?Met?Leu?Thr?Pro?Arg?Trp?Ser

1140 1145 1150

Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu?Leu?Leu?Glu?Ala?Ile?Glu?Gln

1155 1160 1165

Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg?Arg?Gln?Ala?Glu?Arg?Leu?Lys

1170 1175 1180

Pro?Tyr?Val?Ala?Ala?Gln?Leu?Asp?Val?Leu?Pro?Glu?Thr?Phe?Thr?Leu

1185 1190 1195 1200

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

1205 1210 1215

Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu?Ala?Ser?Leu?Lys?Glu?Pro?Met

1220 1225 1230

Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro?Tyr?Ser?Asp?Glu?Ile?Val?Val

1235 1240 1245

Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu?Glu?Pro?Glu?Met?Leu?Trp?Val

1250 1255 1260

Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu?Ile?Ile?Leu?Ile?Val?Ile?Ala

1265 1270 1275 1280

Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr?His?Ser?Pro?Ser?Ser?Lys?Asp

1285 1290 1295

Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser?Leu?Leu?Ala?His?Ser?Ser?Asp

1300 1305 1310

Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr?Gln?Thr?Pro?Gly?Met?Arg?Asp

1315 1320 1325

His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu?Ala?Asp?Asn?Ile?Glu?Arg?Leu

1330 1335 1340

Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp

1345 1350 1355 1360

Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn?Ser?Asn?Leu?Glu?Val?Asn?Lys

1365 1370 1375

Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val

1380 1385 1390

Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro?Gly?Ser?Asp?Tyr?Ile?Asn?Ala

1395 1400 1405

Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln

1410 1415 1420

Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu

1425 1430 1435 1440

Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser

1445 1450 1455

Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ala?Arg?Gly?Thr?Glu?Thr?Cys

1460 1465 1470

Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr

1475 1480 1485

Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys?Ser?Gly?Ser?Ser?Glu?Lys?Arg

1490 1495 1500

Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala?Trp?Pro?Asp?His?Gly?Val?Pro

1505 1510 1515 1520

Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Ala?Cys

1525 1530 1535

Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val

1540 1545 1550

Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Met

1555 1560 1565

Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Cys?Met?Arg

1570 1575 1580

Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Val?Phe?Ile

1585 1590 1595 1600

His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr?Cys?Gly?His?Thr?Glu?Val?Pro

1605 1610 1615

Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln?Lys?Leu?Gly?Gln?Val?Pro?Pro

1620 1625 1630

Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu?Glu?Phe?Lys?Leu?Leu?Ala?Ser

1635 1640 1645

Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn

1650 1655 1660

Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Leu?Thr?Arg

1665 1670 1675 1680

Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn

1685 1690 1695

Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr

1700 1705 1710

Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp

1715 1720 1725

Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met

1730 1735 1740

Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg

1745 1750 1755 1760

Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln

1765 1770 1775

Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser

1780 1785 1790

Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val

1795 1800 1805

Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys

1810 1815 1820

Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Thr?Val?His?Cys?Ser

1825 1830 1835 1840

Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr?Leu?Ser?Ile?Val?Leu

1845 1850 1855

Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Met?Phe?Gln?Thr?Val?Lys

1860 1865 1870

Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr

1875 1880 1885

Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His

1890 1895 1900

Tyr?Ala?Thr

1905

<210>101

<211>1888

<212>PRT

＜213〉people (homo sapiens)

<400>101

Met?Val?Pro?Leu?Val?Pro?Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly

1 5 10 15

Ala?His?Gly?Asp?Ser?Lys?Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln

20 25 30

Thr?Gly?Leu?Ser?Gly?Gly?Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly

35 40 45

Glu?Pro?Lys?Pro?Arg?Ile?Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser

50 55 60

Ser?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val

65 70 75 80

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

85 90 95

Cys?Thr?Ala?Thr?Asn?Ser?Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu

100 105 110

Ser?Val?Leu?Glu?Glu?Glu?Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp

115 120 125

Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met

130 135 140

Leu?Cys?Ala?Ala?Gly?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys

145 150 155 160

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

165 170 175

Leu?Arg?Ser?Gly?Ala?Leu?Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln

180 185 190

Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser

195 200 205

Ala?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe

210 215 220

Ser?Ile?Pro?Pro?Ser?Ser?Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn

225 230 235 240

Leu?Thr?Cys?Val?Ala?Val?Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met

245 250 255

Met?Gly?Ala?Glu?Glu?Leu?Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg

260 265 270

Asn?Val?Leu?Glu?Leu?Ser?Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys

275 280 285

Val?Ala?Ile?Ser?Ser?Leu?Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr

290 295 300

Val?Lys?Ala?Leu?Pro?Lys?Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr

305 310 315 320

Thr?Ala?Thr?Ser?Val?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro

325 330 335

Val?Thr?Tyr?Tyr?Gly?Ile?Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro

340 345 350

Phe?Gln?Glu?Val?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly

355 360 365

Leu?Ser?Pro?Phe?Ser?Glu?Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser

370 375 380

Ile?Gly?Arg?Gly?Pro?Pro?Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu

385 390 395 400

Gln?Ala?Pro?Ser?Ser?Pro?Pro?Arg?Arg?Val?Gln?Ala?Arg?Met?Leu?Ser

405 410 415

Ala?Ser?Thr?Met?Leu?Val?Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly

420 425 430

Leu?Val?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro

435 440 445

Pro?Asn?Ala?Trp?His?Lys?His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr

450 455 460

Val?Gly?Ser?Leu?Leu?Pro?Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala

465 470 475 480

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

485 490 495

Thr?Gln?Gln?Gly?Val?Pro?Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val

500 505 510

Glu?Ser?Asp?Thr?Arg?Ile?Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu

515 520 525

Arg?Ile?Ile?Met?Tyr?Glu?Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp

530 535 540

Gln?Gln?His?Lys?Val?Thr?Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu

545 550 555 560

Asp?Leu?Lys?Pro?Asp?Thr?Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser

565 570 575

Asp?Met?Gly?Val?Gly?Val?Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala

580 585 590

Gln?Ser?Thr?Pro?Ser?Ala?Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met

595 600 605

Gly?Ser?Thr?Thr?Val?Arg?Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser

610 615 620

Arg?Asn?Gly?Val?Ile?Thr?Gln?Tyr?Ser?Val?Ala?His?Glu?Ala?Val?Asp

625 630 635 640

Gly?Glu?Asp?Arg?Gly?Arg?His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His

645 650 655

Ser?Ser?Trp?Asp?Leu?Val?Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val

660 665 670

Trp?Val?Arg?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro

675 680 685

Val?Leu?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys

690 695 700

Val?Glu?Val?Glu?Pro?Leu?Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys

705 710 715 720

Leu?Pro?Val?Pro?Ser?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val

725 730 735

Thr?Tyr?Val?Arg?Leu?Glu?Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile

740 745 750

Gln?Asp?Val?Met?Leu?Ala?Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu

755 760 765

Thr?Pro?Glu?Thr?Thr?Tyr?Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys

770 775 780

Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala

785 790 795 800

Val?Pro?Gly?Arg?Pro?Thr?Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr

805 810 815

Ala?Leu?Leu?Gln?Trp?His?Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu

820 825 830

Gly?Tyr?Arg?Leu?Gln?Tyr?Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr

835 840 845

Ile?Asp?Phe?Gly?Lys?Asp?Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His

850 855 860

Lys?Gly?Thr?Thr?Tyr?Ile?Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly

865 870 875 880

Leu?Gly?Glu?Glu?Phe?Glu?Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro

885 890 895

Ser?Gly?Phe?Pro?Gln?Asn?Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr

900 905 910

Thr?Glu?Leu?Ala?Trp?Asp?Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg

915 920 925

Ile?Ile?Ser?Tyr?Thr?Val?Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu

930 935 940

Leu?Gln?Asn?Ile?Thr?Thr?Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?LeuLys

945 950 955 960

Pro?Asp?Thr?Thr?Tyr?Asp?Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly

965 970 975

Ser?Gly?Pro?Leu?Ser?Pro?Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu

980 985 990

Gln?Val?Phe?Ala?Lys?Asn?Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser

995 1000 1005

Val?Leu?Leu?Ser?Trp?Glu?Val?Pro?Asp?Ser?Tyr?Lys?Ser?Ala?Val?Pro

1010 1015 1020

Phe?Lys?Ile?Leu?Tyr?Asn?Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser

1025 1030 1035 1040

Met?Arg?Lys?Leu?Ile?Ala?Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe

1045 1050 1055

Val?Leu?Met?Ash?Arg?Gly?Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val

1060 1065 1070

Ser?Ile?Arg?Thr?Ala?Pro?Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala

1075 1080 1085

Ser?Ala?Tyr?Ile?Glu?Asp?Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val

1090 1095 1100

Gln?Asp?Pro?Ser?Leu?Val?Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile

1105 1110 1115 1120

Asp?Arg?Val?Gly?Gly?Ser?Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu

1125 1130 1135

Glu?Leu?Glu?Leu?Asp?Glu?Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu

1140 1145 1150

Glu?Gln?Arg?Arg?Arg?Arg?Arg?Gln?Ala?Glu?Arg?Leu?Lys?Pro?Tyr?Val

1155 1160 1165

Ala?Ala?Gln?Leu?Asp?Val?Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys

1170 1175 1180

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

1185 1190 1195 1200

Tyr?Gln?Cys?Phe?Val?Leu?Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys

1205 1210 1215

Arg?Tyr?Ala?Ser?Ser?Pro?Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr

1220 1225 1230

Pro?Ala?Gln?Gln?Gln?Glu?Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro

1235 1240 1245

Val?Leu?Ala?Val?Ile?Leu?Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu

1250 1255 1260

Phe?Lys?Arg?Lys?Arg?Thr?His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser

1265 1270 1275 1280

Ile?Gly?Leu?Lys?Asp?Ser?Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu

1285 1290 1295

Met?Arg?Arg?Leu?Asn?Tyr?Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro

1300 1305 1310

Ile?Pro?Ile?Thr?Asp?Leu?Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn

1315 1320 1325

Asp?Gly?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln

1330 1335 1340

Gln?Phe?Thr?Trp?Glu?Asn?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn

1345 1350 1355 1360

Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr

1365 1370 1375

Ser?Ile?Asp?Gly?Val?Pro?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile

1380 1385 1390

Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

1395 1400 1405

Pro?Glu?Thr?Met?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr

1410 1415 1420

Ala?Thr?Val?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys

1425 1430 1435 1440

Cys?Asp?Gln?Tyr?Trp?Pro?Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile

1445 1450 1455

Gln?Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg

1460 1465 1470

Thr?Phe?Ala?Leu?His?Lys?Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg

1475 1480 1485

Gln?Phe?Gln?Phe?Met?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro

1490 1495 1500

Thr?Pro?Ile?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu

1505 1510 1515 1520

Asp?Ala?Gly?Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1525 1530 1535

Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu

1540 1545 1550

Lys?Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg

1555 1560 1565

Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala

1570 1575 1580

Leu?Leu?Glu?Ala?Ala?Thr?Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn

1585 1590 1595 1600

Leu?Tyr?Ala?His?Ile?Gln?Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser

1605 1610 1615

Val?Thr?Ala?Met?Glu?Leu?Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala

1620 1625 1630

His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys

1635 1640 1645

Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu

1650 1655 1660

Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe

1665 1670 1675 1680

Leu?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro

1685 1690 1695

Leu?Ala?Glu?Ser?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn

1700 1705 1710

Ser?Thr?Ile?Ile?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu

1715 1720 1725

Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr

1730 1735 1740

Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu

1745 1750 1755 1760

Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile

1765 1770 1775

Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr

1780 1785 1790

Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu

1795 1800 1805

Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Thr?Val?His?Cys?Ser?Ala?Gly?Val

1810 1815 1820

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

1825 1830 1835 1840

Arg?Tyr?Glu?Gly?Val?Val?Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg

1845 1850 1855

Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys

1860 1865 1870

Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1875 1880 1885

<210>102

<211>7691

<212>DNA

＜213〉people (homo sapiens)

<400>102

cgggagcggc?gggagcggtg?gcggcggcag?aggcggcggc?tccagcttcg?gctccggctc?60

gggctcgggc?tccggctccg?gctccggctc?cggctccagc?tcgggtggcg?gtggcgggag?120

cgggaccagg?tggaggcggc?ggcggcagag?gagtgggagc?agcggcccta?gcggcttgcg?180

gggggacatg?cggaccgacg?gcccctggat?aggcggaagg?agtggaggcc?ctggtgcccg?240

gcccttggtg?ctgagtatcc?agcaagagtg?accggggtga?agaagcaaag?actcggttga?300

ttgtcctggg?ctgtggctgg?ctgtggagct?agagccctgg?atggcccctg?agccagcccc?360

agggaggacg?atggtgcccc?ttgtgcctgc?actggtgatg?cttggtttgg?tggcaggcgc?420

ccatggtgac?agcaaacctg?tcttcattaa?agtccctgag?gaccagactg?ggctgtcagg?480

aggggtagcc?tccttcgtgt?gccaagctac?aggagaaccc?aagccgcgca?tcacatggat?540

gaagaagggg?aagaaagtca?gctcccagcg?cttcgaggtc?attgagtttg?atgatggggc?600

agggtcagtg?cttcggatcc?agccattgcg?ggtgcagcga?gatgaagcca?tctatgagtg?660

tacagctact?aacagcctgg?gtgagatcaa?cactagtgcc?aagctctcag?tgctcgaaga?720

ggaacagctg?ccccctgggt?tcccttccat?cgacatgggg?cctcagctga?aggtggtgga?780

gaaggcacgc?acagccacca?tgctatgtgc?cgcaggcgga?aatccagacc?ctgagatttc?840

ttggttcaag?gacttccttc?ctgtagaccc?tgccacgagc?aacggccgca?tcaagcagct?900

gcgttcaggt?gccttgcaga?tagagagcag?tgaggaatcc?gaccaaggca?agtacgagtg?960

tgtggcgacc?aactcggcag?gcacacgtta?ctcagcccct?gcgaacctgt?atgtgcgagt?1020

gcgccgcgtg?gctcctcgtt?tctccatccc?tcccagcagc?caggaggtga?tgccaggcgg?1080

cagcgtgaac?ctgacatgcg?tggcagtggg?tgcacccatg?ccctacgtga?agtggatgat?1140

gggggccgag?gagctcacca?aggaggatga?gatgccagtt?ggccgcaacg?tcctggagct?1200

cagcaatgtc?gtacgctctg?ccaactacac?ctgtgtggcc?atctcctcgc?tgggcatgat?1260

cgaggccaca?gcccaggtca?cagtgaaagc?tcttccaaag?cctccgattg?atcttgtggt?1320

gacagagaca?actgccacca?gtgtcaccct?cacctgggac?tctgggaact?cggagcctgt?1380

aacctactat?ggcatccagt?accgcgcagc?gggcacggag?ggcccctttc?aggaggtgga?1440

tggtgtggcc?accacccgct?acagcattgg?cggcctcagc?cctttctcgg?aatatgcctt?1500

ccgcgtgctg?gcggtgaaca?gcatcgggcg?agggccgccc?agcgaggcag?tgcgggcacg?1560

cacgggagaa?caggcgccct?ccagcccacc?gcgccgcgtg?caggcacgca?tgctgagcgc?1620

cagcaccatg?ctggtgcagt?gggagcctcc?cgaggagccc?aacggcctgg?tgcggggata?1680

ccgcgtctac?tatactccgg?actcccgccg?ccccccgaac?gcctggcaca?agcacaacac?1740

cgacgcgggg?ctcctcacga?ccgtgggcag?cctgctgcct?ggcatcacct?acagcctgcg?1800

cgtgcttgcc?ttcaccgccg?tgggcgatgg?ccctcccagc?cccaccatcc?aggtcaagac?1860

gcagcaggga?gtgcctgccc?agcccgcgga?cttccaggcc?gaggtggagt?cggacaccag?1920

gatccagctc?tcgtggctgc?tgccccctca?ggagcggatc?atcatgtatg?aactggtgta?1980

ctgggcggca?gaggacgaag?accaacagca?caaggtcacc?ttcgacccaa?cctcctccta?2040

cacactagag?gacctgaagc?ctgacacact?ctaccgcttc?cagctggctg?cacgctcgga?2100

tatgggggtg?ggcgtcttca?cccccaccat?tgaggcccgc?acagcccagt?ccaccccctc?2160

cgcccctccc?cagaaggtga?tgtgtgtgag?catgggctcc?accacggtcc?gggtaagttg?2220

ggtcccgccg?cctgccgaca?gccgcaacgg?cgttatcacc?cagtactccg?tggcccacga?2280

ggcggtggac?ggcgaggacc?gcgggcggca?tgtggtggat?ggcatcagcc?gtgagcactc?2340

cagctgggac?ctggtgggcc?tggagaagtg?gacggagtac?cgggtgtggg?tgcgggcaca?2400

cacagacgtg?ggccccggcc?ccgagagcag?cccggtgctg?gtgcgcaccg?atgaggacgt?2460

gcccagcggg?cctccgcgga?aggtggaggt?ggagccactg?aactccactg?ctgtgcatgt?2520

ctactggaag?ctgcctgtcc?ccagcaagca?gcatggccag?atccgcggct?accaggtcac?2580

ctacgtgcgg?ctggagaatg?gcgagccccg?tggactcccc?atcatccaag?acgtcatgct?2640

agccgaggcc?caggaaacca?ctatcagcgg?cctgaccccg?gagaccacct?actccgttac?2700

tgttgctgcc?tataccacca?agggggatgg?tgcccgcagc?aagcccaaaa?ttgtcactac?2760

aacaggtgca?gtcccaggcc?ggcccaccat?gatgatcagc?accacggcca?tgaacactgc?2820

gctgctccag?tggcacccac?ccaaggaact?gcctggcgag?ctgctgggct?accggctgca?2880

gtactgccgg?gccgacgagg?cgcggcccaa?caccatagat?ttcggcaagg?atgaccagca?2940

cttcacagtc?accggcctgc?acaaggggac?cacctacatc?ttccggcttg?ctgccaagaa?3000

ccgggctggc?ttgggtgagg?agttcgagaa?ggagatcagg?acccccgagg?acctgcccag?3060

cggcttcccc?caaaacctgc?atgtgacagg?actgaccacg?tctaccacag?aactggcctg?3120

ggacccgcca?gtgctggcgg?agaggaacgg?gcgcatcatc?agctacaccg?tggtgttccg?3180

agacatcaac?agccaacagg?agctgcagaa?catcacgaca?gacacccgct?ttacccttac?3240

tggcctcaag?ccagacacca?cttacgacat?caaggtccgc?gcatggacca?gcaaaggctc?3300

tggcccactc?agccccagca?tccagtcccg?gaccatgccg?gtggagcaag?tgtttgccaa?3360

gaacttccgg?gtggcggctg?caatgaagac?gtctgtgctg?ctcagctggg?aggttcccga?3420

ctcctataag?tcagctgtgc?cctttaagat?tctgtacaat?gggcagagtg?tggaggtgga?3480

cgggcactcg?atgcggaagc?tgatcgcaga?cctgcagccc?aacacagagt?actcgtttgt?3540

gctgatgaac?cgtggcagca?gcgcaggggg?cctgcagcac?ctggtgtcca?tccgcacagc?3600

ccccgacctc?ctgcctcaca?agccgctgcc?tgcctctgcc?tacatagagg?acggccgctt?3660

cgatctctcc?atgccccatg?tgcaagaccc?ctcgcttgtc?aggtggttct?acattgttgt?3720

ggtacccatt?gaccgtgtgg?gcgggagcat?gctgacgcca?aggtggagca?cacccgagga?3780

actggagctg?gacgagcttc?tagaagccat?cgagcaaggc?ggagaggagc?agcggcggcg?3840

gcggcggcag?gcagaacgtc?tgaagccata?tgtggctgct?caactggatg?tgctcccgga?3900

gacctttacc?ttgggggaca?agaagaacta?ccggggcttc?tacaaccggc?ccctgtctcc?3960

ggacttgagc?taccagtgct?ttgtgcttgc?ctccttgaag?gaacccatgg?accagaagcg?4020

ctatgcctcc?agcccctact?cggatgagat?cgtggtccag?gtgacaccag?cccagcagca?4080

ggaggagccg?gagatgctgt?gggtgacggg?tcccgtgctg?gcagtcatcc?tcatcatcct?4140

cattgtcatc?gccatcctct?tgttcaaaag?gaaaaggacc?cactctccgt?cctctaagga?4200

tgagcagtcg?atcggactga?aggactcctt?gctggcccac?tcctctgacc?ctgtggagat?4260

gcggaggctc?aactaccaga?ccccaggtat?gcgagaccac?ccacccatcc?ccatcaccga?4320

cctggcggac?aacatcgagc?gcctcaaagc?caacgatggc?ctcaagttct?cccaggagta?4380

tgagtccatc?gaccctggac?agcagttcac?gtgggagaat?tcaaacctgg?aggtgaacaa?4440

gcccaagaac?cgctatgcga?atgtcatcgc?ctacgaccac?tctcgagtca?tccttacctc?4500

tatcgatggc?gtccccggga?gtgactacat?caatgccaac?tacatcgatg?gctaccgcaa?4560

gcagaatgcc?tacatcgcca?cgcagggccc?cctgcccgag?accatgggcg?atttctggag?4620

aatggtgtgg?gaacagcgca?cggccactgt?ggtcatgatg?acacggctgg?aggagaagtc?4680

ccgggtaaaa?tgtgatcagt?actggccagc?ccgtggcacc?gagacctgtg?gccttattca?4740

ggtgaccctg?ttggacacag?tggagctggc?cacatacact?gtgcgcacct?tcgcactcca?4800

caagagtggc?tccagtgaga?agcgtgagct?gcgtcagttt?cagttcatgg?cctggccaga?4860

ccatggagtt?cctgagtacc?caactcccat?cctggccttc?ctacgacggg?tcaaggcctg?4920

caacccccta?gacgcagggc?ccatggtggt?gcactgcagc?gcgggcgtgg?gccgcaccgg?4980

ctgcttcatc?gtgattgatg?ccatgttgga?gcggatgaag?cacgagaaga?cggtggacat?5040

ctatggccac?gtgacctgca?tgcgatcaca?gaggaactac?atggtgcaga?cggaggacca?5100

gtacgtgttc?atccatgagg?cgctgctgga?ggctgccacg?tgcggccaca?cagaggtgcc?5160

tgcccgcaac?ctgtatgccc?acatccagaa?gctgggccaa?gtgcctccag?gggagagtgt?5220

gaccgccatg?gagctcgagt?tcaagttgct?ggccagctcc?aaggcccaca?cgtcccgctt?5280

catcagcgcc?aacctgccct?gcaacaagtt?caagaaccgg?ctggtgaaca?tcatgcccta?5340

cgaattgacc?cgtgtgtgtc?tgcagcccat?ccgtggtgtg?gagggctctg?actacatcaa?5400

tgccagcttc?ctggatggtt?atagacagca?gaaggcctac?atagctacac?aggggcctct?5460

ggcagagagc?accgaggact?tctggcgcat?gctatgggag?cacaattcca?ccatcatcgt?5520

catgctgacc?aagcttcggg?agatgggcag?ggagaaatgc?caccagtact?ggccagcaga?5580

gcgctctgct?cgctaccagt?actttgttgt?tgacccgatg?gctgagtaca?acatgcccca?5640

gtatatcctg?cgtgagttca?aggtcacgga?tgcccgggat?gggcagtcaa?ggacaatccg?5700

gcagttccag?ttcacagact?ggccagagca?gggcgtgccc?aagacaggcg?agggattcat?5760

tgacttcatc?gggcaggtgc?ataagaccaa?ggagcagttt?ggacaggatg?ggcctatcac?5820

ggtgcactgc?agtgctggcg?tgggccgcac?cggggtgttc?atcactctga?gcatcgtcct?5880

ggagcgcatg?cgctatgagg?gcgtggtcga?catgtttcag?accgtgaaga?ccctgcgtac?5940

acagcgtcct?gccatggtgc?agacagagga?ccagtatcag?ctgtgctacc?gtgcggccct?6000

ggagtacctc?ggcagctttg?accactatgc?aacgtaacta?ccgctcccct?ctcctccgcc?6060

acccccgccg?tggggctccg?gaggggaccc?agctcctctg?agccataccg?accatcgtcc?6120

agccctccta?cgcagatgct?gtcactggca?gagcacagcc?cacggggatc?acagcgtttc?6180

aggaacgttg?ccacaccaat?cagagagcct?agaacatccc?tgggcaagtg?gatggcccag?6240

caggcaggca?ctgtggccct?tctgtccacc?agacccacct?ggagcccgct?tcaagctctc?6300

tgttgcgctc?ccgcatttct?catgcttctt?ctcatggggt?ggggttgggg?caaagcctcc?6360

tttttaatac?attaagtggg?gtagactgag?ggattttagc?ctcttccctc?tgatttttcc?6420

tttcgcgaat?ccgtatctgc?agaatgggcc?actgtagggg?ttggggttta?ttttgttttg?6480

tttttttttt?ttttttgtat?gacttctgct?gaaggacaga?acattgcctt?cctcgtgcag?6540

agctggggct?gccagcctga?gcggaggctc?ggccgtgggc?cgggaggcag?tgctgatccg?6600

gctgctcctc?cagcccttca?gacgagatcc?tgtttcagct?aaatgcaggg?aaactcaatg?6660

tttttttaag?ttttgttttc?cctttaaagc?ctttttttag?gccacattga?cagtggtggg?6720

cggggagaag?atagggaaca?ctcatccctg?gtcgtctatc?ccagtgtgtg?tttaacattc?6780

acagcccaga?accacagatg?tgtctgggag?agcctggcaa?ggcattcctc?atcaccatcg?6840

tgtttgcaaa?ggttaaaaca?aaaacaaaaa?accacaaaaa?taaaaaacaa?aaaaaacaaa?6900

aaacccaaaa?aaaaaaaaaa?aaagagtcag?cccttggctt?ctgcttcaaa?ccctcaagag?6960

gggaagcaac?tccgtgtgcc?tggggttccc?gagggagctg?ctggctgacc?tgggcccaca?7020

gagcctggct?ttggtcccca?gcattgcagt?atggtgtggt?gtttgtaggc?tgtggggtct?7080

ggctgtgtgg?ccaaggtgaa?tagcacaggt?tagggtgtgt?gccacacccc?atgcacctca?7140

gggccaagcg?ggggcgtggc?tggcctttca?ggtccaggcc?agtgggcctg?gtagcacatg?7200

tctgtcctca?gagcaggggc?cagatgattt?tcctccctgg?tttgcagctg?ttttcaaagc?7260

ccccgataat?cgctcttttc?cactccaaga?tgccctcata?aaccaatgtg?gcaagactac?7320

tggacttcta?tcaatggtac?tctaatcagt?ccttattatc?ccagcttgct?gaggggcagg?7380

gagagcgcct?cttcctctgg?gcagcgctat?ctagataggt?aagtgggggc?ggggaagggt?7440

gcatagctgt?tttagctgag?ggacgtggtg?ccgacgtccc?caaacctagc?taggctaagt?7500

caagatcaac?attccagggt?tggtaatgtt?ggatgatgaa?acattcattt?ttaccttgtg?7560

gatgctagtg?ctgtagagtt?cactgttgta?cacagtctgt?tttctatttg?ttaagaaaaa?7620

ctacagcatc?attgcataat?tcttgatggt?aataaatttg?aataatcaga?tttcttacaa?7680

aaaaaaaaaa?a 7691

<210>103

<211>1898

<212>PRT

＜213〉people (homo sapiens)

<400>103

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

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Val?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Ile?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Glu

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Ser?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Ala?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

Pro?Ala?Thr?Ser?Asn?Gly?Arg?Ile?Lys?Gln?Leu?Arg?Ser?Gly?Ala?Leu

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Val?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Ser?Glu?Pro?Val?Thr?Tyr?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Glu?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Pro?Asp?Ser?Arg?Arg?Pro?Pro?Asn?Ala?Trp?His?Lys

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Ile?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Gln?Pro?Ala?Asp?Phe?Gln?Ala?Glu?Val?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Ile?Met?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Asp?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Met?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Ile?Glu?Ala?Arg?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Met?Cys?Val?Ser?Met?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Val?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Gly?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Val

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Tyr?Trp?Lys?Leu?Pro?Val?Pro?Ser?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Leu?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

Ser?Val?Thr?Val?Ala?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser

785 790 795 800

Lys?Pro?Lys?Ile?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Ile?Ser?Thr?Thr?Ala?Met?Asn?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Cys?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Thr?Thr?Tyr?Ile

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Arg?Thr?Pro?Glu?Asp?Leu?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 910

Leu?His?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Ala?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Arg?Ile?Ile?Ser?Tyr?Thr?Val

930 935 940

Val?Phe?Arg?Asp?Ile?Asn?Ser?Gln?Gln?Glu?Leu?Gln?Asn?Ile?Thr?Thr

945 950 955 960

Asp?Thr?Arg?Phe?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

Ile?Lys?Val?Arg?Ala?Trp?Thr?Ser?Lys?Gly?Ser?Gly?Pro?Leu?Ser?Pro

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Ala?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1010 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?His?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Tyr?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Asp?Leu?Ser?Met?Pro?His?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Ser

1125 1130 1135

Met?Leu?Thr?Pro?Arg?Trp?Ser?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Gly?Glu?Glu?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Glu?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Asn?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His?Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Ala?Arg?Gly?Thr?Glu?Thr?Cys?Gly?Leu?Ile?Gln?Val?Thr?Leu?Leu?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Val?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Thr

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu

1875 1880 1885

Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>104

<211>1948

<212>PRT

＜213〉people (homo sapiens)

<400>104

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

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

195 200 205

Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Val

210 215 220

Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Glu?Leu?Arg?Glu?Val

225 230 235 240

Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser?His?Glu?Ile

245 250 255

Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro

260 265 270

Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu

275 280 285

Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr?Asp?Val?Lys

290 295 300

Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu?Gly?Val?Ile

305 310 315 320

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

325 330 335

Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr?Ile?Thr?Trp

340 345 350

Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile?Glu?Tyr?Lys

355 360 365

Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp?Ile?Thr?Thr

370 375 380

Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu?Tyr?Glu?Ile

385 390 395 400

Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser

405 410 415

Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala?Pro?Arg?Asn

420 425 430

Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val?Gln?Trp?Glu

435 440 445

Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr

450 455 460

Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys?His?Asn?Val

465 470 475 480

Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Glu?Asp?Glu?Thr

485 490 495

Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu

500 505 510

Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro?Gly?Gln?Pro

515 520 525

Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile?Thr?Leu?Ser

530 535 540

Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu?Leu?Leu?Phe

545 550 555 560

Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe?Asp?Pro?Thr

565 570 575

Thr Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu?Tyr?Ala?Phe

580 585 590

Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe?Thr?Pro?Val

595 600 605

Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp

610 615 620

Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val?Ser?Trp?Arg

625 630 635 640

Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly?Tyr?Ser?Val

645 650 655

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

660 665 670

Gly?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala?Leu?Glu?Lys

675 680 685

Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu?Val?Gly?Pro

690 695 700

Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro

705 710 715 720

Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn?Ala?Thr?Ala

725 730 735

Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln?His?Gly?Gln

740 745 750

Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly?Ala?Glu?Ala

755 760 765

Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp

770 775 780

Glu?Thr?Asp?Asp?Thr?Ala?Glu?Tyr?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln

785 790 795 800

Pro?Glu?Thr?Ala?Tyr?Ser?Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly

805 810 815

Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val

820 825 830

Leu?Gly?Arg?Pro?Thr?Leu?Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu

835 840 845

Leu?Ala?Arg?Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu

850 855 860

Gly?Tyr?Arg?Leu?Gln?Phe?Gly?Arg?Glu?Asp?Ser?Thr?Pro?Leu?Ala?Thr

865 870 875 880

Leu?Glu?Phe?Pro?Pro?Ser?Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His

885 890 895

Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly

900 905 910

Leu?Gly?Glu?Glu?Ala?Ala?Glu?Val?Leu?Ser?Ile?Pro?Glu?Asp?Thr?Pro

915 920 925

Arg?Gly?His?Pro?Gln?Ile?Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly

930 935 940

Thr?Val?Leu?Leu?Arg?Trp?Leu?Pro?Pro?Val?Pro?Ala?Glu?Arg?Asn?Gly

945 950 955 960

Ala?Ile?Val?Lys?Tyr?Thr?Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly

965 970 975

Pro?Ala?Arg?Glu?Thr?Glu?Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu

980 985 990

Asn?Ala?Leu?Thr?Leu?Gln?Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu

995 1000 1005

Gln?Val?Arg?Ala?His?Thr?Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro

1010 1015 1020

Val?Arg?Tyr?Arg?Thr?Phe?Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe

1025 1030 1035 1040

Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe

1045 1050 1055

Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly

1060 1065 1070

Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His

1075 1080 1085

Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser

1090 1095 1100

Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn

1105 1110 1115 1120

Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly

1125 1130 1135

Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln

1140 1145 1150

Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln

1155 1160 1165

Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu

1170 1175 1180

Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg

1185 1190 1195 1200

Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu

1205 1210 1215

Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp

1220 1225 1230

Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala

1235 1240 1245

Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp

1250 1255 1260

Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu

1265 1270 1275 1280

Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1285 1290 1295

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser

1300 1305 1310

Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala

1315 1320 1325

Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile

1330 1335 1340

Asn?Phe?Gln?Thr?Pro?Asp?Ser?Gly?Leu?Arg?Ser?Pro?Leu?Arg?Glu?Pro

1345 1350 1355 1360

Gly?Phe?His?Phe?Glu?Ser?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala

1365 1370 1375

Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys

1380 1385 1390

Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?AsP?Pro?Gly?Gln?Gln?Phe?Thr?Trp

1395 1400 1405

Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn

1410 1415 1420

Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly

1425 1430 1435 1440

Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg

1445 1450 1455

Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe

1460 1465 1470

Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val

1475 1480 1485

Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr

1490 1495 1500

Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu

1505 1510 1515 1520

Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu

1525 1530 1535

His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe

1540 1545 1550

Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu

1555 1560 1565

Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro

1570 1575 1580

Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile

1585 1590 1595 1600

Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp

1605 1610 1615

Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val

1620 1625 1630

Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala

1635 1640 1645

Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr

1650 1655 1660

Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met

1665 1670 1675 1680

Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg

1685 1690 1695

Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val

1700 1705 1710

Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg

1715 1720 1725

Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr

1730 1735 1740

Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr

1745 1750 1755 1760

Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val

1765 1770 1775

Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln

1780 1785 1790

Tyr?Trp Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp

1795 1800 1805

Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys

1810 1815 1820

Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln

1825 1830 1835 1840

Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe

1845 1850 1855

Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln

1860 1865 1870

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

1875 1880 1885

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

1890 1895 1900

Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro

1905 1910 1915 1920

Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala

1925 1930 1935

Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1940 1945

<210>105

<211>6500

<212>DNA

＜213〉people (homo sapiens)

<400>105

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcagaaac?ctttgaaagc?actccgattc?840

gaggagccct?gcagattgaa?agcagtgagg?aaaccgacca?gggcaaatat?gagtgtgtgg?900

ccaccaacag?cgccggcgtg?cgctactcct?cacctgccaa?cctctacgtg?cgagagcttc?960

gagaagtccg?ccgcgtggcc?ccgcgcttct?ccatcctgcc?catgagccac?gagatcatgc?1020

cagggggcaa?cgtgaacatc?acctgcgtgg?ccgtgggctc?gcccatgcca?tacgtgaagt?1080

ggatgcaggg?ggccgaggac?ctgacccccg?aggatgacat?gcccgtgggt?cggaacgtgc?1140

tggaactcac?agatgtcaag?gactcggcca?actacacctg?cgtggccatg?tccagcctgg?1200

gcgtcattga?ggcggttgct?cagatcacgg?tgaaatctct?ccccaaagct?cccgggactc?1260

ccatggtgac?tgagaacaca?gccaccagca?tcaccatcac?gtgggactcg?ggcaacccag?1320

atcctgtgtc?ctattacgtc?atcgaatata?aatccaagag?ccaagacggg?ccgtatcaga?1380

ttaaagagga?catcaccacc?acacgttaca?gcatcggcgg?cctgagcccc?aactcggagt?1440

acgagatctg?ggtgtcggcc?gtcaactcca?tcggccaggg?gccccccagc?gagtccgtgg?1500

tcacccgcac?aggcgagcag?gccccggcca?gcgcgccgcg?gaacgtgcaa?gcccggatgc?1560

tcagcgcgac?caccatgatt?gtgcagtggg?aggagccggt?ggagcccaac?ggcctgatcc?1620

gcggctaccg?cgtctactac?accatggaac?cggagcaccc?cgtgggcaac?tggcagaagc?1680

acaacgtgga?cgacagcctg?ctgaccaccg?tgggcagcct?gctggaggac?gagacctaca?1740

ccgtgcgggt?gctcgccttc?acctccgtcg?gcgacgggcc?cctctcggac?cccatccagg?1800

tcaagacgca?gcagggagtg?ccgggccagc?ccatgaacct?gcgggccgag?gccaggtcgg?1860

agaccagcat?cacgctgtcc?tggagccccc?cgcggcagga?gagtatcatc?aagtacgagc?1920

tcctcttccg?ggaaggcgac?catggccggg?aggtgggaag?gaccttcgac?ccgacgactt?1980

cctacgtggt?ggaggacctg?aagcccaaca?cggagtacgc?cttccgcctg?gcggcccgct?2040

cgccgcaggg?cctgggcgcc?ttcacccccg?tggtgcggca?gcgcacgctg?cagtccaaac?2100

cgtcagcccc?ccctcaagac?gttaaatgtg?tcagcgtgcg?ctccacggcc?attttggtaa?2160

gttggcgccc?gccgccgccg?gaaacgcaca?acggggccct?ggtgggctac?agcgtccgct?2220

accgaccgct?gggctcagag?gacccggaac?ccaaggaggt?gaacggcatc?cccccgacca?2280

ccactcagat?cctgctggag?gccttggaga?agtggaccca?gtaccgcatc?acgactgtcg?2340

ctcacacaga?ggtgggacca?gggcccgaga?gctcgcccgt?ggtcgtccgc?accgacgagg?2400

atgtgcccag?cgcgccgccg?cggaaggtgg?aggcggaggc?gctcaacgcc?acggccatcc?2460

gcgtgctgtg?gcgctcgccc?gcgcccggcc?ggcagcacgg?ccagatccgc?ggctaccagg?2520

tccactacgt?gcgcatggag?ggcgccgagg?cccgcgggcc?gccgcgcatc?aaggacgtca?2580

tgctggccga?tgcccagtgg?gagacggatg?acacggccga?atatgagatg?gtcatcacaa?2640

acttgcagcc?tgagaccgcg?tactccatca?cggtagccgc?ctacaccatg?aagggcgatg?2700

gcgctcgcag?caaacccaag?gtggttgtga?ccaagggagc?agtgctgggc?cgcccaaccc?2760

tgtcggtgca?gcagaccccc?gagggcagcc?tgctggcacg?ctgggagccc?ccggctggca?2820

ccgcggagga?ccaggtgctg?ggctaccgcc?tgcagtttgg?ccgtgaggac?tcgacgcccc?2880

tggccaccct?ggagttcccg?ccctccgagg?accgctacac?ggcatcaggc?gtgcacaagg?2940

gggccacgta?tgtgttccgg?cttgcggccc?ggagccgcgg?cggcctgggc?gaggaggcag?3000

ccgaggtcct?gagcatcccg?gaggacacgc?cccgtggcca?cccgcagatt?ctggaggcgg?3060

ccggcaacgc?ctcggccggg?accgtccttc?tccgctggct?gccacccgtg?cccgccgagc?3120

gcaacggggc?catcgtcaaa?tacacggtgg?ccgtgcggga?ggccggtgcc?ctgggccctg?3180

cccgagagac?tgagctgccg?gcagcggctg?agccgggcgc?ggagaacgcg?ctcacgctgc?3240

agggcctgaa?gcccgacacg?gcctatgacc?tccaagtgcg?agcccacacg?cgccggggcc?3300

ctggcccctt?cagccccccc?gtccgctacc?ggacgttcct?gcgggaccaa?gtctcgccca?3360

agaacttcaa?ggtgaaaatg?atcatgaaga?catcagttct?gctcagctgg?gagttccctg?3420

acaactacaa?ctcacccaca?ccctacaaga?tccagtacaa?tgggctcaca?ctggatgtgg?3480

atggccgtac?caccaagaag?ctcatcacgc?acctcaagcc?ccacaccttc?tacaactttg?3540

tgctgaccaa?tcgcggcagc?agcctgggcg?gcctccagca?gacggtcacc?gcctggactg?3600

ccttcaacct?gctcaacggc?aagcccagcg?tcgcccccaa?gcctgatgct?gacggcttca?3660

tcatggtgta?tcttcctgac?ggccagagcc?ccgtgcctgt?ccagagctat?ttcattgtga?3720

tggtgccact?gcgcaagtct?cgtggaggcc?aattcctgac?cccgctgggt?agcccagagg?3780

acatggatct?ggaagagctc?atccaggaca?tctcacggct?acagaggcgc?agcctgcggc?3840

actcgcgtca?gctggaggtg?ccccggccct?atattgcagc?tcgcttctct?gtgctgccac?3900

ccacgttcca?tcccggcgac?cagaagcagt?atggcggctt?cgataaccgg?ggcctggagc?3960

ccggccaccg?ctatgtcctc?ttcgtgcttg?ccgtgcttca?gaagagcgag?cctacctttg?4020

cagccagtcc?cttctcagac?cccttccagc?tggataaccc?ggacccccag?cccatcgtgg?4080

atggcgagga?ggggcttatc?tgggtgatcg?ggcctgtgct?ggccgtggtc?ttcataatct?4140

gcattgtcat?tgctatcctg?ctctacaaga?acaaacccga?cagtaaacgc?aaggactcag?4200

aaccccgcac?caaatgcctc?ctgaacaatg?ccgacctcgc?ccctcaccac?cccaaggacc?4260

ctgtggaaat?gagacgcatt?aacttccaga?ctccagattc?aggcctcagg?agccccctca?4320

gggagccggg?gtttcacttt?gaaagcatgc?ttagccaccc?gccaattccc?atcgcagaca?4380

tggcggagca?cacggagcgg?ctcaaggcca?acgacagcct?caagctctcc?caggagtatg?4440

agtccatcga?ccctggacag?cagttcacat?gggaacattc?caacctggaa?gtgaacaagc?4500

cgaagaaccg?ctatgccaac?gtcatcgcct?atgaccactc?ccgtgtcatc?ctccagccca?4560

ttgaaggcat?catgggcagt?gattacatca?atgccaacta?cgtggacggc?taccggcgtc?4620

agaacgcgta?cattgccacg?caggggccgc?tgcctgagac?ctttggggac?ttctggcgta?4680

tggtgtggga?gcagcggtcg?gcgaccatcg?tcatgatgac?gcggctggag?gagaagtcac?4740

ggatcaagtg?tgatcagtat?tggcccaaca?gaggcacgga?gacctacggc?ttcatccagg?4800

tcacgttgct?agataccatc?gagctggcca?cattctgcgt?caggacattc?tctctgcaca?4860

agaatggctc?cagtgagaaa?cgcgaggtcc?gccagttcca?gtttacggcg?tggccggacc?4920

atggcgtgcc?cgaataccca?acgcccttcc?tggctttcct?gcggagagtc?aagacctgca?4980

acccgccaga?tgccggcccc?atcgtggttc?actgcagtgc?cggtgtgggc?cgcacaggct?5040

gctttatcgt?catcgacgcc?atgcttgagc?ggatcaagcc?agagaagaca?gtcgatgtct?5100

atggccacgt?gacgctcatg?aggtcccagc?gcaactacat?ggtgcagacg?gaggaccagt?5160

acagcttcat?ccacgaggcc?ctgctggagg?ccgtgggctg?tggcaacaca?gaagtgcccg?5220

cacgcagcct?ctatgcctac?atccagaagc?tggcccaggt?ggagcctggc?gaacacgtca?5280

ctggcatgga?actcgagttc?aagcggctgg?ctaactccaa?ggcccacacg?tcacgcttca?5340

tcagtgccaa?tctgccttgt?aacaagttca?agaaccgcct?ggtgaacatc?atgccctatg?5400

agagcacacg?ggtctgtctg?caacccatcc?ggggtgtgga?gggctctgac?tacatcaacg?5460

ccagcttcat?tgatggctac?aggcagcaga?aggcctacat?cgcgacacag?gggccgctgg?5520

cggagaccac?ggaagacttc?tggcgcatgc?tgtgggagaa?caattcgacg?atcgtggtga?5580

tgctgaccaa?gctgcgggag?atgggccggg?agaagtgtca?ccagtactgg?ccggccgagc?5640

gctctgcccg?ctaccagtac?tttgtggtag?atccgatggc?agaatacaac?atgcctcagt?5700

atatcctgcg?agagttcaag?gtcacagatg?cccgggatgg?ccagtcccgg?actgtccggc?5760

agttccagtt?cacagactgg?ccggaacagg?gtgtgccaaa?gtcgggggag?ggcttcatcg?5820

acttcattgg?ccaagtgcat?aagactaagg?agcagtttgg?ccaggacggc?cccatctctg?5880

tccactgcag?tgccggcgtg?ggcaggacgg?gcgtcttcat?cacgcttagc?atcgtgctgg?5940

agcggatgcg?gtatgaaggc?gtggtggaca?tctttcagac?ggtgaagatg?ctacgaaccc?6000

agcggccggc?catggtgcag?acagaggatg?agtaccagtt?ctgttaccag?gcggcactgg?6060

agtacctcgg?aagctttgac?cactatgcaa?cctaaagcca?tggtcccccc?caggcccgac?6120

accactggcc?ccggatgcct?ctgcccctcc?cgggcggacc?tcctgaggcc?tggaccccca?6180

gtgggcaggg?caggaggtgg?cagcggcagc?agctgtgttt?ctgcaccatt?tccgaggacg?6240

acgcagcccc?tcgagccccc?ccaccggccc?cggccgcccc?agcgacctcc?ctggcacggc?6300

cgccgccttc?aaatacttgg?cacattcctc?ctttccttcc?aattccaaaa?ccagattccg?6360

gggtgggggg?tggggggatg?gtgagcaaat?aggagtgctc?cccagaacca?gaggagggtg?6420

gggcacagac?catagacgga?cccctcgtcc?tcccccagcg?gtggtagggg?gacccggggg?6480

gctcctcccc?gctctgcacc 6500

<210>106

<211>1910

<212>PRT

＜213〉people (homo sapiens)

<400>106

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser

225 230 235 240

His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu

260 265 270

Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr

275 280 285

Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu

290 295 300

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

305 310 315 320

Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr

325 330 335

Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile

340 345 350

Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp

355 360 365

Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu

370 375 380

Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala

405 410 415

Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val

420 425 430

Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys

450 455 460

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

465 470 475 480

Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp

485 490 495

Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Gly?Gln?Pro?Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile

515 520 525

Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu

530 535 540

Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe

545 550 555 560

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

565 570 575

Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe

580 585 590

Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro

595 600 605

Pro?Gln?Asp?Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val

610 615 620

Ser?Trp?Arg?Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly

625 630 635 640

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

645 650 655

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

660 665 670

Leu?Glu?Lys?Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu

675 680 685

Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu

690 695 700

Asp?Val?Pro?Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn

705 710 715 720

Ala?Thr?Ala?Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln

725 730 735

His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly

740 745 750

Ala?Glu?Ala?Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp

755 760 765

Ala?Gln?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln?Pro?Glu?Thr?Ala?Tyr?Ser

770 775 780

Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys

785 790 795 800

Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val?Leu?Gly?Arg?Pro?Thr?Leu

805 810 815

Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu?Leu?Ala?Arg?Trp?Glu?Pro

820 825 830

Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu?Gly?Tyr?Arg?Leu?Gln?Phe

835 840 845

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

850 855 860

Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His?Lys?Gly?Ala?Thr?Tyr?Val

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly?Leu?Gly?Glu?Glu?Ala?Ala

885 890 895

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

900 905 910

Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly?Thr?Val?Leu?Leu?Arg?Trp

915 920 925

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

930 935 940

Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly?Pro?Ala?Arg?Glu?Thr?Glu

945 950 955 960

Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu?Asn?Ala?Leu?Thr?Leu?Gln

965 970 975

Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu?Gln?Val?Arg?Ala?His?Thr

980 985 990

Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro?Val?Arg?Tyr?Arg?Thr?Phe

995 1000 1005

Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe?Lys?Val?Lys?Met?Ile?Met

1010 1015 1020

Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser

1025 1030 1035 1040

Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly?Leu?Thr?Leu?Asp?Val?Asp

1045 1050 1055

Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His?Leu?Lys?Pro?His?Thr?Phe

1060 1065 1070

Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser?Ser?Leu?Gly?Gly?Leu?Gln

1075 1080 1085

Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn?Leu?Leu?Asn?Gly?Lys?Pro

1090 1095 1100

Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly?Phe?Ile?Met?Val?Tyr?Leu

1105 1110 1115 1120

Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln?Ser?Tyr?Phe?Ile?Val?Met

1125 1130 1135

Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln?Phe?Leu?Thr?Pro?Leu?Gly

1140 1145 1150

Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu?Ile?Gln?Asp?Ile?Ser?Arg

1155 1160 1165

Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg?Gln?Leu?Glu?Val?Pro?Arg

1170 1175 1180

Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu?Pro?Pro?Thr?Phe?His?Pro

1185 1190 1195 1200

Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp?Asn?Arg?Gly?Leu?Glu?Pro

1205 1210 1215

Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala?Val?Leu?Gln?Lys?Ser?Glu

1220 1225 1230

Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp?Pro?Phe?Gln?Leu?Asp?Asn

1235 1240 1245

Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu?Glu?Gly?Leu?Ile?Trp?Val

1250 1255 1260

Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala

1265 1270 1275 1280

Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser?Lys?Arg?Lys?Asp?Ser?Glu

1285 1290 1295

Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala?Asp?Leu?Ala?Pro?His?His

1300 1305 1310

Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile?Asn?Phe?Gln?Thr?Pro?Gly

1315 1320 1325

Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala?Asp?Met?Ala?Glu?His?Thr

1330 1335 1340

Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys?Leu?Ser?Gln?Glu?Tyr?Glu

1345 1350 1355 1360

Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu

1365 1370 1375

Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His

1380 1385 1390

Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly?Ile?Met?Gly?Ser?Asp?Tyr

1395 1400 1405

Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg?Arg?Gln?Asn?Ala?Tyr?Ile

1410 1415 1420

Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met

1425 1430 1435 1440

Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val?Met?Met?Thr?Arg?Leu?Glu

1445 1450 1455

Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Asn?Arg?Gly?Thr

1460 1465 1470

Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Ile?Glu?Leu

1475 1480 1485

Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu?His?Lys?Asn?Gly?Ser?Ser

1490 1495 1500

Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His

1505 1510 1515 1520

Gly?Val Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val

1525 1530 1535

Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Ile?Val?Val?His?Cys?Ser

1540 1545 1550

Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu

1555 1560 1565

Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp?Val?Tyr?Gly?His?Val?Thr

1570 1575 1580

Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr

1585 1590 1595 1600

Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Val?Gly?Cys?Gly?Asn?Thr

1605 1610 1615

Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Ala?Gln

1620 1625 1630

Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg

1635 1640 1645

Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu

1650 1655 1660

Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu

1665 1670 1675 1680

Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp

1685 1690 1695

Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr

1700 1705 1710

Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg

1715 1720 1725

Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu

1730 1735 1740

Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg

1745 1750 1755 1760

Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn

1765 1770 1775

Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp

1780 1785 1790

Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu

1795 1800 1805

Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln

1810 1815 1820

Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val

1825 1830 1835 1840

His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr?Leu?Ser

1845 1850 1855

Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln

1860 1865 1870

Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu

1875 1880 1885

Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser

1890 1895 1900

Phe?Asp?His?Tyr?Ala?Thr

1905 1910

<210>107

<211>6386

<212>DNA

＜213〉people (homo sapiens)

<400>107

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagtcc?gccgcgtggc?cccgcgcttc?tccatcctgc?960

ccatgagcca?cgagatcatg?ccagggggca?acgtgaacat?cacctgcgtg?gccgtgggct?1020

cgcccatgcc?atacgtgaag?tggatgcagg?gggccgagga?cctgaccccc?gaggatgaca?1080

tgcccgtggg?tcggaacgtg?ctggaactca?cagatgtcaa?ggactcggcc?aactacacct?1140

gcgtggccat?gtccagcctg?ggcgtcattg?aggcggttgc?tcagatcacg?gtgaaatctc?1200

tccccaaagc?tcccgggact?cccatggtga?ctgagaacac?agccaccagc?atcaccatca?1260

cgtgggactc?gggcaaccca?gatcctgtgt?cctattacgt?catcgaatat?aaatccaaga?1320

gccaagacgg?gccgtatcag?attaaagagg?acatcaccac?cacacgttac?agcatcggcg?1380

gcctgagccc?caactcggag?tacgagatct?gggtgtcggc?cgtcaactcc?atcggccagg?1440

ggccccccag?cgagtccgtg?gtcacccgca?caggcgagca?ggccccggcc?agcgcgccgc?1500

ggaacgtgca?agcccggatg?ctcagcgcga?ccaccatgat?tgtgcagtgg?gaggagccgg?1560

tggagcccaa?cggcctgatc?cgcggctacc?gcgtctacta?caccatggaa?ccggagcacc?1620

ccgtgggcaa?ctggcagaag?cacaacgtgg?acgacagcct?gctgaccacc?gtgggcagcc?1680

tgctggagga?cgagacctac?accgtgcggg?tgctcgcctt?cacctccgtc?ggcgacgggc?1740

ccctctcgga?ccccatccag?gtcaagacgc?agcagggagt?gccgggccag?cccatgaacc?1800

tgcgggccga?ggccaggtcg?gagaccagca?tcacgctgtc?ctggagcccc?ccgcggcagg?1860

agagtatcat?caagtacgag?ctcctcttcc?gggaaggcga?ccatggccgg?gaggtgggaa?1920

ggaccttcga?cccgacgact?tcctacgtgg?tggaggacct?gaagcccaac?acggagtacg?1980

ccttccgcct?ggcggcccgc?tcgccgcagg?gcctgggcgc?cttcaccccc?gtggtgcggc?2040

agcgcacgct?gcagtccaaa?ccgtcagccc?cccctcaaga?cgttaaatgt?gtcagcgtgc?2100

gctccacggc?cattttggta?agttggcgcc?cgccgccgcc?ggaaacgcac?aacggggccc?2160

tggtgggcta?cagcgtccgc?taccgaccgc?tgggctcaga?ggacccggaa?cccaaggagg?2220

tgaacggcat?ccccccgacc?accactcaga?tcctgctgga?ggccttggag?aagtggaccc?2280

agtaccgcat?cacgactgtc?gctcacacag?aggtgggacc?agggcccgag?agctcgcccg?2340

tggtcgtccg?caccgacgag?gatgtgccca?gcgcgccgcc?gcggaaggtg?gaggcggagg?2400

cgctcaacgc?cacggccatc?cgcgtgctgt?ggcgctcgcc?cgcgcccggc?cggcagcacg?2460

gccagatccg?cggctaccag?gtccactacg?tgcgcatgga?gggcgccgag?gcccgcgggc?2520

cgccgcgcat?caaggacgtc?atgctggccg?atgcccagga?gatggtcatc?acaaacttgc?2580

agcctgagac?cgcgtactcc?atcacggtag?ccgcctacac?catgaagggc?gatggcgctc?2640

gcagcaaacc?caaggtggtt?gtgaccaagg?gagcagtgct?gggccgccca?accctgtcgg?2700

tgcagcagac?ccccgagggc?agcctgctgg?cacgctggga?gcccccggct?ggcaccgcgg?2760

aggaccaggt?gctgggctac?cgcctgcagt?ttggccgtga?ggactcgacg?cccctggcca?2820

ccctggagtt?cccgccctcc?gaggaccgct?acacggcatc?aggcgtgcac?aagggggcca?2880

cgtatgtgtt?ccggcttgcg?gcccggagcc?gcggcggcct?gggcgaggag?gcagccgagg?2940

tcctgagcat?cccggaggac?acgccccgtg?gccacccgca?gattctggag?gcggccggca?3000

acgcctcggc?cgggaccgtc?cttctccgct?ggctgccacc?cgtgcccgcc?gagcgcaacg?3060

gggccatcgt?caaatacacg?gtggccgtgc?gggaggccgg?tgccctgggc?cctgcccgag?3120

agactgagct?gccggcagcg?gctgagccgg?gcgcggagaa?cgcgctcacg?ctgcagggcc?3180

tgaagcccga?cacggcctat?gacctccaag?tgcgagccca?cacgcgccgg?ggccctggcc?3240

ccttcagccc?ccccgtccgc?taccggacgt?tcctgcggga?ccaagtctcg?cccaagaact?3300

tcaaggtgaa?aatgatcatg?aagacatcag?ttctgctcag?ctgggagttc?cctgacaact?3360

acaactcacc?cacaccctac?aagatccagt?acaatgggct?cacactggat?gtggatggcc?3420

gtaccaccaa?gaagctcatc?acgcacctca?agccccacac?cttctacaac?tttgtgctga?3480

ccaatcgcgg?cagcagcctg?ggcggcctcc?agcagacggt?caccgcctgg?actgccttca?3540

acctgctcaa?cggcaagccc?agcgtcgccc?ccaagcctga?tgctgacggc?ttcatcatgg?3600

tgtatcttcc?tgacggccag?agccccgtgc?ctgtccagag?ctatttcatt?gtgatggtgc?3660

cactgcgcaa?gtctcgtgga?ggccaattcc?tgaccccgct?gggtagccca?gaggacatgg?3720

atctggaaga?gctcatccag?gacatctcac?ggctacagag?gcgcagcctg?cggcactcgc?3780

gtcagctgga?ggtgccccgg?ccctatattg?cagctcgctt?ctctgtgctg?ccacccacgt?3840

tccatcccgg?cgaccagaag?cagtatggcg?gcttcgataa?ccggggcctg?gagcccggcc?3900

accgctatgt?cctcttcgtg?cttgccgtgc?ttcagaagag?cgagcctacc?tttgcagcca?3960

gtcccttctc?agaccccttc?cagctggata?acccggaccc?ccagcccatc?gtggatggcg?4020

aggaggggct?tatctgggtg?atcgggcctg?tgctggccgt?ggtcttcata?atctgcattg?4080

tcattgctat?cctgctctac?aagaacaaac?ccgacagtaa?acgcaaggac?tcagaacccc?4140

gcaccaaatg?cctcctgaac?aatgccgacc?tcgcccctca?ccaccccaag?gaccctgtgg?4200

aaatgagacg?cattaacttc?cagactccag?gcatgcttag?ccacccgcca?attcccatcg?4260

cagacatggc?ggagcacacg?gagcggctca?aggccaacga?cagcctcaag?ctctcccagg?4320

agtatgagtc?catcgaccct?ggacagcagt?tcacatggga?acattccaac?ctggaagtga?4380

acaagccgaa?gaaccgctat?gccaacgtca?tcgcctatga?ccactcccgt?gtcatcctcc?4440

agcccattga?aggcatcatg?ggcagtgatt?acatcaatgc?caactacgtg?gacggctacc?4500

ggcgtcagaa?cgcgtacatt?gccacgcagg?ggccgctgcc?tgagaccttt?ggggacttct?4560

ggcgtatggt?gtgggagcag?cggtcggcga?ccatcgtcat?gatgacgcgg?ctggaggaga?4620

agtcacggat?caagtgtgat?cagtattggc?ccaacagagg?cacggagacc?tacggcttca?4680

tccaggtcac?gttgctagat?accatcgagc?tggccacatt?ctgcgtcagg?acattctctc?4740

tgcacaagaa?tggctccagt?gagaaacgcg?aggtccgcca?gttccagttt?acggcgtggc?4800

cggaccatgg?cgtgcccgaa?tacccaacgc?ccttcctggc?tttcctgcgg?agagtcaaga?4860

cctgcaaccc?accagatgcc?ggccccatcg?tggttcactg?cagtgccggt?gtgggccgca?4920

caggctgctt?tatcgtcatc?gacgccatgc?ttgagcggat?caagccagag?aagacagtcg?4980

atgtctatgg?ccacgtgacg?ctcatgaggt?cccagcgcaa?ctacatggtg?cagacggagg?5040

accagtacag?cttcatccac?gaggccctgc?tggaggccgt?gggctgtggc?aacacagaag?5100

tgcccgcacg?cagcctctat?gcctacatcc?agaagctggc?ccaggtggag?cctggcgaac?5160

acgtcactgg?catggaactc?gagttcaagc?ggctggctaa?ctccaaggcc?cacacgtcac?5220

gcttcatcag?tgccaatctg?ccttgtaaca?agttcaagaa?ccgcctggtg?aacatcatgc?5280

cctatgagag?cacacgggtc?tgtctgcaac?ccatccgggg?tgtggagggc?tctgactaca?5340

tcaacgccag?cttcattgat?ggctacaggc?agcagaaggc?ctacatcgcg?acacaggggc?5400

cgctggcgga?gaccacggaa?gacttctggc?gcatgctgtg?ggagaacaat?tcgacgatcg?5460

tggtgatgct?gaccaagctg?cgggagatgg?gccgggagaa?gtgtcaccag?tactggccgg?5520

ccgagcgctc?tgcccgctac?cagtactttg?tggtagatcc?gatggcagaa?tacaacatgc?5580

ctcagtatat?cctgcgagag?ttcaaggtca?cagatgcccg?ggatggccag?tcccggactg?5640

tccggcagtt?ccagttcaca?gactggccgg?aacagggtgt?gccaaagtcg?ggggagggct?5700

tcatcgactt?cattggccaa?gtgcataaga?ctaaggagca?gtttggccag?gacggcccca?5760

tctctgtcca?ctgcagtgcc?ggcgtgggca?ggacgggcgt?cttcatcacg?cttagcatcg?5820

tgctggagcg?gatgcggtat?gaaggcgtgg?tggacatctt?tcagacggtg?aagatgctac?5880

gaacccagcg?gccggccatg?gtgcagacag?aggatgagta?ccagttctgt?taccaggcgg?5940

cactggagta?cctcggaagc?tttgaccact?atgcaaccta?aagccatggt?cccccccagg?6000

cccgacacca?ctggccccgg?atgcctctgc?ccctcccggg?cggacctcct?gaggcctgga?6060

cccccagtgg?gcagggcagg?aggtggcagc?ggcagcagct?gtgtttctgc?accatttccg?6120

aggacgacgc?agcccctcga?gcccccccac?cggccccggc?cgccccagcg?acctccctgg?6180

cacggccgcc?gccttcaaat?acttggcaca?ttcctccttt?ccttccaatt?ccaaaaccag?6240

attccggggt?ggggggtggg?gggatggtga?gcaaatagga?gtgctcccca?gaaccagagg?6300

agggtggggc?acagaccata?gacggacccc?tcgtcctccc?ccagcggtgg?tagggggacc?6360

cggggggctc?ctccccgctc?tgcacc 6386

<210>108

<211>1501

<212>PRT

＜213〉people (homo sapiens)

<400>108

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser

225 230 235 240

His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu

260 265 270

Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr

275 280 285

Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu

290 295 300

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

305 310 315 320

Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr

325 330 335

Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile

340 345 350

Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp

355 360 365

Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu

370 375 380

Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala

405 410 415

Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val

420 425 430

Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys

450 455 460

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

465 470 475 480

Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp

485 490 495

Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Gly?Gln?Pro?Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile

515 520 525

Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu

530 535 540

Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe

545 550 555 560

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

565 570 575

Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe

580 585 590

Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Ile?Ser?Pro?Lys?Asn

595 600 605

Phe?Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

610 615 620

Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn

625 630 635 640

Gly?Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr

645 650 655

His?Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly

660 665 670

Ser?Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe

675 680 685

Asn?Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp

690 695 700

Gly?Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val

705 710 715 720

Gln?Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly

725 730 735

Gln?Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu

740 745 750

Leu?Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser

755 760 765

Arg?Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val

770 775 780

Leu?Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe

785 790 795 800

Asp?Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu

805 810 815

Ala?Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser

820 825 830

Asp?Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly

835 840 845

Glu?Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe

850 855 860

Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp

865 870 875 880

Ser?Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn

885 890 895

Ala?Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg

900 905 910

Ile?Asn?Phe?Gln?Thr?Pro?Gly?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile

915 920 925

Ala?Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu

930 935 940

Lys?Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr

945 950 955 960

Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala

965 970 975

Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu

980 985 990

Gly?Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr

995 1000 1005

Arg?Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr

1010 1015 1020

Phe?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile

1025 1030 1035 1040

Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln

1045 1050 1055

Tyr?Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr

1060 1065 1070

Leu?Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser

1075 1080 1085

Leu?His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln

1090 1095 1100

Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe

1105 1110 1115 1120

Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly

1125 1130 1135

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

1140 1145 1150

Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val

1155 1160 1165

Asp?Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met

1170 1175 1180

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu

1185 1190 1195 1200

Ala?Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala

1205 1210 1215

Tyr?Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly

1220 1225 1230

Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser

1235 1240 1245

Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu

1250 1255 1260

Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile

1265 1270 1275 1280

Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly

1285 1290 1295

Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu

1300 1305 1310

Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile

1315 1320 1325

Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His

1330 1335 1340

Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val

1345 1350 1355 1360

Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe

1365 1370 1375

Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe

1380 1385 1390

Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly

1395 1400 1405

Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly

1410 1415 1420

Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1425 1430 1435 1440

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

1445 1450 1455

Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg

1460 1465 1470

Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala

1475 1480 1485

Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1490 1495 1500

<210>109

<211>5159

<212>DNA

＜213〉people (homo sapiens)

<400>109

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagtcc?gccgcgtggc?cccgcgcttc?tccatcctgc?960

ccatgagcca?cgagatcatg?ccagggggca?acgtgaacat?cacctgcgtg?gccgtgggct?1020

cgcccatgcc?atacgtgaag?tggatgcagg?gggccgagga?cctgaccccc?gaggatgaca?1080

tgcccgtggg?tcggaacgtg?ctggaactca?cagatgtcaa?ggactcggcc?aactacacct?1140

gcgtggccat?gtccagcctg?ggcgtcattg?aggcggttgc?tcagatcacg?gtgaaatctc?1200

tccccaaagc?tcccgggact?cccatggtga?ctgagaacac?agccaccagc?atcaccatca?1260

cgtgggactc?gggcaaccca?gatcctgtgt?cctattacgt?catcgaatat?aaatccaaga?1320

gccaagacgg?gccgtatcag?attaaagagg?acatcaccac?cacacgttac?agcatcggcg?1380

gcctgagccc?caactcggag?tacgagatct?gggtgtcggc?cgtcaactcc?atcggccagg?1440

ggccccccag?cgagtccgtg?gtcacccgca?caggcgagca?ggccccggcc?agcgcgccgc?1500

ggaacgtgca?agcccggatg?ctcagcgcga?ccaccatgat?tgtgcagtgg?gaggagccgg?1560

tggagcccaa?cggcctgatc?cgcggctacc?gcgtctacta?caccatggaa?ccggagcacc?1620

ccgtgggcaa?ctggcagaag?cacaacgtgg?acgacagcct?gctgaccacc?gtgggcagcc?1680

tgctggagga?cgagacctac?accgtgcggg?tgctcgcctt?cacctccgtc?ggcgacgggc?1740

ccctctcgga?ccccatccag?gtcaagacgc?agcagggagt?gccgggccag?cccatgaacc?1800

tgcgggccga?ggccaggtcg?gagaccagca?tcacgctgtc?ctggagcccc?ccgcggcagg?1860

agagtatcat?caagtacgag?ctcctcttcc?gggaaggcga?ccatggccgg?gaggtgggaa?1920

ggaccttcga?cccgacgact?tcctacgtgg?tggaggacct?gaagcccaac?acggagtacg?1980

ccttccgcct?ggcggcccgc?tcgccgcagg?gcctgggcgc?cttcaccccc?gtggtgcggc?2040

agcgcacgct?gcagtccatc?tcgcccaaga?acttcaaggt?gaaaatgatc?atgaagacat?2100

cagttctgct?cagctgggag?ttccctgaca?actacaactc?acccacaccc?tacaagatcc?2160

agtacaatgg?gctcacactg?gatgtggatg?gccgtaccac?caagaagctc?atcacgcacc?2220

tcaagcccca?caccttctac?aactttgtgc?tgaccaatcg?cggcagcagc?ctgggcggcc?2280

tccagcagac?ggtcaccgcc?tggactgcct?tcaacctgct?caacggcaag?cccagcgtcg?2340

cccccaagcc?tgatgctgac?ggcttcatca?tggtgtatct?tcctgacggc?cagagccccg?2400

tgcctgtcca?gagctatttc?attgtgatgg?tgccactgcg?caagtctcgt?ggaggccaat?2460

tcctgacccc?gctgggtagc?ccagaggaca?tggatctgga?agagctcatc?caggacatct?2520

cacggctaca?gaggcgcagc?ctgcggcact?cgcgtcagct?ggaggtgccc?cggccctata?2580

ttgcagctcg?cttctctgtg?ctgccaccca?cgttccatcc?cggcgaccag?aagcagtatg?2640

gcggcttcga?taaccggggc?ctggagcccg?gccaccgcta?tgtcctcttc?gtgcttgccg?2700

tgcttcagaa?gagcgagcct?acctttgcag?ccagtccctt?ctcagacccc?ttccagctgg?2760

ataacccgga?cccccagccc?atcgtggatg?gcgaggaggg?gcttatctgg?gtgatcgggc?2820

ctgtgctggc?cgtggtcttc?ataatctgca?ttgtcattgc?tatcctgctc?tacaagaaca?2880

aacccgacag?taaacgcaag?gactcagaac?cccgcaccaa?atgcctcctg?aacaatgccg?2940

acctcgcccc?tcaccacccc?aaggaccctg?tggaaatgag?acgcattaac?ttccagactc?3000

caggcatgct?tagccacccg?ccaattccca?tcgcagacat?ggcggagcac?acggagcggc?3060

tcaaggccaa?cgacagcctc?aagctctccc?aggagtatga?gtccatcgac?cctggacagc?3120

agttcacatg?ggaacattcc?aacctggaag?tgaacaagcc?gaagaaccgc?tatgccaacg?3180

tcatcgccta?tgaccactcc?cgtgtcatcc?tccagcccat?tgaaggcatc?atgggcagtg?3240

attacatcaa?tgccaactac?gtggacggct?accggcgtca?gaacgcgtac?attgccacgc?3300

aggggccgct?gcctgagacc?tttggggact?tctggcgtat?ggtgtgggag?cagcggtcgg?3360

cgaccatcgt?catgatgacg?cggctggagg?agaagtcacg?gatcaagtgt?gatcagtatt?3420

ggcccaacag?aggcacggag?acctacggct?tcatccaggt?cacgttgcta?gataccatcg?3480

agctggccac?attctgcgtc?aggacattct?ctctgcacaa?gaatggctcc?agtgagaaac?3540

gcgaggtccg?ccagttccag?tttacggcgt?ggccggacca?tggcgtgccc?gaatacccaa?3600

cgcccttcct?ggctttcctg?cggagagtca?agacctgcaa?cccaccagat?gccggcccca?3660

tcgtggttca?ctgcagtgcc?ggtgtgggcc?gcacaggctg?ctttatcgtc?atcgacgcca?3720

tgcttgagcg?gatcaagcca?gagaagacag?tcgatgtcta?tggccacgtg?acgctcatga?3780

ggtcccagcg?caactacatg?gtgcagacgg?aggaccagta?cagcttcatc?cacgaggccc?3840

tgctggaggc?cgtgggctgt?ggcaacacag?aagtgcccgc?acgcagcctc?tatgcctaca?3900

tccagaagct?ggcccaggtg?gagcctggcg?aacacgtcac?tggcatggaa?ctcgagttca?3960

agcggctggc?taactccaag?gcccacacgt?cacgcttcat?cagtgccaat?ctgccttgta?4020

acaagttcaa?gaaccgcctg?gtgaacatca?tgccctatga?gagcacacgg?gtctgtctgc?4080

aacccatccg?gggtgtggag?ggctctgact?acatcaacgc?cagcttcatt?gatggctaca?4140

ggcagcagaa?ggcctacatc?gcgacacagg?ggccgctggc?ggagaccacg?gaagacttct?4200

ggcgcatgct?gtgggagaac?aattcgacga?tcgtggtgat?gctgaccaag?ctgcgggaga?4260

tgggccggga?gaagtgtcac?cagtactggc?cggccgagcg?ctctgcccgc?taccagtact?4320

ttgtggtaga?tccgatggca?gaatacaaca?tgcctcagta?tatcctgcga?gagttcaagg?4380

tcacagatgc?ccgggatggc?cagtcccgga?ctgtccggca?gttccagttc?acagactggc?4440

cggaacaggg?tgtgccaaag?tcgggggagg?gcttcatcga?cttcattggc?caagtgcata?4500

agactaagga?gcagtttggc?caggacggcc?ccatctctgt?ccactgcagt?gccggcgtgg?4560

gcaggacggg?cgtcttcatc?acgcttagca?tcgtgctgga?gcggatgcgg?tatgaaggcg?4620

tggtggacat?ctttcagacg?gtgaagatgc?tacgaaccca?gcggccggcc?atggtgcaga?4680

cagaggatga?gtaccagttc?tgttaccagg?cggcactgga?gtacctcgga?agctttgacc?4740

actatgcaac?ctaaagccat?ggtccccccc?aggcccgaca?ccactggccc?cggatgcctc?4800

tgcccctccc?gggcggacct?cctgaggcct?ggacccccag?tgggcagggc?aggaggtggc?4860

agcggcagca?gctgtgtttc?tgcaccattt?ccgaggacga?cgcagcccct?cgagcccccc?4920

caccggcccc?ggccgcccca?gcgacctccc?tggcacggcc?gccgccttca?aatacttggc?4980

acattcctcc?tttccttcca?attccaaaac?cagattccgg?ggtggggggt?ggggggatgg?5040

tgagcaaata?ggagtgctcc?ccagaaccag?aggagggtgg?ggcacagacc?atagacggac?5100

ccctcgtcct?cccccagcgg?tggtaggggg?acccgggggg?ctcctccccg?ctctgcacc 5159

<210>110

<211>1505

<212>PRT

＜213〉people (homo sapiens)

<400>110

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Leu?Pro?Met?Ser?His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Thr?Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Ser?Leu?Gly?Val?Ile?Glu?Ala?Val?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ser?Leu?Pro?Lys?Ala?Pro?Gly?Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Ile?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser

340 345 350

Tyr?Tyr?Val?Ile?Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln

355 360 365

Ile?Lys?Glu?Asp?Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser

370 375 380

Pro?Asn?Ser?Glu?Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly

385 390 395 400

Gln?Gly?Pro?Pro?Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala

405 410 415

Pro?Ala?Ser?Ala?Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr

420 425 430

Thr?Met?Ile?Val?Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile

435 440 445

Arg?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly

450 455 460

Asn?Trp?Gln?Lys?His?Asn?Val?Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly

465 470 475 480

Ser?Leu?Leu?Glu?Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Val?Gly?Asp?Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln

500 505 510

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

515 520 525

Glu?Thr?Ser?Ile?Thr?Leu?Ser?Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile

530 535 540

Ile?Lys?Tyr?Glu?Leu?Leu?Phe?Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val

545 550 555 560

Gly?Arg?Thr?Phe?Asp?Pro?Thr?Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys

565 570 575

Pro?Asn?Thr?Glu?Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Phe?Thr?Pro?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Ile

595 600 605

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

610 615 620

Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys

625 630 635 640

Ile?Gln?Tyr?Asn?Gly?Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys

645 650 655

Lys?Leu?Ile?Thr?His?Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu

660 665 670

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

675 680 685

Trp?Thr?Ala?Phe?Asn?Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys

690 695 700

Pro?Asp?Ala?Asp?Gly?Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser

705 710 715 720

Pro?Val?Pro?Val?Gln?Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys

725 730 735

Ser?Arg?Gly?Gly?Gln?Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met

740 745 750

Asp?Leu?Glu?Glu?Leu?Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser

755 760 765

Leu?Arg?His?Ser?Arg?Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala

770 775 780

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

785 790 795 800

Tyr?Gly?Gly?Phe?Asp?Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val

805 810 815

Leu?Phe?Val?Leu?Ala?Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala

820 825 830

Ser?Pro?Phe?Ser?Asp?Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro

835 840 845

Ile?Val?Asp?Gly?Glu?Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu

850 855 860

Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys

865 870 875 880

Asn?Lys?Pro?Asp?Ser?Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys

885 890 895

Leu?Leu?Asn?Asn?Ala?Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val

900 905 910

Glu?Met?Arg?Arg?Ile?Asn?Phe?Gln?Thr?Pro?Gly?Met?Leu?Ser?His?Pro

915 920 925

Pro?Ile?Pro?Ile?Ala?Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala

930 935 940

Asn?Asp?Ser?Leu?Lys?Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly

945 950 955 960

Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys

965 970 975

Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu

980 985 990

Gln?Pro?Ile?Glu?Gly?Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr

995 1000 1005

Val?Asp?Gly?Tyr?Arg?Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro

1010 1015 1020

Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg

1025 1030 1035 1040

Ser?Ala?Thr?Ile?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile

1045 1050 1055

Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe

1060 1065 1070

Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val

1075 1080 1085

Arg?Thr?Phe?Ser?Leu?His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val

1090 1095 1100

Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr

1105 1110 1115 1120

Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro

1125 1130 1135

Pro?Asp?Ala?Gly?Pro?Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg

1140 1145 1150

Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro

1155 1160 1165

Glu?Lys?Thr?Val?Asp?Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln

1170 1175 1180

Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu

1185 1190 1195 1200

Ala?Leu?Leu?Glu?Ala?Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg

1205 1210 1215

Ser?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu

1220 1225 1230

His?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys

1235 1240 1245

Ala?His?Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe

1250 1255 1260

Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys

1265 1270 1275 1280

Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser

1285 1290 1295

Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly

1300 1305 1310

Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn

1315 1320 1325

Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg

1330 1335 1340

Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln

1345 1350 1355 1360

Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile

1365 1370 1375

Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr

1380 1385 1390

Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys

1395 1400 1405

Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys

1410 1415 1420

Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly

1425 1430 1435 1440

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

1445 1450 1455

Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu

1460 1465 1470

Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe

1475 1480 1485

Cys?Tyr?Gln?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala

1490 1495 1500

Thr

1505

<210>111

<211>5171

<212>DNA

＜213〉people (homo sapiens)

<400>111

attccatccc?atcaccccat?gatccttccc?cattgtccca?tgaacagccc?ctgcaggacc?60

ctcccctgct?ccatgtgacc?ctccctctgc?ctcctccatg?aaggtctcct?ggatttcccc?120

actcgcctct?cacagccctc?cattgtctct?gcagacgttg?ccccatctga?cgctcggctc?180

gaggcctctc?tgtgagggac?cggggggcca?tccccctcca?gggcggagat?cggaggtcgc?240

tgccaagcat?ggcgcccacc?tggggccctg?gcatggtgtc?tgtggttggt?cccatgggcc?300

tccttgtggt?cctgctcgtt?ggaggctgtg?cagcagaaga?gccccccagg?tttatcaaag?360

aacccaagga?ccagatcggc?gtgtcggggg?gtgtggcctc?tttcgtgtgt?caggccacgg?420

gtgaccccaa?gccacgagtg?acctggaaca?agaagggcaa?gaaggtcaac?tctcagcgct?480

ttgagacgat?tgagtttgat?gagagtgcag?gggcagtgct?gaggatccag?ccgctgagga?540

caccgcggga?tgaaaacgtg?tacgagtgtg?tggcccagaa?ctcggttggg?gagatcacag?600

tccatgccaa?gcttactgtc?ctccgagagg?accagctgcc?ctctggcttc?cccaacatcg?660

acatgggccc?acagttgaag?gtggtggagc?ggacacggac?agccaccatg?ctctgtgcag?720

ccagcggcaa?ccctgaccct?gagatcacct?ggttcaagga?cttcctgcct?gtggatccta?780

gtgccagcaa?tggacgcatc?aaacagctgc?gatcaggagc?cctgcagatt?gaaagcagtg?840

aggaaaccga?ccagggcaaa?tatgagtgtg?tggccaccaa?cagcgccggc?gtgcgctact?900

cctcacctgc?caacctctac?gtgcgagagc?ttcgagaagt?ccgccgcgtg?gccccgcgct?960

tctccatcct?gcccatgagc?cacgagatca?tgccaggggg?caacgtgaac?atcacctgcg?1020

tggccgtggg?ctcgcccatg?ccatacgtga?agtggatgca?gggggccgag?gacctgaccc?1080

ccgaggatga?catgcccgtg?ggtcggaacg?tgctggaact?cacagatgtc?aaggactcgg?1140

ccaactacac?ctgcgtggcc?atgtccagcc?tgggcgtcat?tgaggcggtt?gctcagatca?1200

cggtgaaatc?tctccccaaa?gctcccggga?ctcccatggt?gactgagaac?acagccacca?1260

gcatcaccat?cacgtgggac?tcgggcaacc?cagatcctgt?gtcctattac?gtcatcgaat?1320

ataaatccaa?gagccaagac?gggccgtatc?agattaaaga?ggacatcacc?accacacgtt?1380

acagcatcgg?cggcctgagc?cccaactcgg?agtacgagat?ctgggtgtcg?gccgtcaact?1440

ccatcggcca?ggggcccccc?agcgagtccg?tggtcacccg?cacaggcgag?caggccccgg?1500

ccagcgcgcc?gcggaacgtg?caagcccgga?tgctcagcgc?gaccaccatg?attgtgcagt?1560

gggaggagcc?ggtggagccc?aacggcctga?tccgcggcta?ccgcgtctac?tacaccatgg?1620

aaccggagca?ccccgtgggc?aactggcaga?agcacaacgt?ggacgacagc?ctgctgacca?1680

ccgtgggcag?cctgctggag?gacgagacct?acaccgtgcg?ggtgctcgcc?ttcacctccg?1740

tcggcgacgg?gcccctctcg?gaccccatcc?aggtcaagac?gcagcaggga?gtgccgggcc?1800

agcccatgaa?cctgcgggcc?gaggccaggt?cggagaccag?catcacgctg?tcctggagcc?1860

ccccgcggca?ggagagtatc?atcaagtacg?agctcctctt?ccgggaaggc?gaccatggcc?1920

gggaggtggg?aaggaccttc?gacccgacga?cttcctacgt?ggtggaggac?ctgaagccca?1980

acacggagta?cgccttccgc?ctggcggccc?gctcgccgca?gggcctgggc?gccttcaccc?2040

ccgtggtgcg?gcagcgcacg?ctgcagtcca?tctcgcccaa?gaacttcaag?gtgaaaatga?2100

tcatgaagac?atcagttctg?ctcagctggg?agttccctga?caactacaac?tcacccacac?2160

cctacaagat?ccagtacaat?gggctcacac?tggatgtgga?tggccgtacc?accaagaagc?2220

tcatcacgca?cctcaagccc?cacaccttct?acaactttgt?gctgaccaat?cgcggcagca?2280

gcctgggcgg?cctccagcag?acggtcaccg?cctggactgc?cttcaacctg?ctcaacggca?2340

agcccagcgt?cgcccccaag?cctgatgctg?acggcttcat?catggtgtat?cttcctgacg?2400

gccagagccc?cgtgcctgtc?cagagctatt?tcattgtgat?ggtgccactg?cgcaagtctc?2460

gtggaggcca?attcctgacc?ccgctgggta?gcccagagga?catggatctg?gaagagctca?2520

tccaggacat?ctcacggcta?cagaggcgca?gcctgcggca?ctcgcgtcag?ctggaggtgc?2580

cccggcccta?tattgcagct?cgcttctctg?tgctgccacc?cacgttccat?cccggcgacc?2640

agaagcagta?tggcggcttc?gataaccggg?gcctggagcc?cggccaccgc?tatgtcctct?2700

tcgtgcttgc?cgtgcttcag?aagagcgagc?ctacctttgc?agccagtccc?ttctcagacc?2760

ccttccagct?ggataacccg?gacccccagc?ccatcgtgga?tggcgaggag?gggcttatct?2820

gggtgatcgg?gcctgtgctg?gccgtggtct?tcataatctg?cattgtcatt?gctatcctgc?2880

tctacaagaa?caaacccgac?agtaaacgca?aggactcaga?accccgcacc?aaatgcctcc?2940

tgaacaatgc?cgacctcgcc?cctcaccacc?ccaaggaccc?tgtggaaatg?agacgcatta?3000

acttccagac?tccaggcatg?cttagccacc?cgccaattcc?catcgcagac?atggcggagc?3060

acacggagcg?gctcaaggcc?aacgacagcc?tcaagctctc?ccaggagtat?gagtccatcg?3120

accctggaca?gcagttcaca?tgggaacatt?ccaacctgga?agtgaacaag?ccgaagaacc?3180

gctatgccaa?cgtcatcgcc?tatgaccact?cccgtgtcat?cctccagccc?attgaaggca?3240

tcatgggcag?tgattacatc?aatgccaact?acgtggacgg?ctaccggcgt?cagaacgcgt?3300

acattgccac?gcaggggccg?ctgcctgaga?cctttgggga?cttctggcgt?atggtgtggg?3360

agcagcggtc?ggcgaccatc?gtcatgatga?cgcggctgga?ggagaagtca?cggatcaagt?3420

gtgatcagta?ttggcccaac?agaggcacgg?agacctacgg?cttcatccag?gtcacgttgc?3480

tagataccat?cgagctggcc?acattctgcg?tcaggacatt?ctctctgcac?aagaatggct?3540

ccagtgagaa?acgcgaggtc?cgccagttcc?agtttacggc?gtggccggac?catggcgtgc?3600

ccgaataccc?aacgcccttc?ctggctttcc?tgcggagagt?caagacctgc?aacccaccag?3660

atgccggccc?catcgtggtt?cactgcagtg?ccggtgtggg?ccgcacaggc?tgctttatcg?3720

tcatcgacgc?catgcttgag?cggatcaagc?cagagaagac?agtcgatgtc?tatggccacg?3780

tgacgctcat?gaggtcccag?cgcaactaca?tggtgcagac?ggaggaccag?tacagcttca?3840

tccacgaggc?cctgctggag?gccgtgggct?gtggcaacac?agaagtgccc?gcacgcagcc?3900

tctatgccta?catccagaag?ctggcccagg?tggagcctgg?cgaacacgtc?actggcatgg?3960

aactcgagtt?caagcggctg?gctaactcca?aggcccacac?gtcacgcttc?atcagtgcca?4020

atctgccttg?taacaagttc?aagaaccgcc?tggtgaacat?catgccctat?gagagcacac?4080

gggtctgtct?gcaacccatc?cggggtgtgg?agggctctga?ctacatcaac?gccagcttca?4140

ttgatggcta?caggcagcag?aaggcctaca?tcgcgacaca?ggggccgctg?gcggagacca?4200

cggaagactt?ctggcgcatg?ctgtgggaga?acaattcgac?gatcgtggtg?atgctgacca?4260

agctgcggga?gatgggccgg?gagaagtgtc?accagtactg?gccggccgag?cgctctgccc?4320

gctaccagta?ctttgtggta?gatccgatgg?cagaatacaa?catgcctcag?tatatcctgc?4380

gagagttcaa?ggtcacagat?gcccgggatg?gccagtcccg?gactgtccgg?cagttccagt?4440

tcacagactg?gccggaacag?ggtgtgccaa?agtcggggga?gggcttcatc?gacttcattg?4500

gccaagtgca?taagactaag?gagcagtttg?gccaggacgg?ccccatctct?gtccactgca?4560

gtgccggcgt?gggcaggacg?ggcgtcttca?tcacgcttag?catcgtgctg?gagcggatgc?4620

ggtatgaagg?cgtggtggac?atctttcaga?cggtgaagat?gctacgaacc?cagcggccgg?4680

ccatggtgca?gacagaggat?gagtaccagt?tctgttacca?ggcggcactg?gagtacctcg?4740

gaagctttga?ccactatgca?acctaaagcc?atggtccccc?ccaggcccga?caccactggc?4800

cccggatgcc?tctgcccctc?ccgggcggac?ctcctgaggc?ctggaccccc?agtgggcagg?4860

gcaggaggtg?gcagcggcag?cagctgtgtt?tctgcaccat?ttccgaggac?gacgcagccc?4920

ctcgagcccc?cccaccggcc?ccggccgccc?cagcgacctc?cctggcacgg?ccgccgcctt?4980

caaatacttg?gcacattcct?cctttccttc?caattccaaa?accagattcc?ggggtggggg?5040

gtggggggat?ggtgagcaaa?taggagtgct?ccccagaacc?agaggagggt?ggggcacaga?5100

ccatagacgg?acccctcgtc?ctcccccagc?ggtggtaggg?ggacccgggg?ggctcctccc?5160

cgctctgcac?c 5171

<210>112

<211>1912

<212>PRT

＜213〉people (homo sapiens)

<400>112

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Lys

595 600 605

Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser?Thr

610 615 620

Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn?Gly

625 630 635 640

Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp

645 650 655

Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys?Tyr

660 665 670

Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val?Thr

675 680 685

Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu?Ile

690 695 700

Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu?Val

705 710 715 720

Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro?Val

725 730 735

Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val

740 745 750

Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp?Val

755 760 765

Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr?Glu?His?Asp

770 775 780

Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser?Leu?Thr?Val

785 790 795 800

Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Leu

805 810 815

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

820 825 830

His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro?Pro?Val?Asp

835 840 845

Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly?Arg?Lys?Asp

850 855 860

Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu?Asp?His?Phe

865 870 875 880

Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe?Arg?Leu?Ser

885 890 895

Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys?Glu?Ile?Ser

900 905 910

Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu?His?Ser?Glu

915 920 925

Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro?Pro?Val?Leu

930 935 940

Ala?Glu?Arg?Asn?Gly?Ile?Ile?Thr?Lys?Tyr?Thr?Leu?Leu?Tyr?Arg?Asp

945 950 955 960

Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val?Pro?Ala?Asp

965 970 975

Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp?Val

980 985 990

Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr?Ser?Pro?Ser

995 1000 1005

Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp?Gln?Val?Phe?Ala?Lys?Asn?Phe

1010 1015 1020

His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Ile

1025 1030 1035 1040

Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu?Tyr?Asp?Asp

1045 1050 1055

Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln?Lys?Leu?Ile

1060 1065 1070

Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu?Thr?Asn?Arg

1075 1080 1085

Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala?Lys?Thr?Ala

1090 1095 1100

Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys?Thr?Asn?Leu

1105 1110 1115 1120

Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala?Asn?Glu?Asn

1125 1130 1135

Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys?Ser?Arg?Gly

1140 1145 1150

Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu?Leu?Asp?Glu

1155 1160 1165

Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg?Tyr?Gly?Arg

1170 1175 1180

Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp?Val?Leu?Pro

1185 1190 1195 1200

Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly?Phe?Thr?Asn

1205 1210 1215

Lys Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val?Leu?Ala?Val

1220 1225 1230

Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro?Tyr?Ser?Asp

1235 1240 1245

Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr?Asp?Glu?Glu

1250 1255 1260

Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1265 1270 1275 1280

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys?Arg?Ala?Glu

1285 1290 1295

Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu?Ile?Pro?Ser

1300 1305 1310

His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn?Phe?Gln?Thr

1315 1320 1325

Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu?Leu?Ala?Asp

1330 1335 1340

His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe?Ser?Gln?Glu

1345 1350 1355 1360

Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn

1365 1370 1375

Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr

1380 1385 1390

Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile?Pro?Gly?Ser

1395 1400 1405

Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn?Ala

1410 1415 1420

Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp

1425 1430 1435 1440

Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met?Met?Thr?Lys

1445 1450 1455

Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ser?Arg

1460 1465 1470

Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu?Asp?Thr?Val

1475 1480 1485

Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr?Lys?Asn?Gly

1490 1495 1500

Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp?Pro

1505 1510 1515 1520

Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu?Arg

1525 1530 1535

Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met?Val?Val?His

1540 1545 1550

Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala

1555 1560 1565

Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly?His

1570 1575 1580

Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp

1585 1590 1595 1600

Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val?Thr?Cys?Gly

1605 1610 1615

Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys?Leu

1620 1625 1630

Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe

1635 1640 1645

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

1650 1655 1660

Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met?Pro

1665 1670 1675 1680

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

1685 1690 1695

Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys

1700 1705 1710

Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe

1715 1720 1725

Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr

1730 1735 1740

Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala

1745 1750 1755 1760

Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu

1765 1770 1775

Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala

1780 1785 1790

Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp

1795 1800 1805

Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile

1810 1815 1820

Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile

1825 1830 1835 1840

Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr

1845 1850 1855

Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile

1860 1865 1870

Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln

1875 1880 1885

Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr?Leu

1890 1895 1900

Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1905 1910

<210>113

<211>6263

<212>DNA

＜213〉people (homo sapiens)

<400>113

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaaagccg?1980

tcagctcctc?ctcaagacat?tagttgcacc?agcccaagtt?ccactagtat?tttggtaagt?2040

tggcaacctc?caccagtgga?aaaacagaat?ggcattatca?ctgaatactc?catcaagtac?2100

actgcagtgg?atggggaaga?tgacaagcct?cacgagattt?tgggaattcc?ttcggacact?2160

accaaatacc?ttttggaaca?gctggaaaaa?tggactgaat?accggatcac?tgtgacagcc?2220

catacagatg?tcggccctgg?ccctgagagc?ttgtccgtgt?tgattcgaac?caatgaagat?2280

gttcctagtg?gtcctcctcg?caaagtcgag?gtagaggctg?tcaactcaac?atctgttaaa?2340

gtctcatggc?gctcacccgt?gcccaataaa?cagcatggcc?agataagagg?atatcaggtg?2400

cattatgtga?ggatggaaaa?tggtgagccc?aagggccagc?ccatgctgaa?agatgtcatg?2460

ctggctgatg?cacagtggga?atttgatgat?actactgaac?atgacatgat?catttctggg?2520

ctccagcctg?aaacttccta?ctccctcacc?gtcacagcct?acacaaccaa?aggagatggt?2580

gctcgcagca?agcccaaact?ggtgtccacc?actggggcag?ttccagggaa?acctcggctt?2640

gtgattaacc?acactcagat?gaatactgct?cttattcagt?ggcaccctcc?ggtggacaca?2700

tttggacctc?ttcagggcta?ccgtctaaaa?tttggccgca?aggatatgga?gccacttact?2760

actcttgagt?tctctgaaaa?agaagatcac?tttacagcta?cagacatcca?caagggagca?2820

tcatacgtct?tcaggctctc?agccagaaac?aaagtgggct?ttggggagga?gatggtgaag?2880

gagatttcca?ttccagaaga?agtaccaact?ggattccctc?aaaaccttca?ctcagaaggc?2940

accacttcaa?cctccgtcca?gttatcttgg?caaccacctg?tcctggcaga?gagaaatggc?3000

attatcacca?agtataccct?tctttatagg?gatatcaaca?tcccccttct?cccgatggag?3060

cagcttattg?ttccagctga?caccactatg?acactcactg?gcttaaaacc?agataccaca?3120

tacgatgtaa?aagtacgtgc?tcatacgagc?aaagggcccg?ggccatatag?tcccagtgtc?3180

cagttcagga?cactgcctgt?ggatcaagtg?tttgcaaaaa?attttcatgt?caaagcagta?3240

atgaagactt?ccgtgttgct?gtcttgggag?attccagaga?attataactc?cgccatgcct?3300

ttcaaaattc?tttatgatga?tgggaaaatg?gtagaagaag?tggatggccg?agccacacag?3360

aagttaattg?tcaacctgaa?gcctgagaaa?tcatattcat?ttgtgctgac?aaatcgtgga?3420

aacagtgctg?gtgggctgca?gcacagggtc?acggcaaaga?ctgcaccaga?tgtattacgt?3480

accaagcctg?ccttcattgg?gaagaccaac?ttggatggca?tgattactgt?gcaactgcct?3540

gaagtacctg?caaatgagaa?tataaaaggt?tactacataa?taattgtgcc?tttgaagaaa?3600

tctcgcggga?aatttatcaa?gccatgggag?agtccagatg?aaatggaatt?agatgagctg?3660

cttaaggaga?tatctaggaa?gcgcagaagc?atccgttatg?ggagagaagt?tgaattaaag?3720

ccatatattg?ccgctcactt?tgatgtcctt?cccactgagt?tcaccctggg?ggatgacaag?3780

cattatggtg?gatttacaaa?caagcaactc?caaagtggtc?aagaatatgt?cttctttgtg?3840

ttagcagtaa?tggaacatgc?agagtctaag?atgtatgcaa?ccagccctta?ctccgacccc?3900

gtggtgtcaa?tggatctgga?tccgcagcca?atcacggatg?aagaagaagg?cttgatctgg?3960

gttgtaggtc?ctgtccttgc?agtggtcttt?atcatctgca?ttgtcattgc?tattcttctt?4020

tataaaagga?agagggcaga?gtccgactct?agaaaaagca?gcataccgaa?caataaggag?4080

atcccttcac?accacccaac?agaccctgta?gaactgaggc?gccttaactt?tcaaacaccg?4140

ggtatggcta?gccatcctcc?aatacccatc?ttggaacttg?cagaccacat?tgaaagattg?4200

aaagcaaatg?acaacttgaa?gttttcccag?gaatatgagt?caattgaccc?tggccagcag?4260

ttcacttggg?aacattcaaa?cttggaagta?aacaaaccaa?agaatagata?cgcgaatgta?4320

atcgcatatg?atcattcccg?ggttctccta?tcagctatag?aagggatccc?aggaagtgac?4380

tatgtgaatg?ccaactacat?agatgggtat?aggaagcaaa?atgcctatat?tgcaacacag?4440

ggatctctcc?ccgaaacatt?tggggacttt?tggagaatga?tatgggaaca?acggagtgcc?4500

acagttgtca?tgatgacaaa?actagaagaa?agatcaaggg?tgaagtgtga?ccagtattgg?4560

cctagcagag?gcacagaaac?ccacggactc?gttcaagtaa?cgctgcttga?tactgtggag?4620

ctggccacat?attgtgttcg?aacatttgca?ctttacaaga?atggttcaag?tgagaagaga?4680

gaagtgagac?aattccagtt?caccgcctgg?cctgatcatg?gtgttccaga?acaccctaca?4740

ccttttctag?ctttcttacg?tagagtcaaa?acctgtaacc?ctcccgatgc?tggtccgatg?4800

gttgtgcact?gcagtgcggg?agttggccgg?actggttgct?tcatcgtcat?agatgccatg?4860

ttagaaagaa?taaagcatga?aaaaactgta?gatatttatg?gccatgtaac?tttaatgaga?4920

gcccagagga?actatatggt?tcaaacagaa?gaccaataca?tctttatcca?tgatgcactg?4980

ttagaagcag?tgacttgtgg?aaataccgaa?gtgccagcta?gaaacttgta?tgcctacatt?5040

cagaagctga?cacaaataga?aacgggagag?aatgtcacag?gaatggagct?cgaatttaag?5100

cgtctagcca?gctcaaaagc?tcacacctca?aggtttatca?gtgccaatct?tccatgtaat?5160

aaattcaaaa?atcgccttgt?taatattatg?ccatatgaat?ccacaagggt?atgcctgcag?5220

cctatccgtg?gagtagaagg?atctgattac?atcaatgcca?gttttattga?tggatacaga?5280

caacagaaag?cctacatcgc?tacccagggg?cccttggcag?agaccactga?agacttctgg?5340

cggatgctct?gggaacacaa?ttccaccata?gttgtgatgc?tcaccaagct?gcgtgaaatg?5400

ggcagagaga?aatgtcacca?atactggcca?gcagaacggt?ctgcaagata?ccagtacttt?5460

gttgtagatc?ccatggctga?gtacaacatg?ccacagtata?tcctaaggga?attcaaggtc?5520

acagatgcca?gggacggcca?gtcccgaaca?gtaaggcagt?tccagttcac?tgactggcca?5580

gagcaaggag?tgccaaagtc?cggagaagga?tttattgact?tcatcggcca?agtccataaa?5640

acaaaagaac?agtttggcca?agatggaccc?atttcagtcc?attgcagcgc?gggcgttgga?5700

agaactggag?tcttcataac?gctaagcatt?gttttggaaa?gaatgagata?tgaaggagtt?5760

gtagatatct?tccagactgt?caaaatgtta?agaacacaac?gaccagctat?ggtacagaca?5820

gaggatcaat?atcagttttc?ctatcgtgcc?gcactagagt?acctgggcag?ctttgaccac?5880

tatgcaacgt?agaaacccct?gacccattct?ggatttttac?tacaggccct?tcaatatcca?5940

tggagtctct?tctgagccat?acagggcact?tgagaagtcc?ttcttaactt?ctagctaaca?6000

actacttagt?gggactatta?cacacaaaac?aaattaaaaa?caaattattc?caggtggacc?6060

aagaattctt?tgacatcgcc?ccttcccacc?atactgctca?taataacatt?ttaggggcca?6120

aggggaggga?atgtttaaaa?agaaagtcct?tgatttagtt?ttttagtatt?gtaaagatac?6180

tgctgacctg?tgcttcattt?ctaactgtgt?aaactttttt?ttaacaaaat?gtatcattcg?6240

ataaagtgaa?ttttaaaaaa?gtt 6263

<210>114

<211>1899

<212>PRT

＜213〉people (homo sapiens)

<400>114

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

Gln?Leu?Arg?Ser?Gly?Ala?Leu?Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp

180 185 190

Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr

195 200 205

Ser?Ala?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Val?Arg?Arg?Val?Pro?Pro?Arg

210 215 220

Phe?Ser?Ile?Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val

225 230 235 240

Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp

245 250 255

Met?Leu?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly

260 265 270

Arg?Asn?Val?Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr

275 280 285

Cys?Val?Ala?Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile

290 295 300

Thr?Val?Lys?Ala?Leu?Pro?Lys Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu

305 310 315 320

Ser?Thr?Ala?Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu

325 330 335

Pro?Val?Ser?Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu

340 345 350

Leu?Tyr?Lys?Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala

355 360 365

Gly?Leu?Ser?Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn

370 375 380

Asn?Ile?Gly?Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser

385 390 395 400

Glu?Gln?Ala?Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu

405 410 415

Ser?Ser?Thr?Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn

420 425 430

Gly?Gln?Ile?Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln

435 440 445

His?Val?Asn?Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr

450 455 460

Thr?Ile?Gly?Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu

465 470 475 480

Ala?Phe?Thr?Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val

485 490 495

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

500 505 510

Pro?Glu?Ser?Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser

515 520 525

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

530 535 540

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

545 550 555 560

Gly?Leu?Lys?Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser

565 570 575

Pro?Gln?Gly?Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met

580 585 590

Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro

595 600 605

Ser?Ser?Thr?Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys

610 615 620

Gln?Asn?Gly?Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp

625 630 635 640

Gly?Glu?Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr

645 650 655

Thr?Lys?Tyr?Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile

660 665 670

Thr?Val?Thr?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser

675 680 685

Val?Leu?Ile?Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys

690 695 700

Val?Glu?Val?Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg

705 710 715 720

Ser?Pro?Val?Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val

725 730 735

His?Tyr?Val?Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu

740 745 750

Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr

755 760 765

Glu?His?Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser

770 775 780

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

785 790 795 800

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

805 810 815

Val?Ile?Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro

820 825 830

Pro?Val?Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly

835 840 845

Arg?Lys?Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu

850 855 860

Asp?His?Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe

865 870 875 880

Arg?Leu?Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys

885 890 895

Glu?Ile?Ser?Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu

900 905 910

His?Ser?Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro

915 920 925

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

930 935 940

Tyr?Arg?Asp?Ile?AsnIle?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val

945 950 955 960

Pro?Ala?Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr

965 970 975

Tyr?Asp?Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr

980 985 990

Ser?Pro?Ser?Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp?Gln?Val?Phe?Ala

995 1000 1005

Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser

1010 1015 1020

Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu

1025 1030 1035 1040

Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln

1045 1050 1055

Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu

1060 1065 1070

Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala

1075 1080 1085

Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys

1090 1095 1100

Thr?Asn?Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala

1105 1110 1115 1120

Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys

1125 1130 1135

Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu

1140 1145 1150

Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg

1155 1160 1165

Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp

1170 1175 1180

Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly

1185 1190 1195 1200

Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val

1205 1210 1215

Leu?Ala?Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr

1235 1240 1245

Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val

1250 1255 1260

Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys

1265 1270 1275 1280

Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu

1285 1290 1295

Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn

1300 1305 1310

Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu

1315 1320 1325

Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe

1330 1335 1340

Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu

1345 1350 1355 1360

His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val

1365 1370 1375

Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile

1380 1385 1390

Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys

1395 1400 1405

Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly

1410 1415 1420

Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met

1425 1430 1435 1440

Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp

1445 1450 1455

Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu

1460 1465 1470

Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr

1475 1480 1485

Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr

1490 1495 1500

Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala

1505 1510 1515 1520

Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met

1525 1530 1535

Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val

1540 1545 1550

Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile

1555 1560 1565

Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln

1570 1575 1580

Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val

1585 1590 1595 1600

Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile

1605 1610 1615

Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu

1620 1625 1630

Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe

1635 1640 1645

Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn

1650 1655 1660

Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly

1665 1670 1675 1680

Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg

1685 1690 1695

Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr

1700 1705 1710

Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val

1715 1720 1725

Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr

1730 1735 1740

Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro

1745 1750 1755 1760

Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val

1765 1770 1775

Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe

1780 1785 1790

Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile

1795 1800 1805

Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp

1810 1815 1820

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

1825 1830 1835 1840

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

1845 1850 1855

Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala

1860 1865 1870

Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu

1875 1880 1885

Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

<210>115

<211>246

<212>DNA

＜213〉people (homo sapiens)

<400>115

atgtatttta?cccctaaaga?tggtcatgag?ctctgccata?gccaccaatg?tcttttgata?60

tggttcactg?ttcgagatgt?agtcttgatt?ggcatgaaaa?tgagaggttg?gtccaggagc?120

agtaaagaca?aacataatgc?acgagctcct?tcatatatat?acaagccatt?gcattttgtg?180

gtctcaagat?tcttggactc?atgcagtctt?cggaggatgc?agctaaatct?gtcattgatg?240

atgtag 246

<210>116

<211>1903

<212>PRT

＜213〉people (homo sapiens)

<400>116

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Lys

595 600 605

Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser?Thr

610 615 620

Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn?Gly

625 630 635 640

Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp

645 650 655

Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys?Tyr

660 665 670

Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val?Thr

675 680 685

Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu?Ile

690 695 700

Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu?Val

705 710 715 720

Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro?Val

725 730 735

Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val

740 745 750

Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp?Val

755 760 765

Met?Leu?Ala?Asp?Ala?Gln?Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu

770 775 780

Thr?Ser?Tyr?Ser?Leu?Thr?Val?Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly

785 790 795 800

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

805 810 815

Lys?Pro?Arg?Leu?Val?Ile?Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile

820 825 830

Gln?Trp?His?Pro?Pro?Val?Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg

835 840 845

Leu?Lys?Phe?Gly?Arg?Lys?Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe

850 855 860

Ser?Glu?Lys?Glu?Asp?His?Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala

865 870 875 880

Ser?Tyr?Val?Phe?Arg?Leu?Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu

885 890 895

Glu?Met?Val?Lys?Glu?Ile?SerIle?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe

900 905 910

Pro?Gln?Asn?Leu?His?Ser?Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu

915 920 925

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

930 935 940

Tyr?Thr?Leu?Leu?Tyr?Arg?Asp?Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu

945 950 955 960

Gln?Leu?Ile?Val?Pro?Ala?Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys

965 970 975

Pro?Asp?Thr?Thr?Tyr?Asp?Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly

980 985 990

Pro?Gly?Pro?Tyr?Ser?Pro?Ser?Val?Gln?Phe?Arg?Thr?Leu?Pro?Val?Asp

995 1000 1005

Gln?Val?Phe?Ala?Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser

1010 1015 1020

Val?Leu?Leu?Ser?Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro

1025 1030 1035 1040

Phe?Lys?Ile?Leu?Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly

1045 1050 1055

Arg?Ala?Thr?Gln?Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr

1060 1065 1070

Ser?Phe?Val?Leu?Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His

1075 1080 1085

Arg?Val?Thr?Ala?Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala

1090 1095 1100

Phe?Ile?Gly?Lys?Thr?Asn?Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro

1105 1110 1115 1120

Glu?Val?Pro?Ala?Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val

1125 1130 1135

Pro?Leu?Lys?Lys?Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro

1140 1145 1150

Asp?Glu?Met?Glu?Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg

1155 1160 1165

Arg?Ser?Ile?Arg?Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala

1170 1175 1180

Ala?His?Phe?Asp?Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys

1185 1190 1195 1200

His?Tyr?Gly?Gly?Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr

1205 1210 1215

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

1220 1225 1230

Ala?Thr?Ser?Pro?Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro

1235 1240 1245

Gln?Pro?Ile?Thr?Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro

1250 1255 1260

Val?Leu?Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu

1265 1270 1275 1280

Tyr?Lys?Arg?Lys?Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro

1285 1290 1295

Asn?Asn?Lys?Glu?Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu

1300 1305 1310

Arg?Arg?Leu?Asn?Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile

1315 1320 1325

Pro?Ile?Leu?Glu?Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp

1330 1335 1340

Asn?Leu?Lys?Phe?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln

1345 1350 1355 1360

Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg

1365 1370 1375

Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala

1380 1385 1390

Ile?Glu?Gly?Ile?Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp

1395 1400 1405

Gly?Tyr?Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro

1410 1415 1420

Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala

1425 1430 1435 1440

Thr?Val?Val?Met?Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys

1445 1450 1455

Asp?Gln?Tyr?Trp?Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln

1460 1465 1470

Val?Thr?Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr

1475 1480 1485

Phe?Ala?Leu?Tyr?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln

1490 1495 1500

Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr

1505 1510 1515 1520

Pro?Phe?Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp

1525 1530 1535

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

1540 1545 1550

Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys

1555 1560 1565

Thr?Val?Asp?Ile?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn

1570 1575 1580

Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu

1585 1590 1595 1600

Leu?Glu?Ala?Val?Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu

1605 1610 1615

Tyr?Ala?Tyr?Ile?Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val

1620 1625 1630

Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His

1635 1640 1645

Thr?Ser?Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn

1650 1655 1660

Arg?Leu?Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln

1665 1670 1675 1680

Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile

1685 1690 1695

Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu

1700 1705 1710

Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser

1715 1720 1725

Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys

1730 1735 1740

Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe

1745 1750 1755 1760

Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg

1765 1770 1775

Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg

1780 1785 1790

Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly

1795 1800 1805

Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln

1810 1815 1820

Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly

1825 1830 1835 1840

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

1845 1850 1855

Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr

1860 1865 1870

Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr

1875 1880 1885

Arg?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895 1900

<210>117

<211>6236

<212>DNA

＜213〉people (homo sapiens)

<400>117

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaaagccg?1980

tcagctcctc?ctcaagacat?tagttgcacc?agcccaagtt?ccactagtat?tttggtaagt?2040

tggcaacctc?caccagtgga?aaaacagaat?ggcattatca?ctgaatactc?catcaagtac?2100

actgcagtgg?atggggaaga?tgacaagcct?cacgagattt?tgggaattcc?ttcggacact?2160

accaaatacc?ttttggaaca?gctggaaaaa?tggactgaat?accggatcac?tgtgacagcc?2220

catacagatg?tcggccctgg?ccctgagagc?ttgtccgtgt?tgattcgaac?caatgaagat?2280

gttcctagtg?gtcctcctcg?caaagtcgag?gtagaggctg?tcaactcaac?atctgttaaa?2340

gtctcatggc?gctcacccgt?gcccaataaa?cagcatggcc?agataagagg?atatcaggtg?2400

cattatgtga?ggatggaaaa?tggtgagccc?aagggccagc?ccatgctgaa?agatgtcatg?2460

ctggctgatg?cacaggacat?gatcatttct?gggctccagc?ctgaaacttc?ctactccctc?2520

accgtcacag?cctacacaac?caaaggagat?ggtgctcgca?gcaagcccaa?actggtgtcc?2580

accactgggg?cagttccagg?gaaacctcgg?cttgtgatta?accacactca?gatgaatact?2640

gctcttattc?agtggcaccc?tccggtggac?acatttggac?ctcttcaggg?ctaccgtcta?2700

aaatttggcc?gcaaggatat?ggagccactt?actactcttg?agttctctga?aaaagaagat?2760

cactttacag?ctacagacat?ccacaaggga?gcatcatacg?tcttcaggct?ctcagccaga?2820

aacaaagtgg?gctttgggga?ggagatggtg?aaggagattt?ccattccaga?agaagtacca?2880

actggattcc?ctcaaaacct?tcactcagaa?ggcaccactt?caacctccgt?ccagttatct?2940

tggcaaccac?ctgtcctggc?agagagaaat?ggcattatca?ccaagtatac?ccttctttat?3000

agggatatca?acatccccct?tctcccgatg?gagcagctta?ttgttccagc?tgacaccact?3060

atgacactca?ctggcttaaa?accagatacc?acatacgatg?taaaagtacg?tgctcatacg?3120

agcaaagggc?ccgggccata?tagtcccagt?gtccagttca?ggacactgcc?tgtggatcaa?3180

gtgtttgcaa?aaaattttca?tgtcaaagca?gtaatgaaga?cttccgtgtt?gctgtcttgg?3240

gagattccag?agaattataa?ctccgccatg?cctttcaaaa?ttctttatga?tgatgggaaa?3300

atggtagaag?aagtggatgg?ccgagccaca?cagaagttaa?ttgtcaacct?gaagcctgag?3360

aaatcatatt?catttgtgct?gacaaatcgt?ggaaacagtg?ctggtgggct?gcagcacagg?3420

gtcacggcaa?agactgcacc?agatgtatta?cgtaccaagc?ctgccttcat?tgggaagacc?3480

aacttggatg?gcatgattac?tgtgcaactg?cctgaagtac?ctgcaaatga?gaatataaaa?3540

ggttactaca?taataattgt?gcctttgaag?aaatctcgcg?ggaaatttat?caagccatgg?3600

gagagtccag?atgaaatgga?attagatgag?ctgcttaagg?agatatctag?gaagcgcaga?3660

agcatccgtt?atgggagaga?agttgaatta?aagccatata?ttgccgctca?ctttgatgtc?3720

cttcccactg?agttcaccct?gggggatgac?aagcattatg?gtggatttac?aaacaagcaa?3780

ctccaaagtg?gtcaagaata?tgtcttcttt?gtgttagcag?taatggaaca?tgcagagtct?3840

aagatgtatg?caaccagccc?ttactccgac?cccgtggtgt?caatggatct?ggatccgcag?3900

ccaatcacgg?atgaagaaga?aggcttgatc?tgggttgtag?gtactgtcct?tgcagtggtc?3960

tttatcatct?gcattgtcat?tgctattctt?ctttataaaa?ggaagagggc?agagtccgac?4020

tctagaaaaa?gcagcatacc?gaacaataag?gagatccctt?cacaccaccc?aacagaccct?4080

gtagaactga?ggcgccttaa?ctttcaaaca?ccgggtatgg?ctagccatcc?tccaataccc?4140

atcttggaac?ttgcagacca?cattgaaaga?ttgaaagcaa?atgacaactt?gaagttttcc?4200

caggaatatg?agtcaattga?ccctggccag?cagttcactt?gggaacattc?aaacttggaa?4260

gtaaacaaac?caaagaatag?atacgcgaat?gtaatcgcat?atgatcattc?ccgggttctc?4320

ctatcagcta?tagaagggat?cccaggaagt?gactatgtga?atgccaacta?catagatggg?4380

tataggaagc?aaaatgccta?tattgcaaca?cagggatctc?tccccgaaac?atttggggac?4440

ttttggagaa?tgatatggga?acaacggagt?gccacagttg?tcatgatgac?aaaactagaa?4500

gaaagatcaa?gggtgaagtg?tgaccagtat?tggcctagca?gaggcacaga?aacccacgga?4560

ctcgttcaag?taacgctgct?tgatactgtg?gagctggcca?catattgtgt?tcgaacattt?4620

gcactttaca?agaatggttc?aagtgagaag?agagaagtga?gacaattcca?gttcaccgcc?4680

tggcctgatc?atggtgttcc?agaacaccct?acaccttttc?tagctttctt?acgtagagtc?4740

aaaacctgta?accctcccga?tgctggtccg?atggttgtgc?actgcagtgc?gggagttggc?4800

cggactggtt?gcttcatcgt?catagatgcc?atgttagaaa?gaataaagca?tgaaaaaact?4860

gtagatattt?atggccatgt?aactttaatg?agagcccaga?ggaactatat?ggttcaaaca?4920

gaagaccaat?acatctttat?ccatgatgca?ctgttagaag?cagtgacttg?tggaaatacc?4980

gaagtgccag?ctagaaactt?gtatgcctac?attcagaagc?tgacacaaat?agaaacggga?5040

gagaatgtca?caggaatgga?gctcgaattt?aagcgtctag?ccagctcaaa?agctcacacc?5100

tcaaggttta?tcagtgccaa?tcttccatgt?aataaattca?aaaatcgcct?tgttaatatt?5160

atgccatatg?aatccacaag?ggtatgcctg?cagcctatcc?gtggagtaga?aggatctgat?5220

tacatcaatg?ccagttttat?tgatggatac?agacaacaga?aagcctacat?cgctacccag?5280

gggcccttgg?cagagaccac?tgaagacttc?tggcggatgc?tctgggaaca?caattccacc?5340

atagttgtga?tgctcaccaa?gctgcgtgaa?atgggcagag?agaaatgtca?ccaatactgg?5400

ccagcagaac?ggtctgcaag?ataccagtac?tttgttgtag?atcccatggc?tgagtacaac?5460

atgccacagt?atatcctaag?ggaattcaag?gtcacagatg?ccagggacgg?ccagtcccga?5520

acagtaaggc?agttccagtt?cactgactgg?ccagagcaag?gagtgccaaa?gtccggagaa?5580

ggatttattg?acttcatcgg?ccaagtccat?aaaacaaaag?aacagtttgg?ccaagatgga?5640

cccatttcag?tccattgcag?cgcgggcgtt?ggaagaactg?gagtcttcat?aacgctaagc?5700

attgttttgg?aaagaatgag?atatgaagga?gttgtagata?tcttccagac?tgtcaaaatg?5760

ttaagaacac?aacgaccagc?tatggtacag?acagaggatc?aatatcagtt?ttcctatcgt?5820

gccgcactag?agtacctggg?cagctttgac?cactatgcaa?cgtagaaacc?cctgacccat?5880

tctggatttt?tactacaggc?ccttcaatat?ccatggagtc?tcttctgagc?catacagggc?5940

acttgagaag?tccttcttaa?cttctagcta?acaactactt?agtgggacta?ttacacacaa?6000

aacaaattaa?aaacaaatta?ttccaggtgg?accaagaatt?ctttgacatc?gccccttccc?6060

accatactgc?tcataataac?attttagggg?ccaaggggag?ggaatgttta?aaaagaaagt?6120

ccttgattta?gttttttagt?attgtaaaga?tactgctgac?ctgtgcttca?tttctaactg?6180

tgtaaacttt?tttttaacaa?aatgtatcat?tcgataaagt?gaattttaaa?aaagtt 6236

<210>118

<211>1501

<212>PRT

＜213〉people (homo sapiens)

<400>118

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

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

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

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

225 230 235 240

Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile?Thr

245 250 255

Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu?Gly

260 265 270

Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn?Val

275 280 285

Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala

290 295 300

Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val?Lys

305 310 315 320

Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr?Ala

325 330 335

Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val?Ser

340 345 350

Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr?Lys

355 360 365

Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu?Ser

370 375 380

Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile?Gly

385 390 395 400

Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln?Ala

405 410 415

Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser?Thr

420 425 430

Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln?Ile

435 440 445

Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val?Asn

450 455 460

Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile?Gly

465 470 475 480

Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe?Thr

485 490 495

Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr?Gln

500 505 510

Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu?Ser

515 520 525

Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr?Ile

530 535 540

Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu?Gln

545 550 555 560

Arg?Ile?Thr?Ile?Glu?Pro?Gly?Thr?Ser?Tyr?Arg?Leu?Gln?Gly?Leu?Lys

565 570 575

Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly

580 585 590

Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser?Met

595 600 605

Phe?Ala?Lys?Asn?Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu

610 615 620

Leu?Ser?Trp?Glu?Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys

625 630 635 640

Ile?Leu?Tyr?Asp?Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala

645 650 655

Thr?Gln?Lys?Leu?Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe

660 665 670

Val?Leu?Thr?Asn?Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val

675 680 685

Thr?Ala?Lys?Thr?Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile

690 695 700

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

705 710 715 720

Pro?Ala?Asn?Glu?Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu

725 730 735

Lys?Lys?Ser?Arg?Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu

740 745 750

Met?Glu?Leu?Asp?Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser

755 760 765

Ile?Arg?Tyr?Gly?Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His

770 775 780

Phe?Asp?Val?Leu?Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr

785 790 795 800

Gly?Gly?Phe?Thr?Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe

805 810 815

Phe?Val?Leu?Ala?Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr

820 825 830

Ser?Pro?Tyr?Ser?Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro

835 840 845

Ile?Thr?Asp?Glu?Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu

850 855 860

Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys

865 870 875 880

Arg?Lys?Arg?Ala?Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn

885 890 895

Lys?Glu?Ile?Pro?Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg

900 905 910

Leu?Asn?Phe?Gln?Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile

915 920 925

Leu?Glu?Leu?Ala?Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu

930 935 940

Lys?Phe?Ser?Gln?Glu?Tyr?Glu?SerIle?Asp?Pro?Gly?Gln?Gln?Phe?Thr

945 950 955 960

Trp?Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala

965 970 975

Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu

980 985 990

Gly?Ile?Pro?Gly?Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr

995 1000 1005

Arg?Lys?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr

1010 1015 1020

Phe?Gly?Asp?Phe?Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val

1025 1030 1035 1040

Val?Met?Met?Thr?Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln

1045 1050 1055

Tyr?Trp?Pro?Ser?Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr

1060 1065 1070

Leu?Leu?Asp?Thr?Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala

1075 1080 1085

Leu?Tyr?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln

1090 1095 1100

Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe

1105 1110 1115 1120

Leu?Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly

1125 1130 1135

Pro?Met?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe

1140 1145 1150

Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val

1155 1160 1165

Asp?Ile?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met

1170 1175 1180

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu

1185 1190 1195 1200

Ala?Val?Thr?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala

1205 1210 1215

Tyr?Ile?Gln?Lys?Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly

1220 1225 1230

Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser?Ser?Lys?Ala?His?Thr?Ser

1235 1240 1245

Arg?Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu

1250 1255 1260

Val?Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile

1265 1270 1275 1280

Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly

1285 1290 1295

Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu

1300 1305 1310

Thr?Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile

1315 1320 1325

Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His

1330 1335 1340

Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val

1345 1350 1355 1360

Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe

1365 1370 1375

Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe

1380 1385 1390

Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys Ser?Gly?Glu?Gly

1395 1400 1405

Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly

1410 1415 1420

Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr

1425 1430 1435 1440

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

1445 1450 1455

Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg

1460 1465 1470

Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala

1475 1480 1485

Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1490 1495 1500

<210>119

<211>5030

<212>DNA

＜213〉people (homo sapiens)

<400>119

gctaactcaa?gggagacgtc?tggtgaacac?ccgtgggatc?taaagaacaa?gctctgaaag?60

tgttccagct?gaaatttcag?atcggacaga?ctcgctgcgg?ctccggaggc?agtgattcca?120

agctgctcgc?gcacgctgct?gccaagctgc?aggatggtgc?acgtagccag?gctgctgctg?180

ctgctcctca?ctttcttcct?ccgcacggat?gctgagacac?ctccaaggtt?tacacgaaca?240

cccgttgatc?agacaggggt?ctctggcgga?gttgcctctt?tcatctgcca?agctacggga?300

gacccaagac?ctaaaattgt?ctggaacaaa?aaaggaaaga?aagtcagcaa?tcagagattt?360

gaggtaatag?agtttgacga?tgggtctgga?tcagttctca?gaatacaacc?cttacggact?420

ccgagggatg?aggccattta?tgaatgtgtg?gcctcaaata?atgtgggaga?aataagtgta?480

tccaccagac?tcacagtttt?gcgggaagat?caaattccca?ggggcttccc?taccattgac?540

atgggcccac?agttgaaggt?ggttgagcgt?actcgcacgg?ccaccatgct?ttgtgcagcc?600

agtggtaatc?cggatccaga?aatcacttgg?tttaaagatt?tcttacctgt?ggacacaagc?660

aacaacaatg?gtcgtattaa?gcagttacga?tcagaatcta?ttggtggtac?accaataaga?720

ggagcccttc?agattgagca?gagtgaagag?tctgaccaag?gaaaatatga?gtgtgttgcc?780

accaacagcg?cgggcactcg?ctattccgct?cctgccaatt?tatatgtcag?agagctgcga?840

gaagttcgcc?gtgtcccacc?aagattctct?atcccaccca?ctaatcatga?aatcatgcca?900

ggcggaagcg?ttaatatcac?ctgtgtggcc?gtggggtcac?caatgcctta?tgtaaagtgg?960

atgttggggg?cagaagatct?gacacctgaa?gatgatatgc?caataggaag?aaatgtgcta?1020

gaactgaatg?atgtaagaca?gtcagcaaat?tacacctgtg?ttgctatgtc?aacactgggt?1080

gtcattgaag?caatagcaca?gatcactgtc?aaagccttac?ccaaacctcc?aggaactcct?1140

gtagtgaccg?agagcacagc?tacaagcatc?acactgacgt?gggactctgg?gaaccctgag?1200

cctgtttctt?attacataat?tcagcataaa?cctaaaaact?ctgaggaact?ttacaaagaa?1260

attgatgggg?tggcgaccac?acgctacagt?gtcgctggac?taagtcccta?ctcggattat?1320

gaattcaggg?ttgttgctgt?caataacatt?gggcgggggc?ctcccagcga?acctgtgcta?1380

acacaaacct?cagagcaagc?accatccagt?gccccgaggg?atgtccaggc?acgaatgttg?1440

agttcgacca?ccattttggt?acagtggaag?gaacctgaag?agccaaatgg?acagatccaa?1500

ggatatagag?tttattatac?aatggatccc?actcaacatg?tcaacaactg?gatgaaacac?1560

aatgtagctg?acagccaaat?cactactatt?ggcaacttag?tgccccagaa?aacatattct?1620

gtcaaagtcc?tggcttttac?ctcaattgga?gatggtcccc?tttcaagtga?catacaagtc?1680

atcactcaga?caggagtacc?agggcagcca?ctaaacttca?aagcagaacc?tgagtctgaa?1740

acaagtattt?tgctctcttg?gacacctcca?cgttcagata?ccattgccaa?ctatgaactg?1800

gtctacaaag?atggggagca?tggagaggag?caacgaatta?ccattgagcc?agggacatca?1860

tataggctgc?aaggactgaa?accaaacagc?ttatactatt?tccgtctggc?tgcacgctcc?1920

cctcaaggcc?tgggtgcttc?tactgcagaa?atatcagcta?gaaccatgca?gtcaatgttt?1980

gcaaaaaatt?ttcatgtcaa?agcagtaatg?aagacttccg?tgttgctgtc?ttgggagatt?2040

ccagagaatt?ataactccgc?catgcctttc?aaaattcttt?atgatgatgg?gaaaatggta?2100

gaagaagtgg?atggccgagc?cacacagaag?ttaattgtca?acctgaagcc?tgagaaatca?2160

tattcatttg?tgctgacaaa?tcgtggaaac?agtgctggtg?ggctgcagca?cagggtcacg?2220

gcaaagactg?caccagatgt?attacgtacc?aagcctgcct?tcattgggaa?gaccaacttg?2280

gatggcatga?ttactgtgca?actgcctgaa?gtacctgcaa?atgagaatat?aaaaggttac?2340

tacataataa?ttgtgccttt?gaagaaatct?cgcgggaaat?ttatcaagcc?atgggagagt?2400

ccagatgaaa?tggaattaga?tgagctgctt?aaggagatat?ctaggaagcg?cagaagcatc?2460

cgttatggga?gagaagttga?attaaagcca?tatattgccg?ctcactttga?tgtccttccc?2520

actgagttca?ccctggggga?tgacaagcat?tatggtggat?ttacaaacaa?gcaactccaa?2580

agtggtcaag?aatatgtctt?ctttgtgtta?gcagtaatgg?aacatgcaga?gtctaagatg?2640

tatgcaacca?gcccttactc?cgaccccgtg?gtgtcaatgg?atctggatcc?gcagccaatc?2700

acggatgaag?aagaaggctt?gatctgggtt?gtaggtcctg?tccttgcagt?ggtctttatc?2760

atctgcattg?tcattgctat?tcttctttat?aaaaggaaga?gggcagagtc?cgactctaga?2820

aaaagcagca?taccgaacaa?taaggagatc?ccttcacacc?acccaacaga?ccctgtagaa?2880

ctgaggcgcc?ttaactttca?aacaccgggt?atggctagcc?atcctccaat?acccatcttg?2940

gaacttgcag?accacattga?aagattgaaa?gcaaatgaca?acttgaagtt?ttcccaggaa?3000

tatgagtcaa?ttgaccctgg?ccagcagttc?acttgggaac?attcaaactt?ggaagtaaac?3060

aaaccaaaga?atagatacgc?gaatgtaatc?gcatatgatc?attcccgggt?tctcctatca?3120

gctatagaag?ggatcccagg?aagtgactat?gtgaatgcca?actacataga?tgggtatagg?3180

aagcaaaatg?cctatattgc?aacacaggga?tctctccccg?aaacatttgg?ggacttttgg?3240

agaatgatat?gggaacaacg?gagtgccaca?gttgtcatga?tgacaaaact?agaagaaaga?3300

tcaagggtga?agtgtgacca?gtattggcct?agcagaggca?cagaaaccca?cggactcgtt?3360

caagtaacgc?tgcttgatac?tgtggagctg?gccacatatt?gtgttcgaac?atttgcactt?3420

tacaagaatg?gttcaagtga?gaagagagaa?gtgagacaat?tccagttcac?cgcctggcct?3480

gatcatggtg?ttccagaaca?ccctacacct?tttctagctt?tcttacgtag?agtcaaaacc?3540

tgtaaccctc?ccgatgctgg?tccgatggtt?gtgcactgca?gtgcgggagt?tggccggact?3600

ggttgcttca?tcgtcataga?tgccatgtta?gaaagaataa?agcatgaaaa?aactgtagat?3660

atttatggcc?atgtaacttt?aatgagagcc?cagaggaact?atatggttca?aacagaagac?3720

caatacatct?ttatccatga?tgcactgtta?gaagcagtga?cttgtggaaa?taccgaagtg?3780

ccagctagaa?acttgtatgc?ctacattcag?aagctgacac?aaatagaaac?gggagagaat?3840

gtcacaggaa?tggagctcga?atttaagcgt?ctagccagct?caaaagctca?cacctcaagg?3900

tttatcagtg?ccaatcttcc?atgtaataaa?ttcaaaaatc?gccttgttaa?tattatgcca?3960

tatgaatcca?caagggtatg?cctgcagcct?atccgtggag?tagaaggatc?tgattacatc?4020

aatgccagtt?ttattgatgg?atacagacaa?cagaaagcct?acatcgctac?ccaggggccc?4080

ttggcagaga?ccactgaaga?cttctggcgg?atgctctggg?aacacaattc?caccatagtt?4140

gtgatgctca?ccaagctgcg?tgaaatgggc?agagagaaat?gtcaccaata?ctggccagca?4200

gaacggtctg?caagatacca?gtactttgtt?gtagatccca?tggctgagta?caacatgcca?4260

cagtatatcc?taagggaatt?caaggtcaca?gatgccaggg?acggccagtc?ccgaacagta?4320

aggcagttcc?agttcactga?ctggccagag?caaggagtgc?caaagtccgg?agaaggattt?4380

attgacttca?tcggccaagt?ccataaaaca?aaagaacagt?ttggccaaga?tggacccatt?4440

tcagtccatt?gcagcgcggg?cgttggaaga?actggagtct?tcataacgct?aagcattgtt?4500

ttggaaagaa?tgagatatga?aggagttgta?gatatcttcc?agactgtcaa?aatgttaaga?4560

acacaacgac?cagctatggt?acagacagag?gatcaatatc?agttttccta?tcgtgccgca?4620

ctagagtacc?tgggcagctt?tgaccactat?gcaacgtaga?aacccctgac?ccattctgga?4680

tttttactac?aggcccttca?atatccatgg?agtctcttct?gagccataca?gggcacttga?4740

gaagtccttc?ttaacttcta?gctaacaact?acttagtggg?actattacac?acaaaacaaa?4800

ttaaaaacaa?attattccag?gtggaccaag?aattctttga?catcgcccct?tcccaccata?4860

ctgctcataa?taacatttta?ggggccaagg?ggagggaatg?tttaaaaaga?aagtccttga?4920

tttagttttt?tagtattgta?aagatactgc?tgacctgtgc?ttcatttcta?actgtgtaaa?4980

ctttttttta?acaaaatgta?tcattcgata?aagtgaattt?taaaaaagtt 5030

<210>120

<211>14

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>120

Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser?Val?Val?Thr?Arg

1 5 10

<210>121

<211>22

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>121

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

1 5 10 15

Asp?Glu?Thr?Tyr?Val?Arg

20

<210>122

<211>19

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>122

Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu?Ser?Asp?Pro?Ile

1 5 10 15

Gln?Val?Lys

<210>123

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>123

Thr?Glu?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg

1 5 10 15

<210>124

<211>16

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>124

Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu?Gly?Tyr?Arg

1 5 10 15

<210>125

<211>20

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>125

Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro

1 5 10 15

Thr?Pro?Tyr?Lys

20

<210>126

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP σ fragment

<400>126

Thr?Glu?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg

1 5 10 15

<210>127

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>127

Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser?Val?Leu?Arg

1 5 10 15

<210>128

<211>16

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>128

Ser?Gly?Ala?Leu?Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys

1 5 10 15

<210>129

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>129

Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr?Val

1 5

<210>130

<211>18

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>130

Trp?Met?Leu?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile

1 5 10 15

Gly?Arg

<210>131

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ Ig structural domain

<400>131

Asn?Val?Leu?Glu?Leu?Asn?Asp?Val?Arg

1 5

<210>132

<211>21

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>132

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

1 5 10 15

Ser?Ser?Ala?Pro?Arg

20

<210>133

<211>15

<212>PRT

＜213〉artificial sequence

<220>

＜223〉PTP δ fragment

<400>133

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

1 5 10 15

<210>134

<211>23

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>134

Tyr?Thr?Ala?Val?Asp?Gly?Glu?Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly

1 5 10 15

Ile?Pro?Ser?Asp?Thr?Thr?Lys

20

<210>135

<211>9

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>135

Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys

1 5

<210>136

<211>12

<212>PRT

＜213〉artificial sequence

<220>

＜223〉RPTP δ fragment

<400>136

Gly?Pro?Gly?Pro?Tyr?Ser?Pro?Ser?Val?Gln?Phe?Arg

1 5 10

<210>137

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉FLAG flag sequence

<400>137

Asp?Tyr?Lys?Asp?Asp?Asp?Asp?Lys

1 5

<210>138

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉XPRESS epi-position mark

<400>138

Asp?Leu?Tyr?Asp?Asp?Asp?Asp?Lys

1 5

<210>139

<211>1948

<212>PRT

＜213〉people (homo sapiens)

<400>139

Met?Ala?Pro?Thr?Trp?Gly?Pro?Gly?Met?Val?Ser?Val?Val?Gly?Pro?Met

1 5 10 15

Gly?Leu?Leu?Val?Val?Leu?Leu?Val?Gly?Gly?Cys?Ala?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Lys?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Glu?Phe?Asp?Glu?Ser?Ala?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Val?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

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

195 200 205

Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val?Ala?Thr?Asn?Ser?Ala?Gly?Val

210 215 220

Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr?Val?Arg?Glu?Leu?Arg?Glu?Val

225 230 235 240

Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser?His?Glu?Ile

245 250 255

Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val?Gly?Ser?Pro

260 265 270

Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu

275 280 285

Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr?Asp?Val?Lys

290 295 300

Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu?Gly?Val?Ile

305 310 315 320

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

325 330 335

Thr?Pro?Met?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr?Ile?Thr?Trp

340 345 350

Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile?Glu?Tyr?Lys

355 360 365

Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp?Ile?Thr?Thr

370 375 380

Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu?Tyr?Glu?Ile

385 390 395 400

Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro?Ser?Glu?Ser

405 410 415

Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala?Pro?Arg?Asn

420 425 430

Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val?Gln?Trp?Glu

435 440 445

Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg?Val?Tyr?Tyr

450 455 460

Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys?His?Asn?Val

465 470 475 480

Asp?Asp?Ser?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Glu?Asp?Glu?Thr

485 490 495

Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp?Gly?Pro?Leu

500 505 510

Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro?Gly?Gln?Pro

515 520 525

Met?Asn?Leu?Arg?Ala?Glu?Ala?Arg?Ser?Glu?Thr?Ser?Ile?Thr?Leu?Ser

530 535 540

Trp?Ser?Pro?Pro?Arg?Gln?Glu?Ser?Ile?Ile?Lys?Tyr?Glu?Leu?Leu?Phe

545 550 555 560

Arg?Glu?Gly?Asp?His?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe?Asp?Pro?Thr

565 570 575

Thr?Ser?Tyr?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu?Tyr?Ala?Phe

580 585 590

Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe?Thr?Pro?Val

595 600 605

Val?Arg?Gln?Arg?Thr?Leu?Gln?Ser?Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp

610 615 620

Val?Lys?Cys?Val?Ser?Val?Arg?Ser?Thr?Ala?Ile?Leu?Val?Ser?Trp?Arg

625 630 635 640

Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly?Tyr?Ser?Val

645 650 655

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

660 665 670

Gly?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala?Leu?Glu?Lys

675 680 685

Trp?Thr?Gln?Tyr?Arg?Ile?Thr?Thr?Val?Ala?His?Thr?Glu?Val?Gly?Pro

690 695 700

Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu?Asp?Val?Pro

705 710 715 720

Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn?Ala?Thr?Ala

725 730 735

Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Ala?Pro?Gly?Arg?Gln?His?Gly?Gln

740 745 750

Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly?Ala?Glu?Ala

755 760 765

Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Val?Met?Leu?Ala?Asp?Ala?Gln?Trp

770 775 780

Glu?Thr?Asp?Asp?Thr?Ala?Glu?Tyr?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln

785 790 795 800

Pro?Glu?Thr?Ala?Tyr?Ser?Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly

805 810 815

Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val

820 825 830

Leu?Gly?Arg?Pro?Thr?Leu?Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu

835 840 845

Leu?Ala?Arg?Trp?Glu?Pro?Pro?Ala?Gly?Thr?Ala?Glu?Asp?Gln?Val?Leu

850 855 860

Gly?Tyr?Arg?Leu?Gln?Phe?Gly?Arg?Glu?Asp?Ser?Thr?Pro?Leu?Ala?Thr

865 870 875 880

Leu?Glu?Phe?Pro?Pro?Ser?Glu?Asp?Arg?Tyr?Thr?Ala?Ser?Gly?Val?His

885 890 895

Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Arg?Gly?Gly

900 905 910

Leu?Gly?Glu?Glu?Ala?Ala?Glu?Val?Leu?Ser?Ile?Pro?Glu?Asp?Thr?Pro

915 920 925

Arg?Gly?His?Pro?Gln?Ile?Leu?Glu?Ala?Ala?Gly?Asn?Ala?Ser?Ala?Gly

930 935 940

Thr?Val?Leu?Leu?Arg?Trp?Leu?Pro?Pro?Val?Pro?Ala?Glu?Arg?Asn?Gly

945 950 955 960

Ala?Ile?Val?Lys?Tyr?Thr?Val?Ala?Val?Arg?Glu?Ala?Gly?Ala?Leu?Gly

965 970 975

Pro?Ala?Arg?Glu?Thr?Glu?Leu?Pro?Ala?Ala?Ala?Glu?Pro?Gly?Ala?Glu

980 985 990

Asn?Ala?Leu?Thr?Leu?Gln?Gly?Leu?Lys?Pro?Asp?Thr?Ala?Tyr?Asp?Leu

995 1000 1005

Gln?Val?Arg?Ala?His?Thr?Arg?Arg?Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro

1010 1015 1020

Val?Arg?Tyr?Arg?Thr?Phe?Leu?Arg?Asp?Gln?Val?Ser?Pro?Lys?Asn?Phe

1025 1030 1035 1040

Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu?Phe

1045 1050 1055

Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro?Tyr?Lys?Ile?Gln?Tyr?Asn?Gly

1060 1065 1070

Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr?Thr?Lys?Lys?Leu?Ile?Thr?His

1075 1080 1085

Leu?Lys?Pro?His?Thr?Phe?Tyr?Asn?Phe?Val?Leu?Thr?Asn?Arg?Gly?Ser

1090 1095 1100

Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val?Thr?Ala?Trp?Thr?Ala?Phe?Asn

1105 1110 1115 1120

Leu?Leu?Asn?Gly?Lys?Pro?Ser?Val?Ala?Pro?Lys?Pro?Asp?Ala?Asp?Gly

1125 1130 1135

Phe?Ile?Met?Val?Tyr?Leu?Pro?Asp?Gly?Gln?Ser?Pro?Val?Pro?Val?Gln

1140 1145 1150

Ser?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu?Arg?Lys?Ser?Arg?Gly?Gly?Gln

1155 1160 1165

Phe?Leu?Thr?Pro?Leu?Gly?Ser?Pro?Glu?Asp?Met?Asp?Leu?Glu?Glu?Leu

1170 1175 1180

Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg?Arg?Ser?Leu?Arg?His?Ser?Arg

1185 1190 1195 1200

Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile?Ala?Ala?Arg?Phe?Ser?Val?Leu

1205 1210 1215

Pro?Pro?Thr?Phe?His?Pro?Gly?Asp?Gln?Lys?Gln?Tyr?Gly?Gly?Phe?Asp

1220 1225 1230

Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg?Tyr?Val?Leu?Phe?Val?Leu?Ala

1235 1240 1245

Val?Leu?Gln?Lys?Ser?Glu?Pro?Thr?Phe?Ala?Ala?Ser?Pro?Phe?Ser?Asp

1250 1255 1260

Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro?Gln?Pro?Ile?Val?Asp?Gly?Glu

1265 1270 1275 1280

Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro?Val?Leu?Ala?Val?Val?Phe?Ile

1285 1290 1295

Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Asn?Lys?Pro?Asp?Ser

1300 1305 1310

Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr?Lys?Cys?Leu?Leu?Asn?Asn?Ala

1315 1320 1325

Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp?Pro?Val?Glu?Met?Arg?Arg?Ile

1330 1335 1340

Asn?Phe?Gln?Thr?Pro?Asp?Ser?Gly?Leu?Arg?Ser?Pro?Leu?Arg?Glu?Pro

1345 1350 1355 1360

Gly?Phe?His?Phe?Glu?Ser?Met?Leu?Ser?His?Pro?Pro?Ile?Pro?Ile?Ala

1365 1370 1375

Asp?Met?Ala?Glu?His?Thr?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Ser?Leu?Lys

1380 1385 1390

Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp

1395 1400 1405

Glu?His?Ser?Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn

1410 1415 1420

Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val?Ile?Leu?Gln?Pro?Ile?Glu?Gly

1425 1430 1435 1440

Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Val?Asp?Gly?Tyr?Arg

1445 1450 1455

Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Phe

1460 1465 1470

Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Ile?Val

1475 1480 1485

Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Ile?Lys?Cys?Asp?Gln?Tyr

1490 1495 1500

Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Phe?Ile?Gln?Val?Thr?Leu

1505 1510 1515 1520

Leu?Asp?Thr?Ile?Glu?Leu?Ala?Thr?Phe?Cys?Val?Arg?Thr?Phe?Ser?Leu

1525 1530 1535

His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe

1540 1545 1550

Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Phe?Leu

1555 1560 1565

Ala?Phe?Leu?Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro

1570 1575 1580

Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile

1585 1590 1595 1600

Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile?Lys?Pro?Glu?Lys?Thr?Val?Asp

1605 1610 1615

Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val

1620 1625 1630

Gln?Thr?Glu?Asp?Gln?Tyr?Ser?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala

1635 1640 1645

Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Ser?Leu?Tyr?Ala?Tyr

1650 1655 1660

Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro?Gly?Glu?His?Val?Thr?Gly?Met

1665 1670 1675 1680

Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg

1685 1690 1695

Phe?Ile?Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val

1700 1705 1710

Asn?Ile?Met?Pro?Tyr?Glu?Ser?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg

1715 1720 1725

Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr

1730 1735 1740

Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr

1745 1750 1755 1760

Thr?Glu?Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?Asn?Asn?Ser?Thr?Ile?Val

1765 1770 1775

Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln

1780 1785 1790

Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp

1795 1800 1805

Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys

1810 1815 1820

Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln

1825 1830 1835 1840

Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe

1845 1850 1855

Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln

1860 1865 1870

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

1875 1880 1885

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

1890 1895 1900

Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro

1905 1910 1915 1920

Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr?Gln?Phe?Cys?Tyr?Gln?Ala?Ala

1925 1930 1935

Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1940 1945

<210>140

<211>6412

<212>DNA

＜213〉people (homo sapiens)

<400>140

gcggtggcgg?cggcagaggc?ggcggctcca?gcttcggctc?cggctcgggc?tcgggctccg?60

gctccggctc?cggctccggc?tccagctcgg?gtggcggtgg?cgggagcggg?accaggtgga?120

ggcggcggcg?gcagaggagt?gggagcagcg?gccctagcgg?cttgcggggg?gacatgcgga?180

ccgacggccc?ctggataggc?ggaaggagtg?gaggccctgg?tgcccggccc?ttggtgctga?240

gtatccagca?agagtgaccg?gggtgaagaa?gcaaagactc?ggttgattgt?cctgggctgt?300

ggctggctgt?ggagctagag?ccctggatgg?cccctgagcc?agccccaggg?aggacgatgg?360

tgccccttgt?gcctgcactg?gtgatgcttg?gtttggtggc?aggcgcccat?ggtgacagca?420

aacctgtctt?cattaaagtc?cctgaggacc?agactgggct?gtcaggaggg?gtagcctcct?480

tcgtgtgcca?agctacagga?gaacccaagc?cgcgcatcac?atggatgaag?aaggggaaga?540

aagtcagctc?ccagcgcttc?gaggtcattg?agtttgatga?tggggcaggg?tcagtgcttc?600

ggatccagcc?attgcgggtg?cagcgagatg?aagccatcta?tgagtgtaca?gctactaaca?660

gcctgggtga?gatcaacact?agtgccaagc?tctcagtgct?cgaagaggaa?cagctgcccc?720

ctgggttccc?ttccatcgac?atggggcctc?agctgaaggt?ggtggagaag?gcacgcacag?780

ccaccatgct?atgtgccgca?ggcggaaatc?cagaccctga?gatttcttgg?ttcaaggact?840

tccttcctgt?agaccctgcc?acgagcaacg?gccgcatcaa?gcagctgcgt?tcaggtgcct?900

tgcagataga?gagcagtgag?gaatccgacc?aaggcaagta?cgagtgtgtg?gcgaccaact?960

cggcaggcac?acgttactca?gcccctgcga?acctgtatgt?gcgagtgcgc?cgcgtggctc?1020

ctcgtttctc?catccctccc?agcagccagg?aggtgatgcc?aggcggcagc?gtgaacctga?1080

catgcgtggc?agtgggtgca?cccatgccct?acgtgaagtg?gatgatgggg?gccgaggagc?1140

tcaccaagga?ggatgagatg?ccagttggcc?gcaacgtcct?ggagctcagc?aatgtcgtac?1200

gctctgccaa?ctacacctgt?gtggccatct?cctcgctggg?catgatcgag?gccacagccc?1260

aggtcacagt?gaaagctctt?ccaaagcctc?cgattgatct?tgtggtgaca?gagacaactg?1320

ccaccagtgt?caccctcacc?tgggactctg?ggaactcgga?gcctgtaacc?tactatggca?1380

tccagtaccg?cgcagcgggc?acggagggcc?cctttcagga?ggtggatggt?gtggccacca?1440

cccgctacag?cattggcggc?ctcagccctt?tctcggaata?tgccttccgc?gtgctggcgg?1500

tgaacagcat?cgggcgaggg?ccgcccagcg?aggcagtgcg?ggcacgcacg?ggagaacagg?1560

cgccctccag?cccaccgcgc?cgcgtgcagg?cacgcatgct?gagcgccagc?accatgctgg?1620

tgcagtggga?gcctcccgag?gagcccaacg?gcctggtgcg?gggataccgc?gtctactata?1680

ctccggactc?ccgccgcccc?ccgaacgcct?ggcacaagca?caacaccgac?gcggggctcc?1740

tcacgaccgt?gggcagcctg?ctgcctggca?tcacctacag?cctgcgcgtg?cttgccttca?1800

ccgccgtggg?cgatggccct?cccagcccca?ccatccaggt?caagacgcag?cagggagtgc?1860

ctgcccagcc?cgcggacttc?caggccgagg?tggagtcgga?caccaggatc?cagctctcgt?1920

ggctgctgcc?ccctcaggag?cggatcatca?tgtatgaact?ggtgtactgg?gcggcagagg?1980

acgaagacca?acagcacaag?gtgaccttcg?acccaacctc?ctcctacaca?ctagaggacc?2040

tgaagcctga?cacactctac?cgcttccagc?tggctgcacg?ctcggatatg?ggggtgggcg?2100

tcttcacccc?caccattgag?gcccgcacag?cccagtccac?cccctccgcc?cctccccaga?2160

aggtgatgtg?tgtgagcatg?ggctccacca?cggtccgggt?aagttgggtc?ccgccgcctg?2220

ccgacagccg?caacggcgtt?atcacccagt?actccgtggc?ctacgaggcg?gtggacggcg?2280

aggaccgcgg?gcggcatgtg?gtggatggca?tcagccgtga?gcactccagc?tgggacctgg?2340

tgggcctgga?gaagtggacg?gagtaccggg?tgtgggtgcg?ggcacacaca?gacgtgggcc?2400

ccggccccga?gagcagcccg?gtgctggtgc?gcaccgatga?ggacgtgccc?agcgggcctc?2460

cgcggaaggt?ggaggtggag?ccactgaact?ccactgctgt?gcatgtctac?tggaagctgc?2520

ctgtccccag?caagcagcat?ggccagatcc?gcggctacca?ggtcacctac?gtgcggctgg?2580

agaatggcga?gccccgtgga?ctccccatca?tccaagacgt?catgctagcc?gaggcccagg?2640

aaaccactat?cagcggcctg?accccggaga?ccacctactc?cgttactgtt?gctgcctata?2700

ccaccaaggg?ggatggtgcc?cgcagcaagc?ccaaaattgt?cactacaaca?ggtgcagtcc?2760

caggccggcc?caccatgatg?atcagcacca?cggccatgaa?cactgcgctg?ctccagtggc?2820

acccacccaa?ggaactgcct?ggcgagctgc?tgggctaccg?gctgcagtac?tgccgggccg?2880

acgaggcgcg?gcccaacacc?atagatttcg?gcaaggatga?ccagcacttc?acagtcaccg?2940

gcctgcacaa?ggggaccacc?tacatcttcc?ggcttgctgc?caagaaccgg?gctggcttgg?3000

gtgaggagtt?cgagaaggag?atcaggaccc?ccgaggacct?gcccagcggc?ttcccccaaa?3060

acctgcatgt?gacaggactg?accacgtcta?ccacagaact?ggcctgggac?ccgccagtgc?3120

tggcggagag?gaacgggcgc?atcatcagct?acaccgtggt?gttccgagac?atcaacagcc?3180

aacaggagct?gcagaacatc?acgacagaca?cccgctttac?ccttactggc?ctcaagccag?3240

acaccactta?cgacatcaag?gtccgcgcat?ggaccagcaa?aggctctggc?ccactcagcc?3300

ccagcatcca?gtcccggacc?atgccggtgg?agcaagtgtt?tgccaagaac?ttccgggtgg?3360

cggctgcaat?gaagacgtct?gtgctgctca?gctgggaggt?tcccgactcc?tataagtcag?3420

ctgtgccctt?taagattctg?tacaatgggc?agagtgtgga?ggtggacggg?cactcgatgc?3480

ggaagctgat?cgcagacctg?cagcccaaca?cagagtactc?gtttgtgctg?atgaaccgtg?3540

gcagcagcgc?agggggcctg?cagcacctgg?tgtccatccg?cacagccccc?gacctcctgc?3600

ctcacaagcc?gctgcctgcc?tctgcctaca?tagaggacgg?ccgcttcgat?ctctccatgc?3660

cccatgtgca?agacccctcg?cttgtcaggt?ggttctacat?tgttgtggtg?cccattgacc?3720

gtgtgggcgg?gagcatgctg?acgccaaggt?ggagcacacc?cgaggaactg?gagctggacg?3780

agcttctaga?agccatcgag?caaggcggag?aggagcagcg?gcggcggcgg?cggcaggcag?3840

aacgtctgaa?gccatatgtg?gctgctcaac?tggatgtgct?cccggagacc?tttaccttgg?3900

gggacaagaa?gaactaccgg?ggcttctaca?accggcccct?gtctccggac?ttgagctacc?3960

agtgctttgt?gcttgcctcc?ttgaaggaac?ccatggacca?gaagcgctat?gcctccagcc?4020

cctactcgga?tgagatcgtg?gtccaggtga?caccagccca?gcagcaggag?gagccggaga?4080

tgctgtgggt?gacgggtccc?gtgctggcag?tcatcctcat?catcctcatt?gtcatcgcca?4140

tcctcttgtt?caaaaggaaa?aggacccact?ctccgtcctc?taaggatgag?cagtcgatcg?4200

gactgaagga?ctccttgctg?gcccactcct?ctgaccctgt?ggagatgcgg?aggctcaact?4260

accagacccc?aggtatgcga?gaccacccac?ccatccccat?caccgacctg?gcggacaaca?4320

tcgagcgcct?caaagccaac?gatggcctca?agttctccca?ggagtatgag?tccatcgacc?4380

ctggacagca?gttcacgtgg?gagaattcaa?acctggaggt?gaacaagccc?aagaaccgct?4440

atgcgaatgt?catcgcctac?gaccactctc?gagtcatcct?tacctctatc?gatggcgtcc?4500

ccgggagtga?ctacatcaat?gccaactaca?tcgatggcta?ccgcaagcag?aatgcctaca?4560

ccgccacgca?gggccccctg?cccgagacca?tgggtgattt?ctggaggatg?gtgtgggaac?4620

agcgcacggc?cactgtggtc?atgatgacac?ggctggagga?gaagtcccgg?gtaaaatgtg?4680

atcagtactg?gccagcccgt?ggcaccgaga?cctgtggcct?tattcaggtg?accctgttgg?4740

acacagtgga?gctggccaca?tacactgtgc?gcaccttcgc?actccacaag?agtggctcca?4800

gtgagaagcg?cgagctgcgt?cagtttcagt?tcatggcctg?gccagaccat?ggagttcctg?4860

agtacccaac?tcccatcctg?gccttcctac?gacgggtcaa?ggcctgcaac?cccctagacg?4920

cagggcccat?ggtggtgcac?tgcagcgcgg?gcgtgggccg?caccggctgc?ttcatcgtga?4980

ttgatgccat?gttggagcgg?atgaagcacg?agaagacggt?ggacatctat?ggccacgtga?5040

cctgcatgcg?atcacagagg?aactacatgg?tgcagacgga?ggaccagtac?gtgttcatcc?5100

atgaggcgct?gctggaggct?gccacgtgcg?gccacacaga?ggtgcctgcc?cgcaacctgt?5160

atgcccacat?ccagaagctg?ggccaagtgc?ctccagggga?gagtgtgacc?gccatggagc?5220

tcgagttcaa?gttgctggcc?agctccaagg?cccacacgtc?ccgcttcatc?agcgccaacc?5280

tgccctgcaa?caagttcaag?aaccggctgg?tgaacatcat?gccctacgaa?ttgacccgtg?5340

tgtgtctgca?gcccatccgt?ggtgtggagg?gctctgacta?catcaatgcc?agcttcctgg?5400

atggttatag?acagcagaag?gcctacatag?ctacacaggg?gcctctggca?gagagcaccg?5460

aggacttctg?gcgcatgcta?tgggagcaca?attccaccat?catcgtcatg?ctgaccaagc?5520

ttcgggagat?gggcagggag?aaatgccacc?agtactggcc?agcagagcgc?tctgctcgct?5580

accagtactt?tgttgttgac?ccgatggctg?agtacaacat?gccccagtat?atcctgcgtg?5640

agttcaaggt?cacggatgcc?cgggatgggc?agtcaaggac?aatccggcag?ttccagttca?5700

cagactggcc?agagcagggc?gtgcccaaga?caggcgaggg?attcattgac?ttcatcgggc?5760

aggtgcataa?gaccaaggag?cagtttggac?aggatgggcc?tatcacggtg?cactgcagtg?5820

ctggcgtggg?ccgcaccggg?gtgttcatca?ctctgagcat?cgtcctggag?cgcatgcgct?5880

acgagggcgt?ggtcgacatg?tttcagaccg?tgaagaccct?gcgtacacag?cgtcctgcca?5940

tggtgcagac?agaggaccag?tatcagctgt?gctaccgtgc?ggccctggag?tacctcggca?6000

gctttgacca?ctatgcaacg?taactaccgc?tcccctctcc?tccgccaccc?ccgccgtggg?6060

gctccggagg?ggacccagct?cctctgagcc?ataccgacca?tcgtccagcc?ctcctacgca?6120

gatgctgtca?ctggcagagc?acagcccacg?gggatcacag?cgtttcagga?acgttgccac?6180

accaatcaga?gagcctagaa?catccctggg?caagtggatg?gcccagcagg?caggcactgt?6240

ggcccttctg?tccaccagac?ccacctggag?cccgcttcaa?gctctctgtt?gcgctcccgc?6300

atttctcatg?cttcttctca?tggggtgggg?ttggggcaaa?gcctcctttt?taatacatta?6360

agtggggtag?actgaggaaa?aaaaaaaaaa?aaaaaaaaaa?aaaaaaaaaa?aa 6412

<210>141

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉HA epi-position

<400>141

Tyr?Pro?Tyr?Asp?Val?Asp?Tyr?Ala

1 5

<210>142

<211>12

<212>PRT

＜213〉artificial sequence

<220>

＜223〉protein C mark

<400>142

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

1 5 10

<210>143

<211>8

<212>PRT

＜213〉artificial sequence

<220>

＜223〉HRV3C protease site

<400>143

Leu?Glu?Val?Leu?Phe?Gln?Gly?Pro

1 5

<210>144

<211>186

<212>PRT

＜213〉tanapox virus

<400>144

Met?Ile?Leu?Leu?Ile?Phe?Leu?Cys?Val?Val?Ile?Thr?Asn?Leu?Ser?Pro

1 5 10 15

Ser?Tyr?Cys?Asn?Glu?Tyr?Ile?Asn?Ser?Thr?Ile?Leu?Val?Asn?Ile?Lys

20 25 30

Leu?Gly?Lys?Lys?Thr?Cys?Cys?Asn?Gly?Phe?Thr?Tyr?Leu?Leu?Asp?Asn

35 40 45

Asn?Leu?Glu?Phe?Tyr?Asn?Ile?Met?Tyr?Ser?Asn?Val?Asn?Val?Ser?Ile

50 55 60

Asn?Ile?Glu?Asn?Cys?Tyr?Phe?Asn?Asn?Ser?Ile?Phe?Lys?Asn?Thr?Lys

65 70 75 80

His?Lys?Asn?Ile?Ser?Ile?Leu?Leu?Thr?Ser?Lys?Ser?Asn?Ile?Gln?Lys

85 90 95

Asn?Ile?Ala?Ile?Ile?Pro?Ile?Thr?Cys?Lys?Ile?Thr?Ile?Asp?Ile?Thr

100 105 110

Cys?Thr?Lys?Asn?Gly?Lys?Lys?Lys?Cys?Leu?Ala?Gln?Glu?Lys?Leu?Pro

115 120 125

Lys?Thr?Pro?Asn?Leu?Ile?Tyr?Lys?Thr?Ala?Glu?His?Val?Asn?Gly?Ile

130 135 140

Ile?Asp?Leu?Asn?Ile?Tyr?Gly?Ser?Cys?Val?Lys?Tyr?Val?Tyr?Thr?Arg

145 150 155 160

Val?Asn?Ile?Tyr?Glu?Ile?Ser?Asn?Gly?Asn?Leu?Ile?Tyr?Asp?Gln?Leu

165 170 175

Asp?Ser?Asn?Phe?Leu?Lys?Leu?Asn?Thr?Lys

180 185

<210>145

<211>228

<212>PRT

＜213〉people (homo sapiens)

<400>145

Cys?Asp?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Leu?Leu

1 5 10 15

Gly?Gly?Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu

20 25 30

Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val?Val?Asp?Val?Ser

35 40 45

His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu

50 55 60

Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr

6 570 75 80

Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln?Asp?Trp?Leu?Asn

85 90 95

Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro

100 105 110

Ile?Glu?Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln

115 120 125

Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val

130 135 140

Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val

145 150 155 160

Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr?Lys?Thr?Thr?Pro

165 170 175

Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr

180 185 190

Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe?Ser?Cys?Ser?Val

195 200 205

Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu

210 215 220

Ser?Pro?Gly?Lys

225

<210>146

<211>226

<212>PRT

＜213〉artificial sequence

<220>

＜223〉Tu Bian mutain IgG Fc

<400>146

Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Ala?Glu?Gly?Ala

1 5 10 15

Pro?Ser?Val?Phe?Leu?Phe?Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu?Met?Ile

20 25 30

Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys?Val?Val?Val?Asp?Val?Ser?His?Glu

35 40 45

Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu?Val?His

50 55 60

Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr?Tyr?Arg

65 70 75 80

Val?Val?Ser?Val?Leu?Thr?Val?Leu?His?Gln?Asp?Trp?Leu?Asn?Gly?Lys

85 90 95

Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro?Ile?Glu

100 105 110

Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln?Val?Tyr

115 120 125

Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val?Ser?Leu

130 135 140

Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val?Glu?Trp

145 150 155 160

Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn?Asn?Tyr?Lys?Thr?Thr?Pro?Pro?Val

165 170 175

Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr?Val?Asp

180 185 190

Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn?Val?Phe?Ser?Cys?Ser?Val?Met?His

195 200 205

Glu?Ala?Leu?His?Asn?His?Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu?Ser?Pro

210 215 220

Gly?Lys

225

<210>147

<211>678

<212>DNA

＜213〉artificial sequence

<220>

＜223〉Tu Bian mutain IgG Fc

<400>147

aaaactcaca?catgcccacc?gtgcccagca?cctgaagccg?agggcgcgcc?gtcagtcttc?60

ctcttccccc?caaaacccaa?ggacaccctc?atgatctccc?ggacccctga?ggtcacatgc?120

gtggtggtgg?acgtgagcca?cgaagaccct?gaggtcaagt?tcaactggta?cgtggacggc?180

gtggaggtgc?ataatgccaa?gacaaagccg?cgggaggagc?agtacaacag?cacgtaccgt?240

gtggtcagcg?tcctcaccgt?cctgcaccag?gactggctga?atggcaagga?gtacaagtgc?300

aaggtctcca?acaaagccct?cccagccccc?atcgagaaaa?ccatctccaa?agccaaaggg?360

cagccccgag?aaccacaggt?gtacaccctg?cccccatccc?gggatgagct?gaccaagaac?420

caggtcagcc?tgacctgcct?ggtcaaaggc?ttctatccca?gcgacatcgc?cgtggagtgg?480

gagagcaatg?ggcagccgga?gaacaactac?aagaccacgc?ctcccgtgct?ggactccgac?540

ggctccttct?tcctctatag?caagctcacc?gtggacaaga?gcaggtggca?gcaggggaac?600

gtcttctcat?gctccgtgat?gcatgaggct?ctgcacaacc?actacacgca?gaagagcctc?660

tccctgtctc?cgggtaaa 678

<210>148

<211>18

<212>PRT

＜213〉artificial sequence

<220>

＜223〉Tu Bian mutain IgG Fc

<400>148

Lys?Thr?His?Thr?Cys?Pro?Pro?Cys?Pro?Ala?Pro?Glu?Ala?Glu?Gly?Ala

1 5 10 15

Pro?Ser

<210>149

<211>394

<212>PRT

＜213〉artificial sequence

<220>

＜223〉130L-mutain Fc fusion polypeptide

<400>149

Asn?Glu?Tyr?Ile?Asn?Ser?Thr?Ile?Leu?Val?Asn?Ile?Lys?Leu?Gly?Lys

1 5 10 15

Lys?Thr?Cys?Cys?Asn?Gly?Phe?Thr?Tyr?Leu?Leu?Asp?Asn?Asn?Leu?Glu

20 25 30

Phe?Tyr?Asn?Ile?Met?Tyr?Ser?Asn?Val?Asn?Val?Ser?Ile?Asn?Ile?Glu

35 40 45

Asn?Cys?Tyr?Phe?Asn?Asn?Ser?Ile?Phe?Lys?Asn?Thr?Lys?His?Lys?Asn

50 55 60

Ile?Ser?Ile?Leu?Leu?Thr?Ser?Lys?Ser?Asn?Ile?Gln?Lys?Asn?Ile?Ala

65 70 75 80

Ile?Ile?Pro?Ile?Thr?Cys?Lys?Ile?Thr?Ile?Asp?Ile?Thr?Cys?Thr?Lys

85 90 95

Asn?Gly?Lys?Lys?Lys?Cys?Leu?Ala?Gln?Glu?Lys?Leu?Pro?Lys?Thr?Pro

100 105 110

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

115 120 125

Asn?Ile?Tyr?Gly?Ser?Cys?Val?Lys?Tyr?Val?Tyr?Thr?Arg?Val?Asn?Ile

130 135 140

Tyr?Glu?Ile?Ser?Asn?Gly?Asn?Leu?Ile?Tyr?Asp?Gln?Leu?Asp?Ser?Asn

145 150 155 160

Phe?Leu?Lys?Leu?Asn?Thr?Lys?Ser?Lys?Thr?His?Thr?Cys?Pro?Pro?Cys

165 170 175

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

180 185 190

Lys?Pro?Lys?Asp?Thr?Leu?Met?Ile?Ser?Arg?Thr?Pro?Glu?Val?Thr?Cys

195 200 205

Val?Val?Val?Asp?Val?Ser?His?Glu?Asp?Pro?Glu?Val?Lys?Phe?Asn?Trp

210 215 220

Tyr?Val?Asp?Gly?Val?Glu?Val?His?Asn?Ala?Lys?Thr?Lys?Pro?Arg?Glu

225 230 235 240

Glu?Gln?Tyr?Asn?Ser?Thr?Tyr?Arg?Val?Val?Ser?Val?Leu?Thr?Val?Leu

245 250 255

His?Gln?Asp?Trp?Leu?Asn?Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val?Ser?Asn

260 265 270

Lys?Ala?Leu?Pro?Ala?Pro?Ile?Glu?Lys?Thr?Ile?Ser?Lys?Ala?Lys?Gly

275 280 285

Gln?Pro?Arg?Glu?Pro?Gln?Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg?Asp?Glu

290 295 300

Leu?Thr?Lys?Asn?Gln?Val?Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly?Phe?Tyr

305 310 315 320

Pro?Ser?Asp?Ile?Ala?Val?Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro?Glu?Asn

325 330 335

Asn?Tyr?Lys?Thr?Thr?Pro?Pro?Val?Leu?Asp?Ser?Asp?Gly?Ser?Phe?Phe

340 345 350

Leu?Tyr?Ser?Lys?Leu?Thr?Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln?Gly?Asn

355 360 365

Val?Phe?Ser?Cys?Ser?Val?Met?His?Glu?Ala?Leu?His?Asn?His?Tyr?Thr

370 375 380

Gln?Lys?Ser?Leu?Ser?Leu?Ser?Pro?Gly?Lys

385 390

<210>150

<211>167

<212>PRT

＜213〉tanapox virus

<400>150

Asn?Glu?Tyr?Ile?Asn?Ser?Thr?Ile?Leu?Val?Asn?Ile?Lys?Leu?Gly?Lys

1 5 10 15

LysThr?Cys?Cys?Asn?Gly?Phe?Thr?Tyr?Leu?Leu?Asp?Asn?Asn?Leu?Glu

20 25 30

Phe?Tyr?Asn?Ile?Met?Tyr?Ser?Asn?Val?Asn?Val?Ser?Ile?Asn?Ile?Glu

35 40 45

Asn?Cys?Tyr?Phe?Asn?Asn?Ser?Ile?Phe?Lys?Asn?Thr?Lys?His?Lys?Asn

50 55 60

Ile?Ser?Ile?Leu?Leu?Thr?Ser?Lys?Ser?Asn?Ile?Gln?Lys?Asn?Ile?Ala

65 70 75 80

Ile?Ile?Pro?Ile?Thr?Cys?Lys?Ile?Thr?Ile?Asp?Ile?Thr?Cys?Thr?Lys

85 90 95

Asn?Gly?Lys?Lys?Lys?Cys?Leu?Ala?Gln?Glu?Lys?Leu?Pro?Lys?Thr?Pro

100 105 110

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

115 120 125

Asn?Ile?Tyr?Gly?Ser?Cys?Val?Lys?Tyr?Val?Tyr?Thr?Arg?Val?Asn?Ile

130 135 140

Tyr?Glu?Ile?Ser?Asn?Gly?Asn?Leu?Ile?Tyr?Asp?Gln?Leu?Asp?Ser?Asn

145 150 155 160

Phe?Leu?Lys?Leu?Asn?Thr?Lys

165

<210>15l

<211>19

<212>PRT

＜213〉tanapox virus

<400>151

Met?Ile?Leu?Leu?Ile?Phe?Leu?Cys?Val?Val?Ile?Thr?Asn?Leu?Ser?Pro

1 5 10 15

Ser?Tyr?Cys

<210>152

<211>6

<212>PRT

＜213〉people (homo sapiens)

<400>152

Leu?Leu?Gly?Gly?Pro?Ser

1 5

<210>153

<211>26

<212>PRT

＜213〉people (homo sapiens)

<400>153

Met?Ala?Thr?Gly?Ser?Arg?Tnr?Ser?Leu?Leu?Leu?Ala?Phe?Gly?Leu?Leu

1 5 10 15

Cys?Leu?Pro?Trp?Leu?Gln?Glu?Gly?Ser?Ala

20 25

<210>154

<211>396

<212>PRT

＜213〉artificial sequence

<220>

＜223〉130-Fc fusion polypeptide

<400>154

Asn?Glu?Tyr?Ile?Asn?Ser?Thr?Ile?Leu?Val?Asn?Ile?Lys?Leu?Gly?Lys

1 5 10 15

Lys?Thr?Cys?Cys?Asn?Gly?Phe?Thr?Tyr?Leu?Leu?Asp?Asn?Asn?Leu?Glu

20 25 30

Phe?Tyr?Asn?Ile?Met?Tyr?Ser?Asn?Val?Asn?Val?Ser?Ile?Asn?Ile?Glu

35 40 45

Asn?Cys?Tyr?Phe?Asn?Asn?Ser?Ile?Phe?Lys?Asn?Thr?Lys?His?Lys?Asn

50 55 60

Ile?Ser?Ile?Leu?Leu?Thr?Ser?Lys?Ser?Asn?Ile?Gln?Lys?Asn?Ile?Ala

65 70 75 80

Ile?Ile?Pro?Ile?Thr?Cys?Lys?Ile?Thr?Ile?Asp?Ile?Thr?Cys?Thr?Lys

85 90 95

Asn?Gly?Lys?Lys?Lys?Cys?Leu?Ala?Gln?Glu?Lys?Leu?Pro?Lys?Thr?Pro

100 105 110

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

115 120 125

Asn?Ile?Tyr?Gly?Ser?Cys?Val?Lys?Tyr?Val?Tyr?Thr?Arg?Val?Asn?Ile

130 135 140

Tyr?Glu?Ile?Ser?Asn?Gly?Asn?Leu?Ile?Tyr?Asp?Gln?Leu?Asp?Ser?Asn

145 150 155 160

Phe?Leu?Lys?Leu?Asn?Thr?Lys?Ser?Cys?Asp?Lys?Thr?His?Thr?Cys?Pro

165 170 175

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

180 185 190

Pro?Pro?Lys?Pro?Lys?Asp?Thr?Leu?Met?Ile?Ser?Arg?Thr?Pro?Glu?Val

195 200 205

Thr?Cys?Val?Val?Val?Asp?Val?Ser?His?Glu?Asp?Pro?Glu?Val?Lys?Phe

210 215 220

Asn?Trp?Tyr?Val?Asp?Gly?Val?Glu?Val?His?Asn?Ala?Lys?Thr?Lys?Pro

225 230 235 240

Arg?Glu?Glu?Gln?Tyr?Asn?Ser?Thr?Tyr?Arg?Val?Val?Ser?Val?Leu?Thr

245 250 255

Val?Leu?His?Gln?Asp?Trp?Leu?Asn?Gly?Lys?Glu?Tyr?Lys?Cys?Lys?Val

260 265 270

Ser?Asn?Lys?Ala?Leu?Pro?Ala?Pro?Ile?Glu?Lys?Thr?Ile?Ser?Lys?Ala

275 280 285

Lys?Gly?Gln?Pro?Arg?Glu?Pro?Gln?Val?Tyr?Thr?Leu?Pro?Pro?Ser?Arg

290 295 300

Asp?Glu?Leu?Thr?Lys?Asn?Gln?Val?Ser?Leu?Thr?Cys?Leu?Val?Lys?Gly

305 310 315 320

Phe?Tyr?Pro?Ser?Asp?Ile?Ala?Val?Glu?Trp?Glu?Ser?Asn?Gly?Gln?Pro

325 330 335

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

340 345 350

Phe?Phe?Leu?Tyr?Ser?Lys?Leu?Thr?Val?Asp?Lys?Ser?Arg?Trp?Gln?Gln

355 360 365

Gly?Asn?Val?Phe?Ser?Cys?Ser?Val?Met?His?Glu?Ala?Leu?His?Asn?His

370 375 380

Tyr?Thr?Gln?Lys?Ser?Leu?Ser?Leu?Ser?Pro?Gly?Lys

385 390 395

<210>155

<211>1898

<212>PRT

＜213〉people (homo sapiens)

<220>

＜221〉variant

<222>600，938，1809

＜223〉any amino acid of Xaa=

<400>155

Met?Ala?Pro?Glu?Pro?Ala?Pro?Gly?Arg?Arg?Met?Val?Pro?Leu?Val?Pro

1 5 10 15

Ala?Leu?Val?Met?Leu?Gly?Leu?Met?Ala?Gly?Ala?His?Gly?Asp?Ser?Lys

20 25 30

Pro?Val?Phe?Val?Lys?Val?Pro?Glu?Asp?Gln?Thr?Gly?Leu?Ser?Glu?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Glu?Pro?Lys?Pro?Arg?Ile

50 55 60

Thr?Trp?Met?Lys?Lys?Gly?Lys?Lys?Val?Ser?Ser?Gln?Arg?Phe?Glu?Val

65 70 75 80

Ile?Glu?Phe?Asp?Asp?Gly?Ala?Gly?Ser?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Val?Gln?Arg?Asp?Glu?Ala?Ile?Tyr?Glu?Cys?Thr?Ala?Thr?Asn?Ser

100 105 110

Leu?Gly?Glu?Ile?Asn?Thr?Ser?Ala?Lys?Leu?Ser?Val?Leu?Glu?Glu?Asp

115 120 125

Gln?Leu?Pro?Ser?Gly?Phe?Pro?Thr?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Lys?Gly?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Gly?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Ser?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

2l0 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Pro?Pro?Ser?Ser

225 230 235 240

Gln?Glu?Val?Met?Pro?Gly?Gly?Ser?Val?Asn?Leu?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ala?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Met?Gly?Ala?Glu?Glu?Leu

260 265 270

Thr?Lys?Glu?Asp?Glu?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Ser

275 280 285

Asn?Val?Met?Arg?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Ile?Ser?Ser?Leu

290 295 300

Gly?Met?Ile?Glu?Ala?Thr?Ala?Gln?Val?Thr?Val?Lys?Ala?Leu?Pro?Lys

305 310 315 320

Pro?Pro?Ile?Asp?Leu?Val?Val?Thr?Glu?Thr?Thr?Ala?Thr?Ser?Val?Thr

325 330 335

Leu?Thr?Trp?Asp?Ser?Gly?Asn?Thr?Glu?Pro?Val?Ser?Phe?Tyr?Gly?Ile

340 345 350

Gln?Tyr?Arg?Ala?Ala?Gly?Thr?Asp?Gly?Pro?Phe?Gln?Glu?Val?Asp?Gly

355 360 365

Val?Ala?Ser?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Phe?Ser?Glu

370 375 380

Tyr?Ala?Phe?Arg?Val?Leu?Ala?Val?Asn?Ser?Ile?Gly?Arg?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ala?Val?Arg?Ala?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ser?Ser?Pro

405 410 415

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

420 425 430

Gln?Trp?Glu?Pro?Pro?Glu?Glu?Pro?Asn?Gly?Leu?Val?Arg?Gly?Tyr?Arg

435 440 445

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

450 455 460

His?Asn?Thr?Asp?Ala?Gly?Leu?Leu?Thr?Thr?Val?Gly?Ser?Leu?Leu?Pro

465 470 475 480

Gly?Val?Thr?Tyr?Ser?Leu?Arg?Val?Leu?Ala?Phe?Thr?Ala?Val?Gly?Asp

485 490 495

Gly?Pro?Pro?Ser?Pro?Thr?Ile?Gln?ValLys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Ala?Arg?Ser?Ala?Asp?Phe?Gln?Ala?Asn?Ala?Glu?Ser?Asp?Thr?Arg?Ile

515 520 525

Gln?Leu?Ser?Trp?Leu?Leu?Pro?Pro?Gln?Glu?Arg?Ile?Val?Lys?Tyr?Glu

530 535 540

Leu?Val?Tyr?Trp?Ala?Ala?Glu?Asp?Glu?Gly?Gln?Gln?His?Lys?Val?Thr

545 550 555 560

Phe?Asp?Pro?Thr?Ser?Ser?Tyr?Thr?Leu?Glu?Asp?Leu?Lys?Pro?Asp?Thr

565 570 575

Leu?Tyr?Arg?Phe?Gln?Leu?Ala?Ala?Arg?Ser?Asp?Leu?Gly?Val?Gly?Val

580 585 590

Phe?Thr?Pro?Thr?Val?Glu?Ala?Xaa?Thr?Ala?Gln?Ser?Thr?Pro?Ser?Ala

595 600 605

Pro?Pro?Gln?Lys?Val?Thr?Cys?Val?Ser?Thr?Gly?Ser?Thr?Thr?Val?Arg

610 615 620

Val?Ser?Trp?Val?Pro?Pro?Pro?Ala?Asp?Ser?Arg?Asn?Gly?Ile?Ile?Thr

625 630 635 640

Gln?Tyr?Ser?Val?Ala?Tyr?Glu?Ala?Val?Asp?Gly?Glu?Asp?Arg?Lys?Arg

645 650 655

His?Val?Val?Asp?Gly?Ile?Ser?Arg?Glu?His?Ser?Ser?Trp?Asp?Leu?Leu

660 665 670

Gly?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Trp?Val?Arg?Ala?His?Thr

675 680 685

Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Leu?Val?Arg?Thr?Asp

690 695 700

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

705 710 715 720

Asn?Ser?Thr?Ala?Val?His?Val?Ser?Trp?Lys?Leu?Pro?Val?Pro?Asn?Lys

725 730 735

Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?Thr?Tyr?Val?Arg?Leu?Glu

740 745 750

Asn?Gly?Glu?Pro?Arg?Gly?Gln?Pro?Ile?Ile?Gln?Asp?Val?Met?Leu?Ala

755 760 765

Glu?Ala?Gln?Glu?Thr?Thr?Ile?Ser?Gly?Leu?Thr?Pro?Glu?Thr?Thr?Tyr

770 775 780

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

785 790 795 800

Lys?Pro?Lys?Val?Val?Thr?Thr?Thr?Gly?Ala?Val?Pro?Gly?Arg?Pro?Thr

805 810 815

Met?Met?Val?Ser?Thr?Thr?Ala?Met?His?Thr?Ala?Leu?Leu?Gln?Trp?His

820 825 830

Pro?Pro?Lys?Glu?Leu?Pro?Gly?Glu?Leu?Leu?Gly?Tyr?Arg?Leu?Gln?Tyr

835 840 845

Arg?Arg?Ala?Asp?Glu?Ala?Arg?Pro?Asn?Thr?Ile?Asp?Phe?Gly?Lys?Asp

850 855 860

Asp?Gln?His?Phe?Thr?Val?Thr?Gly?Leu?His?Lys?Gly?Ala?Thr?Tyr?Val

865 870 875 880

Phe?Arg?Leu?Ala?Ala?Lys?Asn?Arg?Ala?Gly?Pro?Gly?Glu?Glu?Phe?Glu

885 890 895

Lys?Glu?Ile?Thr?Thr?Pro?Glu?Asp?Val?Pro?Ser?Gly?Phe?Pro?Gln?Asn

900 905 9l0

Leu?Arg?Val?Thr?Gly?Leu?Thr?Thr?Ser?Thr?Thr?Glu?Leu?Thr?Trp?Asp

915 920 925

Pro?Pro?Val?Leu?Ala?Glu?Arg?Asn?Gly?Xaa?Ile?Thr?Asn?Tyr?Thr?Val

930 935 940

Val?Tyr?Arg?Asp?Ile?Asn?Ser?Gln?Leu?Glu?Leu?Gln?Asn?Val?Thr?Asn

945 950 955 960

Asp?Thr?His?Leu?Thr?Leu?Leu?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

965 970 975

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

980 985 990

Ser?Ile?Gln?Ser?Arg?Thr?Met?Pro?Val?Glu?Gln?Val?Phe?Thr?Lys?Asn

995 1000 1005

Phe?Arg?Val?Ala?Ala?Ala?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

10l0 1015 1020

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

1025 1030 1035 1040

Gly?Gln?Ser?Val?Glu?Val?Asp?Gly?His?Ser?Met?Arg?Lys?Leu?Ile?Ala

1045 1050 1055

Asp?Leu?Gln?Pro?Asn?Thr?Glu?Tyr?Ser?Phe?Val?Leu?Met?Asn?Arg?Gly

1060 1065 1070

Ser?Ser?Ala?Gly?Gly?Leu?Gln?His?Leu?Val?Ser?Ile?Arg?Thr?Ala?Pro

1075 1080 1085

Asp?Leu?Leu?Pro?Gln?Lys?Pro?Leu?Pro?Ala?Ser?Ala?Phe?Ile?Glu?Asp

1090 1095 1100

Gly?Arg?Phe?Ser?Leu?Ser?Met?Pro?Gln?Val?Gln?Asp?Pro?Ser?Leu?Val

1105 1110 1115 1120

Arg?Trp?Phe?Tyr?Ile?Val?Val?Val?Pro?Ile?Asp?Arg?Val?Gly?Gly?Asn

1125 1130 1135

Leu?Leu?Ala?Pro?Arg?Trp?Asn?Thr?Pro?Glu?Glu?Leu?Glu?Leu?Asp?Glu

1140 1145 1150

Leu?Leu?Glu?Ala?Ile?Glu?Gln?Gly?Glu?Glu?Lys?Gln?Arg?Arg?Arg?Arg

1155 1160 1165

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

1170 1175 1180

Leu?Pro?Asp?Thr?Phe?Thr?Leu?Gly?Asp?Lys?Lys?Ser?Tyr?Arg?Gly?Phe

1185 1190 1195 1200

Tyr?Asn?Arg?Pro?Leu?Ser?Pro?Asp?Leu?Ser?Tyr?Gln?Cys?Phe?Val?Leu

1205 1210 1215

Ala?Ser?Leu?Lys?Glu?Pro?Met?Asp?Gln?Lys?Arg?Tyr?Ala?Ser?Ser?Pro

1220 1225 1230

Tyr?Ser?Asp?Glu?Ile?Val?Val?Gln?Val?Thr?Pro?Ala?Gln?Gln?Gln?Glu

1235 1240 1245

Glu?Pro?Glu?Met?Leu?Trp?Val?Thr?Gly?Pro?Val?Leu?Ala?Val?Ile?Leu

1250 1255 1260

Ile?Ile?Leu?Ile?Val?Ile?Ala?Ile?Leu?Leu?Phe?Lys?Arg?Lys?Arg?Thr

1265 1270 1275 1280

His Ser?Pro?Ser?Ser?Lys?Asp?Glu?Gln?Ser?Ile?Gly?Leu?Lys?Asp?Ser

1285 1290 1295

Leu?Leu?Ala?His?Ser?Ser?Asp?Pro?Val?Glu?Met?Arg?Arg?Leu?Asn?Tyr

1300 1305 1310

Gln?Thr?Pro?Gly?Met?Arg?Asp?His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Leu

1315 1320 1325

Ala?Asp?Asn?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Gly?Leu?Lys?Phe?Ser

1330 1335 1340

Gln?Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?Asn

1345 1350 1355 1360

Ser?Asn?Ser?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asp?Val?Ile

1365 1370 1375

Ala?Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Thr?Ser?Ile?Asp?Gly?Val?Pro

1380 1385 1390

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln

1395 1400 1405

Asn?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Pro?Glu?Thr?Met?Gly?Asp

1410 1415 1420

Phe?Trp?Arg?Met?Val?Trp?Glu?Gln?Arg?Thr?Ala?Thr?Val?Val?Met?Met

1425 1430 1435 1440

Thr?Arg?Leu?Glu?Glu?Lys?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro

1445 1450 1455

Val?Arg?Gly?Thr?Glu?Thr?Tyr?Gly?Leu?Ile?Gln?Val?Thr?Leu?Val?Asp

1460 1465 1470

Thr?Val?Glu?Leu?Ala?Thr?Tyr?Thr?Met?Arg?Thr?Phe?Ala?Leu?His?Lys

1475 1480 1485

Ser?Gly?Ser?Ser?Glu?Lys?Arg?Glu?Leu?Arg?Gln?Phe?Gln?Phe?Met?Ala

1490 1495 1500

Trp?Pro?Asp?His?Gly?Val?Pro?Glu?Tyr?Pro?Thr?Pro?Ile?Leu?Ala?Phe

1505 1510 1515 1520

Leu?Arg?Arg?Val?Lys?Ala?Cys?Asn?Pro?Leu?Asp?Ala?Gly?Pro?Met?Val

1525 1530 1535

Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile

1540 1545 1550

Asp?Ala?Met?Leu?Glu?Arg?Met?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr

1555 1560 1565

Gly?His?Val?Thr?Cys?Met?Arg?Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr

1570 1575 1580

Glu?Asp?Gln?Tyr?Val?Phe?Ile?His?Glu?Ala?Leu?Leu?Glu?Ala?Ala?Met

1585 1590 1595 1600

Cys?Gly?His?Thr?Glu?Val?Leu?Ala?Arg?Asn?Leu?Tyr?Ala?His?Ile?Gln

1605 1610 1615

Lys?Leu?Gly?Gln?Val?Pro?Pro?Gly?Glu?Ser?Val?Thr?Ala?Met?Glu?Leu

1620 1625 1630

Glu?Phe?Lys?Leu?Leu?Ala?Asn?Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Val

1635 1640 1645

Ser?Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile

1650 1655 1660

Met?Pro?Tyr?Glu?Leu?Thr?Arg?Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val

1665 1670 1675 1680

Glu?Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Leu?Asp?Gly?Tyr?Arg?Gln

1685 1690 1695

Gln?Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Ser?Thr?Glu

1700 1705 1710

Asp?Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Ile?Val?Met

1715 1720 1725

Leu?Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp

1730 1735 1740

Pro?Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met

1745 1750 1755 1760

Ala?Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr

1765 1770 1775

Asp?Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Ile?Arg?Gln?Phe?Gln?Phe?Thr

1780 1785 1790

Asp?Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Thr?Gly?Glu?Gly?Phe?Ile?Asp

1795 1800 1805

Xaa?Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly

1810 1815 1820

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

1825 1830 1835 1840

Ile?Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val

1845 1850 1855

Asp?Met?Phe?Gln?Thr?Val?Lys?Thr?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met

1860 1865 1870

Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Leu?Cys?Tyr?Arg?Ala?Ala?Leu?Glu

1875 1880 1885

Tyr?Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1890 1895

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＜213〉people (homo sapiens)

<400>156

Met?Ala?Pro?Thr?Trp?Ser?Pro?Ser?Val?Val?Ser?Val?Val?Gly?Pro?Val

1 5 10 15

Gly?Leu?Phe?Leu?Val?Leu?Leu?Ala?Arg?Gly?Cys?Leu?Ala?Glu?Glu?Pro

20 25 30

Pro?Arg?Phe?Ile?Arg?Glu?Pro?Lys?Asp?Gln?Ile?Gly?Val?Ser?Gly?Gly

35 40 45

Val?Ala?Ser?Phe?Val?Cys?Gln?Ala?Thr?Gly?Asp?Pro?Lys?Pro?Arg?Val

50 55 60

Thr?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val?Asn?Ser?Gln?Arg?Phe?Glu?Thr

65 70 75 80

Ile?Asp?Phe?Asp?Glu?Ser?Ser?Gly?Ala?Val?Leu?Arg?Ile?Gln?Pro?Leu

85 90 95

Arg?Thr?Pro?Arg?Asp?Glu?Asn?Val?Tyr?Glu?Cys?Val?Ala?Gln?Asn?Ser

100 105 110

Val?Gly?Glu?Ile?Thr?Ile?His?Ala?Lys?Leu?Thr?Val?Leu?Arg?Glu?Asp

115 120 125

Gln?Leu?Pro?Pro?Gly?Phe?Pro?Asn?Ile?Asp?Met?Gly?Pro?Gln?Leu?Lys

130 135 140

Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr?Met?Leu?Cys?Ala?Ala?Ser?Gly

145 150 155 160

Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe?Lys?Asp?Phe?Leu?Pro?Val?Asp

165 170 175

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

180 185 190

Gln?Ile?Glu?Ser?Ser?Glu?Glu?Thr?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Val?Arg?Tyr?Ser?Ser?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Arg?Arg?Val?Ala?Pro?Arg?Phe?Ser?Ile?Leu?Pro?Met?Ser

225 230 235 240

His?Glu?Ile?Met?Pro?Gly?Gly?Asn?Val?Asn?Ile?Thr?Cys?Val?Ala?Val

245 250 255

Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Gln?Gly?Ala?Glu?Asp?Leu

260 265 270

Thr?Pro?Glu?Asp?Asp?Met?Pro?Val?Gly?Arg?Asn?Val?Leu?Glu?Leu?Thr

275 280 285

Asp?Val?Lys?Asp?Ser?Ala?Asn?Tyr?Thr?Cys?Val?Ala?Met?Ser?Ser?Leu

290 295 300

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

305 310 315 320

Ala?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Asn?Thr?Ala?Thr?Ser?Ile?Thr

325 330 335

Val?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Asp?Pro?Val?Ser?Tyr?Tyr?Val?Ile

340 345 350

Glu?Tyr?Lys?Ser?Lys?Ser?Gln?Asp?Gly?Pro?Tyr?Gln?Ile?Lys?Glu?Asp

355 360 365

Ile?Thr?Thr?Thr?Arg?Tyr?Ser?Ile?Gly?Gly?Leu?Ser?Pro?Asn?Ser?Glu

370 375 380

Tyr?Glu?Ile?Trp?Val?Ser?Ala?Val?Asn?Ser?Ile?Gly?Gln?Gly?Pro?Pro

385 390 395 400

Ser?Glu?Ser?Val?Val?Thr?Arg?Thr?Gly?Glu?Gln?Ala?Pro?Ala?Ser?Ala

405 410 415

Pro?Arg?Asn?Val?Gln?Ala?Arg?Met?Leu?Ser?Ala?Thr?Thr?Met?Ile?Val

420 425 430

Gln?Trp?Glu?Glu?Pro?Val?Glu?Pro?Asn?Gly?Leu?Ile?Arg?Gly?Tyr?Arg

435 440 445

Val?Tyr?Tyr?Thr?Met?Glu?Pro?Glu?His?Pro?Val?Gly?Asn?Trp?Gln?Lys

450 455 460

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

465 470 475 480

Asp?Glu?Thr?Tyr?Thr?Val?Arg?Val?Leu?Ala?Phe?Thr?Ser?Val?Gly?Asp

485 490 495

Gly?Pro?Leu?Ser?Asp?Pro?Ile?Gln?Val?Lys?Thr?Gln?Gln?Gly?Val?Pro

500 505 510

Gly?Gln?Pro?Met?Asn?Leu?Arg?Ala?Glu?Ala?Lys?Ser?Glu?Thr?Ser?Ile

515 520 525

Gly?Leu?Ser?Trp?Ser?Ala?Pro?Arg?Gln?Glu?Ser?Val?Ile?Lys?Tyr?Glu

530 535 540

Leu?Leu?Phe?Arg?Glu?Gly?Asp?Arg?Gly?Arg?Glu?Val?Gly?Arg?Thr?Phe

545 550 555 560

Asp?Pro?Thr?Thr?Ala?Phe?Val?Val?Glu?Asp?Leu?Lys?Pro?Asn?Thr?Glu

565 570 575

Tyr?Ala?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln?Gly?Leu?Gly?Ala?Phe

580 585 590

Thr?Ala?Val?Val?Arg?Gln?Arg?Thr?Leu?Gln?Ala?Lys?Pro?Ser?Ala?Pro

595 600 605

Pro?Gln?Asp?Val?Lys?Cys?Thr?Ser?Leu?Arg?Ser?Thr?Ala?Ile?Leu?Val

610 615 620

Ser?Trp?Arg?Pro?Pro?Pro?Pro?Glu?Thr?His?Asn?Gly?Ala?Leu?Val?Gly

625 630 635 640

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

645 650 655

Glu?Val?Asn?Asn?Ile?Pro?Pro?Thr?Thr?Thr?Gln?Ile?Leu?Leu?Glu?Ala

660 665 670

Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Val?Thr?Ala?Val?Ala?Tyr?Thr?Glu

675 680 685

Val?Gly?Pro?Gly?Pro?Glu?Ser?Ser?Pro?Val?Val?Val?Arg?Thr?Asp?Glu

690 695 700

Asp?Val?Pro?Ser?Ala?Pro?Pro?Arg?Lys?Val?Glu?Ala?Glu?Ala?Leu?Asn

705 710 715 720

Ala?Thr?Ala?Ile?Arg?Val?Leu?Trp?Arg?Ser?Pro?Thr?Pro?Gly?Arg?Gln

725 730 735

His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr?Val?Arg?Met?Glu?Gly

740 745 750

Ala?Glu?Ala?Arg?Gly?Pro?Pro?Arg?Ile?Lys?Asp?Ile?Met?Leu?Ala?Asp

755 760 765

Ala?Gln?Glu?Met?Val?Ile?Thr?Asn?Leu?Gln?Pro?Glu?Thr?Ala?Tyr?Ser

770 775 780

Ile?Thr?Val?Ala?Ala?Tyr?Thr?Met?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys

785 790 795 800

Pro?Lys?Val?Val?Val?Thr?Lys?Gly?Ala?Val?Leu?Gly?Arg?Pro?Thr?Leu

805 810 815

Ser?Val?Gln?Gln?Thr?Pro?Glu?Gly?Ser?Leu?Leu?Ala?Arg?Trp?Glu?Pro

820 825 830

Pro?Ala?Asp?Ala?Ala?Glu?Asp?Pro?Val?Leu?Gly?Tyr?Arg?Leu?Gln?Phe

835 840 845

Gly?Arg?Glu?Asp?Ala?Ala?Pro?Ala?Thr?Leu?Glu?Leu?Ala?Ala?Trp?Glu

850 855 860

Arg?Arg?Phe?Ala?Ala?Pro?Ala?His?Lys?Gly?Ala?Thr?Tyr?Val?Phe?Arg

865 870 875 880

Leu?Ala?Ala?Arg?Gly?Arg?Ala?Gly?Leu?Gly?Glu?Glu?Ala?Ala?Ala?Ala

885 890 895

Leu?Ser?Ile?Pro?Glu?Asp?Ala?Pro?Arg?Gly?Phe?Pro?Gln?Ile?Leu?Gly

900 905 910

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

915 920 925

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

930 935 940

Val?Arg?Glu?Ala?Gly?Ala?Pro?Gly?Pro?Ala?Thr?Glu?Thr?Glu?Leu?Ala

945 950 955 960

Ala?Ala?Ala?Gln?Pro?Gly?Ala?Glu?Thr?Ala?Leu?Thr?Leu?Arg?Gly?Leu

965 970 975

Arg?Pro?Glu?Thr?Ala?Tyr?Glu?Leu?Arg?Val?Arg?Ala?His?Thr?Arg?Arg

980 985 990

Gly?Pro?Gly?Pro?Phe?Ser?Pro?Pro?Leu?Arg?Tyr?Arg?Leu?Ala?Arg?Asp

995 1000 1005

Pro?Val?Ser?Pro?Lys?Asn?Phe?Lys?Val?Lys?Met?Ile?Met?Lys?Thr?Ser

1010 1015 1020

Val?Leu?Leu?Ser?Trp?Glu?Phe?Pro?Asp?Asn?Tyr?Asn?Ser?Pro?Thr?Pro

1025 1030 1035 1040

Tyr?Lys?Ile?Gln?Tyr?Asn?Gly?Leu?Thr?Leu?Asp?Val?Asp?Gly?Arg?Thr

1045 1050 1055

Thr?Lys?Lys?Leu?Ile?Thr?His?Leu?Lys?Pro?His?Thr?Phe?Tyr?As?Phe

1060 1065 1070

Val?Leu?Thr?Asn?Arg?Gly?Ser?Ser?Leu?Gly?Gly?Leu?Gln?Gln?Thr?Val

1075 1080 1085

Thr?Ala?Arg?Thr?Ala?Phe?Asn?Met?Leu?Ser?Gly?Lys?Pro?Ser?Val?Ala

1090 1095 1100

Pro?Lys?Pro?Asp?Asn?Asp?Gly?Phe?Ile?Val?Val?Tyr?Leu?Pro?Asp?Gly

1105 1110 1115 1120

Gln?Ser?Pro?Val?Thr?Val?Gln?Asn?Tyr?Phe?Ile?Val?Met?Val?Pro?Leu

1125 1130 1135

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

1140 1145 1150

Asp?Met?Asp?Leu?Glu?Glu?Leu?Ile?Gln?Asp?Ile?Ser?Arg?Leu?Gln?Arg

1155 1160 1165

Arg?Ser?Leu?Arg?His?Ser?Arg?Gln?Leu?Glu?Val?Pro?Arg?Pro?Tyr?Ile

1170 1175 1180

Ala?Ala?Arg?Phe?Ser?Ile?Leu?Pro?Ala?Val?Phe?His?Pro?Gly?Asn?Gln

1185 1190 1195 1200

Lys?Gln?Tyr?Gly?Gly?Phe?Asp?Asn?Arg?Gly?Leu?Glu?Pro?Gly?His?Arg

1205 1210 1215

Tyr?Val?Leu?Phe?Val?Leu?Ala?Val?Leu?Gln?Lys?Asn?Glu?Pro?Thr?Phe

1220 1225 1230

Ala?Ala?Ser?Pro?Phe?Ser?Asp?Pro?Phe?Gln?Leu?Asp?Asn?Pro?Asp?Pro

1235 1240 1245

Gln?Pro?Ile?Val?Asp?Gly?Glu?Glu?Gly?Leu?Ile?Trp?Val?Ile?Gly?Pro

1250 1255 1260

Val?Leu?Ala?Val?Val?Phe?Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu

1265 1270 1275 1280

Tyr?Lys?Asn?Lys?Pro?Asp?Ser?Lys?Arg?Lys?Asp?Ser?Glu?Pro?Arg?Thr

1285 1290 1295

Lys?Cys?Leu?Leu?Asn?Asn?Ala?Asp?Leu?Ala?Pro?His?His?Pro?Lys?Asp

1300 1305 1310

Pro?Val?Glu?Met?Arg?Arg?Ile?Asn?Phe?Gln?Thr?Pro?Gly?Met?Leu?Ser

1315 1320 1325

His?Pro?Pro?Ile?Pro?Ile?Thr?Asp?Met?Ala?Glu?His?Met?Glu?Arg?Leu

1330 1335 1340

Lys?Ala?Asn?Asp?Ser?Leu?Lys?Leu?Ser?Gln?Glu?Tyr?Glu?Ser?Ile?Asp

1345 1350 1355 1360

Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser?Asn?Leu?Glu?Ala?Asn?Lys

1365 1370 1375

Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala?Tyr?Asp?His?Ser?Arg?Val

1380 1385 1390

Ile?Leu?Gln?Pro?Leu?Glu?Gly?Ile?Met?Gly?Ser?Asp?Tyr?Ile?Asn?Ala

1395 1400 1405

Asn?Tyr?Val?Asp?Gly?Tyr?Arg?Arg?Gln?Asn?Ala?Tyr?Ile?Ala?Thr?Gln

1410 1415 1420

Gly?Pro?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe?Trp?Arg?Met?Val?Trp?Glu

1425 1430 1435 1440

Gln?Arg?Ser?Ala?Thr?Val?Val?Met?Met?Thr?Arg?Leu?Glu?Glu?Lys?Ser

1445 1450 1455

Arg?Ile?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Asn?Arg?Gly?Thr?Glu?Thr?Tyr

1460 1465 1470

Gly?Phe?Ile?Gln?Val?Thr?Leu?Leu?Asp?Thr?Met?Glu?Leu?Ala?Thr?Phe

1475 1480 1485

Cys?Val?Arg?Thr?Phe?Ser?Leu?His?Lys?Asn?Gly?Ser?Ser?Glu?Lys?Arg

1490 1495 1500

Glu?Val?Arg?His?Phe?Gln?Phe?Thr?Ala?Trp?Pro?Asp?His?Gly?Val?Pro

1505 1510 1515 1520

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

1525 1530 1535

Asn?Pro?Pro?Asp?Ala?Gly?Pro?Ile?Val?Val?His?Cys?Ser?Ala?Gly?Val

1540 1545 1550

Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp?Ala?Met?Leu?Glu?Arg?Ile

1555 1560 1565

Lys?Thr?Glu?Lys?Thr?Val?Asp?Val?Tyr?Gly?His?Val?Thr?Leu?Met?Arg

1570 1575 1580

Ser?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu?Asp?Gln?Tyr?Gly?Phe?Ile

1585 1590 1595 1600

His?Glu?Ala?Leu?Leu?Glu?Ala?Val?Gly?Cys?Gly?Asn?Thr?Glu?Val?Pro

1605 1610 1615

Ala?Arg?Ser?Leu?Tyr?Thr?Tyr?Ile?Gln?Lys?Leu?Ala?Gln?Val?Glu?Pro

1620 1625 1630

Gly?Glu?His?Val?Thr?Gly?Met?Glu?Leu?Glu?Phe?Lys?Arg?Leu?Ala?Ser

1635 1640 1645

Ser?Lys?Ala?His?Thr?Ser?Arg?Phe?Ile?Thr?Ala?Ser?Leu?Pro?Cys?Asn

1650 1655 1660

Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Leu?Pro?Tyr?Glu?Ser?Ser?Arg

1665 1670 1675 1680

Val?Cys?Leu?Gln?Pro?Ile?Arg?Gly?Val?Glu?Gly?Ser?Asp?Tyr?Ile?Asn

1685 1690 1695

Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln?Lys?Ala?Tyr?Ile?Ala?Thr

1700 1705 1710

Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp?Phe?Trp?Arg?Ala?Leu?Trp

1715 1720 1725

Glu?Asn?Asn?Ser?Thr?Ile?Val?Val?Met?Leu?Thr?Lys?Leu?Arg?Glu?Met

1730 1735 1740

Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro?Ala?Glu?Arg?Ser?Ala?Arg

1745 1750 1755 1760

Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala?Glu?Tyr?Asn?Met?Pro?Gln

1765 1770 1775

Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp?Ala?Arg?Asp?Gly?Gln?Ser

1780 1785 1790

Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp?Trp?Pro?Glu?Gln?Gly?Ala

1795 1800 1805

Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe?Ile?Gly?Gln?Val?His?Lys

1810 1815 1820

Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro?Ile?Ser?Val?His?Cys?Ser

1825 1830 1835 1840

Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile?Thr?Leu?Ser?Ile?Val?Leu

1845 1850 1855

Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp?Ile?Phe?Gln?Thr?Val?Lys

1860 1865 1870

Val?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val?Gln?Thr?Glu?Asp?Glu?Tyr

1875 1880 1885

Gln?Phe?Cys?Phe?Gln?Ala?Ala?Leu?Glu?Tyr?Leu?Gly?Ser?Phe?Asp?His

1890 1895 1900

Tyr?Ala?Thr

1905

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＜213〉people (homo sapiens)

<400>157

Met?Val?His?Val?Ala?Arg?Leu?Leu?Leu?Leu?Leu?Leu?Thr?Phe?Phe?Leu

1 5 10 15

Arg?Thr?Asp?Ala?Glu?Thr?Pro?Pro?Arg?Phe?Thr?Arg?Thr?Pro?Val?Asp

20 25 30

Gln?Thr?Gly?Val?Ser?Gly?Gly?Val?Ala?Ser?Phe?Ile?Cys?Gln?Ala?Thr

35 40 45

Gly?Asp?Pro?Arg?Pro?Lys?Ile?Val?Trp?Asn?Lys?Lys?Gly?Lys?Lys?Val

50 55 60

Ser?Asn?Gln?Arg?Phe?Glu?Val?Ile?Glu?Phe?Asp?Asp?Gly?Ser?Gly?Ser

65 70 75 80

Val?Leu?Arg?Ile?Gln?Pro?Leu?Arg?Thr?Pro?Arg?Asp?Glu?Ala?Ile?Tyr

85 90 95

Glu?Cys?Val?Ala?Ser?Asn?Asn?Val?Gly?Glu?Ile?Ser?Val?Ser?Thr?Arg

100 105 110

Leu?Thr?Val?Leu?Arg?Glu?Asp?Gln?Ile?Pro?Arg?Gly?Phe?Pro?Thr?Ile

115 120 125

Asp?Met?Gly?Pro?Gln?Leu?Lys?Val?Val?Glu?Arg?Thr?Arg?Thr?Ala?Thr

130 135 140

Met?Leu?Cys?Ala?Ala?Ser?Gly?Asn?Pro?Asp?Pro?Glu?Ile?Thr?Trp?Phe

145 150 155 160

Lys?Asp?Phe?Leu?Pro?Val?Asp?Thr?Ser?Asn?Asn?Asn?Gly?Arg?Ile?Lys

165 170 175

Gln?Leu?Arg?Ser?Gly?Arg?Val?Phe?Lys?Arg?Leu?Asn?Arg?Arg?Ala?Leu

180 185 190

Gln?Ile?Glu?Gln?Ser?Glu?Glu?Ser?Asp?Gln?Gly?Lys?Tyr?Glu?Cys?Val

195 200 205

Ala?Thr?Asn?Ser?Ala?Gly?Thr?Arg?Tyr?Ser?Ala?Pro?Ala?Asn?Leu?Tyr

210 215 220

Val?Arg?Val?Glu?Thr?Pro?Gln?Val?Arg?Arg?Val?Pro?Pro?Arg?Phe?Ser

225 230 235 240

Ile?Pro?Pro?Thr?Asn?His?Glu?Ile?Met?Pro?Gly?Gly?Ser?Val?Asn?Ile

245 250 255

Thr?Cys?Val?Ala?Val?Gly?Ser?Pro?Met?Pro?Tyr?Val?Lys?Trp?Met?Leu

260 265 270

Gly?Ala?Glu?Asp?Leu?Thr?Pro?Glu?Asp?Asp?Met?Pro?Ile?Gly?Arg?Asn

275 280 285

Val?Leu?Glu?Leu?Asn?Asp?Val?Arg?Gln?Ser?Ala?Asn?Tyr?Thr?Cys?Val

290 295 300

Ala?Met?Ser?Thr?Leu?Gly?Val?Ile?Glu?Ala?Ile?Ala?Gln?Ile?Thr?Val

305 310 315 320

Lys?Ala?Leu?Pro?Lys?Pro?Pro?Gly?Thr?Pro?Val?Val?Thr?Glu?Ser?Thr

325 330 335

Ala?Thr?Ser?Ile?Thr?Leu?Thr?Trp?Asp?Ser?Gly?Asn?Pro?Glu?Pro?Val

340 345 350

Ser?Tyr?Tyr?Ile?Ile?Gln?His?Lys?Pro?Lys?Asn?Ser?Glu?Glu?Leu?Tyr

355 360 365

Lys?Glu?Ile?Asp?Gly?Val?Ala?Thr?Thr?Arg?Tyr?Ser?Val?Ala?Gly?Leu

370 375 380

Ser?Pro?Tyr?Ser?Asp?Tyr?Glu?Phe?Arg?Val?Val?Ala?Val?Asn?Asn?Ile

385 390 395 400

Gly?Arg?Gly?Pro?Pro?Ser?Glu?Pro?Val?Leu?Thr?Gln?Thr?Ser?Glu?Gln

405 410 415

Ala?Pro?Ser?Ser?Ala?Pro?Arg?Asp?Val?Gln?Ala?Arg?Met?Leu?Ser?Ser

420 425 430

Thr?Thr?Ile?Leu?Val?Gln?Trp?Lys?Glu?Pro?Glu?Glu?Pro?Asn?Gly?Gln

435 440 445

Ile?Gln?Gly?Tyr?Arg?Val?Tyr?Tyr?Thr?Met?Asp?Pro?Thr?Gln?His?Val

450 455 460

Asn?Asn?Trp?Met?Lys?His?Asn?Val?Ala?Asp?Ser?Gln?Ile?Thr?Thr?Ile

465 470 475 480

Gly?Asn?Leu?Val?Pro?Gln?Lys?Thr?Tyr?Ser?Val?Lys?Val?Leu?Ala?Phe

485 490 495

Thr?Ser?Ile?Gly?Asp?Gly?Pro?Leu?Ser?Ser?Asp?Ile?Gln?Val?Ile?Thr

500 505 510

Gln?Thr?Gly?Val?Pro?Gly?Gln?Pro?Leu?Asn?Phe?Lys?Ala?Glu?Pro?Glu

515 520 525

Ser?Glu?Thr?Ser?Ile?Leu?Leu?Ser?Trp?Thr?Pro?Pro?Arg?Ser?Asp?Thr

530 535 540

Ile?Ala?Asn?Tyr?Glu?Leu?Val?Tyr?Lys?Asp?Gly?Glu?His?Gly?Glu?Glu

545 550 555 560

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

565 570 575

Lys?Pro?Asn?Ser?Leu?Tyr?Tyr?Phe?Arg?Leu?Ala?Ala?Arg?Ser?Pro?Gln

580 585 590

Gly?Leu?Gly?Ala?Ser?Thr?Ala?Glu?Ile?Ser?Ala?Arg?Thr?Met?Gln?Ser

595 600 605

Lys?Pro?Ser?Ala?Pro?Pro?Gln?Asp?Ile?Ser?Cys?Thr?Ser?Pro?Ser?Ser

610 615 620

Thr?Ser?Ile?Leu?Val?Ser?Trp?Gln?Pro?Pro?Pro?Val?Glu?Lys?Gln?Asn

625 630 635 640

Gly?Ile?Ile?Thr?Glu?Tyr?Ser?Ile?Lys?Tyr?Thr?Ala?Val?Asp?Gly?Glu

645 650 655

Asp?Asp?Lys?Pro?His?Glu?Ile?Leu?Gly?Ile?Pro?Ser?Asp?Thr?Thr?Lys

660 665 670

Tyr?Leu?Leu?Glu?Gln?Leu?Glu?Lys?Trp?Thr?Glu?Tyr?Arg?Ile?Thr?Val

675 680 685

Thr?Ala?His?Thr?Asp?Val?Gly?Pro?Gly?Pro?Glu?Ser?Leu?Ser?Val?Leu

690 695 700

Ile?Arg?Thr?Asn?Glu?Asp?Val?Pro?Ser?Gly?Pro?Pro?Arg?Lys?Val?Glu

705 710 715 720

Val?Glu?Ala?Val?Asn?Ser?Thr?Ser?Val?Lys?Val?Ser?Trp?Arg?Ser?Pro

725 730 735

Val?Pro?Asn?Lys?Gln?His?Gly?Gln?Ile?Arg?Gly?Tyr?Gln?Val?His?Tyr

740 745 750

Val?Arg?Met?Glu?Asn?Gly?Glu?Pro?Lys?Gly?Gln?Pro?Met?Leu?Lys?Asp

755 760 765

Val?Met?Leu?Ala?Asp?Ala?Gln?Trp?Glu?Phe?Asp?Asp?Thr?Thr?Glu?His

770 775 780

Asp?Met?Ile?Ile?Ser?Gly?Leu?Gln?Pro?Glu?Thr?Ser?Tyr?Ser?Leu?Thr

785 790 795 800

Val?Thr?Ala?Tyr?Thr?Thr?Lys?Gly?Asp?Gly?Ala?Arg?Ser?Lys?Pro?Lys

805 810 815

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

820 825 830

Asn?His?Thr?Gln?Met?Asn?Thr?Ala?Leu?Ile?Gln?Trp?His?Pro?Pro?Val

835 840 845

Asp?Thr?Phe?Gly?Pro?Leu?Gln?Gly?Tyr?Arg?Leu?Lys?Phe?Gly?Arg?Lys

850 855 860

Asp?Met?Glu?Pro?Leu?Thr?Thr?Leu?Glu?Phe?Ser?Glu?Lys?Glu?Asp?His

865 870 875 880

Phe?Thr?Ala?Thr?Asp?Ile?His?Lys?Gly?Ala?Ser?Tyr?Val?Phe?Arg?Leu

885 890 895

Ser?Ala?Arg?Asn?Lys?Val?Gly?Phe?Gly?Glu?Glu?Met?Val?Lys?Glu?Ile

900 905 910

Ser?Ile?Pro?Glu?Glu?Val?Pro?Thr?Gly?Phe?Pro?Gln?Asn?Leu?His?Ser

915 920 925

Glu?Gly?Thr?Thr?Ser?Thr?Ser?Val?Gln?Leu?Ser?Trp?Gln?Pro?Pro?Val

930 935 940

Leu?Ala?Glu?Arg?Asn?Gly?Ile?Ile?Thr?Lys?Tyr?Thr?Leu?Leu?Tyr?Arg

945 950 955 960

Asp?Ile?Asn?Ile?Pro?Leu?Leu?Pro?Met?Glu?Gln?Leu?Ile?Val?Pro?Ala

965 970 975

Asp?Thr?Thr?Met?Thr?Leu?Thr?Gly?Leu?Lys?Pro?Asp?Thr?Thr?Tyr?Asp

980 985 990

Val?Lys?Val?Arg?Ala?His?Thr?Ser?Lys?Gly?Pro?Gly?Pro?Tyr?Ser?Pro

995 1000 1005

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

1010 1015 1020

Phe?His?Val?Lys?Ala?Val?Met?Lys?Thr?Ser?Val?Leu?Leu?Ser?Trp?Glu

1025 1030 1035 1040

Ile?Pro?Glu?Asn?Tyr?Asn?Ser?Ala?Met?Pro?Phe?Lys?Ile?Leu?Tyr?Asp

1045 1050 1055

Asp?Gly?Lys?Met?Val?Glu?Glu?Val?Asp?Gly?Arg?Ala?Thr?Gln?Lys?Leu

1060 1065 1070

Ile?Val?Asn?Leu?Lys?Pro?Glu?Lys?Ser?Tyr?Ser?Phe?Val?Leu?Thr?Asn

1075 1080 1085

Arg?Gly?Asn?Ser?Ala?Gly?Gly?Leu?Gln?His?Arg?Val?Thr?Ala?Lys?Thr

1090 1095 1100

Ala?Pro?Asp?Val?Leu?Arg?Thr?Lys?Pro?Ala?Phe?Ile?Gly?Lys?Thr?Asn

1105 1110 1115 1120

Leu?Asp?Gly?Met?Ile?Thr?Val?Gln?Leu?Pro?Glu?Val?Pro?Ala?Asn?Glu

1125 1130 1135

Asn?Ile?Lys?Gly?Tyr?Tyr?Ile?Ile?Ile?Val?Pro?Leu?Lys?Lys?Ser?Arg

1140 1145 1150

Gly?Lys?Phe?Ile?Lys?Pro?Trp?Glu?Ser?Pro?Asp?Glu?Met?Glu?Leu?Asp

1155 1160 1165

Glu?Leu?Leu?Lys?Glu?Ile?Ser?Arg?Lys?Arg?Arg?Ser?Ile?Arg?Tyr?Gly

1170 1175 1180

Arg?Glu?Val?Glu?Leu?Lys?Pro?Tyr?Ile?Ala?Ala?His?Phe?Asp?Val?Leu

1185 1190 1195 1200

Pro?Thr?Glu?Phe?Thr?Leu?Gly?Asp?Asp?Lys?His?Tyr?Gly?Gly?Phe?Thr

1205 1210 1215

Asn?Lys?Gln?Leu?Gln?Ser?Gly?Gln?Glu?Tyr?Val?Phe?Phe?Val?Leu?Ala

1220 1225 1230

Val?Met?Glu?His?Ala?Glu?Ser?Lys?Met?Tyr?Ala?Thr?Ser?Pro?Tyr?Ser

1235 1240 1245

Asp?Pro?Val?Val?Ser?Met?Asp?Leu?Asp?Pro?Gln?Pro?Ile?Thr?Asp?Glu

1250 1255 1260

Glu?Glu?Gly?Leu?Ile?Trp?Val?Val?Gly?Pro?Val?Leu?Ala?Val?Val?Phe

1265 1270 1275 1280

Ile?Ile?Cys?Ile?Val?Ile?Ala?Ile?Leu?Leu?Tyr?Lys?Arg?Lys?Arg?Ala

1285 1290 1295

Glu?Ser?Asp?Ser?Arg?Lys?Ser?Ser?Ile?Pro?Asn?Asn?Lys?Glu?Ile?Pro

1300 1305 1310

Ser?His?His?Pro?Thr?Asp?Pro?Val?Glu?Leu?Arg?Arg?Leu?Asn?Phe?Gln

1315 1320 1325

Thr?Pro?Gly?Met?Ala?Ser?His?Pro?Pro?Ile?Pro?Ile?Leu?Glu?Leu?Ala

1330 1335 1340

Asp?His?Ile?Glu?Arg?Leu?Lys?Ala?Asn?Asp?Asn?Leu?Lys?Phe?Ser?Gln

1345 1350 1355 1360

Glu?Tyr?Glu?Ser?Ile?Asp?Pro?Gly?Gln?Gln?Phe?Thr?Trp?Glu?His?Ser

1365 1370 1375

Asn?Leu?Glu?Val?Asn?Lys?Pro?Lys?Asn?Arg?Tyr?Ala?Asn?Val?Ile?Ala

1380 1385 1390

Tyr?Asp?His?Ser?Arg?Val?Leu?Leu?Ser?Ala?Ile?Glu?Gly?Ile?Pro?Gly

1395 1400 1405

Ser?Asp?Tyr?Val?Asn?Ala?Asn?Tyr?Ile?Asp?Gly?Tyr?Arg?Lys?Gln?Asn

1410 1415 1420

Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Ser?Leu?Pro?Glu?Thr?Phe?Gly?Asp?Phe

1425 1430 1435 1440

Trp?Arg?Met?Ile?Trp?Glu?Gln?Arg?Ser?Ala?Thr?Val?Val?Met?Met?Thr

1445 1450 1455

Lys?Leu?Glu?Glu?Arg?Ser?Arg?Val?Lys?Cys?Asp?Gln?Tyr?Trp?Pro?Ser

1460 1465 1470

Arg?Gly?Thr?Glu?Thr?His?Gly?Leu?Val?Gln?Val?Thr?Leu?Leu?Asp?Thr

1475 1480 1485

Val?Glu?Leu?Ala?Thr?Tyr?Cys?Val?Arg?Thr?Phe?Ala?Leu?Tyr?Lys?Asn

1490 1495 1500

Gly?Ser?Ser?Glu?Lys?Arg?Glu?Val?Arg?Gln?Phe?Gln?Phe?Thr?Ala?Trp

1505 1510 1515 1520

Pro?Asp?His?Gly?Val?Pro?Glu?His?Pro?Thr?Pro?Phe?Leu?Ala?Phe?Leu

1525 1530 1535

Arg?Arg?Val?Lys?Thr?Cys?Asn?Pro?Pro?Asp?Ala?Gly?Pro?Met?Val?Val

1540 1545 1550

His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Cys?Phe?Ile?Val?Ile?Asp

1555 1560 1565

Ala?Met?Leu?Glu?Arg?Ile?Lys?His?Glu?Lys?Thr?Val?Asp?Ile?Tyr?Gly

1570 1575 1580

His?Val?Thr?Leu?Met?Arg?Ala?Gln?Arg?Asn?Tyr?Met?Val?Gln?Thr?Glu

1585 1590 1595 1600

Asp?Gln?Tyr?Ile?Phe?Ile?His?Asp?Ala?Leu?Leu?Glu?Ala?Val?Thr?Cys

1605 1610 1615

Gly?Asn?Thr?Glu?Val?Pro?Ala?Arg?Asn?Leu?Tyr?Ala?Tyr?Ile?Gln?Lys

1620 1625 1630

Leu?Thr?Gln?Ile?Glu?Thr?Gly?Glu?Asn?Val?Thr?Gly?Met?Glu?Leu?Glu

1635 1640 1645

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

1650 1655 1660

Ala?Asn?Leu?Pro?Cys?Asn?Lys?Phe?Lys?Asn?Arg?Leu?Val?Asn?Ile?Met

1665 1670 1675 1680

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

1685 1690 1695

Gly?Ser?Asp?Tyr?Ile?Asn?Ala?Ser?Phe?Ile?Asp?Gly?Tyr?Arg?Gln?Gln

1700 1705 1710

Lys?Ala?Tyr?Ile?Ala?Thr?Gln?Gly?Pro?Leu?Ala?Glu?Thr?Thr?Glu?Asp

1715 1720 1725

Phe?Trp?Arg?Met?Leu?Trp?Glu?His?Asn?Ser?Thr?Ile?Val?Val?Met?Leu

1730 1735 1740

Thr?Lys?Leu?Arg?Glu?Met?Gly?Arg?Glu?Lys?Cys?His?Gln?Tyr?Trp?Pro

1745 1750 1755 1760

Ala?Glu?Arg?Ser?Ala?Arg?Tyr?Gln?Tyr?Phe?Val?Val?Asp?Pro?Met?Ala

1765 1770 1775

Glu?Tyr?Asn?Met?Pro?Gln?Tyr?Ile?Leu?Arg?Glu?Phe?Lys?Val?Thr?Asp

1780 1785 1790

Ala?Arg?Asp?Gly?Gln?Ser?Arg?Thr?Val?Arg?Gln?Phe?Gln?Phe?Thr?Asp

1795 1800 1805

Trp?Pro?Glu?Gln?Gly?Val?Pro?Lys?Ser?Gly?Glu?Gly?Phe?Ile?Asp?Phe

1810 1815 1820

Ile?Gly?Gln?Val?His?Lys?Thr?Lys?Glu?Gln?Phe?Gly?Gln?Asp?Gly?Pro

1825 1830 1835 1840

Ile?Ser?Val?His?Cys?Ser?Ala?Gly?Val?Gly?Arg?Thr?Gly?Val?Phe?Ile

1845 1850 1855

Thr?Leu?Ser?Ile?Val?Leu?Glu?Arg?Met?Arg?Tyr?Glu?Gly?Val?Val?Asp

1860 1865 1870

Ile?Phe?Gln?Thr?Val?Lys?Met?Leu?Arg?Thr?Gln?Arg?Pro?Ala?Met?Val

1875 1880 1885

Gln?Thr?Glu?Asp?Gln?Tyr?Gln?Phe?Ser?Tyr?Arg?Ala?Ala?Leu?Glu?Tyr

1890 1895 1900

Leu?Gly?Ser?Phe?Asp?His?Tyr?Ala?Thr

1905 1910

Claims (35)

1. isolated antibody, or its antigen-binding fragment, (a) it is specifically in conjunction with being selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) at least two kinds of receptor-like protein tyrosine phosphatases (RPTP) polypeptide among the RPTP-δ; And (b) its competitive inhibition poxvirus polypeptide and described at least two kinds of RPTP polypeptide combines.

2. isolated antibody, or its antigen-binding fragment, it is specifically in conjunction with at least a receptor-like protein tyrosine phosphatase (RPTP) on the cell surface that is present in immunocyte, wherein said at least a RPTP is RPTP-σ or RPTP-δ, and the RPTP on wherein said antibody or its antigen-binding fragment and the cell surface that is present in immunocyte combine the immunoreactivity that suppresses described immunocyte.

3. according to the antibody of claim 1 or 2, wherein said antibody is polyclonal antibody or monoclonal antibody.

4. according to the antigen-binding fragment of claim 1 or 2, wherein said antigen-binding fragment is selected from F (ab ') ₂, Fab ', Fab, Fd, Fv and strand Fv (scFv).

5. according to the antibody of claim 1 or claim 2, wherein said poxvirus polypeptide is A41L or tanapox virus 130L.

6. bi-specific antibody, it comprises first antigen-bound fraction that (a) can specificity bind receptor sample Protein-tyrosine-phosphatase (RPTP), wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ; And (b) can specificity in conjunction with second antigen-bound fraction of RPTP, wherein said RPTP is selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ, wherein said first antigen-bound fraction is different with described second antigen-bound fraction, and wherein said bi-specific antibody suppresses the immunoreactivity of immunocyte.

7. fusion polypeptide, it comprises immunoglobulin like domain 2 polypeptide of (a) the first receptor-like protein tyrosine phosphatase (RPTP); (b) immunoglobulin like domain 3 polypeptide of the 2nd RPTP; (c) immunoglobulin Fc polypeptide or its mutain, each among a wherein said RPTP and described the 2nd RPTP is to be selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ, and wherein said first and second RPTP are identical or different.

8. the fusion polypeptide of claim 7, a wherein said RPTP is identical with described the 2nd RPTP.

9. the fusion polypeptide of claim 7, a wherein said RPTP is that RPTP-σ and described the 2nd RPTP are RPTP-σ, and wherein said fusion polypeptide also comprises immunoglobulin like domain 1 polypeptide of RPTP-σ; A perhaps wherein said RPTP is that RPTP-δ and described the 2nd RPTP are RPTP-δ, and wherein said fusion polypeptide also comprises immunoglobulin like domain 1 polypeptide of RPTP-δ.

10. composition, it comprises: (a) at least one immunoglobulin like domain 2 polypeptide of the first receptor-like protein tyrosine phosphatase (RPTP) and (b) at least one immunoglobulin like domain 3 polypeptide of the 2nd RPTP, wherein said first and second RPTP are identical or different, and are selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.

11. the composition of claim 10, a wherein said RPTP is identical with described the 2nd RPTP.

12. the composition of claim 10, a wherein said RPTP are that RPTP-σ and described the 2nd RPTP are RPTP-σ, and wherein said composition also comprises immunoglobulin like domain 1 polypeptide of RPTP-σ; A perhaps wherein said RPTP is that RPTP-δ and described the 2nd RPTP are RPTP-δ, and wherein said composition also comprises immunoglobulin like domain 1 polypeptide of RPTP-δ.

13. a composition that comprises polypeptide dimer, wherein said dimer comprises: (a) first monomer, and it comprises immunoglobulin like domain 2 polypeptide and immunoglobulin like domain 3 polypeptide of the first receptor-like protein tyrosine phosphatase (RPTP); (b) second monomer, it comprises immunoglobulin like domain 2 polypeptide and immunoglobulin like domain 3 polypeptide of the 2nd RPTP, wherein said first and second RPTP are identical or different, and are selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) RPTP-δ.

14. the composition of claim 13, a wherein said RPTP is different with described the 2nd RPTP.

15. the composition of claim 13, a wherein said RPTP is identical with described the 2nd RPTP.

16. the composition of claim 13, wherein said first monomer also comprises the immunoglobulin like domain 1 of a RPTP, and wherein said second monomer also comprises the immunoglobulin like domain 1 of described the 2nd RPTP.

17. according to the composition of claim 13, wherein said first monomer and immunoglobulin Fc polypeptide merge, and wherein said second monomer and the fusion of immunoglobulin Fc polypeptide.

18. the composition of claim 10 or claim 13, it also comprises medicinal suitable vehicle.

19. fusion polypeptide, it comprises the poxvirus polypeptide that merges with mutain Fc polypeptide, wherein said mutain Fc polypeptide comprises the aminoacid sequence of the Fc part of the human IgG1's immunoglobulin (Ig) that contains at least one sudden change, wherein said at least one sudden change is replacement or the disappearance at the cysteine residues of hinge area, the cysteine residues that wherein is substituted or lacks is near the N-terminal cysteine residues of wild-type human IgG1 immunoglobulin Fc part hinge area, and wherein said poxvirus polypeptide can be selected from (i) leukocyte common antigen (LCA) associated protein (LAR); (ii) RPTP-σ; (iii) receptor-like protein tyrosine phosphatase (RPTP) combination of RPTP-δ.

20. fusion polypeptide according to claim 19, wherein said mutain Fc polypeptide comprises at least one second sudden change, wherein said at least one second sudden change is at least one amino acid that is substituted in the CH2 structural domain, and consequently described fusion polypeptide is reduced in conjunction with the ability of IgG Fc acceptor.

21. a composition, it comprises according to the fusion polypeptide of claim 7 or claim 19 and medicinal suitable vehicle.

22. a composition, it comprises that (a) is according to the antibody of claim 1 or 2 or its antigen-binding fragment and (b) medicinal suitable vehicle.

23. a composition, it comprises according to the bi-specific antibody of claim 6 and medicinal suitable vehicle.

24. a method that suppresses the immunne response among the experimenter, it comprises to described experimenter uses composition according to claim 18.

25. a method that suppresses the immunne response among the experimenter, it comprises to described experimenter uses composition according to claim 21.

26. a method that suppresses the immunne response among the experimenter, it comprises to described experimenter uses composition according to claim 22.

27. a method that suppresses the immunne response among the experimenter, it comprises to described experimenter uses composition according to claim 23.

28. treat the Immunological diseases among the experimenter or the method for illness for one kind, it comprises to described experimenter uses composition according to claim 18.

29. treat the Immunological diseases among the experimenter or the method for illness for one kind, it comprises to described experimenter uses composition according to claim 21.

30. treat the Immunological diseases among the experimenter or the method for illness for one kind, it comprises to described experimenter uses composition according to claim 22.

31. treat the Immunological diseases among the experimenter or the method for illness for one kind, it comprises to described experimenter uses composition according to claim 23.

32. a production is according to the preparation method of the antibody of claim 1 or 2.

33. a production is according to the preparation method of the bi-specific antibody of claim 6.

34. a production is according to the preparation method of the fusion polypeptide of claim 7 or 19.

35. a production is according to the preparation of compositions method of claim 10 or 13.

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