CN1483740A - Novel human protein with function for suppressing cancer and coding sequence thereof - Google Patents
Novel human protein with function for suppressing cancer and coding sequence thereof Download PDFInfo
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- CN1483740A CN1483740A CNA021370001A CN02137000A CN1483740A CN 1483740 A CN1483740 A CN 1483740A CN A021370001 A CNA021370001 A CN A021370001A CN 02137000 A CN02137000 A CN 02137000A CN 1483740 A CN1483740 A CN 1483740A
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Abstract
The present invention discloses a novel human protein with the function of inhibiting cancers, polynucleotide for coding said polypeptide and method for producing said polypeptide by means of recombination technology. Said invention also discloses the method for curing several diseases, for example, for curing cancers by using said polypeptide. Said also discloses the agonist for resisting said polypeptide and its therapeutic action. Said invention also discloses the application of the polynucleotide coding said human protein with anticancer function.
Description
Technical field
The invention belongs to biological technical field, specifically, the present invention relates to new coding and have the proteic polynucleotide of people of cancer suppressing function and the polypeptide of this polynucleotide encoding.The invention still further relates to the purposes and the preparation of these polynucleotide and polypeptide.
Background technology
The research of people's gene group is international focus at present, removes human chromosome DNA large scale sequencing, outside the method for expressed sequence order-checking (EST), also lacks the screening that begins from function and has the high-throughout method of functional gene.
Cancer is one of principal disease of harm humans health.In order to treat effectively and prophylaxis of tumours, people more and more pay close attention to genetic treatment of tumor at present.Therefore, this area presses for people's albumen and the agonist/inhibitor thereof that development research has cancer suppressing function.
Summary of the invention
The purpose of this invention is to provide the new people's protein polypeptide of a class with cancer suppressing function with and fragment, analogue and derivative.
Another object of the present invention provides the polynucleotide of these polypeptide of coding.
Another object of the present invention provides the method for these polypeptide of production and the purposes of this polypeptide and encoding sequence.
In a first aspect of the present invention, novel isolated protein polypeptide with cancer suppressing function is provided, it comprises the polypeptide of the aminoacid sequence with the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33,36; Or its conservative property variation polypeptide or its active fragments or its reactive derivative.Preferably, this polypeptide is the polypeptide with aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33,36.
In a second aspect of the present invention, a kind of isolating polynucleotide are provided, it comprises a nucleotide sequence, and this nucleotide sequence is shown at least 85% homogeny with a kind of nucleotides sequence that is selected from down group: the polynucleotide of the above-mentioned protein polypeptide with cancer suppressing function of (a) encoding; (b) with polynucleotide (a) complementary polynucleotide.Preferably, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33,36.More preferably, the sequence of these polynucleotide is selected from down group: SEQ ID NO:2,5,8,11,14,17,20,23,26,29,32,35 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 PP14212 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 PP14212 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 LP2654 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 LP2654 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 PP14212 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.
The acquisition of embodiment 1:cDNA gene and the restraining effect that the cancer cells clone is formed
PP14212 obtains by making up the human placenta cDNA library with ordinary method; LP2654, LP3236, LP3298, LP5125, LP5581, LP5624, LP6054, LP6728, LP7097, LP8165 and LP8272 come from the normal hepatocytes cDNA library that makes up with ordinary method.Get the placenta tissue (PP clone) or the normal liver tissue (LP clone) at 3,6,9 monthly ages, (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.Make up the cDNA library of above-mentioned mRNA with pCMV-script TMXR cDNA library construction test kit (Stratagene company).Wherein ThermoScript II is used MMLV-RT-Superscript II (GIBCO BRL) instead, and reverse transcription reaction carries out at 42 ℃.Transform XL 10-Gold recipient cell, obtained the cDNA library of 1 * 106 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 H2O dissolving, treat transfection.Add 0.74 μ l liposome and 9.3 μ l serum-free mediums in every part of DNA sample, behind the mixing, room temperature was placed 10 minutes.Add 150 μ l serum-free mediums in every pipe, divide equally and add 3 holes and grow in 7721 cells of 96 orifice plates, placed 2 hours for 37 ℃, every hole adds 50 μ l serum-free mediums again, 37 ℃ 24 hours.Every hole is changed 100 μ l and is trained liquid entirely, 37 ℃ 24 hours, change the full training liquid 100 μ l that contain G418,37 ℃ 24-48 hour, the limit is observed, the training liquid that G418 concentration does not wait is changed on the limit.After about 2-3 time, there is the clone to form up to the microscopy cell, counting.Find that above-mentioned clone has the cell clone of inhibition formation effect, the result is as shown in the table.
CDNA clone's transfectional cell (7721) clone formation situation
CDNA clones title | CDNA clones number (three repetitions) | Empty carrier clone number (three repetitions) | ||||
????PP14212 | ????14 | ????13 | ????10 | ????22 | ????25 | ????20 |
????LP2654 | ????0 | ????0 | ????0 | ????16 | ????20 | ????13 |
????LP3236 | ????1 | ????2 | ????3 | ????33 | ????28 | ????30 |
????LP3298 | ????1 | ????0 | ????0 | ????39 | ????43 | ????45 |
????LP5125 | ????0 | ????0 | ????0 | ????39 | ????44 | ????42 |
????LP5581 | ????0 | ????2 | ????2 | ????31 | ????38 | ????28 |
????LP5624 | ????0 | ????1 | ????0 | ????31 | ????38 | ????28 |
????LP6054 | ????7 | ????12 | ????6 | ????39 | ????36 | ????27 |
????LP6728 | ????2 | ????0 | ????3 | ????29 | ????34 | ????37 |
????LP7097 | ????2 | ????1 | ????0 | ????25 | ????22 | ????18 |
????LP8165 | ????15 | ????12 | ????10 | ????22 | ????25 | ????20 |
????LP8272 | ????0 | ????3 | ????1 | ????31 | ????34 | ????38 |
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 (SEQID NO:1,4,7,10,13,16,19,22,25,28,31,34).
Embodiment 2: PCR obtains full-length gene from placenta or fetus cDNA:
Get placenta tissue (PP 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 circulation.94 ℃ 30 " 60 ℃ 30 " 72 ℃ of 1 ' 35 circulations, pcr amplification is carried out in 72 ℃ of 10 ' 1 circulations, and acquisition contains the amplified production of each protein gene of complete open reading frame sequence.Amplified production is through sequence verification, and the sequence that records with embodiment 1 conforms to, and changes amplified production over to host cell with routine techniques subsequently, obtains recombinant protein (SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33,36).
Gene specific primer
Clone's title | Special primer 1 (5 ' → 3 ') | SEQ?ID ??NO: | Special primer 2 (3 ' → 5 ') | SEQ?ID ??NO: |
PP14212 | (19)TCAGCCCAGCAATTCGTTT | ????37 | AACTTGGACACTCCGTCTCC(1550) | ????38 |
?LP2654 | (1)GATCAGGTAACGCAGGTGTCG | ????39 | GGGAGGACGCGACCTTTG(1208) | ????40 |
?LP3236 | (11)TGGCTTGGAGTAGCACCTTC | ????41 | GGTTGTACCCCTTTGAGACAG(2038) | ????42 |
?LP3298 | (144)GCACAGTCAAACAGGGCTAAG | ????43 | TACGGGGTCTACCTAAGATGA(1893) | ????44 |
?LP5125 | (47)GGCGGGAACTGAAACTGC | ????45 | ACCAACACCCACCGTCGT(1835) | ????46 |
?LP5581 | (76)TCGTGGGAGGGCTCAACT | ????47 | GTTCTTGTACTAATAGGTCCCC(1850) | ????48 |
?LP5624 | (149)CAGGGTGAAATCCCGTCC | ????49 | ACTCCGTCCTCCTACCTCA(1863) | ????50 |
?LP6054 | (91)CATGGACGGGGAGGAGCA | ????51 | GGAGGGAGGACCGACAGGT(2212) | ????52 |
?LP6728 | (200)TGAATCTATCGTCTCCAATCCG | ????53 | CCCACCCTTCACCCCGAT(3044) | ????54 |
?LP7097 | (135)CCCTCCTCATCTGCCTTTCA | ????55 | AACTTCCACCATCTCCTACCC(1994) | ????56 |
?LP8165 | (73)GCAGACCCCACGTTAGCTG | ????57 | CACTTTGCCGCTCTGAGATGG(1791) | ????58 |
?LP8272 | (5)CAAGGGTGGCAGTCACAGAG | ????59 | CTTGGTCATTGTACTGGGTAGC(994) | ????60 |
Embodiment 3:cDNA cloned sequence is analyzed
1.PP14212
A: nucleotide sequence (SEQ ID NO:1) length: 1637 bases
B: aminoacid sequence (SEQ ID NO:3) length: 288 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:2) clone number and protein name: PP14212
Start code: 64 ATG stop coding: 928 TAG protein molecular weights: 31640.56
2.LP2654
A: nucleotide sequence (SEQ ID NO:4) length: 1363 bases
B: aminoacid sequence (SEQ ID NO:6) length: 288 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:5) clone number and protein name: LP2654
Start code: 221 ATG stop coding: 1085 TAG protein molecular weights: 31535.11
3.LP3236
A: nucleotide sequence (SEQID NO:7) length: 2234 bases
B: aminoacid sequence (SEQ ID NO:9) length: 98 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:8) clone number and protein name: LP3236
Start code: 1171 ATG stop coding: 1465 TAG protein molecular weights: 11036.77
4.LP3298
A: nucleotide sequence (SEQ ID NO:10) length: 2103 bases
B: aminoacid sequence (SEQ ID NO:12) length: 121 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:11) clone number and protein name: LP3298
Start code: 1490 ATG stop coding: 1853 TGA protein molecular weights: 13237.57
5.LP5125
A: nucleotide sequence (SEQ ID NO:13) length: 1906 bases
B: aminoacid sequence (SEQ ID NO:15) length: 321 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:14) clone number and protein name: LP5125
Start code: 70 ATG stop coding: 1033 TAG protein molecular weights: 34205.94
6.LP5581
A: nucleotide sequence (SEQ ID NO:16) length: 2038 bases
B: aminoacid sequence (SEQ ID NO:18) length: 169 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:17) clone number and protein name: LP5581
Start code: 779 ATG stop coding: 1286 TAG protein molecular weights: 18169.49
7.LP5624
A: nucleotide sequence (SEQ ID NO:19) length: 1965 bases
B: aminoacid sequence (SEQ ID NO:21) length: 95 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:20) clone number and protein name: LP5624
Start code: 780 ATG stop coding: 1065 TGA protein molecular weights: 10475.28
8.LP6054
A: nucleotide sequence (SEQID NO:22) length: 2427 bases
B: aminoacid sequence (SEQID NO:24) length: 292 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:23) clone number and protein name: LP6054
Start code: 92 ATG stop coding: 968 TGA protein molecular weights: 33179.50
9.LP6728
A: nucleotide sequence (SEQ ID NO:25) length: 3105 bases
B: aminoacid sequence (SEQ ID NO:27) length: 527 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:26) clone number and protein name: LP6728
Start code: 798 ATG stop coding: 2379 TGA protein molecular weights: 60492.93
10.LP7097
A: nucleotide sequence (SEQ ID NO:28) length: 2141 bases
B: aminoacid sequence (SEQ ID NO:30) length: 183 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:29) clone number and protein name: LP7097
Start code: 1220 ATG stop coding: 1769 TAG protein molecular weights: 19323.13
11.LP8165
A: nucleotide sequence (SEQ ID NO:31) length: 1843 bases
B: aminoacid sequence (SEQ ID NO:33) length: 204 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:32) clone number and protein name: LP8165
Start code: 865 ATG stop coding: 1477 TGA protein molecular weights: 22425.78
12.LP8272
A: nucleotide sequence (SEQ ID NO:34) length: 1083 bases
B: aminoacid sequence (SEQ ID NO:36) length: 179 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:35) clone number and protein name: LP8272
Start code: 448 ATG stop coding: 985 TGA protein molecular weights: 20418.30
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.
<110〉<120〉<130〉025305<160〉60<170〉PatentIn version 3.1<210〉1<211〉1637<212〉DNA<213〉 ( Homo sapiens )<400〉1gggctttcaa cccccacctc agcccagcaa ttcgtttgga gcatgtgaac accttgagcc 60ttgatgagtt ccagtatgtg gtatattatg cagagcattc agagcaaata ctctctctcc 120gagcgcttaa tccgaacaat tgctgccatc cgttccttcc cacatgataa tgtagaggac 180ctcatcagag ggggagcaga tgtgaactgc actcatggca cactgaagcc cttgcactgt 240gcctgtatgg tgtcagatgc tgactgtgtg gagttacttc tggaaaaagg agccgaggtg 300aatgccctgg atgggtataa ccgaacagcc ctccactatg cagcagagaa agatgaggct 360tgtgtggagg tcctattgga gtatggtgca aaccccaatg ctttggatgg caacagagat 420accccacttc actgggcagc ctttaagaac aatgctgagt gtgtgcgggc tctcctagag 480agcggggcct ctgtcaatgc cctggattac aacaatgata caccgctcag ctgggctgcc 540atgaagggaa atcttgagag tgtcagcatc cttctggatt atggcgcaga ggtcagagtc 600atcaacctaa taggccagac acccatctcc cgcctggtgg ctctgctagt caggggactt 660ggaacagaga aagaggactc ttgctttgag ctcctccaca gagctgttgg acactttgaa 720ttgaggaaaa atggcaccat gccacgagag gtggccagag acccgcagct atgtgaaaaa 780ctgactgttc tgtgctcagc tccaggaact ctaaaaacac tcgctcgcta tgccgtgcgc 840cgtagcctgg gactccagta tctccccgat gcagtgaagg gccttccact gccagcttct 900ttgaaggaat acctgttact tttagaatag ccggagaaga tgtttgcacc atcgtgcagg 960cagctctggg tgaggttgtc cctgcagtac tccttgtcac agaaaacaga aaaacagttg 1020ttcctgttgt gtggtttata gatttcgaag caacatgtca caacaataac ctccatagca 1080cctccccttc ccaaaccaaa caacccaaca aaaaaaatcc ctcacttttg ttttctgttt 1140attgcttacc tggcttttta tattgcattt tgcaaaagaa gaggtctccc tcaatcctcc 1200cctttaggga aggagtcaac agtgtaacta aatttctcta ggaagatgga aagtacttaa 1260ataatgtgtg tgtggttttc tttggggacg tggttaacgg tccagaagaa tcccttctag 1320aaagcatttt aggccagcca tggtggctca cgtctgtaat cccaggactt tgggaggctg 1380aggcaggtgg atcacctgag gtcaggagtt cgagcccagc ctgaccaata tgatgaaacc 1440ccgtctctac taaaaataca aaaattagct gggcatggtg gcatgcgcct gtaatcccag 1500ctactcagga ggctgagaca gaagaatcgc ttgaacctgt gaggcagagg ttgcagtgag 1560ccaagatcgc gccattgcac tccagcctgg acaacaagag caaaactgtc tcaaaaaaaa 1620aaaaaaaaaa aaaaaaa 1637<210〉2<211〉1637<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 64 ) .. ( 927 )<223〉<400〉2gggctttcaa cccccacctc agcccagcaa ttcgtttgga gcatgtgaac accttgagcc 60ttg atg agt tcc agt atg tgg tat att atg cag agc att cag agc aaa 108
Met?Ser?Ser?Ser?Met?Trp?Tyr?Ile?Met?Gln?Ser?Ile?Gln?Ser?Lys
1???????????????5???????????????????10??????????????????15tac?tct?ctc?tcc?gag?cgc?tta?atc?cga?aca?att?gct?gcc?atc?cgt?tcc??????156Tyr?Ser?Leu?Ser?Glu?Arg?Leu?Ile?Arg?Thr?Ile?Ala?Ala?Ile?Arg?Ser
20??????????????????25??????????????????30ttc?cca?cat?gat?aat?gta?gag?gac?ctc?atc?aga?ggg?gga?gca?gat?gtg??????204Phe?Pro?His?Asp?Asn?Val?Glu?Asp?Leu?Ile?Arg?Gly?Gly?Ala?Asp?Val
35??????????????????40??????????????????45aac?tgc?act?cat?ggc?aca?ctg?aag?ccc?ttg?cac?tgt?gcc?tgt?atg?gtg??????252Asn?Cys?Thr?His?Gly?Thr?Leu?Lys?Pro?Leu?His?Cys?Ala?Cys?Met?Val
50??????????????????55??????????????????60tca?gat?gct?gac?tgt?gtg?gag?tta?ctt?ctg?gaa?aaa?gga?gcc?gag?gtg??????300Set?Asp?Ala?Asp?Cys?Val?Glu?Leu?Leu?Leu?Glu?Lys?Gly?Ala?Glu?Val
65??????????????????70??????????????????75aat?gcc?ctg?gat?ggg?tat?aac?cga?aca?gcc?ctc?cac?tat?gca?gca?gag??????348Asn?Ala?Leu?Asp?Gly?Tyr?Asn?Arg?Thr?Ala?Leu?His?Tyr?Ala?Ala?Glu80??????????????????85??????????????????90??????????????????95aaa?gat?gag?gct?tgt?gtg?gag?gtc?cta?ttg?gag?tat?ggt?gca?aac?ccc??????396Lys?Asp?Glu?Ala?Cys?Val?Glu?Val?Leu?Leu?Glu?Tyr?Gly?Ala?Asn?Pro
100?????????????????105?????????????????110aat?gct?ttg?gat?ggc?aac?aga?gat?acc?cca?ctt?cac?tgg?gca?gcc?ttt??????444Asn?Ala?Leu?Asp?Gly?Asn?Arg?Asp?Thr?Pro?Leu?His?Trp?Ala?Ala?Phe
115?????????????????120?????????????????125aag?aac?aat?gct?gag?tgt?gtg?cgg?gct?ctc?cta?gag?agc?ggg?gcc?tct??????492Lys?Asn?Asn?Ala?Glu?Cys?Val?Arg?Ala?Leu?Leu?Glu?Ser?Gly?Ala?Ser
130?????????????????135?????????????????140gtc?aat?gcc?ctg?gat?tac?aac?aat?gat?aca?ccg?ctc?agc?tgg?gct?gcc??????540Val?Asn?Ala?Leu?Asp?Tyr?Asn?Asn?Asp?Thr?Pro?Leu?Ser?Trp?Ala?Ala
145?????????????????150?????????????????155atg?aag?gga?aat?ctt?gag?agt?gtc?agc?atc?ctt?ctg?gat?tat?ggc?gca??????588Met?Lys?Gly?Asn?Leu?Glu?Ser?Val?Ser?Ile?Leu?Leu?Asp?Tyr?Gly?Ala160?????????????????165?????????????????170?????????????????175gag?gtc?aga?gtc?atc?aac?cta?ata?ggc?cag?aca?ccc?atc?tcc?cgc?ctg??????636Glu?Val?Arg?Val?Ile?Asn?Leu?Ile?Gly?Gln?Thr?Pro?Ile?Ser?Arg?Leu
180?????????????????185?????????????????190gtg?gct?ctg?cta?gtc?agg?gga?ctt?gga?aca?gag?aaa?gag?gac?tct?tgc??????684Val?Ala?Leu?Leu?Val?Arg?Gly?Leu?Gly?Thr?Glu?Lys?Glu?Asp?Ser?Cys
195?????????????????200?????????????????205ttt?gag?ctc?ctc?cac?aga?gct?gtt?gga?cac?ttt?gaa?ttg?agg?aaa?aat??????732Phe?Glu?Leu?Leu?His?Arg?Ala?Val?Gly?His?Phe?Glu?Leu?Arg?Lys?Asn
210?????????????????215?????????????????220ggc?acc?atg?cca?cga?gag?gtg?gcc?aga?gac?ccg?cag?cta?tgt?gaa?aaa??????780Gly?Thr?Met?Pro?Arg?Glu?Val?Ala?Arg?Asp?Pro?Gln?Leu?Cys?Glu?Lys
225?????????????????230?????????????????235ctg?act?gtt?ctg?tgc?tca?gct?cca?gga?act?cta?aaa?aca?ctc?gct?cgc??????828Leu?Thr?Val?Leu?Cys?Ser?Ala?Pro?Gly?Thr?Leu?Lys?Thr?Leu?Ala?Arg240?????????????????245?????????????????250?????????????????255tat?gcc?gtg?cgc?cgt?agc?ctg?gga?ctc?cag?tat?ctc?ccc?gat?gca?gtg??????876Tyr?Ala?Val?Arg?Arg?Ser?Leu?Gly?Leu?Gln?Tyr?Leu?Pro?Asp?Ala?Val
260?????????????????265?????????????????270aag?ggc?ctt?cca?ctg?cca?gct?tct?ttg?aag?gaa?tac?ctg?tta?ctt?tta??????924Lys?Gly?Leu?Pro?Leu?Pro?Ala?Ser?Leu?Lys?Glu?Tyr?Leu?Leu?Leu?Leu
275 280 285gaa tagccggaga agatgtttgc accatcgtgc aggcagctct gggtgaggtt 977Glugtccctgcag tactccttgt cacagaaaac agaaaaacag ttgttcctgt tgtgtggttt 1037atagatttcg aagcaacatg tcacaacaat aacctccata gcacctcccc ttcccaaacc 1097aaacaaccca acaaaaaaaa tccctcactt ttgttttctg tttattgctt acctggcttt 1157ttatattgca ttttgcaaaa gaagaggtct ccctcaatcc tcccctttag ggaaggagtc 1217aacagtgtaa ctaaatttct ctaggaagat ggaaagtact taaataatgt gtgtgtggtt 1277ttctttgggg acgtggttaa cggtccagaa gaatcccttc tagaaagcat tttaggccag 1337ccatggtggc tcacgtctgt aatcccagga ctttgggagg ctgaggcagg tggatcacct 1397gaggtcagga gttcgagccc agcctgacca atatgatgaa accccgtctc tactaaaaat 1457acaaaaatta gctgggcatg gtggcatgcg cctgtaatcc cagctactca ggaggctgag 1517acagaagaat cgcttgaacc tgtgaggcag aggttgcagt gagccaagat cgcgccattg 1577cactccagcc tggacaacaa gagcaaaact gtctcaaaaa aaaaaaaaaa aaaaaaaaaa 1637<210〉3<211〉288<212〉PRT<213〉 ( Homo sapiens )<400〉3Met Ser Ser Ser Met Trp Tyr Ile Met Gln Ser Ile Gln Ser Lys Tyr1 5 10 15Ser Leu Ser Glu Arg Leu Ile Arg Thr Ile Ala Ala Ile Arg Ser Phe
20??????????????????25??????????????????30Pro?His?Asp?Asn?Val?Glu?Asp?Leu?Ile?Arg?Gly?Gly?Ala?Asp?Val?Asn
35??????????????????40??????????????????45Cys?Thr?His?Gly?Thr?Leu?Lys?Pro?Leu?His?Cys?Ala?Cys?Met?Val?Ser
50??????????????????55??????????????????60Asp?Ala?Asp?Cys?Val?Glu?Leu?Leu?Leu?Glu?Lys?Gly?Ala?Glu?Val?Asn65??????????????????70??????????????????75??????????????????80Ala?Leu?Asp?Gly?Tyr?Asn?Arg?Thr?Ala?Leu?His?Tyr?Ala?Ala?Glu?Lys
85??????????????????90??????????????????95Asp?Glu?Ala?Cys?Val?Glu?Val?Leu?Leu?Glu?Tyr?Gly?Ala?Asn?Pro?Asn
100?????????????????105?????????????????110Ala?Leu?Asp?Gly?Asn?Arg?Asp?Thr?Pro?Leu?His?Trp?Ala?Ala?Phe?Lys
115?????????????????120?????????????????125Asn?Asn?Ala?Glu?Cys?Val?Arg?Ala?Leu?Leu?Glu?Ser?Gly?Ala?Ser?Val
130?????????????????135?????????????????140Asn?Ala?Leu?Asp?Tyr?Asn?Asn?Asp?Thr?Pro?Leu?Ser?Trp?Ala?Ala?Met145?????????????????150?????????????????155?????????????????160Lys?Gly?Asn?Leu?Glu?Ser?Val?Ser?Ile?Leu?Leu?Asp?Tyr?Gly?Ala?Glu
165?????????????????170?????????????????175Val?Arg?Val?Ile?Asn?Leu?Ile?Gly?Gln?Thr?Pro?Ile?Ser?Arg?Leu?Val
180?????????????????185?????????????????190Ala?Leu?Leu?Val?Arg?Gly?Leu?Gly?Thr?Glu?Lys?Glu?Asp?Ser?Cys?Phe
195?????????????????200?????????????????205Glu?Leu?Leu?His?Arg?Ala?Val?Gly?His?Phe?Glu?Leu?Arg?Lys?Asn?Gly
210?????????????????215?????????????????220Thr?Met?Pro?Arg?Glu?Val?Ala?Arg?Asp?Pro?Gln?Leu?Cys?Glu?Lys?Leu225?????????????????230?????????????????235?????????????????240Thr?Val?Leu?Cys?Ser?Ala?Pro?Gly?Thr?Leu?Lys?Thr?Leu?Ala?Arg?Tyr
245?????????????????250?????????????????255Ala?Val?Arg?Arg?Ser?Leu?Gly?Leu?Gln?Tyr?Leu?Pro?Asp?Ala?Val?Lys
260?????????????????265?????????????????270Gly?Leu?Pro?Leu?Pro?Ala?Ser?Leu?Lys?Glu?Tyr?Leu?Leu?Leu?Leu?Glu
275 280 285<210〉4<211〉1363<212〉DNA<213〉 ( Homo sapiens )<400〉4gatcaggtaa cgcaggtgtc gggtcctgcc gcccccacag ccaggtgcac agcgggggcc 60accagcaccg tggcagctga gctcctgtga cggccacgac gggctgcgga ggcaggactc 120cagccgcaag ccccgcgcct tcagcaagca gcccagcacg ggggactact accggcagct 180gggccgctgc cccggcgaga cgctggccgc acgcccgggc atggcgcaca gcgaggaggc 240ggcgctgctt cctgggaacc atgttcctaa cggctgcgcc gcggacccca aggcgtcagg 300ggagctgcca ccgccgcccc caccgccgcc gccgcccctg ccggaggccg cgagttcgcc 360accgccggcc ccgcctctgc ccctcgagag cgctggccct ggctgcgggc agcgccgctc 420ctcctcgtcc accggcagca ccaagtcttt caacatgatg tccccgacgg gcgacaactc 480ggagctactg gctgagatta aggcaggcaa gagcctgaag ccgacgcccc agagcaaggg 540gctgaccaca gtgttctcag gcatcgggca gccggccttc cagcccgatt cgccgctgcc 600ttctgtgtca cctgcactgt caccagtccg gagccccaca ccgccagctg cggggtttca 660gccgctgctc aatggaagct tggttcccgt gccgcccact actcctgcgc cgggagtgca 720gctggacgtg gaggctctca tccccacgca cgatgagcag ggccggccca tccccgagtg 780gaagcgccag gtgatggtgc gcaagatgca gctgaagatg caggaggagg aggagcagag 840gcggaaggag gaggaggagg aggcccggct ggccagcatg cccgcctgga ggcgggacct 900cctgcggaag aagctggaag aagagaggga gcagaagcgg aaagaggagg agcgacagaa 960gcaggaggag ctgcggcggg agaaggaaca gtcagagaag ctgcggacgc tgggctacga 1020tgagagcaag ctggcgccct ggcagcgaca ggtcatcctg aagaaggggg acatcgctaa 1080gtactagagg ccgcagactc ctgtccgcag cctcgcagct ccgtggggcc ctccgcccca 1140gccccagcca gccaggccct ggtggaaagg ctgggagccg cacagccctc ccctcctgcg 1200ctggaaaccc tccctgaccc ccaccctggc cccccgtatc cccagccctt ggcaacactg 1260gagtgcacac gccgccacgg ttgcccagaa aaagtgccca agctgctgac gcaaacaaca 1320acaaatgctg cttatttgca aaaaaaaaaa aaaaaaaaaa aaa 1363<210〉5<211〉1363<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 221 ) .. ( 1084 )<223〉<400〉5gatcaggtaa cgcaggtgtc gggtcctgcc gcccccacag ccaggtgcac agcgggggcc 60accagcaccg tggcagctga gctcctgtga cggccacgac gggctgcgga ggcaggactc 120cagccgcaag ccccgcgcct tcagcaagca gcccagcacg ggggactact accggcagct 180gggccgctgc cccggcgaga cgctggccgc acgcccgggc atg gcg cac agc gag 235
Met?Ala?His?Ser?Glu
1???????????????5gag?gcg?gcg?ctg?ctt?cct?ggg?aac?cat?gtt?cct?aac?ggc?tgc?gcc?gcg??????283Glu?Ala?Ala?Leu?Leu?Pro?Gly?Asn?His?Val?Pro?Asn?Gly?Cys?Ala?Ala
10??????????????????15??????????????????20gac?ccc?aag?gcg?tca?ggg?gag?ctg?cca?ccg?ccg?ccc?cca?ccg?ccg?ccg??????331Asp?Pro?Lys?Ala?Ser?Gly?Glu?Leu?Pro?Pro?Pro?Pro?Pro?Pro?Pro?Pro
25??????????????????30??????????????????35ccg?ccc?ctg?ccg?gag?gcc?gcg?agt?tcg?cca?ccg?ccg?gcc?ccg?cct?ctg??????379Pro?Pro?Leu?Pro?Glu?Ala?Ala?Ser?Ser?Pro?Pro?Pro?Ala?Pro?Pro?Leu
40??????????????????45??????????????????50ccc?ctc?gag?agc?gct?ggc?cct?ggc?tgc?ggg?cag?cgc?cgc?tcc?tcc?tcg????427Pro?Leu?Glu?Ser?Ala?Gly?Pro?Gly?Cys?Gly?Gln?Arg?Arg?Ser?Ser?Ser
55??????????????????60??????????????????65tcc?acc?ggc?agc?acc?aag?tct?ttc?aac?atg?atg?tcc?ccg?acg?ggc?gac????475Ser?Thr?Gly?Ser?Thr?Lys?Ser?Phe?Asn?Met?Met?Ser?Pro?Thr?Gly?Asp70??????????????????75??????????????????80??????????????????85aac?tcg?gag?cta?ctg?gct?gag?att?aag?gca?ggc?aag?agc?ctg?aag?ccg????523Asn?Ser?Glu?Leu?Leu?Ala?Glu?Ile?Lys?Ala?Gly?Lys?Ser?Leu?Lys?Pro
90??????????????????95??????????????????100acg?ccc?cag?agc?aag?ggg?ctg?acc?aca?gtg?ttc?tca?ggc?atc?ggg?cag????571Thr?Pro?Gln?Ser?Lys?Gly?Leu?Thr?Thr?Val?Phe?Ser?Gly?Ile?Gly?Gln
105?????????????????110?????????????????115ccg?gcc?ttc?cag?ccc?gat?tcg?ccg?ctg?cct?tct?gtg?tca?cct?gca?ctg????619Pro?Ala?Phe?Gln?Pro?Asp?Ser?Pro?Leu?Pro?Ser?Val?Ser?Pro?Ala?Leu
120?????????????????125?????????????????130tca?cca?gtc?cgg?agc?ccc?aca?ccg?cca?gct?gcg?ggg?ttt?cag?ccg?ctg????667Ser?Pro?Val?Arg?Ser?Pro?Thr?Pro?Pro?Ala?Ala?Gly?Phe?Gln?Pro?Leu
135?????????????????140?????????????????145ctc?aat?gga?agc?ttg?gtt?ccc?gtg?ccg?ccc?act?act?cct?gcg?ccg?gga????715Leu?Asn?Gly?Ser?Leu?Val?Pro?Val?Pro?Pro?Thr?Thr?Pro?Ala?Pro?Gly150?????????????????155?????????????????160?????????????????165gtg?cag?ctg?gac?gtg?gag?gct?ctc?atc?ccc?acg?cac?gat?gag?cag?ggc????763Val?Gln?Leu?Asp?Val?Glu?Ala?Leu?Ile?Pro?Thr?His?Asp?Glu?Gln?Gly
170?????????????????175?????????????????180cgg?ccc?atc?ccc?gag?tgg?aag?cgc?cag?gtg?atg?gtg?cgc?aag?atg?cag????811Arg?Pro?Ile?Pro?Glu?Trp?Lys?Arg?Gln?Val?Met?Val?Arg?Lys?Met?Gln
185?????????????????190?????????????????195ctg?aag?atg?cag?gag?gag?gag?gag?cag?agg?cgg?aag?gag?gag?gag?gag????859Leu?Lys?Met?Gln?Glu?Glu?Glu?Glu?Gln?Arg?Arg?Lys?Glu?Glu?Glu?Glu
200?????????????????205?????????????????210gag?gcc?cgg?ctg?gcc?agc?atg?ccc?gcc?tgg?agg?cgg?gac?ctc?ctg?cgg????907Glu?Ala?Arg?Leu?Ala?Ser?Met?Pro?Ala?Trp?Arg?Arg?Asp?Leu?Leu?Arg
215?????????????????220?????????????????225aag?aag?ctg?gaa?gaa?gag?agg?gag?cag?aag?cgg?aaa?gag?gag?gag?cga????955Lys?Lys?Leu?Glu?Glu?Glu?Arg?Glu?Gln?Lys?Arg?Lys?Glu?Glu?Glu?Arg230?????????????????235?????????????????240?????????????????245cag?aag?cag?gag?gag?ctg?cgg?cgg?gag?aag?gaa?cag?tca?gag?aag?ctg???1003Gln?Lys?Gln?Glu?Glu?Leu?Arg?Arg?Glu?Lys?Glu?Gln?Ser?Glu?Lys?Leu
250?????????????????255?????????????????260cgg?acg?ctg?ggc?tac?gat?gag?agc?aag?ctg?gcg?ccc?tgg?cag?cga?cag???1051Arg?Thr?Leu?Gly?Tyr?Asp?Glu?Ser?Lys?Leu?Ala?Pro?Trp?Gln?Arg?Gln
265?????????????????270?????????????????275gtc?atc?ctg?aag?aag?ggg?gac?atc?gct?aag?tac?tagaggccgc?agactcctgt?1104Val?Ile?Leu?Lys?Lys?Gly?Asp?Ile?Ala?Lys?Tyr
280 285ccgcagcctc gcagctccgt ggggccctcc gccccagccc cagccagcca ggccctggtg 1164gaaaggctgg gagccgcaca gccctcccct cctgcgctgg aaaccctccc tgacccccac 1224cctggccccc cgtatcccca gcccttggca acactggagt gcacacgccg ccacggttgc 1284ccagaaaaag tgcccaagct gctgacgcaa acaacaacaa atgctgctta tttgcaaaaa 1344aaaaaaaaaa aaaaaaaaa, 1363<210〉6<211〉288<212〉PRT<213〉homo sapiens (Homo sapiens)<400〉6Met Ala His Ser Glu Glu Ala Ala Leu Leu Pro Gly Asn His Val Pro1,5 10 15Asn Gly Cys Ala Ala Asp Pro Lys Ala Ser Gly Glu Leu Pro Pro Pro
20??????????????????25??????????????????30Pro?Pro?Pro?Pro?Pro?Pro?Pro?Leu?Pro?Glu?Ala?Ala?Ser?Ser?Pro?Pro
35??????????????????40??????????????????45Pro?Ala?Pro?Pro?Leu?Pro?Leu?Glu?Ser?Ala?Gly?Pro?Gly?Cys?Gly?Gln
50??????????????????55??????????????????60Arg?Arg?Ser?Ser?Ser?Ser?Thr?Gly?Ser?Thr?Lys?Ser?Phe?Asn?Met?Met65??????????????????70??????????????????75??????????????????80Ser?Pro?Thr?Gly?Asp?Asn?Ser?Glu?Leu?Leu?Ala?Glu?Ile?Lys?Ala?Gly
85??????????????????90??????????????????95Lys?Ser?Leu?Lys?Pro?Thr?Pro?Gln?Ser?Lys?Gly?Leu?Thr?Thr?Val?Phe
100?????????????????105?????????????????110Ser?Gly?Ile?Gly?Gln?Pro?Ala?Phe?Gln?Pro?Asp?Ser?Pro?Leu?Pro?Ser
115?????????????????120?????????????????125Val?Ser?Pro?Ala?Leu?Ser?Pro?Val?Arg?Ser?Pro?Thr?Pro?Pro?Ala?Ala
130?????????????????135?????????????????140Gly?Phe?Gln?Pro?Leu?Leu?Asn?Gly?Ser?Leu?Val?Pro?Val?Pro?Pro?Thr145?????????????????150?????????????????155?????????????????160Thr?Pro?Ala?Pro?Gly?Val?Gln?Leu?Asp?Val?Glu?Ala?Leu?Ile?Pro?Thr
165?????????????????170?????????????????175His?Asp?Glu?Gln?Gly?Arg?Pro?Ile?Pro?Glu?Trp?Lys?Arg?Gln?Val?Met
180?????????????????185?????????????????190Val?Arg?Lys?Met?Gln?Leu?Lys?Met?Gln?Glu?Glu?Glu?Glu?Gln?Arg?Arg
195?????????????????200?????????????????205Lys?Glu?Glu?Glu?Glu?Glu?Ala?Arg?Leu?Ala?Ser?Met?Pro?Ala?Trp?Arg
210?????????????????215?????????????????220Arg?Asp?Leu?Leu?Arg?Lys?Lys?Leu?Glu?Glu?Glu?Arg?Glu?Gln?Lys?Arg225?????????????????230?????????????????235?????????????????240Lys?Glu?Glu?Glu?Arg?Gln?Lys?Gln?Glu?Glu?Leu?Arg?Arg?Glu?Lys?Glu
245?????????????????250?????????????????255Gln?Ser?Glu?Lys?Leu?Arg?Thr?Leu?Gly?Tyr?Asp?Glu?Ser?Lys?Leu?Ala
260?????????????????265?????????????????270Pro?Trp?Gln?Arg?Gln?Val?Ile?Leu?Lys?Lys?Gly?Asp?Ile?Ala?Lys?Tyr
275 280 285<210〉7<211〉2234<212〉DNA<213〉 ( Homo sapiens )<400〉7ggatgtgtcc tggcttggag tagcaccttc tgctaccaca ctgggcctcc actctcctca 60gtgcccaagg ggaggcacct cactctgatc tccctgtggg gtcctcttat gcctgccagt 120aaggatagga gtttggttct agagcagagt ggtctggctt ccaacaagcc cagtgttcta 180ggtgacctca ggttgcccca ggccttcctg taggttggca ctaattggtt tggctgcagc 240tccacttatt aagtagttat ttttattact aacaacctag gcagggtggc ccaggagccc 300gctgggggag gcggtgccag gctcctggct gaggggcagg ctggccccaa ttctgactgg 360ctggctccag tgatcaggac cagggcccca cgtggtgctt tgctggagat ctaggcttgg 420tggggcagct gtggggtaag gggcaggacc agctcaaaga tggggtgggg gcggaggctg 480cctctgcagg gcagagtcct ttggcagtcg ggactgttgg gcatagagga gtcagctcac 540agctcagggc cagagcactg gagaggtctc tggggtgcat acaggaacca ggagtggagc 600tgaagcatgt cctatcccct gccagccctc ccttagtaac agctggcatt tctcgagtcc 660ttcctgagca ccaggcaccg tgttatgtat gcaatttgca aatattatct gattaaatgc 720tcacaataag gctatcagag aggtactatt attatcctta tcttattatt attattatta 780ttatttttaa gaaggagtct gaggcaggag aatctcttga acctgggagg cagagtttgc 840agtgagctga gatggcacca ctgtactcca gcctggccga caaagtgaga ctctgtctca 900aaaaaaaaaa aaaagaaccc aaacttttgg tgttcagcca tgttcccatg ctcactccca 960gggtggtgac tctgggaagg tctcagcctc cttgtctgcc cagttagaat gatctgatgc 1020ccctgctacc atcagacttg ataagtttcc caaagactct ttgcaagaag cactgttctg 1080gagggtggag gagagactaa ttgttcttgc tctcctggcc agagtgggaa gctttggggt 1140ggccggtttg tgggtgcagt ggaccccatc atggagaagt tcaacgcgtc cattgcctac 1200gaccggcacc tttgggaggt ggatgttcaa ggcagcaaag cctacagcag gggcctggag 1260aaggcagggc tcctcaccaa ggccgagatg gaccagatac tccatggcct agacaaggtg 1320gctgaggagt gggcccaggg caccttcaaa ctgaactcca atgatgagga catccacaca 1380gccaatgagc gccgcctgaa ggagctcatt ggtgcaacgg cagggaagct gcacacggga 1440cggagccgga atgaccaggt gctttagccc ctccaccccc tgctccgtgt tgtcccaacc 1500ttgaggagcc cagggggcag ttagagttct gcagcggtcc tggctcctca gggaagcaac 1560acatcggcct ccctgagcac catctcctcc ttgcacaggt ggtcacagac ctcaggctgt 1620ggatgcggca gacctgctcc acgctctcgg gcctcctctg ggagctcatt aggaccatgg 1680tggatcgggc agaggcgtga gtcctacagg gacacccagg gggcagacag aggtgtgatg 1740gaagcctgaa caggagacct agggggcagg ggtgaacagc gtgggggtgc caggccctgg 1800gggacagggg catcccagaa ctccaggatc gaggcagagc agccaggagt gggccatttc 1860ctgcaggccc caatactccc atgccagtct agctcagcag gcagagaaga ctaacccttc 1920gtggggctgg gtgcggtggc tcacgcctgt aatctcagca ctttgggagg ccgaggtggg 1980tggatcacct gaggtcagga gttcgagacc agcctggcca acatggggaa actctgtctc 2040tactaaaaat acaaaaatta ggcaatgtgg tggtgtgcgc ctgtaatccc agctactcgg 2100gagcctgagg cagaagaact gcttgaaccc gggaggagga ggttgcaatg agccgagatc 2160gcgccattgc actccagcct gggctacaga gcgagactcc tgtctcaaaa aaaaagaaaa 2220aaaaaaaaaa aaaa 2234<210〉8<211〉2234<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 1171 ) .. ( 1464 )<223〉<400〉8ggatgtgtcc tggcttggag tagcaccttc tgctaccaca ctgggcctcc actctcctca 60gtgcccaagg ggaggcacct cactctgatc tccctgtggg gtcctcttat gcctgccagt 120aaggatagga gtttggttct agagcagagt ggtctggctt ccaacaagcc cagtgttcta 180ggtgacctca ggttgcccca ggccttcctg taggttggca ctaattggtt tggctgcagc 240tccacttatt aagtagttat ttttattact aacaacctag gcagggtggc ccaggagccc 300gctgggggag gcggtgccag gctcctggct gaggggcagg ctggccccaa ttctgactgg 360ctggctccag tgatcaggac cagggcccca cgtggtgctt tgctggagat ctaggcttgg 420tggggcagct gtggggtaag gggcaggacc agctcaaaga tggggtgggg gcggaggctg 480cctctgcagg gcagagtcct ttggcagtcg ggactgttgg gcatagagga gtcagctcac 540agctcagggc cagagcactg gagaggtctc tggggtgcat acaggaacca ggagtggagc 600tgaagcatgt cctatcccct gccagccctc ccttagtaac agctggcatt tctcgagtcc 660ttcctgagca ccaggcaccg tgttatgtat gcaatttgca aatattatct gattaaatgc 720tcacaataag gctatcagag aggtactatt attatcctta tcttattatt attattatta 780ttatttttaa gaaggagtct gaggcaggag aatctcttga acctgggagg cagagtttgc 840agtgagctga gatggcacca ctgtactcca gcctggccga caaagtgaga ctctgtctca 900aaaaaaaaaa aaaagaaccc aaacttttgg tgttcagcca tgttcccatg ctcactccca 960gggtggtgac tctgggaagg tctcagcctc cttgtctgcc cagttagaat gatctgatgc 1020ccctgctacc atcagacttg ataagtttcc caaagactct ttgcaagaag cactgttctg 1080gagggtggag gagagactaa ttgttcttgc tctcctggcc agagtgggaa gctttggggt 1140ggccggtttg tgggtgcagt ggaccccatc atg gag aag ttc aac gcg tcc att 1194
Met?Glu?Lys?Phe?Asn?Ala?Ser?Ile
1???????????????5gcc?tac?gac?cgg?cac?ctt?tgg?gag?gtg?gat?gtt?caa?ggc?agc?aaa?gcc?????1242Ala?Tyr?Asp?Arg?His?Leu?Trp?Glu?Val?Asp?Val?Gln?Gly?Ser?Lys?Ala
10??????????????????15??????????????????20tac?agc?agg?ggc?ctg?gag?aag?gca?ggg?ctc?ctc?acc?aag?gcc?gag?atg?????1290Tyr?Ser?Arg?Gly?Leu?Glu?Lys?Ala?Gly?Leu?Leu?Thr?Lys?Ala?Glu?Met25??????????????????30??????????????????35??????????????????40gac?cag?ata?ctc?cat?ggc?cta?gac?aag?gtg?gct?gag?gag?tgg?gcc?cag?????1338Asp?Gln?Ile?Leu?His?Gly?Leu?Asp?Lys?Val?Ala?Glu?Glu?Trp?Ala?Gln
45??????????????????50??????????????????55ggc?acc?ttc?aaa?ctg?aac?tcc?aat?gat?gag?gac?atc?cac?aca?gcc?aat?????1386Gly?Thr?Phe?Lys?Leu?Asn?Ser?Asn?Asp?Glu?Asp?Ile?His?Thr?Ala?Asn
60??????????????????65??????????????????70gag?cgc?cgc?ctg?aag?gag?ctc?att?ggt?gca?acg?gca?ggg?aag?ctg?cac?????1434Glu?Arg?Arg?Leu?Lys?Glu?Leu?Ile?Gly?Ala?Thr?Ala?Gly?Lys?Leu?His
75??????????????????80??????????????????85acg?gga?cgg?agc?cgg?aat?gac?cag?gtg?ctt?tagcccctcc?accccctgct???????1484Thr?Gly?Arg?Ser?Arg?Asn?Asp?Gln?Val?Leu
90 95ccgtgttgtc ccaaccttga ggagcccagg gggcagttag agttctgcag cggtcctggc 1544tcctcaggga agcaacacat cggcctccct gagcaccatc tcctccttgc acaggtggtc 1604acagacctca ggctgtggat gcggcagacc tgctccacgc tctcgggcct cctctgggag 1664ctcattagga ccatggtgga tcgggcagag gcgtgagtcc tacagggaca cccagggggc 1724agacagaggt gtgatggaag cctgaacagg agacctaggg ggcaggggtg aacagcgtgg 1784gggtgccagg ccctggggga caggggcatc ccagaactcc aggatcgagg cagagcagcc 1844aggagtgggc catttcctgc aggccccaat actcccatgc cagtctagct cagcaggcag 1904agaagactaa cccttcgtgg ggctgggtgc ggtggctcac gcctgtaatc tcagcacttt 1964gggaggccga ggtgggtgga tcacctgagg tcaggagttc gagaccagcc tggccaacat 2024ggggaaactc tgtctctact aaaaatacaa aaattaggca atgtggtggt gtgcgcctgt 2084aatcccagct actcgggagc ctgaggcaga agaactgctt gaacccggga ggaggaggtt 2144gcaatgagcc gagatcgcgc cattgcactc cagcctgggc tacagagcga gactcctgtc 2204tcaaaaaaaa agaaaaaaaa aaaaaaaaaa 2234<210〉9<21l〉98<212〉PRT<213〉 ( Homo sapiens )<400〉9Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg His Leu Trp Glu1 5 10 15Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly Leu Glu Lys Ala
20??????????????????25??????????????????30Gly?Leu?Leu?Thr?Lys?Ala?Glu?Met?Asp?Gln?Ile?Leu?His?Gly?Leu?Asp
35??????????????????40??????????????????45Lys?Val?Ala?Glu?Glu?Trp?Ala?Gln?Gly?Thr?Phe?Lys?Leu?Asn?Ser?Asn
50??????????????????55??????????????????60Asp?Glu?Asp?Ile?His?Thr?Ala?Asn?Glu?Arg?Arg?Leu?Lys?Glu?Leu?Ile65??????????????????70??????????????????75??????????????????80Gly?Ala?Thr?Ala?Gly?Lys?Leu?His?Thr?Gly?Arg?Ser?Arg?Asn?Asp?Gln
85 90 95Val Leu<210〉10<211〉2103<212〉DNA<213〉 ( Homo sapiens )<400〉10ggtaggggtg tgggcaggag tcttactgtt cattctgctg tgttcactcg agttgcctcc 60acccctcccc caggagatgg agccctggta gcaggaatcc ccattctcag acctcagatg 120ccctctgcac ctgggcactg agagcacagt caaacagggc taagcagctt gtgccgcctg 180gctttccccg ggaacacctg gcccactgtg tgccctagcc ctggacctgt ctccgagtac 240atagacgttt cctgtgtgcc tcctgccagg gagtagtgga gggttaatgg tggttttcgc 300tgtgataaac ctgctttctc ctcaggggca tatcagactt gaaattgaca atttggggtc 360ctgagattga aacaggagtc aaaaccagag cccagggtag ctgcggcccc cggaccacga 420cgcccacttc cccacacctc ctgctgtccc cctctccgca ggtccagccc tctcctggtg 480gccgcgtttg gcgcctgctc tctcaccagg cagtgcaacc accaagcctt ccagaagcac 540ggtcgctcca ccaccacctc cgacatgatc gccgaggtgg gggccgcctt cagcaagctc 600tttgaaacct gagcccgcgc agaccagaag taaacaggca ccttggacgg gggagagcgt 660gtgtgtgatg ggaaaatccg gacccacgcg tgtgctgaag gcgtacggtg cttgccagat 720tttcaacttg agcataaatt ggttgccatt gagaatttaa gaatctggaa tattgcagct 780tttggttaaa cttaatgcat ggttggagat gttatggcga cactaaacaa agtattcctg 840aactttcctt agctccttgg tagtaactgg gaagacagaa atgaagaaaa tcacatgaga 900atgaagaatt ctttagcagc tcaacagagt ttctcggcct gctcccagat cggcgaagtt 960tctacttgtt actctctctg ccggcgccct tcgttcctcc tctgcttccc ttccctagtc 1020tttcctccgg cagggagctg ggcaggggtc cccgggtgtc tccctgagtc ccgactgcac 1080tgactgggtc catcagaggg ctgcttcgtt ctccagctca tcttctttta aagtggtgac 1140tagcttggtg gtatctggct gctggtgttt ggcttattga catactccag ggtaatcaat 1200gatgactttg tttggaaacc cttttggagg caccatggga acagaaggaa acatgagtga 1260cgctgaccct tgagtgtgtg ggtggggagc tctgagacgc ctcctgtccc acgctctccg 1320gtgtccgtgt ctacacaggg gtccccatga tacccaccgg ccccagcagg gcagaccgga 1380ccggggacgg gcacggtgaa gggctgcagc ctggggtctg acgtggcccc tagtgctgtc 1440tcaggagaag gctctggagg acttgaggca tgctgggcct ggtgcagtga tggcgctaag 1500gagacccggg gaaagacagt atcgtggtca cgtatgctta ggaagcagca cagccgtgtc 1560cttagggatg ttcgcgtcca gtaaagacac tggtaactgc ggtttcagcc aacactcttc 1620atggcagtgt cgacctcggg ttagcttctg ttgtctttgt ggatggtttt cctggagcgg 1680cctgacgttg acgtgttctc tggtcccatg tcttagcggg gcatggtacg gttttgtgcc 1740tgacgcgtgc attagggtgt tctcttatac tttcagtagc atctttccac agcaagggcc 1800aaaccctcct ggttcccttc agagtctttt tggcctgatg atgactcttg agtgataccc 1860tgtgatgcag acatgcccca gatggattct actttcttta aaactaggga ctttcaagat 1920taaaaaaaag attgtcacta ctaatttgac gcctaacttc agaagcttca ctgtctacat 1980gtgaactttt ccagaaaaac tgtgccatgg acatttttcc tctggggaat taacatctaa 2040attctggtaa ctattaaaag acagatctgg ttaatttaaa aaaaaaaaaa aaaaaaaaaa 2100aaa 2103<210〉11<211〉2103<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 1490 ) .. ( 1852 )<223〉<400〉11ggtaggggtg tgggcaggag tcttactgtt cattctgctg tgttcactcg agttgcctcc 60acccctcccc caggagatgg agccctggta gcaggaatcc ccattctcag acctcagatg 120ccctctgcac ctgggcactg agagcacagt caaacagggc taagcagctt gtgccgcctg 180gctttccccg ggaacacctg gcccactgtg tgccctagcc ctggacctgt ctccgagtac 240atagacgttt cctgtgtgcc tcctgccagg gagtagtgga gggttaatgg tggttttcgc 300tgtgataaac ctgctttctc ctcaggggca tatcagactt gaaattgaca atttggggtc 360ctgagattga aacaggagtc aaaaccagag cccagggtag ctgcggcccc cggaccacga 420cgcccacttc cccacacctc ctgctgtccc cctctccgca ggtccagccc tctcctggtg 480gccgcgtttg gcgcctgctc tctcaccagg cagtgcaacc accaagcctt ccagaagcac 540ggtcgctcca ccaccacctc cgacatgatc gccgaggtgg gggccgcctt cagcaagctc 600tttgaaacct gagcccgcgc agaccagaag taaacaggca ccttggacgg gggagagcgt 660gtgtgtgatg ggaaaatccg gacccacgcg tgtgctgaag gcgtacggtg cttgccagat 720tttcaacttg agcataaatt ggttgccatt gagaatttaa gaatctggaa tattgcagct 780tttggttaaa cttaatgcat ggttggagat gttatggcga cactaaacaa agtattcctg 840aactttcctt agctccttgg tagtaactgg gaagacagaa atgaagaaaa tcacatgaga 900atgaagaatt ctttagcagc tcaacagagt ttctcggcct gctcccagat cggcgaagtt 960tctacttgtt actctctctg ccggcgccct tcgttcctcc tctgcttccc ttccctagtc 1020tttcctccgg cagggagctg ggcaggggtc cccgggtgtc tccctgagtc ccgactgcac 1080tgactgggtc catcagaggg ctgcttcgtt ctccagctca tcttctttta aagtggtgac 1140tagcttggtg gtatctggct gctggtgttt ggcttattga catactccag ggtaatcaat 1200gatgactttg tttggaaacc cttttggagg caccatggga acagaaggaa acatgagtga 1260cgctgaccct tgagtgtgtg ggtggggagc tctgagacgc ctcctgtccc acgctctccg 1320gtgtccgtgt ctacacaggg gtccccatga tacccaccgg ccccagcagg gcagaccgga 1380ccggggacgg gcacggtgaa gggctgcagc ctggggtctg acgtggcccc tagtgctgtc 1440tcaggagaag gctctggagg acttgaggca tgctgggcct ggtgcagtg atg gcg cta 1498
Met?Ala?Leu
1agg?aga?ccc?ggg?gaa?aga?cag?tat?cgt?ggt?cac?gta?tgc?tta?gga?agc?????1546Arg?Arg?Pro?Gly?Glu?Arg?Gln?Tyr?Arg?Gly?His?Val?Cys?Leu?Gly?Ser
5???????????????????10??????????????????15agc?aca?gcc?gtg?tcc?tta?ggg?atg?ttc?gcg?tcc?agt?aaa?gac?act?ggt?????1594Ser?Thr?Ala?Val?Ser?Leu?Gly?Met?Phe?Ala?Ser?Ser?Lys?Asp?Thr?Gly20??????????????????25??????????????????30??????????????????35aac?tgc?ggt?ttc?agc?caa?cac?tct?tca?tgg?cag?tgt?cga?cct?cgg?gtt?????1642Asn?Cys?Gly?Phe?Ser?Gln?His?Ser?Ser?Trp?Gln?Cys?Arg?Pro?Arg?Val
40??????????????????45??????????????????50agc?ttc?tgt?tgt?ctt?tgt?gga?tgg?ttt?tcc?tgg?agc?ggc?ctg?acg?ttg?????1690Ser?Phe?Cys?Cys?Leu?Cys?Gly?Trp?Phe?Ser?Trp?Ser?Gly?Leu?Thr?Leu
55??????????????????60??????????????????65acg?tgt?tct?ctg?gtc?cca?tgt?ctt?agc?ggg?gca?tgg?tac?ggt?ttt?gtg?????1738Thr?Cys?Ser?Leu?Val?Pro?Cys?Leu?Ser?Gly?Ala?Trp?Tyr?Gly?Phe?Val
70??????????????????75??????????????????80cct?gac?gcg?tgc?att?agg?gtg?ttc?tct?tat?act?ttc?agt?agc?atc?ttt?????1786Pro?Asp?Ala?Cys?Ile?Arg?Val?Phe?Ser?Tyr?Thr?Phe?Ser?Ser?Ile?Phe
85??????????????????90??????????????????95cca?cag?caa?ggg?cca?aac?cct?cct?ggt?tcc?ctt?cag?agt?ctt?ttt?ggc?????1834Pro?Gln?Gln?Gly?Pro?Asn?Pro?Pro?Gly?Ser?Leu?Gln?Ser?Leu?Phe?Gly100?????????????????105?????????????????110?????????????????115ctg?atg?atg?act?ctt?gag?tgataccctg?tgatgcagac?atgccccaga????????????1882Leu?Met?Met?Thr?Leu?Glu
120tggattctac tttctttaaa actagggact ttcaagatta aaaaaaagat tgtcactact 1942aatttgacgc ctaacttcag aagcttcact gtctacatgt gaacttttcc agaaaaactg 2002tgccatggac atttttcctc tggggaatta acatctaaat tctggtaact attaaaagac 2062agatctggtt aatttaaaaa aaaaaaaaaa aaaaaaaaaa a 2103<210〉12<211〉121<212〉PRT<213〉homo sapiens (Homo sapiens)<400〉12Met Ala Leu Arg Arg Pro Gly Glu Arg Gln Tyr Arg Gly His Val Cys1 5 10 15Leu Gly Ser Ser Thr Ala Val Ser Leu Gly Met Phe Ala Ser Ser Lys
20??????????????????25??????????????????30Asp?Thr?Gly?Asn?Cys?Gly?Phe?Ser?Gln?His?Ser?Ser?Trp?Gln?Cys?Arg
35??????????????????40??????????????????45Pro?Arg?Val?Ser?Phe?Cys?Cys?Leu?Cys?Gly?Trp?Phe?Ser?Trp?Ser?Gly
50??????????????????55??????????????????60Leu?Thr?Leu?Thr?Cys?Ser?Leu?Val?Pro?Cys?Leu?Ser?Gly?Ala?Trp?Tyr65??????????????????70??????????????????75??????????????????80Gly?Phe?Val?Pro?Asp?Ala?Cys?Ile?Arg?Val?Phe?Ser?Tyr?Thr?Phe?Ser
85??????????????????90??????????????????95Ser?Ile?Phe?Pro?Gln?Gln?Gly?Pro?Asn?Pro?Pro?Gly?Ser?Leu?Gln?Ser
100?????????????????105?????????????????110Leu?Phe?Gly?Leu?Met?Met?Thr?Leu?Glu
115 120<210〉13<211〉1906<212〉DNA<213〉 ( Homo sapiens )<400〉13ggttacagga ggggcacacc gtccttttgt ctctgccttt gaggttggcg ggaactgaaa 60ctgcagagca tgggggtccc tcgtacccct tcacggacag tgctcttcga gcgggagagg 120acgggcctga cctaccgcgt gccctcgctg ctccccgtgc cccccgggcc caccctgctg 180gcctttgtgg agcagcggct cagccctgac gactcccacg cccaccgcct ggtgctgagg 240aggggcacgc tggccggggg ctccgtgcgg tggggtgccc tgcacgtgct ggggacagca 300gccctggcgg agcaccggtc catgaacccc tgccctgtgc acgatgctgg cacgggcacc 360gtcttcctct tcttcatcgc ggtgctgggc cacacgcctg aggccgtgca gatcgccacg 420ggaaggaacg ccgcgcgcct ctgctgtgtg gccagccgtg acgccggcct ctcgtggggc 480agcgcccggg acctcaccga ggaggccatc ggtggtgccg tgcaggactg ggccacattc 540gctgtgggtc ccggccacgg cgtgcagctg ccctcaggcc gcctgctggt acccgcctac 600acctaccgcg tggaccgccg agagtgtttt ggcaagatct gccggaccag ccctcactcc 660ttcgccttct acagcgatga ccacggccgc acctggcgct gtggaggcct cgtgcccaac 720ctgcgctcag gcgagtgcca gctggcggcg gtggacggtg ggcaggccgg cagcttcctc 780tactgcaatg cccggagccc actgggcagc cgtgtgcagg cgctcagcac tgacgagggc 840acctccttcc tgcccgcaga gcgcgtggct tccctgcccg agactgcctg gggctgccag 900ggcagcatcg tgggcttccc agcccccgcc cccaacaggc acgggatgac agttggtcag 960tgggccccag gagtcccctc cagcctccac tcctcggtcc tggagtccac gaacccccag 1020aggaggctgc tgtagacccc cgtggaggcc aggtgcctgg tgggcccttc agccgtctgc 1080agcctcgggg ggatggcccc aggcagcctg gccccaggcc tggggtcagt ggggatgtgg 1140ggtcctggac cctggcactc cccatgccct ttgctgcccc gccccagagc cccacgtggc 1200tgctgtactc ccacccagtg gggcgcaggg ctcggctaca catgggtatc cgcctgagcc 1260agtccccgct ggacccgcgc agctggacag agccctgggt gatctacgag ggccccagcg 1320gctactccga cctggcgtcc atcgggccgg ctcctgaggg gggcctggtt tttgcctgcc 1380tgtacgagag cggggccagg acctcctatg atgagatttc cttttgtaca ttctccctgc 1440gtgaggtcct ggagaacgtg cccgccagcc ccaagccgcc caaccttggg gacaagcctc 1500gggggtgctg ctggccctcc tgacaggcct tctggccgtg cccatgcccc ttgggtgcct 1560ggggcagagg ggtggaatac gttggggtgc cccacaatag ctgtgggggg ggctcttagt 1620gcaagatcct gtggattaga aacaagttgc tcctcagagc tctcaagcag ggactgctct 1680ttaggaaggg gagcagcggc tgggagtgag cagggcaggg tgggggcagg gtgggggcac 1740gaagtgggcc ctgggtgacc cccacagctc ccttccgagg ctgcagggcc aggcgcggga 1800ccgcaggtag cccagggtgg ttgtgggtgg cagcacttgt ttactggctg ctttctggct 1860cgaaataaag gaatcgtgct tgaaaaaaaa aaaaaaaaaa aaaaaa 1906<210〉14<211〉1906<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 70 ) .. ( 1032 )<223〉<400〉14ggttacagga ggggcacacc gtccttttgt ctctgccttt gaggttggcg ggaactgaaa 60ctgcagagc atg ggg gtc cot cgt acc cct tca cgg aca gtg ctc ttc gag 111
Met?Gly?Val?Pro?Arg?Thr?Pro?Ser?Arg?Thr?Val?Leu?Phe?Glu
1???????????????5???????????????????10cgg?gag?agg?acg?ggc?ctg?acc?tac?cgc?gtg?ccc?tcg?ctg?ctc?ccc?gtg??????159Arg?Glu?Arg?Thr?Gly?Leu?Thr?Tyr?Arg?Val?Pro?Ser?Leu?Leu?Pro?Val15??????????????????20??????????????????25??????????????????30ccc?ccc?ggg?ccc?acc?ctg?ctg?gcc?ttt?gtg?gag?cag?cgg?ctc?agc?cct??????207Pro?Pro?Gly?Pro?Thr?Leu?Leu?Ala?Phe?Val?Glu?Gln?Arg?Leu?Ser?Pro
35??????????????????40??????????????????45gac?gac?tcc?cac?gcc?cac?cgc?ctg?gtg?ctg?agg?agg?ggc?acg?ctg?gcc??????255Asp?Asp?Ser?His?Ala?His?Arg?Leu?Val?Leu?Arg?Arg?Gly?Thr?Leu?Ala
50??????????????????55??????????????????60ggg?ggc?tcc?gtg?cgg?tgg?ggt?gcc?ctg?cac?gtg?ctg?ggg?aca?gca?gcc??????303Gly?Gly?Ser?Val?Arg?Trp?Gly?Ala?Leu?His?Val?Leu?Gly?Thr?Ala?Ala
65??????????????????70??????????????????75ctg?gcg?gag?cac?cgg?tcc?atg?aac?ccc?tgc?cct?gtg?cac?gat?gct?ggc??????351Leu?Ala?Glu?His?Arg?Ser?Met?Asn?Pro?Cys?Pro?Val?His?Asp?Ala?Gly
80??????????????????85??????????????????90acg?ggc?acc?gtc?ttc?ctc?ttc?ttc?atc?gcg?gtg?ctg?ggc?cac?acg?cct??????399Thr?Gly?Thr?Val?Phe?Leu?Phe?Phe?Ile?Ala?Val?Leu?Gly?His?Thr?Pro95??????????????????100?????????????????105?????????????????110gag?gcc?gtg?cag?atc?gcc?acg?gga?agg?aac?gcc?gcg?cgc?ctc?tgc?tgt??????447Glu?Ala?Val?Gln?Ile?Ala?Thr?Gly?Arg?Asn?Ala?Ala?Arg?Leu?Cys?Cys
115?????????????????120?????????????????125gtg?gcc?agc?cgt?gac?gcc?ggc?ctc?tcg?tgg?ggc?agc?gcc?cgg?gac?ctc??????495Val?Ala?Ser?Arg?Asp?Ala?Gly?Leu?Ser?Trp?Gly?Ser?Ala?Arg?Asp?Leu
130?????????????????135?????????????????140acc?gag?gag?gcc?atc?ggt?ggt?gcc?gtg?cag?gac?tgg?gcc?aca?ttc?gct??????543Thr?Glu?Glu?Ala?Ile?Gly?Gly?Ala?Val?Gln?Asp?Trp?Ala?Thr?Phe?Ala
145?????????????????150?????????????????155gtg?ggt?ccc?ggc?cac?ggc?gtg?cag?ctg?ccc?tca?ggc?cgc?ctg?ctg?gta??????591Val?Gly?Pro?Gly?His?Gly?Val?Gln?Leu?Pro?Ser?Gly?Arg?Leu?Leu?Val
160?????????????????165?????????????????170ccc?gcc?tac?acc?tac?cgc?gtg?gac?cgc?cga?gag?tgt?ttt?ggc?aag?atc??????639Pro?Ala?Tyr?Thr?Tyr?Arg?Val?Asp?Arg?Arg?Glu?Cys?Phe?Gly?Lys?Ile175?????????????????180?????????????????185?????????????????190tgc?cgg?acc?agc?cct?cac?tcc?ttc?gcc?ttc?tac?agc?gat?gac?cac?ggc?????687Cys?Arg?Thr?Ser?Pro?His?Ser?Phe?Ala?Phe?Tyr?Ser?Asp?Asp?His?Gly
195?????????????????200?????????????????205cgc?acc?tgg?cgc?tgt?gga?ggc?ctc?gtg?ccc?aac?ctg?cgc?tca?ggc?gag?????735Arg?Thr?Trp?Arg?Cys?Gly?Gly?Leu?Val?Pro?Asn?Leu?Arg?Ser?Gly?Glu
210?????????????????215?????????????????220tgc?cag?ctg?gcg?gcg?gtg?gac?ggt?ggg?cag?gcc?ggc?agc?ttc?ctc?tac?????783Cys?Gln?Leu?Ala?Ala?Val?Asp?Gly?Gly?Gln?Ala?Gly?Ser?Phe?Leu?Tyr
225?????????????????230?????????????????235tgc?aat?gcc?cgg?agc?cca?ctg?ggc?agc?cgt?gtg?cag?gcg?ctc?agc?act?????831Cys?Asn?Ala?Arg?Ser?Pro?Leu?Gly?Ser?Arg?Val?Gln?Ala?Leu?Ser?Thr
240?????????????????245?????????????????250gac?gag?ggc?acc?tcc?ttc?ctg?ccc?gca?gag?cgc?gtg?gct?tcc?ctg?ccc?????879Asp?Glu?Gly?Thr?Ser?Phe?Leu?Pro?Ala?Glu?Arg?Val?Ala?Ser?Leu?Pro255?????????????????260?????????????????265?????????????????270gag?act?gcc?tgg?ggc?tgc?cag?ggc?agc?atc?gtg?ggc?ttc?cca?gcc?ccc?????927Glu?Thr?Ala?Trp?Gly?Cys?Gln?Gly?Ser?Ile?Val?Gly?Phe?Pro?Ala?Pro
275?????????????????280?????????????????285gcc?ccc?aac?agg?cac?ggg?atg?aca?gtt?ggt?cag?tgg?gcc?cca?gga?gtc?????975Ala?Pro?Asn?Arg?His?Gly?Met?Thr?Val?Gly?Gln?Trp?Ala?Pro?Gly?Val
290?????????????????295?????????????????300ccc?tcc?agc?ctc?cac?tcc?tcg?gtc?ctg?gag?tcc?acg?aac?ccc?cag?agg????1023Pro?Ser?Ser?Leu?His?Ser?Ser?Val?Leu?Glu?Ser?Thr?Asn?Pro?Gln?Arg
305?????????????????310?????????????????315agg?ctg?ctg?tagacccccg?tggaggccag?gtgcctggtg?ggcccttcag????????????1072Arg?Leu?Leu
320ccgtctgcag cctcgggggg atggccccag gcagcctggc cccaggcctg gggtcagtgg 1132ggatgtgggg tcctggaccc tggcactccc catgcccttt gctgccccgc cccagagccc 1192cacgtggctg ctgtactccc acccagtggg gcgcagggct cggctacaca tgggtatccg 1252cctgagccag tccccgctgg acccgcgcag ctggacagag ccctgggtga tctacgaggg 1312ccccagcggc tactccgacc tggcgtccat cgggccggct cctgaggggg gcctggtttt 1372tgcctgcctg tacgagagcg gggccaggac ctcctatgat gagatttcct tttgtacatt 1432ctccctgcgt gaggtcctgg agaacgtgcc cgccagcccc aagccgccca accttgggga 1492caagcctcgg gggtgctgct ggccctcctg acaggccttc tggccgtgcc catgcccctt 1552gggtgcctgg ggcagagggg tggaatacgt tggggtgccc cacaatagct gtgggggggg 1612ctcttagtgc aagatcctgt ggattagaaa caagttgctc ctcagagctc tcaagcaggg 1672actgctcttt aggaagggga gcagcggctg ggagtgagca gggcagggtg ggggcagggt 1732gggggcacga agtgggccct gggtgacccc cacagctccc ttccgaggct gcagggccag 1792gcgcgggacc gcaggtagcc cagggtggtt gtgggtggca gcacttgttt actggctgct 1852ttctggctcg aaataaagga atcgtgcttg aaaaaaaaaa aaaaaaaaaa aaaa 1906<210〉15<211〉321<212〉PRT<213〉 ( Homo sapiens )<400〉15Met Gly Val Pro Arg Thr Pro Ser Arg Thr Val Leu Phe Glu Arg Glu1 5 10 15Arg Thr Gly Leu Thr Tyr Arg Val Pro Ser Leu Leu Pro Val Pro Pro
20??????????????????25??????????????????30Gly?Pro?Thr?Leu?Leu?Ala?Phe?Val?Glu?Gln?Arg?Leu?Ser?Pro?Asp?Asp
35??????????????????40??????????????????45Ser?His?Ala?His?Arg?Leu?Val?Leu?Arg?Arg?Gly?Thr?Leu?Ala?Gly?Gly
50??????????????????55??????????????????60Ser?Val?Arg?Trp?Gly?Ala?Leu?His?Val?Leu?Gly?Thr?Ala?Ala?Leu?Ala65??????????????????70??????????????????75??????????????????80Glu?His?Arg?Ser?Met?Asn?Pro?Cys?Pro?Val?His?Asp?Ala?Gly?Thr?Gly
85??????????????????90??????????????????95Thr?Val?Phe?Leu?Phe?Phe?Ile?Ala?Val?Leu?Gly?His?Thr?Pro?Glu?Ala
100?????????????????105?????????????????110Val?Gln?Ile?Ala?Thr?Gly?Arg?Asn?Ala?Ala?Arg?Leu?Cys?Cys?Val?Ala
115?????????????????120?????????????????125Ser?Arg?Asp?Ala?Gly?Leu?Ser?Trp?Gly?Ser?Ala?Arg?Asp?Leu?Thr?Glu
130?????????????????135?????????????????140Glu?Ala?Ile?Gly?Gly?Ala?Val?Gln?Asp?Trp?Ala?Thr?Phe?Ala?Val?Gly145?????????????????150?????????????????155?????????????????160Pro?Gly?His?Gly?Val?Gln?Leu?Pro?Ser?Gly?Arg?Leu?Leu?Val?Pro?Ala
165?????????????????170?????????????????175Tyr?Thr?Tyr?Arg?Val?Asp?Arg?Arg?Glu?Cys?Phe?Gly?Lys?Ile?Cys?Arg
180?????????????????185?????????????????190Thr?Ser?Pro?His?Ser?Phe?Ala?Phe?Tyr?Ser?Asp?Asp?His?Gly?Arg?Thr
195?????????????????200?????????????????205Trp?Arg?Cys?Gly?Gly?Leu?Val?Pro?Asn?Leu?Arg?Ser?Gly?Glu?Cys?Gln
210?????????????????215?????????????????220Leu?Ala?Ala?Val?Asp?Gly?Gly?Gln?Ala?Gly?Ser?Phe?Leu?Tyr?Cys?Asn225?????????????????230?????????????????235?????????????????240Ala?Arg?Ser?Pro?Leu?Gly?Ser?Arg?Val?Gln?Ala?Leu?Ser?Thr?Asp?Glu
245?????????????????250?????????????????255Gly?Thr?Ser?Phe?Leu?Pro?Ala?Glu?Arg?Val?Ala?Ser?Leu?Pro?Glu?Thr
260?????????????????265?????????????????270Ala?Trp?Gly?Cys?Gln?Gly?Ser?Ile?Val?Gly?Phe?Pro?Ala?Pro?Ala?Pro
275?????????????????280?????????????????285Asn?Arg?His?Gly?Met?Thr?Val?Gly?Gln?Trp?Ala?Pro?Gly?Val?Pro?Ser
290 295 300Ser Leu His Ser Ser Val Leu Glu Ser Thr Asn Pro Gln Arg Arg Leu305 310 315 320Leu<210〉16<211〉2038<212〉DNA<213〉 ( Homo sapiens )<400〉16ggctgttcgt ccgggttttt tacgttttaa tttccaggac ttgaactgcc atgtcctctg 60aagaaggaaa gctcttcgtg ggagggctca actttaacac cgacgagcag gcactggaag 120accacttcag cagtttcgga cctatctctg aggtggtcgt tgtcaaggac cgggagactc 180agcggtccag gggttttggt ttcatcacct tcaccaaccc agagcatgct tcagttgcca 240tgagagccat gaacggagag gtggggcctc ctatctgcag agggaccttg tccccatctg 300cggcttcctt cattcttttt gtttttccct ctgtgtctgc tcggggcagc gtggccacca 360agccccgcag tgcccactca caggagcatg actgcctttt gttctagggg gtggagggca 420gcggcagaca gagcctggcc gcctgggagg cgacgactgg tcctgcatga ggccgagaag 480ccacctgtgg atggttgacc tgccttgggc ttaggtagta gagtctgcag acctgtgggc 540ctggcccgga gaggacctcg tgagtcttct gacatggact ctgaagcctc aaaccaagag 600aggtgtctgt ctagccctga tagtcgggca gcttagagga gtggggagga gaactcagcc 660tgagttcagt caagatgtaa gtagtagcaa ggggaacatg gtgcattcag gtcattttgt 720gtgggattct atagctcctg atgaagccat tctggggtaa aggagcttat tctggaacat 780ggcacccaga acctggtgcc cagcaggaat ttttggcctc ttttgcccac ttacccttgc 840ctgctcttcc ctcaccattg ccctgactga ctgccaaccc atcatccttg tgtctcccac 900acttagtctc tggatggtcg tcagatccgt gtggatcatg caggcaagtc tgctcgggga 960accagaggag gtggctttgg ggcccatggg cgtggtcgca gctactctag aggtggtggg 1020gaccagggct atgggagtgg caggtattat gacagtcgac ctggagggta tggatatgga 1080tatggacgtt ccagagacta taatggcaga aaccagggtg gttatgaccg ctactcagga 1140ggaaattaca gagacaatta tgacaactga aatgagacat gcacataata tagatacaca 1200aggaataatt tctgatccag gatcgtcctt ccaaatggct gtatttataa aggtttttgg 1260agctgcactg aagcatctta ttttatagta tatcaacctt ttgtttttaa attgacctgc 1320caaggtagct gaagaccttt tagacagttc catctttttt tttaaatttt ttctgcctat 1380ttaaagacaa attatgggac gtttgtagaa cctgagtatt tttcttttta ccagtttttt 1440agtttgagct cttaggttta ttggagctag caataattgg ttctggcaag tttggccaga 1500ctgacttcaa aaaattaatg tgtatccagg gacattttaa aaacctgtac acagtgttta 1560ttgtggttag gaagcaattt cccaatgtac ctataagaaa tgtgcatcaa gccagcctga 1620ccaacatggt gaaaccccat ctgtactaaa cataaaaaaa ttagcctggc atggtggtgt 1680acgcctgtaa tcccagtgac ttgggaggct gaggcaggag aatcgcttga acccgggagg 1740cggaggttgc agtgagctaa gatcgcgcca ctgtactcca gcctgggcaa cagcgagact 1800ccatctcaaa aaaaaaggaa atgtgtatca agaacatgat tatccagggg tattttttaa 1860ttcagatcat caaactgatt atatagaaga gttggcttta aaatgtttgc aaatgtcttt 1920ttttttttaa tactggaaga aaaaatattc tgttgtgtct catacagtgc ttaggatgtc 1980tttcacagag cttattaaaa agatgaaacc tgagaaaaaa aaaaaaaaaa aaaaaaaa 2038<210〉17<211〉2038<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 779 ) .. ( 1285 )<223〉<400〉17ggctgttcgt ccgggttttt tacgttttaa tttccaggac ttgaactgcc atgtcctctg 60aagaaggaaa gctcttcgtg ggagggctca actttaacac cgacgagcag gcactggaag 120accacttcag cagtttcgga cctatctctg aggtggtcgt tgtcaaggac cgggagactc 180agcggtccag gggttttggt ttcatcacct tcaccaaccc agagcatgct tcagttgcca 240tgagagccat gaacggagag gtggggcctc ctatctgcag agggaccttg tccccatctg 300cggcttcctt cattcttttt gtttttccct ctgtgtctgc tcggggcagc gtggccacca 360agccccgcag tgcccactca caggagcatg actgcctttt gttctagggg gtggagggca 420gcggcagaca gagcctggcc gcctgggagg cgacgactgg tcctgcatga ggccgagaag 480ccacctgtgg atggttgacc tgccttgggc ttaggtagta gagtctgcag acctgtgggc 540ctggcccgga gaggacctcg tgagtcttct gacatggact ctgaagcctc aaaccaagag 600aggtgtctgt ctagccctga tagtcgggca gcttagagga gtggggagga gaactcagcc 660tgagttcagt caagatgtaa gtagtagcaa ggggaacatg gtgcattcag gtcattttgt 720gtgggattct atagctcctg atgaagccat tctggggtaa aggagcttat tctggaac 778atg gca ccc aga acc tgg tgc cca gca gga att ttt ggc ctc ttt tgc 826Met Ala Pro Arg Thr Trp Cys Pro Ala Gly Ile Phe Gly Leu Phe Cys1 5 10 15cca ctt acc ctt gcc tgc tct tcc ctc acc att gcc ctg act gac tgc 874Pro Leu Thr Leu Ala Cys Ser Ser Leu Thr Ile Ala Leu Thr Asp Cys
20??????????????????25??????????????????30caa?ccc?atc?atc?ctt?gtg?tct?ccc?aca?ctt?agt?ctc?tgg?atg?gtc?gtc????922Gln?Pro?Ile?Ile?Leu?Val?Ser?Pro?Thr?Leu?Ser?Leu?Trp?Met?Val?Val
35??????????????????40??????????????????45aga?tcc?gtg?tgg?atc?atg?cag?gca?agt?ctg?ctc?ggg?gaa?cca?gag?gag????970Arg?Ser?Val?Trp?Ile?Met?Gln?Ala?Ser?Leu?Leu?Gly?Glu?Pro?Glu?Glu
50??????????????????55??????????????????60gtg?gct?ttg?ggg?ccc?atg?ggc?gtg?gtc?gca?gct?act?cta?gag?gtg?gtg???1018Val?Ala?Leu?Gly?Pro?Met?Gly?Val?Val?Ala?Ala?Thr?Leu?Glu?Val?Val65??????????????????70??????????????????75??????????????????80ggg?acc?agg?gct?atg?gga?gtg?gca?ggt?att?atg?aca?gtc?gac?ctg?gag???1066Gly?Thr?Arg?Ala?Met?Gly?Val?Ala?Gly?Ile?Met?Thr?Val?Asp?Leu?Glu
85??????????????????90??????????????????95ggt?atg?gat?atg?gat?atg?gac?gtt?cca?gag?act?ata?atg?gca?gaa?acc???1114Gly?Met?Asp?Met?Asp?Met?Asp?Val?Pro?Glu?Thr?Ile?Met?Ala?Glu?Thr
100?????????????????105?????????????????110agg?gtg?gtt?atg?acc?gct?act?cag?gag?gaa?att?aca?gag?aca?att?atg???1162Arg?Val?Val?Met?Thr?Ala?Thr?Gln?Glu?Glu?Ile?Thr?Glu?Thr?Ile?Met
115?????????????????120?????????????????125aca?act?gaa?atg?aga?cat?gca?cat?aat?ata?gat?aca?caa?gga?ata?att???1210Thr?Thr?Glu?Met?Arg?His?Ala?His?Asn?Ile?Asp?Thr?Gln?Gly?Ile?Ile
130?????????????????135?????????????????140tct?gat?cca?gga?tcg?tcc?ttc?caa?atg?gct?gta?ttt?ata?aag?gtt?ttt???1258Ser?Asp?Pro?Gly?Ser?Ser?Phe?Gln?Met?Ala?Val?Phe?Ile?Lys?Val?Phe145?????????????????150?????????????????155?????????????????160gga?gct?gca?ctg?aag?cat?ctt?att?tta?tagtatatca?accttttgtt?????????1305Gly?Ala?Ala?Leu?Lys?His?Leu?Ile?Leu
165tttaaattga cctgccaagg tagctgaaga ccttttagac agttccatct ttttttttaa 1365attttttctg cctatttaaa gacaaattat gggacgtttg tagaacctga gtatttttct 1425ttttaccagt tttttagttt gagctcttag gtttattgga gctagcaata attggttctg 1485gcaagtttgg ccagactgac ttcaaaaaat taatgtgtat ccagggacat tttaaaaacc 1545tgtacacagt gtttattgtg gttaggaagc aatttcccaa tgtacctata agaaatgtgc 1605atcaagccag cctgaccaac atggtgaaac cccatctgta ctaaacataa aaaaattagc 1665ctggcatggt ggtgtacgcc tgtaatccca gtgacttggg aggctgaggc aggagaatcg 1725cttgaacccg ggaggcggag gttgcagtga gctaagatcg cgccactgta ctccagcctg 1785ggcaacagcg agactccatc tcaaaaaaaa aggaaatgtg tatcaagaac atgattatcc 1845aggggtattt tttaattcag atcatcaaac tgattatata gaagagttgg ctttaaaatg 1905tttgcaaatg tctttttttt tttaatactg gaagaaaaaa tattctgttg tgtctcatac 1965agtgcttagg atgtctttca cagagcttat taaaaagatg aaacctgaga aaaaaaaaaa 2025aaaaaaaaaa aaa 2038<210〉18<211〉169<212〉PRT<213〉 ( Homo sapiens )<400〉18Met Ala Pro Arg Thr Trp Cys Pro Ala Gly Ile Phe Gly Leu Phe Cys1 5 10 15Pro Leu Thr Leu Ala Cys Ser Ser Leu Thr Ile Ala Leu Thr Asp Cys
20??????????????????25??????????????????30Gln?Pro?Ile?Ile?Leu?Val?Ser?Pro?Thr?Leu?Ser?Leu?Trp?Met?Val?Val
35??????????????????40??????????????????45Arg?Ser?Val?Trp?Ile?Met?Gln?Ala?Ser?Leu?Leu?Gly?Glu?Pro?Glu?Glu
50??????????????????55??????????????????60Val?Ala?Leu?Gly?Pro?Met?Gly?Val?Val?Ala?Ala?Thr?Leu?Glu?Val?Val65??????????????????70??????????????????75??????????????????80Gly?Thr?Arg?Ala?Met?Gly?Val?Ala?Gly?Ile?Met?Thr?Val?Asp?Leu?Glu
85??????????????????90??????????????????95Gly?Met?Asp?Met?Asp?Met?Asp?Val?Pro?Glu?Thr?Ile?Met?Ala?Glu?Thr
100?????????????????105?????????????????110Arg?Val?Val?Met?Thr?Ala?Thr?Gln?Glu?Glu?Ile?Thr?Glu?Thr?Ile?Met
115?????????????????120?????????????????125Thr?Thr?Glu?Met?Arg?His?Ala?His?Asn?Ile?Asp?Thr?Gln?Gly?Ile?Ile
130?????????????????135?????????????????140Ser?Asp?Pro?Gly?Ser?Ser?Phe?Gln?Met?Ala?Val?Phe?Ile?Lys?Val?Phe145?????????????????150?????????????????155?????????????????160Gly?Ala?Ala?Leu?Lys?His?Leu?Ile?Leu
165<210〉19<211〉1965<212〉DNA<213〉 ( Homo sapiens )<400〉19ggctaatccc atcccctagg ccctaggagg tccctgttaa aaggaccaag tgggccaggt 60gcggtggctc aagcttgtaa tcccagcact ttggggggcc gaggtgggtg gatcacgagg 120tcaggagata agagaccatc ctggccaaca gggtgaaatc ccgtccctac taaaaataga 180aaaagtagtt gggtgtggtg gcgcactgtg tagtcctagc tactcgggag gctgaggttg 240cagtgagcca agatcgcgcc acggcactcc agcctggcaa cagagcgaga ctccatctca 300aaaaaaaagc accaagtgtg ggtctcacag tcctggccct gctccaggcc tttcttcttg 360cctcatccta ctctgtctcc agctccatgc agctattata tttccttaag cgagttgact 420ccttccccat tcacaatgta ctaatttcag aacactcaac ttctacatat acaaattctc 480aaaaatcaat gcctaaaaac tagtgacgta atcgttcatt atttctttct ttcaagaaat 540atttatattg cacaaatcca tgcaacacaa tcgattttct ttctatggca gctggatact 600gtgtgatgac tttctttgta ggttatacac cccatcttga tgacaatgca ttaatgggga 660taaatactcc ccagaagagc ttcggcctgt cctgagatct gcaacacaag gagtttttaa 720cctggaaagt gtgcttaatt cttctactgc ctcttcttga gggctgccta agtacagaaa 780tgtttggtgt cctggagggt gcccaggcta acagtgagaa ttggatagct ccatcagggc 840cttgggcact gggcctatgg agtagcctgt acttcttgct cttttcaaca cttgaaggga 900gagggggccg agttctctcg cagagttgct ctatggcagt ggcagcagcc agctggatat 960cacgggaaaa tgcccgctcc gtgaaacggt catatatgca aagtagcccc caaaggccaa 1020aagagccaag aaaccaaaga acaagccaca caactccagt ttgttgataa aggatgtttt 1080actggggaaa cttacagatg gaagcatggt ctttagcggc agcaatacag gtagatctct 1140gcacctgtta cccccagaac cagggcttat atagcatagg gaaagggtat gtgtgccctg 1200tgcaagacaa tgaaagacta ccctctagaa gaggcaagaa tgctgcatgc atcaaagcct 1260ataatttgtg caacagcatc aaggttgaca tgttcttaca ttagggacag taaattaagt 1320aataatcaga aggcattccc gagacaacgg ctaatcagaa gtgaaaacag caaattagcc 1380tccaacatgg cgtcacttgt gtccccactt cctcttggta atagtcacat gctcaacctt 1440ctactgtgac ttggagcaag tggcttcctt actcttggtt aaggttgttg acctgttaat 1500aaaataagat taaagggcac ataaaaatgt cactggacag atcttgtcag cagccctttg 1560agtgcacaca aaggctatca gtaaagcaga aagcaaagca gatgtgaagc tggggttcta 1620cccaactaag tcaggtgtca gcagcattag aagggccctt ccaaggccgg gcgtggtggc 1680tcacgcctgt aatcccagca ctttgggagg ccgaggcggg cggatcacga ggtcaggaga 1740tcgagatcat cctggctaac acggtgaaac accgtctcta ctaaaaatac aaaaattagc 1800cgggcgtggt ggcgggcgcc tgtagtccca gctactcggg aggctgaggc aggaggatgg 1860agtgaacccg ggaggcagag cttgcagtga gccgagattg cgccactgca ctcccagctt 1920gggaaacaga gagcaagact ccgtctcaaa aaaaaaaaaa aaaaa 1965<210〉20<211〉1965<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 780 ) .. ( 1064 )<223〉<400〉20ggctaatccc atcccctagg ccctaggagg tccctgttaa aaggaccaag tgggccaggt 60gcggtggctc aagcttgtaa tcccagcact ttggggggcc gaggtgggtg gatcacgagg 120tcaggagata agagaccatc ctggccaaca gggtgaaatc ccgtccctac taaaaataga 180aaaagtagtt gggtgtggtg gcgcactgtg tagtcctagc tactcgggag gctgaggttg 240cagtgagcca agatcgcgcc acggcactcc agcctggcaa cagagcgaga ctccatctca 300aaaaaaaagc accaagtgtg ggtctcacag tcctggccct gctccaggcc tttcttcttg 360cctcatccta ctctgtctcc agctccatgc agctattata tttccttaag cgagttgact 420ccttccccat tcacaatgta ctaatttcag aacactcaac ttctacatat acaaattctc 480aaaaatcaat gcctaaaaac tagtgacgta atcgttcatt atttctttct ttcaagaaat 540atttatattg cacaaatcca tgcaacacaa tcgattttct ttctatggca gctggatact 600gtgtgatgac tttctttgta ggttatacac cccatcttga tgacaatgca ttaatgggga 660taaatactcc ccagaagagc ttcggcctgt cctgagatct gcaacacaag gagtttttaa 720cctggaaagt gtgcttaatt cttctactgc ctcttcttga gggctgccta agtacagaa 779atg ttt ggt gtc ctg gag ggt gcc cag gct aac agt gag aat tgg ata 827Met Phe Gly Val Leu Glu Gly Ala Gln Ala Asn Ser Glu Asn Trp Ile1 5 10 15gct cca tca ggg cct tgg gca ctg ggc cta tgg agt agc ctg tac ttc 875Ala Pro Ser Gly Pro Trp Ala Leu Gly Leu Trp Ser Ser Leu Tyr Phe
20??????????????????25??????????????????30ttg?ctc?ttt?tca?aca?ctt?gaa?ggg?aga?ggg?ggc?cga?gtt?ctc?tcg?cag??????923Leu?Leu?Phe?Ser?Thr?Leu?Glu?Gly?Arg?Gly?Gly?Arg?Val?Leu?Ser?Gln
35??????????????????40??????????????????45agt?tgc?tct?atg?gca?gtg?gca?gca?gcc?agc?tgg?ata?tca?cgg?gaa?aat??????971Ser?Cys?Ser?Met?Ala?Val?Ala?Ala?Ala?Ser?Trp?Ile?Ser?Arg?Glu?Asn
50??????????????????55??????????????????60gcc?cgc?tcc?gtg?aaa?cgg?tca?tat?atg?caa?agt?agc?ccc?caa?agg?cca?????1019Ala?Arg?Ser?Val?Lys?Arg?Ser?Tyr?Met?Gln?Ser?Ser?Pro?Gln?Arg?Pro65??????????????????70??????????????????75??????????????????80aaa?gag?cca?aga?aac?caa?aga?aca?agc?cac?aca?act?cca?gtt?tgt?????????1064Lys?Glu?Pro?Arg?Asn?Gln?Arg?Thr?Ser?His?Thr?Thr?Pro?Val?Cys
85 90 95tgataaagga tgttttactg gggaaactta cagatggaag catggtcttt agcggcagca 1124atacaggtag atctctgcac ctgttacccc cagaaccagg gcttatatag catagggaaa 1184gggtatgtgt gccctgtgca agacaatgaa agactaccct ctagaagagg caagaatgct 1244gcatgcatca aagcctataa tttgtgcaac agcatcaagg ttgacatgtt cttacattag 1304ggacagtaaa ttaagtaata atcagaaggc attcccgaga caacggctaa tcagaagtga 1364aaacagcaaa ttagcctcca acatggcgtc acttgtgtcc ccacttcctc ttggtaatag 1424tcacatgctc aaccttctac tgtgacttgg agcaagtggc ttccttactc ttggttaagg 1484ttgttgacct gttaataaaa taagattaaa gggcacataa aaatgtcact ggacagatct 1544tgtcagcagc cctttgagtg cacacaaagg ctatcagtaa agcagaaagc aaagcagatg 1604tgaagctggg gttctaccca actaagtcag gtgtcagcag cattagaagg gcccttccaa 1664ggccgggcgt ggtggctcac gcctgtaatc ccagcacttt gggaggccga ggcgggcgga 1724tcacgaggtc aggagatcga gatcatcctg gctaacacgg tgaaacaccg tctctactaa 1784aaatacaaaa attagccggg cgtggtggcg ggcgcctgta gtcccagcta ctcgggaggc 1844tgaggcagga ggatggagtg aacccgggag gcagagcttg cagtgagccg agattgcgcc 1904actgcactcc cagcttggga aacagagagc aagactccgt ctcaaaaaaa aaaaaaaaaa 1964a 1965<210〉21<211〉95<212〉PRT<213〉 ( Homo sapiens )<400〉21Met Phe Gly Val Leu Glu Gly Ala Gln Ala Asn Ser Glu Asn Trp Ile1 5 10 15Ala Pro Ser Gly Pro Trp Ala Leu Gly Leu Trp Ser Ser Leu Tyr Phe
20??????????????????25??????????????????30Leu?Leu?Phe?Ser?Thr?Leu?Glu?Gly?Arg?Gly?Gly?Arg?Val?Leu?Ser?Gln
35??????????????????40??????????????????45Ser?Cys?Ser?Met?Ala?Val?Ala?Ala?Ala?Ser?Trp?Ile?Ser?Arg?Glu?Asn
50??????????????????55??????????????????60Ala?Arg?Ser?Val?Lys?Arg?Ser?Tyr?Met?Gln?Ser?Ser?Pro?Gln?Arg?Pro65??????????????????70??????????????????75??????????????????80Lys?Glu?Pro?Arg?Asn?Gln?Arg?Thr?Ser?His?Thr?Thr?Pro?Val?Cys
85 90 95<210〉22<211〉2427<212〉DNA<213〉 ( Homo sapiens )<400〉22ggccggctga ggagcgccgc tgcctcgcct cggtacgccg cgcggcgcgg acggcgcgct 60ccccacaggt gcaggaagcc gccgcccagc catggacggg gaggagcagc agccaccgca 120cgaggccaac gtggaacctg ttgtgccgtc agaggcttca gagccggtgc ccagggtgct 180ttctggagac ccccagaacc tgtccgacgt ggacgccttc aacctgctcc tggagatgaa 240gctgaagcgg cggcgtcagc ggcccaacct gccgcgcact gtgacccagt tggtggctga 300ggacgggagc agggtgtacg tggtggggac agcccacttc agcgacgaca gcaagaggga 360cgttgtgaag accatccggg aggtgcagcc tgacgtggta gtcgtggagc tctgccaata 420tcgtgtgtcc atgctgaaga tggacgagag cacgctgctg cgggaggccc aggagctcag 480cctggagaag ctgcagcagg ccgtgaggca gaacgggctc atgtcggggc tgatgcagat 540gctgctgctg aaggtgtctg cacacatcac cgagcagctg ggcatggccc caggtggcga 600gttcagggag gccttcaagg aggccagcaa ggtgcctttc tgcaagttcc acctgggtga 660ccgacccatc cccgtcacct tcaagagggc catcgcagcg ctctccttct ggcagaaggt 720caggctggct tggggcctgt gcttcctgtc agaccccatc agcaaggatg acgtggaacg 780ctgcaagcag aaggacctac tggagcagat gatggccgag atgattggcg agttcccaga 840cctgcaccgc accatcgtct cggagcgcga cgtctaccta acctacatgc tgcgccaggc 900cgcgcggcgc ctcgagctgc ctcgggcctc tgacggtgac ggccgcccgc aggcgtggga 960ccccctgtga ggctgaggcc cgagcaggta ctgacccctt gtccttcccc acagccgagc 1020ccaggaagtg cgtcccctcc gtggtcgtgg gcgtcgtggg catgggccac gtgcctggca 1080tcgagaagaa ctggagcacc gacctcaaca tccaggagat catgaccgtg cccccgccgt 1140ccgtctccgg cagagtgtct cggttggccg tgaaggccgc cttcttcggc ctgctgggct 1200acagcctgta ctggatgggc cgccgcaccg cgagcctggt cctgtcgctg cccgccgcgc 1260agtactgcct gcagagggtg accgaggccc ggcacaagta ggagactgct ccccgcccgc 1320tcgggcccct gaggagccag tgcccccgcg gcacttctgg gtgccaggtg catcctagcc 1380cgccccgagg cccctgccac cccccatggg ggtctgggcc cggcctcgcc tgccctcctg 1440ggccagtcac ccctccccca gcccacccaa ataaaggatt atttaactgt ctgagctcag 1500gcctcccggc agcccctccc ctcccacact gcaggggccg ttccccggct tctggacaag 1560acacccagct ccgagggggc aggggcttat aggaggggcc gaggcgtgcg ctgccctctc 1620agccctggtg gcaggcgggg gacaatggcc actgtcccta cctcactgtg ccttcctgtg 1680ctccggccac aggagcgtcg gcccaggggc ggctcctggg ggctccaggg caggcgagac 1740tgggaaaggc ccagccctgg agctccagcc gaccccaccg tgcccctggc atcctggccc 1800tggccgccac ctccctggca ccgtctgcct gcagggattc tgtgtttttg gcttttttaa 1860tgtcttaaaa tcttttactc aggtaatttt aatttcagag agaaaaactg aagtaaatgt 1920caaaaaacac cagccttaaa tccaaaggga cagaattcgt gttcttgggt ctgtcccgag 1980tgggctcgcg tgcagccaaa catcagctct gggtccaggc gtggcctcag ctgggagcct 2040gtgtcctgag cccccggagc gaaggggtgc ctggggcatc ttggccctct ctgggcagac 2100aatgtgtgca cctatgtgga aggccaagga catgggctgt ggccaggcct gtcccgctca 2160ggccccctgc ccggcggccg tctgtgtgcg gggcctccct cctggctgtc caggacacag 2220cccgtgcagc cccagcctgg acccaggcca tctctggttg tgtctgtgcc gactcggtgt 2280tgaatcaaat caggtgtgcg tcaggagccg gctgtgtcct tcctgccaca ctcggggatt 2340cattccttag aaactgaaat aaattctaat tttggaaaaa aaaaaaaaaa aaaaaaaaaa 2400aaaaaaaaaa aaaaaaaaaa aaaaaaa 2427<210〉23<211〉2427<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 92 ) .. ( 967 )<223〉<400〉23ggccggctga ggagcgccgc tgcctcgcct cggtacgccg cgcggcgcgg acggcgcgct 60ccccacaggt gcaggaagcc gccgcccagc c atg gac ggg gag gag cag cag 112
Met?Asp?Gly?Glu?Glu?Gln?Gln
1???????????????5cca?ccg?cac?gag?gcc?aac?gtg?gaa?cct?gtt?gtg?ccg?tca?gag?gct?tca?????160Pro?Pro?His?Glu?Ala?Asn?Val?Glu?Pro?Val?Val?Pro?Ser?Glu?Ala?Ser
10??????????????????15??????????????????20gag?ccg?gtg?ccc?agg?gtg?ctt?tct?gga?gac?ccc?cag?aac?ctg?tcc?gac?????208Glu?Pro?Val?Pro?Arg?Val?Leu?Ser?Gly?Asp?Pro?Gln?Asn?Leu?Ser?Asp
25??????????????????30??????????????????35gtg?gac?gcc?ttc?aac?ctg?ctc?ctg?gag?atg?aag?ctg?aag?cgg?cgg?cgt?????256Val?Asp?Ala?Phe?Asn?Leu?Leu?Leu?Glu?Met?Lys?Leu?Lys?Arg?Arg?Arg40??????????????????45??????????????????50??????????????????55cag?cgg?ccc?aac?ctg?ccg?cgc?act?gtg?acc?cag?ttg?gtg?gct?gag?gac?????304Gln?Arg?Pro?Asn?Leu?Pro?Arg?Thr?Val?Thr?Gln?Leu?Val?Ala?Glu?Asp
60??????????????????65??????????????????70ggg?agc?agg?gtg?tac?gtg?gtg?ggg?aca?gcc?cac?ttc?agc?gac?gac?agc?????352Gly?Ser?Arg?Val?Tyr?Val?Val?Gly?Thr?Ala?His?Phe?Ser?Asp?Asp?Ser
75??????????????????80??????????????????????85aag?agg?gac?gtt?gtg?aag?acc?atc?cgg?gag?gtg?cag?cct?gac?gtg?gta?????400Lys?Arg?Asp?Val?Val?Lys?Thr?Ile?Arg?Glu?Val?Gln?Pro?Asp?Val?Val
90??????????????????95??????????????????100gtc?gtg?gag?ctc?tgc?caa?tat?cgt?gtg?tcc?atg?ctg?aag?atg?gac?gag?????448Val?Val?Glu?Leu?Cys?Gln?Tyr?Arg?Val?Ser?Met?Leu?Lys?Met?Asp?Glu
105?????????????????110?????????????????115agc?acg?ctg?ctg?cgg?gag?gcc?cag?gag?ctc?agc?ctg?gag?aag?ctg?cag?????496Ser?Thr?Leu?Leu?Arg?Glu?Ala?Gln?Glu?Leu?Ser?Leu?Glu?Lys?Leu?Gln120?????????????????125?????????????????130?????????????????135cag?gcc?gtg?agg?cag?aac?ggg?ctc?atg?tcg?ggg?ctg?atg?cag?atg?ctg?????544Gln?Ala?Val?Arg?Gln?Asn?Gly?Leu?Met?Ser?Gly?Leu?Met?Gln?Met?Leu
140?????????????????145?????????????????150ctg?ctg?aag?gtg?tct?gca?cac?atc?acc?gag?cag?ctg?ggc?atg?gcc?cca?????592Leu?Leu?Lys?Val?Ser?Ala?His?Ile?Thr?Glu?Gln?Leu?Gly?Met?Ala?Pro
155?????????????????160?????????????????165ggt?ggc?gag?ttc?agg?gag?gcc?ttc?aag?gag?gcc?agc?aag?gtg?cct?ttc?????640Gly?Gly?Glu?Phe?Arg?Glu?Ala?Phe?Lys?Glu?Ala?Ser?Lys?Val?Pro?Phe
170?????????????????175?????????????????180tgc?aag?ttc?cac?ctg?ggt?gac?cga?ccc?atc?ccc?gtc?acc?ttc?aag?agg?????688Cys?Lys?Phe?His?Leu?Gly?Asp?Arg?Pro?Ile?Pro?Val?Thr?Phe?Lys?Arg
185?????????????????190?????????????????195gcc?atc?gca?gcg?ctc?tcc?ttc?tgg?cag?aag?gtc?agg?ctg?gct?tgg?ggc?????736Ala?Ile?Ala?Ala?Leu?Ser?Phe?Trp?Gln?Lys?Val?Arg?Leu?Ala?Trp?Gly200?????????????????205?????????????????210?????????????????215ctg?tgc?ttc?ctg?tca?gac?ccc?atc?agc?aag?gat?gac?gtg?gaa?cgc?tgc?????784Leu?Cys?Phe?Leu?Ser?Asp?Pro?Ile?Ser?Lys?Asp?Asp?Val?Glu?Arg?Cys
220?????????????????225?????????????????230aag?cag?aag?gac?cta?ctg?gag?cag?atg?atg?gcc?gag?atg?att?ggc?gag?????832Lys?Gln?Lys?Asp?Leu?Leu?Glu?Gln?Met?Met?Ala?Glu?Met?Ile?Gly?Glu
235?????????????????240?????????????????245ttc?cca?gac?ctg?cac?cgc?acc?atc?gtc?tcg?gag?cgc?gac?gtc?tac?cta?????880Phe?Pro?Asp?Leu?His?Arg?Thr?Ile?Val?Ser?Glu?Arg?Asp?Val?Tyr?Leu
250?????????????????255?????????????????260acc?tac?atg?ctg?cgc?cag?gcc?gcg?cgg?cgc?ctc?gag?ctg?cct?cgg?gcc?????928Thr?Tyr?Met?Leu?Arg?Gln?Ala?Ala?Arg?Arg?Leu?Glu?Leu?Pro?Arg?Ala
265 270 275tct gac ggt gac ggc cgc ccg cag gcg tgg gac ccc ctg tgaggctgag 977Ser Asp Gly Asp Gly Arg Pro Gln Ala Trp Asp Pro Leu280 285 290gcccgagcag gtactgaccc cttgtccttc cccacagccg agcccaggaa gtgcgtcccc 1037tccgtggtcg tgggcgtcgt gggcatgggc cacgtgcctg gcatcgagaa gaactggagc 1097accgacctca acatccagga gatcatgacc gtgcccccgc cgtccgtctc cggcagagtg 1157tctcggttgg ccgtgaaggc cgccttcttc ggcctgctgg gctacagcct gtactggatg 1217ggccgccgca ccgcgagcct ggtcctgtcg ctgcccgccg cgcagtactg cctgcagagg 1277gtgaccgagg cccggcacaa gtaggagact gctccccgcc cgctcgggcc cctgaggagc 1337cagtgccccc gcggcacttc tgggtgccag gtgcatccta gcccgccccg aggcccctgc 1397caccccccat gggggtctgg gcccggcctc gcctgccctc ctgggccagt cacccctccc 1457ccagcccacc caaataaagg attatttaac tgtctgagct caggcctccc ggcagcccct 1517cccctcccac actgcagggg ccgttccccg gcttctggac aagacaccca gctccgaggg 1577ggcaggggct tataggaggg gccgaggcgt gcgctgccct ctcagccctg gtggcaggcg 1637ggggacaatg gccactgtcc ctacctcact gtgccttcct gtgctccggc cacaggagcg 1697tcggcccagg ggcggctcct gggggctcca gggcaggcga gactgggaaa ggcccagccc 1757tggagctcca gccgacccca ccgtgcccct ggcatcctgg ccctggccgc cacctccctg 1817gcaccgtctg cctgcaggga ttctgtgttt ttggcttttt taatgtctta aaatctttta 1877ctcaggtaat tttaatttca gagagaaaaa ctgaagtaaa tgtcaaaaaa caccagcctt 1937aaatccaaag ggacagaatt cgtgttcttg ggtctgtccc gagtgggctc gcgtgcagcc 1997aaacatcagc tctgggtcca ggcgtggcct cagctgggag cctgtgtcct gagcccccgg 2057agcgaagggg tgcctggggc atcttggccc tctctgggca gacaatgtgt gcacctatgt 2117ggaaggccaa ggacatgggc tgtggccagg cctgtcccgc tcaggccccc tgcccggcgg 2177ccgtctgtgt gcggggcctc cctcctggct gtccaggaca cagcccgtgc agccccagcc 2237tggacccagg ccatctctgg ttgtgtctgt gccgactcgg tgttgaatca aatcaggtgt 2297gcgtcaggag ccggctgtgt ccttcctgcc acactcgggg attcattcct tagaaactga 2357aataaattct aattttggaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2417aaaaaaaaaa 2427<210〉24<211〉292<212〉PRT<213〉 ( Homo sapiens )<400〉24Met Asp Gly Glu Glu Gln Gln Pro Pro His Glu Ala Asn Val Glu Pro1 5 10 15Val Val Pro Ser Glu Ala Ser Glu Pro Val Pro Arg Val Leu Ser Gly
20??????????????????25??????????????????30Asp?Pro?Gln?Asn?Leu?Ser?Asp?Val?Asp?Ala?Phe?Asn?Leu?Leu?Leu?Glu
35??????????????????40??????????????????45Met?Lys?Leu?Lys?Arg?Arg?Arg?Gln?Arg?Pro?Asn?Leu?Pro?Arg?Thr?Val
50??????????????????55??????????????????60Thr?Gln?Leu?Val?Ala?Glu?Asp?Gly?Ser?Arg?Val?Tyr?Val?Val?Gly?Thr65??????????????????70??????????????????75??????????????????80Ala?His?Phe?Ser?Asp?Asp?Ser?Lys?Arg?Asp?Val?Val?Lys?Thr?Ile?Arg
85??????????????????90??????????????????95Glu?Val?Gln?Pro?Asp?Val?Val?Val?Val?Glu?Leu?Cys?Gln?Tyr?Arg?Val
100?????????????????105?????????????????110Ser?Met?Leu?Lys?Met?Asp?Glu?Ser?Thr?Leu?Leu?Arg?Glu?Ala?Gln?Glu
115?????????????????120?????????????????125Leu?Ser?Leu?Glu?Lys?Leu?Gln?Gln?Ala?Val?Arg?Gln?Asn?Gly?Leu?Met
130?????????????????135?????????????????140Ser?Gly?Leu?Met?Gln?Met?Leu?Leu?Leu?Lys?Val?Ser?Ala?His?Ile?Thr145?????????????????150?????????????????155?????????????????160Glu?Gln?Leu?Gly?Met?Ala?Pro?Gly?Gly?Glu?Phe?Arg?Glu?Ala?Phe?Lys
165?????????????????170?????????????????175Glu?Ala?Ser?Lys?Val?Pro?Phe?Cys?Lys?Phe?His?Leu?Gly?Asp?Arg?Pro
180?????????????????185?????????????????190Ile?Pro?Val?Thr?Phe?Lys?Arg?Ala?Ile?Ala?Ala?Leu?Ser?Phe?Trp?Gln
195?????????????????200?????????????????205Lys?Val?Arg?Leu?Ala?Trp?Gly?Leu?Cys?Phe?Leu?Ser?Asp?Pro?Ile?Ser
210?????????????????215?????????????????220Lys?Asp?Asp?Val?Glu?Arg?Cys?Lys?Gln?Lys?Asp?Leu?Leu?Glu?Gln?Met225?????????????????230?????????????????235?????????????????240Met?Ala?Glu?Met?Ile?Gly?GluPhe?Pro?Asp?Leu?His?Arg?Thr?Ile?Val
245????????????????250?????????????????255Ser?Glu?Arg?Asp?Val?Tyr?Leu?Thr?Tyr?Met?Leu?Arg?Gln?Ala?Ala?Arg
260?????????????????265?????????????????270Arg?Leu?Glu?Leu?Pro?Arg?Ala?Ser?Asp?Gly?Asp?Gly?Arg?Pro?Gln?Ala
275?????????????????280?????????????????285Trp?Asp?Pro?Leu
290<210〉25<211〉3105<212〉DNA<213〉 ( Homo sapiens )<400〉25gcagcagaag aggatctggg agtctcctct ccttctagct gccaaagata atgatgtcca 60ggccctgaac aagttgctca agtatgagga ttgcaaggtg caccagagag gtaagaagca 120caaatgcagc atgatctcct aggtgagccc cacacatggg gcctcccagg agtgcccagg 180acctcgtgct gttggcctct gaatctatcg tctccaatcc gctgtcccac agaagccata 240taacccacct ctctgtaaat gccaggagcc atgggggaaa cagcgctaca catagcagcc 300ctctatgaca acctggaggc cgccatggtg ctgatggagg ctgccccgga gctggtcttt 360gagcccatga catctgagct ctatgagggt gagggcccac gggtctgggg tgaagagcag 420gagtgactgg ttgggtattt caagtcagtc tctgtgatgg ataatttggg aaagacacag 480gggatctgag cctcctactc tttttttctc ttctctgtct cccttccgtg tcagtcctga 540ctgcccatca cttgaacgcc tgccccctgaaatgccaggg gcctagagaa gaggaagaga 600tgggcagcag ctggatcccc tgggaatcct gaacacccga gagctccctg ttctccatcc 660caggctaccc ctgagggaaa gagactgggg tgcatatggg agggaccccc tgcaggatcc 720tggggacaga cccgtgactg acagctgtct ctgggccagg tcagactgca ctgcacatcg 780ctgttgtgaa ccagaacatg aacctggtgc gagccctgct tgcccgcagg gccagtgtct 840ctgccagagc cacaggcact gccttccgcc gtagtccctg caacctcatc tactttgggg 900agcacccttt gtcctttgct gcctgtgtga acagtgagga gatcgtgcgg ctgctcattg 960agcatggagc tgacatccgg gcccaggact ccctgggaaa cacagtgtta cacatcctca 1020tcctccagcc caacaaaacc tttgcctgcc agatgtacaa cctgttgctg tcctacgaca 1080gacatgggga ccacctgcag cccctggacc tcgtgcccaa tcaccagggt ctcacccctt 1140tcaagctggc tggagtggag ggtaacactg tgatgtttca gcacctgatg cagaagcgga 1200agcacaccca gtggacgtat ggaccactga cctcgactct ctatgacctc acagagatcg 1260actcctcagg ggatgagcag tccctgctgg aacttatcat caccaccaag aagcgggagg 1320ctcgccagat cctggaccag acgccggtga aggagctggt gagcctcaag tggaagcggt 1380acgggcggcc gtacttctgcatgctgggtg ccatatatct gctgtacatc atctgcttca 1440ccatgtgctg catctaccgc cccctcaagc ccaggaccaa taaccgcacg agcccccggg 1500acaacaccct cttacagcag aagctacttc aggaagccta catgacccct aaggacgata 1560tccggctggt cggggagctg gtgactgtca ttggggctat catcatcctg ctggtagagg 1620ttccagacat cttcagaatg ggggtcactc gcttctttgg acagaccatc cttgggggcc 1680cattccatgt cctcatcatc acctatgcct tcatggtgct ggtgaccatg gtgatgcggc 1740tcatcagtgc cagcggggag gtggtaccca tgtcctttgc actcgtgctg ggctggtgca 1800acgtcatgta cttcgcccga ggattccaga tgctaggccc cttcaccatc atgattcaga 1860agatgatttt tggcgacctg atgcgattct gctggctgat ggctgtggtc atcctgggct 1920ttgcttcagc cttctatatc atcttccaga cagaggaccc cgaggagcta ggccacttct 1980acgactaccc catggccctg ttcagcacct tcgagctgtt ccttaccatc atcgatggcc 2040cagccaacta caacgtggac ctgcccttca tgtacagcat cacctatgct gcctttgcca 2100tcatcgccac actgctcatg ctcaacctcc tcattgccat gatgggcgac actcactggc 2160gagtggccca tgagcgggat gagctgtgga gggcccagat tgtggccacc acggtgatgc 2220tggagcggaa gctgcctcgc tgcctgtggc ctcgctccgg gatctgcgga cgggagtatg 2280gcctgggaga ccgctggttc ctgcgggtgg aagacaggca agatctcaac cggcagcgga 2340tccaacgcta cgcacaggcc ttccacaccc cggggctctg aggatttgga caaagactca 2400gtggaaaaac tagagctggg ctgtcccttc agcccccacc tgtcccttcc tatgccctca 2460gtgtctcgaa gtacctcccg cagcagtgcc aattgggaaa ggcttcggca agggaccctg 2520aggagagacc tgcgtgggat aatcaacagg ggtctggagg acggggagag ctgggaatat 2580cagatctgac tgcgtgttct cacttcgctt cctggaactt gctctcattt tcctgggtgc 2640atcaaacaaa acaaaaacca aacacccaga ggtctcatct cccaggcccc aggggagaaa 2700gaggagtagc atgaacgcca aggaatgtac gttgagaatc actgctccag gcctgcatta 2760ctccttcagc tctggggcag aggaagccca gcccaagcac ggggctggca gggcgtgagg 2820aactctcctg tggcctgctc atcacccttc cgacaggagc actgcatgtc agagcacttt 2880aaaaacaggc cagcctgctt gggcgctcgg tctccacccc agggtcataa gtggggagaa 2940gacgcttccc agggcaccca ggcaggtgca gggaagtgca gagcttgtgg aaagcgtgtg 3000agtgagggag acaggaacgg ctctgggggt gggaagtggg gctaggtctt gccaactcca 3060tcttcaataa agtcgttttc ggaaaaaaaa aaaaaaaaaa aaaaa 3105<210〉26<211〉3105<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 798 ) .. ( 2378 )<223〉<400〉26gcagcagaag aggatctggg agtctcctct ccttctagct gccaaagata atgatgtcca 60ggccctgaac aagttgctca agtatgagga ttgcgaggtg caccagagag gtaagaagca 120caaatgcagc atgatctcct aggtgagccc cacacatggg gcctcccagg agtgcccagg 180acctcgtgct gttggcctct gaatctatcg tctccaatcc gctgtcccac agaagccata 240taacccacct ctctgtaaat gccaggagcc atgggggaaa cagcgctaca catagcagcc 300ctctatgaca acctggaggc cgccatggtg ctgatggagg ctgccccgga gctggtcttt 360gagcccatga catctgagct ctatgagggt gagggcccac gggtctgggg tgaagagcag 420gagtgactgg ttgggtattt caagtcagtc tctgtgatgg ataatttggg aaagacacag 480gggatctgag cctcctactc tttttttctc ttctctgtct cccttccgtg tcagtcctga 540ctgcccatca cttgaacgcc tgccccctga aatgccaggg gcctagagaa gaggaagaga 600tgggcagcag ctggatcccc tgggaatcct gaacacccga gagctccctg ttctccatcc 660caggctaccc ctgagggaaa gagactgggg tgcatatggg agggaccccc tgcaggatcc 720tggggacaga cccgtgactg acagctgtct ctgggccagg tcagactgca ctgcacatcg 780ctgttgtgaa ccagaac atg aac ctg gtg cga gcc ctg ctt gcc cgc agg 830
Met?Asn?Leu?Val?Arg?Ala?Leu?Leu?Ala?Arg?Arg
1???????????????5???????????????????10gcc?agt?gtc?tct?gcc?aga?gcc?aca?ggc?act?gcc?ttc?cgc?cgt?agt?ccc???????878Ala?Ser?Val?Ser?Ala?Arg?Ala?Thr?Gly?Thr?Ala?Phe?Arg?Arg?Ser?Pro
15??????????????????20??????????????????25tgc?aac?ctc?atc?tac?ttt?ggg?gag?cac?cct?ttg?tcc?ttt?gct?gcc?tgt???????926Cys?Asn?Leu?Ile?Tyr?Phe?Gly?Glu?His?Pro?Leu?Ser?Phe?Ala?Ala?Cys
30??????????????????35??????????????????40gtg?aac?agt?gag?gag?atc?gtg?cgg?ctg?ctc?att?gag?cat?gga?gct?gac???????974Val?Asn?Ser?Glu?Glu?Ile?Val?Arg?Leu?Leu?Ile?Glu?His?Gly?Ala?Asp
45??????????????????50??????????????????55atc?cgg?gcc?cag?gac?tcc?ctg?gga?aac?aca?gtg?tta?cac?atc?ctc?atc??????1022Ile?Arg?Ala?Gln?Asp?Ser?Leu?Gly?Asn?Thr?Val?Leu?His?Ile?Leu?Ile60??????????????????65??????????????????70??????????????????75ctc?cag?ccc?aac?aaa?acc?ttt?gcc?tgc?cag?atg?tac?aac?ctg?ttg?ctg??????1070Leu?Gln?Pro?Asn?Lys?Thr?Phe?Ala?Cys?Gln?Met?Tyr?Asn?Leu?Leu?Leu
80??????????????????85??????????????????90tcc?tac?gac?aga?cat?ggg?gac?cac?ctg?cag?ccc?ctg?gac?ctc?gtg?ccc??????1118Ser?Tyr?Asp?Arg?His?Gly?Asp?His?Leu?Gln?Pro?Leu?Asp?Leu?Val?Pro
95??????????????????100?????????????????105aat?cac?cag?ggt?ctc?acc?cct?ttc?aag?ctg?gct?gga?gtg?gag?ggt?aac??????1166Asn?His?Gln?Gly?Leu?Thr?Pro?Phe?Lys?Leu?Ala?Gly?Val?Glu?Gly?Asn
110?????????????????115?????????????????120act?gtg?atg?ttt?cag?cac?ctg?atg?cag?aag?cgg?aag?cac?acc?cag?tgg??????1214Thr?Val?Met?Phe?Gln?His?Leu?Met?Gln?Lys?Arg?Lys?His?Thr?Gln?Trp
125?????????????????130?????????????????135acg?tat?gga?cca?ctg?acc?tcg?act?ctc?tat?gac?ctc?aca?gag?atc?gac??????1262Thr?Tyr?Gly?Pro?Leu?Thr?Ser?Thr?Leu?Tyr?Asp?Leu?Thr?Glu?Ile?Asp140?????????????????145?????????????????150?????????????????155tcc?tca?ggg?gat?gag?cag?tcc?ctg?ctg?gaa?ctt?atc?atc?acc?acc?aag??????1310Ser?Ser?Gly?Asp?Glu?Gln?Ser?Leu?Leu?Glu?Leu?Ile?Ile?Thr?Thr?Lys
160?????????????????165?????????????????170aag?cgg?gag?gct?cgc?cag?atc?ctg?gac?cag?acg?ccg?gtg?aag?gag?ctg??????1358Lys?Arg?Glu?Ala?Arg?Gln?Ile?Leu?Asp?Gln?Thr?Pro?Val?Lys?Glu?Leu
175?????????????????180?????????????????185gtg?agc?ctc?aag?tgg?aag?cgg?tac?ggg?cgg?ccg?tac?ttc?tgc?atg?ctg??????1406Val?Ser?Leu?Lys?Trp?Lys?Arg?Tyr?Gly?Arg?Pro?Tyr?Phe?Cys?Met?Leu
190?????????????????195?????????????????200ggt?gcc?ata?tat?ctg?ctg?tac?atc?atc?tgc?ttc?acc?atg?tgc?tgc?atc?????1454Gly?Ala?Ile?Tyr?Leu?Leu?Tyr?Ile?Ile?Cys?Phe?Thr?Met?Cys?Cys?Ile
205?????????????????210?????????????????215tac?cgc?ccc?ctc?aag?ccc?agg?acc?aat?aac?cgc?acg?agc?ccc?cgg?gac?????1502Tyr?Arg?Pro?Leu?Lys?Pro?Arg?Thr?Asn?Asn?Arg?Thr?Ser?Pro?Arg?Asp220?????????????????225?????????????????230?????????????????235aac?acc?ctc?tta?cag?cag?aag?cta?ctt?cag?gaa?gcc?tac?atg?acc?cct?????1550Asn?Thr?Leu?Leu?Gln?Gln?Lys?Leu?Leu?Gln?Glu?Ala?Tyr?Met?Thr?Pro
240?????????????????245?????????????????250aag?gac?gat?atc?cgg?ctg?gtc?ggg?gag?ctg?gtg?act?gtc?att?ggg?gct?????1598Lys?Asp?Asp?Ile?Arg?Leu?Val?Gly?Glu?Leu?Val?Thr?Val?Ile?Gly?Ala
255?????????????????260?????????????????265atc?atc?atc?ctg?ctg?gta?gag?gtt?cca?gac?atc?ttc?aga?atg?ggg?gtc?????1646Ile?Ile?Ile?Leu?Leu?Val?Glu?Val?Pro?Asp?Ile?Phe?Arg?Met?Gly?Val
270?????????????????275?????????????????280act?cgc?ttc?ttt?gga?cag?acc?atc?ctt?ggg?ggc?cca?ttc?cat?gtc?ctc?????1694Thr?Arg?Phe?Phe?Gly?Gln?Thr?Ile?Leu?Gly?Gly?Pro?Phe?His?Val?Leu
285?????????????????290?????????????????295atc?atc?acc?tat?gcc?ttc?atg?gtg?ctg?gtg?acc?atg?gtg?atg?cgg?ctc?????1742Ile?Ile?Thr?Tyr?Ala?Phe?Met?Val?Leu?Val?Thr?Met?Val?Met?Arg?Leu300?????????????????305?????????????????310?????????????????315atc?agt?gcc?agc?ggg?gag?gtg?gta?ccc?atg?tcc?ttt?gca?ctc?gtg?ctg?????1790Ile?Ser?Ala?Ser?Gly?Glu?Val?Val?Pro?Met?Ser?Phe?Ala?Leu?Val?Leu
320?????????????????325?????????????????330ggc?tgg?tgc?aac?gtc?atg?tacttc?gcc?cga?gga?ttc?cag?atg?cta?ggc??????1838Gly?Trp?Cys?Asn?Val?Met?Tyr?Phe?Ala?Arg?Gly?Phe?Gln?Met?Leu?Gly
335?????????????????340?????????????????345ccc?ttc?acc?atc?atg?att?cag?aag?atg?att?ttt?ggc?gac?ctg?atg?cga?????1886Pro?Phe?Thr?Ile?Met?Ile?Gln?Lys?Met?Ile?Phe?Gly?Asp?Leu?Met?Arg
350?????????????????355?????????????????360ttc?tgc?tgg?ctg?atg?gct?gtg?gtc?atc?ctg?ggc?ttt?gct?tca?gcc?ttc?????1934Phe?Cys?Trp?Leu?Met?Ala?Val?Val?Ile?Leu?Gly?Phe?Ala?Ser?Ala?Phe
365?????????????????370?????????????????375tat?atc?atc?ttc?cag?aca?gag?gac?ccc?gag?gag?cta?ggc?cac?ttc?tac?????1982Tyr?Ile?Ile?Phe?Gln?Thr?Glu?Asp?Pro?Glu?Glu?Leu?Gly?His?Phe?Tyr380?????????????????385?????????????????390?????????????????395gac?tac?ccc?atg?gcc?ctg?ttc?agc?acc?ttc?gag?ctg?ttc?ctt?acc?atc?????2030Asp?Tyr?Pro?Met?Ala?Leu?Phe?Ser?Thr?Phe?Glu?Leu?Phe?Leu?Thr?Ile
400?????????????????405?????????????????410atc?gat?ggc?cca?gcc?aac?tac?aac?gtg?gac?ctg?ccc?ttc?atg?tac?agc?????2078Ile?Asp?Gly?Pro?Ala?Asn?Tyr?Asn?Val?Asp?Leu?Pro?Phe?Met?Tyr?Ser
415?????????????????420?????????????????425atc?acc?tat?gct?gcc?ttt?gcc?atc?atc?gcc?aca?ctg?ctc?atg?ctc?aac?????2126Ile?Thr?Tyr?Ala?Ala?Phe?Ala?Ile?Ile?Ala?Thr?Leu?Leu?Met?Leu?Asn
430?????????????????435?????????????????440ctc?ctc?att?gcc?atg?atg?ggc?gac?act?cac?tgg?cga?gtg?gcc?cat?gag?????2174Leu?Leu?Ile?Ala?Met?Met?Gly?Asp?Thr?His?Trp?Arg?Val?Ala?His?Glu
445?????????????????450?????????????????455cgg?gat?gag?ctg?tgg?agg?gcc?cag?att?gtg?gcc?acc?acg?gtg?atg?ctg?????2222Arg?Asp?Glu?Leu?Trp?Arg?Ala?Gln?Ile?Val?Ala?Thr?Thr?Val?Met?Leu460?????????????????465?????????????????470?????????????????475gag?cgg?aag?ctg?cct?cgc?tgc?ctg?tgg?cct?cgc?tcc?ggg?atc?tgc?gga?????2270Glu?Arg?Lys?Leu?Pro?Arg?Cys?Leu?Trp?Pro?Arg?Ser?Gly?Ile?Cys?Gly
480?????????????????485?????????????????490cgg?gag?tat?ggc?ctg?gga?gac?cgc?tgg?ttc?ctg?cgg?gtg?gaa?gac?agg?????2318Arg?Glu?Tyr?Gly?Leu?Gly?Asp?Arg?Trp?Phe?Leu?Arg?Val?Glu?Asp?Arg
495?????????????????500?????????????????505caa?gat?ctc?aac?cgg?cag?cgg?atc?caa?cgc?tac?gca?cag?gcc?ttc?cac?????2366Gln?Asp?Leu?Asn?Arg?Gln?Arg?Ile?Gln?Arg?Tyr?Ala?Gln?Ala?Phe?His
510?????????????????515?????????????????520acc?ccg?ggg?ctc?tgaggatttg?gacaaagact?cagtggaaaa?actagagctg?????????2418Thr?Pro?Gly?Leu
525ggctgtccct tcagccccca cctgtccctt cctatgccct cagtgtctcg aagtacctcc 2478cgcagcagtg ccaattggga aaggcttcgg caagggaccc tgaggagaga cctgcgtggg 2538ataatcaaca ggggtctgga ggacggggag agctgggaat atcagatctg actgcgtgtt 2598ctcacttcgc ttcctggaac ttgctctcat tttcctgggt gcatcaaaca aaacaaaaac 2658caaacaccca gaggtctcat ctcccaggcc ccaggggaga aagaggagta gcatgaacgc 2718caaggaatgt acgttgagaa tcactgctcc aggcctgcat tactccttca gctctggggc 2778agaggaagcc cagcccaagc acggggctgg cagggcgtga ggaactctcc tgtggcctgc 2838tcatcaccct tccgacagga gcactgcatg tcagagcact ttaaaaacag gccagcctgc 2898ttgggcgctc ggtctccacc ccagggtcat aagtggggag aagacgcttc ccagggcacc 2958caggcaggtg cagggaagtg cagagcttgt ggaaagcgtg tgagtgaggg agacaggaac 3018ggctctgggg gtgggaagtg gggctaggtc ttgccaactc catcttcaat aaagtcgttt 3078tcggaaaaaa aaaaaaaaaa aaaaaaa 3105<210〉27<211〉527<212〉PRT<213〉 ( Homo sapiens )<400〉27Met Asn Leu Val Arg Ala Leu Leu Ala Arg Arg Ala Ser Val Ser Ala1 5 10 15Arg Ala Thr Gly Thr Ala Phe Arg Arg Ser Pro Cys Asn Leu Ile Tyr
20??????????????????25??????????????????30Phe?Gly?Glu?His?Pro?Leu?Ser?Phe?Ala?Ala?Cys?Val?Asn?Ser?Glu?Glu
35??????????????????40??????????????????45Ile?Val?Arg?Leu?Leu?Ile?Glu?His?Gly?Ala?Asp?Ile?Arg?Ala?Gln?Asp
50??????????????????55??????????????????60Ser?Leu?Gly?Asn?Thr?Val?Leu?His?Ile?Leu?Ile?Leu?Gln?Pro?Asn?Lys65??????????????????70??????????????????75??????????????????80Thr?Phe?Ala?Cys?Gln?Met?Tyr?Asn?Leu?Leu?Leu?Ser?Tyr?Asp?Arg?His
85??????????????????90??????????????????95Gly?Asp?His?Leu?Gln?Pro?Leu?Asp?Leu?Val?Pro?Asn?His?Gln?Gly?Leu
100?????????????????105?????????????????110Thr?Pro?Phe?Lys?Leu?Ala?Gly?Val?Glu?Gly?Asn?Thr?Val?Met?Phe?Gln
115?????????????????120?????????????????125His?Leu?Met?Gln?Lys?Arg?Lys?His?Thr?Gln?Trp?Thr?Tyr?Gly?Pro?Leu
130?????????????????135?????????????????140Thr?Ser?Thr?Leu?Tyr?Asp?Leu?Thr?Glu?Ile?Asp?Ser?Ser?Gly?Asp?Glu145?????????????????150?????????????????155?????????????????160Gln?Ser?Leu?Leu?Glu?Leu?Ile?Ile?Thr?Thr?Lys?Lys?Arg?Glu?Ala?Arg
165?????????????????170?????????????????175Gln?Ile?Leu?Asp?Gln?Thr?Pro?Val?Lys?Glu?Leu?Val?Ser?Leu?Lys?Trp
180?????????????????185?????????????????190Lys?Arg?Tyr?Gly?Arg?Pro?Tyr?Phe?Cys?Met?Leu?Gly?Ala?Ile?Tyr?Leu
195?????????????????200?????????????????205Leu?Tyr?Ile?Ile?Cys?Phe?Thr?Met?Cys?Cys?Ile?Tyr?Arg?Pro?Leu?Lys
210?????????????????215?????????????????220Pro?Arg?Thr?Asn?Asn?Arg?Thr?Ser?Pro?Arg?Asp?Asn?Thr?Leu?Leu?Gln225?????????????????230?????????????????235?????????????????240Gln?Lys?Leu?Leu?Gln?Glu?Ala?Tyr?Met?Thr?Pro?Lys?Asp?Asp?Ile?Arg
245?????????????????250?????????????????255Leu?Val?Gly?Glu?Leu?Val?Thr?Val?Ile?Gly?Ala?Ile?Ile?Ile?Leu?Leu
260?????????????????265?????????????????270Val?Glu?Val?Pro?Asp?Ile?Phe?Arg?Met?Gly?Val?Thr?Arg?Phe?Phe?Gly
275?????????????????280?????????????????285Gln?Thr?Ile?Leu?Gly?Gly?Pro?Phe?His?Val?Leu?Ile?Ile?Thr?Tyr?Ala
290?????????????????295?????????????????300Phe?Met?Val?Leu?Val?Thr?Met?Val?Met?Arg?Leu?Ile?Ser?Ala?Ser?Gly305?????????????????310?????????????????315?????????????????320Glu?Val?Val?Pro?Met?Ser?Phe?Ala?Leu?Val?Leu?Gly?Trp?Cys?Asn?Val
325?????????????????330?????????????????335Met?Tyr?Phe?Ala?Arg?Gly?Phe?Gln?Met?Leu?Gly?Pro?Phe?Thr?Ile?Met
340?????????????????345?????????????????350Ile?Gln?Lys?Met?Ile?Phe?Gly?Asp?Leu?Met?Arg?Phe?Cys?Trp?Leu?Met
355?????????????????360?????????????????365Ala?Val?Val?Ile?Leu?Gly?Phe?Ala?Ser?Ala?Phe?Tyr?Ile?Ile?Phe?Gln
370?????????????????375?????????????????380Thr?Glu?Asp?Pro?Glu?Glu?Leu?Gly?His?Phe?Tyr?Asp?Tyr?Pro?Met?Ala385?????????????????390?????????????????395?????????????????400Leu?Phe?Ser?Thr?Phe?Glu?Leu?Phe?Leu?Thr?Ile?Ile?Asp?Gly?Pro?Ala
405?????????????????410?????????????????415Asn?Tyr?Asn?Val?Asp?Leu?Pro?Phe?Met?Tyr?Ser?Ile?Thr?Tyr?Ala?Ala
420?????????????????425?????????????????430Phe?Ala?Ile?Ile?Ala?Thr?Leu?Leu?Met?Leu?Asn?Leu?Leu?Ile?Ala?Met
435?????????????????440?????????????????445Met?Gly?Asp?Thr?His?Trp?Arg?Val?Ala?His?Glu?Arg?Asp?Glu?Leu?Trp
450?????????????????455?????????????????460Arg?Ala?Gln?Ile?Val?Ala?Thr?Thr?Val?Met?Leu?Glu?Arg?Lys?Leu?Pro465?????????????????470?????????????????475?????????????????480Arg?Cys?Leu?Trp?Pro?Arg?Ser?Gly?Ile?Cys?Gly?Arg?Glu?Tyr?Gly?Leu
485?????????????????490?????????????????495Gly?Asp?Arg?Trp?Phe?Leu?Arg?Val?Glu?Asp?Arg?Gln?Asp?Leu?Asn?Arg
500?????????????????505?????????????????510Gln?Arg?Ile?Gln?Arg?Tyr?Ala?Gln?Ala?Phe?His?Thr?Pro?Gly?Leu
515 520 525<210〉28<211〉2141<212〉DNA<213〉 ( Homo sapiens )<400〉28ggcgcggcgg cggctgcggc tgggtcgcgg cccgcgctcc cttggcgctc gccttctcgt 60cccgggtccc ctcctcctct ccatctttct tttacttctg gccgccgccc cccccgcccc 120ctccctcttt tctcccctcc tcatctgcct ttcacctccc cgtgcgtctc ccaggaaggg 180agggcgcagc ggcggcggcg gcggcgggag gaggcggcga tgctggcgga ggagggaagg 240aggaggacaa gaggcagctc ccttgagcgt ccccaccagc agtagtcacc gcggcggcgg 300tggcagcggc ggcgggcggc ggcggctctt cctctcgcct gcgctccagg gcttgctgct 360tccagcccgt gccggtcccc ggccgccgcc gccgccccgg ctcccccttg gccaggccgc 420ccgccgcgcg ggctcccccg gcttccccgg cgccggccca ggcggcggcg gccaaactcc 480gcggcgtccc cagggcgcca gcttcgccct cgccgccgcg gccgcgctgc tcttcggctc 540cgacatggaa gatggacctt ctaataatgc gagctgcttc cgaaggctga ccgagtgctt 600cctgagcccc agttcctccc tcttgagcct gtggccactt ggctggagca gatgcgcttc 660cttccacttg ggggtccagc ccaccgggtc cctgtagccg ggtgagggag gccagggcct 720cagaaccccg cgcttccaac tgtgatggca ccgccgttct ccaggactcg gagtgggcgc 780ccggcctccc accccgcgca gtgaccggca tccagagcat ggactggcgg ggtggaaacg 840gttgcacctc cacccagggg acgcaccccc accccgggcc gcgtcctgtt ggtcccgggc 900ttctctgggg tccgggctgg tagagaaaag ggaaggacaa taggtcgcta gggtggaaga 960gaaaggcgcc gccgcctccg actcgcagga tgcgcccccg ggcccactgt ggcgtggcca 1020ctcctcctcg ccacccgcgg gcgcggggcc gagagcgcgc tgaggcagag gtggcagaaa 1080ggcatgtcac ggggggtggg ggacaagatt gagcagaaaa gtcaaggcag gggttcgcta 1140gaaggaagca ggcaggcggg agacagtgag gaaagaggag gcgcccggtg cgcagaggag 1200gggggcgtcg cggtcgcgga tggaggggga gcagggtgag gacgggaaga ccgcggcggg 1260gccgggtagg agcacctccg ggtgcaggag gtcgcgccca tgggcccccg gccgactccg 1320gcgccagtcg gggcgggtgc ggcttcccgc ggcccagagc gcggctccgg agccaccgtc 1380caccgcgtgt gcacccgagc ctttgtctgc gcctcgctca ggagccgcgt ttccgcggcg 1440ccttctctgg gccgacgctc ttccaggatt gctgtttcgg tttcccgctc ccaactgcgg 1500ctcattccca ggctttggcc gacccgggtc tccagggcac ccgaggttga gcccctccct 1560gcggccgaag ctgctccggg ctcaccgccc gctcaggcac ctttggggtg cagcccccgg 1620gctggcgagc gtattcgcgc cgggatcggc cgctccttgc aaccccgctt cccgggcacg 1680ggcgagtcca cggcggccgc gtggtcagcg gcctctcgta cacccgtgcg ggctccggct 1740agcgagtcgc tgcttgcgct tgattggcta gcggggcgcg ggcccaatgc tcccgaagtc 1800ctctgacccc taagtcctcc cccccggtgt ctgcctccca cccccgctgc agtctaggtg 1860gggaaggggt gtggagatgg gtgtgcatgg acagagcatg tggccttctc tgttggccag 1920agatgtggtc agtagaagca cttttcccta ctgaagtgcc ctttggccat gcattgaagg 1980tggtagagga tggggcccca ccagctctcc cggggtgttg gcatcagcct ataggcctgg 2040tctaggactg gggttcctcc tggtccccta tctggtgggc ttgtgaattc tttcttaaga 2100aaataaacat ctgcttttct caaaaaaaaa aaaaaaaaaa a 2141<210〉29<211〉2141<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 1220 ) .. ( 1768 )<223〉<400〉29ggcgcggcgg cggctgcggc tgggtcgcgg cccgcgctcc cttggcgctc gccttctcgt 60cccgggtccc ctcctcctct ccatctttct tttacttctg gccgccgccc cccccgcccc 120ctccctcttt tctcccctcc tcatctgcct ttcacctccc cgtgcgtctc ccaggaaggg 180agggcgcagc ggcggcggcg gcggcgggag gaggcggcga tgctggcgga ggagggaagg 240aggaggacaa gaggcagctc ccttgagcgt ccccaccagc agtagtcacc gcggcggcgg 300tggcagcggc ggcgggcggc ggcggctctt cctctcgcct gcgctccagg gcttgctgct 360tccagcccgt gccggtcccc ggccgccgcc gccgccccgg ctcccccttg gccaggccgc 420ccgccgcgcg ggctcccccg gcttccccgg cgccggccca ggcggcggcg gccaaactcc 480gcggcgtccc cagggcgcca gcttcgccct cgccgccgcg gccgcgctgc tcttcggctc 540cgacatggaa gatggacctt ctaataatgc gagctgcttc cgaaggctga ccgagtgctt 600cctgagcccc agttcctccc tcttgagcct gtggccactt ggctggagca gatgcgcttc 660cttccacttg ggggtccagc ccaccgggtc cctgtagccg ggtgagggag gccagggcct 720cagaaccccg cgcttccaac tgtgatggca ccgccgttct ccaggactcg gagtgggcgc 780ccggcctccc accccgcgca gtgaccggca tccagagcat ggactggcgg ggtggaaacg 840gttgcacctc cacccagggg acgcaccccc accccgggcc gcgtcctgtt ggtcccgggc 900ttctctgggg tccgggctgg tagagaaaag ggaaggacaa taggtcgcta gggtggaaga 960gaaaggcgcc gccgcctccg actcgcagga tgcgcccccg ggcccactgt ggcgtggcca 1020ctcctcctcg ccacccgcgg gcgcggggcc gagagcgcgc tgaggcagag gtggcagaaa 1080ggcatgtcac ggggggtggg ggacaagatt gagcagaaaa gtcaaggcag gggttcgcta 1140gaaggaagca ggcaggcggg agacagtgag gaaagaggag gcgcccggtg cgcagaggag 1200gggggcgtcg cggtcgcgg atg gag ggg gag cag ggt gag gac ggg aag acc 1252
Met?Glu?Gly?Glu?Gln?Gly?Glu?Asp?Gly?Lys?Thr
1???????????????5???????????????????10gcg?gcg?ggg?ccg?ggt?agg?agc?acc?tcc?ggg?tgc?agg?agg?tcg?cgc?cca?????1300Ala?Ala?Gly?Pro?Gly?Arg?Ser?Thr?Ser?Gly?Cys?Arg?Arg?Ser?Arg?Pro
15??????????????????20??????????????????25tgg?gcc?ccc?ggc?cga?ctc?cgg?cgc?cag?tcg?ggg?cgg?gtg?cgg?ctt?ccc?????1348Trp?Ala?Pro?Gly?Arg?Leu?Arg?Arg?Gln?Ser?Gly?Arg?Val?Arg?Leu?Pro
30??????????????????35??????????????????40gcg?gcc?cag?agc?gcg?gct?ccg?gag?cca?ccg?tcc?acc?gcg?tgt?gca?ccc?????1396Ala?Ala?Gln?Ser?Ala?Ala?Pro?Glu?Pro?Pro?Ser?Thr?Ala?Cys?Ala?Pro
45??????????????????50??????????????????55gag?cct?ttg?tct?gcg?cct?cgc?tca?gga?gcc?gcg?ttt?ccg?cgg?cgc?ctt?????1444Glu?Pro?Leu?Ser?Ala?Pro?Arg?Ser?Gly?Ala?Ala?Phe?Pro?Arg?Arg?Leu60??????????????????65??????????????????70??????????????????75ctc?tgg?gcc?gac?gct?ctt?cca?gga?ttg?ctg?ttt?cgg?ttt?ccc?gct?ccc?????1492Leu?Trp?Ala?Asp?Ala?Leu?Pro?Gly?Leu?Leu?Phe?Arg?Phe?Pro?Ala?Pro
80??????????????????85??????????????????90aac?tgc?ggc?tca?ttc?cca?ggc?ttt?ggc?cga?ccc?ggg?tct?cca?ggg?cac?????1540Asn?Cys?Gly?Ser?Phe?Pro?Gly?Phe?Gly?Arg?Pro?Gly?Ser?Pro?Gly?His
95??????????????????100?????????????????105ccg?agg?ttg?agc?ccc?tcc?ctg?cgg?ccg?aag?ctg?ctc?cgg?gct?cac?cgc?????1588Pro?Arg?Leu?Ser?Pro?Ser?Leu?Arg?Pro?Lys?Leu?Leu?Arg?Ala?His?Arg
110?????????????????115?????????????????120ccg?ctc?agg?cac?ctt?tgg?ggt?gca?gcc?ccc?ggg?ctg?gcg?agc?gta?ttc?????1636Pro?Leu?Arg?His?Leu?Trp?Gly?Ala?Ala?Pro?Gly?Leu?Ala?Ser?Val?Phe
125?????????????????130?????????????????135gcg?ccg?gga?tcg?gcc?gct?cct?tgc?aac?ccc?gct?tcc?cgg?gca?cgg?gcg?????1684Ala?Pro?Gly?Ser?Ala?Ala?Pro?Cys?Asn?Pro?Ala?Ser?Arg?Ala?Arg?Ala140?????????????????145?????????????????150?????????????????155agt?cca?cgg?cgg?ccg?cgt?ggt?cag?cgg?cct?ctc?gta?cac?ccg?tgc?ggg?????1732Ser?Pro?Arg?Arg?Pro?Arg?Gly?Gln?Arg?Pro?Leu?Val?His?Pro?Cys?Gly
160?????????????????165?????????????????170ctc?cgg?cta?gcg?agt?cgc?tgc?ttg?cgc?ttg?att?ggc?tagcggggcg??????????1778Leu?Arg?Leu?Ala?Ser?Arg?Cys?Leu?Arg?Leu?Ile?Gly
175 180cgggcccaat gctcccgaag tcctctgacc cctaagtcct cccccccggt gtctgcctcc 1838cacccccgct gcagtctagg tggggaaggg gtgtggagat gggtgtgcat ggacagagca 1898tgtggccttc tctgttggcc agagatgtgg tcagtagaag cacttttccc tactgaagtg 1958ccctttggcc atgcattgaa ggtggtagag gatggggccc caccagctct cccggggtgt 2018tggcatcagc ctataggcct ggtctaggac tggggttcct cctggtcccc tatctggtgg 2078gcttgtgaat tctttcttaa gaaaataaac atctgctttt ctcaaaaaaa aaaaaaaaaa 2138aaa 2141<210〉30<211〉183<212〉PRT<213〉 ( Homo sapiens )<400〉30Met Glu Gly Glu Gln Gly Glu Asp Gly Lys Thr Ala Ala Gly Pro Gly1 5 10 15Arg Ser Thr Ser Gly Cys Arg Arg Ser Arg Pro Trp Ala Pro Gly Arg
20??????????????????25??????????????????30Leu?Arg?Arg?Gln?Ser?Gly?Arg?Val?Arg?Leu?Pro?Ala?Ala?Gln?Ser?Ala
35??????????????????40??????????????????45Ala?Pro?Glu?Pro?Pro?Ser?Thr?Ala?Cys?Ala?Pro?Glu?Pro?Leu?Ser?Ala
50??????????????????55??????????????????60Pro?Arg?Ser?Gly?Ala?Ala?Phe?Pro?Arg?Arg?Leu?Leu?Trp?Ala?Asp?Ala65??????????????????70??????????????????75??????????????????80Leu?Pro?Gly?Leu?Leu?Phe?Arg?Phe?Pro?Ala?Pro?Asn?Cys?Gly?Ser?Phe
85??????????????????90??????????????????95Pro?Gly?Phe?Gly?Arg?Pro?Gly?Ser?Pro?Gly?His?Pro?Arg?Leu?Ser?Pro
100?????????????????105?????????????????110Ser?Leu?Arg?Pro?Lys?Leu?Leu?Arg?Ala?His?Arg?Pro?Leu?Arg?His?Leu
115?????????????????120?????????????????125Trp?Gly?Ala?Ala?Pro?Gly?Leu?Ala?Ser?Val?Phe?Ala?Pro?Gly?Ser?Ala
130?????????????????135?????????????????140Ala?Pro?Cys?Asn?Pro?Ala?Ser?Arg?Ala?Arg?Ala?Ser?Pro?Arg?Arg?Pro145?????????????????150?????????????????155?????????????????160Arg?Gly?Gln?Arg?Pro?Leu?Val?His?Pro?Cys?Gly?Leu?Arg?Leu?Ala?Ser
165?????????????????170?????????????????175Arg?Cys?Leu?Arg?Leu?Ile?Gly
180<210〉31<211〉1843<212〉DNA<213〉 ( Homo sapiens )<400〉31gaggaagtag agcccgggac cgccaggcca ccaccggccg cctcagccat ggacgcgtcc 60ctggagaaga tagcagaccc cacgttagct gaaatgggaa aaaacttgaa ggaggcagtg 120aagatgctgg aggacagtca gagaagaaca gaagaggaaa atggaaagaa gctcatatcc 180ggagatattc caggcccact ccagggcagt gggcaagata tggtgagcat cctccagtta 240gttcagaatc tcatgcatgg agatgaagat gaggagcccc agagccccag gtaatgaacc 300tggcagcttc tcttttcaag taatccaaaa tattggagaa caaggtcata tggctttgtt 360gggacatagt ctgggagctt atatttcaac tctggacaaa gagaagctga gaaaacttac 420aactaggata ctttcagata ccaccttatg gctatgcaga attttcagat atgaaaatgg 480gtgtgcttat ttccacgaag aggaaagaga aggacttgca aagatatgta ggcttgccat 540tcattctcga tatgaagact tcgtagtgga tggcttcaat gtgttatata acaagaagcc 600tgtcatatat cttagtgctg ctgctagacc tggcctgggc caataccttt gtaatcagct 660cggcttgccc ttcccctgct tgtgccgtgt accctgtaac actgtgtttg gatcccagca 720gtaggacaca cagacaagat tgggagattg aaagaactct gtgagcagta tggcatatgg 780cttcatgtgg agggtgtgaa tctggcaaca ttggctctgg gttatgtctc ctcatcagtg 840ctggctgcag ccaaatgtga tagcatgacg atgactcctg gcccgtggct gggtttgcca 900gctgttcctg cggtgacact gtataaacac gatgaccctg ccttgacttt agttgctggt 960cttacatcaa ataagcccac agacaaactc cgtgccctgc ctctgtggtt atctttacaa 1020tacttgggac ttgatgggtt tgtggagagg atcaagcatg cctgtcaact gagtcaacgg 1080ttgcaggaaa gtttgaagaa agtgaattac atcaaaatct tggtggaaga tgagctcagc 1140tccccagtgg tggtgttcag atttttccag gaattaccag gctcagatcc ggtgtttaaa 1200gccgtcccag tgcccaacat gacaccttca ggagtcggcc gggagaggca ctcgtgtgac 1260gcgctgaatc gctggctggg agaacagctg aagcagctgg tgcctgcaag cggcctcaca 1320gtcatggatc tggaagctga gggcacgtgt ttgcggttca gccctttgat gaccgcagca 1380gggtggtccc actgtgggac cacaaccagg tatgactgtg tgagaagcag gctcactacc 1440aggctaccag ggagcacagg ggagcaggcg ccaccttgag gcataaaccc agagaaacaa 1500gacctccaag acggccaggc actggggcac acgccggtaa cacagcaccg tgggagctga 1560gacggaagga tcgcctgagc ccaggatttt gaaaccaccc tgggcaacac agtgagaccc 1620cgtatctaca aaaaaataca cattagccag gcatggcggc atgcgcctgg ggtcccaagt 1680actcgggagg tagaggagag aaaaatcact tgagcccaga gaggtcaagg ctacagggag 1740ctgagatcgc atcactgtac tccagctggg gtgaaacggc gagactctac ctcaaaaata 1800aataaataca tacataatta ataaataaaa aaaaaaaaaa aaa 1843<210〉32<211〉1843<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 865 ) .. ( 1476 )<223〉<400〉32gaggaagtag agcccgggac cgccaggcca ccaccggccg cctcagccat ggacgcgtcc 60ctggagaaga tagcagaccc cacgttagct gaaatgggaa aaaacttgaa ggaggcagtg 120aagatgctgg aggacagtca gagaagaaca gaagaggaaa atggaaagaa gctcatatcc 180ggagatattc caggcccact ccagggcagt gggcaagata tggtgagcat cctccagtta 240gttcagaatc tcatgcatgg agatgaagat gaggagcccc agagccccag gtaatgaacc 300tggcagcttc tcttttcaag taatccaaaa tattggagaa caaggtcata tggctttgtt 360gggacatagt ctgggagctt atatttcaac tctggacaaa gagaagctga gaaaacttac 420aactaggata ctttcagata ccaccttatg gctatgcaga attttcagat atgaaaatgg 480gtgtgcttat ttccacgaag aggaaagaga aggacttgca aagatatgta ggcttgccat 540tcattctcga tatgaagact tcgtagtgga tggcttcaat gtgttatata acaagaagcc 600tgtcatatat cttagtgctg ctgctagacc tggcctgggc caataccttt gtaatcagct 660cggcttgccc ttcccctgct tgtgccgtgt accctgtaac actgtgtttg gatcccagca 720gtaggacaca cagacaagat tgggagattg aaagaactct gtgagcagta tggcatatgg 780cttcatgtgg agggtgtgaa tctggcaaca ttggctctgg gttatgtctc ctcatcagtg 840ctggctgcag ccaaatgtga tagc atg acg atg act cct ggc ccg tgg ctg 891
Met?Thr?Met?Thr?Pro?Gly?Pro?Trp?Leu
1???????????????5ggt?ttg?cca?gct?gtt?cct?gcg?gtg?aca?ctg?tat?aaa?cac?gat?gac?cct?????939Gly?Leu?Pro?Ala?Val?Pro?Ala?Val?Thr?Leu?Tyr?Lys?His?Asp?Asp?Pro10??????????????????15??????????????????20??????????????????25gcc?ttg?act?tta?gtt?gct?ggt?ctt?aca?tca?aat?aag?ccc?aca?gac?aaa?????987Ala?Leu?Thr?Leu?Val?Ala?Gly?Leu?Thr?Ser?Asn?Lys?Pro?Thr?Asp?Lys
30??????????????????35??????????????????40ctc?cgt?gcc?ctg?cct?ctg?tgg?tta?tct?tta?caa?tac?ttg?gga?ctt?gat????1035Leu?Arg?Ala?Leu?Pro?Leu?Trp?Leu?Ser?Leu?Gln?Tyr?Leu?Gly?Leu?Asp
45??????????????????50??????????????????55ggg?ttt?gtg?gag?agg?atc?aag?cat?gcc?tgt?caa?ctg?agt?caa?cgg?ttg????1083Gly?Phe?Val?Glu?Arg?Ile?Lys?His?Ala?Cys?Gln?Leu?Ser?Gln?Arg?Leu
60??????????????????65??????????????????70cag?gaa?agt?ttg?aag?aaa?gtg?aat?tac?atc?aaa?atc?ttg?gtg?gaa?gat????1131Gln?Glu?Ser?Leu?Lys?Lys?Val?Asn?Tyr?Ile?Lys?Ile?Leu?Val?Glu?Asp
75??????????????????80??????????????????85gag?ctc?agc?tcc?cca?gtg?gtg?gtg?ttc?aga?ttt?ttc?cag?gaa?tta?cca????1179Glu?Leu?Ser?Ser?Pro?Val?Val?Val?Phe?Arg?Phe?Phe?Gln?Glu?Leu?Pro90??????????????????95??????????????????100?????????????????105ggc?tca?gat?ccg?gtg?ttt?aaa?gcc?gtc?cca?gtg?ccc?aac?atg?aca?cct????1227Gly?Ser?Asp?Pro?Val?Phe?Lys?Ala?Val?Pro?Val?Pro?Asn?Met?Thr?Pro
110?????????????????115?????????????????120tca?gga?gtc?ggc?cgg?gag?agg?cac?tcg?tgt?gac?gcg?ctg?aat?cgc?tgg????1275Ser?Gly?Val?Gly?Arg?Glu?Arg?His?Ser?Cys?Asp?Ala?Leu?Asn?Arg?Trp
125?????????????????130?????????????????135ctg?gga?gaa?cag?ctg?aag?cag?ctg?gtg?cct?gca?agc?ggc?ctc?aca?gtc????1323Leu?Gly?Glu?Gln?Leu?Lys?Gln?Leu?Val?Pro?Ala?Ser?Gly?Leu?Thr?Val
140?????????????????145?????????????????150atg?gat?ctg?gaa?gct?gag?ggc?acg?tgt?ttg?cgg?ttc?agc?cct?ttg?atg????1371Met?Asp?Leu?Glu?Ala?Glu?Gly?Thr?Cys?Leu?Arg?Phe?Ser?Pro?Leu?Met
155?????????????????160?????????????????165acc?gca?gca?ggg?tgg?tcc?cac?tgt?ggg?acc?aca?acc?agg?tat?gac?tgt????1419Thr?Ala?Ala?Gly?Trp?Ser?His?Cys?Gly?Thr?Thr?Thr?Arg?Tyr?Asp?Cys170?????????????????175?????????????????180?????????????????185gtg?aga?agc?agg?ctc?act?acc?agg?cta?cca?ggg?agc?aca?ggg?gag?cag????1467Val?Arg?Ser?Arg?Leu?Thr?Thr?Arg?Leu?Pro?Gly?Ser?Thr?Gly?Glu?Gln
190 195 200gcg cca cct tgaggcataa acccagagaa acaagacctc caagacggcc 1516Ala Pro Pro aggcactggg gcacacgccg gtaacacagc accgtgggag ctgagacgga aggatcgcct 1576gagcccagga ttttgaaacc accctgggca acacagtgag accccgtatc tacaaaaaaa 1636tacacattag ccaggcatgg cggcatgcgc ctggggtccc aagtactcgg gaggtagagg 1696agagaaaaat cacttgagcc cagagaggtc aaggctacag ggagctgaga tcgcatcact 1756gtactccagc tggggtgaaa cggcgagact ctacctcaaa aataaataaa tacatacata 1816attaataaat aaaaaaaaaa aaaaaaa 1843<210〉33<211〉204<212〉PRT<213〉 ( Homo sapiens )<400〉33Met Thr Met Thr Pro Gly Pro Trp Leu Gly Leu Pro Ala Val Pro Ala1 5 10 15Val Thr Leu Tyr Lys His Asp Asp Pro Ala Leu Thr Leu Val Ala Gly
20??????????????????25??????????????????30Leu?Thr?Ser?Asn?Lys?Pro?Thr?Asp?Lys?Leu?Arg?Ala?Leu?Pro?Leu?Trp
35??????????????????40??????????????????45Leu?Ser?Leu?Gln?Tyr?Leu?Gly?Leu?Asp?Gly?Phe?Val?Glu?Arg?Ile?Lys
50??????????????????55??????????????????60His?Ala?Cys?Gln?Leu?Ser?Gln?Arg?Leu?Gln?Glu?Ser?Leu?Lys?Lys?Val65??????????????????70??????????????????75??????????????????80Asn?Tyr?Ile?Lys?Ile?Leu?Val?Glu?Asp?Glu?Leu?Ser?Ser?Pro?Val?Val
85??????????????????90??????????????????95Val?Phe?Arg?Phe?Phe?Gln?Glu?Leu?Pro?Gly?Ser?Asp?Pro?Val?Phe?Lys
100?????????????????105?????????????????110Ala?Val?Pro?Val?Pro?Asn?Met?Thr?Pro?Ser?Gly?Val?Gly?Arg?Glu?Arg
115?????????????????120?????????????????125His?Ser?Cys?Asp?Ala?Leu?Asn?Arg?Trp?Leu?Gly?Glu?Gln?Leu?Lys?Gln
130?????????????????135?????????????????140Leu?Val?Pro?Ala?Ser?Gly?Leu?Thr?Val?Met?Asp?Leu?Glu?Ala?Glu?Gly145?????????????????150?????????????????155?????????????????160Thr?Cys?Leu?Arg?Phe?Ser?Pro?Leu?Met?Thr?Ala?Ala?Gly?Trp?Ser?His
165?????????????????170?????????????????175Cys?Gly?Thr?Thr?Thr?Arg?Tyr?Asp?Cys?Val?Arg?Ser?Arg?Leu?Thr?Thr
180?????????????????185?????????????????190Arg?Leu?Pro?Gly?Ser?Thr?Gly?Glu?Gln?Ala?Pro?Pro
195 200<210〉34<211〉1083<212〉DNA<213〉 ( Homo sapiens )<400〉34gagccaaggg tggcagtcac agagatgttc acacaaagga gcctccttct gctgagacag 60gcagcacagg gtcccctcca ggaagtggcc atggtaatga gggtttctcc ctccaggccg 120ggactgacac cactggccag gaagtggctg aagctcagct ggatgaggat ggggatttgg 180acgtggtgag aagaccacga gccgcctctg attccaaccc agcagggcct ctgagagaca 240aggtacatcc catgattcta gcacaggaag aagacgacgt cctgggagag gaagcacaag 300gcagcccgca cgatatcatc agaataggtg tggcggggcg ccctgctcct ggcagactac 360atcctgttcc gacaggacct cttccgagga tgtacagcgc tggagctcgg ggccggcacg 420gggctcgcta gcatcatcgc agccaccatg gcacggaccg tttattgtac agatgtcggt 480gcagatctct tgtccatgtg ccagcgaaac attgccctca acagccacct ggctgccact 540ggaggtggta tagttagggt caaagaactg gactggctga aggacgacct ctgcacagat 600cccaaggtcc ccttcagttg gtcacaagag gaaatttctg acctgtacga tcacaccacc 660atcctgtttg cagccgaagt gttttacgac gacgacttga ctgatgctgt gtttaaaacg 720ctctcccgac tcgcccacag attgaaaaat gcctgcacag ccatactgtc ggtggagaag 780aggctcaact tcacactgag acacttggac gtcacatgtg aagcctacga tcacttccgc 840tcctgcctgc acgcgctgga gcagctcaca gatggcaagc tgcgcttcgt ggtggagccc 900gtggaggcct ccttcccaca gctcctggtt tacgagcgcc tccagcagct ggagctctgg 960aagatcatcg cagaaccagt aacatgaccc atcgcctcca ccaggcgcgg cgtctcgact 1020gttcttagag tgtatttcta gtaaaatcag aagctcacca aagcaaaaaa aaaaaaaaaa 1080aaa 1083<210〉35<211〉1083<212〉DNA<213〉 ( Homo sapiens )<220〉<221〉CDS<222〉 ( 448 ) .. ( 984 )<223〉<400〉35gagccaaggg tggcagtcac agagatgttc acacaaagga gcctccttct gctgagacag 60gcagcacagg gtcccctcca ggaagtggcc atggtaatga gggtttctcc ctccaggccg 120ggactgacac cactggccag gaagtggctg aagctcagct ggatgaggat ggggatttgg 180acgtggtgag aagaccacga gccgcctctg attccaaccc agcagggcct ctgagagaca 240aggtacatcc catgattcta gcacaggaag aagacgacgt cctgggagag gaagcacaag 300gcagcccgca cgatatcatc agaataggtg tggcggggcg ccctgctcct ggcagactac 360atcctgttcc gacaggacct cttccgagga tgtacagcgc tggagctcgg ggccggcacg 420gggctcgcta gcatcatcgc agccacc atg gca cgg acc gtt tat tgt aca gat 474
Met?Ala?Arg?Thr?Val?Tyr?Cys?Thr?Asp
1???????????????5gtc?ggt?gca?gat?ctc?ttg?tcc?atg?tgc?cag?cga?aac?att?gcc?ctc?aac??????522Val?Gly?Ala?Asp?Leu?Leu?Ser?Met?Cys?Gln?Arg?Asn?Ile?Ala?Leu?Asn10??????????????????15??????????????????20??????????????????25agc?cac?ctg?gct?gcc?act?gga?ggt?ggt?ata?gtt?agg?gtc?aaa?gaa?ctg??????570Ser?His?Leu?Ala?Ala?Thr?Gly?Gly?Gly?Ile?Val?Arg?Val?Lys?Glu?Leu
30??????????????????35??????????????????40gac?tgg?ctg?aag?gac?gac?ctc?tgc?aca?gat?ccc?aag?gtc?ccc?ttc?agt??????618Asp?Trp?Leu?Lys?Asp?Asp?Leu?Cys?Thr?Asp?Pro?Lys?Val?Pro?Phe?Ser
45??????????????????50??????????????????55tgg?tca?caa?gag?gaa?att?tct?gac?ctg?tac?gat?cac?acc?acc?atc?ctg??????666Trp?Ser?Gln?Glu?Glu?Ile?Ser?Asp?Leu?Tyr?Asp?His?Thr?Thr?Ile?Leu
60??????????????????65??????????????????70ttt?gca?gcc?gaa?gtg?ttt?tac?gac?gac?gac?ttg?act?gat?gct?gtg?ttt??????714Phe?Ala?Ala?Glu?Val?Phe?Tyr?Asp?Asp?Asp?Leu?Thr?Asp?Ala?Val?Phe
75??????????????????80??????????????????85aaa?acg?ctc?tcc?cga?ctc?gcc?cac?aga?ttg?aaa?aat?gcc?tgc?aca?gcc??????762Lys?Thr?Leu?Ser?Arg?Leu?Ala?His?Arg?Leu?Lys?Asn?Ala?Cys?Thr?Ala90??????????????????95??????????????????100?????????????????105ata?ctg?tcg?gtg?gag?aag?agg?ctc?aac?ttc?aca?ctg?aga?cac?ttg?gac??????810Ile?Leu?Ser?Val?Glu?Lys?Arg?Leu?Asn?Phe?Thr?Leu?Arg?His?Leu?Asp
110?????????????????115?????????????????120gtc?aca?tgt?gaa?gcc?tac?gat?cac?ttc?cgc?tcc?tgc?ctg?cac?gcg?ctg??????858Val?Thr?Cys?Glu?Ala?Tyr?Asp?His?Phe?Arg?Ser?Cys?Leu?His?Ala?Leu
125?????????????????130?????????????????135gag?cag?ctc?aca?gat?ggc?aag?ctg?cgc?ttc?gtg?gtg?gag?ccc?gtg?gag??????906Glu?Gln?Leu?Thr?Asp?Gly?Lys?Leu?Arg?Phe?Val?Val?Glu?Pro?Val?Glu
140?????????????????145?????????????????150gcc?tcc?ttc?cca?cag?ctc?ctg?gtt?tac?gag?cgc?ctc?cag?cag?ctg?gag??????954Ala?Ser?Phe?Pro?Gln?Leu?Leu?Val?Tyr?Glu?Arg?Leu?Gln?Gln?Leu?Glu
155 160 165ctc tgg aag atc atc gca gaa cca gta aca tgacccatcg cctccaccag 1004Leu Trp Lys Ile Ile Ala Glu Pro Val Thr170 175gcgcggcgtc tcgactgttc ttagagtgta tttctagtaa aatcagaagc tcaccaaagc 1064aaaaaaaaaa aaaaaaaaa, 1083<210〉36<211〉179<212〉PRT<213〉homo sapiens (Homo sapiens)<400〉36Met Ala Arg Thr Val Tyr Cys Thr Asp Val Gly Ala Asp Leu Leu Ser1,5 10 15Met Cys Gln Arg Asn Ile Ala Leu Asn Ser His Leu Ala Ala Thr Gly
20??????????????????25??????????????????30Gly?Gly?Ile?Val?Arg?Val?Lys?Glu?Leu?Asp?Trp?Leu?Lys?Asp?Asp?Leu
35??????????????????40??????????????????45Cys?Thr?Asp?Pro?Lys?Val?Pro?Phe?Ser?Trp?Ser?Gln?Glu?Glu?Ile?Ser
50??????????????????55??????????????????60Asp?Leu?Tyr?Asp?His?Thr?Thr?Ile?Leu?Phe?Ala?Ala?Glu?Val?Phe?Tyr65??????????????????70??????????????????75??????????????????80Asp?Asp?Asp?Leu?Thr?Asp?Ala?Val?Phe?Lys?Thr?Leu?Ser?Arg?Leu?Ala
85??????????????????90??????????????????95His?Arg?Leu?Lys?Asn?Ala?Cys?Thr?Ala?Ile?Leu?Ser?Val?Glu?Lys?Arg
100?????????????????105?????????????????110Leu?Asn?Phe?Thr?Leu?Arg?His?Leu?Asp?Val?Thr?Cys?Glu?Ala?Tyr?Asp
115?????????????????120?????????????????125His?Phe?Arg?Ser?Cys?Leu?His?Ala?Leu?Glu?Gln?Leu?Thr?Asp?Gly?Lys
130?????????????????135?????????????????140Leu?Arg?Phe?Val?Val?Glu?Pro?Val?Glu?Ala?Ser?Phe?Pro?Gln?Leu?Leu145?????????????????150?????????????????155?????????????????160Val?Tyr?Glu?Arg?Leu?Gln?Gln?Leu?Glu?Leu?Trp?Lys?Ile?Ile?Ala?Glu
165 170 175Pro Val Thr<210〉37<211〉19<212〉DNA<213〉<400〉37tcagcccagc aattcgttt 19<210〉38<211〉20<212〉DNA<213〉<400〉38aacttggaca ctccgtctcc 20<210〉39<211〉21<212〉DNA<213〉<400〉39gatcaggtaa cgcaggtgtc g 21<210〉40<211〉18<212〉DNA<213〉<400〉40gggaggacgc gacctttg 18<210〉41<211〉20<212〉DNA<213〉<400〉41tggcttggag tagcaccttc 20<210〉42<211〉21<212〉DNA<213〉<400〉42ggttgtaccc ctttgagaca g 21<210〉43<211〉21<212〉DNA<213〉<400〉43gcacagtcaa acagggctaa g 21<210〉44<211〉21<212〉DNA<213〉<400〉44tacggggtct acctaagatg a 21<210〉45<211〉18<212〉DNA<213〉<400〉45ggcgggaact gaaactgc 18<210〉46<211〉18<212〉DNA<213〉<400〉46accaacaccc accgtcgt 18<210〉47<211〉18<212〉DNA<213〉<400〉47tcgtgggagg gctcaact 18<210〉48<211〉22<212〉DNA<213〉<400〉48gttcttgtac taataggtcc cc 22<210〉49<211〉18<212〉DNA<213〉<400〉49cagggtgaaa tcccgtcc 18<210〉50<211〉19<212〉DNA<213〉<400〉50actccgtcct cctacctca 19<210〉51<211〉18<212〉DNA<213〉<400〉51catggacggg gaggagca 18<210〉52<211〉19<212〉DNA<213〉<400〉52ggagggagga ccgacaggt 19<210〉53<211〉22<212〉DNA<213〉<400〉53tgaatctatc gtctccaatc cg 22<210〉54<211〉18<212〉DNA<213〉<400〉54cccacccttc accccgat 18<210〉55<211〉20<212〉DNA<213〉<400〉55ccctcctcat ctgcctttca 20<210〉56<211〉21<212〉DNA<213〉<400〉56aacttccacc atctcctacc c 21<210〉57<211〉19<212〉DNA<213〉<400〉57gcagacccca cgttagctg 19<210〉58<211〉21<212〉DNA<213〉<400〉58cactttgccg ctctgagatg g 21<210〉59<211〉20<212〉DNA<213〉<400〉59caagggtggc agtcacagag 20<210〉60<211〉22<212〉DNA<213〉<400〉60cttggtcatt gtactgggta gc 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:3,6,9,12,15,18,21,24,27,30,33,36;
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:3,6,9,12,15,18,21,24,27,30,33,36.
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:3,6,9,12,15,18,21,24,27,30,33,36.
5. polynucleotide as claimed in claim 3 is characterized in that, the sequence of these polynucleotide is selected from down group:
SEQ ID NO:2,5,8,11,14,17,20,23,26,29,32,35 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.
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CNB021370001A CN1229386C (en) | 2002-09-16 | 2002-09-16 | Novel human protein with function for suppressing cancer and coding sequence thereof |
AU2003255098A AU2003255098A1 (en) | 2002-08-07 | 2003-08-07 | A novel homo protein with cancer suppressing function and its coding sequence |
PCT/CN2003/000639 WO2004014946A1 (en) | 2002-08-07 | 2003-08-07 | A novel homo protein with cancer suppressing function and its coding sequence |
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CN1229386C CN1229386C (en) | 2005-11-30 |
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Cited By (1)
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WO2022152236A1 (en) * | 2021-01-15 | 2022-07-21 | 同宜医药(苏州)有限公司 | Anti-trpv6 monoclonal antibody and application thereof |
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Cited By (1)
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WO2022152236A1 (en) * | 2021-01-15 | 2022-07-21 | 同宜医药(苏州)有限公司 | Anti-trpv6 monoclonal antibody and application thereof |
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