CN1222616C - Novel human protein with cancer-inhibiting function and coding sequence thereof - Google Patents

Abstract

The present invention discloses a novel human protein with the function of inhibiting cancer, polynucleotide for encoding the polypeptide and a method for preparing the polypeptide by a recombinant technology. The present invention also discloses a method of using the polypeptide to treat various diseases, such as cancers. The present invention also discloses an antagonist of the polypeptide and a therapeutic effect thereof. The present invention also discloses the application of the polynucleotide for encoding the human protein with the function of inhibiting cancer.

Description

New people's albumen and encoding sequence thereof with cancer suppressing function

Technical field

The invention belongs to biological technical field, specifically, the present invention relates to new coding and have the proteic polynucleotide of people of cancer suppressing function and the polypeptide of this polynucleotide encoding.The invention still further relates to the purposes and the preparation of these polynucleotide and polypeptide.

Background technology

The research of people's gene group is international focus at present, removes human chromosome DNA large scale sequencing, outside the method for expressed sequence order-checking (EST), also lacks the screening that begins from function and has the high-throughout method of functional gene.

Cancer is one of principal disease of harm humans health.In order to treat effectively and prophylaxis of tumours, people more and more pay close attention to genetic treatment of tumor at present.Therefore, this area presses for people's albumen and the agonist/inhibitor thereof that development research has cancer suppressing function.

Summary of the invention

The purpose of this invention is to provide the new people's protein polypeptide of a class with cancer suppressing function with and fragment, analogue and derivative.

Another object of the present invention provides the polynucleotide of these polypeptide of coding.

Another object of the present invention provides the method for these polypeptide of production and the purposes of this polypeptide and encoding sequence.

In a first aspect of the present invention, novel isolated protein polypeptide with cancer suppressing function is provided, it comprises the polypeptide of the aminoacid sequence with the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30; Or its conservative property variation polypeptide or its active fragments or its reactive derivative.Preferably, this polypeptide is the polypeptide with aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30.

In a second aspect of the present invention, a kind of isolating polynucleotide are provided, it comprises a nucleotide sequence, and this nucleotide sequence is shown at least 85% homogeny with a kind of nucleotides sequence that is selected from down group: the polynucleotide of the above-mentioned protein polypeptide with cancer suppressing function of (a) encoding; (b) with polynucleotide (a) complementary polynucleotide.Preferably, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30.More preferably, the sequence of these polynucleotide is selected from down group: SEQ ID NO:2,5,8,11,14,17,20,23,26,29 coding region sequence or full length sequence.

In a third aspect of the present invention, the carrier that contains above-mentioned polynucleotide is provided, and has been transformed or host cell of transduceing or the host cell that is directly transformed or transduce by above-mentioned polynucleotide by this carrier.

In a fourth aspect of the present invention, the preparation method who prepares the polypeptide of the protein-active with cancer suppressing function is provided, this method comprises: (a) have under the proteic condition of cancer suppressing function suitable the expression, cultivate the above-mentioned host cell that is transformed or transduce; (b) from culture, isolate the polypeptide of protein-active with cancer suppressing function.

In a fifth aspect of the present invention, provide and above-mentioned protein polypeptide specificity bonded antibody with cancer suppressing function.The nucleic acid molecule that can be used for detecting also is provided, and it contains, and continuous 10 Nucleotide are to full length nucleotide in the above-mentioned polynucleotide, and preferably it contains the about 15-1000 of a successive Nucleotide.

In a sixth aspect of the present invention, a kind of pharmaceutical composition is provided, it contains the protein polypeptide and the pharmaceutically acceptable carrier with cancer suppressing function of the present invention of safe and effective amount.These pharmaceutical compositions can be treated illnesss such as cancer and cellular abnormality propagation.

Others of the present invention are because the disclosure of this paper is conspicuous to those skilled in the art.

Embodiment

The present invention adopts large-scale cDNA clone transfection cancer cells, has on the basis of cancer suppressing action in acquisition, proves new gene through order-checking, further obtains full length cDNA clone.DNA transfection evidence, the albumen with cancer suppressing function of the present invention has the effect that suppresses clone's formation, its inhibiting rate 〉=50% to liver cancer cell 7721.

As used herein, " isolating " is meant that material separates (if natural substance, primal environment promptly is a natural surroundings) from its primal environment.Do not have separation and purification as polynucleotide under the native state in the active somatic cell and polypeptide, but same polynucleotide or polypeptide as from native state with in other materials that exist separately, then for separation and purification.

As used herein, " isolating albumen or polypeptide with cancer suppressing function " is meant that the protein polypeptide with cancer suppressing function is substantially free of natural relative other albumen, lipid, carbohydrate or other material.Those skilled in the art can have the albumen of cancer suppressing function with the purified technology of protein purifying of standard.Basically pure polypeptide can produce single master tape on non-reduced polyacrylamide gel.

Polypeptide of the present invention can be recombinant polypeptide, natural polypeptides, synthetic polypeptide, preferred recombinant polypeptide.Polypeptide of the present invention can be the product of natural purifying, or the product of chemosynthesis, or uses recombinant technology to produce from protokaryon or eucaryon host (for example, bacterium, yeast, higher plant, insect and mammalian cell).The host used according to the recombinant production scheme, polypeptide of the present invention can be glycosylated, maybe can be nonglycosylated.Polypeptide of the present invention also can comprise or not comprise initial methionine residues.

The present invention also comprises the proteic fragment of the people with cancer suppressing function, derivative and analogue.As used herein, term " fragment ", " derivative " are meant with " analogue " and keep natural identical biological function or the active polypeptide of people's albumen with cancer suppressing function of the present invention basically.Polypeptide fragment of the present invention, derivative or analogue can be that (i) has one or more conservative or substituted polypeptide of non-conservation amino-acid residue (preferred conservative amino acid residue), and the amino-acid residue of such replacement can be also can not encoded by genetic code, or (ii) in one or more amino-acid residues, has a polypeptide of substituted radical, or (iii) mature polypeptide and another compound (such as the compound that prolongs the polypeptide transformation period, polyoxyethylene glycol for example) merge formed polypeptide, or (iv) additional aminoacid sequence is fused to this peptide sequence and the polypeptide that forms (as leader sequence or secretion sequence or be used for the sequence or the proteinogen sequence of this polypeptide of purifying).According to the instruction of this paper, these fragments, derivative and analogue belong to the known scope of those skilled in the art.

Polynucleotide of the present invention can be dna form or rna form.Dna form comprises the DNA of cDNA, genomic dna or synthetic.DNA can be strand or double-stranded.DNA can be coding strand or noncoding strand.Be example with LP4790 albumen (in this application, its clone numbering is adopted in proteinic name), the coding region sequence of encoding mature polypeptide can be identical with the coding region sequence shown in the SEQ ID NO:2 or the varient of degeneracy.As used herein, " varient of degeneracy " is meant that for LP4790 coding has the protein of SEQ ID NO:3, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ ID NO:2.Be example with LP4791 albumen again, the coding region sequence of encoding mature polypeptide can be identical with the coding region sequence shown in the SEQ ID NO:5 or the varient of degeneracy; " varient of degeneracy " is meant that for LP4791 coding has the protein of SEQ ID NO:6, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ ID NO:5.Have the albumen of cancer suppressing function for of the present invention other, can the rest may be inferred.

The polynucleotide of encoding mature polypeptide comprise: the encoding sequence of an encoding mature polypeptide; The encoding sequence of mature polypeptide and various additional code sequence; Encoding sequence of mature polypeptide (with optional additional code sequence) and non-coding sequence.

Term " polynucleotide of coded polypeptide " can be the polynucleotide that comprise this polypeptide of encoding, and also can be the polynucleotide that also comprise additional code and/or non-coding sequence.

The invention still further relates to the varient of above-mentioned polynucleotide, its coding has the polypeptide of identical aminoacid sequence or fragment, analogue and the derivative of polypeptide with the present invention.The varient of these polynucleotide can be the allelic variant of natural generation or the varient that non-natural takes place.These nucleotide diversity bodies comprise and replace varient, deletion mutation body and insert varient.As known in the art, allelic variant is the replacement form of polynucleotide, and it may be replacement, disappearance or the insertion of one or more Nucleotide, but can be from not changing the function of its encoded polypeptides in fact.

The invention still further relates to and above-mentioned sequence hybridization and two sequences between have at least 50%, preferably at least 70%, the polynucleotide of at least 80% homogeny more preferably.The present invention be more particularly directed under stringent condition and the interfertile polynucleotide of polynucleotide of the present invention.In the present invention, " stringent condition " is meant: (1) than hybridization under low ionic strength and the comparatively high temps and wash-out, as 0.2 * SSC, and 0.1%SDS, 60 ℃; Or (2) hybridization the time is added with denaturing agent, as 50% (v/v) methane amide, 0.1% calf serum/0.1%Ficoll, 42 ℃ etc.; Or (3) only at the homogeny between the two sequences at least more than 95%, be more preferably 97% and just hybridize when above.And the polypeptide of interfertile polynucleotide encoding has identical biological function (is example with LP4790 albumen) and activity with the mature polypeptide shown in the SEQ IDNO:3.

The invention still further relates to nucleic acid fragment with above-mentioned sequence hybridization.As used herein, the length of " nucleic acid fragment " contains 15 Nucleotide at least, better is at least 30 Nucleotide, is more preferably at least 50 Nucleotide, preferably more than at least 100 Nucleotide.The amplification technique (as PCR) that nucleic acid fragment can be used for nucleic acid has the proteic polynucleotide of cancer suppressing function to determine and/or to separate to encode.

Polypeptide among the present invention and polynucleotide preferably provide with isolating form, more preferably are purified to homogeneous.

Dna sequence dna of the present invention can obtain with several method.For example, with hybridization technique DNA isolation well known in the art.These technology including, but not limited to: 1) with probe and genome or the hybridization of cDNA library to detect homology nucleotide sequence and 2) antibody screening of expression library to be to detect the dna fragmentation of the clone with common structure feature.

The proteic specific DNA fragment sequence that coding has cancer suppressing function produces also and can obtain with following method: 1) separate double chain DNA sequence from genomic dna; 2) the chemical synthesising DNA sequence is to obtain the double-stranded DNA of required polypeptide.

When the whole aminoacid sequence of the polypeptide product of needs was known, the direct chemical of dna sequence dna is synthetic to be the method for often selecting for use.When if required amino acid whose whole sequence is not known, the direct chemical of dna sequence dna is synthetic to be impossible, and the method for selecting for use is the separation of cDNA sequence.The standard method that separates interested cDNA is from the donorcells separating mRNA of this gene of high expression level and carries out reverse transcription, forms plasmid or phage cDNA library.Extract the existing multiple proven technique of method of mRNA, test kit also can obtain (Qiagene) from commercial channels.And the construction cDNA library also is usual method (Sambrook, et al., Molecular Cloning, A Laboratory Manual, Cold SpringHarbor Laboratory.New York, 1989).Also can obtain the cDNA library of commercial offers, as the different cDNA library of Clontech company.When being used in combination the polymeric enzyme reaction technology, even few expression product also can be cloned.

Available ordinary method is screened gene of the present invention from these cDNA libraries.These methods include, but is not limited to: (1) DNA-DNA or DNA-RNA hybridization; (2) function of marker gene occurs or forfeiture; (3) mensuration has the level of the proteic transcript of cancer suppressing function; (4), detect the protein product of genetic expression by immunological technique or mensuration biologic activity.Aforesaid method can singly be used, but also several different methods combined utilization.

In (1) kind method, hybridizing used probe is and any a part of homology of polynucleotide of the present invention that at least 15 Nucleotide of its length better are at least 30 Nucleotide, are more preferably at least 50 Nucleotide, preferably at least 100 Nucleotide.In addition, the length of probe within 2kb, preferably is within the 1kb usually.Probe used herein is the dna sequence dna of chemosynthesis on the basis of gene DNA sequence information of the present invention normally.Gene of the present invention itself or fragment are certainly as probe.The mark of dna probe can be used radio isotope, fluorescein or enzyme (as alkaline phosphatase) etc.

In (4) kind method, detect the protein product of protein gene expression and can use immunological technique such as Western blotting, radioimmunoprecipitation, enzyme-linked immunosorbent assay (ELISA) etc. with cancer suppressing function.

Use method (Saiki, the et al.Science 1985 of round pcr DNA amplification/RNA; 230:1350-1354) be optimized for acquisition gene of the present invention.When particularly being difficult to obtain the cDNA of total length from the library, can preferably use RACE method (the terminal rapid amplifying method of RACE-cDNA), the primer that is used for PCR can suitably be selected according to sequence information of the present invention disclosed herein, and available ordinary method is synthetic.Available ordinary method is as the DNA/RNA fragment by gel electrophoresis separation and purifying amplification.

The gene of the present invention that obtains as mentioned above, perhaps the available ordinary method of mensuration of the nucleotide sequence of various dna fragmentations etc. such as dideoxy chain termination (Sanger et al.PNAS, 1977,74:5463-5467).This class nucleotide sequencing is available commercial sequencing kit etc. also.In order to obtain the cDNA sequence of total length, order-checking need be carried out repeatedly.Sometimes need to measure a plurality of clones' cDNA sequence, just can be spliced into the cDNA sequence of total length.

The present invention also relates to comprise the carrier of polynucleotide of the present invention, and the host cell that produces through genetically engineered with carrier of the present invention or albumen coded sequence with cancer suppressing function, and the method that produces polypeptide of the present invention through recombinant technology.

By the recombinant DNA technology of routine, can utilize polymerized nucleoside acid sequence of the present invention to can be used to express or produce the protein polypeptide with cancer suppressing function of reorganization.In general following steps are arranged:

(1). have the proteic polynucleotide of people (or varient) of cancer suppressing function with coding of the present invention, or transform or the transduction proper host cell with the recombinant expression vector that contains these polynucleotide;

(2). the host cell of in suitable medium, cultivating;

(3). separation, protein purification from substratum or cell.

Among the present invention, the people's albumen polynucleotide sequence with cancer suppressing function can be inserted in the recombinant expression vector.Term " recombinant expression vector " refers to that bacterial plasmid well known in the art, phage, yeast plasmid, vegetable cell virus, mammalian cell virus are as adenovirus, retrovirus or other carriers.The carrier of Shi Yonging includes but not limited in the present invention: the expression vector based on T7 of expressing in bacterium; The pMSXND expression vector of in mammalian cell, expressing and at the carrier that derives from baculovirus of expressed in insect cells.In a word, as long as can duplicate in host and stablize, any plasmid and carrier can be used.A key character of expression vector is to contain replication orgin, promotor, marker gene and translation controlling elements usually.

Method well-known to those having ordinary skill in the art can be used to make up and contains people's encoding histone dna sequence dna with cancer suppressing function and suitable transcribing/the translate expression vector of control signal.These methods comprise extracorporeal recombinant DNA technology, DNA synthetic technology, the interior recombinant technology of body etc.Described dna sequence dna can effectively be connected on the suitable promotor in the expression vector, and is synthetic to instruct mRNA.The representative example of these promotors has: colibacillary lac or trp promotor; Lambda particles phage P _LPromotor; Eukaryotic promoter comprises LTRs and some other known may command gene expression promoter in protokaryon or eukaryotic cell or its virus of CMV immediate early promoter, early stage and late period SV40 promotor, retrovirus.Expression vector also comprises ribosome bind site and the transcription terminator that translation initiation is used.

In addition, expression vector preferably comprises one or more selected markers, to be provided for selecting the phenotypic character of transformed host cells, cultivate Tetrahydrofolate dehydrogenase, neomycin resistance and the green fluorescent protein (GFP) of usefulness as eukaryotic cell, or be used for colibacillary tsiklomitsin or amicillin resistance.

Comprise the carrier of above-mentioned suitable dna sequence dna and suitable promotor or control sequence, can be used to transform appropriate host cell, so that it can marking protein.

Host cell can be a prokaryotic cell prokaryocyte, as bacterial cell; Or eukaryotic cell such as low, as yeast cell; Or higher eucaryotic cells, as mammalian cell.Representative example has: intestinal bacteria, streptomyces; The bacterial cell of Salmonella typhimurium; Fungal cell such as yeast; Vegetable cell; The insect cell of fruit bat S2 or Sf9; The zooblast of CHO, COS or Bowes melanoma cells etc.

When polynucleotide of the present invention are expressed in higher eucaryotic cells, be enhanced if will make to transcribe when in carrier, inserting enhancer sequence.Enhanser is the cis acting factor of DNA, and nearly 10 to 300 base pairs act on promotor transcribing with enhancing gene usually.Can for example be included in the SV40 enhanser of 100 to 270 base pairs of replication origin side in late period one, at the polyoma enhanser of replication origin side in late period one and adenovirus enhanser etc.

Persons skilled in the art all know how to select appropriate carriers, promotor, enhanser and host cell.

Can carry out with routine techniques well known to those skilled in the art with the recombinant DNA transformed host cell.When the host was prokaryotic organism such as intestinal bacteria, the competent cell that can absorb DNA can be used CaCl in exponential growth after date results ₂Method is handled, and used step is well-known in this area.Alternative is to use MgCl ₂If desired, transforming also the method for available electroporation carries out.When the host is an eukaryote, can select following DNA transfection method for use: coprecipitation of calcium phosphate method, conventional mechanical method such as microinjection, electroporation, liposome packing etc.

The transformant that obtains can be cultivated with ordinary method, expresses the polypeptide of coded by said gene of the present invention.According to used host cell, used substratum can be selected from various conventional substratum in the cultivation.Under the condition that is suitable for the host cell growth, cultivate.After host cell grows into suitable cell density, induce the promotor of selection with suitable method (as temperature transition or chemical induction), cell is cultivated for some time again.

Recombinant polypeptide in the above methods can wrap by in cell, extracellular or on cytolemma, express or be secreted into the extracellular.If desired, can utilize its physics, the separating by various separation methods with other characteristic and the albumen of purification of Recombinant of chemistry.These methods are well-known to those skilled in the art.The example of these methods includes, but are not limited to: conventional renaturation handles, with protein precipitant handle (salt analysis method), centrifugal, the broken bacterium of infiltration, superly handle, the combination of super centrifugal, sieve chromatography (gel-filtration), adsorption chromatography, ion exchange chromatography, high performance liquid chromatography (HPLC) and other various liquid chromatography (LC) technology and these methods.

The people's albumen or the polypeptide with cancer suppressing function of reorganization are of use in many ways.These purposes include, but is not limited to: directly have the disease (as cancer) due to the low or forfeiture of the protein function of cancer suppressing function as pharmacological agent and be used to screen and promote or antagonism has antibody, polypeptide or other part of the protein function of cancer suppressing function.For example, antibody can be used for activating or suppressing to have the proteic function of people of cancer suppressing function.The people's protein screening peptide library that has a cancer suppressing function with the reorganization of expressing can be used for seeking the peptide molecule that can suppress or stimulate the people's protein function with cancer suppressing function of therapeutic value.

The present invention also provides screening of medicaments to improve (agonist) or check the method that (antagonist) has the proteic medicament of people of cancer suppressing function to identify.Agonist improves the biological function such as stimulate cellular proliferation of the people's albumen with cancer suppressing function, and antagonist prevention disorder such as the various cancer relevant with cell hyperproliferation with treatment.For example, can be in the presence of medicine, the proteic film preparation of people that mammalian cell or expression is had cancer suppressing function is cultivated with the people's albumen with cancer suppressing function of mark.Measure the medicine raising then or check this interactional ability.

The proteic antagonist of people with cancer suppressing function comprises antibody, compound, acceptor disappearance thing and the analogue etc. that filter out.The proteic antagonist of people with cancer suppressing function can and be eliminated its function with the people's protein binding with cancer suppressing function, or suppresses to have the proteic generation of people of cancer suppressing function, or combines with the avtive spot of polypeptide and to make polypeptide can not bring into play biological function.The proteic antagonist of people with cancer suppressing function can be used for therepic use.

In screening during as the compound of antagonist, albumen of the present invention can be added during bioanalysis measures, determine by measuring albumen and the interaction between its acceptor that compounds affect has cancer suppressing function whether compound is antagonist.With the same quadrat method of above-mentioned SCREENED COMPOUND, can filter out the acceptor disappearance thing and the analogue of antagonist action.

Polypeptide of the present invention can be directly used in disease treatment, for example, and various malignant tumours and cellular abnormality propagation etc.

Polypeptide of the present invention, and fragment, derivative, analogue or their cell can be used as antigen to produce antibody.These antibody can be polyclone or monoclonal antibody.Polyclonal antibody can obtain by the method with this polypeptide direct injection animal.The technology of preparation monoclonal antibody comprises hybridoma technology, three knurl technology, people B-quadroma technology, EBV-hybridoma technology etc.

Can be with polypeptide of the present invention and antagonist and suitable pharmaceutical carrier combination back use.These carriers can be water, glucose, ethanol, salt, damping fluid, glycerine and their combination.Composition comprises the polypeptide or the antagonist of safe and effective amount and carrier and the vehicle that does not influence effect of drugs.These compositions can be used as medicine and are used for disease treatment.

The present invention also provides medicine box or the test kit that contains one or more containers, and one or more medicinal compositions compositions of the present invention are housed in the container.With these containers, can have by the given indicative prompting of government authorities of making, using or selling medicine or biological products, the government authorities that this prompting reflects production, uses or sells permits it to use on human body.In addition, polypeptide of the present invention can be used in combination with other treatment compound.

Pharmaceutical composition can be with mode administration easily, as by in part, intravenously, intraperitoneal, intramuscular, subcutaneous, the nose or the route of administration of intracutaneous.Albumen with cancer suppressing function comes administration with the amount that treats and/or prevents concrete indication effectively.The proteic amount with cancer suppressing function and the dosage range that are applied to the patient will depend on many factors, as administering mode, person's to be treated healthiness condition and diagnostician's judgement.

The proteic polynucleotide of people with cancer suppressing function also can be used for multiple therapeutic purpose.Gene therapy technology can be used for treating since have that the proteic nothing of cancer suppressing function is expressed or the proteic expression with cancer suppressing function of unusual/non-activity due to cell proliferation, growth or metabolic disturbance.The gene therapy vector of reorganization can be used for treating the protein expression with cancer suppressing function or the disease of active caused by abnormal.Deriving from the expression vector of virus such as protein gene that retrovirus, adenovirus, adeno-associated virus (AAV), hsv, parvovirus etc. can be used for having cancer suppressing function is transferred in the cell.The method that structure carries the recombinant viral vector of the protein gene with cancer suppressing function be found in existing document (Sambrook, etal.).The people protein gene of reorganization with cancer suppressing function can be packaged in the liposome and be transferred in the cell in addition.

Suppress to have cancer suppressing function people's protein mRNA oligonucleotide (comprising sense-rna and DNA) and ribozyme also within the scope of the invention.Ribozyme is the enzyme sample RNA molecule that a kind of energy specificity is decomposed specific RNA, and its mechanism of action is to carry out the endonuclease effect after ribozyme molecule and the hybridization of complementary target RNA-specific.The RNA of antisense and DNA and ribozyme can obtain with existing any RNA or DNA synthetic technology, as the technology widespread use of solid phase phosphoamide chemical synthesis synthetic oligonucleotide.Antisense rna molecule can be transcribed acquisition by the dna sequence dna of this RNA that encodes in external or body.This dna sequence dna has been incorporated into the downstream of rna polymerase promoter of carrier.In order to increase the stability of nucleic acid molecule, available several different methods is modified it, and as increasing the sequence length of both sides, the connection between the ribonucleoside is used phosphoric acid thioester bond or peptide bond but not phosphodiester bond.

Polynucleotide imports tissue or intracellular method comprises: directly be injected into polynucleotide in the in-vivo tissue; Or external by carrier (as virus, phage or plasmid etc.) earlier with the polynucleotide transfered cell in, again cell is transplanted in the body etc.

Polypeptide of the present invention also can be used as the peptide spectrum analysis, for example, the polypeptide available physical, chemistry or enzyme carry out the specificity cutting, and carry out the two-dimentional or three-dimensional gel electrophoresis analysis of one dimension.

The present invention also provides the antibody at the people's proteantigen determinant with cancer suppressing function.These antibody include, but is not limited to: the fragment that polyclonal antibody, monoclonal antibody, chimeric antibody, single-chain antibody, Fab fragment and Fab expression library produce.These antibody can prepare with ordinary method.The anti-proteic antibody of people with cancer suppressing function can be used in the immunohistochemistry technology, detects the people's albumen with cancer suppressing function in the biopsy specimen.

With the also available labelled with radioisotope of the protein bound monoclonal antibody of the people with cancer suppressing function, inject in the body and can follow the tracks of its position and distribution.Antibody among the present invention can be used for treating or prevents and the relevant disease of people's albumen with cancer suppressing function.The antibody that gives suitable dosage can stimulate or block proteic generation of the people with cancer suppressing function or activity.

Antibody also can be used for designing the immunotoxin at a certain privileged sites in the body.As have cancer suppressing function people's albumen high-affinity monoclonal antibody can with bacterium or plant poison (as diphtheria toxin, ricin, abrine etc.) covalent attachment.

Available people's albumen or the polypeptide immune animal of the production of polyclonal antibody with cancer suppressing function, as rabbit, mouse, rat etc.Multiple adjuvant can be used for the enhancing immunity reaction, includes but not limited to freund's adjuvant etc.

Have cancer suppressing function people's protein monoclonal antibody can with hybridoma technology production (Kohler and Milstein.Nature, 1975,256:495-497).With the variable region bonded chimeric antibody in human constant region and inhuman source can with existing technology production (Morrison et al, PNAS, 1985,81:6851).And the technology of existing manufacture order chain antibody (U.S.PatNo.4946778) also can be used for producing the anti-proteic single-chain antibody of people with cancer suppressing function.

Can be incorporated into the rondom polypeptide storehouse that solid formation forms by the various amino acid that may make up by screening with the protein bound peptide molecule of the present invention obtains.During screening, must carry out mark to people's protein molecular with cancer suppressing function.

The invention still further relates to quantitatively and detection and localization has the diagnostic testing process of people's protein level of cancer suppressing function.These tests are known in the art, and comprise that FISH measures and radioimmunoassay.The people's protein level that is detected in the test with cancer suppressing function, the disease that can have the importance of people's albumen in various diseases of cancer suppressing function with laying down a definition and be used to diagnose albumen to work with cancer suppressing function.

Proteic polynucleotide with cancer suppressing function can be used for having the diagnosis and the treatment of the protein related diseases of cancer suppressing function.Aspect diagnosis, the proteic polynucleotide with cancer suppressing function can be used for detecting have cancer suppressing function proteic expression whether or under morbid state, have an abnormal exprssion of cancer suppressing function.As the protein D NA sequence with cancer suppressing function can be used for the hybridization of biopsy specimen is had with judgement the proteic abnormal expression of cancer suppressing function.Hybridization technique comprises the Southern blotting, Northern blotting, in situ hybridization etc.These technological methods all are disclosed mature technologies, and relevant test kit all can obtain from commercial channels.Part or all of polynucleotide of the present invention can be used as probe stationary on microarray (Microarray) or DNA chip (being called " gene chip " again), is used for analyzing the differential expression analysis and the gene diagnosis of tissue gene.Carry out RNA-polymerase chain reaction (RT-PCR) amplification in vitro with the special primer of the albumen with cancer suppressing function and also can detect proteic transcription product with cancer suppressing function.

The sudden change that detection has the protein gene of cancer suppressing function also can be used for diagnosing the relevant disease of albumen with cancer suppressing function.Form with protein mutation of cancer suppressing function comprises that to have point mutation that the protein D NA sequence of cancer suppressing function compares, transposition, disappearance, reorganization and other any unusual etc. with normal wild type.Available existing technology such as Southern blotting, dna sequence analysis, PCR and in situ hybridization detect sudden change.In addition, sudden change might influence proteic expression, therefore can judge indirectly that with Northern blotting, Western blotting gene has or not sudden change.

Sequence of the present invention identifies it also is valuable to karyomit(e).These sequences can be specifically at certain bar human chromosome particular location and and can with its hybridization.At present, need to identify the concrete site of each gene on the karyomit(e).Yet have only chromosomal marker thing seldom to can be used for the marker chromosomes position now based on actual sequence data (repetition polymorphism).For these sequences are associated with disease related gene.The first step is positioned dna sequence dna of the present invention on the karyomit(e) exactly.

In brief, prepare PCR primer (preferred 15-35bp), sequence can be positioned on the karyomit(e) according to cDNA.Then, these primers are used for the somatocyte hybrid cell that the PCR screening contains each bar human chromosome.Have only those hybrid cells that contain corresponding to the people's gene of primer can produce the fragment of amplification.

The PCR localization method of somatocyte hybrid cell is that DNA is navigated to concrete chromosomal quick method.Use Oligonucleolide primers of the present invention,, can utilize one group to realize inferior location from specific chromosomal fragment or a large amount of genomic clone by similar approach.Other the similar strategy that can be used for chromosomal localization comprises in situ hybridization, uses the karyomit(e) prescreen and the hybridization preliminary election of the airflow classification of mark, thereby makes up the special cDNA storehouse of karyomit(e).

The cDNA clone is carried out fluorescence in situ hybridization (FISH) with Metaphase Chromosome, can in a step, accurately carry out chromosomal localization.The summary of this technology is referring to Verma etc., Human Chromosomes:a Manual of BasicTechniques, Pergamon Press, New York (1988).

In case sequence is positioned to chromosome position accurately, the physical location of this sequence on karyomit(e) just can be associated with the gene map data.These data for example are found in, V.Mckusick, Mendelian Inheritance in Man (can by with the online acquisition of Johns Hopkins University Welch Medical Library).Can pass through linkage analysis then, determine gene and navigated to relation between the disease on the chromosomal region already.

Then, need to measure ill and not cDNA between diseased individuals or genome sequence difference.If observe certain sudden change in some or all of diseased individuals, and this sudden change is not observed in any normal individual, then this sudden change may be the cause of disease of disease.More ill and diseased individuals not is usually directed at first seek the variation of structure in the karyomit(e), as from the horizontal visible of karyomit(e) or use based on detectable disappearance of the PCR of cDNA sequence or transposition.

Pyrenoids thuja acid full length sequence or its fragment with cancer suppressing function of the present invention can obtain with the method for pcr amplification method, recombination method or synthetic usually.For the pcr amplification method, can be disclosed according to the present invention about nucleotide sequence, especially open reading frame sequence designs primer, and with commercially available cDNA storehouse or by the prepared cDNA storehouse of ordinary method well known by persons skilled in the art as template, amplification and must relevant sequence.When sequence is longer, usually needs to carry out twice or pcr amplification repeatedly, and then the fragment that each time amplifies is stitched together by proper order.

In case obtained relevant sequence, just can obtain relevant sequence in large quantity with recombination method.This normally is cloned into carrier with it, changes cell again over to, separates obtaining relevant sequence then from the host cell after the propagation by ordinary method.

In addition, also the method for available synthetic is synthesized relevant sequence, especially fragment length more in short-term.Usually, by first synthetic a plurality of small segments, and then connect and to obtain the very long fragment of sequence.

At present, can be fully come the dna sequence dna of code book invention albumen (or its fragment, or derivatives thereof) by chemosynthesis.This dna sequence dna can be introduced then in the various dna moleculars (as carrier) and cell in this area.In addition, also can will suddenly change and introduce in the protein sequence of the present invention by chemosynthesis.

In addition, because the albumen with cancer suppressing function of the present invention has the natural acid sequence that is derived from the people, therefore, compare with the albumen of the same clan that derives from other species, estimate to have higher active and/or lower side effect (for example in the intravital immunogenicity of people lower or do not have) being applied to man-hour.

Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to people such as normal condition such as Sambrook, molecular cloning: laboratory manual (New York:Cold Spring Harbor LaboratoryPress, 1989) condition described in, or the condition of advising according to manufacturer.Notice that in Nucleotide and amino acid composite sequence, (1) provides the position that initial sum stops first Nucleotide of coding, (2) molecular weight unit is dalton.

The acquisition of embodiment 1:cDNA gene and the restraining effect that the cancer cells clone is formed

LP4790, LP4791, LP4941, LP5085, LP5161, LP5852, LP5910, LP7057, LP9056 and LP9167 come from the normal hepatocytes cDNA library that makes up with ordinary method.Get normal liver tissue (LP clone), (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.Make up the cDNA library of above-mentioned mRNA with pCMV-script TMXR cDNA library construction test kit (Stratagene company).Wherein ThermoScript II is used MMLV-RT-Superscript II (GIBCO BRL) instead, and reverse transcription reaction carries out at 42 ℃.Transform XL 10-Gold recipient cell, obtained the cDNA library of 1 * 106cfu/ μ g cDNA titre.The first round is picking cDNA clone at random, is probe with high abundance cDNA clone with the cDNA clone who has proved cancer inhibitor cell growth function thereafter, screening by hybridization cDNA library, weak positive and negative clone of picking.With Qiagen 96 orifice plate plasmid extraction test kits, carry out the extraction of plasmid DNA by shop instruction.Plasmid DNA and empty carrier transfection simultaneously hepatoma cell line 7721.After the 100ng DNA alcohol precipitation drying, add 6 μ l H2O dissolving, treat transfection.Add 0.74 μ l liposome and 9.3 μ l serum-free mediums in every part of DNA sample, behind the mixing, room temperature was placed 10 minutes.Add 150 μ l serum-free mediums in every pipe, divide equally and add 3 holes and grow in 7721 cells of 96 orifice plates, placed 2 hours for 37 ℃, every hole adds 50 μ l serum-free mediums again, 37 ℃ 24 hours.Every hole is changed 100 μ l and is trained liquid entirely, 37 ℃ 24 hours, change the full training liquid 100 μ l that contain G418,37 ℃ 24-48 hour, the limit is observed, the training liquid that G418 concentration does not wait is changed on the limit.After about 2-3 time, there is the clone to form up to the microscopy cell, counting.Find that above-mentioned clone has the cell clone of inhibition formation effect, the result is as shown in the table.

CDNA clone's transfectional cell (7721) clone formation situation

CDNA clones title	CDNA clones number (three repetitions)			Empty carrier clone number (three repetitions)
							LP4790	1	0	2	29	30	35
LP4791	1	1	0	29	30	35
							LP4941	1	2	1	32	20	36
LP5085	0	0	0	39	44	42
							LP5161	0	1	1	20	18	22
LP5852	3	1	1	38	32	26
							LP5910	1	2	0	51	29	48
LP7057	0	1	4	25	22	18
							LP9056	1	0	0	36	40	36
LP9167	0	0	0	10	13	8

The cDNA clone is adopted two deoxidation cessation method, on the ABI377 automatic dna sequencer, measure the nucleotide sequence of the nearly 500bp of one end.After the analysis, be defined as novel gene cloning, carry out the other end order-checking, do not obtain full length cDNA sequence yet, the design primer checks order once more, up to obtaining full length sequence (SEQ ID NO:1,4,7,10,13,16,19,22,25,28).

Embodiment 2: PCR obtains full-length gene from liver cDNA:

Get normal liver tissue (LP clone), (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.With MMLV-RT-Superscript II (GIBCOBRL), ThermoScript II is carried out reverse transcription reaction at 42 ℃, obtains placenta cDNA.Utilize the special primer (as shown in the table) of each gene, by 97 ℃ of 3 ' 1 circulations.94 ℃ 30 " 60 ℃ 30 " 72 ℃ of 1 ' 35 circulations, pcr amplification is carried out in 72 ℃ of 10 ' 1 circulations, and acquisition contains the amplified production of each protein gene of complete open reading frame sequence.Amplified production is through sequence verification, and the sequence that records with embodiment 1 conforms to, and changes amplified production over to host cell with routine techniques subsequently, obtains recombinant protein (SEQ ID NO:3,6,9,12,15,18,21,24,27,30).

Gene specific primer

Clone's title	Special primer 1 (5 ' → 3 ')	SEQ ID NO：	Special primer 2 (3 ' → 5 ')	SEQ ID NO：
					LP4790	(3)GGCACCTCAGCAACCAGT	31	CGAAACTAACTAAACCCGA(3584)	32
LP4791	(145)CAGTCTTCGCTCACTACAGCC	33	CCAATCCAAAATGACCCCGT(2325)	34
					LP4941	(15)AAGATGAATCCGTTGATCTCG	35	TCGTTTGACAGGTCTTCCCT(2813)	36
LP5085	(139)AAGCCCTACAGTGCAGAGGA	37	GAGAACCACAAAGTACGACG(2233)	38
					LP5161	(61)GAAGAGGAGGAGGAAGAGGAG	39	GTGGAAGGGACACTTTGTTC(3651)	40
LP5852	(66)CTTTCAGCTCGGCTGCTC	41	GTACCTCATATCGCAGTAGGG(2587)	42
					LP5910	(78)GAGGGTGCGGAGGACAAC	43	CAAGGACGGTGACATGAGGT(3218)	44
LP7057	(59)CTTGTTCCTGCCGCTTTC	45	TGTCTACTACTGACGTTTTACT(2579)	46
					LP9056	(26)ATCGTCGGCCAGTTTATCC	47	AATGGGGAACGACAAGTCTC(2682)	48
LP9167	(1)GGGAGGGCAGACTCTGGG	49	AGTGCGGTACGGGTGGTG(2742)	50

Annotate: in the bracket is the correspondence position of primer in each gene DNA sequence.

Embodiment 3:cDNA cloned sequence is analyzed

1.LP4790

A: nucleotide sequence (SEQ ID NO:1) length: 3657 bases

B: aminoacid sequence (SEQ ID NO:3) length: 185 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:2) clone number and protein name: LP4790 start code: 2441ATG stops coding: 2996TAG protein molecular weight: 20778.75

2.LP4791

A: nucleotide sequence (SEQ ID NO:4) length: 2350 bases

B: aminoacid sequence (SEQ ID NO:6) length: 101 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:5) clone number and protein name: LP4791 start code: 647ATG stops coding: 950TAG protein molecular weight: 11200.29

3.LP4941

A: nucleotide sequence (SEQ ID NO:7) length: 2837 bases

B: aminoacid sequence (SEQ ID NO:9) length: 303 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:8) clone number and protein name: LP4941 start code: 134ATG stops coding: 1043TGA protein molecular weight: 34340.95

4.LP5085

A: nucleotide sequence (SEQ ID NO:10) length: 2280 bases

B: aminoacid sequence (SEQ ID NO:12) length: 148 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:11) clone number and protein name: LP5085 start code: 627ATG stops coding: 1071TAG protein molecular weight: 16212.66

5.LP5161

A: nucleotide sequence (SEQ ID NO:13) length: 3750 bases

B: aminoacid sequence (SEQ ID NO:15) length: 383 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:14) clone number and protein name: LP5161 start code: 688ATG stops coding: 1837TGA protein molecular weight: 42218.46

6.LP5852

A: nucleotide sequence (SEQ ID NO:16) length: 2730 bases

B: aminoacid sequence (SEQ ID NO:18) length: 101 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:17) clone number and protein name: LP5852 start code: 1216ATG stops coding: 1519TGA protein molecular weight: 10843.61

7.LP5910

A: nucleotide sequence (SEQ ID NO:19) length: 3260 bases

B: aminoacid sequence (SEQ ID NO:21) length: 187 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:20) clone number and protein name: LP5910 start code: 1310ATG stops coding: 1871TGA protein molecular weight: 19866.41

8.LP7057

A: nucleotide sequence (SEQ ID NO:22) length: 2692 bases

B: aminoacid sequence (SEQ ID NO:24) length: 113 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:23) clone number and protein name: LP7057 start code: 2238ATG stops coding: 2577TGA protein molecular weight: 12875.58

9.LP9056

A: nucleotide sequence (SEQ ID NO:25) length: 2769 bases

B: aminoacid sequence (SEQ ID NO:27) length: 563 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:26) clone number and protein name: LP9056 start code: 742ATG stops coding: 2431TGA protein molecular weight: 63543.64

10.LP9167

A: nucleotide sequence (SEQ ID NO:28) length: 3226 bases

B: aminoacid sequence (SEQ ID NO:30) length: 137 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:29) clone number and protein name: LP9167 start code: 38ATG stops coding: 449TGA protein molecular weight: 15172.09

All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.

Sequence table

＜110〉Shanghai Xinshijie Gene Techn Development Co., Ltd.

＜120〉have new the people's albumen and the encoding sequence thereof of cancer suppressing function

<130>026810

<160>50

<170>PatentIn version 3.1

<210>1

<211>3657

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>1

ggggcacctc agcaaccagt agccatgcgc ggcttggagg agtcggggcc tcggcctaca 60

gcgaccccgt gcggctgcgt taagccggct ctggagacag ggaatctttt aactgagcca 120

gtcggctact tggaatcttg tttctcggcc aagaatggta ctccaagaca gccatccatt 180

tgtagctatt ctcgagcctg tttgaggatt agaaagagga tctttaataa tcctgaacat 240

tccttgatgg gcctagaaca gtttttctca tgtttggaag gtctagtcat gccaaatgga 300

aaaagaaagg aaggtctggt aaaggatttt gtttgttttt cacaaaaatg gtcatttgag 360

ctgtaaggca aaagtgcagc ctcctaggct gaatggtgca aagactggag ttttttccac 420

aaggagccct catcgtccca atgcaatagg actgaccctg gccaagctgg aaaaggtaga 480

agccttgggg aaatggacag atatcatggc tgcagtgctg atgtcaactg tgctgtgtgg 540

caggagtctg ggatgaatca cactacaagg acaaacattg gtcaggttgt agaagtttta 600

aactagtttt aactgtgtgt tcgtatataa cctagttacg catttatgga aagcattcca 660

ttctgaccta acagatgcat ttgttataga ggcagcagat gaaatggcag gtaaactagg 720

agtcaagaga ccattccagg cttcagcctg ctggttgtga agtgggcaaa ggagaaggac 780

ctgcttcctc tgtgattcca cagaatattt tgagaatctt gtaagagaga agttctaaaa 840

ctactttttc aggctattgg acactaaata gatgagagca gttattttgc ttgttctttc 900

ccagaacttg aactctccca ctggattgta ctcaactggg ccttaggtag ttttctcaga 960

aaaattcagt agctgatcca ccttgaattt tatcaatttg taatggctaa caaacttgga 1020

tagcaagtac tagaagattt tatgattatt cagggacata ttttctagca ctgaatatgt 1080

gccagacatt gtcctaggtg ctagagctat agtgataaac aaatcagatg aaagtagaaa 1140

tccatgccct aaagaactta atgtttcaat tgggaaggtc aagtcagata ggttaaaagg 1200

caaacacagt agcactgtag acattactat ataagcttta tggcaactag tgtttgtgca 1260

gtgctttaca gttagtaaac agtgttcacg taccttatct cacagtggct ttgtgggttt 1320

gacaaagtag caatcctcat ctcataggtg aggaaactag ggctctttaa gattagataa 1380

tctgtctaat agcatccagc caggtggtca tctgactcta aatcctttga agtcttactt 1440

atgctacagt gcctttcttt ttcctacaga tattgttagg cataattcat catctagcaa 1500

gtccagaatc atctttccag agttccagct cattcataat aacatgtttc agaaatcagg 1560

gtcctgtatt agttacgttt ttcttaaatg gagacggaat caaatgtgac tgcatgtagt 1620

ttttctgttc tcatttggcc tattttccaa gagtaaggtt agtagatggc tatttgtagc 1680

agtaactgga cagcatctgt ccagtgggac agctggagac ttgtctttag tatttggtaa 1740

tgctgactta tgtgctgctt aatcttttga gtcttgatgg atgtattaga tttctattgt 1800

tgtgtaacaa attaccacag aatcatcagt ttaaacaaca cacatgtatt atgtgtttga 1860

aacattatta tgtatctgtg ggtcagaagg atgggcacag cttaactagg tcatctgctt 1920

aggtctcact agactgcaat taaattgtca gctgatatga gttcttatct ggaggcttga 1980

ccatggaaga atctgcttaa gctcactcag actgttggcc acattgattt ccttgccatc 2040

gtagtaggac tgggggcccc agattcttgc tggttgttgg ctggaggctg ccctcagtgt 2100

ctaaaggctg tttgcagttc cttgctatgt gggcttccta gcacgcctgc ctacttcagc 2160

aagccttcaa ggagagtctc tcgagtgagt cttccagcca gcagcagtgc taatgaaaag 2220

catagtcact ggagggacat catacctctt ttgccatatt ctgttggtta gaagccagtc 2280

acactcaagg ggaaggatta tataagggca tgaacttcag gaggtgcggg tcacagggcc 2340

acttttggat ctgtttgcca cagtaagaac cttcattggt cccacagaga tatactgagg 2400

actactatat ccctggaaca gaagcaccag tgatacaaag atgagttggt cccagcctgt 2460

gttaaggggc ctgcctgcgt ctagggatga agactctaag caggtcacta ccctaccgtg 2520

gggaaagcgc tctagcagag gtggagctat atacctttct ggaattgaca tgatacatgg 2580

cacacccgta ctagacatca agccctacat agctgagtat gactcaccgc aaaatgtgat 2640

ggagccttta gcagacttta atttacagaa taaccaacat acaccaaaca ctgtgtccca 2700

gtctgacagc aagactgaca gctgtgacca gcgacagctc tcagggtgtg atgagccaca 2760

accccaccat agcactaaga ggaaacctaa atgtcctgaa gacagaactt cagaagaaaa 2820

ctacctgaca cacagtgaca cagccagaat tcagcaagca tttcctatgc acagggagat 2880

agcagtggat tttggtttgg aatcaagacg tgatcagagt tccagcgtgg cagaagaaca 2940

aattggccca tattgcccag agaagagctt ttcagagaaa ggtacagaca gaagctagaa 3000

agagtggaag gagcagcagt cttgcaagga agcagggcag agacacagcc catggcccct 3060

cactgccctg ctggaagggc tgatggagct ccccgcagca tggttcctgc ctgggtgaca 3120

gaggctcctg tggccacttt agaagtgcgg tttactcctc atgccgagat ggaccttggg 3180

cagctcagtt cacaagatgt tggtcaggcg tcatttaaat attttcagtc agcagaggaa 3240

gcaaagcgtg ccattgaggc tgtgctgtca gcggatcctc ggtctgtgta ccgccggaag 3300

ctttgccagg accgcctttt ctactttact gtagacatag cgcatgtcac ttgctggttt 3360

ggtgatggct ttgcagaggt gctgaggatc aagccggctt ctgagcctgt tcatatgact 3420

ggccctgtgg ggtccttggt gtctctaggg tcttaaggag cctccctcat gtctttaagg 3480

tagcatcatt gatctttgga tgtggctttt ggattttctg aacaagctaa tgttgtgtca 3540

agaagcaaca ctttgtgatc tcatggcttt gattgatttg ggctgttcaa aatgtttatt 3600

tgaaaaacgt ataccttaat aaacttaaca aagagatata aaaaaaaaaa aaaaaaa 3657

<210>2

<211>3657

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(2441)..(2995)

<223>

<400>2

ggggcacctc agcaaccagt agccatgcgc ggcttggagg agtcggggcc tcggcctaca 60

gcgaccccgt gcggctgcgt taagccggct ctggagacag ggaatctttt aactgagcca 120

gtcggctact tggaatcttg tttctcggcc aagaatggta ctccaagaca gccatccatt 180

tgtagctatt ctcgagcctg tttgaggatt agaaagagga tctttaataa tcctgaacat 240

tccttgatgg gcctagaaca gtttttctca tgtttggaag gtctagtcat gccaaatgga 300

aaaagaaagg aaggtctggt aaaggatttt gtttgttttt cacaaaaatg gtcatttgag 360

ctgtaaggca aaagtgcagc ctcctaggct gaatggtgca aagactggag ttttttccac 420

aaggagccct catcgtccca atgcaatagg actgaccctg gccaagctgg aaaaggtaga 480

agccttgggg aaatggacag atatcatggc tgcagtgctg atgtcaactg tgctgtgtgg 540

caggagtctg ggatgaatca cactacaagg acaaacattg gtcaggttgt agaagtttta 600

aactagtttt aactgtgtgt tcgtatataa cctagttacg catttatgga aagcattcca 660

ttctgaccta acagatgcat ttgttataga ggcagcagat gaaatggcag gtaaactagg 720

agtcaagaga ccattccagg cttcagcctg ctggttgtga agtgggcaaa ggagaaggac 780

ctgcttcctc tgtgattcca cagaatattt tgagaatctt gtaagagaga agttctaaaa 840

ctactttttc aggctattgg acactaaata gatgagagca gttattttgc ttgttctttc 900

ccagaacttg aactctccca ctggattgta ctcaactggg ccttaggtag ttttctcaga 960

aaaattcagt agctgatcca ccttgaattt tatcaatttg taatggctaa caaacttgga 1020

tagcaagtac tagaagattt tatgattatt cagggacata ttttctagca ctgaatatgt 1080

gccagacatt gtcctaggtg ctagagctat agtgataaac aaatcagatg aaagtagaaa 1140

tccatgccct aaagaactta atgtttcaat tgggaaggtc aagtcagata ggttaaaagg 1200

caaacacagt agcactgtag acattactat ataagcttta tggcaactag tgtttgtgca 1260

gtgctttaca gttagtaaac agtgttcacg taccttatct cacagtggct ttgtgggttt 1320

gacaaagtag caatcctcat ctcataggtg aggaaactag ggctctttaa gattagataa 1380

tctgtctaat agcatccagc caggtggtca tctgactcta aatcctttga agtcttactt 1440

atgctacagt gcctttcttt ttcctacaga tattgttagg cataattcat catctagcaa 1500

gtccagaatc atctttccag agttccagct cattcataat aacatgtttc agaaatcagg 1560

gtcctgtatt agttacgttt ttcttaaatg gagacggaat caaatgtgac tgcatgtagt 1520

ttttctgttc tcatttggcc tattttccaa gagtaaggtt agtagatggc tatttgtagc 1680

agtaactgga cagcatctgt ccagtgggac agctggagac ttgtctttag tatttggtaa 1740

tgctgactta tgtgctgctt aatcttttga gtcttgatgg atgtattaga tttctattgt 1800

tgtgtaacaa attaccacag aatcatcagt ttaaacaaca cacatgtatt atgtgtttga 1860

aacattatta tgtatctgtg ggtcagaagg atgggcacag cttaactagg tcatctgctt 1920

aggtctcact agactgcaat taaattgtca gctgatatga gttcttatct ggaggcttga 1980

ccatggaaga atctgcttaa gctcactcag actgttggcc acattgattt ccttgccatc 2040

gtagtaggac tgggggcccc agattcttgc tggttgttgg ctggaggctg ccctcagtgt 2100

ctaaaggctg tttgcagttc cttgctatgt gggcttccta gcacgcctgc ctacttcagc 2160

aagccttcaa ggagagtctc tcgagtgagt cttccagcca gcagcagtgc taatgaaaag 2220

catagtcact ggagggacat catacctctt ttgccatatt ctgttggtta gaagccagtc 2280

acactcaagg ggaaggatta tataagggca tgaacttcag gaggtgcggg tcacagggcc 2340

acttttggat ctgtttgcca cagtaagaac cttcattggt cccacagaga tatactgagg 2400

actactatat ccctggaaca gaagcaccag tgatacaaag atg agt tgg tcc cag 2455

Met Ser Trp Ser Gln

1 5

cct gtg tta agg ggc ctg cct gcg tct agg gat gaa gac tct aag cag 2503

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

10 15 20

gtc act acc cta ccg tgg gga aag cgc tct agc aga ggt gga gct ata 2551

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

25 30 35

tac ctt tct gga att gac atg ata cat ggc aca ccc gta cta gac atc 2599

Tyr Leu Ser Gly Ile Asp Met Ile His Gly Thr Pro Val Leu Asp Ile

40 45 50

aag ccc tac ata gct gag tat gac tca ccg caa aat gtg atg gag cct 2647

Lys Pro Tyr Ile Ala Glu Tyr Asp Ser Pro Gln Asn Val Met Glu Pro

55 60 65

tta gca gac ttt aat tta cag aat aac caa cat aca cca aac act gtg 2695

Leu Ala Asp Phe Asn Leu Gln Asn Asn Gln His Thr Pro Asn Thr Val

70 75 80 85

tcc cag tct gac agc aag act gac agc tgt gac cag cga cag ctc tca 2743

Ser Gln Ser Asp Ser Lys Thr Asp Ser Cys Asp Gln Arg Gln Leu Ser

90 95 100

ggg tgt gat gag cca caa ccc cac cat agc act aag agg aaa cct aaa 2791

Gly Cys Asp Glu Pro Gln Pro His His Ser Thr Lys Arg Lys Pro Lys

105 110 115

tgt cct gaa gac aga act tca gaa gaa aac tac ctg aca cac agt gac 2839

Cys Pro Glu Asp Arg Thr Ser Glu Glu Asn Tyr Leu Thr His Ser Asp

120 125 130

aca gcc aga att cag caa gca ttt cct atg cac agg gag ata gca gtg 2887

Thr Ala Arg Ile Gln Gln Ala Phe Pro Met His Arg Glu Ile Ala Val

135 140 145

gat ttt ggt ttg gaa tea aga cgt gat cag agt tcc agc gtg gca gaa 2935

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

150 155 160 165

gaa caa att ggc cca tat tgc cca gag aag agc ttt tca gag aaa ggt 2983

Glu Gln Ile Gly Pro Tyr Cys Pro Glu Lys Ser Phe Ser Glu Lys Gly

170 175 180

aca gac aga agc tagaaagagt ggaaggagca gcagtcttgc aaggaagcag 3035

Thr Asp Arg Ser

185

ggcagagaca cagcccatgg cccctcactg ccctgctgga agggctgatg gagctccccg 3095

cagcatggtt cctgcctggg tgacagaggc tcctgtggcc actttagaag tgcggtttac 3155

tcctcatgcc gagatggacc ttgggcagct cagttcacaa gatgttggtc aggcgtcatt 3215

taaatatttt cagtcagcag aggaagcaaa gcgtgccatt gaggctgtgc tgtcagcgga 3275

tcctcggtct gtgtaccgcc ggaagctttg ccaggaccgc cttttctact ttactgtaga 3335

catagcgcat gtcacttgct ggtttggtga tggctttgca gaggtgctga ggatcaagcc 3395

ggcttctgag cctgttcata tgactggccc tgtggggtcc ttggtgtctc tagggtctta 3455

aggagcctcc ctcatgtctt taaggtagca tcattgatct ttggatgtgg cttttggatt 3515

ttctgaacaa gctaatgttg tgtcaagaag caacactttg tgatctcatg gctttgattg 3575

atttgggctg ttcaaaatgt ttatttgaaa aacgtatacc ttaataaact taacaaagag 3635

atataaaaaa aaaaaaaaaa aa 3657

<210>3

<211>185

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>3

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

1 5 10 15

Glu Asp Ser Lys Gln Val Thr Thr Leu Pro Trp Gly Lys Arg Ser Ser

20 25 30

Arg Gly Gly Ala Ile Tyr Leu Ser Gly Ile Asp Met Ile His Gly Thr

35 40 45

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

50 55 60

Asn Val Met Glu Pro Leu Ala Asp Phe Asn Leu Gln Asn Asn Gln His

65 70 75 80

Thr Pro Asn Thr Val Ser Gln Ser Asp Ser Lys Thr Asp Ser Cys Asp

85 90 95

Gln Arg Gln Leu Ser Gly Cys Asp Glu Pro Gln Pro His His Ser Thr

100 105 110

Lys Arg Lys Pro Lys Cys Pro Glu Asp Arg Thr Ser Glu Glu Asn Tyr

115 120 125

Leu Thr His Ser Asp Thr Ala Arg Ile Gln Gln Ala Phe Pro Met His

130 135 140

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

145 150 155 160

Ser Ser Val Ala Glu Glu Gln Ile Gly Pro Tyr Cys Pro Glu Lys Ser

165 170 175

Phe Ser Glu Lys Gly Thr Asp Arg Ser

180 185

<210>4

<211>2350

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>4

gcgggcttac atccaaatac agatttaccc cagaagagaa tgaaacaatg ttcagaaccc 60

ctgaaaactg tgttcaagga agtcagctgg atttttttga gacaggggtc ttgctcttgt 120

tgcccaggct ggaatgcaat ggtgcagtct tcgctcacta cagcctctac cgctcctgct 180

caggtaatcc ttccacctca gccccctgag tagctgggac tgcaggcaca cgccaccatg 240

ccaggctgat ttttgtattt tttgtagaga ctgtgtttca ccgtattgcc cgggctggtc 300

ttgaactctt ggactcaagc aatccacctg cctcggcctc ccaaagtgct cacaggcatg 360

aggcaacgtg cccagcctca tttgatactt ttaaaataca tttttaatat ttttttcctc 420

caagatgcct tccccattgt gtaagtttca ggtcttacaa acctggatcc accccagcag 480

tctgagttgc atatatacat acctcctatt tacatgtccc tcctcccact attatgtcac 540

ctttctaaac accgcaattg ggagatgaga caatgcgcag gaacgaagaa ctgttctggt 600

gaagaggacc caggggcagt gagagggggc tagggacaaa aggtgaatgg ggagctggtt 660

caggttagaa gaatgggtgc atgtgagggg catttggaga atgcgagctg ggggagggag 720

agtggctgag cctgtaggca cagtagacac atgtagtaat gacggggatg tgttatgccc 780

cacaccaggt gttgtcctac atcaatgggg tcacaacaag caaacctgga gtatccttgg 840

tctactccat gccctcccgg aacctgtccc tgcggctgga gggtctccag gagaaagact 900

ctggccccta cagctgctcc gtgaatgtgc aagacaaaca aggcaaatct aggggccaca 960

gcatcaaaac cttagaactc aatgtactgg gtgagtgaga agcagatttc cggacccctc 1020

cccacctgca ctgggaggtc tggtgagtct ctctcctaaa tgacaaaagt tggaggagga 1080

acaaatgaag cgacagaagg gtgcagggca gagggagagg atctgtgggt ctcctgggtg 1140

gtgggtttta atctgtctcc ccctgcccag ttcctccagc tcctccatcc tgccgtctcc 1200

agggtgtgcc ccatgtgggg gcaaacgtga ccctgagctg ccagtctcca aggagtaagc 1260

ccgctgtcca ataccagtgg gatcggcagc ttccatcctt ccagactttc tttgcaccag 1320

cattagatgt catccgtggg tctttaagcc tcaccaacct ttcgtcttcc atggctggag 1380

tctatgtctg caaggcccac aatgaggtgg gcactgccca atgtaatgtg acgctggaag 1440

tgagcacagg tcagtgaggg ggcctggagc tgcagtggtt gctggagctg ttgtgggtac 1500

cctggttgga ctggggttgc tggctgggct ggtcctcttg taccaccgcc ggggcaaggc 1560

cctggaggag ccagccaatg atatcaagga ggatgccatt gctccccgga ccctgccctg 1620

gcccaagagc tcagacacaa tctccaagaa tgggaccctt tcctctgtca cctccgcacg 1680

agccctccgg ccaccccatg gccctcccag gcctggtgca ttgaccccca cgcccagtct 1740

ctccagccag gccctgccct caccaagact gcccacgaca gatggggccc accctcaacc 1800

aatatccccc atccctggtg gggtttcttc ctctggcttg agccgcatgg gtgctgtgcc 1860

tgtgatggtg cctgcccaga gtcaagctgg ctctctggta tgatgacccc accactcatt 1920

ggctaaagga tttggggtct ctccttccta taggggtcac ctctagcaca gaggcctgag 1980

tcatgggaaa gagtcacact cctgaccctt agtactctgc ccccacctct ctttactgtg 2040

ggaaaaccat ctcagtaaga cctaagtgtc caggagacag aaggagaaga ggaagtggat 2100

ctggaattgg gaggagcctc cacccacccc tgactcctcc ttatgaagcc agctgctgaa 2160

attagctact caccaagagt gaggggcaga gacttccagt cactgagtct cccaggcccc 2220

cttgatctgt accccacccc tatctaacac cacccttggc tcccactcca gctccctgta 2280

ttgatataac ctgtcaggct ggcttggtta ggttttactg gggcagagga tagggaatct 2340

cttattaaaa 2350

<210>5

<211>2350

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(647)..(949)

<223>

<400>5

gcgggcttac atccaaatac agatttaccc cagaagagaa tgaaacaatg ttcagaaccc 60

ctgaaaactg tgttcaagga agtcagctgg atttttttga gacaggggtc ttgctcttgt 120

tgcccaggct ggaatgcaat ggtgcagtct tcgctcacta cagcctctac cgctcctgct 180

caggtaatcc ttccacctca gccccctgag tagctgggac tgcaggcaca cgccaccatg 240

ccaggctgat ttttgtattt tttgtagaga ctgtgtttca ccgtattgcc cgggctggtc 300

ttgaactctt ggactcaagc aatccacctg cctcggcctc ccaaagtgct cacaggcatg 360

aggcaacgtg cccagcctca tttgatactt ttaaaataca tttttaatat ttttttcctc 420

caagatgcct tccccattgt gtaagtttca ggtcttacaa acctggatcc accccagcag 480

tctgagttgc atatatacat acctcctatt tacatgtccc tcctcccact attatgtcac 540

ctttctaaac accgcaattg ggagatgaga caatgcgcag gaacgaagaa ctgttctggt 600

gaagaggacc caggggcagt gagagggggc tagggacaaa aggtga atg ggg agc 655

Met Gly Ser

1

tgg ttc agg tta gaa gaa tgg gtg cat gtg agg ggc att tgg aga atg 703

Trp Phe Arg Leu Glu Glu Trp Val His Val Arg Gly Ile Trp Arg Met

5 10 15

cga gct ggg gga ggg aga gtg gct gag cct gta ggc aca gta gac aca 751

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

20 25 30 35

tgt agt aat gac ggg gat gtg tta tgc ccc aca cca ggt gtt gtc cta 799

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

40 45 50

cat caa tgg ggt cac aac aag caa acc tgg agt atc ctt ggt cta ctc 847

His Gln Trp Gly His Asn Lys Gln Thr Trp Ser Ile Leu Gly Leu Leu

55 60 65

cat gcc ctc ccg gaa cct gtc cct gcg gct gga ggg tct cca gga gaa 895

His Ala Leu Pro Glu Pro Val Pro Ala Ala Gly Gly Ser Pro Gly Glu

70 75 80

aga ctc tgg ccc cta cag ctg ctc cgt gaa tgt gca aga caaaca agg 943

Arg Leu Trp Pro Leu Gln Leu Leu Arg Glu Cys Ala Arg Gln Thr Arg

85 90 95

caa atc taggggccac agcatcaaaa ccttagaact caatgtactg ggtgagtgag 999

Gln Ile

100

aagcagattt ccggacccct ccccacctgc actgggaggt ctggtgagtc tctctcctaa 1059

atgacaaaag ttggaggagg aacaaatgaa gcgacagaag ggtgcagggc agagggagag 1119

gatctgtggg tctcctgggt ggtgggtttt aatctgtctc cccctgccca gttcctccag 1179

ctcctccatc ctgccgtctc cagggtgtgc cccatgtggg ggcaaacgtg accctgagct 1239

gccagtctcc aaggagtaag cccgctgtcc aataccagtg ggatcggcag cttccatcct 1299

tccagacttt ctttgcacca gcattagatg tcatccgtgg gtctttaagc ctcaccaacc 1359

tttcgtcttc catggctgga gtctatgtct gcaaggccca caatgaggtg ggcactgccc 1419

aatgtaatgt gacgctggaa gtgagcacag gtcagtgagg gggcctggag ctgcagtggt 1479

tgctggagct gttgtgggta ccctggttgg actggggttg ctggctgggc tggtcctctt 1539

gtaccaccgc cggggcaagg ccctggagga gccagccaat gatatcaagg aggatgccat 1599

tgctccccgg accctgccct ggcccaagag ctcagacaca atctccaaga atgggaccct 1659

ttcctctgtc acctccgcac gagccctccg gccaccccat ggccctccca ggcctggtgc 1719

attgaccccc acgcccagtc tctccagcca ggccctgccc tcaccaagac tgcccacgac 1779

agatggggcc caccctcaac caatatcccc catccctggt ggggtttctt cctctggctt 1839

gagccgcatg ggtgctgtgc ctgtgatggt gcctgcccag agtcaagctg gctctctggt 1899

atgatgaccc caccactcat tggctaaagg atttggggtc tctccttcct ataggggtca 1959

cctctagcac agaggcctga gtcatgggaa agagtcacac tcctgaccct tagtactctg 2019

cccccacctc tctttactgt gggaaaacca tctcagtaag acctaagtgt ccaggagaca 2079

gaaggagaag aggaagtgga tctggaattg ggaggagcct ccacccaccc ctgactcctc 2139

cttatgaagc cagctgctga aattagctac tcaccaagag tgaggggcag agacttccag 2199

tcactgagtc tcccaggccc ccttgatctg taccccaccc ctatctaaca ccacccttgg 2259

ctcccactcc agctccctgt attgatataa cctgtcaggc tggcttggtt aggttttact 2319

ggggcagagg atagggaatc tcttattaaa a 2350

<210>6

<211>101

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>6

Met Gly Ser Trp Phe Arg Leu Glu Glu Trp Val His Val Arg Gly Ile

1 5 10 15

Trp Arg Met Arg Ala Gly Gly Gly Arg Val Ala Glu Pro Val Gly Thr

20 25 30

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

35 40 45

Val Val Leu His Gln Trp Gly His Asn Lys Gln Thr Trp Ser Ile Leu

50 55 60

Gly Leu Leu His Ala Leu Pro Glu Pro Val Pro Ala Ala Gly Gly Ser

65 70 75 80

Pro Gly Glu Arg Leu Trp Pro Leu Gln Leu Leu Arg Glu Cys Ala Arg

85 90 95

Gln Thr Arg Gln Ile

100

<210>7

<211>2837

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>7

ggtcgaggtg tgcaaagatg aatccgttga tctcgaggaa tttcgaagct acctggagaa 60

gcgttttgac tttgagcaag ttactgtgaa aaaattcagg acttgggctg agcggcggca 120

attcaatcgg gaaatgaagc ggaagcaggc ggagtccgag aggcccatct tgccagccaa 180

tcagaagctc attactttat cagtgcaaga tgcacccaca aagaaagagt ttgttattaa 240

ccccaacggg aaatccgagg tctgcatcct gcacgagtac atgcagcgtg tcctcaaggt 300

ccgccctgtc tataatttct ttgaatgtga gaacccaagt gagccttttg gtgcctcggt 360

gaccattgat ggtgtgactt acggatctgg aactgcaagc agcaaaaaac ttgcgaagaa 420

taaagctgcc cgagctacac tggaaatcct catccctgac tttgttaaac agacctctga 480

agagaagccc aaagacagtg aagaactcga gtattttaac cacatcagca tcgaggactc 540

gcgggtctac gagctgacca gcaaggctgg gctgttgtct ccatatcaga tcctccacga 600

gtgccttaaa agaaaccatg ggatgggtga cacgtctatc aagtttgaag tggttcctgg 660

gaaaaaccag aagagtgaat acgtcatggc gtgtggcaag cacacagtgc gcgggtggtg 720

taagaacaag agagttggaa agcagttagc ctcacagaag atccttcagc tgctgcaccc 780

acatgtcaag aactgggggt ctttactgcg catgtatggc cgtgagagca gcaagatggt 840

caagcaggag acatcggaca agagtgtgat tgagctgcag cagtatgcca agaagaacaa 900

gcccaacctg cacatcctca gcaagctcca agaggagatg aagaggctag ctgaggaaag 960

ggaggagact cgaaagaagc ccaagatgtc cattgtggcg tccgcccagc ctggcggtga 1020

gcccctgtgc accgtggacg tgtgagggag gtggcacggg ccagggcgcg ggggccgcca 1080

gccgcacttc tgaggagacc agcagtcatg catcgtgcac cacagtgtca ggcctccaac 1140

ccacgctcct tccctgtggc caacctgtgg gcccggcctt agggtggagg ctttagtgta 1200

cagggacagc catggccaca cagcacacat gtggagcagc ggctctccct ggaaagctcc 1260

aggcctgaat ggatggactc agcgactgca ccagtggcag ctggtgactg tggacagtgg 1320

tggaccctgc ttctgtgcac ctgctgcagg ctctttttat gaaggctttc atgaatttta 1380

gtatgtaata cgcactgacg acacatgatg cttggatgac agatgagagg ggatggctga 1440

gtcctgtggc tggcccgtga tgccaggtgg cccatgtgcc cagggcgcct gcagggctgc 1500

tacagggacc tggtcaggag gtgcacatgg tgccctgccc tcacccaccc tctgtgtttc 1560

cccttctttg aaaaggtaga agagaaagga atattttaaa cctttttggc ttaaacagaa 1620

ttttagcatc agaactagct ttctgggatt ggaggcaaac catcaaggtg gtccctctcc 1680

agtctggaca cgatgccagc aaggatgacg tcctgccacc tcctggagtt accctggcct 1740

cctagggtcc ctttttctga tgaagtctta attccctaaa agcgcctctt tggacactga 1800

ggccctctct gcctttcctg gcctccggca acagtttttt acaaagattt tttgcagtcg 1860

agtccatatg tccacccatt gatttttaaa gcttttgtga tattttagca ttttgaaaga 1920

ctttcacagt gagagtagaa ggtagatttg gaatcatgca ttttagcaag tggacttgtt 1980

gaaacaggaa gcaagagcct tcagtgtagc ccattcttga tccagagctg ttgcctgtga 2040

cagcggtttc tctggatgtc aaaggcagct gcctggtgcc cagcttgctt ctcgactggt 2100

ggcccctatg ggtgggtgtg cgatggaaat gtgttcctgc cggagtctga ggcaccaggg 2160

tgtgctcaaa ggctggccct ggtggtggac tggcacctgt gcagagtgcc gtgtgcttgt 2220

ggtgcgccat ctgaagcaag agtccagcgt tctgccgtgt ctgtccccca ccatgccccc 2280

tacaggcggt actgatggcg cttttttttt ttttttttct gtcaggaaaa caatgttggc 2340

ctgtgggccg cccacaacat atccttccct cactacctgt gtgaccaagg ttggcttctg 2400

ttgaccttta aaaaagaaac cctcaactca aattgctata attagacact tgcttctgtc 2460

ttgcctcctg tctgcagctg tgaatagtca tttgactgtg actgttgccc ttagccagcc 2520

agatgcgcct gtgaaccaaa gctttgtgca catgtgttcc cctaaaggtt ggggagcctc 2580

gctgtgtttt gctgttccca ggcaccacca cagcaggtgc tgccatactc ttgtggtctc 2640

tgtgcgcccc ccccccccca cccgtctgcc aagcatgggt atgaatcgtg cacacagcca 2700

tgcttcaagg ccggggcagg ggagcctgtg ctgatgccat ccagggcact gggctgtgcc 2760

tggaaggcga gccttgattg tctgaacaca taaagcaaac tgtccagaag ggaaaaaaaa 2820

aaaaaaaaaa aaaaaaa 2837

<210>8

<211>2837

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(134)..(1042)

<223>

<400>8

ggtcgaggtg tgcaaagatg aatccgttga tctcgaggaa tttcgaagct acctggagaa 60

gcgttttgac tttgagcaag ttactgtgaa aaaattcagg acttgggctg agcggcggca 120

attcaatcgg gaa atg aag cgg aag cag gcg gag tcc gag agg ccc atc 169

Met Lys Arg Lys Gln Ala Glu Ser Glu Arg Pro Ile

1 5 10

ttg cca gcc aat cag aag ctc att act tta tca gtg caa gat gca ccc 217

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

15 20 25

aca aag aaa gag ttt gtt att aac ccc aac ggg aaa tcc gag gtc tgc 265

Thr Lys Lys Glu Phe Val Ile Asn Pro Asn Gly Lys Ser Glu Val Cys

30 35 40

atc ctg cac gag tac atg cag cgt gtc ctc aag gtc cgc cct gtc tat 313

Ile Leu His Glu Tyr Met Gln Arg Val Leu Lys Val Arg Pro Val Tyr

45 50 55 60

aat ttc ttt gaa tgt gag aac cca agt gag cct ttt ggt gcc tcg gtg 361

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

65 70 75

acc att gat ggt gtg act tac gga tct gga act gca agc agc aaa aaa 409

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

80 85 90

ctt gcg aag aat aaa gct gcc cga gct aca ctg gaa atc ctc atc cct 457

Leu Ala Lys Asn Lys Ala Ala Arg Ala Thr Leu Glu Ile Leu Ile Pro

95 100 105

gac ttt gtt aaa cag acc tct gaa gag aag ccc aaa gac agt gaa gaa 505

Asp Phe Val Lys Gln Thr Ser Glu Glu Lys Pro Lys Asp Ser Glu Glu

110 115 120

ctc gag tat ttt aac cac atc agc atc gag gac tcg cgg gtc tac gag 553

Leu Glu Tyr Phe Asn His Ile Ser Ile Glu Asp Ser Arg Val Tyr Glu

125 130 135 140

ctg acc agc aag gct ggg ctg ttg tct cca tat cag atc ctc cac gag 601

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

145 150 155

tgc ctt aaa aga aac cat ggg atg ggt gac acg tct atc aag ttt gaa 649

Cys Leu Lys Arg Asn His Gly Met Gly Asp Thr Ser Ile Lys Phe Glu

160 165 170

gtg gtt cct ggg aaa aac cag aag agt gaa tac gtc atg gcg tgt ggc 697

Val Val Pro Gly Lys Asn Gln Lys Ser Glu Tyr Val Met Ala Cys Gly

175 180 185

aag cac aca gtg cgc ggg tgg tgt aag aac aag aga gtt gga aag cag 745

Lys His Thr Val Arg Gly Trp Cys Lys Asn Lys Arg Val Gly Lys Gln

190 195 200

tta gcc tca cag aag atc ctt cag ctg ctg cac cca cat gtc aag aac 793

Leu Ala Ser Gln Lys Ile Leu Gln Leu Leu His Pro His Val Lys Asn

205 210 215 220

tgg ggg tct tta ctg cgc atg tat ggc cgt gag agc agc aag atg gtc 841

Trp Gly Ser Leu Leu Arg Met Tyr Gly Arg Glu Ser Ser Lys Met Val

225 230 235

aag cag gag aca tcg gac aag agt gtg att gag ctg cag cag tat gcc 889

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

240 245 250

aag aag aac aag ccc aac ctg cac atc ctc agc aag ctc caa gag gag 937

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

255 260 265

atg aag agg cta gct gag gaa agg gag gag act cga aag aag ccc aag 985

Met Lys Arg Leu Ala Glu Glu Arg Glu Glu Thr Arg Lys Lys Pro Lys

270 275 280

atg tcc att gtg gcg tcc gcc cag cct ggc ggt gag ccc ctg tgc acc 1033

Met Ser Ile Val Ala Ser Ala Gln Pro Gly Gly Glu Pro Leu Cys Thr

285 290 295 300

gtg gac gtg tgagggaggt ggcacgggcc agggcgcggg ggccgccagc 1082

Val Asp Val

cgcacttctg aggagaccag cagtcatgca tcgtgcacca cagtgtcagg cctccaaccc 1142

acgctccttc cctgtggcca acctgtgggc ccggccttag ggtggaggct ttagtgtaca 1202

gggacagcca tggccacaca gcacacatgt ggagcagcgg ctctccctgg aaagctccag 1262

gcctgaatgg atggactcag cgactgcacc agtggcagct ggtgactgtg gacagtggtg 1322

gaccctgctt ctgtgcacct gctgcaggct ctttttatga aggctttcat gaattttagt 1382

atgtaatacg cactgacgac acatgatgct tggatgacag atgagagggg atggctgagt 1442

cctgtggctg gcccgtgatg ccaggtggcc catgtgccca gggcgcctgc agggctgcta 1502

cagggacctg gtcaggaggt gcacatggtg ccctgccctc acccaccctc tgtgtttccc 1562

cttctttgaa aaggtagaag agaaaggaat attttaaacc tttttggctt aaacagaatt 1622

ttagcatcag aactagcttt ctgggattgg aggcaaacca tcaaggtggt ccctctccag 1682

tctggacacg atgccagcaa ggatgacgtc ctgccacctc ctggagttac cctggcctcc 1742

tagggtccct ttttctgatg aagtcttaat tccctaaaag cgcctctttg gacactgagg 1802

ccctctctgc ctttcctggc ctccggcaac agttttttac aaagattttt tgcagtcgag 1862

tccatatgtc cacccattga tttttaaagc ttttgtgata ttttagcatt ttgaaagact 1922

ttcacagtga gagtagaagg tagatttgga atcatgcatt ttagcaagtg gacttgttga 1982

aacaggaagc aagagccttc agtgtagccc attcttgatc cagagctgtt gcctgtgaca 2042

gcggtttctc tggatgtcaa aggcagctgc ctggtgccca gcttgcttct cgactggtgg 2102

cccctatggg tgggtgtgcg atggaaatgt gttcctgccg gagtctgagg caccagggtg 2162

tgctcaaagg ctggccctgg tggtggactg gcacctgtgc agagtgccgt gtgcttgtgg 2222

tgcgccatct gaagcaagag tccagcgttc tgccgtgtct gtcccccacc atgcccccta 2282

caggcggtac tgatggcgct tttttttttt ttttttctgt caggaaaaca atgttggcct 2342

gtgggccgcc cacaacatat ccttccctca ctacctgtgt gaccaaggtt ggcttctgtt 2402

gacctttaaa aaagaaaccc tcaactcaaa ttgctataat tagacacttg cttctgtctt 2462

gcctcctgtc tgcagctgtg aatagtcatt tgactgtgac tgttgccctt agccagccag 2522

atgcgcctgt gaaccaaagc tttgtgcaca tgtgttcccc taaaggttgg ggagcctcgc 2582

tgtgttttgc tgttcccagg caccaccaca gcaggtgctg ccatactctt gtggtctctg 2642

tgcgcccccc cccccccacc cgtctgccaa gcatgggtat gaatcgtgca cacagccatg 2702

cttcaaggcc ggggcagggg agcctgtgct gatgccatcc agggcactgg gctgtgcctg 2762

gaaggcgagc cttgattgtc tgaacacata aagcaaactg tccagaaggg aaaaaaaaaa 2822

aaaaaaaaaa aaaaa 2837

<210>9

<211>303

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>9

Met Lys Arg Lys Gln Ala Glu Ser Glu Arg Pro Ile Leu Pro Ala Asn

1 5 10 15

Gln Lys Leu Ile Thr Leu Ser Val Gln Asp Ala Pro Thr Lys Lys Glu

20 25 30

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

35 40 45

Tyr Met Gln Arg Val Leu Lys Val Arg Pro Val Tyr Asn Phe Phe Glu

50 55 60

Cys Glu Asn Pro Ser Glu Pro Phe Gly Ala Ser Val Thr Ile Asp Gly

65 70 75 80

Val Thr Tyr Gly Ser Gly Thr Ala Ser Ser Lys Lys Leu Ala Lys Asn

85 90 95

Lys Ala Ala Arg Ala Thr Leu Glu Ile Leu Ile Pro Asp Phe Val Lys

100 105 110

Gln Thr Ser Glu Glu Lys Pro Lys Asp Ser Glu Glu Leu Glu Tyr Phe

115 120 125

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

130 135 140

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

145 150 155 160

Asn His Gly Met Gly Asp Thr Ser Ile Lys Phe Glu Val Val Pro Gly

165 170 175

Lys Asn Gln Lys Ser Glu Tyr Val Met Ala Cys Gly Lys His Thr Val

180 185 190

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

195 200 205

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

210 215 220

Leu Arg Met Tyr Gly Arg Glu Ser Ser Lys Met Val Lys Gln Glu Thr

225 230 235 240

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

245 250 255

Pro Asn Leu His Ile Leu Ser Lys Leu Gln Glu Glu Met Lys Arg Leu

260 265 270

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

275 280 285

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

290 295 300

<210>10

<211>2280

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>10

gcgtctttta cagaatgtgg gatcctcgag ctaagatgag ggcatccctc acgttcacac 60

ccctggtggc atctgccagc cctgttctgg ggacaaggcg ggctttcgtg ggagccatgc 120

tcagcctgcc aggaagccaa gccctacagt gcagaggaaa cagaatttca acgggaagct 180

ggtttgcttc ataccattgg gatctgctgg taaagctgtt atttgggttt agggactgat 240

cccttgcagt ttacttctgg atcaccatga atggccaaga tggtggcaga acacgctgtg 300

gaccctgagt tagagacaat gcaaatgttg gattgggtgt aattcttttt gaatcccaga 360

tccagtctgt acttgaatat gagcagaaga tctacaagaa tgctgacagg gaaccgtgtt 420

aagacccagc acccctattc ccaggagctt ctggcctgac catctgcagc caaagcacta 480

acagggacag atatgggaat gtccaccttt gatccgcatc ctgcacaata gtggtcccac 540

catggctgcc acttttttat actatttgga gaaaagacct tgtataaatt cgaggcccga 600

gtgactaacg tctctgtcac acggaaatgg gtacttggtg gcatagagaa acacaattag 660

ccactttttc agctacactt ctcactcagc tgcaccctac acttctcact caggtgcacc 720

cccttctgct gtcctttccc caacgtactg ggtcccgagc gtggtgggta tttgccacac 780

tgggtgccag ctcagcagcc ccccacctct ctttattctc tccaaagctg gtctttctga 840

ctatcattgt ggtaggggga ggacagatgc taaaggtgga agctgacctg gagaaagaga 900

cacacggggt gactgtggca aaggacagct ggaaaagaaa ctctatcact tcttcattgg 960

caaccacaag gcacccgagg ccatggcact cccagaggct gtgcgcagag ccaagcctct 1020

caacctcttc tggccctgcg tcctgcagcg aagtctctgc tgtaagacag tagactcctt 1080

cgatgaggtg ctcaaaaatg ctacccgggg tggtggtgtc tggcttgcag tctggcccag 1140

ttcagagaaa gttgcagaga tcaggggcca aggatgtcat agccccaggt tgtcctcagg 1200

gtcgcaatcc tagggcaggg tgtgcatgga agcaagaact atggaaacct agctccagtc 1260

tgcaggctct gagcccctag ttcctcactc cagcggggct ccctcactgc acagaaccca 1320

ccccttctgt gtgggcactg ctgaccacac agatgaccca gacccaaaga gcctggcaga 1380

agctctgtgg ttggagctgg gctccgtctc caggtctggt tcagggggat caggaaggct 1440

cttttccacc tgtggcttca ctggcccttt gagatttcct atctcaccgt tacttcagtt 1500

acccttgcag ggggccaggg agtcaagaat ataccgtgtt cctccagggt ttaagccggc 1560

catgccttcc cgagagcata accaacttga caggggtgcc cagttacccc acaaactgaa 1620

ggaaggagat ccttcccccg tccccaggag tgctctcaac cagcctcaga aagcttgaga 1680

agatggaccc tttgcccacc agggttaatt cctggtgggg cagctcggct gtgatcaggg 1740

caaccaaacc tataggaagc cttccagtgt gagctggaat tagactgaac atgtgcttgg 1800

gcctgcctct ccctagacgc agttgcgggg cactccaggg aatgaaccag ctcaagtgtg 1860

tccctaacag cagcctggag ctacccccaa tccctcacag cctgaccctc ctcattccat 1920

cagatgcatt tgtagaatcg gggcaaattt ccttatttat ttatggccca tgcctttccc 1980

cctcttcatc ctgatcccgt tttgctttga agagacccca gtaaccaaaa aacagcctcc 2040

agaagccaaa accatgcctg gatctcccat agcttctcct ttgcttccag gagaaagttc 2100

actgaaaaaa aaatatcttc tggcttcttg tgtgtacaga gacaacagaa ctcggtgggg 2160

aaacgggaat cttttctgca ccaaagctgc ttctaaagca gaaagcagtg gggctcttgg 2220

tgtttcatgc tgccttattt atattaaagg aagaattaaa tcttaaaaaa aaaaaaaaaa 2280

<210>11

<211>2280

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(627)..(1070)

<223>

<400>11

gcgtctttta cagaatgtgg gatcctcgag ctaagatgag ggcatccctc acgttcacac 60

ccctggtggc atctgccagc cctgttctgg ggacaaggcg ggctttcgtg ggagccatgc 120

tcagcctgcc aggaagccaa gccctacagt gcagaggaaa cagaatttca acgggaagct 180

ggtttgcttc ataccattgg gatctgctgg taaagctgtt atttgggttt agggactgat 240

cccttgcagt ttacttctgg atcaccatga atggccaaga tggtggcaga acacgctgtg 300

gaccctgagt tagagacaat gcaaatgttg gattgggtgt aattcttttt gaatcccaga 360

tccagtctgt acttgaatat gagcagaaga tctacaagaa tgctgacagg gaaccgtgtt 420

aagacccagc acccctattc ccaggagctt ctggcctgac catctgcagc caaagcacta 480

acagggacag atatgggaat gtccaccttt gatccgcatc ctgcacaata gtggtcccac 540

catggctgcc acttttttat actatttgga gaaaagacct tgtataaatt cgaggcccga 600

gtgactaacg tctctgtcac acggaa atg ggt act tgg tgg cat aga gaa aca 653

Met Gly Thr Trp Trp His Arg Glu Thr

1 5

caa tta gcc act ttt tca gct aca ctt ctc act cag ctg cac cct aca 701

Gln Leu Ala Thr Phe Ser Ala Thr Leu Leu Thr Gln Leu His Pro Thr

10 15 20 25

ctt ctc act cag gtg cac ccc ctt ctg ctg tcc ttt ccc caa cgt act 749

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

30 35 40

ggg tcc cga gcg tgg tgg gta ttt gcc aca ctg ggt gcc agc tca gca 797

Gly Ser Arg Ala Trp Trp Val Phe Ala Thr Leu Gly Ala Ser Ser Ala

45 50 55

gcc ccc cac ctc tct tta ttc tct cca aag ctg gtc ttt ctg act atc 845

Ala Pro His Leu Ser Leu Phe Ser Pro Lys Leu Val Phe Leu Thr Ile

60 65 70

att gtg gta ggg gga gga cag atg cta aag gtg gaa gct gac ctg gag 893

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

75 80 85

aaa gag aca cac ggg gtg act gtg gca aag gac agc tgg aaa aga aac 941

Lys Glu Thr His Gly Val Thr Val Ala Lys Asp Ser Trp Lys Arg Asn

90 95 100 105

tct atc act tct tca ttg gca acc aca agg cac ccg agg cca tgg cac 989

Ser Ile Thr Ser Ser Leu Ala Thr Thr Arg His Pro Arg Pro Trp His

110 115 120

tcc cag agg ctg tgc gca gag cca agc ctc tca acc tct tct ggc cct 1037

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

125 130 135

gcg tcc tgc agc gaa gtc tct gct gta aga cag tagactcctt cgatgaggtg 1090

Ala Ser Cys Ser Glu Val Ser Ala Val Arg Gln

140 145

ctcaaaaatg ctacccgggg tggtggtgtc tggcttgcag tctggcccag ttcagagaaa 1150

gttgcagaga tcaggggcca aggatgtcat agccccaggt tgtcctcagg gtcgcaatcc 1210

tagggcaggg tgtgcatgga agcaagaact atggaaacct agctccagtc tgcaggctct 1270

gagcccctag ttcctcactc cagcggggct ccctcactgc acagaaccca ccccttctgt 1330

gtgggcactg ctgaccacac agatgaccca gacccaaaga gcctggcaga agctctgtgg 1390

ttggagctgg gctccgtctc caggtctggt tcagggggat caggaaggct cttttccacc 1450

tgtggcttca ctggcccttt gagatttcct atctcaccgt tacttcagtt acccttgcag 1510

ggggccaggg agtcaagaat ataccgtgtt cctccagggt ttaagccggc catgccttcc 1570

cgagagcata accaacttga caggggtgcc cagttacccc acaaactgaa ggaaggagat 1630

ccttcccccg tccccaggag tgctctcaac cagcctcaga aagcttgaga agatggaccc 1690

tttgcccacc agggttaatt cctggtgggg cagctcggct gtgatcaggg caaccaaacc 1750

tataggaagc cttccagtgt gagctggaat tagactgaac atgtgcttgg gcctgcctct 1810

ccctagacgc agttgcgggg cactccaggg aatgaaccag ctcaagtgtg tccctaacag 1870

cagcctggag ctacccccaa tccctcacag cctgaccctc ctcattccat cagatgcatt 1930

tgtagaatcg gggcaaattt ccttatttat ttatggccca tgcctttccc cctcttcatc 1990

ctgatcccgt tttgctttga agagacccca gtaaccaaaa aacagcctcc agaagccaaa 2050

accatgcctg gatctcccat agcttctcct ttgcttccag gagaaagttc actgaaaaaa 2110

aaatatcttc tggcttcttg tgtgtacaga gacaacagaa ctcggtgggg aaacgggaat 2170

cttttctgca ccaaagctgc ttctaaagca gaaagcagtg gggctcttgg tgtttcatgc 2230

tgccttattt atattaaagg aagaattaaa tcttaaaaaa aaaaaaaaaa 2280

<210>12

<211>148

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>12

Met Gly Thr Trp Trp His Arg Glu Thr Gln Leu Ala Thr Phe Ser Ala

1 5 10 15

Thr Leu Leu Thr Gln Leu His Pro Thr Leu Leu Thr Gln Val His Pro

20 25 30

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

35 40 45

Phe Ala Thr Leu Gly Ala Ser Ser Ala Ala Pro His Leu Ser Leu Phe

50 55 60

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

65 70 75 80

Met Leu Lys Val Glu Ala Asp Leu Glu Lys Glu Thr His Gly Val Thr

85 90 95

Val Ala Lys Asp Ser Trp Lys Arg Asn Ser Ile Thr Ser Ser Leu Ala

100 105 110

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

115 120 125

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

130 135 140

Ala Val Arg Gln

145

<210>13

<211>3750

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>13

gtcgaagcgg ctgcagagcc ggtaacggtg gtggcggctg ttgggccaaa ggcgaaagac 60

gaagaggagg aggaagagga gccgctgcca ccgtgcgagg cggtgcgctg ggccccagtg 120

ggggcggtgg cggaggcccg gcctggggca accgcgtttt tagaagaggc gacggccgag 180

gagcctggcg cggccccggg ctccccgccg gattcgccgg gccggacgct gcggcggctg 240

cgggcagagc ggcggcggct ggactcggcg ctgctggcgc tgtcctcgca cttcgcgcag 300

gtgcagttcc gcctgcgcca ggtggtgcgc ggggcgccgg cggagcagca gcgccttctg 360

cgggagctcg aagacttcgc cttccgcggc tgccctcacg tcctaggtta cgaagggccc 420

ggcgaccccg ccagcgatga gggcgatggg ctgccagggg accggccacg gttgcggggc 480

gaggaccagg gcttgagtga gcaggaaaag caagagcgtc tggaaaccca aagggagaag 540

cagaaagaac tgatactgca gctcaagacc cagctagatg acctggaaac gtttgcctat 600

caagagggca gttatgactc gctgccacag tccgtggtgt tggaaagaca gcgggtgatc 660

atagatgagt taataaagaa actggacatg aatctgaatg aggacatcag ttccctgtcc 720

actgaagagc ttcgtcagcg tgtagatgca gcagtggctc agatcgtcaa cccagcccga 780

gtcaaagaac agttggttga gcaactgaaa actcagatcc gagaccttga gatgtttatc 840

aacttcatcc aagatgaagt gggaagcccc ttgcagacag gtggtggaca ctgtgagtgc 900

aaggccggtg ggaagacagg aaatggctgc agcagaacag gcagcagcag aacgcctcca 960

ggaaacagca aaacaaaggc agaggatgtg aagaaagtcc gggagacggg gctgcacctg 1020

atgcggcgag cgctggccgt gctccagatc tttgctgtta gccagtttgg ttgtgccaca 1080

ggccagatcc ctccaaccct gtggcagagg gtccaggctg acagagacta ctctcccttg 1140

ctgaagaggc tggaggtgtc agtggacaga gtgaagcagc tagccttgag gcagcagcca 1200

catgaccatg tcatcacctc tgccaacctc caggacctct ctctgggagg caaggatgag 1260

ctgactatgg ctgtgcggaa ggagctaacg gtggctgtga gggacctgct ggcccatgga 1320

ctgtatgcct cctccccagg gatgagcctt gttatggctc ctattgcttg tttgctgcca 1380

gccttctcct cggccccaga ggccatgcac ccgtgggagc tctttgtaaa gtactaccat 1440

gctaagaacg gccgtgctta tgtggaatcc ccagcccgga agctctccca gtccttcgcc 1500

cttcctgtta cgggaggcac tgttgtcacc cccaaacaga gcctactgac agccatccac 1560

atggtgctga cagagcatga cccttttaag cgcagtgcag actcagaatt gaaggccttg 1620

gtgtgcatgg cactgaatga gcagcgtctg gtgtcctggg tgaacctcat ctgcaagtcc 1680

gggtcactca tcgagcctca ctaccagccc tggagctaca tggcacacac aggctttgag 1740

agtgccctca acctgctcag tcgcctcagc agcctcaagt ttagcctccc tgtagatctg 1800

gctgtgcgcc agctcaaaaa catcaaagat gccttttgat gagagtgccc taaccccaga 1860

caagctcctt gttcagtagg gatagatgtg ctagtcttct agcataggag caaggaatca 1920

gaggtggggt taaaggcatt tttcccagac cctgctcagg cagtcggcca aatgagtgca 1980

aagtctgttt tccccaccaa cttagctctc ggaaagatgt gctggaggga ccctcttgtt 2040

aagaaggttc tgccaggccg ggcgcggtgg ctcacacctg taatcccagc actttgggag 2100

gccgaggcgg gcggatcaca aggtcaggag ttcgagacca tcctgtctaa cacggtgaaa 2160

ccccatctct actaaaaata caaaaaaatt agtcggacat ggtggcaggc acctgtagtc 2220

ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccaggaggcg gagcttgcag 2280

tgagccaaga tcgcgccact gcactccagc ctgggcgaca gagtgagact ccgtctcaaa 2340

aaaaaaaaag aaggttgtac ccacagtata cgtgtgggca cttgtgcttg agcctgtatt 2400

aaaggaatca ggccaggcac agtggctcac gcctgtaatc tcagcacatt gggaggctga 2460

ggtgggcgga tcacctgagg tcaggagttc aagaccagcc tggccaacat ggtgaaaccc 2520

catctctact aaaaatacaa aaattagcta ggcggggtag tgcatgcctg taatcccagc 2580

tactcaggag gctgaggccg gagaatcgct tgagcccgag aggtggagac tgcagtaagc 2640

caagatcatg ccactgcact ccagcctggg caacacaggg agactccatc tcaaaaaaaa 2700

aaaaaaaaaa aaaaagacat tcaacttgag gctcctgtta gttaagctat cttctttcac 2760

ttgaagcagg tttgagaggc ctaggccaga atttaaattc cttttatgaa tagatttccc 2820

tttcttcctg accccaaggt cagaggagac tatatattcc atggctgcct ctaagactag 2880

gaataggaat atctgaaaac agcatttcta agggtggtaa ccacaggtcg attttaatac 2940

gagtcctttt tcttgtagag gtaagtaaaa tcttcctgac aaggtagtcc tcttttcacg 3000

gcacagacaa tgggctttct gtttatgagg ggtgagaagt gatgtttgtt actatgttct 3060

ccagcaagta aacattcctc tgctcacctc ccaacaagac taacagtctt tttagaagta 3120

aatatattca agacaaacga gaaaatcctg gctacccaag tcgagtatat acaggaatac 3180

aaatcggtaa ccagcagctg ttcctcaggt tgtgactcac tgagcaccac ttgtcctgga 3240

ggctggatga tggaggacat ctggttatag gtactgtagc agggataggt gccacaggag 3300

gataggaact acagcagatc gctgtttcca gaacggggag gagtatctca ttgtgaaaca 3360

gactctagag tggttctatt tggtcttcag tgttttagcc tcattagttc atatttggca 3420

tgcagcttgt ggtgagtact gttctaggac tggccaaaaa tgggcaaaat gtatcactcc 3480

aaacactact gattcagcat tgttttcatg tcttaaaatt gccacctgca ctttgtttct 3540

gcactattat gtagtgcatt ttaacttaaa ttttttccag caacatgtta cttatttaag 3600

atacattact gatatttcat tataattagt tcaccttccc tgtgaaacaa gagaattgta 3660

aaatgttgtg gaaaatgata catatgtgga tgctaatgaa atcatagtat tttgtgtagc 3720

ttctctgaaa aaaaaaaaaa aaaaaaaaaa 3750

<210>14

<211>3750

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(688)..(1836)

<223>

<400>14

gtcgaagcgg ctgcagagcc ggtaacggtg gtggcggctg ttgggccaaa ggcgaaagac 60

gaagaggagg aggaagagga gccgctgcca ccgtgcgagg cggtgcgctg ggccccagtg 120

ggggcggtgg cggaggcccg gcctggggca accgcgtttt tagaagaggc gacggccgag 180

gagcctggcg cggccccggg ctccccgccg gattcgccgg gccggacgct gcggcggctg 240

cgggcagagc ggcggcggct ggactcggcg ctgctggcgc tgtcctcgca cttcgcgcag 300

gtgcagttcc gcctgcgcca ggtggtgcgc ggggcgccgg cggagcagca gcgccttctg 360

cgggagctcg aagacttcgc cttccgcggc tgccctcacg tcctaggtta cgaagggccc 420

ggcgaccccg ccagcgatga gggcgatggg ctgccagggg accggccacg gttgcggggc 480

gaggaccagg gcttgagtga gcaggaaaag caagagcgtc tggaaaccca aagggagaag 540

cagaaagaac tgatactgca gctcaagacc cagctagatg acctggaaac gtttgcctat 600

caagagggca gttatgactc gctgccacag tccgtggtgt tggaaagaca gcgggtgatc 660

atagatgagt taataaagaa actggac atg aat ctg aat gag gac atc agt tcc 714

Met Asn Leu Asn Glu Asp Ile Ser Ser

1 5

ctg tcc act gaa gag ctt cgt cag cgt gta gat gca gca gtg gct cag 762

Leu Ser Thr Glu Glu Leu Arg Gln Arg Val Asp Ala Ala Val Ala Gln

10 15 20 25

atc gtc aac cca gcc cga gtc aaa gaa cag ttg gtt gag caa ctg aaa 810

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

30 35 40

act cag atc cga gac ctt gag atg ttt atc aac ttc atc caa gat gaa 858

Thr Gln Ile Arg Asp Leu Glu Met Phe Ile Asn Phe Ile Gln Asp Glu

45 50 55

gtg gga agc ccc ttg cag aca ggt ggt gga cac tgt gag tgc aag gcc 906

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

60 65 70

ggt ggg aag aca gga aat ggc tgc agc aga aca ggc agc agc aga acg 954

Gly Gly Lys Thr Gly Asn Gly Cys Ser Arg Thr Gly Ser Ser Arg Thr

75 80 85

cct cca gga aac agc aaa aca aag gca gag gat gtg aag aaa gtc cgg 1002

Pro Pro Gly Asn Ser Lys Thr Lys Ala Glu Asp Val Lys Lys Val Arg

90 95 100 105

gag acg ggg ctg cac ctg atg cgg cga gcg ctg gcc gtg ctc cag atc 1050

Glu Thr Gly Leu His Leu Met Arg Arg Ala Leu Ala Val Leu Gln Ile

110 115 120

ttt gct gtt agc cag ttt ggt tgt gcc aca ggc cag atc cct cca acc 1098

Phe Ala Val Ser Gln Phe Gly Cys Ala Thr Gly Gln Ile Pro Pro Thr

125 130 135

ctg tgg cag agg gtc cag gct gac aga gac tac tct ccc ttg ctg aag 1146

Leu Trp Gln Arg Val Gln Ala Asp Arg Asp Tyr Ser Pro Leu Leu Lys

140 145 150

agg ctg gag gtg tca gtg gac aga gtg aag cag cta gcc ttg agg cag 1194

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

155 160 165

cag cca cat gac cat gtc atc acc tct gcc aac ctc cag gac ctc tct 1242

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

170 175 180 185

ctg gga ggc aag gat gag ctg act atg gct gtg cgg aag gag cta acg 1290

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

190 195 200

gtg gct gtg agg gac ctg ctg gcc cat gga ctg tat gcc tcc tcc cca 1338

Val Ala Val Arg Asp Leu Leu Ala His Gly Leu Tyr Ala Ser Ser Pro

205 210 215

ggg atg agc ctt gtt atg gct cct att gct tgt ttg ctg cca gcc ttc 1386

Gly Met Ser Leu Val Met Ala Pro Ile Ala Cys Leu Leu Pro Ala Phe

220 225 230

tcc tcg gcc cca gag gcc atg cac ccg tgg gag ctc ttt gta aag tac 1434

Ser Ser Ala Pro Glu Ala Met His Pro Trp Glu Leu Phe Val Lys Tyr

235 240 245

tac cat gct aag aac ggc cgt gct tat gtg gaa tcc cca gcc cgg aag 1482

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

250 255 260 265

ctc tcc cag tcc ttc gcc ctt cct gtt acg gga ggc act gtt gtc acc 1530

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

270 275 280

ccc aaa cag agc cta ctg aca gcc atc cac atg gtg ctg aca gag cat 1578

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

285 290 295

gac cct ttt aag cgc agt gca gac tca gaa ttg aag gcc ttg gtg tgc 1626

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

300 305 310

atg gca ctg aat gag cag cgt ctg gtg tcc tgg gtg aac ctc atc tgc 1674

Met Ala Leu Asn Glu Gln Arg Leu Val Ser Trp Val Asn Leu Ile Cys

315 320 325

aag tcc ggg tca ctc atc gag cct cac tac cag ccc tgg agc tac atg 1722

Lys Ser Gly Ser Leu Ile Glu Pro His Tyr Gln Pro Trp Ser Tyr Met

330 335 340 345

gca cac aca ggc ttt gag agt gcc ctc aac ctg ctc agt cgc ctc agc 1770

Ala His Thr Gly Phe Glu Ser Ala Leu Asn Leu Leu Ser Arg Leu Ser

350 355 360

agc ctc aag ttt agc ctc cct gta gat ctg gct gtg cgc cag ctc aaa 1818

Ser Leu Lys Phe Ser Leu Pro Val Asp Leu Ala Val Arg Gln Leu Lys

365 370 375

aac atc aaa gat gcc ttt tgatgagagt gccctaaccc cagacaagct 1866

Asn Ile Lys Asp Ala Phe

380

ccttgttcag tagggataga tgtgctagtc ttctagcata ggagcaagga atcagaggtg 1926

gggttaaagg catttttccc agaccctgct caggcagtcg gccaaatgag tgcaaagtct 1986

gttttcccca ccaacttagc tctcggaaag atgtgctgga gggaccctct tgttaagaag 2046

gttctgccag gccgggcgcg gtggctcaca cctgtaatcc cagcactttg ggaggccgag 2106

gcgggcggat cacaaggtca ggagttcgag accatcctgt ctaacacggt gaaaccccat 2166

ctctactaaa aatacaaaaa aattagtcgg acatggtggc aggcacctgt agtcccagct 2226

actcgggagg ctgaggcagg agaatggcgt gaacccagga ggcggagctt gcagtgagcc 2286

aagatcgcgc cactgcactc cagcctgggc gacagagtga gactccgtct caaaaaaaaa 2346

aaagaaggtt gtacccacag tatacgtgtg ggcacttgtg cttgagcctg tattaaagga 2406

atcaggccag gcacagtggc tcacgcctgt aatctcagca cattgggagg ctgaggtggg 2466

cggatcacct gaggtcagga gttcaagacc agcctggcca acatggtgaa accccatctc 2526

tactaaaaat acaaaaatta gctaggcggg gtagtgcatg cctgtaatcc cagctactca 2586

ggaggctgag gccggagaat cgcttgagcc cgagaggtgg agactgcagt aagccaagat 2646

catgccactg cactccagcc tgggcaacac agggagactc catctcaaaa aaaaaaaaaa 2706

aaaaaaaaag acattcaact tgaggctcct gttagttaag ctatcttctt tcacttgaag 2766

caggtttgag aggcctaggc cagaatttaa attcctttta tgaatagatt tccctttctt 2826

cctgacccca aggtcagagg agactatata ttccatggct gcctctaaga ctaggaatag 2886

gaatatctga aaacagcatt tctaagggtg gtaaccacag gtcgatttta atacgagtcc 2946

tttttcttgt agaggtaagt aaaatcttcc tgacaaggta gtcctctttt cacggcacag 3006

acaatgggct ttctgtttat gaggggtgag aagtgatgtt tgttactatg ttctccagca 3066

agtaaacatt cctctgctca cctcccaaca agactaacag tctttttaga agtaaatata 3126

ttcaagacaa acgagaaaat cctggctacc caagtcgagt atatacagga atacaaatcg 3186

gtaaccagca gctgttcctc aggttgtgac tcactgagca ccacttgtcc tggaggctgg 3246

atgatggagg acatctggtt ataggtactg tagcagggat aggtgccaca ggaggatagg 3306

aactacagca gatcgctgtt tccagaacgg ggaggagtat ctcattgtga aacagactct 3366

agagtggttc tatttggtct tcagtgtttt agcctcatta gttcatattt ggcatgcagc 3426

ttgtggtgag tactgttcta ggactggcca aaaatgggca aaatgtatca ctccaaacac 3486

tactgattca gcattgtttt catgtcttaa aattgccacc tgcactttgt ttctgcacta 3546

ttatgtagtg cattttaact taaatttttt ccagcaacat gttacttatt taagatacat 3606

tactgatatt tcattataat tagttcacct tccctgtgaa acaagagaat tgtaaaatgt 3666

tgtggaaaat gatacatatg tggatgctaa tgaaatcata gtattttgtg tagcttctct 3726

gaaaaaaaaa aaaaaaaaaa aaaa 3750

<210>15

<211>383

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>15

Met Asn Leu Asn Glu Asp Ile Ser Ser Leu Ser Thr Glu Glu Leu Arg

1 5 10 15

Gln Arg Val Asp Ala Ala Val Ala Gln Ile Val Asn Pro Ala Arg Val

20 25 30

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

35 40 45

Met Phe Ile Asn Phe Ile Gln Asp Glu Val Gly Ser Pro Leu Gln Thr

50 55 60

Gly Gly Gly His Cys Glu Cys Lys Ala Gly Gly Lys Thr Gly Asn Gly

65 70 75 80

Cys Ser Arg Thr Gly Ser Ser Arg Thr Pro Pro Gly Asn Ser Lys Thr

85 90 95

Lys Ala Glu Asp Val Lys Lys Val Arg Glu Thr Gly Leu His Leu Met

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

Thr Met Ala Val Arg Lys Glu Leu Thr Val Ala Val Arg Asp Leu Leu

195 200 205

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

210 215 220

Pro Ile Ala Cys Leu Leu Pro Ala Phe Ser Ser Ala Pro Glu Ala Met

225 230 235 240

His Pro Trp Glu Leu Phe Val Lys Tyr Tyr His Ala Lys Asn Gly Arg

245 250 255

Ala Tyr Val Glu Ser Pro Ala Arg Lys Leu Ser Gln Ser Phe Ala Leu

260 265 270

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

275 280 285

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

290 295 300

Asp Ser Glu Leu Lys Ala Leu Val Cys Met Ala Leu Asn Glu Gln Arg

305 310 315 320

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

325 330 335

Pro His Tyr Gln Pro Trp Ser Tyr Met Ala His Thr Gly Phe Glu Ser

340 345 350

Ala Leu Asn Leu Leu Ser Arg Leu Ser Ser Leu Lys Phe Ser Leu Pro

355 360 365

Val Asp Leu Ala Val Arg Gln Leu Lys Asn Ile Lys Asp Ala Phe

370 375 380

<210>16

<211>2730

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>16

gcgctcctcc ggtggccgaa cgtcgctttc gggagctgtg gtccccgcaa gccgcggttc 60

ccggcctttc agctcggctg ctccctgggt ggtggggccg aggcgcaccc ccttctgccc 120

gggcccggag tgcggaggcg cagcccggga gaggggctga aggggggcag gcagtcctcg 180

ggcgcgagtg tgcagcgccc tctgggcgtg gacgcggagc gcgctccagg tgcgcaggac 240

tcctagctct cttggggaac gctttctggg gcagggcggg gacccggggg cgatggggcc 300

ttcaaccgac gggcaaacac acacagacac accccggctg tcctccagct gcgatgcggc 360

tcgctgcgcc ccgccggccc agattctccc gtacgctcgc gttcttcctg cactccacaa 420

agtgctggag acttggggcc ttagtttaaa cagctgcacc cgcacggaag ggctgcaaga 480

aaaaggggga cgggggcgga gttcgcagcg tctttctgtg gaagacaacg ccctctctct 540

tcatctgagc taaaaggaaa aataagtaac ttctttgttc cccggtgacc tcgggcacgc 600

ggatctgagg agcaccgtgc agttgctgct ccttcgagat cccctgcgag gccctgggcc 660

tcagttcaaa aagctgtgga aggcctgcgg gtgtagggga aacggccgag agagcaaagg 720

ggaagaaccg gacgggccct gcccacatct ggcaggcagg agagatggtg ccaaacgacc 780

ttcgcacctg ggccctgaga ccaaagatgg cgtcgtcctc ccctgtcttc cctaggcgga 840

aggcaagaac ttgggtcggc ctgagctggg gaccaagaaa atatcgggaa gtgtccagtg 900

ttcctcttta aaagaattaa accttcctgg gccacgcagg gactgaccgt gggaccctgg 960

actctcctcc accttccacc gtggagcagg ctctggagcc gagcagcctc ctgcgtcccc 1020

atctcatccc cccactcctc ctcacagcac taaaagatga tggcctgctt gtacccctgc 1080

tcctgagcac ctgtttgacc tcaaagagct ctcgcttttg gggtgtccgt ctccccaagt 1140

ctgtctaggg ggcaggaaga ccttcatcag ggttcttggg ggccgatgtg ggctcgctga 1200

gtgcctgagt gatggatggt ctcacagcac ggcaccacgg aggtccagcc gagctcgagg 1260

agtccctgtg gattaaaaat gcccttttcg aaggttctac ctctaccaga gggtggctcc 1320

acagatccct tcaacccagt atggtggaaa aataggaatt ttggaatctt acctttctct 1380

actgctcaca acagaggaaa ctggggtcag ggaggatttg atggagtctt ttcatttttt 1440

aaaagtcact cacggccaag cgcggtggct cacgcctgtg accccagcac tttgggaggc 1500

cgaggcgggc agatcacctg aggtcaggag ttctcgacca gcctggctaa cacggtgaat 1560

ccccatctct actaaaaata caaaaattag ccggatatgg tggcaggtgc tataatccca 1620

gctactcggg aggctgaggc agggagaatc gcctcgacct ctcgggttca aacaattctc 1680

ccgcctcagc ctcctaaata gctgggatta cagtcgcacg ccaccacagg ccggctaatt 1740

ttttatttat ttatttattt tgatttttag tagagacaag gtttcaccat attggtcagg 1800

ctggtcttga actcccaacc tcaggtgata cacccgtctc ggcctcccaa agcgctggga 1860

ttgcaggcgt gagccaccgt gcctggccct tatacttgtc ttcttgagtg catgtgtgag 1920

gctttctcta gaagtagagc tctggattat aggtataaac atcttcaact ttctcaggaa 1980

ttgttgtaag caattgctct aagcaaattg ctctccaaag ggcttatagt aatttacact 2040

cccaacagca gttatgagca tttccatttt tctacatcct cctatgactt ggtgttgggc 2100

cttttatatt ttgccagctg atgcaagtaa aattatatct tattgctgtt tgagtctgac 2160

catccttccc attaggaaat gttttgctga agcctttagt tgccgactgg ttgggcagac 2220

acttctgttt acttatcaca tctgttttcc tctttctcag taagagattc cttaaatttc 2280

aattgggctt atggctattt aaaataaaga ttacctttcc ctgcctctct tacagccacg 2340

cgtagccaca tgattagggt cttgccagtg gcacatgagc agaagtggta catgcacttt 2400

cagaaaggtg tcaagcatgc tctccttccc ttttctgttt tctcctgggc ggaatacaga 2460

tctgatggct gcctctgaag cagccttctt ggaccatgaa gtgaacatgg gaacagaggc 2520

catccacagc agaggaacaa gttaaaggaa gcatgggtcc ctgccccatg gagtatagcg 2580

tcatccctgg actgcccacg cagacttata catgatggga aaatgtctct ttttgtttgt 2640

ttaggacact gtttctctga attttctctc acttgccagc aattctaatc ctaaaaatac 2700

actgatgaat tcaaaaaaaa aaaaaaaaaa 2730

<210>17

<211>2730

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(1216)..(1518)

<223>

<400>17

gcgctcctcc ggtggccgaa cgtcgctttc gggagctgtg gtccccgcaa gccgcggttc 60

ccggcctttc agctcggctg ctccctgggt ggtggggccg aggcgcaccc ccttctgccc 120

gggcccggag tgcggaggcg cagcccggga gaggggctga aggggggcag gcagtcctcg 180

ggcgcgagtg tgcagcgccc tctgggcgtg gacgcggagc gcgctccagg tgcgcaggac 240

tcctagctct cttggggaac gctttctggg gcagggcggg gacccggggg cgatggggcc 300

ttcaaccgac gggcaaacac acacagacac accccggctg tcctccagct gcgatgcggc 360

tcgctgcgcc ccgccggccc agattctccc gtacgctcgc gttcttcctg cactccacaa 420

agtgctggag acttggggcc ttagtttaaa cagctgcacc cgcacggaag ggctgcaaga 480

aaaaggggga cgggggcgga gttcgcagcg tctttctgtg gaagacaacg ccctctctct 540

tcatctgagc taaaaggaaa aataagtaac ttctttgttc cccggtgacc tcgggcacgc 600

ggatctgagg agcaccgtgc agttgctgct ccttcgagat cccctgcgag gccctgggcc 660

tcagttcaaa aagctgtgga aggcctgcgg gtgtagggga aacggccgag agagcaaagg 720

ggaagaaccg gacgggccct gcccacatct ggcaggcagg agagatggtg ccaaacgacc 780

ttcgcacctg ggccctgaga ccaaagatgg cgtcgtcctc ccctgtcttc cctaggcgga 840

aggcaagaac ttgggtcggc ctgagctggg gaccaagaaa atatcgggaa gtgtccagtg 900

ttcctcttta aaagaattaa accttcctgg gccacgcagg gactgaccgt gggaccctgg 960

actctcctcc accttccacc gtggagcagg ctctggagcc gagcagcctc ctgcgtcccc 1020

atctcatccc cccactcctc ctcacagcac taaaagatga tggcctgctt gtacccctgc 1080

tcctgagcac ctgtttgacc tcaaagagct ctcgcttttg gggtgtccgt ctccccaagt 1140

ctgtctaggg ggcaggaaga ccttcatcag ggttcttggg ggccgatgtg ggctcgctga 1200

gtgcctgagt gatgg atg gtc tca cag cac ggc acc acg gag gtc cag ccg 1251

Met Val Ser Gln His Gly Thr Thr Glu Val Gln Pro

1 5 10

agc tcg agg agt ccc tgt gga tta aaa atg ccc ttt tcg aag gtt cta 1299

Ser Ser Arg Ser Pro Cys Gly Leu Lys Met Pro Phe Ser Lys Val Leu

15 20 25

cct cta cca gag ggt ggc tcc aca gat ccc ttc aac cca gta tgg tgg 1347

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

30 35 40

aaa aat agg aat ttt gga atc tta cct ttc tct act gct cac aac aga 1395

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

45 50 55 60

gga aac tgg ggt cag gga gga ttt gat gga gtc ttt tca ttt ttt aaa 1443

Gly Asn Trp Gly Gln Gly Gly Phe Asp Gly Val Phe Ser Phe Phe Lys

65 70 75

agt cac tca cgg cca agc gcg gtg gct cac gcc tgt gac ccc agc act 1491

Ser His Ser Arg Pro Ser Ala Val Ala His Ala Cys Asp Pro Ser Thr

80 85 90

ttg gga ggc cga ggc ggg cag atc acc tgaggtcagg agttctcgac 1538

Leu Gly Gly Arg Gly Gly Gln Ile Thr

95 100

cagcctggct aacacggtga atccccatct ctactaaaaa tacaaaaatt agccggatat 1598

ggtggcaggt gctataatcc cagctactcg ggaggctgag gcagggagaa tcgcctcgac 1658

ctctcgggtt caaacaattc tcccgcctca gcctcctaaa tagctgggat tacagtcgca 1718

cgccaccaca ggccggctaa ttttttattt atttatttat tttgattttt agtagagaca 1778

aggtttcacc atattggtca ggctggtctt gaactcccaa cctcaggtga tacacccgtc 1838

tcggcctccc aaagcgctgg gattgcaggc gtgagccacc gtgcctggcc cttatacttg 1898

tcttcttgag tgcatgtgtg aggctttctc tagaagtaga gctctggatt ataggtataa 1958

acatcttcaa ctttctcagg aattgttgta agcaattgct ctaagcaaat tgctctccaa 2018

agggcttata gtaatttaca ctcccaacag cagttatgag catttccatt tttctacatc 2078

ctcctatgac ttggtgttgg gccttttata ttttgccagc tgatgcaagt aaaattatat 2138

cttattgctg tttgagtctg accatccttc ccattaggaa atgttttgct gaagccttta 2198

gttgccgact ggttgggcag acacttctgt ttacttatca catctgtttt cctctttctc 2258

agtaagagat tccttaaatt tcaattgggc ttatggctat ttaaaataaa gattaccttt 2318

ccctgcctct cttacagcca cgcgtagcca catgattagg gtcttgccag tggcacatga 2378

gcagaagtgg tacatgcact ttcagaaagg tgtcaagcat gctctccttc ccttttctgt 2438

tttctcctgg gcggaataca gatctgatgg ctgcctctga agcagccttc ttggaccatg 2498

aagtgaacat gggaacagag gccatccaca gcagaggaac aagttaaagg aagcatgggt 2558

ccctgcccca tggagtatag cgtcatccct ggactgccca cgcagactta tacatgatgg 2618

gaaaatgtct ctttttgttt gtttaggaca ctgtttctct gaattttctc tcacttgcca 2678

gcaattctaa tcctaaaaat acactgatga attcaaaaaa aaaaaaaaaa aa 2730

<210>18

<21l>101

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>18

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

1 5 10 15

Pro Cys Gly Leu Lys Met Pro Phe Ser Lys Val Leu Pro Leu Pro Glu

20 25 30

Gly Gly Ser Thr Asp Pro Phe Asn Pro Val Trp Trp Lys Asn Arg Asn

35 40 45

Phe Gly Ile Leu Pro Phe Ser Thr Ala His Asn Arg Gly Asn Trp Gly

50 55 60

Gln Gly Gly Phe Asp Gly Val Phe Ser Phe Phe Lys Ser His Ser Arg

65 70 75 80

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

85 90 95

Gly Gly Gln Ile Thr

100

<210>19

<211>3260

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>19

gggggatccg tgctgccatg gagcgtgccg gcaagcagga gatgctgctg aagccacata 60

gccgtgtcca ggtattcgag ggtgcggagg acaacctccc ggaccgcgat gcgctgcggg 120

ctgcactggc catccagcaa ctggctgagg gactcacagc tgatgacctg ctgctcgtgc 180

tgatctcagg tgtggtacca cattggccca agactgttgg tggggggtgc accacctgat 240

ctctcaggtc ttcgagagat caggtctgag cccccggggt cacagggtaa agttaggagc 300

aagggaggtg gtgaggagcc tggatggtga ctcctgggtt gccttgggct agtcgtctgg 360

cctcccctga gctgtggagt cctccccctg agctgacctt ttcggtgaca gtgagagggt 420

gcatggggag cacataatgc agggcctgac acatccgtag agtccttgga aaatgtcact 480

gctattgctg ctgtctgtac taatgtcacc tggggctagg ccctcagacc tcatggagtc 540

ctctccttga tcttccattg tgtgccccct gccctgcctc ctgttctagt ctcttaagga 600

gtagttagtt cttccggtgc ctactgggac ctggggtacc ccaaggcagg ggcaacctca 660

ggtggccagg atgtggtgac tgtacacata ttgcatatcc acaggggggc accctaaccc 720

cacctttcca gccccctttt tctaatgtgg gcttgtcacc cctgcttgcc tggttccctg 780

ggttgggata gcccctctac ctgataccct cattgtcttg agaggtgggg gttcagctct 840

gctgcctgcc cccatcccac ctgtcacact ggaggagaag cagacactca ctagactgct 900

ggcagcccgt ggagccacca tccaggagtt gaacaccatt cggaaggccc tgtcccagct 960

caagggtggg gggctggctc aggccgccta ccctgcccag gtggtgagcc tcatcctgtc 1020

agatgtggtg gggggggggc accctgtgga ggtgattgcc agtggcccca ccgtggccag 1080

ttcccacaat gtgcaagatt gcctgcatat cctcaatcgc tacggcctcc gtgcagccct 1140

gccacgttct gtgaagactg tgctgtctcg ggccgactct gacccccatg ggccacacac 1200

ctgtggccat gtcctgaatg tgatcattgg ctctaatgtg ctggcgctag ctgaggccca 1260

gcggcaggcc gaggcactgg gctaccaggc tgtgttgctg agtgcagcca tgcaaggtga 1320

tgtaaaaagt atggcccagt tctacgggct gctggcccat gtggctagaa cccgcctcac 1380

cccatccatg gctggggctt ctgtggagga agatgcacag ctccatgagc tggcagctga 1440

gcttcagatc ccagacctgc agctggagga ggctctggag accatggcat ggggaagggg 1500

cccagtctgc ctgctggctg gtggcgagcc cacagtacag ctgcagggct cgggcagggg 1560

tggccggaac caggaactgg ccctgcgtgt tggagcagag ttgagaaggt ggccgctggg 1620

gccgatagat gtgctgtttt tgagcggtgg caccgatggg caggatgggc ccacagaggc 1680

tgctggggcc tgggtcacac ctgagcttgc cagccaggct gcagctgagg gcctggacat 1740

agccaccttc ctagcccaca atgactcaca taccttcttc tgctgcctcc agggtggggc 1800

acacctgctg cacacaggga tgacaggtac caatgtcatg gacacccacc tcttgttcct 1860

gcggcctcgg tgatggcata ggtcacattt tgggagttca gaggaggcct acaagggcaa 1920

gccagactgg cagatggggg cttcccccta cccctgagga tgaggacaag cccctcggcc 1980

agttcagcgt tcccgtgctt ctcccttggg cagcctctct cttgagcccc tcaccctgtt 2040

tctttctgtg aagcgagaat gtctgaaaat aaataggacc atgccatggg aaaaaaaaaa 2100

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160

aaaaacggca cgaggcggca cgaggcaagc ttgtagtcag aagaactcgc ctgggaggga 2220

tcgctcctgg gagatccgaa cgcgggaggg cctggagcgc ggcggcagct ggatagcatt 2280

cgggcccatc cgaataagcg gtaaatggat catttctggg gcctccctga ctcctcttcc 2340

agagcctcct accgacctgc tctgtcccct ccttccttca tgccctccac tcttccctaa 2400

atgcaagtct cctccccaag cccatgtcct cctcggcttc ccctctgctc tcctcaccgg 2460

tctcactcag tcaacttcaa gtctgagcct tctctgcctg tctccttcca ttctcacctt 2520

tcctgtcaca ccagatcact cttctcccag gctgtccctc gtgccaaact tttttggtaa 2580

atcttcctta atgatctaga aacagtctct cccttctttc tattccataa tggtccttca 2640

aaaccccaac cctcgccggg cgcggtggct cacgcctgta atcccagcac tttggaaggc 2700

cgaggtgggc ggatcataag gtcaggagat cgagaccatc ctggctaaca aggtgaaaca 2760

ctatctctac taaaaataca ggaaaaaaaa aaattagccg ggcgtggggg cgggcccctg 2820

tagtcccagg tactcgggag gctgaggcag gagaatggcg tgaacccggg aggcggagct 2880

tgcaatgagc caagatcttg ccactgcact ccagcctggg cgacagagca agactctgtc 2940

tcaaaaaaaa aaaaagttaa atttggccag gcacagtggc tcacacctgt aatcccaaca 3000

ctttgggagg ccaaggtgtg ccagatagct tgagccccag agtttgagag cagtctgggc 3060

aacatagtga gaccttcttg agaccttctt ctctacaaaa aatttaaaaa ttagccagga 3120

acctgtagtt ccagctactc gggaggctga ggtgggagaa tcacctgagc ccaggaggtc 3180

aaggctgcag tgagctgtgt tcctgccact gtactccagc ctgggtgaca gtaagacctt 3240

gtaaaaaaaa aaaaaaaaaa 3260

<210>20

<211>3260

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(1310)..(1870)

<223>

<400>20

gggggatccg tgctgccatg gagcgtgccg gcaagcagga gatgctgctg aagccacata 60

gccgtgtcca ggtattcgag ggtgcggagg acaacctccc ggaccgcgat gcgctgcggg 120

ctgcactggc catccagcaa ctggctgagg gactcacagc tgatgacctg ctgctcgtgc 180

tgatctcagg tgtggtacca cattggccca agactgttgg tggggggtgc accacctgat 240

ctctcaggtc ttcgagagat caggtctgag cccccggggt cacagggtaa agttaggagc 300

aagggaggtg gtgaggagcc tggatggtga ctcctgggtt gccttgggct agtcgtctgg 360

cctcccctga gctgtggagt cctccccctg agctgacctt ttcggtgaca gtgagagggt 420

gcatggggag cacataatgc agggcctgac acatccgtag agtccttgga aaatgtcact 480

gctattgctg ctgtctgtac taatgtcacc tggggctagg ccctcagacc tcatggagtc 540

ctctccttga tcttccattg tgtgccccct gccctgcctc ctgttctagt ctcttaagga 600

gtagttagtt cttccggtgc ctactgggac ctggggtacc ccaaggcagg ggcaacctca 660

ggtggccagg atgtggtgac tgtacacata ttgcatatcc acaggggggc accctaaccc 720

cacctttcca gccccctttt tctaatgtgg gcttgtcacc cctgcttgcc tggttccctg 780

ggttgggata gcccctctac ctgataccct cattgtcttg agaggtgggg gttcagctct 840

gctgcctgcc cccatcccac ctgtcacact ggaggagaag cagacactca ctagactgct 900

ggcagcccgt ggagccacca tccaggagtt gaacaccatt cggaaggccc tgtcccagct 960

caagggtggg gggctggctc aggccgccta ccctgcccag gtggtgagcc tcatcctgtc 1020

agatgtggtg gggggggggc accctgtgga ggtgattgcc agtggcccca ccgtggccag 1080

ttcccacaat gtgcaagatt gcctgcatat cctcaatcgc tacggcctcc gtgcagccct 1140

gccacgttct gtgaagactg tgctgtctcg ggccgactct gacccccatg ggccacacac 1200

ctgtggccat gtcctgaatg tgatcattgg ctctaatgtg ctggcgctag ctgaggccca 1260

gcggcaggcc gaggcactgg gctaccaggc tgtgttgctg agtgcagcc atg caa ggt 1318

Met Gln Gly

1

gat gta aaa agt atg gcc cag ttc tac ggg ctg ctg gcc cat gtg gct 1366

Asp Val Lys Ser Met Ala Gln Phe Tyr Gly Leu Leu Ala His Val Ala

5 10 15

aga acc cgc ctc acc cca tcc atg gct ggg gct tct gtg gag gaa gat 1414

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

20 25 30 35

gca cag ctc cat gag ctg gca gct gag ctt cag atc cca gac ctg cag 1462

Ala Gln Leu His Glu Leu Ala Ala Glu Leu Gln Ile Pro Asp Leu Gln

40 45 50

ctg gag gag gct ctg gag acc atg gca tgg gga agg ggc cca gtc tgc 1510

Leu Glu Glu Ala Leu Glu Thr Met Ala Trp Gly Arg Gly Pro Val Cys

55 60 65

ctg ctg gct ggt ggc gag ccc aca gta cag ctg cag ggc tcg ggc agg 1558

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

70 75 80

ggt ggc cgg aac cag gaa ctg gcc ctg cgt gtt gga gca gag ttg aga 1606

Gly Gly Arg Asn Gln Glu Leu Ala Leu Arg Val Gly Ala Glu Leu Arg

85 90 95

agg tgg ccg ctg ggg ccg ata gat gtg ctg ttt ttg agc ggt ggc acc 1654

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

100 105 110 115

gat ggg cag gat ggg ccc aca gag gct gct ggg gcc tgg gtc aca cct 1702

Asp Gly Gln Asp Gly Pro Thr Glu Ala Ala Gly Ala Trp Val Thr Pro

120 125 130

gag ctt gcc agc cag gct gca gct gag ggc ctg gac ata gcc acc ttc 1750

Glu Leu Ala Ser Gln Ala Ala Ala Glu Gly Leu Asp Ile Ala Thr Phe

135 140 145

cta gcc cac aat gac tca cat acc ttc ttc tgc tgc ctc cag ggt ggg 1798

Leu Ala His Asn Asp Ser His Thr Phe Phe Cys Cys Leu Gln Gly Gly

150 155 160

gca cac ctg ctg cac aca ggg atg aca ggt acc aat gtc atg gac acc 1846

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

165 170 175

cac ctc ttg ttc ctg cgg cct cgg tgatggcata ggtcacattt tgggagttca 1900

His Leu Leu Phe Leu Arg Pro Arg

180 185

gaggaggcct acaagggcaa gccagactgg cagatggggg cttcccccta cccctgagga 1960

tgaggacaag cccctcggcc agttcagcgt tcccgtgctt ctcccttggg cagcctctct 2020

cttgagcccc tcaccctgtt tctttctgtg aagcgagaat gtctgaaaat aaataggacc 2080

atgccatggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2140

aaaaaaaaaa aaaaaaaaaa aaaaacggca cgaggcggca cgaggcaagc ttgtagtcag 2200

aagaactcgc ctgggaggga tcgctcctgg gagatccgaa cgcgggaggg cctggagcgc 2260

ggcggcagct ggatagcatt cgggcccatc cgaataagcg gtaaatggat catttctggg 2320

gcctccctga ctcctcttcc agagcctcct accgacctgc tctgtcccct ccttccttca 2380

tgccctccac tcttccctaa atgcaagtct cctccccaag cccatgtcct cctcggcttc 2440

ccctctgctc tcctcaccgg tctcactcag tcaacttcaa gtctgagcct tctctgcctg 2500

tctccttcca ttctcacctt tcctgtcaca ccagatcact cttctcccag gctgtccctc 2560

gtgccaaact tttttggtaa atcttcctta atgatctaga aacagtctct cccttctttc 2620

tattccataa tggtccttca aaaccccaac cctcgccggg cgcggtggct cacgcctgta 2680

atcccagcac tttggaaggc cgaggtgggc ggatcataag gtcaggagat cgagaccatc 2740

ctggctaaca aggtgaaaca ctatctctac taaaaataca ggaaaaaaaa aaattagccg 2800

ggcgtggggg cgggcccctg tagtcccagg tactcgggag gctgaggcag gagaatggcg 2860

tgaacccggg aggcggagct tgcaatgagc caagatcttg ccactgcact ccagcctggg 2920

cgacagagca agactctgtc tcaaaaaaaa aaaaagttaa atttggccag gcacagtggc 2980

tcacacctgt aatcccaaca ctttgggagg ccaaggtgtg ccagatagct tgagccccag 3040

agtttgagag cagtctgggc aacatagtga gaccttcttg agaccttctt ctctacaaaa 3100

aatttaaaaa ttagccagga acctgtagtt ccagctactc gggaggctga ggtgggagaa 3160

tcacctgagc ccaggaggtc aaggctgcag tgagctgtgt tcctgccact gtactccagc 3220

ctgggtgaca gtaagacctt gtaaaaaaaa aaaaaaaaaa 3260

<210>21

<211>187

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>21

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

1 5 10 15

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

20 25 30

Glu Glu Asp Ala Gln Leu His Glu Leu Ala Ala Glu Leu Gln Ile Pro

35 40 45

Asp Leu Gln Leu Glu Glu Ala Leu Glu Thr Met Ala Trp Gly Arg Gly

50 55 60

Pro Val Cys Leu Leu Ala Gly Gly Glu Pro Thr Val Gln Leu Gln Gly

65 70 75 80

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

85 90 95

Glu Leu Arg Arg Trp Pro Leu Gly Pro Ile Asp Val Leu Phe Leu Ser

100 105 110

Gly Gly Thr Asp Gly Gln Asp Gly Pro Thr Glu Ala Ala Gly Ala Trp

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Met Asp Thr His Leu Leu Phe Leu Arg Pro Arg

180 185

<210>22

<211>2692

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>22

gcggaagcgg cggccgggcc gccctgcgcc cgggcggggc cctgcggtgt ggccgtggct 60

tgttcctgcc gctttcgcac cctgcggccc cccacccagt gcagcagtgc gggcgggcgt 120

gagcctcggt gcaccaggag gcccttcccg cgggaggcgc tgggctcgcg ctaattgggg 180

cggggggggg ggcggcgggg gaggagggaa ctggcgcgcg gcttggtttc cattagagac 240

gcaaagtttc tgctccggga ggaggcggcg gcgccgcggg ctcgtcgcct gggggagcag 300

aagcgggtgg gaggtgcggg tggccttggc cgcagccctg gtgcgcgggg gccgggggtg 360

gtgaccctcc tggccgagga ggggcggcgt ccagacgccc gctcgggggc cgccttcccc 420

cccacgcctg cccccgggca cgcgccctgc ccggtccctc gccccgcgcc acttccagtc 480

cgcagagaga tgccctccac gtttctgctt tctctgcagc ctctagattg ccagatgcga 540

ctgtgcgcct cgctgggtgt gttttccaca gccccttcct cctcggcgtg cagggctgac 600

atcaccgact gcgtttctgg tttggcgggt ggggagatgg ttccccgcag ggttctggta 660

cacctttgcc cccagggcta gcgccatttg ggggaggagg ttttcgttgt cgagaaagtt 720

ggatgctcct ggtaacccct ctaacaagag agttctgtag cgaggtggga ctgttctccc 780

cataaggtga cagtttctct tgcgaggtgt ggcagcgctt cctgttgtac aagacagatg 840

ttgccttggc gttacgtaaa tcatcgtgtc tccgtcattt aaagaaagcc aatttttagt 900

gattgaggta gaaagaaaga tccgtttata atttgtaaaa acaaattttc acccagaatc 960

aatatattgg aacaccattc ctactgttaa agttttcact taagagcata aacttcatca 1020

gctttctatt aggacttatt ttgtaattgg cttcttaggc atccttcttt aaaagagaaa 1080

tccacgttag ctctccttga ggtctcgagt tccctcggct ggaggcacag gttcagtgga 1140

gaccaaataa tgcaggtgaa ttaccttcgt ggccattact gcctcgaacg aagtgtgttt 1200

attaagaaca gttcttatgt cattcttaag gtaggtaggg ttaatactct ccagcaaatt 1260

tagtagatac tgtttgccag aaaagagagg agtatatata gtttgataat tattgtgtag 1320

ttttctgtgt acttaatttt tgcagttttg taacacttca tttgtaagat ggtaccattt 1380

tttcctggct tctgaatcat aggatagttt gacccagggc attagccatt gtaatggtag 1440

gcttttaaca aataactgcc taatttaaag gattggaaag catttgttac atggaaatga 1500

agttggtggc gtacccagtt gctgtatctt tattttttgt acttaattat ttctcataaa 1560

atggatataa aagcctgtta atccaaccca atgccattat gtaacgccag tttggagatt 1620

tcgagggcct ggagcagtgc gcaaggtgcg ctgaaagcct gcccctggat gagatcctta 1680

tcctggctgt gatggcagtg gcagtgggct gggtcccttg ttgagtggaa agggggactg 1740

cggtgtccat ggtgcagtag gtggcgctct tctgtcttag agcctgccgc cactgcagct 1800

ggtgccaagg ggccttctgc cactagaggt gccatttttc acatgatgaa cttagcctag 1860

ttagatcgca gagcaagctg taagccatgg gcccagaaaa gaaaacttga agtgagcaga 1920

tgttgtcact tccttgtaat cctttgttaa aatagcataa ggagttttct ttattctatt 1980

tactttcatt aaatgaccgt gctacaggtt tcaaaggatt ttaagattga tttttgaaag 2040

atcacaatat taaaagtata actggaaaat ctatgttgaa atcaaccaaa catgtcgtgg 2100

actgaatgat aaccttttct ttcttcatat aggctgatca gctgaccgaa gaacagattg 2160

ctgaattcaa ggaagccttc tccctatttg ataaagatgg cgatggcacc atcacaacaa 2220

aggaacttgg aactgtcatg aggtcactgg gtcagaaccc aacagaagct gaattgcagg 2280

atatgatcaa tgaagtggat gctgatggta atggcaccat tgacttcccc gaatttttga 2340

ctatgatggc tagaaaaatg aaagatacag atagtgaaga agaaatccgt gaggcattcc 2400

gagtctttga caaggatggc aatggttata tcagtgcagc agaactacgt cacgtcatga 2460

caaacttagg agaaaaacta acagatgaag aagtagatga aatgatcaga gaagcagata 2520

ttgatggaga cggacaagtc aactatgaag aattcgtaca gatgatgact gcaaaatgaa 2580

gacctacttt caactccttt ttcccccctc tagaagaatc aaattgaatc ttttacttac 2640

ctcttgccaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2692

<210>23

<211>2692

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(2238)..(2576)

<223>

<400>23

gcggaagcgg cggccgggcc gccctgcgcc cgggcggggc cctgcggtgt ggccgtggct 60

tgttcctgcc gctttcgcac cctgcggccc cccacccagt gcagcagtgc gggcgggcgt 120

gagcctcggt gcaccaggag gcccttcccg cgggaggcgc tgggctcgcg ctaattgggg 180

cggggggggg ggcggcgggg gaggagggaa ctggcgcgcg gcttggtttc cattagagac 240

gcaaagtttc tgctccggga ggaggcggcg gcgccgcggg ctcgtcgcct gggggagcag 300

aagcgggtgg gaggtgcggg tggccttggc cgcagccctg gtgcgcgggg gccgggggtg 360

gtgaccctcc tggccgagga ggggcggcgt ccagacgccc gctcgggggc cgccttcccc 420

cccacgcctg cccccgggca cgcgccctgc ccggtccctc gccccgcgcc acttccagtc 480

cgcagagaga tgccctccac gtttctgctt tctctgcagc ctctagattg ccagatgcga 540

ctgtgcgcct cgctgggtgt gttttccaca gccccttcct cctcggcgtg cagggctgac 600

atcaccgact gcgtttctgg tttggcgggt ggggagatgg ttccccgcag ggttctggta 660

cacctttgcc cccagggcta gcgccatttg ggggaggagg ttttcgttgt cgagaaagtt 720

ggatgctcct ggtaacccct ctaacaagag agttctgtag cgaggtggga ctgttctccc 780

cataaggtga cagtttctct tgcgaggtgt ggcagcgctt cctgttgtac aagacagatg 840

ttgccttggc gttacgtaaa tcatcgtgtc tccgtcattt aaagaaagcc aatttttagt 900

gattgaggta gaaagaaaga tccgtttata atttgtaaaa acaaattttc acccagaatc 960

aatatattgg aacaccattc ctactgttaa agttttcact taagagcata aacttcatca 1020

gctttctatt aggacttatt ttgtaattgg cttcttaggc atccttcttt aaaagagaaa 1080

tccacgttag ctctccttga ggtctcgagt tccctcggct ggaggcacag gttcagtgga 1140

gaccaaataa tgcaggtgaa ttaccttcgt ggccattact gcctcgaacg aagtgtgttt 1200

attaagaaca gttcttatgt cattcttaag gtaggtaggg ttaatactct ccagcaaatt 1260

tagtagatac tgtttgccag aaaagagagg agtatatata gtttgataat tattgtgtag 1320

ttttctgtgt acttaatttt tgcagttttg taacacttca tttgtaagat ggtaccattt 1380

tttcctggct tctgaatcat aggatagttt gacccagggc attagccatt gtaatggtag 1440

gcttttaaca aataactgcc taatttaaag gattggaaag catttgttac atggaaatga 1500

agttggtggc gtacccagtt gctgtatctt tattttttgt acttaattat ttctcataaa 1560

atggatataa aagcctgtta atccaaccca atgccattat gtaacgccag tttggagatt 1620

tcgagggcct ggagcagtgc gcaaggtgcg ctgaaagcct gcccctggat gagatcctta 1680

tcctggctgt gatggcagtg gcagtgggct gggtcccttg ttgagtggaa agggggactg 1740

cggtgtccat ggtgcagtag gtggcgctct tctgtcttag agcctgccgc cactgcagct 1800

ggtgccaagg ggccttctgc cactagaggt gccatttttc acatgatgaa cttagcctag 1860

ttagatcgca gagcaagctg taagccatgg gcccagaaaa gaaaacttga agtgagcaga 1920

tgttgtcact tccttgtaat cctttgttaa aatagcataa ggagttttct ttattctatt 1980

tactttcatt aaatgaccgt gctacaggtt tcaaaggatt ttaagattga tttttgaaag 2040

atcacaatat taaaagtata actggaaaat ctatgttgaa atcaaccaaa catgtcgtgg 2100

actgaatgat aaccttttct ttcttcatat aggctgatca gctgaccgaa gaacagattg 2160

ctgaattcaa ggaagccttc tccctatttg ataaagatgg cgatggcacc atcacaacaa 2220

aggaacttgg aactgtc atg agg tca ctg ggt cag aac cca aca gaa gct 2270

Met Arg Ser Leu Gly Gln Asn Pro Thr Glu Ala

1 5 10

gaa ttg cag gat atg atc aat gaa gtg gat gct gat ggt aat ggc acc 2318

Glu Leu Gln Asp Met Ile Asn Glu Val Asp Ala Asp Gly Asn Gly Thr

15 20 25

att gac ttc ccc gaa ttt ttg act atg atg gct aga aaa atg aaa gat 2366

Ile Asp Phe Pro Glu Phe Leu Thr Met Met Ala Arg Lys Met Lys Asp

30 35 40

aca gat agt gaa gaa gaa atc cgt gag gca ttc cga gtc ttt gac aag 2414

Thr Asp Ser Glu Glu Glu Ile Arg Glu Ala Phe Arg Val Phe Asp Lys

45 50 55

gat ggc aat ggt tat atc agt gca gca gaa cta cgt cac gtc atg aca 2462

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

60 65 70 75

aac tta gga gaa aaa cta aca gat gaa gaa gta gat gaa atg atc aga 2510

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

80 85 90

gaa gca gat att gat gga gac gga caa gtc aac tat gaa gaa ttc gta 2558

Glu Ala Asp Ile Asp Gly Asp Gly Gln Val Asn Tyr Glu Glu Phe Val

95 100 105

cag atg atg act gca aaa tgaagaccta ctttcaactc ctttttcccc 2606

Gln Met Met Thr Ala Lys

110

cctctagaag aatcaaattg aatcttttac ttacctcttg ccaaaaaaaa aaaaaaaaaa 2666

aaaaaaaaaa aaaaaaaaaa aaaaaa 2692

<210>24

<211>113

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>24

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

1 5 10 15

Ile Asn Glu Val Asp Ala Asp Gly Asn Gly Thr Ile Asp Phe Pro Glu

20 25 30

Phe Leu Thr Met Met Ala Arg Lys Met Lys Asp Thr Asp Ser Glu Glu

35 40 45

Glu Ile Arg Glu Ala Phe Arg Val Phe Asp Lys Asp Gly Asn Gly Tyr

50 55 60

Ile Ser Ala Ala Glu Leu Arg His Val Met Thr Asn Leu Gly Glu Lys

65 70 75 80

Leu Thr Asp Glu Glu Val Asp Glu Met Ile Arg Glu Ala Asp Ile Asp

85 90 95

Gly Asp Gly Gln Val Asn Tyr Glu Glu Phe Val Gln Met Met Thr Ala

100 105 110

Lys

<210>25

<211>2769

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>25

gtcttggtct tctggcctgg cggcgatcgt cggccagttt atccctcgga gttgcactgg 60

cagacacgcc gctactttgt agcgggtttc gggcgggcca cgcgtgcggc gacaggaacc 120

caaccccggc cgaccttggg ctccaggaat tcgttgtcta cgtctgcgga ggtgcggcag 180

cctcagtttt aagcgcagga aggcaataga ggctgtgctc tgaacctttc cctcacgatg 240

atcttctgcc tgttgaccat cctggtgtct ttcccatgtg gccctgtatg gttggcatgg 300

ttcctgtctt taggacttgt gatcaagtat atctgaaagt ttttagaaga aaagatgtgt 360

tgtaacctcc ctggaaaaag aagagacctt atgaagtact gctaaccacc tacatagtca 420

tcaaaataaa attcctgaat ttgtacaagc cacaggaagc tagattgaga tcattatatg 480

acaactggaa ggccaaggct atgggttacc tcaaattgag gaattttggc acctactcac 540

aggctccatg agcagatgaa gtagacagct ttactcagta tctcagacca agaacttcat 600

ctccatctcc aactagctga aacatcttcc ctcctcaacc tggaaaattc tctgacttag 660

aaatttaaac aaaaccctcc cctttcattg aatctccatt gtctggagtt tgcttgtttt 720

aatctagcct gttcctccac tatgggctcc ctttcaaact atgccctgct tcaactaacc 780

cttactgctt ttttgacaat tctagtacaa cctcagcacc tgcttgctcc agttttccgg 840

acactatcta tcttgactaa tcagtctaat tgctggttat gtgaacatct agataatgca 900

gaacaacccg aactagtttt tgttcctgcc agtgcaagca cctggtggac ctattctgga 960

caatggatgt atgaaagggt gtggtatcca caagcagaag tacagaatca ctctacttcc 1020

tcctatcgta aagtgacttg gcactgggaa gcctccatgg aagctcaagg tctatccttt 1080

gctcaagtaa ggttattgga gggaaatttt tctctttgcg tagaaaataa aaatggcagt 1140

ggacccttcc taggtaatat acctaaacaa tactgtaatc aaatactatg gtttgattct 1200

acagatggca ccttcatgcc ctctatagat gttacaaatg aatccaggaa cgatgatgat 1260

gatacaagtg tttgcctagg cactagacaa tgttcctggt ttgcaggttg cacaaaccgg 1320

acctggaaca gctcagctgt tcccttgatt ggtctgccca atacccaaga ctacaaatgg 1380

gtagatcgaa attctggatt gacctggtca ggtaatgaca cctgtctcta tagctgccaa 1440

aaccaaacca aaggccttct gtaccagcta tttcgcaacc tattttgctc ttatggcctg 1500

acagaggcac atgggaaatg gagatgtgca gatgccagca taactaatga caaaggtcat 1560

gatggacacc ggacccccac ctggtggctc acaggttcca atctgacctt gtctgtgaac 1620

aactctggcc tctttttttt gtgcggcaat ggggtgtaca aagggtttcc acctaaatgg 1680

tctgggcgat gtggacttgg gtatcttgta ccttccctca ccagatacct caccttaaat 1740

gctagccaaa ttacaaacct gagatccttc attcataaag taacaccgca tagatgcacc 1800

caaggagaca cagacaatcc acctctgtat tgcaacccca aggacaattc aacaataagg 1860

gccctttttc caagtttggg aacttatgat ttagaaaagg caattctaaa catttccaaa 1920

gcaatggaac aggaattcag tgccactaag cagaccttgg aagcacacca atcaaaagtt 1980

agcagtttag cctctgcatc ccgaaaggat catgtcttgg atataccgac cacccaacga 2040

caaacggctt gtggaactgt tggcaaacag tgttgcctct atataaatta ttcggaagaa 2100

ataaagtcta atatacagcg tctccacgaa gcatccgaga acctgaagaa tgtaccgtta 2160

cttgattggc aaggcatatt tgcaaaagtg ggagactggt tcagatcatg gggctatgtg 2220

cttttaattg ttcttttctg cttattcatc tttgttttaa tctatgttcg tgtctttcgc 2280

aaatctcgca gatcccttaa ctcccaacct ctgaacctag ccttatctcc acagcaatca 2340

gcacagctcc ttgtcagtga aacttcatgt caagtttcaa atagggcaat gaagggacta 2400

acaacccatc aatatgacac aagtctactt tgagaatatt tgaacaaaca gcagctgcag 2460

acaaaaagcc ttagctaaac tttgatgagt aaagcaggtc ttaccgagaa ttcagctgcc 2520

aaaaccctcc tctgagtgtt cctcttataa gggcacttag cactaggacc tcccaaggta 2580

ttgtaaataa gccttatcag aactttttgt agtttcattc tgaagcctta agacacacac 2640

cataaagctg atctgtaaac ccttacccct tgctgttcag agagctactc tttgtagtgt 2700

tcttgcatgc atatataata aatgtttttt ctattgatct gttaaaaaaa aaaaaaaaaa 2760

aaaaaaaaa 2769

<210>26

<211>2769

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(742)..(2430)

<223>

<400>26

gtcttggtct tctggcctgg cggcgatcgt cggccagttt atccctcgga gttgcactgg 60

cagacacgcc gctactttgt agcgggtttc gggcgggcca cgcgtgcggc gacaggaacc 120

caaccccggc cgaccttggg ctccaggaat tcgttgtcta cgtctgcgga ggtgcggcag 180

cctcagtttt aagcgcagga aggcaataga ggctgtgctc tgaacctttc cctcacgatg 240

atcttctgcc tgttgaccat cctggtgtct ttcccatgtg gccctgtatg gttggcatgg 300

ttcctgtctt taggacttgt gatcaagtat atctgaaagt ttttagaaga aaagatgtgt 360

tgtaacctcc ctggaaaaag aagagacctt atgaagtact gctaaccacc tacatagtca 420

tcaaaataaa attcctgaat ttgtacaagc cacaggaagc tagattgaga tcattatatg 480

acaactggaa ggccaaggct atgggttacc tcaaattgag gaattttggc acctactcac 540

aggctccatg agcagatgaa gtagacagct ttactcagta tctcagacca agaacttcat 600

ctccatctcc aactagctga aacatcttcc ctcctcaacc tggaaaattc tctgacttag 660

aaatttaaac aaaaccctcc cctttcattg aatctccatt gtctggagtt tgcttgtttt 720

aatctagcct gttcctccac t atg ggc tcc ctt tca aac tat gcc ctg ctt 771

Met Gly Ser Leu Ser Asn Tyr Ala Leu Leu

1 5 10

caa cta acc ctt act gct ttt ttg aca att cta gta caa cct cag cac 819

Gln Leu Thr Leu Thr Ala Phe Leu Thr Ile Leu Val Gln Pro Gln His

15 20 25

ctg ctt gct cca gtt ttc cgg aca cta tct atc ttg act aat cag tct 867

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

30 35 40

aat tgc tgg tta tgt gaa cat cta gat aat gca gaa caa ccc gaa cta 915

Asn Cys Trp Leu Cys Glu His Leu Asp Asn Ala Glu Gln Pro Glu Leu

45 50 55

gtt ttt gtt cct gcc agt gca agc acc tgg tgg acc tat tct gga caa 963

Val Phe Val Pro Ala Ser Ala Ser Thr Trp Trp Thr Tyr Ser Gly Gln

60 65 70

tgg atg tat gaa agg gtg tgg tat cca caa gca gaa gta cag aat cac 1011

Trp Met Tyr Glu Arg Val Trp Tyr Pro Gln Ala Glu Val Gln Asn His

75 80 85 90

tct act tcc tcc tat cgt aaa gtg act tgg cac tgg gaa gcc tcc atg 1059

Ser Thr Ser Ser Tyr Arg Lys Val Thr Trp His Trp Glu Ala Ser Met

95 100 105

gaa gct caa ggt cta tcc ttt gct caa gta agg tta ttg gag gga aat 1107

Glu Ala Gln Gly Leu Ser Phe Ala Gln Val Arg Leu Leu Glu Gly Asn

110 115 120

ttt tct ctt tgc gta gaa aat aaa aat ggc agt gga ccc ttc cta ggt 1155

Phe Ser Leu Cys Val Glu Asn Lys Asn Gly Ser Gly Pro Phe Leu Gly

125 130 135

aat ata cct aaa caa tac tgt aat caa ata cta tgg ttt gat tct aca 1203

Asn Ile Pro Lys Gln Tyr Cys Asn Gln Ile Leu Trp Phe Asp Ser Thr

140 145 150

gat ggc acc ttc atg ccc tct ata gat gtt aca aat gaa tcc agg aac 1251

Asp Gly Thr Phe Met Pro Ser Ile Asp Val Thr Asn Glu Ser Arg Asn

155 160 165 170

gat gat gat gat aca agt gtt tgc cta ggc act aga caa tgt tcc tgg 1299

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

175 180 185

ttt gca ggt tgc aca aac cgg acc tgg aac agc tca gct gtt ccc ttg 1347

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

190 195 200

att ggt ctg ccc aat acc caa gac tac aaa tgg gta gat cga aat tct 1395

Ile Gly Leu Pro Asn Thr Gln Asp Tyr Lys Trp Val Asp Arg Asn Ser

205 210 215

gga ttg acc tgg tca ggt aat gac acc tgt ctc tat agc tgc caa aac 1443

Gly Leu Thr Trp Ser Gly Asn Asp Thr Cys Leu Tyr Ser Cys Gln Asn

220 225 230

caa acc aaa ggc ctt ctg tac cag cta ttt cgc aac cta ttt tgc tct 1491

Gln Thr Lys Gly Leu Leu Tyr Gln Leu Phe Arg Asn Leu Phe Cys Ser

235 240 245 250

tat ggc ctg aca gag gca cat ggg aaa tgg aga tgt gca gat gcc agc 1539

Tyr Gly Leu Thr Glu Ala His Gly Lys Trp Arg Cys Ala Asp Ala Ser

255 260 265

ata act aat gac aaa ggt cat gat gga cac cgg acc ccc acc tgg tgg 1587

Ile Thr Asn Asp Lys Gly His Asp Gly His Arg Thr Pro Thr Trp Trp

270 275 280

ctc aca ggt tcc aat ctg acc ttg tct gtg aac aac tct ggc ctc ttt 1635

Leu Thr Gly Ser Asn Leu Thr Leu Ser Val Asn Asn Ser Gly Leu Phe

285 290 295

ttt ttg tgc ggc aat ggg gtg tac aaa ggg ttt cca cct aaa tgg tct 1683

Phe Leu Cys Gly Asn Gly Val Tyr Lys Gly Phe Pro Pro Lys Trp Ser

300 305 310

ggg cga tgt gga ctt ggg tat ctt gta cct tcc ctc acc aga tac ctc 1731

Gly Arg Cys Gly Leu Gly Tyr Leu Val Pro Ser Leu Thr Arg Tyr Leu

315 320 325 330

acc tta aat gct agc caa att aca aac ctg aga tcc ttc att cat aaa 1779

Thr Leu Asn Ala Ser Gln Ile Thr Asn Leu Arg Ser Phe Ile His Lys

335 340 345

gta aca ccg cat aga tgc acc caa gga gac aca gac aat cca cct ctg 1827

Val Thr Pro His Arg Cys Thr Gln Gly Asp Thr Asp Asn Pro Pro Leu

350 355 360

tat tgc aac ccc aag gac aat tca aca ata agg gcc ctt ttt cca agt 1875

Tyr Cys Asn Pro Lys Asp Asn Ser Thr Ile Arg Ala Leu Phe Pro Ser

365 370 375

ttg gga act tat gat tta gaa aag gca att cta aac att tcc aaa gca 1923

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

380 385 390

atg gaa cag gaa ttc agt gcc act aag cag acc ttg gaa gca cac caa 1971

Met Glu Gln Glu Phe Ser Ala Thr Lys Gln Thr Leu Glu Ala His Gln

395 400 405 410

tca aaa gtt agc agt tta gcc tct gca tcc cga aag gat cat gtc ttg 2019

Ser Lys Val Ser Ser Leu Ala Ser Ala Ser Arg Lys Asp His Val Leu

415 420 425

gat ata ccg acc acc caa cga caa acg gct tgt gga act gtt ggc aaa 2067

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

430 435 440

cag tgt tgc ctc tat ata aat tat tcg gaa gaa ata aag tct aat ata 2115

Gln Cys Cys Leu Tyr Ile Asn Tyr Ser Glu Glu Ile Lys Ser Asn Ile

445 450 455

cag cgt ctc cac gaa gca tcc gag aac ctg aag aat gta ccg tta ctt 2163

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

460 465 470

gat tgg caa ggc ata ttt gca aaa gtg gga gac tgg ttc aga tca tgg 2211

Asp Trp Gln Gly Ile Phe Ala Lys Val Gly Asp Trp Phe Arg Ser Trp

475 480 485 490

ggc tat gtg ctt tta att gtt ctt ttc tgc tta ttc atc ttt gtt tta 2259

Gly Tyr Val Leu Leu Ile Val Leu Phe Cys Leu Phe Ile Phe Val Leu

495 500 505

atc tat gtt cgt gtc ttt cgc aaa tct cgc aga tcc ctt aac tcc caa 2307

Ile Tyr Val Arg Val Phe Arg Lys Ser Arg Arg Ser Leu Asn Ser Gln

510 515 520

cct ctg aac cta gcc tta tct cca cag caa tca gca cag ctc ctt gtc 2355

Pro Leu Asn Leu Ala Leu Ser Pro Gln Gln Ser Ala Gln Leu Leu Val

525 530 535

agt gaa act tca tgt caa gtt tca aat agg gca atg aag gga cta aca 2403

Ser Glu Thr Ser Cys Gln Val Ser Asn Arg Ala Met Lys Gly Leu Thr

540 545 550

acc cat caa tat gac aca agt cta ctt tgagaatatt tgaacaaaca 2450

Thr His Gln Tyr Asp Thr Ser Leu Leu

555 560

gcagctgcag acaaaaagcc ttagctaaac tttgatgagt aaagcaggtc ttaccgagaa 2510

ttcagctgcc aaaaccctcc tctgagtgtt cctcttataa gggcacttag cactaggacc 2570

tcccaaggta ttgtaaataa gccttatcag aactttttgt agtttcattc tgaagcctta 2630

agacacacac cataaagctg atctgtaaac ccttacccct tgctgttcag agagctactc 2690

tttgtagtgt tcttgcatgc atatataata aatgtttttt ctattgatct gttaaaaaaa 2750

aaaaaaaaaa aaaaaaaaa 2769

<210>27

<21l>563

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>27

Met Gly Ser Leu Ser Asn Tyr Ala Leu Leu Gln Leu Thr Leu Thr Ala

1 5 10 15

Phe Leu Thr Ile Leu Val Gln Pro Gln His Leu Leu Ala Pro Val Phe

20 25 30

Arg Thr Leu Ser Ile Leu Thr Asn Gln Ser Asn Cys Trp Leu Cys Glu

35 40 45

His Leu Asp Asn Ala Glu Gln Pro Glu Leu Val Phe Val Pro Ala Ser

50 55 60

Ala Ser Thr Trp Trp Thr Tyr Ser Gly Gln Trp Met Tyr Glu Arg Val

65 70 75 80

Trp Tyr Pro Gln Ala Glu Val Gln Asn His Ser Thr Ser Ser Tyr Arg

85 90 95

Lys Val Thr Trp His Trp Glu Ala Ser Met Glu Ala Gln Gly Leu Ser

100 105 110

Phe Ala Gln Val Arg Leu Leu Glu Gly Asn Phe Ser Leu Cys Val Glu

115 120 125

Asn Lys Asn Gly Ser Gly Pro Phe Leu Gly Asn Ile Pro Lys Gln Tyr

130 135 140

Cys Asn Gln Ile Leu Trp Phe Asp Ser Thr Asp Gly Thr Phe Met Pro

145 150 155 160

Ser Ile Asp Val Thr Asn Glu Ser Arg Asn Asp Asp Asp Asp Thr Ser

165 170 175

Val Cys Leu Gly Thr Arg Gln Cys Ser Trp Phe Ala Gly Cys Thr Asn

180 185 190

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

195 200 205

Gln Asp Tyr Lys Trp Val Asp Arg Asn Ser Gly Leu Thr Trp Ser Gly

210 215 220

Asn Asp Thr Cys Leu Tyr Ser Cys Gln Asn Gln Thr Lys Gly Leu Leu

225 230 235 240

Tyr Gln Leu Phe Arg Asn Leu Phe Cys Ser Tyr Gly Leu Thr Glu Ala

245 250 255

His Gly Lys Trp Arg Cys Ala Asp Ala Ser Ile Thr Asn Asp Lys Gly

260 265 270

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

275 280 285

Thr Leu Ser Val Asn Asn Ser Gly Leu Phe Phe Leu Cys Gly Asn Gly

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

Thr Gln Gly Asp Thr Asp Asn Pro Pro Leu Tyr Cys Asn Pro Lys Asp

355 360 365

Asn Ser Thr Ile Arg Ala Leu Phe Pro Ser Leu Gly Thr Tyr Asp Leu

370 375 380

Glu Lys Ala Ile Leu Asn Ile Ser Lys Ala Met Glu Gln Glu Phe Ser

385 390 395 400

Ala Thr Lys Gln Thr Leu Glu Ala His Gln Ser Lys Val Ser Ser Leu

405 410 415

Ala Ser Ala Ser Arg Lys Asp His Val Leu Asp Ile Pro Thr Thr Gln

420 425 430

Arg Gln Thr Ala Cys Gly Thr Val Gly Lys Gln Cys Cys Leu Tyr Ile

435 440 445

Asn Tyr Ser Glu Glu Ile Lys Ser Asn Ile Gln Arg Leu His Glu Ala

450 455 460

Ser Glu Asn Leu Lys Asn Val Pro Leu Leu Asp Trp Gln Gly Ile Phe

465 470 475 480

Ala Lys Val Gly Asp Trp Phe Arg Ser Trp Gly Tyr Val Leu Leu Ile

485 490 495

Val Leu Phe Cys Leu Phe Ile Phe Val Leu Ile Tyr Val Arg Val Phe

500 505 510

Arg Lys Ser Arg Arg Ser Leu Asn Ser Gln Pro Leu Asn Leu Ala Leu

515 520 525

Ser Pro Gln Gln Ser Ala Gln Leu Leu Val Ser Glu Thr Ser Cys Gln

530 535 540

Val Ser Asn Arg Ala Met Lys Gly Leu Thr Thr His Gln Tyr Asp Thr

545 550 555 560

Ser Leu Leu

<210>28

<211>3226

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<400>28

gggagggcag actctgggcg ccactcccgg gccggtcatg aacgggccgg cggacggcga 60

agtggactac aaaaaaaaat accggaatct gaagcggaag ctcaagttcc tcatctacga 120

gcacgagtgc ttccaggagg agctgaggaa agcgcaaagg aaattactga aggtgtcccg 180

ggacaagagt ttcctcctag accgacttct gcagtacgag aacgtggatg aagactcttc 240

ggactcagat gccactgcat catcagataa cagcgagacg gaggggacac ccaagttgtc 300

tgacacaccg gcccctaaga ggaagagaag ccctccgctg gggggcgccc cctctccctc 360

cagcctctcc ctgcctcctt caacagggtt tccccttcag gcctccgggg tcccctcccc 420

atacctgagc tcggaacggg gccaggcctg actgaggaga gcaaagccca ggacagcatc 480

ctgctgctgc ccggcccttc tgtgctcggg agccccggga gccgcactca tcaccatctc 540

ttttgttttt ccatcctcct tctgtttgca tttcttcccc caccctcacc ccggtccatt 600

ccgcctccca tctccatccc cgctcccgcc cgcagctggc ctcctcccgc taccccccat 660

tcccttctga ctacctggcc ctgcagctgc ccgagcccag tcccctgagg cccaagcggg 720

agaaacggcc ccgcctgccc cggaaactca aggtaccctg acgtgggggt gctagggagg 780

ggcaggacgg caggaggaca gtcacctgag ggaggctgaa ggcgggggcc tgtcagagaa 840

ccatgaacag ttaatttggg gacccagtca gcacttagca ctgaggggtg gatcacagaa 900

gtctcggctt acaggcttgt atggagacaa tcagggcaga accagccttg gaggacccgg 960

tgtgcagatg ccagggatcc cgccctttca tggctgcagt gtagcggggc caggctcatt 1020

ttcccagggg ggcgtgttgt gtgatgccag gtagccccag accgggtcag gattatggga 1080

tctagagtca agtcaagact gcctgttaga aaccacgtgg ccttgagcag gtctctgcta 1140

ccctctaggc ctcctaggct tggcacctat agggcgagtg gtcctactcg atgtgaccag 1200

caagcgcccc tggagcgcct cctgttacac ggcagtgcac aaagcagacc agtgcctgcc 1260

ctcacagagc tcacagtcta gcaagatagg cagaaaacac accagaaaag taggtacttg 1320

tggagaagaa cagagcgagg tccagagcat ggggacgcca gggggacgag gctgacactt 1380

agggcccagc agtctgggat gttcttgatc agagacttac aggaaatggc agcaagctgt 1440

gtggctcctg ggcagtgttt ctgtcgggca gagtctgtgt ttgggagaaa agtaagcagg 1500

gaattgggtc ccggagcagg tcagaggggg agctcatgag gtgccagtgt gcaggattcg 1560

ctgtgaatga agccttggag acagcagttc cctggcgggg cgcaggttgc aggtgtggag 1620

ggggagtgat ctaattgcat cttaacaaaa ttgcagacac tggtggtcag agaacagact 1680

gagcggtgga gtgagttggg acgggagtga ggaggccacc acggtaaacc aggccaaggg 1740

cagagggtcc agagggagct gcggacccat ttcagagaat gagcatggga gttcctggag 1800

gacctggtgt gggctgtgcg ggagagaggc caggatgcct ccagggcttt agtctgagca 1860

cgagtggagt ctccctccct ggagatggga gggctgtggg accacaggct tggaggaaaa 1920

ctgagtctgg ccgcggatgt gtcagatgcc atctggaaag gcagctagat agcggcccgt 1980

gaggggctgc gcatttggaa gccgccaggc tggcggtaga tgcaagcctt gggagagatg 2040

gggatgggct gaggggcaga gcggagtggg gaccaactgg gcggctccca gggttctgga 2100

gccagaagca gaatgagagg ccgcatttgc ggtggtctgg agtacaggat ctggagctct 2160

aatcccaact ctgccgtttt ctccgtgtga ccttggccct gtgaggcttc acctcttgag 2220

cctgagaagc agaggggagc gggagtccct gaagggccag gggagtgagg agatggaagg 2280

aagggagtcc aagcagagga aggatagctg tgaagacaga agcagtggcg gcattgtgcg 2340

gagaatgtga gtgaagggat gaaaatcgct cggcccgtgc ctggccccta gtctgtgttt 2400

tagagcgcgc gctctggctg ccgtgcggag gagctggatc tgggagaggc tgcgggcagg 2460

gagtccagtt aggaggctgg gaccgcagcc cagatggcgg tgggaccccc cgactgccct 2520

gtgggagggc cgctgacctt ccctggccgg ggttctgggg ctggggtcgg acaaaaccct 2580

taaccccctt ccacccccta agatgccccc ccccacgatc ctgagcacgg tccctcggca 2640

gatgttcagc gatgcaggta gcggggacga tgccttggat ggagacgatg acctggtgat 2700

cgacatcccg gagtgaccgt gacatcacgc catgcccacc acggccccgc ccggcgccct 2760

ccccgtgcca gcacacacga gtccagcttc ctcggaggtg tttattgatg cccagctgcc 2820

atgctccggc cactgacaca accagaaaag gcgtaaacat gcacgggtgt cccccaggag 2880

ggtggcaggg gccctgcctt caaaccccgg ccccctccag gggacagtta tttaaacgag 2940

tggccgggag catctgccac ctgctgggga ggcagagacc ctgcaatggc cacctcttta 3000

aaagggcagc tgtacagggc taggtttttt caatgaagtt tctgtattaa aggagtggct 3060

ctggataaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3120

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3180

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 3226

<210>29

<211>3226

<212>DNA

＜213〉homo sapiens (Homo sapiens)

<220>

<221>CDS

<222>(38)..(448)

<223>

<400>29

gggagggcag actctgggcg ccactcccgg gccggtc atg aac ggg ccg gcg gac 55

Met Asn Gly Pro Ala Asp

1 5

ggc gaa gtg gac tac aaa aaa aaa tac cgg aat ctg aag cgg aag ctc 103

Gly Glu Val Asp Tyr Lys Lys Lys Tyr Arg Asn Leu Lys Arg Lys Leu

10 15 20

aag ttc ctc atc tac gag cac gag tgc ttc cag gag gag ctg agg aaa 151

Lys Phe Leu Ile Tyr Glu His Glu Cys Phe Gln Glu Glu Leu Arg Lys

25 30 35

gcg caa agg aaa tta ctg aag gtg tcc cgg gac aag agt ttc ctc cta 199

Ala Gln Arg Lys Leu Leu Lys Val Ser Arg Asp Lys Ser Phe Leu Leu

40 45 50

gac cga ctt ctg cag tac gag aac gtg gat gaa gac tct tcg gac tca 247

Asp Arg Leu Leu Gln Tyr Glu Asn Val Asp Glu Asp Ser Ser Asp Ser

55 60 65 70

gat gcc act gca tca tca gat aac agc gag acg gag ggg aca ccc aag 295

Asp Ala Thr Ala Ser Ser Asp Asn Ser Glu Thr Glu Gly Thr Pro Lys

75 80 85

ttg tct gac aca ccg gcc cct aag agg aag aga agc cct ccg ctg ggg 343

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

90 95 100

ggc gcc ccc tct ccc tcc agc ctc tcc ctg cct cct tca aca ggg ttt 391

Gly Ala Pro Ser Pro Ser Ser Leu Ser Leu Pro Pro Ser Thr Gly Phe

105 110 115

ccc ctt cag gcc tcc ggg gtc ccc tcc cca tac ctg agc tcg gaa cgg 439

Pro Leu Gln Ala Ser Gly Val Pro Ser Pro Tyr Leu Ser Ser Glu Arg

120 125 130

ggc cag gcc tgactgagga gagcaaagcc caggacagca tcctgctgct 488

Gly Gln Ala

135

gcccggccct tctgtgctcg ggagccccgg gagccgcact catcaccatc tcttttgttt 548

ttccatcctc cttctgtttg catttcttcc cccaccctca ccccggtcca ttccgcctcc 608

catctccatc cccgctcccg cccgcagctg gcctcctccc gctacccccc attcccttct 668

gactacctgg ccctgcagct gcccgagccc agtcccctga ggcccaagcg ggagaaacgg 728

ccccgcctgc cccggaaact caaggtaccc tgacgtgggg gtgctaggga ggggcaggac 788

ggcaggagga cagtcacctg agggaggctg aaggcggggg cctgtcagag aaccatgaac 848

agttaatttg gggacccagt cagcacttag cactgagggg tggatcacag aagtctcggc 908

ttacaggctt gtatggagac aatcagggca gaaccagcct tggaggaccc ggtgtgcaga 968

tgccagggat cccgcccttt catggctgca gtgtagcggg gccaggctca ttttcccagg 1028

ggggcgtgtt gtgtgatgcc aggtagcccc agaccgggtc aggattatgg gatctagagt 1088

caagtcaaga ctgcctgtta gaaaccacgt ggccttgagc aggtctctgc taccctctag 1148

gcctcctagg cttggcacct atagggcgag tggtcctact cgatgtgacc agcaagcgcc 1208

cctggagcgc ctcctgttac acggcagtgc acaaagcaga ccagtgcctg ccctcacaga 1268

gctcacagtc tagcaagata ggcagaaaac acaccagaaa agtaggtact tgtggagaag 1328

aacagagcga ggtccagagc atggggacgc cagggggacg aggctgacac ttagggccca 1388

gcagtctggg atgttcttga tcagagactt acaggaaatg gcagcaagct gtgtggctcc 1448

tgggcagtgt ttctgtcggg cagagtctgt gtttgggaga aaagtaagca gggaattggg 1508

tcccggagca ggtcagaggg ggagctcatg aggtgccagt gtgcaggatt cgctgtgaat 1568

gaagccttgg agacagcagt tccctggcgg ggcgcaggtt gcaggtgtgg agggggagtg 1628

atctaattgc atcttaacaa aattgcagac actggtggtc agagaacaga ctgagcggtg 1688

gagtgagttg ggacgggagt gaggaggcca ccacggtaaa ccaggccaag ggcagagggt 1748

ccagagggag ctgcggaccc atttcagaga atgagcatgg gagttcctgg aggacctggt 1808

gtgggctgtg cgggagagag gccaggatgc ctccagggct ttagtctgag cacgagtgga 1868

gtctccctcc ctggagatgg gagggctgtg ggaccacagg cttggaggaa aactgagtct 1928

ggccgcggat gtgtcagatg ccatctggaa aggcagctag atagcggccc gtgaggggct 1988

gcgcatttgg aagccgccag gctggcggta gatgcaagcc ttgggagaga tggggatggg 2048

ctgaggggca gagcggagtg gggaccaact gggcggctcc cagggttctg gagccagaag 2108

cagaatgaga ggccgcattt gcggtggtct ggagtacagg atctggagct ctaatcccaa 2168

ctctgccgtt ttctccgtgt gaccttggcc ctgtgaggct tcacctcttg agcctgagaa 2228

gcagagggga gcgggagtcc ctgaagggcc aggggagtga ggagatggaa ggaagggagt 2288

ccaagcagag gaaggatagc tgtgaagaca gaagcagtgg cggcattgtg cggagaatgt 2348

gagtgaaggg atgaaaatcg ctcggcccgt gcctggcccc tagtctgtgt tttagagcgc 2408

gcgctctggc tgccgtgcgg aggagctgga tctgggagag gctgcgggca gggagtccag 2468

ttaggaggct gggaccgcag cccagatggc ggtgggaccc cccgactgcc ctgtgggagg 2528

gccgctgacc ttccctggcc ggggttctgg ggctggggtc ggacaaaacc cttaaccccc 2588

ttccaccccc taagatgccc ccccccacga tcctgagcac ggtccctcgg cagatgttca 2648

gcgatgcagg tagcggggac gatgccttgg atggagacga tgacctggtg atcgacatcc 2708

cggagtgacc gtgacatcac gccatgccca ccacggcccc gcccggcgcc ctccccgtgc 2768

cagcacacac gagtccagct tcctcggagg tgtttattga tgcccagctg ccatgctccg 2828

gccactgaca caaccagaaa aggcgtaaac atgcacgggt gtcccccagg agggtggcag 2888

gggccctgcc ttcaaacccc ggccccctcc aggggacagt tatttaaacg agtggccggg 2948

agcatctgcc acctgctggg gaggcagaga ccctgcaatg gccacctctt taaaagggca 3008

gctgtacagg gctaggtttt ttcaatgaag tttctgtatt aaaggagtgg ctctggataa 3068

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3128

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3188

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 3226

<210>30

<211>137

<212>PRT

＜213〉homo sapiens (Homo sapiens)

<400>30

Met Asn Gly Pro Ala Asp Gly Glu Val Asp Tyr Lys Lys Lys Tyr Arg

1 5 10 15

Asn Leu Lys Arg Lys Leu Lys Phe Leu Ile Tyr Glu His Glu Cys Phe

20 25 30

Gln Glu Glu Leu Arg Lys Ala Gln Arg Lys Leu Leu Lys Val Ser Arg

35 40 45

Asp Lys Ser Phe Leu Leu Asp Arg Leu Leu Gln Tyr Glu Asn Val Asp

50 55 60

Glu Asp Ser Ser Asp Ser Asp Ala Thr Ala Ser Ser Asp Asn Ser Glu

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

Tyr Leu Ser Ser Glu Arg Gly Gln Ala

130 135

<210>31

<211>18

<212>DNA

＜213〉primer

<400>31

ggcacctcag caaccagt 18

<210>32

<211>19

<212>DNA

＜213〉primer

<400>32

cgaaactaac taaacccga 19

<210>33

<211>21

<212>DNA

＜213〉primer

<400>33

cagtcttcgc tcactacagc c 21

<210>34

<211>20

<212>DNA

＜213〉primer

<400>34

ccaatccaaa atgaccccgt 20

<210>35

<211>21

<212>DNA

＜213〉primer

<400>35

aagatgaatc cgttgatctc g 21

<210>36

<211>20

<212>DNA

＜213〉primer

<400>36

tcgtttgaca ggtcttccct 20

<210>37

<211>20

<212>DNA

＜213〉primer

<400>37

aagccctaca gtgcagagga 20

<210>38

<211>20

<212>DNA

＜213〉primer

<400>38

gagaaccaca aagtacgacg 20

<210>39

<211>21

<212>DNA

＜213〉primer

<400>39

gaagaggagg aggaagagga g 21

<210>40

<211>20

<212>DNA

＜213〉primer

<400>40

gtggaaggga cactttgttc 20

<210>41

<211>18

<212>DNA

＜213〉primer

<400>41

ctttcagctc ggctgctc 18

<210>42

<211>21

<212>DNA

＜213〉primer

<400>42

gtacctcata tcgcagtagg g 21

<210>43

<211>18

<212>DNA

＜213〉primer

<400>43

gagggtgcgg aggacaac 18

<210>44

<211>20

<212>DNA

＜213〉primer

<400>44

caaggacggt gacatgaggt 20

<210>45

<211>18

<212>DNA

＜213〉primer

<400>45

cttgttcctg ccgctttc 18

<210>46

<211>22

<212>DNA

＜213〉primer

<400>46

tgtctactac tgacgtttta ct 22

<210>47

<211>19

<212>DNA

＜213〉primer

<400>47

atcgtcggcc agtttatcc 19

<210>48

<211>20

<212>DNA

＜213〉primer

<400>48

aatggggaac gacaagtctc 20

<210>49

<211>18

<212>DNA

＜213〉primer

<400>49

gggagggcag actctggg 18

<210>50

<211>18

<212>DNA

＜213〉primer

<400>50

agtgcggtac gggtggtg 18

Claims (5)

1. isolating polynucleotide is characterized in that, it is selected from down group:

(a) coding has the polynucleotide of the polypeptide of the function that suppresses hepatoma cell line 7721 growths, and described polypeptide has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27 or 30;

(b) with the complete complementary polynucleotide of polynucleotide (a).

2. polynucleotide as claimed in claim 1 is characterized in that, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,21,27 or 30.

3. polynucleotide as claimed in claim 1 is characterized in that, the sequence of these polynucleotide is selected from down group:

SEQ ID NO:2,5,8,11,14,17,20,23,26,29 coding region sequence or full length sequence.

4. a carrier is characterized in that, it contains the described polynucleotide of claim 1.

5. a genetically engineered host cell is characterized in that, it is a kind of host cell that is selected from down group:

(a) host cell that transforms or transduce with the described carrier of claim 4;

(b) host cell that transforms or transduce with the described polynucleotide of claim 1.