CN1483741A - Novel human protein with cancer-suppressing function and coding sequence thereof - Google Patents

Abstract

The present invention discloses a novel human protein with anticancer function, polynucleotide for coding said polypeptide and method for producing said polypeptide by means of recombination technology. Said invention also discloses the method for using said polypeptide to curing several diseases, such as various cancers. Said invention also discloses the agonist for resisting said polypeptide and its therapeutic action. Said invention also discloses the application of said polynucleotide coding said novel human protein with anticancer function.

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; 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.

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.More preferably, the sequence of these polynucleotide is selected from down group: SEQ ID NO:2,5,8,11,14 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 FP17425 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 FP17425 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 FP17469 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 FP17469 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 FP17425 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 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.

Embodiment

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

FP17425, FP17469, FP18279 and FP18798 come from ordinary method make up human fetal cDNA library; LP3587 comes from the normal hepatocytes cDNA library that makes up with ordinary method.Get fetal tissue (FP clone) or 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 1 * 10 ⁶The cDNA library of cfu/ 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 H ₂Transfection is treated in the O dissolving.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)
							?FP17425	????8	????8	????7	????23	????27	????25
?FP17469	????11	????9	????7	????23	????27	????25
							?FP18279	????9	????12	????11	????32	????35	????40
?FP18798	????0	????1	????0	????30	????24	????27
							?LP3587	????0	????1	????0	????48	????41	????50

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 N0:1,4,7,10,13).

Embodiment 2: PCR obtains full-length gene from placenta or fetus cDNA:

Get fetal tissue (FP clone) or 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 (GIBCO BRL), 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 circulation, pcr amplification is carried out in 72 ℃ of 10 ' 1 circulation, 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).

Gene specific primer

Clone's title	Special primer 1 (5 ' → 3 ')	SEQ?ID ????NO：	Special primer 2 (3 ' → 5 ')	SEQ?ID ??NO：
					FP17425	(81)AGGTGACGACAGAGGCAAAA	????16	?CAGGAAATGGGAGGGTCGG(3812)	??17
FP17469	(103)ACCTGTGCCTCCCTGACG	????18	?TCGTTGGTTAGGTTGTCGC(2626)	??19

FP18279	(33)ACGGAGCCGATGGAACCT	????20	?ATGAACCGTCCGACTCCGT(2017)	??21
					FP18798	(186)ATATCCTGTTTGCCCCAACTC	????22	?TCCACTCAGACCCCTAACCT(3450)	??23
LP3587	(86)TGACGACGGAGACCTTTGTG	????24	?CGTTATTCTCGCTTTGAGGTAG(1239)	??25

Embodiment 3:cDNA cloned sequence is analyzed

1.FP17425

A: nucleotide sequence (SEQ ID NO:1) length: 3903 bases

B: aminoacid sequence (SEQ ID NO:3) length: 508 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:2) clone number and protein name: FP17425

Start code: 101 ATG stop coding: 1625 TGA protein molecular weights: 58264.64

2.FP17469

A: nucleotide sequence (SEQ ID NO:4) length: 2675 bases

B: aminoacid sequence (SEQ ID NO:6) length: 140 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:5) clone number and protein name: FP17469

Start code: 706 ATG stop coding: 1126 TAG protein molecular weights: 15090.60

3.FP18279

A: nucleotide sequence (SEQID NO:7) length: 2164 bases

B: aminoacid sequence (SEQ ID NO:9) length: 338 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:8) clone number and protein name: FP18279

Start code: 116 ATG stop coding: 1130 TAA protein molecular weights: 38391.04

4.FP18798

A: nucleotide sequence (SEQ ID NO:10) length: 3577 bases

B: aminoacid sequence (SEQ ID NO:12) length: 325 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:11) clone number and protein name: FP18798

Start code: 2279 ATG stop coding: 3254 TGA protein molecular weights: 34966.09

5.LP3587

A: nucleotide sequence (SEQ ID NO:13) length: 1388 bases

B: aminoacid sequence (SEQ ID NO:15) length: 100 amino acid

C. Nucleotide and amino acid composite sequence (SEQ ID NO:14) clone number and protein name: LP3587

Start code: 381 ATG stop coding: 681 TAG protein molecular weights: 10434.71

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 but new people's albumen and coded sequence＜130 thereof of cancer function 024919＜160〉25＜170〉PatentIn, version, 3.1＜210〉1＜211〉3903＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜400〉1gaggctacag, cagcacatac, aggagctaga, ggcccacctt, gaggctgagg, agggtgcgcg, 60gcagaagctg, cagctggaga, aggtgacgac, agaggcaaaa, atgaagaaat, ttgaagagga, 120cctgctgctc, ctggaagacc, agaattccaa, gctgagcaag, gagcggaagc, tgctggaaga, 180tcgtctggcc, gagttctcat, cccaggcagc, tgaggaggag, gagaaggtca, agagcctcaa, 240taagctacgg, ctcaaatatg, aggccacaat, cgcagacatg, gaggaccgcc, tacggaagga, 300ggagaagggt, cgccaggagc, tggagaagct, gaagcggagg, ctggatgggg, agagctcaga, 360gctgcaggag, cagatggtgg, agcagcaaca, gcgggcagag, gagctgcggg, cccagctggg, 420ccggaaggag, gaggagctgc, aggctgccct, ggccagggca, gaagacgagg, gtggggcccg, 480ggcccagctg, ctgaaatccc, tgcgggaggc, tcaagcagcc, ctggccgagg, cccaggagga, 540cctggagtct, gagcgtgtgg, ccaggaccaa, ggcggagaag, cagcgccggg, acctgggcga, 600ggagctggag, gcgctgcggg, gcgagctgga, ggacacgctg, gactccacca, acgcacagca, 660ggagctccgg, tccaagaggg, aacaggaggt, gacggagctg, aagaagactc, tggaggagga, 720gactcgcatc, cacgaggcgg, cagtgcagga, gctgaggcag, cgccacggcc, aggccctggg, 780ggagctggcg, gagcagctgg, agcaggcccg, gaggggcaaa, ggtgcatggg, agaagacccg, 840gctggccctg, gaggccgagg, tgtccgagct, gcgggcagaa, ctgagcagcc, tgcagactgc, 900acgtcaggag, ggtgagcagc, ggaggcgccg, cctggagtta, cagctgcagg, aggtgcaggg, 960ccgggctggt, gatggggaga, gggcacgagc, ggaggctgct, gagaagctgc, agcgagccca, 1020ggctgaactg, gagaatgtgt, ctggggcgct, gaacgaggct, gagtccaaaa, ccatccgtct, 1080tagcaaggag, ctgagcagca, cagaagccca, gctgcacgat, gcccaggagc, tgctgcagga, 1140ggagaccagg, gcgaaattgg, ccttggggtc, ccgggtgcga, gccatggagg, ctgaggcagc, 1200cgggctgcgt, gagcagctgg, aggaggaggc, agctgccagg, gaacgggcgg, gccgtgaact, 1260gcagactgcc, caggcccagc, tttccgagtg, gcggcggcgc, caggaggagg, aggcaggggc, 1320actggaggca, ggggaggagg, cacggcgccg, ggcagcccgg, gaggccgagg, ccctgaccca, 1380gcgcctggca, gaaaagacag, agaccgtgga, tcggctggag, cggggccgcc, gccggctgca, 1440gcaggagctg, gacgacgcca, ccatggacct, ggagcagcag, cggcagcttg, tgagcaccct, 1500ggagaagaag, cagcgcaagt, ttgaccagct, tctggcagag, gagaaggcag, ctgtacttcg, 1560ggcagtggag, gaacgtgagc, ggccgaggca, gagggccggg, agcgtgaggc, tcgggccctg, 1620tcactgacac, gggcactgga, ggaggagcag, gaggcacgtg, aggagctgga, gcggcagaac, 1680cgggccctgc, gggctgagct, ggaggcactg, ctgagcagca, aggatgacgt, cggcaagagc, 1740gtgcatgagc, tggaacgagc, ctgccgggta, gcagaacagg, cagccaatga, tctgcgagca, 1800caggtgacag, aactggagga, tgagctgaca, gcggccgagg, atgccaagct, gcgtctggag, 1860gtgactgtgc, aggctctcaa, gactcagcat, gagcgtgacc, tgcagggccg, tgatgaggct, 1920ggtgaagaga, ggcggaggca, gctggccaag, cagctgagag, atgcagaggt, ggagcgggat, 1980gaggagcgga, agcagcgcac, tctggccgtg, gctgcccgca, agaagctgga, gggagagctg, 2040gaggagctga, aggctcagat, ggcctctgcc, ggccagggca, aggaggaggc, ggtgaagcag, 2100cttcgcaaga, tgcaggccca, gatgaaggag, ctatggcggg, aggtggagga, gacacgcacc, 2160tcccgggagg, agatcttctc, ccagaatcgg, gaaagtgaaa, agcgcctcaa, gggcctggag, 2220gctgaggtgc, tgcggctgca, ggaggaactg, gccgcctcgg, accgtgctcg, gcggcaggcc, 2280cagcaggacc, gggatgagat, ggcagatgag, gtggccaatg, gtaaccttag, caaggcagcc, 2340attctggagg, agaagcgtca, gctggagggg, cgcctggggg, cagttggagg, aagagctgga, 2400ggaggagcag, agcaactcag, agctgctcaa, tgaccgctac, cgcaagctgc, tcctgcaggt, 2460agagtcactg, accacagagc, tgtcagctga, gcgcagtttc, tcagccaagg, cagagagcgg, 2520gcggcagcag, ctggaacggc, agatccagga, gctacgggga, cgcctgggtg, aggaggatgc, 2580tggggcccgt, gcccgccaca, agatgaccat, tgctgccctt, gagtctaagt, tggcccaggc, 2640tgaggagcag, ctagagcaag, agaccagaga, gcgcatcctc, tctggaaagc, tggtgcgcag, 2700agctgagaag, cggcttaaag, aggtggtgct, ccaggtggag, gaggagcgga, gggtggctga, 2760ccagctccgg, gaccagctgg, agaagggaaa, ccttcgagtc, aagcagctga, agcggcagct, 2820ggaggaggcc, gaggaggagg, catcccgggc, tcaggccggc, cgccggaggc, tgcagcgtga, 2880gctggaagat, gtcacagagt, cggccgagtc, catgaaccgt, gaagtgacca, cactgaggaa, 2940ccggcttcga, cgcggccccc, tcaccttcac, cacccgcacg, gtgcgccagg, tcttccgact, 3000agaggagggc, gtggcatccg, acgaggaggc, agaggaagca, cagcctgggt, ctgggccatc, 3060cccggagcct, gaggggtccc, caccagccca, cccccagtga, ccctaccctg, tccccagatg, 3120cactaacaga, tggggcccag, cccccttcct, ccctggaccc, cacgggcccc, tgtcccagga, 3180accccgccct, ctgacttctt, gccctttgga, aatggtgcag, cactctggca, tttatcaccc, 3240ccacctgggt, cccctgcaac, ctcccatcaa, aggatgaccc, ctaaacacag, aggagcgggg, 3300caggcaggga, ggcaatgact, ggagctacct, tgcttgttgg, gggactgggt, acagttggca, 3360agctgtgttt, ccatcagctc, cctgtcctcc, tttcttccct, cgttattgat, ctatagacat, 3420taggaaggga, gtgagacggc, tcctccacca, tcctcagcca, gtgcaaccca, ttccctctgc, 3480ttctctctct, ctctctctct, ctccctccct, ctccttccct, accctctcac, catctttctt, 3540ggcctctctg, agggtctctc, tgtgcatctt, tttaggaatc, tcgctctcac, tctctacgta, 3600gccactctcc, ttcccccatt, tctgcgtcca, cccctgaact, cctgagcgac, agaagcccca, 3660ggcctccacc, agccttgaac, ccttgcaaag, gggcaggaca, aggggacccc, tctcactcct, 3720gctgctgccc, atgctctgcc, ctcccttctg, gttgctctga, gggttcggag, cttccctctg, 3780ggactaaagg, agtgtccttt, accctcccag, cctccaggct, ctggcagaaa, taaactccaa, 3840cccgactgga, aaaaaaaaaa, aaaaaaaaaa, aaaaaaaaaa, aaaaaaaaaa, aaaaaaaaaa, 3900aaa, 3903＜210〉2＜211〉3903＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜220〉＜221〉CDS＜222 〉, (101) .., (1624)＜223〉＜400〉2gaggctacag, cagcacatac, aggagctaga, ggcccacctt, gaggctgagg, agggtgcgcg, 60gcagaagctg, cagctggaga, aggtgacgac, agaggcaaaa, atg, aag, aaa, ttt, gaa, 115

Met?Lys?Lys?Phe?Glu

1???????????????5gag?gac?ctg?ctg?ctc?ctg?gaa?gac?cag?aat?tcc?aag?ctg?agc?aag?gag?????163Glu?Asp?Leu?Leu?Leu?Leu?Glu?Asp?Gln?Asn?Ser?Lys?Leu?Ser?Lys?Glu

10??????????????????15??????????????????20cgg?aag?ctg?ctg?gaa?gat?cgt?ctg?gcc?gag?ttc?tca?tcc?cag?gca?gct?????211Arg?Lys?Leu?Leu?Glu?Asp?Arg?Leu?Ala?Glu?Phe?Ser?Ser?Gln?Ala?Ala

25??????????????????30??????????????????35gag?gag?gag?gag?aag?gtc?aag?agc?ctc?aat?aag?cta?cgg?ctc?aaa?tat??????259Glu?Glu?Glu?Glu?Lys?Val?Lys?Ser?Leu?Asn?Lys?Leu?Arg?Leu?Lys?Tyr

40??????????????????45??????????????????50gag?gcc?aca?atc?gca?gac?atg?gag?gac?cgc?cta?cgg?aag?gag?gag?aag??????307Glu?Ala?Thr?Ile?Ala?Asp?Met?Glu?Asp?Arg?Leu?Arg?Lys?Glu?Glu?Lys

55??????????????????60??????????????????65ggt?cgc?cag?gag?ctg?gag?aag?ctg?aag?cgg?agg?ctg?gat?ggg?gag?agc??????355Gly?Arg?Gln?Glu?Leu?Glu?Lys?Leu?Lys?Arg?Arg?Leu?Asp?Gly?Glu?Ser70??????????????????75??????????????????80??????????????????85tca?gag?ctg?cag?gag?cag?atg?gtg?gag?cag?caa?cag?cgg?gca?gag?gag??????403Ser?Glu?Leu?Gln?Glu?Gln?Met?Val?Glu?Gln?Gln?Gln?Arg?Ala?Glu?Glu

90??????????????????95??????????????????100ctg?cgg?gcc?cag?ctg?ggc?cgg?aag?gag?gag?gag?ctg?cag?gct?gcc?ctg??????451Leu?Arg?Ala?Gln?Leu?Gly?Arg?Lys?Glu?Glu?Glu?Leu?Gln?Ala?Ala?Leu

105?????????????????110?????????????????115gcc?agg?gca?gaa?gac?gag?ggt?ggg?gcc?cgg?gcc?cag?ctg?ctg?aaa?tcc??????499Ala?Arg?Ala?Glu?Asp?Glu?Gly?Gly?Ala?Arg?Ala?Gln?Leu?Leu?Lys?Ser

120?????????????????125?????????????????130ctg?cgg?gag?gct?caa?gca?gcc?ctg?gcc?gag?gcc?cag?gag?gac?ctg?gag??????547Leu?Arg?Glu?Ala?Gln?Ala?Ala?Leu?Ala?Glu?Ala?Gln?Glu?Asp?Leu?Glu

135?????????????????140?????????????????145tct?gag?cgt?gtg?gcc?agg?acc?aag?gcg?gag?aag?cag?cgc?cgg?gac?ctg??????595Ser?Glu?Arg?Val?Ala?Arg?Thr?Lys?Ala?Glu?Lys?Gln?Arg?Arg?Asp?Leu150?????????????????155?????????????????160?????????????????165ggc?gag?gag?ctg?gag?gcg?ctg?cgg?ggc?gag?ctg?gag?gac?acg?ctg?gac??????643Gly?Glu?Glu?Leu?Glu?Ala?Leu?Arg?Gly?Glu?Leu?Glu?Asp?Thr?Leu?Asp

170?????????????????175?????????????????180tcc?acc?aac?gca?cag?cag?gag?ctc?cgg?tcc?aag?agg?gaa?cag?gag?gtg??????691Ser?Thr?Asn?Ala?Gln?Gln?Glu?Leu?Arg?Ser?Lys?Arg?Glu?Gln?Glu?Val

185?????????????????190?????????????????195acg?gag?ctg?aag?aag?act?ctg?gag?gag?gag?act?cgc?atc?cac?gag?gcg??????739Thr?Glu?Leu?Lys?Lys?Thr?Leu?Glu?Glu?Glu?Thr?Arg?Ile?His?Glu?Ala

200?????????????????205?????????????????210gca?gtg?cag?gag?ctg?agg?cag?cgc?cac?ggc?cag?gcc?ctg?ggg?gag?ctg??????787Ala?Val?Gln?Glu?Leu?Arg?Gln?Arg?His?Gly?Gln?Ala?Leu?Gly?Glu?Leu

215?????????????????220?????????????????225gcg?gag?cag?ctg?gag?cag?gcc?cgg?agg?ggc?aaa?ggt?gca?tgg?gag?aag??????835Ala?Glu?Gln?Leu?Glu?Gln?Ala?Arg?Arg?Gly?Lys?Gly?Ala?Trp?Glu?Lys230?????????????????235?????????????????240?????????????????245acc?cgg?ctg?gcc?ctg?gag?gcc?gag?gtg?tcc?gag?ctg?cgg?gca?gaa?ctg??????883Thr?Arg?Leu?Ala?Leu?Glu?Ala?Glu?Val?Ser?Glu?Leu?Arg?Ala?Glu?Leu

250?????????????????255?????????????????260agc?agc?ctg?cag?act?gca?cgt?cag?gag?ggt?gag?cag?cgg?agg?cgc?cgc??????931Ser?Ser?Leu?Gln?Thr?Ala?Arg?Gln?Glu?Gly?Glu?Gln?Arg?Arg?Arg?Arg

265?????????????????270?????????????275ctg?gag?tta?cag?ctg?cag?gag?gtg?cag?ggc?cgg?gct?ggt?gat?ggg?gag??????979Leu?Glu?Leu?Gln?Leu?Gln?Glu?Val?Gln?Gly?Arg?Ala?Gly?Asp?Gly?Glu

280?????????????????285?????????????????290agg?gca?cga?gcg?gag?gct?gct?gag?aag?ctg?cag?cga?gcc?cag?gct?gaa?????1027Arg?Ala?Arg?Ala?Glu?Ala?Ala?Glu?Lys?Leu?Gln?Arg?Ala?Gln?Ala?Glu

295?????????????????300?????????????????305ctg?gag?aat?gtg?tct?ggg?gcg?ctg?aac?gag?gct?gag?tcc?aaa?acc?atc?????1075Leu?Glu?Asn?Val?Ser?Gly?Ala?Leu?Asn?Glu?Ala?Glu?Ser?Lys?Thr?Ile310?????????????????315?????????????????320?????????????????325cgt?ctt?agc?aag?gag?ctg?agc?agc?aca?gaa?gcc?cag?ctg?cac?gat?gcc?????1123Arg?Leu?Ser?Lys?Glu?Leu?Ser?Ser?Thr?Glu?Ala?Gln?Leu?His?Asp?Ala

330?????????????????335?????????????????340cag?gag?ctg?ctg?cag?gag?gag?acc?agg?gcg?aaa?ttg?gcc?ttg?ggg?tcc?????1171Gln?Glu?Leu?Leu?Gln?Glu?Glu?Thr?Arg?Ala?Lys?Leu?Ala?Leu?Gly?Ser

345?????????????????350?????????????????355cgg?gtg?cga?gcc?atg?gag?gct?gag?gca?gcc?ggg?ctg?cgt?gag?cag?ctg?????1219Arg?Val?Arg?Ala?Met?Glu?Ala?Glu?Ala?Ala?Gly?Leu?Arg?Glu?Gln?Leu

360?????????????????365?????????????????370gag?gag?gag?gca?gct?gcc?agg?gaa?cgg?gcg?ggc?cgt?gaa?ctg?cag?act?????1267Glu?Glu?Glu?Ala?Ala?Ala?Arg?Glu?Arg?Ala?Gly?Arg?Glu?Leu?Gln?Thr

375?????????????????380?????????????????385gcc?cag?gcc?cag?ctt?tcc?gag?tgg?cgg?cgg?cgc?cag?gag?gag?gag?gca?????1315Ala?Gln?Ala?Gln?Leu?Ser?Glu?Trp?Arg?Arg?Arg?Gln?Glu?Glu?Glu?Ala390?????????????????395?????????????????400?????????????????405ggg?gca?ctg?gag?gca?ggg?gag?gag?gca?cgg?cgc?cgg?gca?gcc?cgg?gag?????1363Gly?Ala?Leu?Glu?Ala?Gly?Glu?Glu?Ala?Arg?Arg?Arg?Ala?Ala?Arg?Glu

410?????????????????415?????????????????420gcc?gag?gcc?ctg?acc?cag?cgc?ctg?gca?gaa?aag?aca?gag?acc?gtg?gat?????1411Ala?Glu?Ala?Leu?Thr?Gln?Arg?Leu?Ala?Glu?Lys?Thr?Glu?Thr?Val?Asp

425?????????????????430?????????????????435cgg?ctg?gag?cgg?ggc?cgc?cgc?cgg?ctg?cag?cag?gag?ctg?gac?gac?gcc?????1459Arg?Leu?Glu?Arg?Gly?Arg?Arg?Arg?Leu?Gln?Gln?Glu?Leu?Asp?Asp?Ala

440?????????????????445?????????????????450acc?atg?gac?ctg?gag?cag?cag?cgg?cag?ctt?gtg?agc?acc?ctg?gag?aag?????1507Thr?Met?Asp?Leu?Glu?Gln?Gln?Arg?Gln?Leu?Val?Ser?Thr?Leu?Glu?Lys

455?????????????????460?????????????????465aag?cag?cgc?aag?ttt?gac?cag?ctt?ctg?gca?gag?gag?aag?gca?gct?gta?????1555Lys?Gln?Arg?Lys?Phe?Asp?Gln?Leu?Leu?Ala?Glu?Glu?Lys?Ala?Ala?Val470?????????????????475?????????????????480?????????????????485ctt?cgg?gca?gtg?gag?gaa?cgt?gag?cgg?ccg?agg?cag?agg?gcc?ggg?agc?????1603Leu?Arg?Ala?Val?Glu?Glu?Arg?Glu?Arg?Pro?Arg?Gln?Arg?Ala?Gly?Ser

490?????????????????495?????????????????500gtg?agg?ctc?ggg?ccc?tgt?cac?tgacacgggc?actggaggag?gagcaggagg????????1654Val?Arg?Leu?Gly?Pro?Cys?His

505cacgtgagga, gctggagcgg, cagaaccggg, ccctgcgggc, tgagctggag, gcactgctga, 1714gcagcaagga, tgacgtcggc, aagagcgtgc, atgagctgga, acgagcctgc, cgggtagcag, 1774aacaggcagc, caatgatctg, cgagcacagg, tgacagaact, ggaggatgag, ctgacagcgg, 1834ccgaggatgc, caagctgcgt, ctggaggtga, ctgtgcaggc, tctcaagact, cagcatgagc, 1894gtgacctgca, gggccgtgat, gaggctggtg, aagagaggcg, gaggcagctg, gccaagcagc, 1954tgagagatgc, agaggtggag, cgggatgagg, agcggaagca, gcgcactctg, gccgtggctg, 2014cccgcaagaa, gctggaggga, gagctggagg, agctgaaggc, tcagatggcc, tctgccggcc, 2074agggcaagga, ggaggcggtg, aagcagcttc, gcaagatgca, ggcccagatg, aaggagctat, 2134ggcgggaggt, ggaggagaca, cgcacctccc, gggaggagat, cttctcccag, aatcgggaaa, 2194gtgaaaagcg, cctcaagggc, ctggaggctg, aggtgctgcg, gctgcaggag, gaactggccg, 2254cctcggaccg, tgctcggcgg, caggcccagc, aggaccggga, tgagatggca, gatgaggtgg, 2314ccaatggtaa, ccttagcaag, gcagccattc, tggaggagaa, gcgtcagctg, gaggggcgcc, 2374tgggggcagt, tggaggaaga, gctggaggag, gagcagagca, actcagagct, gctcaatgac, 2434cgctaccgca, agctgctcct, gcaggtagag, tcactgacca, cagagctgtc, agctgagcgc, 2494agtttctcag, ccaaggcaga, gagcgggcgg, cagcagctgg, aacggcagat, ccaggagcta, 2554cggggacgcc, tgggtgagga, ggatgctggg, gcccgtgccc, gccacaagat, gaccattgct, 2614gcccttgagt, ctaagttggc, ccaggctgag, gagcagctag, agcaagagac, cagagagcgc, 2674atcctctctg, gaaagctggt, gcgcagagct, gagaagcggc, ttaaagaggt, ggtgctccag, 2734gtggaggagg, agcggagggt, ggctgaccag, ctccgggacc, agctggagaa, gggaaacctt, 2794cgagtcaagc, agctgaagcg, gcagctggag, gaggccgagg, aggaggcatc, ccgggctcag, 2854gccggccgcc, ggaggctgca, gcgtgagctg, gaagatgtca, cagagtcggc, cgagtccatg, 2914aaccgtgaag, tgaccacact, gaggaaccgg, cttcgacgcg, gccccctcac, cttcaccacc, 2974cgcacggtgc, gccaggtctt, ccgactagag, gagggcgtgg, catccgacga, ggaggcagag, 3034gaagcacagc, ctgggtctgg, gccatccccg, gagcctgagg, ggtccccacc, agcccacccc, 3094cagtgaccct, accctgtccc, cagatgcact, aacagatggg, gcccagcccc, cttcctccct, 3154ggaccccacg, ggcccctgtc, ccaggaaccc, cgccctctga, cttcttgccc, tttggaaatg, 3214gtgcagcact, ctggcattta, tcacccccac, ctgggtcccc, tgcaacctcc, catcaaagga, 3274tgacccctaa, acacagagga, gcggggcagg, cagggaggca, atgactggag, ctaccttgct, 3334tgttggggga, ctgggtacag, ttggcaagct, gtgtttccat, cagctccctg, tcctcctttc, 3394ttccctcgtt, attgatctat, agacattagg, aagggagtga, gacggctcct, ccaccatcct, 3454cagccagtgc, aacccattcc, ctctgcttct, ctctctctct, ctctctctcc, ctccctctcc, 3514ttccctaccc, tctcaccatc, tttcttggcc, tctctgaggg, tctctctgtg, catcttttta, 3574ggaatctcgc, tctcactctc, tacgtagcca, ctctccttcc, cccatttctg, cgtccacccc, 3634tgaactcctg, agcgacagaa, gccccaggcc, tccaccagcc, ttgaaccctt, gcaaaggggc, 3694aggacaaggg, gacccctctc, actcctgctg, ctgcccatgc, tctgccctcc, cttctggttg, 3754ctctgagggt, tcggagcttc, cctctgggac, taaaggagtg, tcctttaccc, tcccagcctc, 3814caggctctgg, cagaaataaa, ctccaacccg, actggaaaaa, aaaaaaaaaa, aaaaaaaaaa, 3874aaaaaaaaaa, aaaaaaaaaa, aaaaaaaaa, 3903＜210〉3＜21l〉508＜212〉PRT＜213〉homo sapiens, (Homo, sapiens)＜400〉3Met, Lys, Lys, Phe, Glu, Glu, Asp, Leu, Leu, Leu, Leu, Glu, Asp, Gln, Asn, Ser1, 5, 10, 15Lys, Leu, Ser, Lys, Glu, Arg, Lys, Leu, Leu, Glu, Asp, Arg, Leu, Ala, Glu, Phe

20??????????????????25??????????????????30Ser?Ser?Gln?Ala?Ala?Glu?Glu?Glu?Glu?Lys?Val?Lys?Ser?Leu?Asn?Lys

35??????????????????40??????????????????45Leu?Arg?Leu?Lys?Tyr?Glu?Ala?Thr?Ile?Ala?Asp?Met?Glu?Asp?Arg?Leu

50??????????????????55??????????????????60Arg?Lys?Glu?Glu?Lys?Gly?Arg?Gln?Glu?Leu?Glu?Lys?Leu?Lys?Arg?Arg65??????????????????70??????????????????75??????????????????80Leu?Asp?Gly?Glu?Ser?Ser?Glu?Leu?Gln?Glu?Gln?Met?Val?Glu?Gln?Gln

85??????????????????90??????????????????95Gln?Arg?Ala?Glu?Glu?Leu?Arg?Ala?Gln?Leu?Gly?Arg?Lys?Glu?Glu?Glu

100?????????????????105?????????????????110Leu?Gln?Ala?Ala?Leu?Ala?Arg?Ala?Glu?Asp?Glu?Gly?Gly?Ala?Arg?Ala

115?????????????????120?????????????????125Gln?Leu?Leu?Lys?Ser?Leu?Arg?Glu?Ala?Gln?Ala?Ala?Leu?Ala?Glu?Ala

130?????????????????135?????????????????140Gln?Glu?Asp?Leu?Glu?Ser?Glu?Arg?Val?Ala?Arg?Thr?Lys?Ala?Glu?Lys145?????????????????150?????????????????155?????????????????160Gln?Arg?Arg?Asp?Leu?Gly?Glu?Glu?Leu?Glu?Ala?Leu?Arg?Gly?Glu?Leu

165?????????????????170?????????????????175Glu?Asp?Thr?Leu?Asp?Ser?Thr?Asn?Ala?Gln?Gln?Glu?Leu?Arg?Ser?Lys

180?????????????????185?????????????????190Arg?Glu?Gln?Glu?Val?Thr?Glu?Leu?Lys?Lys?Thr?Leu?Glu?Glu?Glu?Thr

195?????????????????200?????????????????205Arg?Ile?His?Glu?Ala?Ala?Val?Gln?Glu?Leu?Arg?Gln?Arg?His?Gly?Gln

210?????????????????215?????????????????220Ala?Leu?Gly?Glu?Leu?Ala?Glu?Gln?Leu?Glu?Gln?Ala?Arg?Arg?Gly?Lys225?????????????????230?????????????????235?????????????????240Gly?Ala?Trp?Glu?Lys?Thr?Arg?Leu?Ala?Leu?Glu?Ala?Glu?Val?Ser?Glu

245?????????????????250?????????????????255Leu?Arg?Ala?Glu?Leu?Ser?Ser?Leu?Gln?Thr?Ala?Arg?Gln?Glu?Gly?Glu

260?????????????????265?????????????????270Gln?Arg?Arg?Arg?Arg?Leu?Glu?Leu?Gln?Leu?Gln?Glu?Val?Gln?Gly?Arg

275?????????????????280?????????????????285Ala?Gly?Asp?Gly?Glu?Arg?Ala?Arg?Ala?Glu?Ala?Ala?Glu?Lys?Leu?Gln

290?????????????????295?????????????????300Arg?Ala?Gln?Ala?Glu?Leu?Glu?Asn?Val?Ser?Gly?Ala?Leu?Asn?Glu?Ala305?????????????????310?????????????????315?????????????????320Glu?Ser?Lys?Thr?Ile?Arg?Leu?Ser?Lys?Glu?Leu?Ser?Ser?Thr?Glu?Ala

325?????????????????330?????????????????335Gln?Leu?His?Asp?Ala?Gln?Glu?Leu?Leu?Gln?Glu?Glu?Thr?Arg?Ala?Lys

340?????????????????345?????????????????350Leu?Ala?Leu?Gly?Ser?Arg?Val?Arg?Ala?Met?Glu?Ala?Glu?Ala?Ala?Gly

355?????????????????360?????????????????365Leu?Arg?Glu?Gln?Leu?Glu?Glu?Glu?Ala?Ala?Ala?Arg?Glu?Arg?Ala?Gly

370?????????????????375?????????????????380Arg?Glu?Leu?Gln?Thr?Ala?Gln?Ala?Gln?Leu?Ser?Glu?Trp?Arg?Arg?Arg385?????????????????390?????????????????395?????????????????400Gln?Glu?Glu?Glu?Ala?Gly?Ala?Leu?Glu?Ala?Gly?Glu?Glu?Ala?Arg?Arg

405?????????????????410?????????????????415Arg?Ala?Ala?Arg?Glu?Ala?Glu?Ala?Leu?Thr?Gln?Arg?Leu?Ala?Glu?Lys

420?????????????????425?????????????????430Thr?Glu?Thr?Val?Asp?Arg?Leu?Glu?Arg?Gly?Arg?Arg?Arg?Leu?Gln?Gln

435?????????????????440?????????????????445Glu?Leu?Asp?Asp?Ala?Thr?Met?Asp?Leu?Glu?Gln?Gln?Arg?Gln?Leu?Val

450?????????????????455?????????????????460Ser?Thr?Leu?Glu?Lys?Lys?Gln?Arg?Lys?Phe?Asp?Gln?Leu?Leu?Ala?Glu465?????????????????470?????????????????475?????????????????480Glu?Lys?Ala?Ala?Val?Leu?Arg?Ala?Val?Glu?Glu?Arg?Glu?Arg?Pro?Arg

485?????????????????490?????????????????495Gln?Arg?Ala?Gly?Ser?Val?Arg?Leu?Gly?Pro?Cys?His

500, 505＜210〉4＜211〉2675＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜400〉4gtttttaatt, tttttttgtt, ttttgttttt, tgtttttttc, gagacggagt, cttgctctgt, 60cacccaggct, ggagtgcagt, ggcgcaatct, cagctcactg, caacctgtgc, ctccctgacg, 120caagcgattc, tcatgcctca, gcctcccaag, tagctgggac, tacaggcgcc, tgccaccacg, 180cctggctaat, tttagaattt, tagtagagat, gaggttttga, catgttggcc, aggctggtct, 240cgaactcctg, acctcaggtg, atccgcctac, tttggcctcc, ctaagtgctg, gcattacagg, 300cctgagccac, cacgcctggc, ctacatgatg, tgtttctgtc, ctgcctgacc, tacatggtgt, 360gtttctgccc, tgcgtattac, acacacacac, acacacatgt, gcgtgcacac, acacttctaa, 420ggacgtggcc, ccatctggct, ttgtctctcc, agttgtcctt, gccctgcccc, cctccccaga, 480ggtgctgccc, agtgctggtg, tggccacaca, tggctacatc, attgtgcagg, cagagctccc, 540tgcctgccca, gcctcagggc, tctgcacgct, cacacctaga, tcctcatctt, cctccatgtc, 600tctgcccagc, atagccccga, gcccctggaa, gctggtaccc, ctcagtgtgc, tcacacgtgg, 660caaggccgag, gtggccccag, gcaggggcca, taccaggcac, aaaccatgca, cgctggcatg, 720ggtgcgggga, tcacacgaat, gcctcctgga, aggaaagggc, tacttgtagg, aatgttactg, 780atgaggcaag, atgccaagga, cttccctgca, gggatcaaag, atcaggacac, gaccccttcc, 840tcacacaccc, acctcagacc, tgggagagga, ctgtgtgtcc, cccactgccc, catcggatgc, 900tctgggctct, gcctcaggga, actcgggttt, ggggaaatgt, ctatttcaga, agtactggag, 960tggccagtgt, ggcagtggcc, actcagggtg, ggctgggtcc, tgagacccat, ccccgacacc, 1020tctcctgctg, aaccctcagg, ctgctcccca, caccagggtg, tgactgaggg, gtacacaggc, 1080ctggatttct, ggtgtgagga, aggggctagc, acctcccctg, ttgtgtagcc, agcacaggca, 1140caatttgtgg, gtttggtgca, ggtaagtggt, gcgtgggaaa, aggacagtgt, tagaggtccc, 1200cactccgtgg, tctaggatca, tgaaaggtga, acacacaagt, acacaaatgt, gccatgccct, 1260ggcatggggc, ttatgtgtgc, acaggcaagg, cactcggtgt, gtgtgtgcgg, accccagggt, 1320cccaggtcat, gtgaagcgta, cgtgtgtgtg, cattgtatgt, gtgtgtacat, tgtgtgtgca, 1380ttgtgtgtgc, atgtggccaa, acagatgtga, cctcccagaa, cacagtaccc, ctccacctct, 1440acccgagctc, agacagccga, gctctccctt, gtcctgtgtg, tgtgtcagtg, tggccacgtg, 1500cgtaacccca, ggtgggctgt, cctgagctgg, gggcctgcct, gtcccttccc, agaacgcccc, 1560tctgcaggac, aggaagtctg, ccccaagtct, ggccacggcc, ctcctgctcc, catctcgggc, 1620tgcttgggag, acatcagagc, aggccccagc, ccccagtccc, ctcttccggc, cgcctggaca, 1680ggacccccat, tcagcccagg, tgtttccgga, agtcccacgg, ccttggggcc, acaggagaag, 1740ggttgaagcg, tggctggggc, accactcccc, ccacctggag, tggcattggg, cccacagctg, 1800cccatctctg, ggcctcaggt, ggaccagggg, atctctaagg, gtctgctgtg, ccctttctat, 1860gcgtcctcca, catcctatga, tgtgcctgct, tgttggctgc, tgtctgtgtg, cgtcctggca, 1920tgttgtctgg, aggctggtgt, cttttgcatg, ttcttggaca, aatgtgtgct, acctgcccag, 1980gcgcctgcaa, ccattgagcc, cacatgtgcc, ccacgtgtgc, cctgcgggtg, gtcccgggcc, 2040tggccagggc, tcagtgctcc, tcttccccct, cctccctgtt, cccacccctc, atgaagcaca, 2100ctgcgtgtcc, atcccatgta, cccgtgggtc, gacgcacgct, cttgccacgc, cctgagcgtg, 2160tacacatgat, gtgttctatg, cattcaccct, gccccccagc, ccgccctgca, gaggacaaga, 2220tgggtggccc, cggctccctt, tcccctaacc, gcccctgccc, gctgtgcagc, cgtgtgcgtt, 2280ggcgtgtgtt, tctgtgtcac, tggcgtgtca, cgtgatgtag, ccgtgtttgc, tgacatgagc, 2340ccctgccccc, ttctctgttt, ctccgttggt, ttctagagct, ctctccctcc, ccttctcaga, 2400ggggacagga, ctcctggggt, ctggctgggg, cccagagcca, ggccgccctc, tcctgttagc, 2460cctcagagtc, ccatttctat, tggtgaccaa, cttgcaaatg, gataaaacac, aggaaaatcc, 2520tgcccccccc, ttcctccctg, catgtcctgt, ccccagagcc, ccccacccca, ccctgggcca, 2580ggtcaggccc, tgtgggacgg, gagaaatagc, aaccaatcca, acagcgggaa, aaaaaaaaaa, 2640aaaaaaaaaa, aaaaaaaaaa, aaaaaaaaaa, aaaaa, 2675＜210〉5＜211〉2675＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜220〉＜221〉CDS＜222 〉, (706) .., (1125)＜223〉＜400〉5gtttttaatt, tttttttgtt, ttttgttttt, tgtttttttc, gagacggagt, cttgctctgt, 60cacccaggct, ggagtgcagt, ggcgcaatct, cagctcactg, caacctgtgc, ctccctgacg, 120caagcgattc, tcatgcctca, gcctcccaag, tagctgggac, tacaggcgcc, tgccaccacg, 180cctggctaat, tttagaattt, tagtagagat, gaggttttga, catgttggcc, aggctggtct, 240cgaactcctg, acctcaggtg, atccgcctac, tttggcctcc, ctaagtgctg, gcattacagg, 300cctgagccac, cacgcctggc, ctacatgatg, tgtttctgtc, ctgcctgacc, tacatggtgt, 360gtttctgccc, tgcgtattac, acacacacac, acacacatgt, gcgtgcacac, acacttctaa, 420ggacgtggcc, ccatctggct, ttgtctctcc, agttgtcctt, gccctgcccc, cctccccaga, 480ggtgctgccc, agtgctggtg, tggccacaca, tggctacatc, attgtgcagg, cagagctccc, 540tgcctgccca, gcctcagggc, tctgcacgct, cacacctaga, tcctcatctt, cctccatgtc, 600tctgcccagc, atagccccga, gcccctggaa, gctggtaccc, ctcagtgtgc, tcacacgtgg, 660caaggccgag, gtggccccag, gcaggggcca, taccaggcac, aaacc, atg, cac, gct, ggc, 717

Met?His?Ala?Gly

1atg?ggt?gcg?ggg?atc?aca?cga?atg?cct?cct?gga?agg?aaa?ggg?cta?ctt??????765Met?Gly?Ala?Gly?Ile?Thr?Arg?Met?Pro?Pro?Gly?Arg?Lys?Gly?Leu?Leu5???????????????????10??????????????????15??????????????????20gta?gga?atg?tta?ctg?atg?agg?caa?gat?gcc?aag?gac?ttc?cct?gca?ggg??????813Val?Gly?Met?Leu?Leu?Met?Arg?Gln?Asp?Ala?Lys?Asp?Phe?Pro?Ala?Gly

25??????????????????30??????????????????35atc?aaa?gat?cag?gac?acg?acc?cct?tcc?tca?cac?acc?cac?ctc?aga?cct??????861Ile?Lys?Asp?Gln?Asp?Thr?Thr?Pro?Ser?Ser?His?Thr?His?Leu?Arg?Pro

40??????????????????45??????????????????50ggg?aga?gga?ctg?tgt?gtc?ccc?cac?tgc?ccc?atc?gga?tgc?tct?ggg?ctc??????909Gly?Arg?Gly?Leu?Cys?Val?Pro?His?Cys?Pro?Ile?Gly?Cys?Ser?Gly?Leu

55??????????????????60??????????????????65tgc?ctc?agg?gaa?ctc?ggg?ttt?ggg?gaa?atg?tct?att?tca?gaa?gta?ctg??????957Cys?Leu?Arg?Glu?Leu?Gly?Phe?Gly?Glu?Met?Ser?Ile?Ser?Glu?Val?Leu

70??????????????????75??????????????????80gag?tgg?cca?gtg?tgg?cag?tgg?cca?ctc?agg?gtg?ggc?tgg?gtc?ctg?aga?????1005Glu?Trp?Pro?Val?Trp?Gln?Trp?Pro?Leu?Arg?Val?Gly?Trp?Val?Leu?Arg85??????????????????90??????????????????95??????????????????100ccc?atc?ccc?gac?acc?tct?cct?gct?gaa?ccc?tca?ggc?tgc?tcc?cca?cac?????1053Pro?Ile?Pro?Asp?Thr?Ser?Pro?Ala?Glu?Pro?Ser?Gly?Cys?Ser?Pro?His

105?????????????????110?????????????????115cag?ggt?gtg?act?gag?ggg?tac?aca?ggc?ctg?gat?ttc?tgg?tgt?gag?gaa?????1101Gln?Gly?Val?Thr?Glu?Gly?Tyr?Thr?Gly?Leu?Asp?Phe?Trp?Cys?Glu?Glu

120?????????????????125?????????????????130ggg?gct?agc?acc?tcc?cct?gtt?gtg?tagccagcac?aggcacaatt?tgtgggtttg????1155Gly?Ala?Ser?Thr?Ser?Pro?Val?Val

135, 140gtgcaggtaa, gtggtgcgtg, ggaaaaggac, agtgttagag, gtccccactc, cgtggtctag, 1215gatcatgaaa, ggtgaacaca, caagtacaca, aatgtgccat, gccctggcat, ggggcttatg, 1275tgtgcacagg, caaggcactc, ggtgtgtgtg, tgcggacccc, agggtcccag, gtcatgtgaa, 1335gcgtacgtgt, gtgtgcattg, tatgtgtgtg, tacattgtgt, gtgcattgtg, tgtgcatgtg, 1395gccaaacaga, tgtgacctcc, cagaacacag, tacccctcca, cctctacccg, agctcagaca, 1455gccgagctct, cccttgtcct, gtgtgtgtgt, cagtgtggcc, acgtgcgtaa, ccccaggtgg, 1515gctgtcctga, gctgggggcc, tgcctgtccc, ttcccagaac, gcccctctgc, aggacaggaa, 1575gtctgcccca, agtctggcca, cggccctcct, gctcccatct, cgggctgctt, gggagacatc, 1635agagcaggcc, ccagccccca, gtcccctctt, ccggccgcct, ggacaggacc, cccattcagc, 1695ccaggtgttt, ccggaagtcc, cacggccttg, gggccacagg, agaagggttg, aagcgtggct, 1755ggggcaccac, tccccccacc, tggagtggca, ttgggcccac, agctgcccat, ctctgggcct, 1815caggtggacc, aggggatctc, taagggtctg, ctgtgccctt, tctatgcgtc, ctccacatcc, 1875tatgatgtgc, ctgcttgttg, gctgctgtct, gtgtgcgtcc, tggcatgttg, tctggaggct, 1935ggtgtctttt, gcatgttctt, ggacaaatgt, gtgctacctg, cccaggcgcc, tgcaaccatt, 1995gagcccacat, gtgccccacg, tgtgccctgc, gggtggtccc, gggcctggcc, agggctcagt, 2055gctcctcttc, cccctcctcc, ctgttcccac, ccctcatgaa, gcacactgcg, tgtccatccc, 2115atgtacccgt, gggtcgacgc, acgctcttgc, cacgccctga, gcgtgtacac, atgatgtgtt, 2175ctatgcattc, accctgcccc, ccagcccgcc, ctgcagagga, caagatgggt, ggccccggct, 2235ccctttcccc, taaccgcccc, tgcccgctgt, gcagccgtgt, gcgttggcgt, gtgtttctgt, 2295gtcactggcg, tgtcacgtga, tgtagccgtg, tttgctgaca, tgagcccctg, cccccttctc, 2355tgtttctccg, ttggtttcta, gagctctctc, cctccccttc, tcagagggga, caggactcct, 2415ggggtctggc, tggggcccag, agccaggccg, ccctctcctg, ttagccctca, gagtcccatt, 2475tctattggtg, accaacttgc, aaatggataa, aacacaggaa, aatcctgccc, cccccttcct, 2535ccctgcatgt, cctgtcccca, gagcccccca, ccccaccctg, ggccaggtca, ggccctgtgg, 2595gacgggagaa, atagcaacca, atccaacagc, gggaaaaaaa, aaaaaaaaaa, aaaaaaaaaa, 2655aaaaaaaaaa, aaaaaaaaaa, 2675＜210〉6＜211〉140＜212〉PRT＜213〉homo sapiens, (Homo, sapiens)＜400〉6Met, His, Ala, Gly, Met, Gly, Ala, Gly, Ile, Thr, Arg, Met, Pro, Pro, Gly, Arg1, 5, 10, 15Lys, Gly, Leu, Leu, Val, Gly, Met, Leu, Leu, Met, Arg, Gln, Asp, Ala, Lys, Asp

20??????????????????25??????????????????30Phe?Pro?Ala?Gly?Ile?Lys?Asp?Gln?Asp?Thr?Thr?Pro?Ser?Ser?His?Thr

35??????????????????40??????????????????45His?Leu?Arg?Pro?Gly?Arg?Gly?Leu?Cys?Val?Pro?His?Cys?Pro?Ile?Gly

50??????????????????55??????????????????60Cys?Ser?Gly?Leu?Cys?Leu?Arg?Glu?Leu?Gly?Phe?Gly?Glu?Met?Ser?Ile65??????????????????70??????????????????75??????????????????80Ser?Glu?Val?Leu?Glu?Trp?Pro?Val?Trp?Gln?Trp?Pro?Leu?Arg?Val?Gly

85??????????????????90??????????????????95Trp?Val?Leu?Arg?Pro?Ile?Pro?Asp?Thr?Ser?Pro?Ala?Glu?Pro?Ser?Gly

100?????????????????105?????????????????110Cys?Ser?Pro?His?Gln?Gly?Val?Thr?Glu?Gly?Tyr?Thr?Gly?Leu?Asp?Phe

115?????????????????120?????????????????125Trp?Cys?Glu?Glu?Gly?Ala?Ser?Thr?Ser?Pro?Val?Val

130, 135, 140＜210〉7＜211〉2164＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜400〉7gcgggcccga, gcccacagag, tccatggaac, ccacggagcc, gatggaacct, acggagccca, 60tggaacctac, ggagcccatg, ggaacctacg, gagcccatgg, gaacctacgg, agcccatgga, 120accggcgcgg, agcgcgcacc, gtgggggcga, ggcgctgctg, cgggagctgg, aggtgctggt, 180gcaggacgtg, gtgaggacga, gctcctggtg, ggagcgccac, ggcgtggact, gcgccatcct, 240cgcgctcagc, ctcttcgcct, tgccggcagg, cttcctgtgc, ctgcgctggg, agaatgccct, 300ggtctttgca, tccggcatca, ccatcttggg, tgtgtgccac, tacacactca, ctgtcaaggg, 360cagccacctg, gccactcatg, gggccctcac, cgagtccaaa, cgctggagca, agatctggct, 420gcttttcttt, gtggaggtgt, gcacagcctt, cactgcagag, cacgccacgc, atgggcacgt, 480caagatgcac, catgcctaca, ccaacgtggt, gggcctgggg, gactccagca, cgtggaggct, 540gccttgcctc, aaccgctatg, tctacatgtt, ccttgctcct, ttcctcctcc, ccatcgccac, 600tccactggtg, gctgtcgagc, ggctgaggaa, ggtggagctc, gggacagccc, tgcggacgct, 660ggccctgatt, tctctgggcc, tttattctca, ctactggctg, ctcctgaacg, tgtcaggctt, 720caagaacccc, agctcagccc, tgggctgcat, gttcctcacc, agatccctgt, tggcccaccc, 780ctacctccac, gtcaacatct, tccagcacat, cggactgccc, atgttctccc, gggacaacaa, 840gccccgtcgg, attcacatga, tgagcctggg, ggtgcttaac, ctggcccggc, tgcccgtgct, 900ggactgggcg, ttcggccact, cgatcatcag, ctgccatgtg, gaacaccatc, tattccccag, 960gctctctgat, aacatgtgcc, tgaaggtgaa, gcccgtggtg, tcccagttcc, tacgtgagaa, 1020gcagctaccg, tacaacgagg, actcatacct, ggctcgcttc, cagctgtttc, tccgtcgcta, 1080tgaggaattc, atggtgcagg, ccccacccat, cactgagctt, gtggggctgt, aatgaggccg, 1140ggccggtgca, gccaccctgc, ccctccctgg, cctggccctg, gccctcctgc, tgctgctggt, 1200ccagggggtg, tggctcagtg, gctggtggtg, gacctggaga, gtggaggcac, cggccaggca, 1260ggggggcagg, ggagctcagg, cctggggtct, gggggccacc, tgccttgcgt, gcttttctgg, 1320gttttgaggg, gtgtctgggg, gaagcggtaa, tggtggctgt, gcattctggt, cagtctggac, 1380ctcagcaact, tcatctcagg, actaaagagc, tgggtccttc, cccctgctcc, atctgagcct, 1440tggtagggtt, aaagggaggt, gacagggtga, agagggatcc, tgtgcagggg, ccacctggga, 1500gatagcaggg, ggcacagaga, gagcagggtc, agctccctcg, gctgggacct, ccctggcatt, 1560gggagagccc, cacacggcct, tggctattgc, ttccttcagg, ctctgccacc, aaggtgccct, 1620ctccccgggg, accttagggt, gagcttgctt, ttggcaggcc, ttcctcgatc, ctcagccaaa, 1680ggaacctgtg, caagacactg, gctcagcagt, tccccaggcc, acagtatcag, caagataaaa, 1740gtgagtgtgt, tttgtcggga, gggaactcca, ggggaagtga, ggggagaagg, ttccccaggg, 1800acagagttag, ggaaagagta, taaatagcca, gccaggggcg, gtggctcatg, cctgtaatcc, 1860cggcactttg, ggaggccaag, gcgggtggat, cgcgagatca, ggagctcgag, accaccctgg, 1920ccaacatggt, gaaaccccgt, ctctactaaa, aatacaaaaa, attggctgga, tgtggtggca, 1980tacacttgta, gtcccagcta, cttggcaggc, tgaggcagaa, gaatcacctg, aacccgggag, 2040gtggaggttg, cagtgagcca, agattgcacc, attgcattcc, agcctgggtg, acagagcgag, 2100actccatctc, aaaaaaataa, aaaaataaaa, aataagactc, ccgttcaaaa, aaaaaaaaaa, 2160aaaa, 2164＜210〉8＜211〉2164＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜220〉＜221〉CDS＜222 〉, (116) .., (1129)＜223〉＜400〉8gcgggcccga, gcccacagag, tccatggaac, ccacggagcc, gatggaacct, acggagccca, 60tggaacctac, ggagcccatg, ggaacctacg, gagcccatgg, gaacctacgg, agccc, atg, 118

Met

1gaa?ccg?gcg?cgg?agc?gcg?cac?cgt?ggg?ggc?gag?gcg?ctg?ctg?cgg?gag?????166Glu?Pro?Ala?Arg?Ser?Ala?His?Arg?Gly?Gly?Glu?Ala?Leu?Leu?Arg?Glu

5???????????????????10??????????????????15ctg?gag?gtg?ctg?gtg?cag?gac?gtg?gtg?agg?acg?agc?tcc?tgg?tgg?gag?????214Leu?Glu?Val?Leu?Val?Gln?Asp?Val?Val?Arg?Thr?Ser?Ser?Trp?Trp?Glu

20??????????????????25??????????????????30cgc?cac?ggc?gtg?gac?tgc?gcc?atc?ctc?gcg?ctc?agc?ctc?ttc?gcc?ttg?????262Arg?His?Gly?Val?Asp?Cys?Ala?Ile?Leu?Ala?Leu?Ser?Leu?Phe?Ala?Leu

35??????????????????40??????????????????45ccg?gca?ggc?ttc?ctg?tgc?ctg?cgc?tgg?gag?aat?gcc?ctg?gtc?ttt?gca?????310Pro?Ala?Gly?Phe?Leu?Cys?Leu?Arg?Trp?Glu?Asn?Ala?Leu?Val?Phe?Ala50??????????????????55??????????????????60??????????????????65tcc?ggc?atc?acc?atc?ttg?ggt?gtg?tgc?cac?tac?aca?ctc?act?gtc?aag?????358Ser?Gly?Ile?Thr?Ile?Leu?Gly?Val?Cys?His?Tyr?Thr?Leu?Thr?Val?Lys

70??????????????????75??????????????????80ggc?agc?cac?ctg?gcc?act?cat?ggg?gcc?ctc?acc?gag?tcc?aaa?cgc?tgg??????406Gly?Ser?His?Leu?Ala?Thr?His?Gly?Ala?Leu?Thr?Glu?Ser?Lys?Arg?Trp

85??????????????????90??????????????????95agc?aag?atc?tgg?ctg?ctt?ttc?ttt?gtg?gag?gtg?tgc?aca?gcc?ttc?act??????454Ser?Lys?Ile?Trp?Leu?Leu?Phe?Phe?Val?Glu?Val?Cys?Thr?Ala?Phe?Thr

100?????????????????105?????????????????110gca?gag?cac?gcc?acg?cat?ggg?cac?gtc?aag?atg?cac?cat?gcc?tac?acc??????502Ala?Glu?His?Ala?Thr?His?Gly?His?Val?Lys?Met?His?His?Ala?Tyr?Thr

115?????????????????120?????????????????125aac?gtg?gtg?ggc?ctg?ggg?gac?tcc?agc?acg?tgg?agg?ctg?cct?tgc?ctc??????550Asn?Val?Val?Gly?Leu?Gly?Asp?Ser?Ser?Thr?Trp?Arg?Leu?Pro?Cys?Leu130?????????????????135?????????????????140?????????????????145aac?cgc?tat?gtc?tac?atg?ttc?ctt?gct?cct?ttc?ctc?ctc?ccc?atc?gcc??????598Asn?Arg?Tyr?Val?Tyr?Met?Phe?Leu?Ala?Pro?Phe?Leu?Leu?Pro?Ile?Ala

150?????????????????155?????????????????160act?cca?ctg?gtg?gct?gtc?gag?cgg?ctg?agg?aag?gtg?gag?ctc?ggg?aca??????646Thr?Pro?Leu?Val?Ala?Val?Glu?Arg?Leu?Arg?Lys?Val?Glu?Leu?Gly?Thr

165?????????????????170?????????????????175gcc?ctg?cgg?acg?ctg?gcc?ctg?att?tct?ctg?ggc?ctt?tat?tct?cac?tac??????694Ala?Leu?Arg?Thr?Leu?Ala?Leu?Ile?Ser?Leu?Gly?Leu?Tyr?Ser?His?Tyr

180?????????????????185?????????????????190tgg?ctg?ctc?ctg?aac?gtg?tca?ggc?ttc?aag?aac?ccc?agc?tca?gcc?ctg??????742Trp?Leu?Leu?Leu?Asn?Val?Ser?Gly?Phe?Lys?Asn?Pro?Ser?Ser?Ala?Leu

195?????????????????200?????????????????205ggc?tgc?atg?ttc?ctc?acc?aga?tcc?ctg?ttg?gcc?cac?ccc?tac?ctc?cac??????790Gly?Cys?Met?Phe?Leu?Thr?Arg?Ser?Leu?Leu?Ala?His?Pro?Tyr?Leu?His210?????????????????215?????????????????220?????????????????225gtc?aac?atc?ttc?cag?cac?atc?gga?ctg?ccc?atg?ttc?tcc?cgg?gac?aac??????838Val?Asn?Ile?Phe?Gln?His?Ile?Gly?Leu?Pro?Met?Phe?Ser?Arg?Asp?Asn

230?????????????????235?????????????????240aag?ccc?cgt?cgg?att?cac?atg?atg?agc?ctg?ggg?gtg?ctt?aac?ctg?gcc??????886Lys?Pro?Arg?Arg?Ile?His?Met?Met?Ser?Leu?Gly?Val?Leu?Asn?Leu?Ala

245?????????????????250?????????????????255cgg?ctg?ccc?gtg?ctg?gac?tgg?gcg?ttc?ggc?cac?tcg?atc?atc?agc?tgc??????934Arg?Leu?Pro?Val?Leu?Asp?Trp?Ala?Phe?Gly?His?Ser?Ile?Ile?Ser?Cys

260?????????????????265?????????????????????270cat?gtg?gaa?cac?cat?cta?ttc?ccc?agg?ctc?tct?gat?aac?atg?tgc?ctg??????982His?Val?Glu?His?His?Leu?Phe?Pro?Arg?Leu?Ser?Asp?Asn?Met?Cys?Leu

275?????????????????280?????????????????285aag?gtg?aag?ccc?gtg?gtg?tcc?cag?ttc?cta?cgt?gag?aag?cag?cta?ccg?????1030Lys?Val?Lys?Pro?Val?Val?Ser?Gln?Phe?Leu?Arg?Glu?Lys?Gln?Leu?Pro290?????????????????295?????????????????300?????????????????305tac?aac?gag?gac?tca?tac?ctg?gct?cgc?ttc?cag?ctg?ttt?ctc?cgt?cgc?????1078Tyr?Asn?Glu?Asp?Ser?Tyr?Leu?Ala?Arg?Phe?Gln?Leu?Phe?Leu?Arg?Arg

310?????????????????315?????????????????320tat?gag?gaa?ttc?atg?gtg?cag?gcc?cca?ccc?atc?act?gag?ctt?gtg?ggg?????1126Tyr?Glu?Glu?Phe?Met?Val?Gln?Ala?Pro?Pro?Ile?Thr?Glu?Leu?Val?Gly

325, 330, 335ctg, taatgaggcc, gggccggtgc, agccaccctg, cccctccctg, gcctggccct, 1179Leuggccctcctg, ctgctgctgg, tccagggggt, gtggctcagt, ggctggtggt, ggacctggag, 1239agtggaggca, ccggccaggc, aggggggcag, gggagctcag, gcctggggtc, tgggggccac, 1299ctgccttgcg, tgcttttctg, ggttttgagg, ggtgtctggg, ggaagcggta, atggtggctg, 1359tgcattctgg, tcagtctgga, cctcagcaac, ttcatctcag, gactaaagag, ctgggtcctt, 1419ccccctgctc, catctgagcc, ttggtagggt, taaagggagg, tgacagggtg, aagagggatc, 1479ctgtgcaggg, gccacctggg, agatagcagg, gggcacagag, agagcagggt, cagctccctc, 1539ggctgggacc, tccctggcat, tgggagagcc, ccacacggcc, ttggctattg, cttccttcag, 1599gctctgccac, caaggtgccc, tctccccggg, gaccttaggg, tgagcttgct, tttggcaggc, 1659cttcctcgat, cctcagccaa, aggaacctgt, gcaagacact, ggctcagcag, ttccccaggc, 1719cacagtatca, gcaagataaa, agtgagtgtg, ttttgtcggg, agggaactcc, aggggaagtg, 1779aggggagaag, gttccccagg, gacagagtta, gggaaagagt, ataaatagcc, agccaggggc, 1839ggtggctcat, gcctgtaatc, ccggcacttt, gggaggccaa, ggcgggtgga, tcgcgagatc, 1899aggagctcga, gaccaccctg, gccaacatgg, tgaaaccccg, tctctactaa, aaatacaaaa, 1959aattggctgg, atgtggtggc, atacacttgt, agtcccagct, acttggcagg, ctgaggcaga, 2019agaatcacct, gaacccggga, ggtggaggtt, gcagtgagcc, aagattgcac, cattgcattc, 2079cagcctgggt, gacagagcga, gactccatct, caaaaaaata, aaaaaataaa, aaataagact, 2139cccgttcaaa, aaaaaaaaaa, aaaaa, 2164＜210〉9＜21l〉338＜212〉PRT＜213〉homo sapiens, (Homo, sapiens)＜400〉9Met, Glu, Pro, Ala, Arg, Ser, Ala, His, Arg, Gly, Gly, Glu, Ala, Leu, Leu, Arg1, 5, 10, 15Glu, Leu, Glu, Val, Leu, Val, Gln, Asp, Val, Val, Arg, Thr, Ser, Ser, Trp, Trp

20??????????????????25??????????????????30Glu?Arg?His?Gly?Val?Asp?Cys?Ala?Ile?Leu?Ala?Leu?Ser?Leu?Phe?Ala

35??????????????????40??????????????????45Leu?Pro?Ala?Gly?Phe?Leu?Cys?Leu?Arg?Trp?Glu?Asn?Ala?Leu?Val?Phe

50??????????????????55??????????????????60Ala?Ser?Gly?Ile?Thr?Ile?Leu?Gly?Val?Cys?His?Tyr?Thr?Leu?Thr?Val65??????????????????70??????????????????75??????????????????80Lys?Gly?Ser?His?Leu?Ala?Thr?His?Gly?Ala?Leu?Thr?Glu?Ser?Lys?Arg

85??????????????????90??????????????????95Trp?Ser?Lys?Ile?Trp?Leu?Leu?Phe?Phe?Val?Glu?Val?Cys?Thr?Ala?Phe

100?????????????????105?????????????????110Thr?Ala?Glu?His?Ala?Thr?His?Gly?His?Val?Lys?Met?His?His?Ala?Tyr

115?????????????????120?????????????????125Thr?Asn?Val?Val?Gly?Leu?Gly?Asp?Ser?Ser?Thr?Trp?Arg?Leu?Pro?Cys

130?????????????????135?????????????????140Leu?Asn?Arg?Tyr?Val?Tyr?Met?Phe?Leu?Ala?Pro?Phe?Leu?Leu?Pro?Ile145?????????????????150?????????????????155?????????????????160Ala?Thr?Pro?Leu?Val?Ala?Val?Glu?Arg?Leu?Arg?Lys?Val?Glu?Leu?Gly

165?????????????????170?????????????????175Thr?Ala?Leu?Arg?Thr?Leu?Ala?Leu?Ile?Ser?Leu?Gly?Leu?Tyr?Ser?His

180?????????????????185?????????????????190Tyr?Trp?Leu?Leu?Leu?Asn?Val?Ser?Gly?Phe?Lys?Asn?Pro?Ser?Ser?Ala

195?????????????????200?????????????????205Leu?Gly?Cys?Met?Phe?Leu?Thr?Arg?Ser?Leu?Leu?Ala?His?Pro?Tyr?Leu

210?????????????????215?????????????????220His?Val?Asn?Ile?Phe?Gln?His?Ile?Gly?Leu?Pro?Met?Phe?Ser?Arg?Asp225?????????????????230?????????????????235?????????????????240Asn?Lys?Pro?Arg?Arg?Ile?His?Met?Met?Ser?Leu?Gly?Val?Leu?Asn?Leu

245?????????????????250?????????????????255Ala?Arg?Leu?Pro?Val?Leu?Asp?Trp?Ala?Phe?Gly?His?Ser?Ile?Ile?Ser

260?????????????????265?????????????????270Cys?His?Val?Glu?His?His?Leu?Phe?Pro?Arg?Leu?Ser?Asp?Asn?Met?Cys

275?????????????????280?????????????????285Leu?Lys?Val?Lys?Pro?Val?Val?Ser?Gln?Phe?Leu?Arg?Glu?Lys?Gln?Leu

290?????????????????295?????????????????300Pro?Tyr?Asn?Glu?Asp?Ser?Tyr?Leu?Ala?Arg?Phe?Gln?Leu?Phe?Leu?Arg305?????????????????310?????????????????315?????????????????320Arg?Tyr?Glu?Glu?Phe?Met?Val?Gln?Ala?Pro?Pro?Ile?Thr?Glu?Leu?Val

325330335 Gly Leu < 210 > 10 < 211 > 3577 <212> DNA < 213 > Homo (Homo sapiens) <400 > 10 gagatggctg gagatggtgc taaggccagg ctgatggggg tggggtgggg cagacacatg 60 gggaggggtt tccaagtttg tttcccatgg tggccacggc agcagctgcc tgatgccatc 120 ccagaggttt ctgcagaggt ggtgctcggg aggtgggaca tcagtcacac acatccagaa 180 gtaagatatc ctgtttgccc caactctcac taaccttgac cgtgctgcct ccctctctgg 240 ggctctggga ggaagaatgt tctgcagagg tttgtacatc tctgagagtc ctgcctaagc 300 ctgccagccc ttactacacc accattttcc tccagcccct acccactggg gaacagaaac 360 agagccagag aggaattgag agatggagag agaatgaggt agagacaggc ttggtgagtg 420 tttagctagg gggagtgagg gagagtgagg tgagacatgg catgacaggg agcacagaga 480 gagggagtag ccagccttag atgtaagaga gggcccctcc caatgccaga tctggcttgc 540 aggctccccc agcttttata gagcggccca aggaagaata tttccaagaa gtagggcggg 600 catggctcat cccctgctcc gcccaaggga ccctcctcct gttgtctctt ggaccaaggt 660 aaggctcctg agccgctctg cctgtaccca cgcccactac acccctgcct ctcgtgcccc 720 agccattttg tgggagggag ggtgtgggaa ggagaaggct gtcagaggca gggtggggag 780 gaactggagc tgcctggaga gatgaggggc gcctttggtg aggggtggct gcgtgtgtcc 840 tcagggctca ccagtggttc tgtaggtggg ccgggggctg caaggccagg cccaggtgga 900 cagcaacagc agcctcatcc tgcgaccatt gaccaaggag gcccacgggc actgggaatg 960 cagtgccagc aatgctgtgg cccgagtggc cacctccacg aacgtctacg tgctgggcac 1020 tagccctcat gttgtcacca atgtgtccgt ggtggctttg cccaagggtg ccaatgtctc 1080 ctgggagcct ggctttgatg gtggttatct gcagagattc agtgtctggt acaccccact 1140 ggccaagcgt cctgaccgaa tgcaccatga ctgggtgtcc ttggcagtgc ctgtgggggc 1200 tgctcacctc ctagtgccag ggctgcagcc ccacacccag taccagttca gcgtgctagc 1260 tcagaacaag ctggggagtg gtcccttcag cgaaatcgtc ttgtctgctc cggaagggct 1320 tcctaccacg ccagctgcac ccgggcttcc cccaacagag ataccgcctc ccctgtcccc 1380 tccgcggggt ctggtggcag tgaggacacc ccggggggta ctcctgcatt gggatccccc 1440 agagctggtc cctaagagac tggatggcta cgtcttggaa ggccggcaag gctcccaggg 1500 ctgggaggtg ctggacccgg ctgtggcagg cacagaaaca gagctgctgg tgccaggcct 1560 catcaaggta tgtgcgaaag gcgatacaga gagaggcctc ctaggggctc tcctgcgtcc 1620 ttctccattc cccaaactct atcttctcat cttgatttga gctcttcacc tctgcgtcct 1680 acctcaccct tccgtcccac gtgcacggtc tttccgcgcc ccgctgggtt gggcggtgct 1740 gggccctgac ctccctcctg gtaccccatc cccatcgcag gatgttctct acgagttccg 1800 cctcgtggcc ttcgcgggca gcttcgtcag cgaccccagc aacacggcca acgtctccac 1860 ttccggtctg gaggtctacc cttcgcgcac gcagctgccg ggcctcctgc ctcagcccgt 1920 gctggccggc gtggtgggcg gagtctgctt tctgggagtg gccgtccttg tgagcatcct 1980 ggccggctgc ctcctgaacc ggcgcagggc tgcccgccgc cgccgcaagc gcctccgcca 2040 agatccacct cttatcttct ctccgaccgg gaagtcagct gcaccctctg ctctgggctc 2100 aggcagtcct gacagcgtgg cgaagctgaa gctccaggga tccccagtcc ccagcctgcg 2160 ccagagtctg ctctgggggg atcctgccgg aactcccagc ccccacccgg atcctccatc 2220 tagccgggga cccttacctc tggagcccat ttgccggggc ccagacgggc gctttgtgat 2280 ggggcccact gtggcggccc cccaggaaag gtcaggccgg gagcaggcag aacctcggac 2340 tccagcccag cgtctggccc ggtcctttga ctgtagcagc agcagcccca gtggggcacc 2400 ccagcccctc tgcattgaag acatcagccc tgtggcaccc cctccagcag ccccacccag 2460 tcccttgcca ggtcctggac ccctgctcca gtacctgagc ctgcccttct tccgagagat 2520 gaatgtggat ggggactggc ccccgcttga ggagcccagc cctgctgcac ccccagatta 2580 catggatacc cggcgctgtc ccacctcatc tttccttcgt tctccagaaa cccctcctgt 2640 atcccccagg gaatcacttc ctggggctgt ggtaggggct ggggccactg cagagccccc 2700 ttacacagcc ctggctgact ggacactgag ggagcggctg ctgccaggcc ttctccctgc 2760 tgcccctcga ggcagcctca ccagccagag cagtgggcga ggcagcgctt cgttcctgcg 2820 gcccccctcc acagccccct ctgcaggagg cagctacctc agccctgctc caggagacac 2880 cagcagctgg gccagtggcc ctgagagatg gccccgaagg gagcatgtgg tgacagtcag 2940 caagaggagg aacacatctg tggacgagaa ctatgagtgg gactcagaat tccctgggga 3000 catggaattg ctggagactt tgcacctggg cttggccagc tcccggctca gacctgaagc 3060 tgagccagag ctaggtgtga agactccaga ggagggctgc ctcctgaaca ctgcccatgt 3120 tactggccct gaggcccgct gtgctgccct tcgggaggaa ttcctggcct tccgccgccg 3180 ccgagatgct actagggctc ggctaccagc ctatcgacag ccagtccccc accccgaaca 3240 ggccactctg ctgtgaacat ccctgatgtg aggctgtgaa aaggcatatg gacctgcaaa 3300 ggaggccccc aaccagacag acctagtttc aaacgagggc actgcccctg cctgcccctt 3360 tggtgcccag gcacagaccc tgatagtggg tttgggtcac cttggtatgg aatgtatgtg 3420 ctgaccccct aggtgagtct ggggattgga acagggatct taggtctgcc tctctctctc 3480 tctctctctc tctctctctc tctgtgtgtg tgtgtgtgtg tgtgaagttt tttacaggtg 3540 aataaacaaa gtttgaaaga aaaaaaaaaa aaaaaaa 3577 < 210 > 11 < 211 > 3577 <212> DNA < 213 > Homo (Homo sapiens) < 220 > <221> CDS < 222 > ( 2279 ) .. ( 3253 ) < 223 > < 400> 11 gagatggctg gagatggtgc taaggccagg ctgatggggg tggggtgggg cagacacatg 60 gggaggggtt tccaagtttg tttcccatgg tggccacggc agcagctgcc tgatgccatc 120 ccagaggttt ctgcagaggt ggtgctcggg aggtgggaca tcagtcacac acatccagaa 180 gtaagatatc ctgtttgccc caactctcac taaccttgac cgtgctgcct ccctctctgg 240 ggctctggga ggaagaatgt tctgcagagg tttgtacatc tctgagagtc ctgcctaagc 300 ctgccagccc ttactacacc accattttcc tccagcccct acccactggg gaacagaaac 360 agagccagag aggaattgag agatggagag agaatgaggt agagacaggc ttggtgagtg 420 tttagctagg gggagtgagg gagagtgagg tgagacatgg catgacaggg agcacagaga 480 gagggagtag ccagccttag atgtaagaga gggcccctcc caatgccaga tctggcttgc 540 aggctccccc agcttttata gagcggccca aggaagaata tttccaagaa gtagggcggg 600 catggctcat cccctgctcc gcccaaggga ccctcctcct gttgtctctt ggaccaaggt 660 aaggctcctg agccgctctg cctgtaccca cgcccactac acccctgcct ctcgtgcccc 720 agccattttg tgggagggag ggtgtgggaa ggagaaggct gtcagaggca gggtggggag 780 gaactggagc tgcctggaga gatgaggggc gcctttggtg aggggtggct gcgtgtgtcc 840 tcagggctca ccagtggttc tgtaggtggg ccgggggctg caaggccagg cccaggtgga 900 cagcaacagc agcctcatcc tgcgaccatt gaccaaggag gcccacgggc actgggaatg 960 cagtgccagc aatgctgtgg cccgagtggc cacctccacg aacgtctacg tgctgggcac 1020 tagccctcat gttgtcacca atgtgtccgt ggtggctttg cccaagggtg ccaatgtctc 1080 ctgggagcct ggctttgatg gtggttatct gcagagattc agtgtctggt acaccccact 1140 ggccaagcgt cctgaccgaa tgcaccatga ctgggtgtcc ttggcagtgc ctgtgggggc 1200 tgctcacctc ctagtgccag ggctgcagcc ccacacccag taccagttca gcgtgctagc 1260 tcagaacaag ctggggagtg gtcccttcag cgaaatcgtc ttgtctgctc cggaagggct 1320 tcctaccacg ccagctgcac ccgggcttcc cccaacagag ataccgcctc ccctgtcccc 1380 tccgcggggt ctggtggcag tgaggacacc ccggggggta ctcctgcatt gggatccccc 1440 agagctggtc cctaagagac tggatggcta cgtcttggaa ggccggcaag gctcccaggg 1500 ctgggaggtg ctggacccgg ctgtggcagg cacagaaaca gagctgctgg tgccaggcct 1560 catcaaggta tgtgcgaaag gcgatacaga gagaggcctc ctaggggctc tcctgcgtcc 1620 ttctccattc cccaaactct atcttctcat cttgatttga gctcttcacc tctgcgtcct 1680 acctcaccct tccgtcccac gtgcacggtc tttccgcgcc ccgctgggtt gggcggtgct 1740 gggccctgac ctccctcctg gtaccccatc cccatcgcag gatgttctct acgagttccg 1800 cctcgtggcc ttcgcgggca gcttcgtcag cgaccccagc aacacggcca acgtctccac 1860 ttccggtctg gaggtctacc cttcgcgcac gcagctgccg ggcctcctgc ctcagcccgt 1920 gctggccggc gtggtgggcg gagtctgctt tctgggagtg gccgtccttg tgagcatcct 1980 ggccggctgc ctcctgaacc ggcgcagggc tgcccgccgc cgccgcaagc gcctccgcca 2040 agatccacct cttatcttct ctccgaccgg gaagtcagct gcaccctctg ctctgggctc 2100 aggcagtcct gacagcgtgg cgaagctgaa gctccaggga tccccagtcc ccagcctgcg 2160 ccagagtctg ctctgggggg atcctgccgg aactcccagc ccccacccgg atcctccatc 2220 tagccgggga cccttacctc tggagcccat ttgccggggc ccagacgggc gctttgtg 2278 atg ggg ccc act gtg gcg gcc ccc cag gaa agg tca ggc cgg gag cag 2326 Met Gly Pro Thr Val Ala Ala Pro Gln Glu Arg Ser Gly Arg Glu Gln 151015 gca gaa cct cgg act cca gcc cag cgt ctg gcc cgg tcc ttt gac tgt 2374 Ala Glu Pro Arg Thr Pro Ala Gln Arg Leu Ala Arg Ser Phe Asp Cys

20??????????????????25??????????????????30agc?agc?agc?agc?ccc?agt?ggg?gca?ccc?cag?ccc?ctc?tgc?att?gaa?gac?????2422Ser?Ser?Ser?Ser?Pro?Ser?Gly?Ala?Pro?Gln?Pro?Leu?Cys?Ile?Glu?Asp

35??????????????????40??????????????????45atc?agc?cct?gtg?gca?ccc?cct?cca?gca?gcc?cca?ccc?agt?ccc?ttg?cca?????2470Ile?Ser?Pro?Val?Ala?Pro?Pro?Pro?Ala?Ala?Pro?Pro?Ser?Pro?Leu?Pro

50??????????????????55??????????????????60ggt?cct?gga?ccc?ctg?ctc?cag?tac?ctg?agc?ctg?ccc?ttc?ttc?cga?gag?????2518Gly?Pro?Gly?Pro?Leu?Leu?Gln?Tyr?Leu?Ser?Leu?Pro?Phe?Phe?Arg?Glu65??????????????????70??????????????????75??????????????????80atg?aat?gtg?gat?ggg?gac?tgg?ccc?ccg?ctt?gag?gag?ccc?agc?cct?gct?????2566Met?Asn?Val?Asp?Gly?Asp?Trp?Pro?Pro?Leu?Glu?Glu?Pro?Ser?Pro?Ala

85??????????????????90??????????????????95gca?ccc?cca?gat?tac?atg?gat?acc?cgg?cgc?tgt?ccc?acc?tca?tct?ttc?????2614Ala?Pro?Pro?Asp?Tyr?Met?Asp?Thr?Arg?Arg?Cys?Pro?Thr?Ser?Ser?Phe

100?????????????????105?????????????????110ctt?cgt?tct?cca?gaa?acc?cct?cct?gta?tcc?ccc?agg?gaa?tca?ctt?cct?????2662Leu?Arg?Ser?Pro?Glu?Thr?Pro?Pro?Val?Ser?Pro?Arg?Glu?Ser?Leu?Pro

115?????????????120?????????????????????125ggg?gct?gtg?gta?ggg?gct?ggg?gcc?act?gca?gag?ccc?cct?tac?aca?gcc?????2710Gly?Ala?Val?Val?Gly?Ala?Gly?Ala?Thr?Ala?Glu?Pro?Pro?Tyr?Thr?Ala

130?????????????????135?????????????????140ctg?gct?gac?tgg?aca?ctg?agg?gag?cgg?ctg?ctg?cca?ggc?ctt?ctc?cct?????2758Leu?Ala?Asp?Trp?Thr?Leu?Arg?Glu?Arg?Leu?Leu?Pro?Gly?Leu?Leu?Pro145?????????????????150?????????????????155?????????????????160gct?gcc?cct?cga?ggc?agc?ctc?acc?agc?cag?agc?agt?ggg?cga?ggc?agc????2806Ala?Ala?Pro?Arg?Gly?Ser?Leu?Thr?Ser?Gln?Ser?Ser?Gly?Arg?Gly?Ser

165?????????????????170?????????????????175gct?tcg?ttc?ctg?cgg?ccc?ccc?tcc?aca?gcc?ccc?tct?gca?gga?ggc?agc????2854Ala?Ser?Phe?Leu?Arg?Pro?Pro?Ser?Thr?Ala?Pro?Ser?Ala?Gly?Gly?Ser

180?????????????????185?????????????????190tac?ctc?agc?cct?gct?cca?gga?gac?acc?agc?agc?tgg?gcc?agt?ggc?cot????2902Tyr?Leu?Ser?Pro?Ala?Pro?Gly?Asp?Thr?Ser?Ser?Trp?Ala?Ser?Gly?Pro

195?????????????????200?????????????????205gag?aga?tgg?ccc?cga?agg?gag?cat?gtg?gtg?aca?gtc?agc?aag?agg?agg????2950Glu?Arg?Trp?Pro?Arg?Arg?Glu?His?Val?Val?Thr?Val?Ser?Lys?Arg?Arg

210?????????????????215?????????????????220aac?aca?tct?gtg?gac?gag?aac?tat?gag?tgg?gac?tca?gaa?ttc?cct?ggg????2998Asn?Thr?Ser?Val?Asp?Glu?Asn?Tyr?Glu?Trp?Asp?Ser?Glu?Phe?Pro?Gly225?????????????????230?????????????????235?????????????????240gac?atg?gaa?ttg?ctg?gag?act?ttg?cac?ctg?ggc?ttg?gcc?agc?tcc?cgg????3046Asp?Met?Glu?Leu?Leu?Glu?Thr?Leu?His?Leu?Gly?Leu?Ala?Ser?Ser?Arg

245?????????????????250?????????????????255ctc?aga?cct?gaa?gct?gag?cca?gag?cta?ggt?gtg?aag?act?cca?gag?gag????3094Leu?Arg?Pro?Glu?Ala?Glu?Pro?Glu?Leu?Gly?Val?Lys?Thr?Pro?Glu?Glu

260?????????????????265?????????????????270ggc?tgc?ctc?ctg?aac?act?gcc?cat?gtt?act?ggc?cct?gag?gcc?cgc?tgt????3142Gly?Cys?Leu?Leu?Asn?Thr?Ala?His?Val?Thr?Gly?Pro?Glu?Ala?Arg?Cys

275?????????????????280?????????????????285gct?gcc?ctt?cgg?gag?gaa?ttc?ctg?gcc?ttc?cgc?cgc?cgc?cga?gat?gct????3190Ala?Ala?Leu?Arg?Glu?Glu?Phe?Leu?Ala?Phe?Arg?Arg?Arg?Arg?Asp?Ala

290?????????????????295?????????????????300act?agg?gct?cgg?cta?cca?gcc?tat?cga?cag?cca?gtc?ccc?cac?ccc?gaa????3238Thr?Arg?Ala?Arg?Leu?Pro?Ala?Tyr?Arg?Gln?Pro?Val?Pro?His?Pro?Glu305?????????????????310?????????????????315?????????????????320cag?gcc?act?ctg?ctg?tgaacatccc?tgatgtgagg?ctgtgaaaag?gcatatggac????3293Gln?Ala?Thr?Leu?Leu

325ctgcaaagga ggcccccaac cagacagacc tagtttcaaa cgagggcact gcccctgcct 3353gcccctttgg tgcccaggca cagaccctga tagtgggttt gggtcacctt ggtatggaat 3413gtatgtgctg accccctagg tgagtctggg gattggaaca gggatcttag gtctgcctct 3473ctctctctct ctctctctct ctctctctct gtgtgtgtgt gtgtgtgtgt gaagtttttt 3533acaggtgaat aaacaaagtt tgaaagaaaa aaaaaaaaaa aaaa 3577 <210> 12 <211> 325 <212> PRT <213> Homo (Homo sapiens ) <400> 12Met Gly Pro Thr Val Ala Ala Pro Gln Glu Arg Ser Gly Arg Glu Gln1 5 10 15Ala Glu Pro Arg Thr Pro Ala Gln Arg Leu Ala Arg Ser Phe Asp Cys

20??????????????????25??????????????????30Ser?Ser?Ser?Ser?Pro?Ser?Gly?Ala?Pro?Gln?Pro?Leu?Cys?Ile?Glu?Asp

35??????????????????40??????????????????45Ile?Ser?Pro?Val?Ala?Pro?Pro?Pro?Ala?Ala?Pro?Pro?Ser?Pro?Leu?Pro

50??????????????????55??????????????????60Gly?Pro?Gly?Pro?Leu?Leu?Gln?Tyr?Leu?Ser?Leu?Pro?Phe?Phe?Arg?Glu65??????????????????70??????????????????75??????????????????80Met?Asn?Val?Asp?Gly?Asp?Trp?Pro?Pro?Leu?Glu?Glu?Pro?Ser?Pro?Ala

85??????????????????90??????????????????95Ala?Pro?Pro?Asp?Tyr?Met?Asp?Thr?Arg?Arg?Cys?Pro?Thr?Ser?Ser?Phe

100?????????????????105?????????????????110Leu?Arg?Ser?Pro?Glu?Thr?Pro?Pro?Val?Ser?Pro?Arg?Glu?Ser?Leu?Pro

115?????????????????120?????????????????125Gly?Ala?Val?Val?Gly?Ala?Gly?Ala?Thr?Ala?Glu?Pro?Pro?Tyr?Thr?Ala

130?????????????????135?????????????????140Leu?Ala?Asp?Trp?Thr?Leu?Arg?Glu?Arg?Leu?Leu?Pro?Gly?Leu?Leu?Pro145?????????????????150?????????????????155?????????????????160Ala?Ala?Pro?Arg?Gly?Ser?Leu?Thr?Ser?Gln?Ser?Ser?Gly?Arg?Gly?Ser

165?????????????????170?????????????????175Ala?Ser?Phe?Leu?Arg?Pro?Pro?Ser?Thr?Ala?Pro?Ser?Ala?Gly?Gly?Ser

180?????????????????185?????????????????190Tyr?Leu?Ser?Pro?Ala?Pro?Gly?Asp?Thr?Ser?Ser?Trp?Ala?Ser?Gly?Pro

195?????????????????200?????????????????205Glu?Arg?Trp?Pro?Arg?Arg?Glu?His?Val?Val?Thr?Val?Ser?Lys?Arg?Arg

210?????????????????215?????????????????220Asn?Thr?Ser?Val?Asp?Glu?Asn?Tyr?Glu?Trp?Asp?Ser?Glu?Phe?Pro?Gly225?????????????????230?????????????????235?????????????????240Asp?Met?Glu?Leu?Leu?Glu?Thr?Leu?His?Leu?Gly?Leu?Ala?Ser?Ser?Arg

245?????????????????250?????????????????255Leu?Arg?Pro?Glu?Ala?Glu?Pro?Glu?Leu?Gly?Val?Lys?Thr?Pro?Glu?Glu

260?????????????????265?????????????????270Gly?Cys?Leu?Leu?Asn?Thr?Ala?His?Val?Thr?Gly?Pro?Glu?Ala?Arg?Cys

275?????????????????280?????????????????285Ala?Ala?Leu?Arg?Glu?Glu?Phe?Leu?Ala?Phe?Arg?Arg?Arg?Arg?Asp?Ala

290?????????????????295?????????????????300Thr?Arg?Ala?Arg?Leu?Pro?Ala?Tyr?Arg?Gln?Pro?Val?Pro?His?Pro?Glu305?????????????????310?????????????????315?????????????????320Gln?Ala?Thr?Leu?Leu

325＜210〉13＜211〉1388＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜400〉13gagcctgtgg, ctccccctgc, gggctgctca, gcggcgtgca, cagtcctgcc, ggctggcttg, 60gtggggtgcc, gaggctcagg, cagcatgacg, acggagacct, ttgtgaagga, tatcaagcct, 120ggctcaagaa, tctgaacctt, atcttcattg, tgctggagac, aggccgagtg, accaagacaa, 180aggacgggca, tgaggttcgg, acctgcaaag, tggcggacaa, aacaggcagc, atcaatatct, 240ctgtctggga, cgatgttggc, aatctgatcc, agcctgggga, cattatccgg, ctcaccaaag, 300ggtacgcttc, agttttcaaa, ggttgtctga, cactatatac, tggccgtggg, ggtgatctgc, 360agaagattgg, agaattctgt, atggtttatt, ctgaggttcc, taacttcagt, gagccaaacc, 420cagagtacag, cacccagcag, gcacccaaca, aggcggtgca, gaacgacagc, aacccttcag, 480cttcccagcc, taccactgga, ccctctgctg, cctctccagc, ctctgagaac, cagaatggga, 540atggactgag, tgccccacca, ggtcccggtg, gtggcccaca, tcccccctca, tactccctcc, 600cacccaccca, gcacccgaat, cactcgaagc, cagcccaacc, acacacctgc, aggcccgcct, 660ggcccttcca, gcaaccctgt, tagtaacggc, aaagaaaccc, ggaggagcag, caagagatag, 720catgacattc, tttcttcctg, ccaccaacca, catcccaagt, gtcccctgga, gagcaagata, 780gccttccact, gattggctgg, tgtagcagta, ttttagccac, tgaacttcag, tggagggtgg, 840tgagcagtgt, ccttatccac, cctaatctca, tactccctca, ttgtccagct, gaactacctg, 900tcccctggga, gtcaggaccc, tctgcctgct, ctctttcctc, tttagaaatg, gcagttactg, 960gctgggcgca, gtggctcacg, cttgtaatcc, cagcactttg, ggaagccgag, gtgggcggat, 1020cacctgaggt, cgggagttca, agaccagcct, gaccaacatg, gagaaacccc, gtgtctacta, 1080aaaatacaga, attagccagg, catggtggcg, tatgcctgta, atcccagcta, cttaggaggc, 1140tgaggcagga, gaatctcttg, aaaccgggag, gcggaggttg, aggtgagccg, aaattgcacc, 1200attgcactcc, agcctgggca, ataagagcga, aactccatct, caaaaaaaaa, gaaagaaaga, 1260aagaaagaaa, gaaagaaatg, gcagttacca, tctgtttctt, ctgtgtgaga, catgggagtc, 1320taactgaagt, ctctccttcc, taataaatgt, taccactctt, aaaaaaaaaa, aaaaaaaaaa, 1380aaaaaaaa, 1388＜210〉14＜211〉1388＜212〉DNA＜213〉homo sapiens, (Homo, sapiens)＜220〉＜221〉CDS＜222 〉, (381) .., (680)＜223〉＜400〉14gagcctgtgg, ctccccctgc, gggctgctca, gcggcgtgca, cagtcctgcc, ggctggcttg, 60gtggggtgcc, gaggctcagg, cagcatgacg, acggagacct, ttgtgaagga, tatcaagcct, 120ggctcaagaa, tctgaacctt, atcttcattg, tgctggagac, aggccgagtg, accaagacaa, 180aggacgggca, tgaggttcgg, acctgcaaag, tggcggacaa, aacaggcagc, atcaatatct, 240ctgtctggga, cgatgttggc, aatctgatcc, agcctgggga, cattatccgg, ctcaccaaag, 300ggtacgcttc, agttttcaaa, ggttgtctga, cactatatac, tggccgtggg, ggtgatctgc, 360agaagattgg, agaattctgt, atg, gtt, tat, tct, gag, gtt, cct, aac, ttc, agt, gag, 413

Met?Val?Tyr?Ser?Glu?Val?Pro?Asn?Phe?Ser?Glu

1???????????????5???????????????????10cca?aac?cca?gag?tac?agc?acc?cag?cag?gca?ccc?aac?aag?gcg?gtg?cag??????461Pro?Asn?Pro?Glu?Tyr?Ser?Thr?Gln?Gln?Ala?Pro?Asn?Lys?Ala?Val?Gln

15??????????????????20??????????????????25aac?gac?agc?aac?cct?tca?gct?tcc?cag?cct?acc?act?gga?ccc?tct?gct??????509Asn?Asp?Ser?Asn?Pro?Ser?Ala?Ser?Gln?Pro?Thr?Thr?Gly?Pro?Ser?Ala

30??????????????????35??????????????????40gcc?tct?cca?gcc?tct?gag?aac?cag?aat?ggg?aat?gga?ctg?agt?gcc?cca??????557Ala?Ser?Pro?Ala?Ser?Glu?Asn?Gln?Asn?Gly?Asn?Gly?Leu?Ser?Ala?Pro

45??????????????????50??????????????????55cca?ggt?ccc?ggt?ggt?ggc?cca?cat?ccc?ccc?tca?tac?tcc?ctc?cca?ccc??????605Pro?Gly?Pro?Gly?Gly?Gly?Pro?His?Pro?Pro?Ser?Tyr?Ser?Leu?Pro?Pro60??????????????????65??????????????????70??????????????????75acc?cag?cac?ccg?aat?cac?tcg?aag?cca?gcc?caa?cca?cac?acc?tgc?agg??????653Thr?Gln?His?Pro?Asn?His?Ser?Lys?Pro?Ala?Gln?Pro?His?Thr?Cys?Arg

80??????????????????85??????????????????90ccc?gcc?tgg?ccc?ttc?cag?caa?ccc?tgt?tagtaacggc?aaagaaaccc????????????700Pro?Ala?Trp?Pro?Phe?Gln?Gln?Pro?Cys

95, 100ggaggagcag, caagagatag, catgacattc, tttcttcctg, ccaccaacca, catcccaagt, 760gtcccctgga, gagcaagata, gccttccact, gattggctgg, tgtagcagta, ttttagccac, 820tgaacttcag, tggagggtgg, tgagcagtgt, ccttatccac, cctaatctca, tactccctca, 880ttgtccagct, gaactacctg, tcccctggga, gtcaggaccc, tctgcctgct, ctctttcctc, 940tttagaaatg, gcagttactg, gctgggcgca, gtggctcacg, cttgtaatcc, cagcactttg, 1000ggaagccgag, gtgggcggat, cacctgaggt, cgggagttca, agaccagcct, gaccaacatg, 1060gagaaacccc, gtgtctacta, aaaatacaga, attagccagg, catggtggcg, tatgcctgta, 1120atcccagcta, cttaggaggc, tgaggcagga, gaatctcttg, aaaccgggag, gcggaggttg, 1180aggtgagccg, aaattgcacc, attgcactcc, agcctgggca, ataagagcga, aactccatct, 1240caaaaaaaaa, gaaagaaaga, aagaaagaaa, gaaagaaatg, gcagttacca, tctgtttctt, 1300ctgtgtgaga, catgggagtc, taactgaagt, ctctccttcc, taataaatgt, taccactctt, 1360aaaaaaaaaa, aaaaaaaaaa, aaaaaaaa, 1388＜210〉15＜211〉100＜212〉PRT＜213〉homo sapiens, (Homo, sapiens)＜400〉15Met, Val, Tyr, Ser, Glu, Val, Pro, Asn, Phe, Ser, Glu, Pro, Asn, Pro, Glu, Tyr1, 5, 10, 15Ser, Thr, Gln, Gln, Ala, Pro, Asn, Lys, Ala, Val, Gln, Asn, Asp, Ser, Asn, Pro

20??????????????????25??????????????????30Ser?Ala?Ser?Gln?Pro?Thr?Thr?Gly?Pro?Ser?Ala?Ala?Ser?Pro?Ala?Ser

35??????????????????40??????????????????45Glu?Asn?Gln?Asn?Gly?Asn?Gly?Leu?Ser?Ala?Pro?Pro?Gly?Pro?Gly?Gly

50??????????????????55??????????????????60Gly?Pro?His?Pro?Pro?Ser?Tyr?Ser?Leu?Pro?Pro?Thr?Gln?His?Pro?Asn65??????????????????70??????????????????75??????????????????80His?Ser?Lys?Pro?Ala?Gln?Pro?His?Thr?Cys?Arg?Pro?Ala?Trp?Pro?Phe

85??????????????????90??????????????????95Gln?Gln?Pro?Cys

100＜210〉16＜211〉20＜212〉DNA＜213〉primer＜400〉16aggtgacgac, agaggcaaaa, 20＜210〉17＜211〉19＜212〉DNA＜213〉primer＜400〉17caggaaatgg, gagggtcgg, 19＜210〉18＜211〉18＜212〉DNA＜213〉primer＜400〉18acctgtgcct, ccctgacg, 18＜210〉19＜211〉19＜212〉DNA＜213〉primer＜400〉19tcgttggtta, ggttgtcgc, 19＜210〉20＜211〉18＜212〉DNA＜213〉primer＜400〉20acggagccga, tggaacct, 18＜210〉21＜211〉19＜212〉DNA＜213〉primer＜400〉21atgaaccgtc, cgactccgt, 19＜210〉22＜211〉21＜212〉DNA＜213〉primer＜400〉22atatcctgtt, tgccccaact, c, 21＜210〉23＜211〉20＜212〉DNA＜213〉primer＜400〉23tccactcaga, cccctaacct, 20＜210〉24＜211〉20＜212〉DNA＜213〉primer＜400〉24tgacgacgga, gacctttgtg, 20＜210〉25＜211〉22＜212〉DNA＜213〉primer＜400〉25cgttattctc, gctttgaggt, ag, 22

Claims (10)

1. isolating people's albumen with cancer suppressing function is characterized in that, it comprises the polypeptide of the aminoacid sequence with the group of being selected from down: SEQ ID NO:3,6,9,12,15;

Or its conservative property variation polypeptide or its active fragments or its reactive derivative.

2. polypeptide as claimed in claim 1 is characterized in that, this polypeptide is the polypeptide with aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15.

3. isolating polynucleotide is characterized in that, 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:

(a) coding is as the polynucleotide of polypeptide as described in claim 1 and 2;

(b) with polynucleotide (a) complementary polynucleotide.

4. polynucleotide as claimed in claim 3 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.

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

SEQ ID NO:2,5,8,11,14 coding region sequence or full length sequence.

6. a carrier is characterized in that, it contains the described polynucleotide of claim 3.

7. 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 6;

(b) host cell that transforms or transduce with the described polynucleotide of claim 3.

8. the preparation method of the polypeptide of the people's protein-active with cancer suppressing function is characterized in that this method comprises:

(a) have under the proteic condition of people of cancer suppressing function suitable the expression, cultivate the described host cell of claim 7;

(b) from culture, isolate the polypeptide of people's protein-active with cancer suppressing function.

9. energy and the described people's protein-specific bonded antibody of claim 1 with cancer suppressing function.

10. a pharmaceutical composition is characterized in that, it contains the described polypeptide of claim 1 and the pharmaceutically acceptable carrier of safe and effective amount.