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

Novel human protein with cancer-inhibiting function and coding sequence thereof Download PDF

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CN1222616C
CN1222616C CNB021454353A CN02145435A CN1222616C CN 1222616 C CN1222616 C CN 1222616C CN B021454353 A CNB021454353 A CN B021454353A CN 02145435 A CN02145435 A CN 02145435A CN 1222616 C CN1222616 C CN 1222616C
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CN1502626A (en
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顾健人
杨胜利
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SHANGHAI XINSHIJIE GENE TECHN DEVELOPMENT Co Ltd
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SHANGHAI XINSHIJIE GENE TECHN DEVELOPMENT Co Ltd
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Priority to PCT/CN2003/000639 priority patent/WO2004014946A1/en
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Abstract

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

Description

New people's albumen and encoding sequence thereof with cancer suppressing function
Technical field
The invention belongs to biological technical field, specifically, the present invention relates to new coding and have the proteic polynucleotide of people of cancer suppressing function and the polypeptide of this polynucleotide encoding.The invention still further relates to the purposes and the preparation of these polynucleotide and polypeptide.
Background technology
The research of people's gene group is international focus at present, removes human chromosome DNA large scale sequencing, outside the method for expressed sequence order-checking (EST), also lacks the screening that begins from function and has the high-throughout method of functional gene.
Cancer is one of principal disease of harm humans health.In order to treat effectively and prophylaxis of tumours, people more and more pay close attention to genetic treatment of tumor at present.Therefore, this area presses for people's albumen and the agonist/inhibitor thereof that development research has cancer suppressing function.
Summary of the invention
The purpose of this invention is to provide the new people's protein polypeptide of a class with cancer suppressing function with and fragment, analogue and derivative.
Another object of the present invention provides the polynucleotide of these polypeptide of coding.
Another object of the present invention provides the method for these polypeptide of production and the purposes of this polypeptide and encoding sequence.
In a first aspect of the present invention, novel isolated protein polypeptide with cancer suppressing function is provided, it comprises the polypeptide of the aminoacid sequence with the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30; Or its conservative property variation polypeptide or its active fragments or its reactive derivative.Preferably, this polypeptide is the polypeptide with aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30.
In a second aspect of the present invention, a kind of isolating polynucleotide are provided, it comprises a nucleotide sequence, and this nucleotide sequence is shown at least 85% homogeny with a kind of nucleotides sequence that is selected from down group: the polynucleotide of the above-mentioned protein polypeptide with cancer suppressing function of (a) encoding; (b) with polynucleotide (a) complementary polynucleotide.Preferably, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27,30.More preferably, the sequence of these polynucleotide is selected from down group: SEQ ID NO:2,5,8,11,14,17,20,23,26,29 coding region sequence or full length sequence.
In a third aspect of the present invention, the carrier that contains above-mentioned polynucleotide is provided, and has been transformed or host cell of transduceing or the host cell that is directly transformed or transduce by above-mentioned polynucleotide by this carrier.
In a fourth aspect of the present invention, the preparation method who prepares the polypeptide of the protein-active with cancer suppressing function is provided, this method comprises: (a) have under the proteic condition of cancer suppressing function suitable the expression, cultivate the above-mentioned host cell that is transformed or transduce; (b) from culture, isolate the polypeptide of protein-active with cancer suppressing function.
In a fifth aspect of the present invention, provide and above-mentioned protein polypeptide specificity bonded antibody with cancer suppressing function.The nucleic acid molecule that can be used for detecting also is provided, and it contains, and continuous 10 Nucleotide are to full length nucleotide in the above-mentioned polynucleotide, and preferably it contains the about 15-1000 of a successive Nucleotide.
In a sixth aspect of the present invention, a kind of pharmaceutical composition is provided, it contains the protein polypeptide and the pharmaceutically acceptable carrier with cancer suppressing function of the present invention of safe and effective amount.These pharmaceutical compositions can be treated illnesss such as cancer and cellular abnormality propagation.
Others of the present invention are because the disclosure of this paper is conspicuous to those skilled in the art.
Embodiment
The present invention adopts large-scale cDNA clone transfection cancer cells, has on the basis of cancer suppressing action in acquisition, proves new gene through order-checking, further obtains full length cDNA clone.DNA transfection evidence, the albumen with cancer suppressing function of the present invention has the effect that suppresses clone's formation, its inhibiting rate 〉=50% to liver cancer cell 7721.
As used herein, " isolating " is meant that material separates (if natural substance, primal environment promptly is a natural surroundings) from its primal environment.Do not have separation and purification as polynucleotide under the native state in the active somatic cell and polypeptide, but same polynucleotide or polypeptide as from native state with in other materials that exist separately, then for separation and purification.
As used herein, " isolating albumen or polypeptide with cancer suppressing function " is meant that the protein polypeptide with cancer suppressing function is substantially free of natural relative other albumen, lipid, carbohydrate or other material.Those skilled in the art can have the albumen of cancer suppressing function with the purified technology of protein purifying of standard.Basically pure polypeptide can produce single master tape on non-reduced polyacrylamide gel.
Polypeptide of the present invention can be recombinant polypeptide, natural polypeptides, synthetic polypeptide, preferred recombinant polypeptide.Polypeptide of the present invention can be the product of natural purifying, or the product of chemosynthesis, or uses recombinant technology to produce from protokaryon or eucaryon host (for example, bacterium, yeast, higher plant, insect and mammalian cell).The host used according to the recombinant production scheme, polypeptide of the present invention can be glycosylated, maybe can be nonglycosylated.Polypeptide of the present invention also can comprise or not comprise initial methionine residues.
The present invention also comprises the proteic fragment of the people with cancer suppressing function, derivative and analogue.As used herein, term " fragment ", " derivative " are meant with " analogue " and keep natural identical biological function or the active polypeptide of people's albumen with cancer suppressing function of the present invention basically.Polypeptide fragment of the present invention, derivative or analogue can be that (i) has one or more conservative or substituted polypeptide of non-conservation amino-acid residue (preferred conservative amino acid residue), and the amino-acid residue of such replacement can be also can not encoded by genetic code, or (ii) in one or more amino-acid residues, has a polypeptide of substituted radical, or (iii) mature polypeptide and another compound (such as the compound that prolongs the polypeptide transformation period, polyoxyethylene glycol for example) merge formed polypeptide, or (iv) additional aminoacid sequence is fused to this peptide sequence and the polypeptide that forms (as leader sequence or secretion sequence or be used for the sequence or the proteinogen sequence of this polypeptide of purifying).According to the instruction of this paper, these fragments, derivative and analogue belong to the known scope of those skilled in the art.
Polynucleotide of the present invention can be dna form or rna form.Dna form comprises the DNA of cDNA, genomic dna or synthetic.DNA can be strand or double-stranded.DNA can be coding strand or noncoding strand.Be example with LP4790 albumen (in this application, its clone numbering is adopted in proteinic name), the coding region sequence of encoding mature polypeptide can be identical with the coding region sequence shown in the SEQ ID NO:2 or the varient of degeneracy.As used herein, " varient of degeneracy " is meant that for LP4790 coding has the protein of SEQ ID NO:3, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ ID NO:2.Be example with LP4791 albumen again, the coding region sequence of encoding mature polypeptide can be identical with the coding region sequence shown in the SEQ ID NO:5 or the varient of degeneracy; " varient of degeneracy " is meant that for LP4791 coding has the protein of SEQ ID NO:6, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ ID NO:5.Have the albumen of cancer suppressing function for of the present invention other, can the rest may be inferred.
The polynucleotide of encoding mature polypeptide comprise: the encoding sequence of an encoding mature polypeptide; The encoding sequence of mature polypeptide and various additional code sequence; Encoding sequence of mature polypeptide (with optional additional code sequence) and non-coding sequence.
Term " polynucleotide of coded polypeptide " can be the polynucleotide that comprise this polypeptide of encoding, and also can be the polynucleotide that also comprise additional code and/or non-coding sequence.
The invention still further relates to the varient of above-mentioned polynucleotide, its coding has the polypeptide of identical aminoacid sequence or fragment, analogue and the derivative of polypeptide with the present invention.The varient of these polynucleotide can be the allelic variant of natural generation or the varient that non-natural takes place.These nucleotide diversity bodies comprise and replace varient, deletion mutation body and insert varient.As known in the art, allelic variant is the replacement form of polynucleotide, and it may be replacement, disappearance or the insertion of one or more Nucleotide, but can be from not changing the function of its encoded polypeptides in fact.
The invention still further relates to and above-mentioned sequence hybridization and two sequences between have at least 50%, preferably at least 70%, the polynucleotide of at least 80% homogeny more preferably.The present invention be more particularly directed under stringent condition and the interfertile polynucleotide of polynucleotide of the present invention.In the present invention, " stringent condition " is meant: (1) than hybridization under low ionic strength and the comparatively high temps and wash-out, as 0.2 * SSC, and 0.1%SDS, 60 ℃; Or (2) hybridization the time is added with denaturing agent, as 50% (v/v) methane amide, 0.1% calf serum/0.1%Ficoll, 42 ℃ etc.; Or (3) only at the homogeny between the two sequences at least more than 95%, be more preferably 97% and just hybridize when above.And the polypeptide of interfertile polynucleotide encoding has identical biological function (is example with LP4790 albumen) and activity with the mature polypeptide shown in the SEQ IDNO:3.
The invention still further relates to nucleic acid fragment with above-mentioned sequence hybridization.As used herein, the length of " nucleic acid fragment " contains 15 Nucleotide at least, better is at least 30 Nucleotide, is more preferably at least 50 Nucleotide, preferably more than at least 100 Nucleotide.The amplification technique (as PCR) that nucleic acid fragment can be used for nucleic acid has the proteic polynucleotide of cancer suppressing function to determine and/or to separate to encode.
Polypeptide among the present invention and polynucleotide preferably provide with isolating form, more preferably are purified to homogeneous.
Dna sequence dna of the present invention can obtain with several method.For example, with hybridization technique DNA isolation well known in the art.These technology including, but not limited to: 1) with probe and genome or the hybridization of cDNA library to detect homology nucleotide sequence and 2) antibody screening of expression library to be to detect the dna fragmentation of the clone with common structure feature.
The proteic specific DNA fragment sequence that coding has cancer suppressing function produces also and can obtain with following method: 1) separate double chain DNA sequence from genomic dna; 2) the chemical synthesising DNA sequence is to obtain the double-stranded DNA of required polypeptide.
When the whole aminoacid sequence of the polypeptide product of needs was known, the direct chemical of dna sequence dna is synthetic to be the method for often selecting for use.When if required amino acid whose whole sequence is not known, the direct chemical of dna sequence dna is synthetic to be impossible, and the method for selecting for use is the separation of cDNA sequence.The standard method that separates interested cDNA is from the donorcells separating mRNA of this gene of high expression level and carries out reverse transcription, forms plasmid or phage cDNA library.Extract the existing multiple proven technique of method of mRNA, test kit also can obtain (Qiagene) from commercial channels.And the construction cDNA library also is usual method (Sambrook, et al., Molecular Cloning, A Laboratory Manual, Cold SpringHarbor Laboratory.New York, 1989).Also can obtain the cDNA library of commercial offers, as the different cDNA library of Clontech company.When being used in combination the polymeric enzyme reaction technology, even few expression product also can be cloned.
Available ordinary method is screened gene of the present invention from these cDNA libraries.These methods include, but is not limited to: (1) DNA-DNA or DNA-RNA hybridization; (2) function of marker gene occurs or forfeiture; (3) mensuration has the level of the proteic transcript of cancer suppressing function; (4), detect the protein product of genetic expression by immunological technique or mensuration biologic activity.Aforesaid method can singly be used, but also several different methods combined utilization.
In (1) kind method, hybridizing used probe is and any a part of homology of polynucleotide of the present invention that at least 15 Nucleotide of its length better are at least 30 Nucleotide, are more preferably at least 50 Nucleotide, preferably at least 100 Nucleotide.In addition, the length of probe within 2kb, preferably is within the 1kb usually.Probe used herein is the dna sequence dna of chemosynthesis on the basis of gene DNA sequence information of the present invention normally.Gene of the present invention itself or fragment are certainly as probe.The mark of dna probe can be used radio isotope, fluorescein or enzyme (as alkaline phosphatase) etc.
In (4) kind method, detect the protein product of protein gene expression and can use immunological technique such as Western blotting, radioimmunoprecipitation, enzyme-linked immunosorbent assay (ELISA) etc. with cancer suppressing function.
Use method (Saiki, the et al.Science 1985 of round pcr DNA amplification/RNA; 230:1350-1354) be optimized for acquisition gene of the present invention.When particularly being difficult to obtain the cDNA of total length from the library, can preferably use RACE method (the terminal rapid amplifying method of RACE-cDNA), the primer that is used for PCR can suitably be selected according to sequence information of the present invention disclosed herein, and available ordinary method is synthetic.Available ordinary method is as the DNA/RNA fragment by gel electrophoresis separation and purifying amplification.
The gene of the present invention that obtains as mentioned above, perhaps the available ordinary method of mensuration of the nucleotide sequence of various dna fragmentations etc. such as dideoxy chain termination (Sanger et al.PNAS, 1977,74:5463-5467).This class nucleotide sequencing is available commercial sequencing kit etc. also.In order to obtain the cDNA sequence of total length, order-checking need be carried out repeatedly.Sometimes need to measure a plurality of clones' cDNA sequence, just can be spliced into the cDNA sequence of total length.
The present invention also relates to comprise the carrier of polynucleotide of the present invention, and the host cell that produces through genetically engineered with carrier of the present invention or albumen coded sequence with cancer suppressing function, and the method that produces polypeptide of the present invention through recombinant technology.
By the recombinant DNA technology of routine, can utilize polymerized nucleoside acid sequence of the present invention to can be used to express or produce the protein polypeptide with cancer suppressing function of reorganization.In general following steps are arranged:
(1). have the proteic polynucleotide of people (or varient) of cancer suppressing function with coding of the present invention, or transform or the transduction proper host cell with the recombinant expression vector that contains these polynucleotide;
(2). the host cell of in suitable medium, cultivating;
(3). separation, protein purification from substratum or cell.
Among the present invention, the people's albumen polynucleotide sequence with cancer suppressing function can be inserted in the recombinant expression vector.Term " recombinant expression vector " refers to that bacterial plasmid well known in the art, phage, yeast plasmid, vegetable cell virus, mammalian cell virus are as adenovirus, retrovirus or other carriers.The carrier of Shi Yonging includes but not limited in the present invention: the expression vector based on T7 of expressing in bacterium; The pMSXND expression vector of in mammalian cell, expressing and at the carrier that derives from baculovirus of expressed in insect cells.In a word, as long as can duplicate in host and stablize, any plasmid and carrier can be used.A key character of expression vector is to contain replication orgin, promotor, marker gene and translation controlling elements usually.
Method well-known to those having ordinary skill in the art can be used to make up and contains people's encoding histone dna sequence dna with cancer suppressing function and suitable transcribing/the translate expression vector of control signal.These methods comprise extracorporeal recombinant DNA technology, DNA synthetic technology, the interior recombinant technology of body etc.Described dna sequence dna can effectively be connected on the suitable promotor in the expression vector, and is synthetic to instruct mRNA.The representative example of these promotors has: colibacillary lac or trp promotor; Lambda particles phage P LPromotor; Eukaryotic promoter comprises LTRs and some other known may command gene expression promoter in protokaryon or eukaryotic cell or its virus of CMV immediate early promoter, early stage and late period SV40 promotor, retrovirus.Expression vector also comprises ribosome bind site and the transcription terminator that translation initiation is used.
In addition, expression vector preferably comprises one or more selected markers, to be provided for selecting the phenotypic character of transformed host cells, cultivate Tetrahydrofolate dehydrogenase, neomycin resistance and the green fluorescent protein (GFP) of usefulness as eukaryotic cell, or be used for colibacillary tsiklomitsin or amicillin resistance.
Comprise the carrier of above-mentioned suitable dna sequence dna and suitable promotor or control sequence, can be used to transform appropriate host cell, so that it can marking protein.
Host cell can be a prokaryotic cell prokaryocyte, as bacterial cell; Or eukaryotic cell such as low, as yeast cell; Or higher eucaryotic cells, as mammalian cell.Representative example has: intestinal bacteria, streptomyces; The bacterial cell of Salmonella typhimurium; Fungal cell such as yeast; Vegetable cell; The insect cell of fruit bat S2 or Sf9; The zooblast of CHO, COS or Bowes melanoma cells etc.
When polynucleotide of the present invention are expressed in higher eucaryotic cells, be enhanced if will make to transcribe when in carrier, inserting enhancer sequence.Enhanser is the cis acting factor of DNA, and nearly 10 to 300 base pairs act on promotor transcribing with enhancing gene usually.Can for example be included in the SV40 enhanser of 100 to 270 base pairs of replication origin side in late period one, at the polyoma enhanser of replication origin side in late period one and adenovirus enhanser etc.
Persons skilled in the art all know how to select appropriate carriers, promotor, enhanser and host cell.
Can carry out with routine techniques well known to those skilled in the art with the recombinant DNA transformed host cell.When the host was prokaryotic organism such as intestinal bacteria, the competent cell that can absorb DNA can be used CaCl in exponential growth after date results 2Method is handled, and used step is well-known in this area.Alternative is to use MgCl 2If desired, transforming also the method for available electroporation carries out.When the host is an eukaryote, can select following DNA transfection method for use: coprecipitation of calcium phosphate method, conventional mechanical method such as microinjection, electroporation, liposome packing etc.
The transformant that obtains can be cultivated with ordinary method, expresses the polypeptide of coded by said gene of the present invention.According to used host cell, used substratum can be selected from various conventional substratum in the cultivation.Under the condition that is suitable for the host cell growth, cultivate.After host cell grows into suitable cell density, induce the promotor of selection with suitable method (as temperature transition or chemical induction), cell is cultivated for some time again.
Recombinant polypeptide in the above methods can wrap by in cell, extracellular or on cytolemma, express or be secreted into the extracellular.If desired, can utilize its physics, the separating by various separation methods with other characteristic and the albumen of purification of Recombinant of chemistry.These methods are well-known to those skilled in the art.The example of these methods includes, but are not limited to: conventional renaturation handles, with protein precipitant handle (salt analysis method), centrifugal, the broken bacterium of infiltration, superly handle, the combination of super centrifugal, sieve chromatography (gel-filtration), adsorption chromatography, ion exchange chromatography, high performance liquid chromatography (HPLC) and other various liquid chromatography (LC) technology and these methods.
The people's albumen or the polypeptide with cancer suppressing function of reorganization are of use in many ways.These purposes include, but is not limited to: directly have the disease (as cancer) due to the low or forfeiture of the protein function of cancer suppressing function as pharmacological agent and be used to screen and promote or antagonism has antibody, polypeptide or other part of the protein function of cancer suppressing function.For example, antibody can be used for activating or suppressing to have the proteic function of people of cancer suppressing function.The people's protein screening peptide library that has a cancer suppressing function with the reorganization of expressing can be used for seeking the peptide molecule that can suppress or stimulate the people's protein function with cancer suppressing function of therapeutic value.
The present invention also provides screening of medicaments to improve (agonist) or check the method that (antagonist) has the proteic medicament of people of cancer suppressing function to identify.Agonist improves the biological function such as stimulate cellular proliferation of the people's albumen with cancer suppressing function, and antagonist prevention disorder such as the various cancer relevant with cell hyperproliferation with treatment.For example, can be in the presence of medicine, the proteic film preparation of people that mammalian cell or expression is had cancer suppressing function is cultivated with the people's albumen with cancer suppressing function of mark.Measure the medicine raising then or check this interactional ability.
The proteic antagonist of people with cancer suppressing function comprises antibody, compound, acceptor disappearance thing and the analogue etc. that filter out.The proteic antagonist of people with cancer suppressing function can and be eliminated its function with the people's protein binding with cancer suppressing function, or suppresses to have the proteic generation of people of cancer suppressing function, or combines with the avtive spot of polypeptide and to make polypeptide can not bring into play biological function.The proteic antagonist of people with cancer suppressing function can be used for therepic use.
In screening during as the compound of antagonist, albumen of the present invention can be added during bioanalysis measures, determine by measuring albumen and the interaction between its acceptor that compounds affect has cancer suppressing function whether compound is antagonist.With the same quadrat method of above-mentioned SCREENED COMPOUND, can filter out the acceptor disappearance thing and the analogue of antagonist action.
Polypeptide of the present invention can be directly used in disease treatment, for example, and various malignant tumours and cellular abnormality propagation etc.
Polypeptide of the present invention, and fragment, derivative, analogue or their cell can be used as antigen to produce antibody.These antibody can be polyclone or monoclonal antibody.Polyclonal antibody can obtain by the method with this polypeptide direct injection animal.The technology of preparation monoclonal antibody comprises hybridoma technology, three knurl technology, people B-quadroma technology, EBV-hybridoma technology etc.
Can be with polypeptide of the present invention and antagonist and suitable pharmaceutical carrier combination back use.These carriers can be water, glucose, ethanol, salt, damping fluid, glycerine and their combination.Composition comprises the polypeptide or the antagonist of safe and effective amount and carrier and the vehicle that does not influence effect of drugs.These compositions can be used as medicine and are used for disease treatment.
The present invention also provides medicine box or the test kit that contains one or more containers, and one or more medicinal compositions compositions of the present invention are housed in the container.With these containers, can have by the given indicative prompting of government authorities of making, using or selling medicine or biological products, the government authorities that this prompting reflects production, uses or sells permits it to use on human body.In addition, polypeptide of the present invention can be used in combination with other treatment compound.
Pharmaceutical composition can be with mode administration easily, as by in part, intravenously, intraperitoneal, intramuscular, subcutaneous, the nose or the route of administration of intracutaneous.Albumen with cancer suppressing function comes administration with the amount that treats and/or prevents concrete indication effectively.The proteic amount with cancer suppressing function and the dosage range that are applied to the patient will depend on many factors, as administering mode, person's to be treated healthiness condition and diagnostician's judgement.
The proteic polynucleotide of people with cancer suppressing function also can be used for multiple therapeutic purpose.Gene therapy technology can be used for treating since have that the proteic nothing of cancer suppressing function is expressed or the proteic expression with cancer suppressing function of unusual/non-activity due to cell proliferation, growth or metabolic disturbance.The gene therapy vector of reorganization can be used for treating the protein expression with cancer suppressing function or the disease of active caused by abnormal.Deriving from the expression vector of virus such as protein gene that retrovirus, adenovirus, adeno-associated virus (AAV), hsv, parvovirus etc. can be used for having cancer suppressing function is transferred in the cell.The method that structure carries the recombinant viral vector of the protein gene with cancer suppressing function be found in existing document (Sambrook, etal.).The people protein gene of reorganization with cancer suppressing function can be packaged in the liposome and be transferred in the cell in addition.
Suppress to have cancer suppressing function people's protein mRNA oligonucleotide (comprising sense-rna and DNA) and ribozyme also within the scope of the invention.Ribozyme is the enzyme sample RNA molecule that a kind of energy specificity is decomposed specific RNA, and its mechanism of action is to carry out the endonuclease effect after ribozyme molecule and the hybridization of complementary target RNA-specific.The RNA of antisense and DNA and ribozyme can obtain with existing any RNA or DNA synthetic technology, as the technology widespread use of solid phase phosphoamide chemical synthesis synthetic oligonucleotide.Antisense rna molecule can be transcribed acquisition by the dna sequence dna of this RNA that encodes in external or body.This dna sequence dna has been incorporated into the downstream of rna polymerase promoter of carrier.In order to increase the stability of nucleic acid molecule, available several different methods is modified it, and as increasing the sequence length of both sides, the connection between the ribonucleoside is used phosphoric acid thioester bond or peptide bond but not phosphodiester bond.
Polynucleotide imports tissue or intracellular method comprises: directly be injected into polynucleotide in the in-vivo tissue; Or external by carrier (as virus, phage or plasmid etc.) earlier with the polynucleotide transfered cell in, again cell is transplanted in the body etc.
Polypeptide of the present invention also can be used as the peptide spectrum analysis, for example, the polypeptide available physical, chemistry or enzyme carry out the specificity cutting, and carry out the two-dimentional or three-dimensional gel electrophoresis analysis of one dimension.
The present invention also provides the antibody at the people's proteantigen determinant with cancer suppressing function.These antibody include, but is not limited to: the fragment that polyclonal antibody, monoclonal antibody, chimeric antibody, single-chain antibody, Fab fragment and Fab expression library produce.These antibody can prepare with ordinary method.The anti-proteic antibody of people with cancer suppressing function can be used in the immunohistochemistry technology, detects the people's albumen with cancer suppressing function in the biopsy specimen.
With the also available labelled with radioisotope of the protein bound monoclonal antibody of the people with cancer suppressing function, inject in the body and can follow the tracks of its position and distribution.Antibody among the present invention can be used for treating or prevents and the relevant disease of people's albumen with cancer suppressing function.The antibody that gives suitable dosage can stimulate or block proteic generation of the people with cancer suppressing function or activity.
Antibody also can be used for designing the immunotoxin at a certain privileged sites in the body.As have cancer suppressing function people's albumen high-affinity monoclonal antibody can with bacterium or plant poison (as diphtheria toxin, ricin, abrine etc.) covalent attachment.
Available people's albumen or the polypeptide immune animal of the production of polyclonal antibody with cancer suppressing function, as rabbit, mouse, rat etc.Multiple adjuvant can be used for the enhancing immunity reaction, includes but not limited to freund's adjuvant etc.
Have cancer suppressing function people's protein monoclonal antibody can with hybridoma technology production (Kohler and Milstein.Nature, 1975,256:495-497).With the variable region bonded chimeric antibody in human constant region and inhuman source can with existing technology production (Morrison et al, PNAS, 1985,81:6851).And the technology of existing manufacture order chain antibody (U.S.PatNo.4946778) also can be used for producing the anti-proteic single-chain antibody of people with cancer suppressing function.
Can be incorporated into the rondom polypeptide storehouse that solid formation forms by the various amino acid that may make up by screening with the protein bound peptide molecule of the present invention obtains.During screening, must carry out mark to people's protein molecular with cancer suppressing function.
The invention still further relates to quantitatively and detection and localization has the diagnostic testing process of people's protein level of cancer suppressing function.These tests are known in the art, and comprise that FISH measures and radioimmunoassay.The people's protein level that is detected in the test with cancer suppressing function, the disease that can have the importance of people's albumen in various diseases of cancer suppressing function with laying down a definition and be used to diagnose albumen to work with cancer suppressing function.
Proteic polynucleotide with cancer suppressing function can be used for having the diagnosis and the treatment of the protein related diseases of cancer suppressing function.Aspect diagnosis, the proteic polynucleotide with cancer suppressing function can be used for detecting have cancer suppressing function proteic expression whether or under morbid state, have an abnormal exprssion of cancer suppressing function.As the protein D NA sequence with cancer suppressing function can be used for the hybridization of biopsy specimen is had with judgement the proteic abnormal expression of cancer suppressing function.Hybridization technique comprises the Southern blotting, Northern blotting, in situ hybridization etc.These technological methods all are disclosed mature technologies, and relevant test kit all can obtain from commercial channels.Part or all of polynucleotide of the present invention can be used as probe stationary on microarray (Microarray) or DNA chip (being called " gene chip " again), is used for analyzing the differential expression analysis and the gene diagnosis of tissue gene.Carry out RNA-polymerase chain reaction (RT-PCR) amplification in vitro with the special primer of the albumen with cancer suppressing function and also can detect proteic transcription product with cancer suppressing function.
The sudden change that detection has the protein gene of cancer suppressing function also can be used for diagnosing the relevant disease of albumen with cancer suppressing function.Form with protein mutation of cancer suppressing function comprises that to have point mutation that the protein D NA sequence of cancer suppressing function compares, transposition, disappearance, reorganization and other any unusual etc. with normal wild type.Available existing technology such as Southern blotting, dna sequence analysis, PCR and in situ hybridization detect sudden change.In addition, sudden change might influence proteic expression, therefore can judge indirectly that with Northern blotting, Western blotting gene has or not sudden change.
Sequence of the present invention identifies it also is valuable to karyomit(e).These sequences can be specifically at certain bar human chromosome particular location and and can with its hybridization.At present, need to identify the concrete site of each gene on the karyomit(e).Yet have only chromosomal marker thing seldom to can be used for the marker chromosomes position now based on actual sequence data (repetition polymorphism).For these sequences are associated with disease related gene.The first step is positioned dna sequence dna of the present invention on the karyomit(e) exactly.
In brief, prepare PCR primer (preferred 15-35bp), sequence can be positioned on the karyomit(e) according to cDNA.Then, these primers are used for the somatocyte hybrid cell that the PCR screening contains each bar human chromosome.Have only those hybrid cells that contain corresponding to the people's gene of primer can produce the fragment of amplification.
The PCR localization method of somatocyte hybrid cell is that DNA is navigated to concrete chromosomal quick method.Use Oligonucleolide primers of the present invention,, can utilize one group to realize inferior location from specific chromosomal fragment or a large amount of genomic clone by similar approach.Other the similar strategy that can be used for chromosomal localization comprises in situ hybridization, uses the karyomit(e) prescreen and the hybridization preliminary election of the airflow classification of mark, thereby makes up the special cDNA storehouse of karyomit(e).
The cDNA clone is carried out fluorescence in situ hybridization (FISH) with Metaphase Chromosome, can in a step, accurately carry out chromosomal localization.The summary of this technology is referring to Verma etc., Human Chromosomes:a Manual of BasicTechniques, Pergamon Press, New York (1988).
In case sequence is positioned to chromosome position accurately, the physical location of this sequence on karyomit(e) just can be associated with the gene map data.These data for example are found in, V.Mckusick, Mendelian Inheritance in Man (can by with the online acquisition of Johns Hopkins University Welch Medical Library).Can pass through linkage analysis then, determine gene and navigated to relation between the disease on the chromosomal region already.
Then, need to measure ill and not cDNA between diseased individuals or genome sequence difference.If observe certain sudden change in some or all of diseased individuals, and this sudden change is not observed in any normal individual, then this sudden change may be the cause of disease of disease.More ill and diseased individuals not is usually directed at first seek the variation of structure in the karyomit(e), as from the horizontal visible of karyomit(e) or use based on detectable disappearance of the PCR of cDNA sequence or transposition.
Pyrenoids thuja acid full length sequence or its fragment with cancer suppressing function of the present invention can obtain with the method for pcr amplification method, recombination method or synthetic usually.For the pcr amplification method, can be disclosed according to the present invention about nucleotide sequence, especially open reading frame sequence designs primer, and with commercially available cDNA storehouse or by the prepared cDNA storehouse of ordinary method well known by persons skilled in the art as template, amplification and must relevant sequence.When sequence is longer, usually needs to carry out twice or pcr amplification repeatedly, and then the fragment that each time amplifies is stitched together by proper order.
In case obtained relevant sequence, just can obtain relevant sequence in large quantity with recombination method.This normally is cloned into carrier with it, changes cell again over to, separates obtaining relevant sequence then from the host cell after the propagation by ordinary method.
In addition, also the method for available synthetic is synthesized relevant sequence, especially fragment length more in short-term.Usually, by first synthetic a plurality of small segments, and then connect and to obtain the very long fragment of sequence.
At present, can be fully come the dna sequence dna of code book invention albumen (or its fragment, or derivatives thereof) by chemosynthesis.This dna sequence dna can be introduced then in the various dna moleculars (as carrier) and cell in this area.In addition, also can will suddenly change and introduce in the protein sequence of the present invention by chemosynthesis.
In addition, because the albumen with cancer suppressing function of the present invention has the natural acid sequence that is derived from the people, therefore, compare with the albumen of the same clan that derives from other species, estimate to have higher active and/or lower side effect (for example in the intravital immunogenicity of people lower or do not have) being applied to man-hour.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to people such as normal condition such as Sambrook, molecular cloning: laboratory manual (New York:Cold Spring Harbor LaboratoryPress, 1989) condition described in, or the condition of advising according to manufacturer.Notice that in Nucleotide and amino acid composite sequence, (1) provides the position that initial sum stops first Nucleotide of coding, (2) molecular weight unit is dalton.
The acquisition of embodiment 1:cDNA gene and the restraining effect that the cancer cells clone is formed
LP4790, LP4791, LP4941, LP5085, LP5161, LP5852, LP5910, LP7057, LP9056 and LP9167 come from the normal hepatocytes cDNA library that makes up with ordinary method.Get normal liver tissue (LP clone), (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.Make up the cDNA library of above-mentioned mRNA with pCMV-script TMXR cDNA library construction test kit (Stratagene company).Wherein ThermoScript II is used MMLV-RT-Superscript II (GIBCO BRL) instead, and reverse transcription reaction carries out at 42 ℃.Transform XL 10-Gold recipient cell, obtained the cDNA library of 1 * 106cfu/ μ g cDNA titre.The first round is picking cDNA clone at random, is probe with high abundance cDNA clone with the cDNA clone who has proved cancer inhibitor cell growth function thereafter, screening by hybridization cDNA library, weak positive and negative clone of picking.With Qiagen 96 orifice plate plasmid extraction test kits, carry out the extraction of plasmid DNA by shop instruction.Plasmid DNA and empty carrier transfection simultaneously hepatoma cell line 7721.After the 100ng DNA alcohol precipitation drying, add 6 μ l H2O dissolving, treat transfection.Add 0.74 μ l liposome and 9.3 μ l serum-free mediums in every part of DNA sample, behind the mixing, room temperature was placed 10 minutes.Add 150 μ l serum-free mediums in every pipe, divide equally and add 3 holes and grow in 7721 cells of 96 orifice plates, placed 2 hours for 37 ℃, every hole adds 50 μ l serum-free mediums again, 37 ℃ 24 hours.Every hole is changed 100 μ l and is trained liquid entirely, 37 ℃ 24 hours, change the full training liquid 100 μ l that contain G418,37 ℃ 24-48 hour, the limit is observed, the training liquid that G418 concentration does not wait is changed on the limit.After about 2-3 time, there is the clone to form up to the microscopy cell, counting.Find that above-mentioned clone has the cell clone of inhibition formation effect, the result is as shown in the table.
CDNA clone's transfectional cell (7721) clone formation situation
CDNA clones title CDNA clones number (three repetitions) Empty carrier clone number (three repetitions)
LP4790 1 0 2 29 30 35
LP4791 1 1 0 29 30 35
LP4941 1 2 1 32 20 36
LP5085 0 0 0 39 44 42
LP5161 0 1 1 20 18 22
LP5852 3 1 1 38 32 26
LP5910 1 2 0 51 29 48
LP7057 0 1 4 25 22 18
LP9056 1 0 0 36 40 36
LP9167 0 0 0 10 13 8
The cDNA clone is adopted two deoxidation cessation method, on the ABI377 automatic dna sequencer, measure the nucleotide sequence of the nearly 500bp of one end.After the analysis, be defined as novel gene cloning, carry out the other end order-checking, do not obtain full length cDNA sequence yet, the design primer checks order once more, up to obtaining full length sequence (SEQ ID NO:1,4,7,10,13,16,19,22,25,28).
Embodiment 2: PCR obtains full-length gene from liver cDNA:
Get normal liver tissue (LP clone), (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.With MMLV-RT-Superscript II (GIBCOBRL), ThermoScript II is carried out reverse transcription reaction at 42 ℃, obtains placenta cDNA.Utilize the special primer (as shown in the table) of each gene, by 97 ℃ of 3 ' 1 circulations.94 ℃ 30 " 60 ℃ 30 " 72 ℃ of 1 ' 35 circulations, pcr amplification is carried out in 72 ℃ of 10 ' 1 circulations, and acquisition contains the amplified production of each protein gene of complete open reading frame sequence.Amplified production is through sequence verification, and the sequence that records with embodiment 1 conforms to, and changes amplified production over to host cell with routine techniques subsequently, obtains recombinant protein (SEQ ID NO:3,6,9,12,15,18,21,24,27,30).
Gene specific primer
Clone's title Special primer 1 (5 ' → 3 ') SEQ ID NO: Special primer 2 (3 ' → 5 ') SEQ ID NO:
LP4790 (3)GGCACCTCAGCAACCAGT 31 CGAAACTAACTAAACCCGA(3584) 32
LP4791 (145)CAGTCTTCGCTCACTACAGCC 33 CCAATCCAAAATGACCCCGT(2325) 34
LP4941 (15)AAGATGAATCCGTTGATCTCG 35 TCGTTTGACAGGTCTTCCCT(2813) 36
LP5085 (139)AAGCCCTACAGTGCAGAGGA 37 GAGAACCACAAAGTACGACG(2233) 38
LP5161 (61)GAAGAGGAGGAGGAAGAGGAG 39 GTGGAAGGGACACTTTGTTC(3651) 40
LP5852 (66)CTTTCAGCTCGGCTGCTC 41 GTACCTCATATCGCAGTAGGG(2587) 42
LP5910 (78)GAGGGTGCGGAGGACAAC 43 CAAGGACGGTGACATGAGGT(3218) 44
LP7057 (59)CTTGTTCCTGCCGCTTTC 45 TGTCTACTACTGACGTTTTACT(2579) 46
LP9056 (26)ATCGTCGGCCAGTTTATCC 47 AATGGGGAACGACAAGTCTC(2682) 48
LP9167 (1)GGGAGGGCAGACTCTGGG 49 AGTGCGGTACGGGTGGTG(2742) 50
Annotate: in the bracket is the correspondence position of primer in each gene DNA sequence.
Embodiment 3:cDNA cloned sequence is analyzed
1.LP4790
A: nucleotide sequence (SEQ ID NO:1) length: 3657 bases
B: aminoacid sequence (SEQ ID NO:3) length: 185 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:2) clone number and protein name: LP4790 start code: 2441ATG stops coding: 2996TAG protein molecular weight: 20778.75
2.LP4791
A: nucleotide sequence (SEQ ID NO:4) length: 2350 bases
B: aminoacid sequence (SEQ ID NO:6) length: 101 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:5) clone number and protein name: LP4791 start code: 647ATG stops coding: 950TAG protein molecular weight: 11200.29
3.LP4941
A: nucleotide sequence (SEQ ID NO:7) length: 2837 bases
B: aminoacid sequence (SEQ ID NO:9) length: 303 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:8) clone number and protein name: LP4941 start code: 134ATG stops coding: 1043TGA protein molecular weight: 34340.95
4.LP5085
A: nucleotide sequence (SEQ ID NO:10) length: 2280 bases
B: aminoacid sequence (SEQ ID NO:12) length: 148 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:11) clone number and protein name: LP5085 start code: 627ATG stops coding: 1071TAG protein molecular weight: 16212.66
5.LP5161
A: nucleotide sequence (SEQ ID NO:13) length: 3750 bases
B: aminoacid sequence (SEQ ID NO:15) length: 383 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:14) clone number and protein name: LP5161 start code: 688ATG stops coding: 1837TGA protein molecular weight: 42218.46
6.LP5852
A: nucleotide sequence (SEQ ID NO:16) length: 2730 bases
B: aminoacid sequence (SEQ ID NO:18) length: 101 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:17) clone number and protein name: LP5852 start code: 1216ATG stops coding: 1519TGA protein molecular weight: 10843.61
7.LP5910
A: nucleotide sequence (SEQ ID NO:19) length: 3260 bases
B: aminoacid sequence (SEQ ID NO:21) length: 187 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:20) clone number and protein name: LP5910 start code: 1310ATG stops coding: 1871TGA protein molecular weight: 19866.41
8.LP7057
A: nucleotide sequence (SEQ ID NO:22) length: 2692 bases
B: aminoacid sequence (SEQ ID NO:24) length: 113 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:23) clone number and protein name: LP7057 start code: 2238ATG stops coding: 2577TGA protein molecular weight: 12875.58
9.LP9056
A: nucleotide sequence (SEQ ID NO:25) length: 2769 bases
B: aminoacid sequence (SEQ ID NO:27) length: 563 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:26) clone number and protein name: LP9056 start code: 742ATG stops coding: 2431TGA protein molecular weight: 63543.64
10.LP9167
A: nucleotide sequence (SEQ ID NO:28) length: 3226 bases
B: aminoacid sequence (SEQ ID NO:30) length: 137 amino acid
C. Nucleotide and amino acid composite sequence (SEQ ID NO:29) clone number and protein name: LP9167 start code: 38ATG stops coding: 449TGA protein molecular weight: 15172.09
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Sequence table
<110〉Shanghai Xinshijie Gene Techn Development Co., Ltd.
<120〉have new the people's albumen and the encoding sequence thereof of cancer suppressing function
<130>026810
<160>50
<170>PatentIn version 3.1
<210>1
<211>3657
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>1
ggggcacctc agcaaccagt agccatgcgc ggcttggagg agtcggggcc tcggcctaca 60
gcgaccccgt gcggctgcgt taagccggct ctggagacag ggaatctttt aactgagcca 120
gtcggctact tggaatcttg tttctcggcc aagaatggta ctccaagaca gccatccatt 180
tgtagctatt ctcgagcctg tttgaggatt agaaagagga tctttaataa tcctgaacat 240
tccttgatgg gcctagaaca gtttttctca tgtttggaag gtctagtcat gccaaatgga 300
aaaagaaagg aaggtctggt aaaggatttt gtttgttttt cacaaaaatg gtcatttgag 360
ctgtaaggca aaagtgcagc ctcctaggct gaatggtgca aagactggag ttttttccac 420
aaggagccct catcgtccca atgcaatagg actgaccctg gccaagctgg aaaaggtaga 480
agccttgggg aaatggacag atatcatggc tgcagtgctg atgtcaactg tgctgtgtgg 540
caggagtctg ggatgaatca cactacaagg acaaacattg gtcaggttgt agaagtttta 600
aactagtttt aactgtgtgt tcgtatataa cctagttacg catttatgga aagcattcca 660
ttctgaccta acagatgcat ttgttataga ggcagcagat gaaatggcag gtaaactagg 720
agtcaagaga ccattccagg cttcagcctg ctggttgtga agtgggcaaa ggagaaggac 780
ctgcttcctc tgtgattcca cagaatattt tgagaatctt gtaagagaga agttctaaaa 840
ctactttttc aggctattgg acactaaata gatgagagca gttattttgc ttgttctttc 900
ccagaacttg aactctccca ctggattgta ctcaactggg ccttaggtag ttttctcaga 960
aaaattcagt agctgatcca ccttgaattt tatcaatttg taatggctaa caaacttgga 1020
tagcaagtac tagaagattt tatgattatt cagggacata ttttctagca ctgaatatgt 1080
gccagacatt gtcctaggtg ctagagctat agtgataaac aaatcagatg aaagtagaaa 1140
tccatgccct aaagaactta atgtttcaat tgggaaggtc aagtcagata ggttaaaagg 1200
caaacacagt agcactgtag acattactat ataagcttta tggcaactag tgtttgtgca 1260
gtgctttaca gttagtaaac agtgttcacg taccttatct cacagtggct ttgtgggttt 1320
gacaaagtag caatcctcat ctcataggtg aggaaactag ggctctttaa gattagataa 1380
tctgtctaat agcatccagc caggtggtca tctgactcta aatcctttga agtcttactt 1440
atgctacagt gcctttcttt ttcctacaga tattgttagg cataattcat catctagcaa 1500
gtccagaatc atctttccag agttccagct cattcataat aacatgtttc agaaatcagg 1560
gtcctgtatt agttacgttt ttcttaaatg gagacggaat caaatgtgac tgcatgtagt 1620
ttttctgttc tcatttggcc tattttccaa gagtaaggtt agtagatggc tatttgtagc 1680
agtaactgga cagcatctgt ccagtgggac agctggagac ttgtctttag tatttggtaa 1740
tgctgactta tgtgctgctt aatcttttga gtcttgatgg atgtattaga tttctattgt 1800
tgtgtaacaa attaccacag aatcatcagt ttaaacaaca cacatgtatt atgtgtttga 1860
aacattatta tgtatctgtg ggtcagaagg atgggcacag cttaactagg tcatctgctt 1920
aggtctcact agactgcaat taaattgtca gctgatatga gttcttatct ggaggcttga 1980
ccatggaaga atctgcttaa gctcactcag actgttggcc acattgattt ccttgccatc 2040
gtagtaggac tgggggcccc agattcttgc tggttgttgg ctggaggctg ccctcagtgt 2100
ctaaaggctg tttgcagttc cttgctatgt gggcttccta gcacgcctgc ctacttcagc 2160
aagccttcaa ggagagtctc tcgagtgagt cttccagcca gcagcagtgc taatgaaaag 2220
catagtcact ggagggacat catacctctt ttgccatatt ctgttggtta gaagccagtc 2280
acactcaagg ggaaggatta tataagggca tgaacttcag gaggtgcggg tcacagggcc 2340
acttttggat ctgtttgcca cagtaagaac cttcattggt cccacagaga tatactgagg 2400
actactatat ccctggaaca gaagcaccag tgatacaaag atgagttggt cccagcctgt 2460
gttaaggggc ctgcctgcgt ctagggatga agactctaag caggtcacta ccctaccgtg 2520
gggaaagcgc tctagcagag gtggagctat atacctttct ggaattgaca tgatacatgg 2580
cacacccgta ctagacatca agccctacat agctgagtat gactcaccgc aaaatgtgat 2640
ggagccttta gcagacttta atttacagaa taaccaacat acaccaaaca ctgtgtccca 2700
gtctgacagc aagactgaca gctgtgacca gcgacagctc tcagggtgtg atgagccaca 2760
accccaccat agcactaaga ggaaacctaa atgtcctgaa gacagaactt cagaagaaaa 2820
ctacctgaca cacagtgaca cagccagaat tcagcaagca tttcctatgc acagggagat 2880
agcagtggat tttggtttgg aatcaagacg tgatcagagt tccagcgtgg cagaagaaca 2940
aattggccca tattgcccag agaagagctt ttcagagaaa ggtacagaca gaagctagaa 3000
agagtggaag gagcagcagt cttgcaagga agcagggcag agacacagcc catggcccct 3060
cactgccctg ctggaagggc tgatggagct ccccgcagca tggttcctgc ctgggtgaca 3120
gaggctcctg tggccacttt agaagtgcgg tttactcctc atgccgagat ggaccttggg 3180
cagctcagtt cacaagatgt tggtcaggcg tcatttaaat attttcagtc agcagaggaa 3240
gcaaagcgtg ccattgaggc tgtgctgtca gcggatcctc ggtctgtgta ccgccggaag 3300
ctttgccagg accgcctttt ctactttact gtagacatag cgcatgtcac ttgctggttt 3360
ggtgatggct ttgcagaggt gctgaggatc aagccggctt ctgagcctgt tcatatgact 3420
ggccctgtgg ggtccttggt gtctctaggg tcttaaggag cctccctcat gtctttaagg 3480
tagcatcatt gatctttgga tgtggctttt ggattttctg aacaagctaa tgttgtgtca 3540
agaagcaaca ctttgtgatc tcatggcttt gattgatttg ggctgttcaa aatgtttatt 3600
tgaaaaacgt ataccttaat aaacttaaca aagagatata aaaaaaaaaa aaaaaaa 3657
<210>2
<211>3657
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(2441)..(2995)
<223>
<400>2
ggggcacctc agcaaccagt agccatgcgc ggcttggagg agtcggggcc tcggcctaca 60
gcgaccccgt gcggctgcgt taagccggct ctggagacag ggaatctttt aactgagcca 120
gtcggctact tggaatcttg tttctcggcc aagaatggta ctccaagaca gccatccatt 180
tgtagctatt ctcgagcctg tttgaggatt agaaagagga tctttaataa tcctgaacat 240
tccttgatgg gcctagaaca gtttttctca tgtttggaag gtctagtcat gccaaatgga 300
aaaagaaagg aaggtctggt aaaggatttt gtttgttttt cacaaaaatg gtcatttgag 360
ctgtaaggca aaagtgcagc ctcctaggct gaatggtgca aagactggag ttttttccac 420
aaggagccct catcgtccca atgcaatagg actgaccctg gccaagctgg aaaaggtaga 480
agccttgggg aaatggacag atatcatggc tgcagtgctg atgtcaactg tgctgtgtgg 540
caggagtctg ggatgaatca cactacaagg acaaacattg gtcaggttgt agaagtttta 600
aactagtttt aactgtgtgt tcgtatataa cctagttacg catttatgga aagcattcca 660
ttctgaccta acagatgcat ttgttataga ggcagcagat gaaatggcag gtaaactagg 720
agtcaagaga ccattccagg cttcagcctg ctggttgtga agtgggcaaa ggagaaggac 780
ctgcttcctc tgtgattcca cagaatattt tgagaatctt gtaagagaga agttctaaaa 840
ctactttttc aggctattgg acactaaata gatgagagca gttattttgc ttgttctttc 900
ccagaacttg aactctccca ctggattgta ctcaactggg ccttaggtag ttttctcaga 960
aaaattcagt agctgatcca ccttgaattt tatcaatttg taatggctaa caaacttgga 1020
tagcaagtac tagaagattt tatgattatt cagggacata ttttctagca ctgaatatgt 1080
gccagacatt gtcctaggtg ctagagctat agtgataaac aaatcagatg aaagtagaaa 1140
tccatgccct aaagaactta atgtttcaat tgggaaggtc aagtcagata ggttaaaagg 1200
caaacacagt agcactgtag acattactat ataagcttta tggcaactag tgtttgtgca 1260
gtgctttaca gttagtaaac agtgttcacg taccttatct cacagtggct ttgtgggttt 1320
gacaaagtag caatcctcat ctcataggtg aggaaactag ggctctttaa gattagataa 1380
tctgtctaat agcatccagc caggtggtca tctgactcta aatcctttga agtcttactt 1440
atgctacagt gcctttcttt ttcctacaga tattgttagg cataattcat catctagcaa 1500
gtccagaatc atctttccag agttccagct cattcataat aacatgtttc agaaatcagg 1560
gtcctgtatt agttacgttt ttcttaaatg gagacggaat caaatgtgac tgcatgtagt 1520
ttttctgttc tcatttggcc tattttccaa gagtaaggtt agtagatggc tatttgtagc 1680
agtaactgga cagcatctgt ccagtgggac agctggagac ttgtctttag tatttggtaa 1740
tgctgactta tgtgctgctt aatcttttga gtcttgatgg atgtattaga tttctattgt 1800
tgtgtaacaa attaccacag aatcatcagt ttaaacaaca cacatgtatt atgtgtttga 1860
aacattatta tgtatctgtg ggtcagaagg atgggcacag cttaactagg tcatctgctt 1920
aggtctcact agactgcaat taaattgtca gctgatatga gttcttatct ggaggcttga 1980
ccatggaaga atctgcttaa gctcactcag actgttggcc acattgattt ccttgccatc 2040
gtagtaggac tgggggcccc agattcttgc tggttgttgg ctggaggctg ccctcagtgt 2100
ctaaaggctg tttgcagttc cttgctatgt gggcttccta gcacgcctgc ctacttcagc 2160
aagccttcaa ggagagtctc tcgagtgagt cttccagcca gcagcagtgc taatgaaaag 2220
catagtcact ggagggacat catacctctt ttgccatatt ctgttggtta gaagccagtc 2280
acactcaagg ggaaggatta tataagggca tgaacttcag gaggtgcggg tcacagggcc 2340
acttttggat ctgtttgcca cagtaagaac cttcattggt cccacagaga tatactgagg 2400
actactatat ccctggaaca gaagcaccag tgatacaaag atg agt tgg tcc cag 2455
Met Ser Trp Ser Gln
1 5
cct gtg tta agg ggc ctg cct gcg tct agg gat gaa gac tct aag cag 2503
Pro Val Leu Arg Gly Leu Pro Ala Ser Arg Asp Glu Asp Ser Lys Gln
10 15 20
gtc act acc cta ccg tgg gga aag cgc tct agc aga ggt gga gct ata 2551
Val Thr Thr Leu Pro Trp Gly Lys Arg Ser Ser Arg Gly Gly Ala Ile
25 30 35
tac ctt tct gga att gac atg ata cat ggc aca ccc gta cta gac atc 2599
Tyr Leu Ser Gly Ile Asp Met Ile His Gly Thr Pro Val Leu Asp Ile
40 45 50
aag ccc tac ata gct gag tat gac tca ccg caa aat gtg atg gag cct 2647
Lys Pro Tyr Ile Ala Glu Tyr Asp Ser Pro Gln Asn Val Met Glu Pro
55 60 65
tta gca gac ttt aat tta cag aat aac caa cat aca cca aac act gtg 2695
Leu Ala Asp Phe Asn Leu Gln Asn Asn Gln His Thr Pro Asn Thr Val
70 75 80 85
tcc cag tct gac agc aag act gac agc tgt gac cag cga cag ctc tca 2743
Ser Gln Ser Asp Ser Lys Thr Asp Ser Cys Asp Gln Arg Gln Leu Ser
90 95 100
ggg tgt gat gag cca caa ccc cac cat agc act aag agg aaa cct aaa 2791
Gly Cys Asp Glu Pro Gln Pro His His Ser Thr Lys Arg Lys Pro Lys
105 110 115
tgt cct gaa gac aga act tca gaa gaa aac tac ctg aca cac agt gac 2839
Cys Pro Glu Asp Arg Thr Ser Glu Glu Asn Tyr Leu Thr His Ser Asp
120 125 130
aca gcc aga att cag caa gca ttt cct atg cac agg gag ata gca gtg 2887
Thr Ala Arg Ile Gln Gln Ala Phe Pro Met His Arg Glu Ile Ala Val
135 140 145
gat ttt ggt ttg gaa tea aga cgt gat cag agt tcc agc gtg gca gaa 2935
Asp Phe Gly Leu Glu Ser Arg Arg Asp Gln Ser Ser Ser Val Ala Glu
150 155 160 165
gaa caa att ggc cca tat tgc cca gag aag agc ttt tca gag aaa ggt 2983
Glu Gln Ile Gly Pro Tyr Cys Pro Glu Lys Ser Phe Ser Glu Lys Gly
170 175 180
aca gac aga agc tagaaagagt ggaaggagca gcagtcttgc aaggaagcag 3035
Thr Asp Arg Ser
185
ggcagagaca cagcccatgg cccctcactg ccctgctgga agggctgatg gagctccccg 3095
cagcatggtt cctgcctggg tgacagaggc tcctgtggcc actttagaag tgcggtttac 3155
tcctcatgcc gagatggacc ttgggcagct cagttcacaa gatgttggtc aggcgtcatt 3215
taaatatttt cagtcagcag aggaagcaaa gcgtgccatt gaggctgtgc tgtcagcgga 3275
tcctcggtct gtgtaccgcc ggaagctttg ccaggaccgc cttttctact ttactgtaga 3335
catagcgcat gtcacttgct ggtttggtga tggctttgca gaggtgctga ggatcaagcc 3395
ggcttctgag cctgttcata tgactggccc tgtggggtcc ttggtgtctc tagggtctta 3455
aggagcctcc ctcatgtctt taaggtagca tcattgatct ttggatgtgg cttttggatt 3515
ttctgaacaa gctaatgttg tgtcaagaag caacactttg tgatctcatg gctttgattg 3575
atttgggctg ttcaaaatgt ttatttgaaa aacgtatacc ttaataaact taacaaagag 3635
atataaaaaa aaaaaaaaaa aa 3657
<210>3
<211>185
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>3
Met Ser Trp Ser Gln Pro Val Leu Arg Gly Leu Pro Ala Ser Arg Asp
1 5 10 15
Glu Asp Ser Lys Gln Val Thr Thr Leu Pro Trp Gly Lys Arg Ser Ser
20 25 30
Arg Gly Gly Ala Ile Tyr Leu Ser Gly Ile Asp Met Ile His Gly Thr
35 40 45
Pro Val Leu Asp Ile Lys Pro Tyr Ile Ala Glu Tyr Asp Ser Pro Gln
50 55 60
Asn Val Met Glu Pro Leu Ala Asp Phe Asn Leu Gln Asn Asn Gln His
65 70 75 80
Thr Pro Asn Thr Val Ser Gln Ser Asp Ser Lys Thr Asp Ser Cys Asp
85 90 95
Gln Arg Gln Leu Ser Gly Cys Asp Glu Pro Gln Pro His His Ser Thr
100 105 110
Lys Arg Lys Pro Lys Cys Pro Glu Asp Arg Thr Ser Glu Glu Asn Tyr
115 120 125
Leu Thr His Ser Asp Thr Ala Arg Ile Gln Gln Ala Phe Pro Met His
130 135 140
Arg Glu Ile Ala Val Asp Phe Gly Leu Glu Ser Arg Arg Asp Gln Ser
145 150 155 160
Ser Ser Val Ala Glu Glu Gln Ile Gly Pro Tyr Cys Pro Glu Lys Ser
165 170 175
Phe Ser Glu Lys Gly Thr Asp Arg Ser
180 185
<210>4
<211>2350
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>4
gcgggcttac atccaaatac agatttaccc cagaagagaa tgaaacaatg ttcagaaccc 60
ctgaaaactg tgttcaagga agtcagctgg atttttttga gacaggggtc ttgctcttgt 120
tgcccaggct ggaatgcaat ggtgcagtct tcgctcacta cagcctctac cgctcctgct 180
caggtaatcc ttccacctca gccccctgag tagctgggac tgcaggcaca cgccaccatg 240
ccaggctgat ttttgtattt tttgtagaga ctgtgtttca ccgtattgcc cgggctggtc 300
ttgaactctt ggactcaagc aatccacctg cctcggcctc ccaaagtgct cacaggcatg 360
aggcaacgtg cccagcctca tttgatactt ttaaaataca tttttaatat ttttttcctc 420
caagatgcct tccccattgt gtaagtttca ggtcttacaa acctggatcc accccagcag 480
tctgagttgc atatatacat acctcctatt tacatgtccc tcctcccact attatgtcac 540
ctttctaaac accgcaattg ggagatgaga caatgcgcag gaacgaagaa ctgttctggt 600
gaagaggacc caggggcagt gagagggggc tagggacaaa aggtgaatgg ggagctggtt 660
caggttagaa gaatgggtgc atgtgagggg catttggaga atgcgagctg ggggagggag 720
agtggctgag cctgtaggca cagtagacac atgtagtaat gacggggatg tgttatgccc 780
cacaccaggt gttgtcctac atcaatgggg tcacaacaag caaacctgga gtatccttgg 840
tctactccat gccctcccgg aacctgtccc tgcggctgga gggtctccag gagaaagact 900
ctggccccta cagctgctcc gtgaatgtgc aagacaaaca aggcaaatct aggggccaca 960
gcatcaaaac cttagaactc aatgtactgg gtgagtgaga agcagatttc cggacccctc 1020
cccacctgca ctgggaggtc tggtgagtct ctctcctaaa tgacaaaagt tggaggagga 1080
acaaatgaag cgacagaagg gtgcagggca gagggagagg atctgtgggt ctcctgggtg 1140
gtgggtttta atctgtctcc ccctgcccag ttcctccagc tcctccatcc tgccgtctcc 1200
agggtgtgcc ccatgtgggg gcaaacgtga ccctgagctg ccagtctcca aggagtaagc 1260
ccgctgtcca ataccagtgg gatcggcagc ttccatcctt ccagactttc tttgcaccag 1320
cattagatgt catccgtggg tctttaagcc tcaccaacct ttcgtcttcc atggctggag 1380
tctatgtctg caaggcccac aatgaggtgg gcactgccca atgtaatgtg acgctggaag 1440
tgagcacagg tcagtgaggg ggcctggagc tgcagtggtt gctggagctg ttgtgggtac 1500
cctggttgga ctggggttgc tggctgggct ggtcctcttg taccaccgcc ggggcaaggc 1560
cctggaggag ccagccaatg atatcaagga ggatgccatt gctccccgga ccctgccctg 1620
gcccaagagc tcagacacaa tctccaagaa tgggaccctt tcctctgtca cctccgcacg 1680
agccctccgg ccaccccatg gccctcccag gcctggtgca ttgaccccca cgcccagtct 1740
ctccagccag gccctgccct caccaagact gcccacgaca gatggggccc accctcaacc 1800
aatatccccc atccctggtg gggtttcttc ctctggcttg agccgcatgg gtgctgtgcc 1860
tgtgatggtg cctgcccaga gtcaagctgg ctctctggta tgatgacccc accactcatt 1920
ggctaaagga tttggggtct ctccttccta taggggtcac ctctagcaca gaggcctgag 1980
tcatgggaaa gagtcacact cctgaccctt agtactctgc ccccacctct ctttactgtg 2040
ggaaaaccat ctcagtaaga cctaagtgtc caggagacag aaggagaaga ggaagtggat 2100
ctggaattgg gaggagcctc cacccacccc tgactcctcc ttatgaagcc agctgctgaa 2160
attagctact caccaagagt gaggggcaga gacttccagt cactgagtct cccaggcccc 2220
cttgatctgt accccacccc tatctaacac cacccttggc tcccactcca gctccctgta 2280
ttgatataac ctgtcaggct ggcttggtta ggttttactg gggcagagga tagggaatct 2340
cttattaaaa 2350
<210>5
<211>2350
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(647)..(949)
<223>
<400>5
gcgggcttac atccaaatac agatttaccc cagaagagaa tgaaacaatg ttcagaaccc 60
ctgaaaactg tgttcaagga agtcagctgg atttttttga gacaggggtc ttgctcttgt 120
tgcccaggct ggaatgcaat ggtgcagtct tcgctcacta cagcctctac cgctcctgct 180
caggtaatcc ttccacctca gccccctgag tagctgggac tgcaggcaca cgccaccatg 240
ccaggctgat ttttgtattt tttgtagaga ctgtgtttca ccgtattgcc cgggctggtc 300
ttgaactctt ggactcaagc aatccacctg cctcggcctc ccaaagtgct cacaggcatg 360
aggcaacgtg cccagcctca tttgatactt ttaaaataca tttttaatat ttttttcctc 420
caagatgcct tccccattgt gtaagtttca ggtcttacaa acctggatcc accccagcag 480
tctgagttgc atatatacat acctcctatt tacatgtccc tcctcccact attatgtcac 540
ctttctaaac accgcaattg ggagatgaga caatgcgcag gaacgaagaa ctgttctggt 600
gaagaggacc caggggcagt gagagggggc tagggacaaa aggtga atg ggg agc 655
Met Gly Ser
1
tgg ttc agg tta gaa gaa tgg gtg cat gtg agg ggc att tgg aga atg 703
Trp Phe Arg Leu Glu Glu Trp Val His Val Arg Gly Ile Trp Arg Met
5 10 15
cga gct ggg gga ggg aga gtg gct gag cct gta ggc aca gta gac aca 751
Arg Ala Gly Gly Gly Arg Val Ala Glu Pro Val Gly Thr Val Asp Thr
20 25 30 35
tgt agt aat gac ggg gat gtg tta tgc ccc aca cca ggt gtt gtc cta 799
Cys Ser Asn Asp Gly Asp Val Leu Cys Pro Thr Pro Gly Val Val Leu
40 45 50
cat caa tgg ggt cac aac aag caa acc tgg agt atc ctt ggt cta ctc 847
His Gln Trp Gly His Asn Lys Gln Thr Trp Ser Ile Leu Gly Leu Leu
55 60 65
cat gcc ctc ccg gaa cct gtc cct gcg gct gga ggg tct cca gga gaa 895
His Ala Leu Pro Glu Pro Val Pro Ala Ala Gly Gly Ser Pro Gly Glu
70 75 80
aga ctc tgg ccc cta cag ctg ctc cgt gaa tgt gca aga caaaca agg 943
Arg Leu Trp Pro Leu Gln Leu Leu Arg Glu Cys Ala Arg Gln Thr Arg
85 90 95
caa atc taggggccac agcatcaaaa ccttagaact caatgtactg ggtgagtgag 999
Gln Ile
100
aagcagattt ccggacccct ccccacctgc actgggaggt ctggtgagtc tctctcctaa 1059
atgacaaaag ttggaggagg aacaaatgaa gcgacagaag ggtgcagggc agagggagag 1119
gatctgtggg tctcctgggt ggtgggtttt aatctgtctc cccctgccca gttcctccag 1179
ctcctccatc ctgccgtctc cagggtgtgc cccatgtggg ggcaaacgtg accctgagct 1239
gccagtctcc aaggagtaag cccgctgtcc aataccagtg ggatcggcag cttccatcct 1299
tccagacttt ctttgcacca gcattagatg tcatccgtgg gtctttaagc ctcaccaacc 1359
tttcgtcttc catggctgga gtctatgtct gcaaggccca caatgaggtg ggcactgccc 1419
aatgtaatgt gacgctggaa gtgagcacag gtcagtgagg gggcctggag ctgcagtggt 1479
tgctggagct gttgtgggta ccctggttgg actggggttg ctggctgggc tggtcctctt 1539
gtaccaccgc cggggcaagg ccctggagga gccagccaat gatatcaagg aggatgccat 1599
tgctccccgg accctgccct ggcccaagag ctcagacaca atctccaaga atgggaccct 1659
ttcctctgtc acctccgcac gagccctccg gccaccccat ggccctccca ggcctggtgc 1719
attgaccccc acgcccagtc tctccagcca ggccctgccc tcaccaagac tgcccacgac 1779
agatggggcc caccctcaac caatatcccc catccctggt ggggtttctt cctctggctt 1839
gagccgcatg ggtgctgtgc ctgtgatggt gcctgcccag agtcaagctg gctctctggt 1899
atgatgaccc caccactcat tggctaaagg atttggggtc tctccttcct ataggggtca 1959
cctctagcac agaggcctga gtcatgggaa agagtcacac tcctgaccct tagtactctg 2019
cccccacctc tctttactgt gggaaaacca tctcagtaag acctaagtgt ccaggagaca 2079
gaaggagaag aggaagtgga tctggaattg ggaggagcct ccacccaccc ctgactcctc 2139
cttatgaagc cagctgctga aattagctac tcaccaagag tgaggggcag agacttccag 2199
tcactgagtc tcccaggccc ccttgatctg taccccaccc ctatctaaca ccacccttgg 2259
ctcccactcc agctccctgt attgatataa cctgtcaggc tggcttggtt aggttttact 2319
ggggcagagg atagggaatc tcttattaaa a 2350
<210>6
<211>101
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>6
Met Gly Ser Trp Phe Arg Leu Glu Glu Trp Val His Val Arg Gly Ile
1 5 10 15
Trp Arg Met Arg Ala Gly Gly Gly Arg Val Ala Glu Pro Val Gly Thr
20 25 30
Val Asp Thr Cys Ser Asn Asp Gly Asp Val Leu Cys Pro Thr Pro Gly
35 40 45
Val Val Leu His Gln Trp Gly His Asn Lys Gln Thr Trp Ser Ile Leu
50 55 60
Gly Leu Leu His Ala Leu Pro Glu Pro Val Pro Ala Ala Gly Gly Ser
65 70 75 80
Pro Gly Glu Arg Leu Trp Pro Leu Gln Leu Leu Arg Glu Cys Ala Arg
85 90 95
Gln Thr Arg Gln Ile
100
<210>7
<211>2837
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>7
ggtcgaggtg tgcaaagatg aatccgttga tctcgaggaa tttcgaagct acctggagaa 60
gcgttttgac tttgagcaag ttactgtgaa aaaattcagg acttgggctg agcggcggca 120
attcaatcgg gaaatgaagc ggaagcaggc ggagtccgag aggcccatct tgccagccaa 180
tcagaagctc attactttat cagtgcaaga tgcacccaca aagaaagagt ttgttattaa 240
ccccaacggg aaatccgagg tctgcatcct gcacgagtac atgcagcgtg tcctcaaggt 300
ccgccctgtc tataatttct ttgaatgtga gaacccaagt gagccttttg gtgcctcggt 360
gaccattgat ggtgtgactt acggatctgg aactgcaagc agcaaaaaac ttgcgaagaa 420
taaagctgcc cgagctacac tggaaatcct catccctgac tttgttaaac agacctctga 480
agagaagccc aaagacagtg aagaactcga gtattttaac cacatcagca tcgaggactc 540
gcgggtctac gagctgacca gcaaggctgg gctgttgtct ccatatcaga tcctccacga 600
gtgccttaaa agaaaccatg ggatgggtga cacgtctatc aagtttgaag tggttcctgg 660
gaaaaaccag aagagtgaat acgtcatggc gtgtggcaag cacacagtgc gcgggtggtg 720
taagaacaag agagttggaa agcagttagc ctcacagaag atccttcagc tgctgcaccc 780
acatgtcaag aactgggggt ctttactgcg catgtatggc cgtgagagca gcaagatggt 840
caagcaggag acatcggaca agagtgtgat tgagctgcag cagtatgcca agaagaacaa 900
gcccaacctg cacatcctca gcaagctcca agaggagatg aagaggctag ctgaggaaag 960
ggaggagact cgaaagaagc ccaagatgtc cattgtggcg tccgcccagc ctggcggtga 1020
gcccctgtgc accgtggacg tgtgagggag gtggcacggg ccagggcgcg ggggccgcca 1080
gccgcacttc tgaggagacc agcagtcatg catcgtgcac cacagtgtca ggcctccaac 1140
ccacgctcct tccctgtggc caacctgtgg gcccggcctt agggtggagg ctttagtgta 1200
cagggacagc catggccaca cagcacacat gtggagcagc ggctctccct ggaaagctcc 1260
aggcctgaat ggatggactc agcgactgca ccagtggcag ctggtgactg tggacagtgg 1320
tggaccctgc ttctgtgcac ctgctgcagg ctctttttat gaaggctttc atgaatttta 1380
gtatgtaata cgcactgacg acacatgatg cttggatgac agatgagagg ggatggctga 1440
gtcctgtggc tggcccgtga tgccaggtgg cccatgtgcc cagggcgcct gcagggctgc 1500
tacagggacc tggtcaggag gtgcacatgg tgccctgccc tcacccaccc tctgtgtttc 1560
cccttctttg aaaaggtaga agagaaagga atattttaaa cctttttggc ttaaacagaa 1620
ttttagcatc agaactagct ttctgggatt ggaggcaaac catcaaggtg gtccctctcc 1680
agtctggaca cgatgccagc aaggatgacg tcctgccacc tcctggagtt accctggcct 1740
cctagggtcc ctttttctga tgaagtctta attccctaaa agcgcctctt tggacactga 1800
ggccctctct gcctttcctg gcctccggca acagtttttt acaaagattt tttgcagtcg 1860
agtccatatg tccacccatt gatttttaaa gcttttgtga tattttagca ttttgaaaga 1920
ctttcacagt gagagtagaa ggtagatttg gaatcatgca ttttagcaag tggacttgtt 1980
gaaacaggaa gcaagagcct tcagtgtagc ccattcttga tccagagctg ttgcctgtga 2040
cagcggtttc tctggatgtc aaaggcagct gcctggtgcc cagcttgctt ctcgactggt 2100
ggcccctatg ggtgggtgtg cgatggaaat gtgttcctgc cggagtctga ggcaccaggg 2160
tgtgctcaaa ggctggccct ggtggtggac tggcacctgt gcagagtgcc gtgtgcttgt 2220
ggtgcgccat ctgaagcaag agtccagcgt tctgccgtgt ctgtccccca ccatgccccc 2280
tacaggcggt actgatggcg cttttttttt ttttttttct gtcaggaaaa caatgttggc 2340
ctgtgggccg cccacaacat atccttccct cactacctgt gtgaccaagg ttggcttctg 2400
ttgaccttta aaaaagaaac cctcaactca aattgctata attagacact tgcttctgtc 2460
ttgcctcctg tctgcagctg tgaatagtca tttgactgtg actgttgccc ttagccagcc 2520
agatgcgcct gtgaaccaaa gctttgtgca catgtgttcc cctaaaggtt ggggagcctc 2580
gctgtgtttt gctgttccca ggcaccacca cagcaggtgc tgccatactc ttgtggtctc 2640
tgtgcgcccc ccccccccca cccgtctgcc aagcatgggt atgaatcgtg cacacagcca 2700
tgcttcaagg ccggggcagg ggagcctgtg ctgatgccat ccagggcact gggctgtgcc 2760
tggaaggcga gccttgattg tctgaacaca taaagcaaac tgtccagaag ggaaaaaaaa 2820
aaaaaaaaaa aaaaaaa 2837
<210>8
<211>2837
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(134)..(1042)
<223>
<400>8
ggtcgaggtg tgcaaagatg aatccgttga tctcgaggaa tttcgaagct acctggagaa 60
gcgttttgac tttgagcaag ttactgtgaa aaaattcagg acttgggctg agcggcggca 120
attcaatcgg gaa atg aag cgg aag cag gcg gag tcc gag agg ccc atc 169
Met Lys Arg Lys Gln Ala Glu Ser Glu Arg Pro Ile
1 5 10
ttg cca gcc aat cag aag ctc att act tta tca gtg caa gat gca ccc 217
Leu Pro Ala Asn Gln Lys Leu Ile Thr Leu Ser Val Gln Asp Ala Pro
15 20 25
aca aag aaa gag ttt gtt att aac ccc aac ggg aaa tcc gag gtc tgc 265
Thr Lys Lys Glu Phe Val Ile Asn Pro Asn Gly Lys Ser Glu Val Cys
30 35 40
atc ctg cac gag tac atg cag cgt gtc ctc aag gtc cgc cct gtc tat 313
Ile Leu His Glu Tyr Met Gln Arg Val Leu Lys Val Arg Pro Val Tyr
45 50 55 60
aat ttc ttt gaa tgt gag aac cca agt gag cct ttt ggt gcc tcg gtg 361
Asn Phe Phe Glu Cys Glu Asn Pro Ser Glu Pro Phe Gly Ala Ser Val
65 70 75
acc att gat ggt gtg act tac gga tct gga act gca agc agc aaa aaa 409
Thr Ile Asp Gly Val Thr Tyr Gly Ser Gly Thr Ala Ser Ser Lys Lys
80 85 90
ctt gcg aag aat aaa gct gcc cga gct aca ctg gaa atc ctc atc cct 457
Leu Ala Lys Asn Lys Ala Ala Arg Ala Thr Leu Glu Ile Leu Ile Pro
95 100 105
gac ttt gtt aaa cag acc tct gaa gag aag ccc aaa gac agt gaa gaa 505
Asp Phe Val Lys Gln Thr Ser Glu Glu Lys Pro Lys Asp Ser Glu Glu
110 115 120
ctc gag tat ttt aac cac atc agc atc gag gac tcg cgg gtc tac gag 553
Leu Glu Tyr Phe Asn His Ile Ser Ile Glu Asp Ser Arg Val Tyr Glu
125 130 135 140
ctg acc agc aag gct ggg ctg ttg tct cca tat cag atc ctc cac gag 601
Leu Thr Ser Lys Ala Gly Leu Leu Ser Pro Tyr Gln Ile Leu His Glu
145 150 155
tgc ctt aaa aga aac cat ggg atg ggt gac acg tct atc aag ttt gaa 649
Cys Leu Lys Arg Asn His Gly Met Gly Asp Thr Ser Ile Lys Phe Glu
160 165 170
gtg gtt cct ggg aaa aac cag aag agt gaa tac gtc atg gcg tgt ggc 697
Val Val Pro Gly Lys Asn Gln Lys Ser Glu Tyr Val Met Ala Cys Gly
175 180 185
aag cac aca gtg cgc ggg tgg tgt aag aac aag aga gtt gga aag cag 745
Lys His Thr Val Arg Gly Trp Cys Lys Asn Lys Arg Val Gly Lys Gln
190 195 200
tta gcc tca cag aag atc ctt cag ctg ctg cac cca cat gtc aag aac 793
Leu Ala Ser Gln Lys Ile Leu Gln Leu Leu His Pro His Val Lys Asn
205 210 215 220
tgg ggg tct tta ctg cgc atg tat ggc cgt gag agc agc aag atg gtc 841
Trp Gly Ser Leu Leu Arg Met Tyr Gly Arg Glu Ser Ser Lys Met Val
225 230 235
aag cag gag aca tcg gac aag agt gtg att gag ctg cag cag tat gcc 889
Lys Gln Glu Thr Ser Asp Lys Ser Val Ile Glu Leu Gln Gln Tyr Ala
240 245 250
aag aag aac aag ccc aac ctg cac atc ctc agc aag ctc caa gag gag 937
Lys Lys Asn Lys Pro Asn Leu His Ile Leu Ser Lys Leu Gln Glu Glu
255 260 265
atg aag agg cta gct gag gaa agg gag gag act cga aag aag ccc aag 985
Met Lys Arg Leu Ala Glu Glu Arg Glu Glu Thr Arg Lys Lys Pro Lys
270 275 280
atg tcc att gtg gcg tcc gcc cag cct ggc ggt gag ccc ctg tgc acc 1033
Met Ser Ile Val Ala Ser Ala Gln Pro Gly Gly Glu Pro Leu Cys Thr
285 290 295 300
gtg gac gtg tgagggaggt ggcacgggcc agggcgcggg ggccgccagc 1082
Val Asp Val
cgcacttctg aggagaccag cagtcatgca tcgtgcacca cagtgtcagg cctccaaccc 1142
acgctccttc cctgtggcca acctgtgggc ccggccttag ggtggaggct ttagtgtaca 1202
gggacagcca tggccacaca gcacacatgt ggagcagcgg ctctccctgg aaagctccag 1262
gcctgaatgg atggactcag cgactgcacc agtggcagct ggtgactgtg gacagtggtg 1322
gaccctgctt ctgtgcacct gctgcaggct ctttttatga aggctttcat gaattttagt 1382
atgtaatacg cactgacgac acatgatgct tggatgacag atgagagggg atggctgagt 1442
cctgtggctg gcccgtgatg ccaggtggcc catgtgccca gggcgcctgc agggctgcta 1502
cagggacctg gtcaggaggt gcacatggtg ccctgccctc acccaccctc tgtgtttccc 1562
cttctttgaa aaggtagaag agaaaggaat attttaaacc tttttggctt aaacagaatt 1622
ttagcatcag aactagcttt ctgggattgg aggcaaacca tcaaggtggt ccctctccag 1682
tctggacacg atgccagcaa ggatgacgtc ctgccacctc ctggagttac cctggcctcc 1742
tagggtccct ttttctgatg aagtcttaat tccctaaaag cgcctctttg gacactgagg 1802
ccctctctgc ctttcctggc ctccggcaac agttttttac aaagattttt tgcagtcgag 1862
tccatatgtc cacccattga tttttaaagc ttttgtgata ttttagcatt ttgaaagact 1922
ttcacagtga gagtagaagg tagatttgga atcatgcatt ttagcaagtg gacttgttga 1982
aacaggaagc aagagccttc agtgtagccc attcttgatc cagagctgtt gcctgtgaca 2042
gcggtttctc tggatgtcaa aggcagctgc ctggtgccca gcttgcttct cgactggtgg 2102
cccctatggg tgggtgtgcg atggaaatgt gttcctgccg gagtctgagg caccagggtg 2162
tgctcaaagg ctggccctgg tggtggactg gcacctgtgc agagtgccgt gtgcttgtgg 2222
tgcgccatct gaagcaagag tccagcgttc tgccgtgtct gtcccccacc atgcccccta 2282
caggcggtac tgatggcgct tttttttttt ttttttctgt caggaaaaca atgttggcct 2342
gtgggccgcc cacaacatat ccttccctca ctacctgtgt gaccaaggtt ggcttctgtt 2402
gacctttaaa aaagaaaccc tcaactcaaa ttgctataat tagacacttg cttctgtctt 2462
gcctcctgtc tgcagctgtg aatagtcatt tgactgtgac tgttgccctt agccagccag 2522
atgcgcctgt gaaccaaagc tttgtgcaca tgtgttcccc taaaggttgg ggagcctcgc 2582
tgtgttttgc tgttcccagg caccaccaca gcaggtgctg ccatactctt gtggtctctg 2642
tgcgcccccc cccccccacc cgtctgccaa gcatgggtat gaatcgtgca cacagccatg 2702
cttcaaggcc ggggcagggg agcctgtgct gatgccatcc agggcactgg gctgtgcctg 2762
gaaggcgagc cttgattgtc tgaacacata aagcaaactg tccagaaggg aaaaaaaaaa 2822
aaaaaaaaaa aaaaa 2837
<210>9
<211>303
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>9
Met Lys Arg Lys Gln Ala Glu Ser Glu Arg Pro Ile Leu Pro Ala Asn
1 5 10 15
Gln Lys Leu Ile Thr Leu Ser Val Gln Asp Ala Pro Thr Lys Lys Glu
20 25 30
Phe Val Ile Asn Pro Asn Gly Lys Ser Glu Val Cys Ile Leu His Glu
35 40 45
Tyr Met Gln Arg Val Leu Lys Val Arg Pro Val Tyr Asn Phe Phe Glu
50 55 60
Cys Glu Asn Pro Ser Glu Pro Phe Gly Ala Ser Val Thr Ile Asp Gly
65 70 75 80
Val Thr Tyr Gly Ser Gly Thr Ala Ser Ser Lys Lys Leu Ala Lys Asn
85 90 95
Lys Ala Ala Arg Ala Thr Leu Glu Ile Leu Ile Pro Asp Phe Val Lys
100 105 110
Gln Thr Ser Glu Glu Lys Pro Lys Asp Ser Glu Glu Leu Glu Tyr Phe
115 120 125
Asn His Ile Ser Ile Glu Asp Ser Arg Val Tyr Glu Leu Thr Ser Lys
130 135 140
Ala Gly Leu Leu Ser Pro Tyr Gln Ile Leu His Glu Cys Leu Lys Arg
145 150 155 160
Asn His Gly Met Gly Asp Thr Ser Ile Lys Phe Glu Val Val Pro Gly
165 170 175
Lys Asn Gln Lys Ser Glu Tyr Val Met Ala Cys Gly Lys His Thr Val
180 185 190
Arg Gly Trp Cys Lys Asn Lys Arg Val Gly Lys Gln Leu Ala Ser Gln
195 200 205
Lys Ile Leu Gln Leu Leu His Pro His Val Lys Asn Trp Gly Ser Leu
210 215 220
Leu Arg Met Tyr Gly Arg Glu Ser Ser Lys Met Val Lys Gln Glu Thr
225 230 235 240
Ser Asp Lys Ser Val Ile Glu Leu Gln Gln Tyr Ala Lys Lys Asn Lys
245 250 255
Pro Asn Leu His Ile Leu Ser Lys Leu Gln Glu Glu Met Lys Arg Leu
260 265 270
Ala Glu Glu Arg Glu Glu Thr Arg Lys Lys Pro Lys Met Ser Ile Val
275 280 285
Ala Ser Ala Gln Pro Gly Gly Glu Pro Leu Cys Thr Val Asp Val
290 295 300
<210>10
<211>2280
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>10
gcgtctttta cagaatgtgg gatcctcgag ctaagatgag ggcatccctc acgttcacac 60
ccctggtggc atctgccagc cctgttctgg ggacaaggcg ggctttcgtg ggagccatgc 120
tcagcctgcc aggaagccaa gccctacagt gcagaggaaa cagaatttca acgggaagct 180
ggtttgcttc ataccattgg gatctgctgg taaagctgtt atttgggttt agggactgat 240
cccttgcagt ttacttctgg atcaccatga atggccaaga tggtggcaga acacgctgtg 300
gaccctgagt tagagacaat gcaaatgttg gattgggtgt aattcttttt gaatcccaga 360
tccagtctgt acttgaatat gagcagaaga tctacaagaa tgctgacagg gaaccgtgtt 420
aagacccagc acccctattc ccaggagctt ctggcctgac catctgcagc caaagcacta 480
acagggacag atatgggaat gtccaccttt gatccgcatc ctgcacaata gtggtcccac 540
catggctgcc acttttttat actatttgga gaaaagacct tgtataaatt cgaggcccga 600
gtgactaacg tctctgtcac acggaaatgg gtacttggtg gcatagagaa acacaattag 660
ccactttttc agctacactt ctcactcagc tgcaccctac acttctcact caggtgcacc 720
cccttctgct gtcctttccc caacgtactg ggtcccgagc gtggtgggta tttgccacac 780
tgggtgccag ctcagcagcc ccccacctct ctttattctc tccaaagctg gtctttctga 840
ctatcattgt ggtaggggga ggacagatgc taaaggtgga agctgacctg gagaaagaga 900
cacacggggt gactgtggca aaggacagct ggaaaagaaa ctctatcact tcttcattgg 960
caaccacaag gcacccgagg ccatggcact cccagaggct gtgcgcagag ccaagcctct 1020
caacctcttc tggccctgcg tcctgcagcg aagtctctgc tgtaagacag tagactcctt 1080
cgatgaggtg ctcaaaaatg ctacccgggg tggtggtgtc tggcttgcag tctggcccag 1140
ttcagagaaa gttgcagaga tcaggggcca aggatgtcat agccccaggt tgtcctcagg 1200
gtcgcaatcc tagggcaggg tgtgcatgga agcaagaact atggaaacct agctccagtc 1260
tgcaggctct gagcccctag ttcctcactc cagcggggct ccctcactgc acagaaccca 1320
ccccttctgt gtgggcactg ctgaccacac agatgaccca gacccaaaga gcctggcaga 1380
agctctgtgg ttggagctgg gctccgtctc caggtctggt tcagggggat caggaaggct 1440
cttttccacc tgtggcttca ctggcccttt gagatttcct atctcaccgt tacttcagtt 1500
acccttgcag ggggccaggg agtcaagaat ataccgtgtt cctccagggt ttaagccggc 1560
catgccttcc cgagagcata accaacttga caggggtgcc cagttacccc acaaactgaa 1620
ggaaggagat ccttcccccg tccccaggag tgctctcaac cagcctcaga aagcttgaga 1680
agatggaccc tttgcccacc agggttaatt cctggtgggg cagctcggct gtgatcaggg 1740
caaccaaacc tataggaagc cttccagtgt gagctggaat tagactgaac atgtgcttgg 1800
gcctgcctct ccctagacgc agttgcgggg cactccaggg aatgaaccag ctcaagtgtg 1860
tccctaacag cagcctggag ctacccccaa tccctcacag cctgaccctc ctcattccat 1920
cagatgcatt tgtagaatcg gggcaaattt ccttatttat ttatggccca tgcctttccc 1980
cctcttcatc ctgatcccgt tttgctttga agagacccca gtaaccaaaa aacagcctcc 2040
agaagccaaa accatgcctg gatctcccat agcttctcct ttgcttccag gagaaagttc 2100
actgaaaaaa aaatatcttc tggcttcttg tgtgtacaga gacaacagaa ctcggtgggg 2160
aaacgggaat cttttctgca ccaaagctgc ttctaaagca gaaagcagtg gggctcttgg 2220
tgtttcatgc tgccttattt atattaaagg aagaattaaa tcttaaaaaa aaaaaaaaaa 2280
<210>11
<211>2280
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(627)..(1070)
<223>
<400>11
gcgtctttta cagaatgtgg gatcctcgag ctaagatgag ggcatccctc acgttcacac 60
ccctggtggc atctgccagc cctgttctgg ggacaaggcg ggctttcgtg ggagccatgc 120
tcagcctgcc aggaagccaa gccctacagt gcagaggaaa cagaatttca acgggaagct 180
ggtttgcttc ataccattgg gatctgctgg taaagctgtt atttgggttt agggactgat 240
cccttgcagt ttacttctgg atcaccatga atggccaaga tggtggcaga acacgctgtg 300
gaccctgagt tagagacaat gcaaatgttg gattgggtgt aattcttttt gaatcccaga 360
tccagtctgt acttgaatat gagcagaaga tctacaagaa tgctgacagg gaaccgtgtt 420
aagacccagc acccctattc ccaggagctt ctggcctgac catctgcagc caaagcacta 480
acagggacag atatgggaat gtccaccttt gatccgcatc ctgcacaata gtggtcccac 540
catggctgcc acttttttat actatttgga gaaaagacct tgtataaatt cgaggcccga 600
gtgactaacg tctctgtcac acggaa atg ggt act tgg tgg cat aga gaa aca 653
Met Gly Thr Trp Trp His Arg Glu Thr
1 5
caa tta gcc act ttt tca gct aca ctt ctc act cag ctg cac cct aca 701
Gln Leu Ala Thr Phe Ser Ala Thr Leu Leu Thr Gln Leu His Pro Thr
10 15 20 25
ctt ctc act cag gtg cac ccc ctt ctg ctg tcc ttt ccc caa cgt act 749
Leu Leu Thr Gln Val His Pro Leu Leu Leu Ser Phe Pro Gln Arg Thr
30 35 40
ggg tcc cga gcg tgg tgg gta ttt gcc aca ctg ggt gcc agc tca gca 797
Gly Ser Arg Ala Trp Trp Val Phe Ala Thr Leu Gly Ala Ser Ser Ala
45 50 55
gcc ccc cac ctc tct tta ttc tct cca aag ctg gtc ttt ctg act atc 845
Ala Pro His Leu Ser Leu Phe Ser Pro Lys Leu Val Phe Leu Thr Ile
60 65 70
att gtg gta ggg gga gga cag atg cta aag gtg gaa gct gac ctg gag 893
Ile Val Val Gly Gly Gly Gln Met Leu Lys Val Glu Ala Asp Leu Glu
75 80 85
aaa gag aca cac ggg gtg act gtg gca aag gac agc tgg aaa aga aac 941
Lys Glu Thr His Gly Val Thr Val Ala Lys Asp Ser Trp Lys Arg Asn
90 95 100 105
tct atc act tct tca ttg gca acc aca agg cac ccg agg cca tgg cac 989
Ser Ile Thr Ser Ser Leu Ala Thr Thr Arg His Pro Arg Pro Trp His
110 115 120
tcc cag agg ctg tgc gca gag cca agc ctc tca acc tct tct ggc cct 1037
Ser Gln Arg Leu Cys Ala Glu Pro Ser Leu Ser Thr Ser Ser Gly Pro
125 130 135
gcg tcc tgc agc gaa gtc tct gct gta aga cag tagactcctt cgatgaggtg 1090
Ala Ser Cys Ser Glu Val Ser Ala Val Arg Gln
140 145
ctcaaaaatg ctacccgggg tggtggtgtc tggcttgcag tctggcccag ttcagagaaa 1150
gttgcagaga tcaggggcca aggatgtcat agccccaggt tgtcctcagg gtcgcaatcc 1210
tagggcaggg tgtgcatgga agcaagaact atggaaacct agctccagtc tgcaggctct 1270
gagcccctag ttcctcactc cagcggggct ccctcactgc acagaaccca ccccttctgt 1330
gtgggcactg ctgaccacac agatgaccca gacccaaaga gcctggcaga agctctgtgg 1390
ttggagctgg gctccgtctc caggtctggt tcagggggat caggaaggct cttttccacc 1450
tgtggcttca ctggcccttt gagatttcct atctcaccgt tacttcagtt acccttgcag 1510
ggggccaggg agtcaagaat ataccgtgtt cctccagggt ttaagccggc catgccttcc 1570
cgagagcata accaacttga caggggtgcc cagttacccc acaaactgaa ggaaggagat 1630
ccttcccccg tccccaggag tgctctcaac cagcctcaga aagcttgaga agatggaccc 1690
tttgcccacc agggttaatt cctggtgggg cagctcggct gtgatcaggg caaccaaacc 1750
tataggaagc cttccagtgt gagctggaat tagactgaac atgtgcttgg gcctgcctct 1810
ccctagacgc agttgcgggg cactccaggg aatgaaccag ctcaagtgtg tccctaacag 1870
cagcctggag ctacccccaa tccctcacag cctgaccctc ctcattccat cagatgcatt 1930
tgtagaatcg gggcaaattt ccttatttat ttatggccca tgcctttccc cctcttcatc 1990
ctgatcccgt tttgctttga agagacccca gtaaccaaaa aacagcctcc agaagccaaa 2050
accatgcctg gatctcccat agcttctcct ttgcttccag gagaaagttc actgaaaaaa 2110
aaatatcttc tggcttcttg tgtgtacaga gacaacagaa ctcggtgggg aaacgggaat 2170
cttttctgca ccaaagctgc ttctaaagca gaaagcagtg gggctcttgg tgtttcatgc 2230
tgccttattt atattaaagg aagaattaaa tcttaaaaaa aaaaaaaaaa 2280
<210>12
<211>148
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>12
Met Gly Thr Trp Trp His Arg Glu Thr Gln Leu Ala Thr Phe Ser Ala
1 5 10 15
Thr Leu Leu Thr Gln Leu His Pro Thr Leu Leu Thr Gln Val His Pro
20 25 30
Leu Leu Leu Ser Phe Pro Gln Arg Thr Gly Ser Arg Ala Trp Trp Val
35 40 45
Phe Ala Thr Leu Gly Ala Ser Ser Ala Ala Pro His Leu Ser Leu Phe
50 55 60
Ser Pro Lys Leu Val Phe Leu Thr Ile Ile Val Val Gly Gly Gly Gln
65 70 75 80
Met Leu Lys Val Glu Ala Asp Leu Glu Lys Glu Thr His Gly Val Thr
85 90 95
Val Ala Lys Asp Ser Trp Lys Arg Asn Ser Ile Thr Ser Ser Leu Ala
100 105 110
Thr Thr Arg His Pro Arg Pro Trp His Ser Gln Arg Leu Cys Ala Glu
115 120 125
Pro Ser Leu Ser Thr Ser Ser Gly Pro Ala Ser Cys Ser Glu Val Ser
130 135 140
Ala Val Arg Gln
145
<210>13
<211>3750
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>13
gtcgaagcgg ctgcagagcc ggtaacggtg gtggcggctg ttgggccaaa ggcgaaagac 60
gaagaggagg aggaagagga gccgctgcca ccgtgcgagg cggtgcgctg ggccccagtg 120
ggggcggtgg cggaggcccg gcctggggca accgcgtttt tagaagaggc gacggccgag 180
gagcctggcg cggccccggg ctccccgccg gattcgccgg gccggacgct gcggcggctg 240
cgggcagagc ggcggcggct ggactcggcg ctgctggcgc tgtcctcgca cttcgcgcag 300
gtgcagttcc gcctgcgcca ggtggtgcgc ggggcgccgg cggagcagca gcgccttctg 360
cgggagctcg aagacttcgc cttccgcggc tgccctcacg tcctaggtta cgaagggccc 420
ggcgaccccg ccagcgatga gggcgatggg ctgccagggg accggccacg gttgcggggc 480
gaggaccagg gcttgagtga gcaggaaaag caagagcgtc tggaaaccca aagggagaag 540
cagaaagaac tgatactgca gctcaagacc cagctagatg acctggaaac gtttgcctat 600
caagagggca gttatgactc gctgccacag tccgtggtgt tggaaagaca gcgggtgatc 660
atagatgagt taataaagaa actggacatg aatctgaatg aggacatcag ttccctgtcc 720
actgaagagc ttcgtcagcg tgtagatgca gcagtggctc agatcgtcaa cccagcccga 780
gtcaaagaac agttggttga gcaactgaaa actcagatcc gagaccttga gatgtttatc 840
aacttcatcc aagatgaagt gggaagcccc ttgcagacag gtggtggaca ctgtgagtgc 900
aaggccggtg ggaagacagg aaatggctgc agcagaacag gcagcagcag aacgcctcca 960
ggaaacagca aaacaaaggc agaggatgtg aagaaagtcc gggagacggg gctgcacctg 1020
atgcggcgag cgctggccgt gctccagatc tttgctgtta gccagtttgg ttgtgccaca 1080
ggccagatcc ctccaaccct gtggcagagg gtccaggctg acagagacta ctctcccttg 1140
ctgaagaggc tggaggtgtc agtggacaga gtgaagcagc tagccttgag gcagcagcca 1200
catgaccatg tcatcacctc tgccaacctc caggacctct ctctgggagg caaggatgag 1260
ctgactatgg ctgtgcggaa ggagctaacg gtggctgtga gggacctgct ggcccatgga 1320
ctgtatgcct cctccccagg gatgagcctt gttatggctc ctattgcttg tttgctgcca 1380
gccttctcct cggccccaga ggccatgcac ccgtgggagc tctttgtaaa gtactaccat 1440
gctaagaacg gccgtgctta tgtggaatcc ccagcccgga agctctccca gtccttcgcc 1500
cttcctgtta cgggaggcac tgttgtcacc cccaaacaga gcctactgac agccatccac 1560
atggtgctga cagagcatga cccttttaag cgcagtgcag actcagaatt gaaggccttg 1620
gtgtgcatgg cactgaatga gcagcgtctg gtgtcctggg tgaacctcat ctgcaagtcc 1680
gggtcactca tcgagcctca ctaccagccc tggagctaca tggcacacac aggctttgag 1740
agtgccctca acctgctcag tcgcctcagc agcctcaagt ttagcctccc tgtagatctg 1800
gctgtgcgcc agctcaaaaa catcaaagat gccttttgat gagagtgccc taaccccaga 1860
caagctcctt gttcagtagg gatagatgtg ctagtcttct agcataggag caaggaatca 1920
gaggtggggt taaaggcatt tttcccagac cctgctcagg cagtcggcca aatgagtgca 1980
aagtctgttt tccccaccaa cttagctctc ggaaagatgt gctggaggga ccctcttgtt 2040
aagaaggttc tgccaggccg ggcgcggtgg ctcacacctg taatcccagc actttgggag 2100
gccgaggcgg gcggatcaca aggtcaggag ttcgagacca tcctgtctaa cacggtgaaa 2160
ccccatctct actaaaaata caaaaaaatt agtcggacat ggtggcaggc acctgtagtc 2220
ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccaggaggcg gagcttgcag 2280
tgagccaaga tcgcgccact gcactccagc ctgggcgaca gagtgagact ccgtctcaaa 2340
aaaaaaaaag aaggttgtac ccacagtata cgtgtgggca cttgtgcttg agcctgtatt 2400
aaaggaatca ggccaggcac agtggctcac gcctgtaatc tcagcacatt gggaggctga 2460
ggtgggcgga tcacctgagg tcaggagttc aagaccagcc tggccaacat ggtgaaaccc 2520
catctctact aaaaatacaa aaattagcta ggcggggtag tgcatgcctg taatcccagc 2580
tactcaggag gctgaggccg gagaatcgct tgagcccgag aggtggagac tgcagtaagc 2640
caagatcatg ccactgcact ccagcctggg caacacaggg agactccatc tcaaaaaaaa 2700
aaaaaaaaaa aaaaagacat tcaacttgag gctcctgtta gttaagctat cttctttcac 2760
ttgaagcagg tttgagaggc ctaggccaga atttaaattc cttttatgaa tagatttccc 2820
tttcttcctg accccaaggt cagaggagac tatatattcc atggctgcct ctaagactag 2880
gaataggaat atctgaaaac agcatttcta agggtggtaa ccacaggtcg attttaatac 2940
gagtcctttt tcttgtagag gtaagtaaaa tcttcctgac aaggtagtcc tcttttcacg 3000
gcacagacaa tgggctttct gtttatgagg ggtgagaagt gatgtttgtt actatgttct 3060
ccagcaagta aacattcctc tgctcacctc ccaacaagac taacagtctt tttagaagta 3120
aatatattca agacaaacga gaaaatcctg gctacccaag tcgagtatat acaggaatac 3180
aaatcggtaa ccagcagctg ttcctcaggt tgtgactcac tgagcaccac ttgtcctgga 3240
ggctggatga tggaggacat ctggttatag gtactgtagc agggataggt gccacaggag 3300
gataggaact acagcagatc gctgtttcca gaacggggag gagtatctca ttgtgaaaca 3360
gactctagag tggttctatt tggtcttcag tgttttagcc tcattagttc atatttggca 3420
tgcagcttgt ggtgagtact gttctaggac tggccaaaaa tgggcaaaat gtatcactcc 3480
aaacactact gattcagcat tgttttcatg tcttaaaatt gccacctgca ctttgtttct 3540
gcactattat gtagtgcatt ttaacttaaa ttttttccag caacatgtta cttatttaag 3600
atacattact gatatttcat tataattagt tcaccttccc tgtgaaacaa gagaattgta 3660
aaatgttgtg gaaaatgata catatgtgga tgctaatgaa atcatagtat tttgtgtagc 3720
ttctctgaaa aaaaaaaaaa aaaaaaaaaa 3750
<210>14
<211>3750
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(688)..(1836)
<223>
<400>14
gtcgaagcgg ctgcagagcc ggtaacggtg gtggcggctg ttgggccaaa ggcgaaagac 60
gaagaggagg aggaagagga gccgctgcca ccgtgcgagg cggtgcgctg ggccccagtg 120
ggggcggtgg cggaggcccg gcctggggca accgcgtttt tagaagaggc gacggccgag 180
gagcctggcg cggccccggg ctccccgccg gattcgccgg gccggacgct gcggcggctg 240
cgggcagagc ggcggcggct ggactcggcg ctgctggcgc tgtcctcgca cttcgcgcag 300
gtgcagttcc gcctgcgcca ggtggtgcgc ggggcgccgg cggagcagca gcgccttctg 360
cgggagctcg aagacttcgc cttccgcggc tgccctcacg tcctaggtta cgaagggccc 420
ggcgaccccg ccagcgatga gggcgatggg ctgccagggg accggccacg gttgcggggc 480
gaggaccagg gcttgagtga gcaggaaaag caagagcgtc tggaaaccca aagggagaag 540
cagaaagaac tgatactgca gctcaagacc cagctagatg acctggaaac gtttgcctat 600
caagagggca gttatgactc gctgccacag tccgtggtgt tggaaagaca gcgggtgatc 660
atagatgagt taataaagaa actggac atg aat ctg aat gag gac atc agt tcc 714
Met Asn Leu Asn Glu Asp Ile Ser Ser
1 5
ctg tcc act gaa gag ctt cgt cag cgt gta gat gca gca gtg gct cag 762
Leu Ser Thr Glu Glu Leu Arg Gln Arg Val Asp Ala Ala Val Ala Gln
10 15 20 25
atc gtc aac cca gcc cga gtc aaa gaa cag ttg gtt gag caa ctg aaa 810
Ile Val Asn Pro Ala Arg Val Lys Glu Gln Leu Val Glu Gln Leu Lys
30 35 40
act cag atc cga gac ctt gag atg ttt atc aac ttc atc caa gat gaa 858
Thr Gln Ile Arg Asp Leu Glu Met Phe Ile Asn Phe Ile Gln Asp Glu
45 50 55
gtg gga agc ccc ttg cag aca ggt ggt gga cac tgt gag tgc aag gcc 906
Val Gly Ser Pro Leu Gln Thr Gly Gly Gly His Cys Glu Cys Lys Ala
60 65 70
ggt ggg aag aca gga aat ggc tgc agc aga aca ggc agc agc aga acg 954
Gly Gly Lys Thr Gly Asn Gly Cys Ser Arg Thr Gly Ser Ser Arg Thr
75 80 85
cct cca gga aac agc aaa aca aag gca gag gat gtg aag aaa gtc cgg 1002
Pro Pro Gly Asn Ser Lys Thr Lys Ala Glu Asp Val Lys Lys Val Arg
90 95 100 105
gag acg ggg ctg cac ctg atg cgg cga gcg ctg gcc gtg ctc cag atc 1050
Glu Thr Gly Leu His Leu Met Arg Arg Ala Leu Ala Val Leu Gln Ile
110 115 120
ttt gct gtt agc cag ttt ggt tgt gcc aca ggc cag atc cct cca acc 1098
Phe Ala Val Ser Gln Phe Gly Cys Ala Thr Gly Gln Ile Pro Pro Thr
125 130 135
ctg tgg cag agg gtc cag gct gac aga gac tac tct ccc ttg ctg aag 1146
Leu Trp Gln Arg Val Gln Ala Asp Arg Asp Tyr Ser Pro Leu Leu Lys
140 145 150
agg ctg gag gtg tca gtg gac aga gtg aag cag cta gcc ttg agg cag 1194
Arg Leu Glu Val Ser Val Asp Arg Val Lys Gln Leu Ala Leu Arg Gln
155 160 165
cag cca cat gac cat gtc atc acc tct gcc aac ctc cag gac ctc tct 1242
Gln Pro His Asp His Val Ile Thr Ser Ala Asn Leu Gln Asp Leu Ser
170 175 180 185
ctg gga ggc aag gat gag ctg act atg gct gtg cgg aag gag cta acg 1290
Leu Gly Gly Lys Asp Glu Leu Thr Met Ala Val Arg Lys Glu Leu Thr
190 195 200
gtg gct gtg agg gac ctg ctg gcc cat gga ctg tat gcc tcc tcc cca 1338
Val Ala Val Arg Asp Leu Leu Ala His Gly Leu Tyr Ala Ser Ser Pro
205 210 215
ggg atg agc ctt gtt atg gct cct att gct tgt ttg ctg cca gcc ttc 1386
Gly Met Ser Leu Val Met Ala Pro Ile Ala Cys Leu Leu Pro Ala Phe
220 225 230
tcc tcg gcc cca gag gcc atg cac ccg tgg gag ctc ttt gta aag tac 1434
Ser Ser Ala Pro Glu Ala Met His Pro Trp Glu Leu Phe Val Lys Tyr
235 240 245
tac cat gct aag aac ggc cgt gct tat gtg gaa tcc cca gcc cgg aag 1482
Tyr His Ala Lys Asn Gly Arg Ala Tyr Val Glu Ser Pro Ala Arg Lys
250 255 260 265
ctc tcc cag tcc ttc gcc ctt cct gtt acg gga ggc act gtt gtc acc 1530
Leu Ser Gln Ser Phe Ala Leu Pro Val Thr Gly Gly Thr Val Val Thr
270 275 280
ccc aaa cag agc cta ctg aca gcc atc cac atg gtg ctg aca gag cat 1578
Pro Lys Gln Ser Leu Leu Thr Ala Ile His Met Val Leu Thr Glu His
285 290 295
gac cct ttt aag cgc agt gca gac tca gaa ttg aag gcc ttg gtg tgc 1626
Asp Pro Phe Lys Arg Ser Ala Asp Ser Glu Leu Lys Ala Leu Val Cys
300 305 310
atg gca ctg aat gag cag cgt ctg gtg tcc tgg gtg aac ctc atc tgc 1674
Met Ala Leu Asn Glu Gln Arg Leu Val Ser Trp Val Asn Leu Ile Cys
315 320 325
aag tcc ggg tca ctc atc gag cct cac tac cag ccc tgg agc tac atg 1722
Lys Ser Gly Ser Leu Ile Glu Pro His Tyr Gln Pro Trp Ser Tyr Met
330 335 340 345
gca cac aca ggc ttt gag agt gcc ctc aac ctg ctc agt cgc ctc agc 1770
Ala His Thr Gly Phe Glu Ser Ala Leu Asn Leu Leu Ser Arg Leu Ser
350 355 360
agc ctc aag ttt agc ctc cct gta gat ctg gct gtg cgc cag ctc aaa 1818
Ser Leu Lys Phe Ser Leu Pro Val Asp Leu Ala Val Arg Gln Leu Lys
365 370 375
aac atc aaa gat gcc ttt tgatgagagt gccctaaccc cagacaagct 1866
Asn Ile Lys Asp Ala Phe
380
ccttgttcag tagggataga tgtgctagtc ttctagcata ggagcaagga atcagaggtg 1926
gggttaaagg catttttccc agaccctgct caggcagtcg gccaaatgag tgcaaagtct 1986
gttttcccca ccaacttagc tctcggaaag atgtgctgga gggaccctct tgttaagaag 2046
gttctgccag gccgggcgcg gtggctcaca cctgtaatcc cagcactttg ggaggccgag 2106
gcgggcggat cacaaggtca ggagttcgag accatcctgt ctaacacggt gaaaccccat 2166
ctctactaaa aatacaaaaa aattagtcgg acatggtggc aggcacctgt agtcccagct 2226
actcgggagg ctgaggcagg agaatggcgt gaacccagga ggcggagctt gcagtgagcc 2286
aagatcgcgc cactgcactc cagcctgggc gacagagtga gactccgtct caaaaaaaaa 2346
aaagaaggtt gtacccacag tatacgtgtg ggcacttgtg cttgagcctg tattaaagga 2406
atcaggccag gcacagtggc tcacgcctgt aatctcagca cattgggagg ctgaggtggg 2466
cggatcacct gaggtcagga gttcaagacc agcctggcca acatggtgaa accccatctc 2526
tactaaaaat acaaaaatta gctaggcggg gtagtgcatg cctgtaatcc cagctactca 2586
ggaggctgag gccggagaat cgcttgagcc cgagaggtgg agactgcagt aagccaagat 2646
catgccactg cactccagcc tgggcaacac agggagactc catctcaaaa aaaaaaaaaa 2706
aaaaaaaaag acattcaact tgaggctcct gttagttaag ctatcttctt tcacttgaag 2766
caggtttgag aggcctaggc cagaatttaa attcctttta tgaatagatt tccctttctt 2826
cctgacccca aggtcagagg agactatata ttccatggct gcctctaaga ctaggaatag 2886
gaatatctga aaacagcatt tctaagggtg gtaaccacag gtcgatttta atacgagtcc 2946
tttttcttgt agaggtaagt aaaatcttcc tgacaaggta gtcctctttt cacggcacag 3006
acaatgggct ttctgtttat gaggggtgag aagtgatgtt tgttactatg ttctccagca 3066
agtaaacatt cctctgctca cctcccaaca agactaacag tctttttaga agtaaatata 3126
ttcaagacaa acgagaaaat cctggctacc caagtcgagt atatacagga atacaaatcg 3186
gtaaccagca gctgttcctc aggttgtgac tcactgagca ccacttgtcc tggaggctgg 3246
atgatggagg acatctggtt ataggtactg tagcagggat aggtgccaca ggaggatagg 3306
aactacagca gatcgctgtt tccagaacgg ggaggagtat ctcattgtga aacagactct 3366
agagtggttc tatttggtct tcagtgtttt agcctcatta gttcatattt ggcatgcagc 3426
ttgtggtgag tactgttcta ggactggcca aaaatgggca aaatgtatca ctccaaacac 3486
tactgattca gcattgtttt catgtcttaa aattgccacc tgcactttgt ttctgcacta 3546
ttatgtagtg cattttaact taaatttttt ccagcaacat gttacttatt taagatacat 3606
tactgatatt tcattataat tagttcacct tccctgtgaa acaagagaat tgtaaaatgt 3666
tgtggaaaat gatacatatg tggatgctaa tgaaatcata gtattttgtg tagcttctct 3726
gaaaaaaaaa aaaaaaaaaa aaaa 3750
<210>15
<211>383
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>15
Met Asn Leu Asn Glu Asp Ile Ser Ser Leu Ser Thr Glu Glu Leu Arg
1 5 10 15
Gln Arg Val Asp Ala Ala Val Ala Gln Ile Val Asn Pro Ala Arg Val
20 25 30
Lys Glu Gln Leu Val Glu Gln Leu Lys Thr Gln Ile Arg Asp Leu Glu
35 40 45
Met Phe Ile Asn Phe Ile Gln Asp Glu Val Gly Ser Pro Leu Gln Thr
50 55 60
Gly Gly Gly His Cys Glu Cys Lys Ala Gly Gly Lys Thr Gly Asn Gly
65 70 75 80
Cys Ser Arg Thr Gly Ser Ser Arg Thr Pro Pro Gly Asn Ser Lys Thr
85 90 95
Lys Ala Glu Asp Val Lys Lys Val Arg Glu Thr Gly Leu His Leu Met
100 105 110
Arg Arg Ala Leu Ala Val Leu Gln Ile Phe Ala Val Ser Gln Phe Gly
115 120 125
Cys Ala Thr Gly Gln Ile Pro Pro Thr Leu Trp Gln Arg Val Gln Ala
130 135 140
Asp Arg Asp Tyr Ser Pro Leu Leu Lys Arg Leu Glu Val Ser Val Asp
145 150 155 160
Arg Val Lys Gln Leu Ala Leu Arg Gln Gln Pro His Asp His Val Ile
165 170 175
Thr Ser Ala Asn Leu Gln Asp Leu Ser Leu Gly Gly Lys Asp Glu Leu
180 185 190
Thr Met Ala Val Arg Lys Glu Leu Thr Val Ala Val Arg Asp Leu Leu
195 200 205
Ala His Gly Leu Tyr Ala Ser Ser Pro Gly Met Ser Leu Val Met Ala
210 215 220
Pro Ile Ala Cys Leu Leu Pro Ala Phe Ser Ser Ala Pro Glu Ala Met
225 230 235 240
His Pro Trp Glu Leu Phe Val Lys Tyr Tyr His Ala Lys Asn Gly Arg
245 250 255
Ala Tyr Val Glu Ser Pro Ala Arg Lys Leu Ser Gln Ser Phe Ala Leu
260 265 270
Pro Val Thr Gly Gly Thr Val Val Thr Pro Lys Gln Ser Leu Leu Thr
275 280 285
Ala Ile His Met Val Leu Thr Glu His Asp Pro Phe Lys Arg Ser Ala
290 295 300
Asp Ser Glu Leu Lys Ala Leu Val Cys Met Ala Leu Asn Glu Gln Arg
305 310 315 320
Leu Val Ser Trp Val Asn Leu Ile Cys Lys Ser Gly Ser Leu Ile Glu
325 330 335
Pro His Tyr Gln Pro Trp Ser Tyr Met Ala His Thr Gly Phe Glu Ser
340 345 350
Ala Leu Asn Leu Leu Ser Arg Leu Ser Ser Leu Lys Phe Ser Leu Pro
355 360 365
Val Asp Leu Ala Val Arg Gln Leu Lys Asn Ile Lys Asp Ala Phe
370 375 380
<210>16
<211>2730
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>16
gcgctcctcc ggtggccgaa cgtcgctttc gggagctgtg gtccccgcaa gccgcggttc 60
ccggcctttc agctcggctg ctccctgggt ggtggggccg aggcgcaccc ccttctgccc 120
gggcccggag tgcggaggcg cagcccggga gaggggctga aggggggcag gcagtcctcg 180
ggcgcgagtg tgcagcgccc tctgggcgtg gacgcggagc gcgctccagg tgcgcaggac 240
tcctagctct cttggggaac gctttctggg gcagggcggg gacccggggg cgatggggcc 300
ttcaaccgac gggcaaacac acacagacac accccggctg tcctccagct gcgatgcggc 360
tcgctgcgcc ccgccggccc agattctccc gtacgctcgc gttcttcctg cactccacaa 420
agtgctggag acttggggcc ttagtttaaa cagctgcacc cgcacggaag ggctgcaaga 480
aaaaggggga cgggggcgga gttcgcagcg tctttctgtg gaagacaacg ccctctctct 540
tcatctgagc taaaaggaaa aataagtaac ttctttgttc cccggtgacc tcgggcacgc 600
ggatctgagg agcaccgtgc agttgctgct ccttcgagat cccctgcgag gccctgggcc 660
tcagttcaaa aagctgtgga aggcctgcgg gtgtagggga aacggccgag agagcaaagg 720
ggaagaaccg gacgggccct gcccacatct ggcaggcagg agagatggtg ccaaacgacc 780
ttcgcacctg ggccctgaga ccaaagatgg cgtcgtcctc ccctgtcttc cctaggcgga 840
aggcaagaac ttgggtcggc ctgagctggg gaccaagaaa atatcgggaa gtgtccagtg 900
ttcctcttta aaagaattaa accttcctgg gccacgcagg gactgaccgt gggaccctgg 960
actctcctcc accttccacc gtggagcagg ctctggagcc gagcagcctc ctgcgtcccc 1020
atctcatccc cccactcctc ctcacagcac taaaagatga tggcctgctt gtacccctgc 1080
tcctgagcac ctgtttgacc tcaaagagct ctcgcttttg gggtgtccgt ctccccaagt 1140
ctgtctaggg ggcaggaaga ccttcatcag ggttcttggg ggccgatgtg ggctcgctga 1200
gtgcctgagt gatggatggt ctcacagcac ggcaccacgg aggtccagcc gagctcgagg 1260
agtccctgtg gattaaaaat gcccttttcg aaggttctac ctctaccaga gggtggctcc 1320
acagatccct tcaacccagt atggtggaaa aataggaatt ttggaatctt acctttctct 1380
actgctcaca acagaggaaa ctggggtcag ggaggatttg atggagtctt ttcatttttt 1440
aaaagtcact cacggccaag cgcggtggct cacgcctgtg accccagcac tttgggaggc 1500
cgaggcgggc agatcacctg aggtcaggag ttctcgacca gcctggctaa cacggtgaat 1560
ccccatctct actaaaaata caaaaattag ccggatatgg tggcaggtgc tataatccca 1620
gctactcggg aggctgaggc agggagaatc gcctcgacct ctcgggttca aacaattctc 1680
ccgcctcagc ctcctaaata gctgggatta cagtcgcacg ccaccacagg ccggctaatt 1740
ttttatttat ttatttattt tgatttttag tagagacaag gtttcaccat attggtcagg 1800
ctggtcttga actcccaacc tcaggtgata cacccgtctc ggcctcccaa agcgctggga 1860
ttgcaggcgt gagccaccgt gcctggccct tatacttgtc ttcttgagtg catgtgtgag 1920
gctttctcta gaagtagagc tctggattat aggtataaac atcttcaact ttctcaggaa 1980
ttgttgtaag caattgctct aagcaaattg ctctccaaag ggcttatagt aatttacact 2040
cccaacagca gttatgagca tttccatttt tctacatcct cctatgactt ggtgttgggc 2100
cttttatatt ttgccagctg atgcaagtaa aattatatct tattgctgtt tgagtctgac 2160
catccttccc attaggaaat gttttgctga agcctttagt tgccgactgg ttgggcagac 2220
acttctgttt acttatcaca tctgttttcc tctttctcag taagagattc cttaaatttc 2280
aattgggctt atggctattt aaaataaaga ttacctttcc ctgcctctct tacagccacg 2340
cgtagccaca tgattagggt cttgccagtg gcacatgagc agaagtggta catgcacttt 2400
cagaaaggtg tcaagcatgc tctccttccc ttttctgttt tctcctgggc ggaatacaga 2460
tctgatggct gcctctgaag cagccttctt ggaccatgaa gtgaacatgg gaacagaggc 2520
catccacagc agaggaacaa gttaaaggaa gcatgggtcc ctgccccatg gagtatagcg 2580
tcatccctgg actgcccacg cagacttata catgatggga aaatgtctct ttttgtttgt 2640
ttaggacact gtttctctga attttctctc acttgccagc aattctaatc ctaaaaatac 2700
actgatgaat tcaaaaaaaa aaaaaaaaaa 2730
<210>17
<211>2730
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(1216)..(1518)
<223>
<400>17
gcgctcctcc ggtggccgaa cgtcgctttc gggagctgtg gtccccgcaa gccgcggttc 60
ccggcctttc agctcggctg ctccctgggt ggtggggccg aggcgcaccc ccttctgccc 120
gggcccggag tgcggaggcg cagcccggga gaggggctga aggggggcag gcagtcctcg 180
ggcgcgagtg tgcagcgccc tctgggcgtg gacgcggagc gcgctccagg tgcgcaggac 240
tcctagctct cttggggaac gctttctggg gcagggcggg gacccggggg cgatggggcc 300
ttcaaccgac gggcaaacac acacagacac accccggctg tcctccagct gcgatgcggc 360
tcgctgcgcc ccgccggccc agattctccc gtacgctcgc gttcttcctg cactccacaa 420
agtgctggag acttggggcc ttagtttaaa cagctgcacc cgcacggaag ggctgcaaga 480
aaaaggggga cgggggcgga gttcgcagcg tctttctgtg gaagacaacg ccctctctct 540
tcatctgagc taaaaggaaa aataagtaac ttctttgttc cccggtgacc tcgggcacgc 600
ggatctgagg agcaccgtgc agttgctgct ccttcgagat cccctgcgag gccctgggcc 660
tcagttcaaa aagctgtgga aggcctgcgg gtgtagggga aacggccgag agagcaaagg 720
ggaagaaccg gacgggccct gcccacatct ggcaggcagg agagatggtg ccaaacgacc 780
ttcgcacctg ggccctgaga ccaaagatgg cgtcgtcctc ccctgtcttc cctaggcgga 840
aggcaagaac ttgggtcggc ctgagctggg gaccaagaaa atatcgggaa gtgtccagtg 900
ttcctcttta aaagaattaa accttcctgg gccacgcagg gactgaccgt gggaccctgg 960
actctcctcc accttccacc gtggagcagg ctctggagcc gagcagcctc ctgcgtcccc 1020
atctcatccc cccactcctc ctcacagcac taaaagatga tggcctgctt gtacccctgc 1080
tcctgagcac ctgtttgacc tcaaagagct ctcgcttttg gggtgtccgt ctccccaagt 1140
ctgtctaggg ggcaggaaga ccttcatcag ggttcttggg ggccgatgtg ggctcgctga 1200
gtgcctgagt gatgg atg gtc tca cag cac ggc acc acg gag gtc cag ccg 1251
Met Val Ser Gln His Gly Thr Thr Glu Val Gln Pro
1 5 10
agc tcg agg agt ccc tgt gga tta aaa atg ccc ttt tcg aag gtt cta 1299
Ser Ser Arg Ser Pro Cys Gly Leu Lys Met Pro Phe Ser Lys Val Leu
15 20 25
cct cta cca gag ggt ggc tcc aca gat ccc ttc aac cca gta tgg tgg 1347
Pro Leu Pro Glu Gly Gly Ser Thr Asp Pro Phe Asn Pro Val Trp Trp
30 35 40
aaa aat agg aat ttt gga atc tta cct ttc tct act gct cac aac aga 1395
Lys Asn Arg Asn Phe Gly Ile Leu Pro Phe Ser Thr Ala His Asn Arg
45 50 55 60
gga aac tgg ggt cag gga gga ttt gat gga gtc ttt tca ttt ttt aaa 1443
Gly Asn Trp Gly Gln Gly Gly Phe Asp Gly Val Phe Ser Phe Phe Lys
65 70 75
agt cac tca cgg cca agc gcg gtg gct cac gcc tgt gac ccc agc act 1491
Ser His Ser Arg Pro Ser Ala Val Ala His Ala Cys Asp Pro Ser Thr
80 85 90
ttg gga ggc cga ggc ggg cag atc acc tgaggtcagg agttctcgac 1538
Leu Gly Gly Arg Gly Gly Gln Ile Thr
95 100
cagcctggct aacacggtga atccccatct ctactaaaaa tacaaaaatt agccggatat 1598
ggtggcaggt gctataatcc cagctactcg ggaggctgag gcagggagaa tcgcctcgac 1658
ctctcgggtt caaacaattc tcccgcctca gcctcctaaa tagctgggat tacagtcgca 1718
cgccaccaca ggccggctaa ttttttattt atttatttat tttgattttt agtagagaca 1778
aggtttcacc atattggtca ggctggtctt gaactcccaa cctcaggtga tacacccgtc 1838
tcggcctccc aaagcgctgg gattgcaggc gtgagccacc gtgcctggcc cttatacttg 1898
tcttcttgag tgcatgtgtg aggctttctc tagaagtaga gctctggatt ataggtataa 1958
acatcttcaa ctttctcagg aattgttgta agcaattgct ctaagcaaat tgctctccaa 2018
agggcttata gtaatttaca ctcccaacag cagttatgag catttccatt tttctacatc 2078
ctcctatgac ttggtgttgg gccttttata ttttgccagc tgatgcaagt aaaattatat 2138
cttattgctg tttgagtctg accatccttc ccattaggaa atgttttgct gaagccttta 2198
gttgccgact ggttgggcag acacttctgt ttacttatca catctgtttt cctctttctc 2258
agtaagagat tccttaaatt tcaattgggc ttatggctat ttaaaataaa gattaccttt 2318
ccctgcctct cttacagcca cgcgtagcca catgattagg gtcttgccag tggcacatga 2378
gcagaagtgg tacatgcact ttcagaaagg tgtcaagcat gctctccttc ccttttctgt 2438
tttctcctgg gcggaataca gatctgatgg ctgcctctga agcagccttc ttggaccatg 2498
aagtgaacat gggaacagag gccatccaca gcagaggaac aagttaaagg aagcatgggt 2558
ccctgcccca tggagtatag cgtcatccct ggactgccca cgcagactta tacatgatgg 2618
gaaaatgtct ctttttgttt gtttaggaca ctgtttctct gaattttctc tcacttgcca 2678
gcaattctaa tcctaaaaat acactgatga attcaaaaaa aaaaaaaaaa aa 2730
<210>18
<21l>101
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>18
Met Val Ser Gln His Gly Thr Thr Glu Val Gln Pro Ser Ser Arg Ser
1 5 10 15
Pro Cys Gly Leu Lys Met Pro Phe Ser Lys Val Leu Pro Leu Pro Glu
20 25 30
Gly Gly Ser Thr Asp Pro Phe Asn Pro Val Trp Trp Lys Asn Arg Asn
35 40 45
Phe Gly Ile Leu Pro Phe Ser Thr Ala His Asn Arg Gly Asn Trp Gly
50 55 60
Gln Gly Gly Phe Asp Gly Val Phe Ser Phe Phe Lys Ser His Ser Arg
65 70 75 80
Pro Ser Ala Val Ala His Ala Cys Asp Pro Ser Thr Leu Gly Gly Arg
85 90 95
Gly Gly Gln Ile Thr
100
<210>19
<211>3260
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>19
gggggatccg tgctgccatg gagcgtgccg gcaagcagga gatgctgctg aagccacata 60
gccgtgtcca ggtattcgag ggtgcggagg acaacctccc ggaccgcgat gcgctgcggg 120
ctgcactggc catccagcaa ctggctgagg gactcacagc tgatgacctg ctgctcgtgc 180
tgatctcagg tgtggtacca cattggccca agactgttgg tggggggtgc accacctgat 240
ctctcaggtc ttcgagagat caggtctgag cccccggggt cacagggtaa agttaggagc 300
aagggaggtg gtgaggagcc tggatggtga ctcctgggtt gccttgggct agtcgtctgg 360
cctcccctga gctgtggagt cctccccctg agctgacctt ttcggtgaca gtgagagggt 420
gcatggggag cacataatgc agggcctgac acatccgtag agtccttgga aaatgtcact 480
gctattgctg ctgtctgtac taatgtcacc tggggctagg ccctcagacc tcatggagtc 540
ctctccttga tcttccattg tgtgccccct gccctgcctc ctgttctagt ctcttaagga 600
gtagttagtt cttccggtgc ctactgggac ctggggtacc ccaaggcagg ggcaacctca 660
ggtggccagg atgtggtgac tgtacacata ttgcatatcc acaggggggc accctaaccc 720
cacctttcca gccccctttt tctaatgtgg gcttgtcacc cctgcttgcc tggttccctg 780
ggttgggata gcccctctac ctgataccct cattgtcttg agaggtgggg gttcagctct 840
gctgcctgcc cccatcccac ctgtcacact ggaggagaag cagacactca ctagactgct 900
ggcagcccgt ggagccacca tccaggagtt gaacaccatt cggaaggccc tgtcccagct 960
caagggtggg gggctggctc aggccgccta ccctgcccag gtggtgagcc tcatcctgtc 1020
agatgtggtg gggggggggc accctgtgga ggtgattgcc agtggcccca ccgtggccag 1080
ttcccacaat gtgcaagatt gcctgcatat cctcaatcgc tacggcctcc gtgcagccct 1140
gccacgttct gtgaagactg tgctgtctcg ggccgactct gacccccatg ggccacacac 1200
ctgtggccat gtcctgaatg tgatcattgg ctctaatgtg ctggcgctag ctgaggccca 1260
gcggcaggcc gaggcactgg gctaccaggc tgtgttgctg agtgcagcca tgcaaggtga 1320
tgtaaaaagt atggcccagt tctacgggct gctggcccat gtggctagaa cccgcctcac 1380
cccatccatg gctggggctt ctgtggagga agatgcacag ctccatgagc tggcagctga 1440
gcttcagatc ccagacctgc agctggagga ggctctggag accatggcat ggggaagggg 1500
cccagtctgc ctgctggctg gtggcgagcc cacagtacag ctgcagggct cgggcagggg 1560
tggccggaac caggaactgg ccctgcgtgt tggagcagag ttgagaaggt ggccgctggg 1620
gccgatagat gtgctgtttt tgagcggtgg caccgatggg caggatgggc ccacagaggc 1680
tgctggggcc tgggtcacac ctgagcttgc cagccaggct gcagctgagg gcctggacat 1740
agccaccttc ctagcccaca atgactcaca taccttcttc tgctgcctcc agggtggggc 1800
acacctgctg cacacaggga tgacaggtac caatgtcatg gacacccacc tcttgttcct 1860
gcggcctcgg tgatggcata ggtcacattt tgggagttca gaggaggcct acaagggcaa 1920
gccagactgg cagatggggg cttcccccta cccctgagga tgaggacaag cccctcggcc 1980
agttcagcgt tcccgtgctt ctcccttggg cagcctctct cttgagcccc tcaccctgtt 2040
tctttctgtg aagcgagaat gtctgaaaat aaataggacc atgccatggg aaaaaaaaaa 2100
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160
aaaaacggca cgaggcggca cgaggcaagc ttgtagtcag aagaactcgc ctgggaggga 2220
tcgctcctgg gagatccgaa cgcgggaggg cctggagcgc ggcggcagct ggatagcatt 2280
cgggcccatc cgaataagcg gtaaatggat catttctggg gcctccctga ctcctcttcc 2340
agagcctcct accgacctgc tctgtcccct ccttccttca tgccctccac tcttccctaa 2400
atgcaagtct cctccccaag cccatgtcct cctcggcttc ccctctgctc tcctcaccgg 2460
tctcactcag tcaacttcaa gtctgagcct tctctgcctg tctccttcca ttctcacctt 2520
tcctgtcaca ccagatcact cttctcccag gctgtccctc gtgccaaact tttttggtaa 2580
atcttcctta atgatctaga aacagtctct cccttctttc tattccataa tggtccttca 2640
aaaccccaac cctcgccggg cgcggtggct cacgcctgta atcccagcac tttggaaggc 2700
cgaggtgggc ggatcataag gtcaggagat cgagaccatc ctggctaaca aggtgaaaca 2760
ctatctctac taaaaataca ggaaaaaaaa aaattagccg ggcgtggggg cgggcccctg 2820
tagtcccagg tactcgggag gctgaggcag gagaatggcg tgaacccggg aggcggagct 2880
tgcaatgagc caagatcttg ccactgcact ccagcctggg cgacagagca agactctgtc 2940
tcaaaaaaaa aaaaagttaa atttggccag gcacagtggc tcacacctgt aatcccaaca 3000
ctttgggagg ccaaggtgtg ccagatagct tgagccccag agtttgagag cagtctgggc 3060
aacatagtga gaccttcttg agaccttctt ctctacaaaa aatttaaaaa ttagccagga 3120
acctgtagtt ccagctactc gggaggctga ggtgggagaa tcacctgagc ccaggaggtc 3180
aaggctgcag tgagctgtgt tcctgccact gtactccagc ctgggtgaca gtaagacctt 3240
gtaaaaaaaa aaaaaaaaaa 3260
<210>20
<211>3260
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(1310)..(1870)
<223>
<400>20
gggggatccg tgctgccatg gagcgtgccg gcaagcagga gatgctgctg aagccacata 60
gccgtgtcca ggtattcgag ggtgcggagg acaacctccc ggaccgcgat gcgctgcggg 120
ctgcactggc catccagcaa ctggctgagg gactcacagc tgatgacctg ctgctcgtgc 180
tgatctcagg tgtggtacca cattggccca agactgttgg tggggggtgc accacctgat 240
ctctcaggtc ttcgagagat caggtctgag cccccggggt cacagggtaa agttaggagc 300
aagggaggtg gtgaggagcc tggatggtga ctcctgggtt gccttgggct agtcgtctgg 360
cctcccctga gctgtggagt cctccccctg agctgacctt ttcggtgaca gtgagagggt 420
gcatggggag cacataatgc agggcctgac acatccgtag agtccttgga aaatgtcact 480
gctattgctg ctgtctgtac taatgtcacc tggggctagg ccctcagacc tcatggagtc 540
ctctccttga tcttccattg tgtgccccct gccctgcctc ctgttctagt ctcttaagga 600
gtagttagtt cttccggtgc ctactgggac ctggggtacc ccaaggcagg ggcaacctca 660
ggtggccagg atgtggtgac tgtacacata ttgcatatcc acaggggggc accctaaccc 720
cacctttcca gccccctttt tctaatgtgg gcttgtcacc cctgcttgcc tggttccctg 780
ggttgggata gcccctctac ctgataccct cattgtcttg agaggtgggg gttcagctct 840
gctgcctgcc cccatcccac ctgtcacact ggaggagaag cagacactca ctagactgct 900
ggcagcccgt ggagccacca tccaggagtt gaacaccatt cggaaggccc tgtcccagct 960
caagggtggg gggctggctc aggccgccta ccctgcccag gtggtgagcc tcatcctgtc 1020
agatgtggtg gggggggggc accctgtgga ggtgattgcc agtggcccca ccgtggccag 1080
ttcccacaat gtgcaagatt gcctgcatat cctcaatcgc tacggcctcc gtgcagccct 1140
gccacgttct gtgaagactg tgctgtctcg ggccgactct gacccccatg ggccacacac 1200
ctgtggccat gtcctgaatg tgatcattgg ctctaatgtg ctggcgctag ctgaggccca 1260
gcggcaggcc gaggcactgg gctaccaggc tgtgttgctg agtgcagcc atg caa ggt 1318
Met Gln Gly
1
gat gta aaa agt atg gcc cag ttc tac ggg ctg ctg gcc cat gtg gct 1366
Asp Val Lys Ser Met Ala Gln Phe Tyr Gly Leu Leu Ala His Val Ala
5 10 15
aga acc cgc ctc acc cca tcc atg gct ggg gct tct gtg gag gaa gat 1414
Arg Thr Arg Leu Thr Pro Ser Met Ala Gly Ala Ser Val Glu Glu Asp
20 25 30 35
gca cag ctc cat gag ctg gca gct gag ctt cag atc cca gac ctg cag 1462
Ala Gln Leu His Glu Leu Ala Ala Glu Leu Gln Ile Pro Asp Leu Gln
40 45 50
ctg gag gag gct ctg gag acc atg gca tgg gga agg ggc cca gtc tgc 1510
Leu Glu Glu Ala Leu Glu Thr Met Ala Trp Gly Arg Gly Pro Val Cys
55 60 65
ctg ctg gct ggt ggc gag ccc aca gta cag ctg cag ggc tcg ggc agg 1558
Leu Leu Ala Gly Gly Glu Pro Thr Val Gln Leu Gln Gly Ser Gly Arg
70 75 80
ggt ggc cgg aac cag gaa ctg gcc ctg cgt gtt gga gca gag ttg aga 1606
Gly Gly Arg Asn Gln Glu Leu Ala Leu Arg Val Gly Ala Glu Leu Arg
85 90 95
agg tgg ccg ctg ggg ccg ata gat gtg ctg ttt ttg agc ggt ggc acc 1654
Arg Trp Pro Leu Gly Pro Ile Asp Val Leu Phe Leu Ser Gly Gly Thr
100 105 110 115
gat ggg cag gat ggg ccc aca gag gct gct ggg gcc tgg gtc aca cct 1702
Asp Gly Gln Asp Gly Pro Thr Glu Ala Ala Gly Ala Trp Val Thr Pro
120 125 130
gag ctt gcc agc cag gct gca gct gag ggc ctg gac ata gcc acc ttc 1750
Glu Leu Ala Ser Gln Ala Ala Ala Glu Gly Leu Asp Ile Ala Thr Phe
135 140 145
cta gcc cac aat gac tca cat acc ttc ttc tgc tgc ctc cag ggt ggg 1798
Leu Ala His Asn Asp Ser His Thr Phe Phe Cys Cys Leu Gln Gly Gly
150 155 160
gca cac ctg ctg cac aca ggg atg aca ggt acc aat gtc atg gac acc 1846
Ala His Leu Leu His Thr Gly Met Thr Gly Thr Asn Val Met Asp Thr
165 170 175
cac ctc ttg ttc ctg cgg cct cgg tgatggcata ggtcacattt tgggagttca 1900
His Leu Leu Phe Leu Arg Pro Arg
180 185
gaggaggcct acaagggcaa gccagactgg cagatggggg cttcccccta cccctgagga 1960
tgaggacaag cccctcggcc agttcagcgt tcccgtgctt ctcccttggg cagcctctct 2020
cttgagcccc tcaccctgtt tctttctgtg aagcgagaat gtctgaaaat aaataggacc 2080
atgccatggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2140
aaaaaaaaaa aaaaaaaaaa aaaaacggca cgaggcggca cgaggcaagc ttgtagtcag 2200
aagaactcgc ctgggaggga tcgctcctgg gagatccgaa cgcgggaggg cctggagcgc 2260
ggcggcagct ggatagcatt cgggcccatc cgaataagcg gtaaatggat catttctggg 2320
gcctccctga ctcctcttcc agagcctcct accgacctgc tctgtcccct ccttccttca 2380
tgccctccac tcttccctaa atgcaagtct cctccccaag cccatgtcct cctcggcttc 2440
ccctctgctc tcctcaccgg tctcactcag tcaacttcaa gtctgagcct tctctgcctg 2500
tctccttcca ttctcacctt tcctgtcaca ccagatcact cttctcccag gctgtccctc 2560
gtgccaaact tttttggtaa atcttcctta atgatctaga aacagtctct cccttctttc 2620
tattccataa tggtccttca aaaccccaac cctcgccggg cgcggtggct cacgcctgta 2680
atcccagcac tttggaaggc cgaggtgggc ggatcataag gtcaggagat cgagaccatc 2740
ctggctaaca aggtgaaaca ctatctctac taaaaataca ggaaaaaaaa aaattagccg 2800
ggcgtggggg cgggcccctg tagtcccagg tactcgggag gctgaggcag gagaatggcg 2860
tgaacccggg aggcggagct tgcaatgagc caagatcttg ccactgcact ccagcctggg 2920
cgacagagca agactctgtc tcaaaaaaaa aaaaagttaa atttggccag gcacagtggc 2980
tcacacctgt aatcccaaca ctttgggagg ccaaggtgtg ccagatagct tgagccccag 3040
agtttgagag cagtctgggc aacatagtga gaccttcttg agaccttctt ctctacaaaa 3100
aatttaaaaa ttagccagga acctgtagtt ccagctactc gggaggctga ggtgggagaa 3160
tcacctgagc ccaggaggtc aaggctgcag tgagctgtgt tcctgccact gtactccagc 3220
ctgggtgaca gtaagacctt gtaaaaaaaa aaaaaaaaaa 3260
<210>21
<211>187
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>21
Met Gln Gly Asp Val Lys Ser Met Ala Gln Phe Tyr Gly Leu Leu Ala
1 5 10 15
His Val Ala Arg Thr Arg Leu Thr Pro Ser Met Ala Gly Ala Ser Val
20 25 30
Glu Glu Asp Ala Gln Leu His Glu Leu Ala Ala Glu Leu Gln Ile Pro
35 40 45
Asp Leu Gln Leu Glu Glu Ala Leu Glu Thr Met Ala Trp Gly Arg Gly
50 55 60
Pro Val Cys Leu Leu Ala Gly Gly Glu Pro Thr Val Gln Leu Gln Gly
65 70 75 80
Ser Gly Arg Gly Gly Arg Asn Gln Glu Leu Ala Leu Arg Val Gly Ala
85 90 95
Glu Leu Arg Arg Trp Pro Leu Gly Pro Ile Asp Val Leu Phe Leu Ser
100 105 110
Gly Gly Thr Asp Gly Gln Asp Gly Pro Thr Glu Ala Ala Gly Ala Trp
115 120 125
Val Thr Pro Glu Leu Ala Ser Gln Ala Ala Ala Glu Gly Leu Asp Ile
130 135 140
Ala Thr Phe Leu Ala His Asn Asp Ser His Thr Phe Phe Cys Cys Leu
145 150 155 160
Gln Gly Gly Ala His Leu Leu His Thr Gly Met Thr Gly Thr Asn Val
165 170 175
Met Asp Thr His Leu Leu Phe Leu Arg Pro Arg
180 185
<210>22
<211>2692
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>22
gcggaagcgg cggccgggcc gccctgcgcc cgggcggggc cctgcggtgt ggccgtggct 60
tgttcctgcc gctttcgcac cctgcggccc cccacccagt gcagcagtgc gggcgggcgt 120
gagcctcggt gcaccaggag gcccttcccg cgggaggcgc tgggctcgcg ctaattgggg 180
cggggggggg ggcggcgggg gaggagggaa ctggcgcgcg gcttggtttc cattagagac 240
gcaaagtttc tgctccggga ggaggcggcg gcgccgcggg ctcgtcgcct gggggagcag 300
aagcgggtgg gaggtgcggg tggccttggc cgcagccctg gtgcgcgggg gccgggggtg 360
gtgaccctcc tggccgagga ggggcggcgt ccagacgccc gctcgggggc cgccttcccc 420
cccacgcctg cccccgggca cgcgccctgc ccggtccctc gccccgcgcc acttccagtc 480
cgcagagaga tgccctccac gtttctgctt tctctgcagc ctctagattg ccagatgcga 540
ctgtgcgcct cgctgggtgt gttttccaca gccccttcct cctcggcgtg cagggctgac 600
atcaccgact gcgtttctgg tttggcgggt ggggagatgg ttccccgcag ggttctggta 660
cacctttgcc cccagggcta gcgccatttg ggggaggagg ttttcgttgt cgagaaagtt 720
ggatgctcct ggtaacccct ctaacaagag agttctgtag cgaggtggga ctgttctccc 780
cataaggtga cagtttctct tgcgaggtgt ggcagcgctt cctgttgtac aagacagatg 840
ttgccttggc gttacgtaaa tcatcgtgtc tccgtcattt aaagaaagcc aatttttagt 900
gattgaggta gaaagaaaga tccgtttata atttgtaaaa acaaattttc acccagaatc 960
aatatattgg aacaccattc ctactgttaa agttttcact taagagcata aacttcatca 1020
gctttctatt aggacttatt ttgtaattgg cttcttaggc atccttcttt aaaagagaaa 1080
tccacgttag ctctccttga ggtctcgagt tccctcggct ggaggcacag gttcagtgga 1140
gaccaaataa tgcaggtgaa ttaccttcgt ggccattact gcctcgaacg aagtgtgttt 1200
attaagaaca gttcttatgt cattcttaag gtaggtaggg ttaatactct ccagcaaatt 1260
tagtagatac tgtttgccag aaaagagagg agtatatata gtttgataat tattgtgtag 1320
ttttctgtgt acttaatttt tgcagttttg taacacttca tttgtaagat ggtaccattt 1380
tttcctggct tctgaatcat aggatagttt gacccagggc attagccatt gtaatggtag 1440
gcttttaaca aataactgcc taatttaaag gattggaaag catttgttac atggaaatga 1500
agttggtggc gtacccagtt gctgtatctt tattttttgt acttaattat ttctcataaa 1560
atggatataa aagcctgtta atccaaccca atgccattat gtaacgccag tttggagatt 1620
tcgagggcct ggagcagtgc gcaaggtgcg ctgaaagcct gcccctggat gagatcctta 1680
tcctggctgt gatggcagtg gcagtgggct gggtcccttg ttgagtggaa agggggactg 1740
cggtgtccat ggtgcagtag gtggcgctct tctgtcttag agcctgccgc cactgcagct 1800
ggtgccaagg ggccttctgc cactagaggt gccatttttc acatgatgaa cttagcctag 1860
ttagatcgca gagcaagctg taagccatgg gcccagaaaa gaaaacttga agtgagcaga 1920
tgttgtcact tccttgtaat cctttgttaa aatagcataa ggagttttct ttattctatt 1980
tactttcatt aaatgaccgt gctacaggtt tcaaaggatt ttaagattga tttttgaaag 2040
atcacaatat taaaagtata actggaaaat ctatgttgaa atcaaccaaa catgtcgtgg 2100
actgaatgat aaccttttct ttcttcatat aggctgatca gctgaccgaa gaacagattg 2160
ctgaattcaa ggaagccttc tccctatttg ataaagatgg cgatggcacc atcacaacaa 2220
aggaacttgg aactgtcatg aggtcactgg gtcagaaccc aacagaagct gaattgcagg 2280
atatgatcaa tgaagtggat gctgatggta atggcaccat tgacttcccc gaatttttga 2340
ctatgatggc tagaaaaatg aaagatacag atagtgaaga agaaatccgt gaggcattcc 2400
gagtctttga caaggatggc aatggttata tcagtgcagc agaactacgt cacgtcatga 2460
caaacttagg agaaaaacta acagatgaag aagtagatga aatgatcaga gaagcagata 2520
ttgatggaga cggacaagtc aactatgaag aattcgtaca gatgatgact gcaaaatgaa 2580
gacctacttt caactccttt ttcccccctc tagaagaatc aaattgaatc ttttacttac 2640
ctcttgccaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2692
<210>23
<211>2692
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(2238)..(2576)
<223>
<400>23
gcggaagcgg cggccgggcc gccctgcgcc cgggcggggc cctgcggtgt ggccgtggct 60
tgttcctgcc gctttcgcac cctgcggccc cccacccagt gcagcagtgc gggcgggcgt 120
gagcctcggt gcaccaggag gcccttcccg cgggaggcgc tgggctcgcg ctaattgggg 180
cggggggggg ggcggcgggg gaggagggaa ctggcgcgcg gcttggtttc cattagagac 240
gcaaagtttc tgctccggga ggaggcggcg gcgccgcggg ctcgtcgcct gggggagcag 300
aagcgggtgg gaggtgcggg tggccttggc cgcagccctg gtgcgcgggg gccgggggtg 360
gtgaccctcc tggccgagga ggggcggcgt ccagacgccc gctcgggggc cgccttcccc 420
cccacgcctg cccccgggca cgcgccctgc ccggtccctc gccccgcgcc acttccagtc 480
cgcagagaga tgccctccac gtttctgctt tctctgcagc ctctagattg ccagatgcga 540
ctgtgcgcct cgctgggtgt gttttccaca gccccttcct cctcggcgtg cagggctgac 600
atcaccgact gcgtttctgg tttggcgggt ggggagatgg ttccccgcag ggttctggta 660
cacctttgcc cccagggcta gcgccatttg ggggaggagg ttttcgttgt cgagaaagtt 720
ggatgctcct ggtaacccct ctaacaagag agttctgtag cgaggtggga ctgttctccc 780
cataaggtga cagtttctct tgcgaggtgt ggcagcgctt cctgttgtac aagacagatg 840
ttgccttggc gttacgtaaa tcatcgtgtc tccgtcattt aaagaaagcc aatttttagt 900
gattgaggta gaaagaaaga tccgtttata atttgtaaaa acaaattttc acccagaatc 960
aatatattgg aacaccattc ctactgttaa agttttcact taagagcata aacttcatca 1020
gctttctatt aggacttatt ttgtaattgg cttcttaggc atccttcttt aaaagagaaa 1080
tccacgttag ctctccttga ggtctcgagt tccctcggct ggaggcacag gttcagtgga 1140
gaccaaataa tgcaggtgaa ttaccttcgt ggccattact gcctcgaacg aagtgtgttt 1200
attaagaaca gttcttatgt cattcttaag gtaggtaggg ttaatactct ccagcaaatt 1260
tagtagatac tgtttgccag aaaagagagg agtatatata gtttgataat tattgtgtag 1320
ttttctgtgt acttaatttt tgcagttttg taacacttca tttgtaagat ggtaccattt 1380
tttcctggct tctgaatcat aggatagttt gacccagggc attagccatt gtaatggtag 1440
gcttttaaca aataactgcc taatttaaag gattggaaag catttgttac atggaaatga 1500
agttggtggc gtacccagtt gctgtatctt tattttttgt acttaattat ttctcataaa 1560
atggatataa aagcctgtta atccaaccca atgccattat gtaacgccag tttggagatt 1620
tcgagggcct ggagcagtgc gcaaggtgcg ctgaaagcct gcccctggat gagatcctta 1680
tcctggctgt gatggcagtg gcagtgggct gggtcccttg ttgagtggaa agggggactg 1740
cggtgtccat ggtgcagtag gtggcgctct tctgtcttag agcctgccgc cactgcagct 1800
ggtgccaagg ggccttctgc cactagaggt gccatttttc acatgatgaa cttagcctag 1860
ttagatcgca gagcaagctg taagccatgg gcccagaaaa gaaaacttga agtgagcaga 1920
tgttgtcact tccttgtaat cctttgttaa aatagcataa ggagttttct ttattctatt 1980
tactttcatt aaatgaccgt gctacaggtt tcaaaggatt ttaagattga tttttgaaag 2040
atcacaatat taaaagtata actggaaaat ctatgttgaa atcaaccaaa catgtcgtgg 2100
actgaatgat aaccttttct ttcttcatat aggctgatca gctgaccgaa gaacagattg 2160
ctgaattcaa ggaagccttc tccctatttg ataaagatgg cgatggcacc atcacaacaa 2220
aggaacttgg aactgtc atg agg tca ctg ggt cag aac cca aca gaa gct 2270
Met Arg Ser Leu Gly Gln Asn Pro Thr Glu Ala
1 5 10
gaa ttg cag gat atg atc aat gaa gtg gat gct gat ggt aat ggc acc 2318
Glu Leu Gln Asp Met Ile Asn Glu Val Asp Ala Asp Gly Asn Gly Thr
15 20 25
att gac ttc ccc gaa ttt ttg act atg atg gct aga aaa atg aaa gat 2366
Ile Asp Phe Pro Glu Phe Leu Thr Met Met Ala Arg Lys Met Lys Asp
30 35 40
aca gat agt gaa gaa gaa atc cgt gag gca ttc cga gtc ttt gac aag 2414
Thr Asp Ser Glu Glu Glu Ile Arg Glu Ala Phe Arg Val Phe Asp Lys
45 50 55
gat ggc aat ggt tat atc agt gca gca gaa cta cgt cac gtc atg aca 2462
Asp Gly Asn Gly Tyr Ile Ser Ala Ala Glu Leu Arg His Val Met Thr
60 65 70 75
aac tta gga gaa aaa cta aca gat gaa gaa gta gat gaa atg atc aga 2510
Asn Leu Gly Glu Lys Leu Thr Asp Glu Glu Val Asp Glu Met Ile Arg
80 85 90
gaa gca gat att gat gga gac gga caa gtc aac tat gaa gaa ttc gta 2558
Glu Ala Asp Ile Asp Gly Asp Gly Gln Val Asn Tyr Glu Glu Phe Val
95 100 105
cag atg atg act gca aaa tgaagaccta ctttcaactc ctttttcccc 2606
Gln Met Met Thr Ala Lys
110
cctctagaag aatcaaattg aatcttttac ttacctcttg ccaaaaaaaa aaaaaaaaaa 2666
aaaaaaaaaa aaaaaaaaaa aaaaaa 2692
<210>24
<211>113
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>24
Met Arg Ser Leu Gly Gln Asn Pro Thr Glu Ala Glu Leu Gln Asp Met
1 5 10 15
Ile Asn Glu Val Asp Ala Asp Gly Asn Gly Thr Ile Asp Phe Pro Glu
20 25 30
Phe Leu Thr Met Met Ala Arg Lys Met Lys Asp Thr Asp Ser Glu Glu
35 40 45
Glu Ile Arg Glu Ala Phe Arg Val Phe Asp Lys Asp Gly Asn Gly Tyr
50 55 60
Ile Ser Ala Ala Glu Leu Arg His Val Met Thr Asn Leu Gly Glu Lys
65 70 75 80
Leu Thr Asp Glu Glu Val Asp Glu Met Ile Arg Glu Ala Asp Ile Asp
85 90 95
Gly Asp Gly Gln Val Asn Tyr Glu Glu Phe Val Gln Met Met Thr Ala
100 105 110
Lys
<210>25
<211>2769
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>25
gtcttggtct tctggcctgg cggcgatcgt cggccagttt atccctcgga gttgcactgg 60
cagacacgcc gctactttgt agcgggtttc gggcgggcca cgcgtgcggc gacaggaacc 120
caaccccggc cgaccttggg ctccaggaat tcgttgtcta cgtctgcgga ggtgcggcag 180
cctcagtttt aagcgcagga aggcaataga ggctgtgctc tgaacctttc cctcacgatg 240
atcttctgcc tgttgaccat cctggtgtct ttcccatgtg gccctgtatg gttggcatgg 300
ttcctgtctt taggacttgt gatcaagtat atctgaaagt ttttagaaga aaagatgtgt 360
tgtaacctcc ctggaaaaag aagagacctt atgaagtact gctaaccacc tacatagtca 420
tcaaaataaa attcctgaat ttgtacaagc cacaggaagc tagattgaga tcattatatg 480
acaactggaa ggccaaggct atgggttacc tcaaattgag gaattttggc acctactcac 540
aggctccatg agcagatgaa gtagacagct ttactcagta tctcagacca agaacttcat 600
ctccatctcc aactagctga aacatcttcc ctcctcaacc tggaaaattc tctgacttag 660
aaatttaaac aaaaccctcc cctttcattg aatctccatt gtctggagtt tgcttgtttt 720
aatctagcct gttcctccac tatgggctcc ctttcaaact atgccctgct tcaactaacc 780
cttactgctt ttttgacaat tctagtacaa cctcagcacc tgcttgctcc agttttccgg 840
acactatcta tcttgactaa tcagtctaat tgctggttat gtgaacatct agataatgca 900
gaacaacccg aactagtttt tgttcctgcc agtgcaagca cctggtggac ctattctgga 960
caatggatgt atgaaagggt gtggtatcca caagcagaag tacagaatca ctctacttcc 1020
tcctatcgta aagtgacttg gcactgggaa gcctccatgg aagctcaagg tctatccttt 1080
gctcaagtaa ggttattgga gggaaatttt tctctttgcg tagaaaataa aaatggcagt 1140
ggacccttcc taggtaatat acctaaacaa tactgtaatc aaatactatg gtttgattct 1200
acagatggca ccttcatgcc ctctatagat gttacaaatg aatccaggaa cgatgatgat 1260
gatacaagtg tttgcctagg cactagacaa tgttcctggt ttgcaggttg cacaaaccgg 1320
acctggaaca gctcagctgt tcccttgatt ggtctgccca atacccaaga ctacaaatgg 1380
gtagatcgaa attctggatt gacctggtca ggtaatgaca cctgtctcta tagctgccaa 1440
aaccaaacca aaggccttct gtaccagcta tttcgcaacc tattttgctc ttatggcctg 1500
acagaggcac atgggaaatg gagatgtgca gatgccagca taactaatga caaaggtcat 1560
gatggacacc ggacccccac ctggtggctc acaggttcca atctgacctt gtctgtgaac 1620
aactctggcc tctttttttt gtgcggcaat ggggtgtaca aagggtttcc acctaaatgg 1680
tctgggcgat gtggacttgg gtatcttgta ccttccctca ccagatacct caccttaaat 1740
gctagccaaa ttacaaacct gagatccttc attcataaag taacaccgca tagatgcacc 1800
caaggagaca cagacaatcc acctctgtat tgcaacccca aggacaattc aacaataagg 1860
gccctttttc caagtttggg aacttatgat ttagaaaagg caattctaaa catttccaaa 1920
gcaatggaac aggaattcag tgccactaag cagaccttgg aagcacacca atcaaaagtt 1980
agcagtttag cctctgcatc ccgaaaggat catgtcttgg atataccgac cacccaacga 2040
caaacggctt gtggaactgt tggcaaacag tgttgcctct atataaatta ttcggaagaa 2100
ataaagtcta atatacagcg tctccacgaa gcatccgaga acctgaagaa tgtaccgtta 2160
cttgattggc aaggcatatt tgcaaaagtg ggagactggt tcagatcatg gggctatgtg 2220
cttttaattg ttcttttctg cttattcatc tttgttttaa tctatgttcg tgtctttcgc 2280
aaatctcgca gatcccttaa ctcccaacct ctgaacctag ccttatctcc acagcaatca 2340
gcacagctcc ttgtcagtga aacttcatgt caagtttcaa atagggcaat gaagggacta 2400
acaacccatc aatatgacac aagtctactt tgagaatatt tgaacaaaca gcagctgcag 2460
acaaaaagcc ttagctaaac tttgatgagt aaagcaggtc ttaccgagaa ttcagctgcc 2520
aaaaccctcc tctgagtgtt cctcttataa gggcacttag cactaggacc tcccaaggta 2580
ttgtaaataa gccttatcag aactttttgt agtttcattc tgaagcctta agacacacac 2640
cataaagctg atctgtaaac ccttacccct tgctgttcag agagctactc tttgtagtgt 2700
tcttgcatgc atatataata aatgtttttt ctattgatct gttaaaaaaa aaaaaaaaaa 2760
aaaaaaaaa 2769
<210>26
<211>2769
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(742)..(2430)
<223>
<400>26
gtcttggtct tctggcctgg cggcgatcgt cggccagttt atccctcgga gttgcactgg 60
cagacacgcc gctactttgt agcgggtttc gggcgggcca cgcgtgcggc gacaggaacc 120
caaccccggc cgaccttggg ctccaggaat tcgttgtcta cgtctgcgga ggtgcggcag 180
cctcagtttt aagcgcagga aggcaataga ggctgtgctc tgaacctttc cctcacgatg 240
atcttctgcc tgttgaccat cctggtgtct ttcccatgtg gccctgtatg gttggcatgg 300
ttcctgtctt taggacttgt gatcaagtat atctgaaagt ttttagaaga aaagatgtgt 360
tgtaacctcc ctggaaaaag aagagacctt atgaagtact gctaaccacc tacatagtca 420
tcaaaataaa attcctgaat ttgtacaagc cacaggaagc tagattgaga tcattatatg 480
acaactggaa ggccaaggct atgggttacc tcaaattgag gaattttggc acctactcac 540
aggctccatg agcagatgaa gtagacagct ttactcagta tctcagacca agaacttcat 600
ctccatctcc aactagctga aacatcttcc ctcctcaacc tggaaaattc tctgacttag 660
aaatttaaac aaaaccctcc cctttcattg aatctccatt gtctggagtt tgcttgtttt 720
aatctagcct gttcctccac t atg ggc tcc ctt tca aac tat gcc ctg ctt 771
Met Gly Ser Leu Ser Asn Tyr Ala Leu Leu
1 5 10
caa cta acc ctt act gct ttt ttg aca att cta gta caa cct cag cac 819
Gln Leu Thr Leu Thr Ala Phe Leu Thr Ile Leu Val Gln Pro Gln His
15 20 25
ctg ctt gct cca gtt ttc cgg aca cta tct atc ttg act aat cag tct 867
Leu Leu Ala Pro Val Phe Arg Thr Leu Ser Ile Leu Thr Asn Gln Ser
30 35 40
aat tgc tgg tta tgt gaa cat cta gat aat gca gaa caa ccc gaa cta 915
Asn Cys Trp Leu Cys Glu His Leu Asp Asn Ala Glu Gln Pro Glu Leu
45 50 55
gtt ttt gtt cct gcc agt gca agc acc tgg tgg acc tat tct gga caa 963
Val Phe Val Pro Ala Ser Ala Ser Thr Trp Trp Thr Tyr Ser Gly Gln
60 65 70
tgg atg tat gaa agg gtg tgg tat cca caa gca gaa gta cag aat cac 1011
Trp Met Tyr Glu Arg Val Trp Tyr Pro Gln Ala Glu Val Gln Asn His
75 80 85 90
tct act tcc tcc tat cgt aaa gtg act tgg cac tgg gaa gcc tcc atg 1059
Ser Thr Ser Ser Tyr Arg Lys Val Thr Trp His Trp Glu Ala Ser Met
95 100 105
gaa gct caa ggt cta tcc ttt gct caa gta agg tta ttg gag gga aat 1107
Glu Ala Gln Gly Leu Ser Phe Ala Gln Val Arg Leu Leu Glu Gly Asn
110 115 120
ttt tct ctt tgc gta gaa aat aaa aat ggc agt gga ccc ttc cta ggt 1155
Phe Ser Leu Cys Val Glu Asn Lys Asn Gly Ser Gly Pro Phe Leu Gly
125 130 135
aat ata cct aaa caa tac tgt aat caa ata cta tgg ttt gat tct aca 1203
Asn Ile Pro Lys Gln Tyr Cys Asn Gln Ile Leu Trp Phe Asp Ser Thr
140 145 150
gat ggc acc ttc atg ccc tct ata gat gtt aca aat gaa tcc agg aac 1251
Asp Gly Thr Phe Met Pro Ser Ile Asp Val Thr Asn Glu Ser Arg Asn
155 160 165 170
gat gat gat gat aca agt gtt tgc cta ggc act aga caa tgt tcc tgg 1299
Asp Asp Asp Asp Thr Ser Val Cys Leu Gly Thr Arg Gln Cys Ser Trp
175 180 185
ttt gca ggt tgc aca aac cgg acc tgg aac agc tca gct gtt ccc ttg 1347
Phe Ala Gly Cys Thr Asn Arg Thr Trp Asn Ser Ser Ala Val Pro Leu
190 195 200
att ggt ctg ccc aat acc caa gac tac aaa tgg gta gat cga aat tct 1395
Ile Gly Leu Pro Asn Thr Gln Asp Tyr Lys Trp Val Asp Arg Asn Ser
205 210 215
gga ttg acc tgg tca ggt aat gac acc tgt ctc tat agc tgc caa aac 1443
Gly Leu Thr Trp Ser Gly Asn Asp Thr Cys Leu Tyr Ser Cys Gln Asn
220 225 230
caa acc aaa ggc ctt ctg tac cag cta ttt cgc aac cta ttt tgc tct 1491
Gln Thr Lys Gly Leu Leu Tyr Gln Leu Phe Arg Asn Leu Phe Cys Ser
235 240 245 250
tat ggc ctg aca gag gca cat ggg aaa tgg aga tgt gca gat gcc agc 1539
Tyr Gly Leu Thr Glu Ala His Gly Lys Trp Arg Cys Ala Asp Ala Ser
255 260 265
ata act aat gac aaa ggt cat gat gga cac cgg acc ccc acc tgg tgg 1587
Ile Thr Asn Asp Lys Gly His Asp Gly His Arg Thr Pro Thr Trp Trp
270 275 280
ctc aca ggt tcc aat ctg acc ttg tct gtg aac aac tct ggc ctc ttt 1635
Leu Thr Gly Ser Asn Leu Thr Leu Ser Val Asn Asn Ser Gly Leu Phe
285 290 295
ttt ttg tgc ggc aat ggg gtg tac aaa ggg ttt cca cct aaa tgg tct 1683
Phe Leu Cys Gly Asn Gly Val Tyr Lys Gly Phe Pro Pro Lys Trp Ser
300 305 310
ggg cga tgt gga ctt ggg tat ctt gta cct tcc ctc acc aga tac ctc 1731
Gly Arg Cys Gly Leu Gly Tyr Leu Val Pro Ser Leu Thr Arg Tyr Leu
315 320 325 330
acc tta aat gct agc caa att aca aac ctg aga tcc ttc att cat aaa 1779
Thr Leu Asn Ala Ser Gln Ile Thr Asn Leu Arg Ser Phe Ile His Lys
335 340 345
gta aca ccg cat aga tgc acc caa gga gac aca gac aat cca cct ctg 1827
Val Thr Pro His Arg Cys Thr Gln Gly Asp Thr Asp Asn Pro Pro Leu
350 355 360
tat tgc aac ccc aag gac aat tca aca ata agg gcc ctt ttt cca agt 1875
Tyr Cys Asn Pro Lys Asp Asn Ser Thr Ile Arg Ala Leu Phe Pro Ser
365 370 375
ttg gga act tat gat tta gaa aag gca att cta aac att tcc aaa gca 1923
Leu Gly Thr Tyr Asp Leu Glu Lys Ala Ile Leu Asn Ile Ser Lys Ala
380 385 390
atg gaa cag gaa ttc agt gcc act aag cag acc ttg gaa gca cac caa 1971
Met Glu Gln Glu Phe Ser Ala Thr Lys Gln Thr Leu Glu Ala His Gln
395 400 405 410
tca aaa gtt agc agt tta gcc tct gca tcc cga aag gat cat gtc ttg 2019
Ser Lys Val Ser Ser Leu Ala Ser Ala Ser Arg Lys Asp His Val Leu
415 420 425
gat ata ccg acc acc caa cga caa acg gct tgt gga act gtt ggc aaa 2067
Asp Ile Pro Thr Thr Gln Arg Gln Thr Ala Cys Gly Thr Val Gly Lys
430 435 440
cag tgt tgc ctc tat ata aat tat tcg gaa gaa ata aag tct aat ata 2115
Gln Cys Cys Leu Tyr Ile Asn Tyr Ser Glu Glu Ile Lys Ser Asn Ile
445 450 455
cag cgt ctc cac gaa gca tcc gag aac ctg aag aat gta ccg tta ctt 2163
Gln Arg Leu His Glu Ala Ser Glu Asn Leu Lys Asn Val Pro Leu Leu
460 465 470
gat tgg caa ggc ata ttt gca aaa gtg gga gac tgg ttc aga tca tgg 2211
Asp Trp Gln Gly Ile Phe Ala Lys Val Gly Asp Trp Phe Arg Ser Trp
475 480 485 490
ggc tat gtg ctt tta att gtt ctt ttc tgc tta ttc atc ttt gtt tta 2259
Gly Tyr Val Leu Leu Ile Val Leu Phe Cys Leu Phe Ile Phe Val Leu
495 500 505
atc tat gtt cgt gtc ttt cgc aaa tct cgc aga tcc ctt aac tcc caa 2307
Ile Tyr Val Arg Val Phe Arg Lys Ser Arg Arg Ser Leu Asn Ser Gln
510 515 520
cct ctg aac cta gcc tta tct cca cag caa tca gca cag ctc ctt gtc 2355
Pro Leu Asn Leu Ala Leu Ser Pro Gln Gln Ser Ala Gln Leu Leu Val
525 530 535
agt gaa act tca tgt caa gtt tca aat agg gca atg aag gga cta aca 2403
Ser Glu Thr Ser Cys Gln Val Ser Asn Arg Ala Met Lys Gly Leu Thr
540 545 550
acc cat caa tat gac aca agt cta ctt tgagaatatt tgaacaaaca 2450
Thr His Gln Tyr Asp Thr Ser Leu Leu
555 560
gcagctgcag acaaaaagcc ttagctaaac tttgatgagt aaagcaggtc ttaccgagaa 2510
ttcagctgcc aaaaccctcc tctgagtgtt cctcttataa gggcacttag cactaggacc 2570
tcccaaggta ttgtaaataa gccttatcag aactttttgt agtttcattc tgaagcctta 2630
agacacacac cataaagctg atctgtaaac ccttacccct tgctgttcag agagctactc 2690
tttgtagtgt tcttgcatgc atatataata aatgtttttt ctattgatct gttaaaaaaa 2750
aaaaaaaaaa aaaaaaaaa 2769
<210>27
<21l>563
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>27
Met Gly Ser Leu Ser Asn Tyr Ala Leu Leu Gln Leu Thr Leu Thr Ala
1 5 10 15
Phe Leu Thr Ile Leu Val Gln Pro Gln His Leu Leu Ala Pro Val Phe
20 25 30
Arg Thr Leu Ser Ile Leu Thr Asn Gln Ser Asn Cys Trp Leu Cys Glu
35 40 45
His Leu Asp Asn Ala Glu Gln Pro Glu Leu Val Phe Val Pro Ala Ser
50 55 60
Ala Ser Thr Trp Trp Thr Tyr Ser Gly Gln Trp Met Tyr Glu Arg Val
65 70 75 80
Trp Tyr Pro Gln Ala Glu Val Gln Asn His Ser Thr Ser Ser Tyr Arg
85 90 95
Lys Val Thr Trp His Trp Glu Ala Ser Met Glu Ala Gln Gly Leu Ser
100 105 110
Phe Ala Gln Val Arg Leu Leu Glu Gly Asn Phe Ser Leu Cys Val Glu
115 120 125
Asn Lys Asn Gly Ser Gly Pro Phe Leu Gly Asn Ile Pro Lys Gln Tyr
130 135 140
Cys Asn Gln Ile Leu Trp Phe Asp Ser Thr Asp Gly Thr Phe Met Pro
145 150 155 160
Ser Ile Asp Val Thr Asn Glu Ser Arg Asn Asp Asp Asp Asp Thr Ser
165 170 175
Val Cys Leu Gly Thr Arg Gln Cys Ser Trp Phe Ala Gly Cys Thr Asn
180 185 190
Arg Thr Trp Asn Ser Ser Ala Val Pro Leu Ile Gly Leu Pro Asn Thr
195 200 205
Gln Asp Tyr Lys Trp Val Asp Arg Asn Ser Gly Leu Thr Trp Ser Gly
210 215 220
Asn Asp Thr Cys Leu Tyr Ser Cys Gln Asn Gln Thr Lys Gly Leu Leu
225 230 235 240
Tyr Gln Leu Phe Arg Asn Leu Phe Cys Ser Tyr Gly Leu Thr Glu Ala
245 250 255
His Gly Lys Trp Arg Cys Ala Asp Ala Ser Ile Thr Asn Asp Lys Gly
260 265 270
His Asp Gly His Arg Thr Pro Thr Trp Trp Leu Thr Gly Ser Asn Leu
275 280 285
Thr Leu Ser Val Asn Asn Ser Gly Leu Phe Phe Leu Cys Gly Asn Gly
290 295 300
Val Tyr Lys Gly Phe Pro Pro Lys Trp Ser Gly Arg Cys Gly Leu Gly
305 310 315 320
Tyr Leu Val Pro Ser Leu Thr Arg Tyr Leu Thr Leu Asn Ala Ser Gln
325 330 335
Ile Thr Asn Leu Arg Ser Phe Ile His Lys Val Thr Pro His Arg Cys
340 345 350
Thr Gln Gly Asp Thr Asp Asn Pro Pro Leu Tyr Cys Asn Pro Lys Asp
355 360 365
Asn Ser Thr Ile Arg Ala Leu Phe Pro Ser Leu Gly Thr Tyr Asp Leu
370 375 380
Glu Lys Ala Ile Leu Asn Ile Ser Lys Ala Met Glu Gln Glu Phe Ser
385 390 395 400
Ala Thr Lys Gln Thr Leu Glu Ala His Gln Ser Lys Val Ser Ser Leu
405 410 415
Ala Ser Ala Ser Arg Lys Asp His Val Leu Asp Ile Pro Thr Thr Gln
420 425 430
Arg Gln Thr Ala Cys Gly Thr Val Gly Lys Gln Cys Cys Leu Tyr Ile
435 440 445
Asn Tyr Ser Glu Glu Ile Lys Ser Asn Ile Gln Arg Leu His Glu Ala
450 455 460
Ser Glu Asn Leu Lys Asn Val Pro Leu Leu Asp Trp Gln Gly Ile Phe
465 470 475 480
Ala Lys Val Gly Asp Trp Phe Arg Ser Trp Gly Tyr Val Leu Leu Ile
485 490 495
Val Leu Phe Cys Leu Phe Ile Phe Val Leu Ile Tyr Val Arg Val Phe
500 505 510
Arg Lys Ser Arg Arg Ser Leu Asn Ser Gln Pro Leu Asn Leu Ala Leu
515 520 525
Ser Pro Gln Gln Ser Ala Gln Leu Leu Val Ser Glu Thr Ser Cys Gln
530 535 540
Val Ser Asn Arg Ala Met Lys Gly Leu Thr Thr His Gln Tyr Asp Thr
545 550 555 560
Ser Leu Leu
<210>28
<211>3226
<212>DNA
<213〉homo sapiens (Homo sapiens)
<400>28
gggagggcag actctgggcg ccactcccgg gccggtcatg aacgggccgg cggacggcga 60
agtggactac aaaaaaaaat accggaatct gaagcggaag ctcaagttcc tcatctacga 120
gcacgagtgc ttccaggagg agctgaggaa agcgcaaagg aaattactga aggtgtcccg 180
ggacaagagt ttcctcctag accgacttct gcagtacgag aacgtggatg aagactcttc 240
ggactcagat gccactgcat catcagataa cagcgagacg gaggggacac ccaagttgtc 300
tgacacaccg gcccctaaga ggaagagaag ccctccgctg gggggcgccc cctctccctc 360
cagcctctcc ctgcctcctt caacagggtt tccccttcag gcctccgggg tcccctcccc 420
atacctgagc tcggaacggg gccaggcctg actgaggaga gcaaagccca ggacagcatc 480
ctgctgctgc ccggcccttc tgtgctcggg agccccggga gccgcactca tcaccatctc 540
ttttgttttt ccatcctcct tctgtttgca tttcttcccc caccctcacc ccggtccatt 600
ccgcctccca tctccatccc cgctcccgcc cgcagctggc ctcctcccgc taccccccat 660
tcccttctga ctacctggcc ctgcagctgc ccgagcccag tcccctgagg cccaagcggg 720
agaaacggcc ccgcctgccc cggaaactca aggtaccctg acgtgggggt gctagggagg 780
ggcaggacgg caggaggaca gtcacctgag ggaggctgaa ggcgggggcc tgtcagagaa 840
ccatgaacag ttaatttggg gacccagtca gcacttagca ctgaggggtg gatcacagaa 900
gtctcggctt acaggcttgt atggagacaa tcagggcaga accagccttg gaggacccgg 960
tgtgcagatg ccagggatcc cgccctttca tggctgcagt gtagcggggc caggctcatt 1020
ttcccagggg ggcgtgttgt gtgatgccag gtagccccag accgggtcag gattatggga 1080
tctagagtca agtcaagact gcctgttaga aaccacgtgg ccttgagcag gtctctgcta 1140
ccctctaggc ctcctaggct tggcacctat agggcgagtg gtcctactcg atgtgaccag 1200
caagcgcccc tggagcgcct cctgttacac ggcagtgcac aaagcagacc agtgcctgcc 1260
ctcacagagc tcacagtcta gcaagatagg cagaaaacac accagaaaag taggtacttg 1320
tggagaagaa cagagcgagg tccagagcat ggggacgcca gggggacgag gctgacactt 1380
agggcccagc agtctgggat gttcttgatc agagacttac aggaaatggc agcaagctgt 1440
gtggctcctg ggcagtgttt ctgtcgggca gagtctgtgt ttgggagaaa agtaagcagg 1500
gaattgggtc ccggagcagg tcagaggggg agctcatgag gtgccagtgt gcaggattcg 1560
ctgtgaatga agccttggag acagcagttc cctggcgggg cgcaggttgc aggtgtggag 1620
ggggagtgat ctaattgcat cttaacaaaa ttgcagacac tggtggtcag agaacagact 1680
gagcggtgga gtgagttggg acgggagtga ggaggccacc acggtaaacc aggccaaggg 1740
cagagggtcc agagggagct gcggacccat ttcagagaat gagcatggga gttcctggag 1800
gacctggtgt gggctgtgcg ggagagaggc caggatgcct ccagggcttt agtctgagca 1860
cgagtggagt ctccctccct ggagatggga gggctgtggg accacaggct tggaggaaaa 1920
ctgagtctgg ccgcggatgt gtcagatgcc atctggaaag gcagctagat agcggcccgt 1980
gaggggctgc gcatttggaa gccgccaggc tggcggtaga tgcaagcctt gggagagatg 2040
gggatgggct gaggggcaga gcggagtggg gaccaactgg gcggctccca gggttctgga 2100
gccagaagca gaatgagagg ccgcatttgc ggtggtctgg agtacaggat ctggagctct 2160
aatcccaact ctgccgtttt ctccgtgtga ccttggccct gtgaggcttc acctcttgag 2220
cctgagaagc agaggggagc gggagtccct gaagggccag gggagtgagg agatggaagg 2280
aagggagtcc aagcagagga aggatagctg tgaagacaga agcagtggcg gcattgtgcg 2340
gagaatgtga gtgaagggat gaaaatcgct cggcccgtgc ctggccccta gtctgtgttt 2400
tagagcgcgc gctctggctg ccgtgcggag gagctggatc tgggagaggc tgcgggcagg 2460
gagtccagtt aggaggctgg gaccgcagcc cagatggcgg tgggaccccc cgactgccct 2520
gtgggagggc cgctgacctt ccctggccgg ggttctgggg ctggggtcgg acaaaaccct 2580
taaccccctt ccacccccta agatgccccc ccccacgatc ctgagcacgg tccctcggca 2640
gatgttcagc gatgcaggta gcggggacga tgccttggat ggagacgatg acctggtgat 2700
cgacatcccg gagtgaccgt gacatcacgc catgcccacc acggccccgc ccggcgccct 2760
ccccgtgcca gcacacacga gtccagcttc ctcggaggtg tttattgatg cccagctgcc 2820
atgctccggc cactgacaca accagaaaag gcgtaaacat gcacgggtgt cccccaggag 2880
ggtggcaggg gccctgcctt caaaccccgg ccccctccag gggacagtta tttaaacgag 2940
tggccgggag catctgccac ctgctgggga ggcagagacc ctgcaatggc cacctcttta 3000
aaagggcagc tgtacagggc taggtttttt caatgaagtt tctgtattaa aggagtggct 3060
ctggataaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3120
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3180
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 3226
<210>29
<211>3226
<212>DNA
<213〉homo sapiens (Homo sapiens)
<220>
<221>CDS
<222>(38)..(448)
<223>
<400>29
gggagggcag actctgggcg ccactcccgg gccggtc atg aac ggg ccg gcg gac 55
Met Asn Gly Pro Ala Asp
1 5
ggc gaa gtg gac tac aaa aaa aaa tac cgg aat ctg aag cgg aag ctc 103
Gly Glu Val Asp Tyr Lys Lys Lys Tyr Arg Asn Leu Lys Arg Lys Leu
10 15 20
aag ttc ctc atc tac gag cac gag tgc ttc cag gag gag ctg agg aaa 151
Lys Phe Leu Ile Tyr Glu His Glu Cys Phe Gln Glu Glu Leu Arg Lys
25 30 35
gcg caa agg aaa tta ctg aag gtg tcc cgg gac aag agt ttc ctc cta 199
Ala Gln Arg Lys Leu Leu Lys Val Ser Arg Asp Lys Ser Phe Leu Leu
40 45 50
gac cga ctt ctg cag tac gag aac gtg gat gaa gac tct tcg gac tca 247
Asp Arg Leu Leu Gln Tyr Glu Asn Val Asp Glu Asp Ser Ser Asp Ser
55 60 65 70
gat gcc act gca tca tca gat aac agc gag acg gag ggg aca ccc aag 295
Asp Ala Thr Ala Ser Ser Asp Asn Ser Glu Thr Glu Gly Thr Pro Lys
75 80 85
ttg tct gac aca ccg gcc cct aag agg aag aga agc cct ccg ctg ggg 343
Leu Ser Asp Thr Pro Ala Pro Lys Arg Lys Arg Ser Pro Pro Leu Gly
90 95 100
ggc gcc ccc tct ccc tcc agc ctc tcc ctg cct cct tca aca ggg ttt 391
Gly Ala Pro Ser Pro Ser Ser Leu Ser Leu Pro Pro Ser Thr Gly Phe
105 110 115
ccc ctt cag gcc tcc ggg gtc ccc tcc cca tac ctg agc tcg gaa cgg 439
Pro Leu Gln Ala Ser Gly Val Pro Ser Pro Tyr Leu Ser Ser Glu Arg
120 125 130
ggc cag gcc tgactgagga gagcaaagcc caggacagca tcctgctgct 488
Gly Gln Ala
135
gcccggccct tctgtgctcg ggagccccgg gagccgcact catcaccatc tcttttgttt 548
ttccatcctc cttctgtttg catttcttcc cccaccctca ccccggtcca ttccgcctcc 608
catctccatc cccgctcccg cccgcagctg gcctcctccc gctacccccc attcccttct 668
gactacctgg ccctgcagct gcccgagccc agtcccctga ggcccaagcg ggagaaacgg 728
ccccgcctgc cccggaaact caaggtaccc tgacgtgggg gtgctaggga ggggcaggac 788
ggcaggagga cagtcacctg agggaggctg aaggcggggg cctgtcagag aaccatgaac 848
agttaatttg gggacccagt cagcacttag cactgagggg tggatcacag aagtctcggc 908
ttacaggctt gtatggagac aatcagggca gaaccagcct tggaggaccc ggtgtgcaga 968
tgccagggat cccgcccttt catggctgca gtgtagcggg gccaggctca ttttcccagg 1028
ggggcgtgtt gtgtgatgcc aggtagcccc agaccgggtc aggattatgg gatctagagt 1088
caagtcaaga ctgcctgtta gaaaccacgt ggccttgagc aggtctctgc taccctctag 1148
gcctcctagg cttggcacct atagggcgag tggtcctact cgatgtgacc agcaagcgcc 1208
cctggagcgc ctcctgttac acggcagtgc acaaagcaga ccagtgcctg ccctcacaga 1268
gctcacagtc tagcaagata ggcagaaaac acaccagaaa agtaggtact tgtggagaag 1328
aacagagcga ggtccagagc atggggacgc cagggggacg aggctgacac ttagggccca 1388
gcagtctggg atgttcttga tcagagactt acaggaaatg gcagcaagct gtgtggctcc 1448
tgggcagtgt ttctgtcggg cagagtctgt gtttgggaga aaagtaagca gggaattggg 1508
tcccggagca ggtcagaggg ggagctcatg aggtgccagt gtgcaggatt cgctgtgaat 1568
gaagccttgg agacagcagt tccctggcgg ggcgcaggtt gcaggtgtgg agggggagtg 1628
atctaattgc atcttaacaa aattgcagac actggtggtc agagaacaga ctgagcggtg 1688
gagtgagttg ggacgggagt gaggaggcca ccacggtaaa ccaggccaag ggcagagggt 1748
ccagagggag ctgcggaccc atttcagaga atgagcatgg gagttcctgg aggacctggt 1808
gtgggctgtg cgggagagag gccaggatgc ctccagggct ttagtctgag cacgagtgga 1868
gtctccctcc ctggagatgg gagggctgtg ggaccacagg cttggaggaa aactgagtct 1928
ggccgcggat gtgtcagatg ccatctggaa aggcagctag atagcggccc gtgaggggct 1988
gcgcatttgg aagccgccag gctggcggta gatgcaagcc ttgggagaga tggggatggg 2048
ctgaggggca gagcggagtg gggaccaact gggcggctcc cagggttctg gagccagaag 2108
cagaatgaga ggccgcattt gcggtggtct ggagtacagg atctggagct ctaatcccaa 2168
ctctgccgtt ttctccgtgt gaccttggcc ctgtgaggct tcacctcttg agcctgagaa 2228
gcagagggga gcgggagtcc ctgaagggcc aggggagtga ggagatggaa ggaagggagt 2288
ccaagcagag gaaggatagc tgtgaagaca gaagcagtgg cggcattgtg cggagaatgt 2348
gagtgaaggg atgaaaatcg ctcggcccgt gcctggcccc tagtctgtgt tttagagcgc 2408
gcgctctggc tgccgtgcgg aggagctgga tctgggagag gctgcgggca gggagtccag 2468
ttaggaggct gggaccgcag cccagatggc ggtgggaccc cccgactgcc ctgtgggagg 2528
gccgctgacc ttccctggcc ggggttctgg ggctggggtc ggacaaaacc cttaaccccc 2588
ttccaccccc taagatgccc ccccccacga tcctgagcac ggtccctcgg cagatgttca 2648
gcgatgcagg tagcggggac gatgccttgg atggagacga tgacctggtg atcgacatcc 2708
cggagtgacc gtgacatcac gccatgccca ccacggcccc gcccggcgcc ctccccgtgc 2768
cagcacacac gagtccagct tcctcggagg tgtttattga tgcccagctg ccatgctccg 2828
gccactgaca caaccagaaa aggcgtaaac atgcacgggt gtcccccagg agggtggcag 2888
gggccctgcc ttcaaacccc ggccccctcc aggggacagt tatttaaacg agtggccggg 2948
agcatctgcc acctgctggg gaggcagaga ccctgcaatg gccacctctt taaaagggca 3008
gctgtacagg gctaggtttt ttcaatgaag tttctgtatt aaaggagtgg ctctggataa 3068
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3128
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3188
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 3226
<210>30
<211>137
<212>PRT
<213〉homo sapiens (Homo sapiens)
<400>30
Met Asn Gly Pro Ala Asp Gly Glu Val Asp Tyr Lys Lys Lys Tyr Arg
1 5 10 15
Asn Leu Lys Arg Lys Leu Lys Phe Leu Ile Tyr Glu His Glu Cys Phe
20 25 30
Gln Glu Glu Leu Arg Lys Ala Gln Arg Lys Leu Leu Lys Val Ser Arg
35 40 45
Asp Lys Ser Phe Leu Leu Asp Arg Leu Leu Gln Tyr Glu Asn Val Asp
50 55 60
Glu Asp Ser Ser Asp Ser Asp Ala Thr Ala Ser Ser Asp Asn Ser Glu
65 70 75 80
Thr Glu Gly Thr Pro Lys Leu Ser Asp Thr Pro Ala Pro Lys Arg Lys
85 90 95
Arg Ser Pro Pro Leu Gly Gly Ala Pro Ser Pro Ser Ser Leu Ser Leu
100 105 110
Pro Pro Ser Thr Gly Phe Pro Leu Gln Ala Ser Gly Val Pro Ser Pro
115 120 125
Tyr Leu Ser Ser Glu Arg Gly Gln Ala
130 135
<210>31
<211>18
<212>DNA
<213〉primer
<400>31
ggcacctcag caaccagt 18
<210>32
<211>19
<212>DNA
<213〉primer
<400>32
cgaaactaac taaacccga 19
<210>33
<211>21
<212>DNA
<213〉primer
<400>33
cagtcttcgc tcactacagc c 21
<210>34
<211>20
<212>DNA
<213〉primer
<400>34
ccaatccaaa atgaccccgt 20
<210>35
<211>21
<212>DNA
<213〉primer
<400>35
aagatgaatc cgttgatctc g 21
<210>36
<211>20
<212>DNA
<213〉primer
<400>36
tcgtttgaca ggtcttccct 20
<210>37
<211>20
<212>DNA
<213〉primer
<400>37
aagccctaca gtgcagagga 20
<210>38
<211>20
<212>DNA
<213〉primer
<400>38
gagaaccaca aagtacgacg 20
<210>39
<211>21
<212>DNA
<213〉primer
<400>39
gaagaggagg aggaagagga g 21
<210>40
<211>20
<212>DNA
<213〉primer
<400>40
gtggaaggga cactttgttc 20
<210>41
<211>18
<212>DNA
<213〉primer
<400>41
ctttcagctc ggctgctc 18
<210>42
<211>21
<212>DNA
<213〉primer
<400>42
gtacctcata tcgcagtagg g 21
<210>43
<211>18
<212>DNA
<213〉primer
<400>43
gagggtgcgg aggacaac 18
<210>44
<211>20
<212>DNA
<213〉primer
<400>44
caaggacggt gacatgaggt 20
<210>45
<211>18
<212>DNA
<213〉primer
<400>45
cttgttcctg ccgctttc 18
<210>46
<211>22
<212>DNA
<213〉primer
<400>46
tgtctactac tgacgtttta ct 22
<210>47
<211>19
<212>DNA
<213〉primer
<400>47
atcgtcggcc agtttatcc 19
<210>48
<211>20
<212>DNA
<213〉primer
<400>48
aatggggaac gacaagtctc 20
<210>49
<211>18
<212>DNA
<213〉primer
<400>49
gggagggcag actctggg 18
<210>50
<211>18
<212>DNA
<213〉primer
<400>50
agtgcggtac gggtggtg 18

Claims (5)

1. isolating polynucleotide is characterized in that, it is selected from down group:
(a) coding has the polynucleotide of the polypeptide of the function that suppresses hepatoma cell line 7721 growths, and described polypeptide has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,18,21,24,27 or 30;
(b) with the complete complementary polynucleotide of polynucleotide (a).
2. polynucleotide as claimed in claim 1 is characterized in that, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:3,6,9,12,15,21,27 or 30.
3. polynucleotide as claimed in claim 1 is characterized in that, the sequence of these polynucleotide is selected from down group:
SEQ ID NO:2,5,8,11,14,17,20,23,26,29 coding region sequence or full length sequence.
4. a carrier is characterized in that, it contains the described polynucleotide of claim 1.
5. a genetically engineered host cell is characterized in that, it is a kind of host cell that is selected from down group:
(a) host cell that transforms or transduce with the described carrier of claim 4;
(b) host cell that transforms or transduce with the described polynucleotide of claim 1.
CNB021454353A 2002-08-07 2002-11-20 Novel human protein with cancer-inhibiting function and coding sequence thereof Expired - Fee Related CN1222616C (en)

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CNB021454353A CN1222616C (en) 2002-11-20 2002-11-20 Novel human protein with cancer-inhibiting function and coding sequence thereof
PCT/CN2003/000639 WO2004014946A1 (en) 2002-08-07 2003-08-07 A novel homo protein with cancer suppressing function and its coding sequence
AU2003255098A AU2003255098A1 (en) 2002-08-07 2003-08-07 A novel homo protein with cancer suppressing function and its coding sequence

Applications Claiming Priority (1)

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CA3066894A1 (en) * 2017-06-22 2018-12-27 Institut Gustave Roussy Human endogenous retroviral protein

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