CN1199998C - Human protein with suppression to cancer cell growth and its coding sequence - Google Patents

Abstract

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

Description

New people's albumen and encoding sequence thereof with anticancer growth 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:2,5,8,11,14,17,20,23,26,29,32; 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:2,5,8,11,14,17,20,23,26,29,32.

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:2,5,8,11,14,17,20,23,26,29,32.More preferably, the sequence of these polynucleotide is selected from down group: SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33 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 10-800 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.

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 to cancer cells (liver cancer cell), and its inhibiting rate is more than 50% or 50%.

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 PP9284 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:3 or the varient of degeneracy.As used herein, " varient of degeneracy " is meant that in the present invention coding has the protein of SEQ ID NO:2, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ IDNO:3.Be example with PP9320 albumen (in this application, its clone numbering is adopted in proteinic name) again, the coding region sequence of encoding mature polypeptide can be identical with the coding region sequence shown in the SEQ ID NO:6 or the varient of degeneracy.As used herein, " varient of degeneracy " is meant that in the present invention coding has the protein of SEQ ID NO:5, but with the differentiated nucleotide sequence of coding region sequence shown in the SEQ ID NO:6.Have the albumen of cancer suppressing function for 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 PP9284 albumen) and activity with the mature polypeptide shown in the SEQ IDNO:2.

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.

In the above-mentioned method of mentioning, isolation of genomic DNA is least commonly used.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 Spring Harbor 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.

Recombinant DNA technology (Science, 1984 by routine; 224:1431), 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: and the expression vector based on T7 of in bacterium, expressing (Rosenberg, et al.Gene, 1987,56:125); The pMSXND expression vector of in mammalian cell, expressing (Lee and Nathans, J Bio Chem.263:3521,1988) 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 (Sambroook, et al.) such as extracorporeal recombinant DNA technology, DNA synthetic technology, the interior recombinant technologys of body.Described dna sequence dna can effectively be connected on the suitable promotor in the expression vector, and is synthetic to instruct mRNA.The representative example of these promotors has: colibacillary lac or trp promotor; Lambda particles phage P _LPromotor; Eukaryotic promoter comprises LTRs and some other known may command gene expression promoter in protokaryon or eukaryotic cell or its virus of CMV immediate early promoter, early stage and late period SV40 promotor, retrovirus.Expression vector also comprises ribosome bind site and the transcription terminator that translation initiation is used.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to people such as normal condition such as Sambrook, molecular cloning: laboratory manual (New York:Cold Spring Harbor LaboratoryPress, 1989) condition described in, or the condition of advising according to manufacturer.

Embodiment

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

PP9284, PP9320, PP10122, PP12744, PP13624, PP13671, PP13759, PP14328, PP14450, PP14733 and PP14762 obtain by making up the human placenta cDNA library with ordinary method.Get the placenta tissue at 3,6,10 monthly ages, (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.Make up the cDNA library of above-mentioned mRNA with pCMV-scriptTMXR 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 the XL10-Gold recipient cell, obtained 1 * 10 ⁶The cDNA library of cfu/ μ g cDNA titre.The first round is picking cDNA clone at random, is probe with high abundance cDNA clone with the cDNA clone who has proved cancer inhibitor cell growth function thereafter, screening by hybridization cDNA library, weak positive and negative clone of picking.With Qiagen 96 orifice plate plasmid extraction test kits, carry out the extraction of plasmid DNA by shop instruction.Plasmid DNA and empty carrier transfection simultaneously hepatoma cell line 7721.After the 100ng DNA alcohol precipitation drying, add 6 μ l H ₂Transfection is treated in the O dissolving.Add 0.74 μ l liposome and 9.3 μ l serum-free mediums in every part of DNA sample, behind the mixing, room temperature was placed 10 minutes.Add 150 μ l serum-free mediums in every pipe, divide equally and add 3 holes and grow in 7721 cells of 96 orifice plates, placed 2 hours for 37 ℃, every hole adds 50 μ l serum-free mediums again, 37 ℃ 24 hours.Every hole is changed 100 μ l and is trained liquid entirely, 37 ℃ 24 hours, change the full training liquid 100 μ l that contain G418,37 ℃ 24～48 hours, the limit is observed, the training liquid that G418 concentration does not wait is changed on the limit.After about 2～3 times, there is the clone to form up to the microscopy cell, counting.Find that above 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)
			PP9284 PP9320 PP10122 PP12744 PP13624 PP13671 PP13759 PP14328 PP14450 PP14733 PP14762	13 19 16 15 19 12 13 17 20 9 15 14 3 2 1 0 0 0 0 0 0 7 3 5 0 0 0 12 10 9 8 7 3	23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25 23 28 25

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:1,4,7,10,13,16,19,22,25,28,31).

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

Get the placenta tissue at 3,6,10 monthly ages, (GIBCO BRL company) extracts total RNA by manufacturer's specification sheets with Trizol reagent, extracts mRNA with the mRNA test kit (Pharmacia company) of purifying.With MMLV-RT-SuperscriptII (GIBCO BRL), ThermoScript II is carried out reverse transcription reaction at 42 ℃, obtains placenta cDNA.Utilize the different primer of commentaries on classics (as shown in the table) of each gene, by 97 ℃ of 31 circulations.94 ℃ 30 ", 60 ℃ 30 ", 72 ℃ 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:2,5,8,11,14,17,20,23,26,29,32).

Gene specific primer

Clone's title	Special primer 1 (5 ' → 3 ')	Special primer 2 (5 ' → 3 ')
			PP9284 PP9320 PP10122 PP12744 PP13624 PP13671 PP13759 PP14328 PP14450 PP14733 PP14762	TCTCCCAAATCTCCCAGATG GCTTCTCCCCACGATTTTT GGAGGCCATTTATTTGCTGA CGCTGTTCCATTGTGAGCTA GAGGCCTGAGTTGGGCTC CAGCTCAGAGCAGGGGTG AGCAGATCCATACTGGAAAATG AACTCATTGACTCCGCCAAC GATGAGGTGCCTCCACAACT CCTGATTCACTATTGCCTGG AAGAAGCCCACTGGTACCCT	CTCCAACGTGTTGGTCAGAG GCTGGAGTCTCCCCAACAT TTTAAGAGACGGGGTCTTGC CACTTCCTACCGGCCACAC CGTGTCCATCTCTCCAGTCA CAGGCTTCTCTTGACGCAGT GCTGTTGTCGCTCGCTCA TTCCCTGCCATTCTGGATAG GCTGCGTTTCACTCAGCAT CAAAATCAAAGTGGAAGAATAAGAAC CTGCACCCCTACCACTTGTT

Embodiment 3:cDNA cloned sequence is analyzed

1.PP9284

A: nucleotide sequence (SEQ ID NO:1) length: 2394

1 GGGACCTCAG ACGTATAGTT TTCTCAGATT TCTGTGCTTT CTGGGGCTGG GCTACTAGTG

61 GAAGAAAGCA GTCTATTCTG TCTTCTCCCA AATCTCCCAG ATGCCCAGTC TGTTGAAGGA

121 GGAGCAGAAC CAGGGGGCCT TTCCCGCTGA GGCCCGACCT GTGTCTCCTT CAAATGACAC

181 GCGGGACTCA GGGCCTTCCC ATGACCATGG GGCCCAGGGG GCGTCACCTG GCCCAGGGCC

241 CAGTGCTAGA AACAGATGAC CCCAGGAGGA GGAGGCAGGG CAGGAGGGAA GCTGGCAGGG

301 CTGGGATGGT CAGCCAGGCT GAGGGGCGGA CTCGCACCAG GATGGAGCTA GGAAATGATC

361 CAGGTGTGTT TGGCGGCTGC AGGTGGGTCC GCATGGCTGT GCAGGGAGGG AAGGGCTGCG

421 TGGCAGGAGA GCAGCCGGGG GAGGCCCAGA CTCTGCTGAA GAGATGCCTG TTGTGCCGGC

481 CTCCACATCC GCTGCCCGCT CCTTCCGGAG CTCCTGCCCC GCCATGCTCA GCCTGACTCT

541 GACCAACACG TTGGAGAGAA GAATGATCCC TTTGTGCTAT TAAGCTTGCT TATTTGGTTT

601 CTAAGTGCTT CATGCGAACC TAGAGGAAA4 AATTATTTTC CACCTTTGTT TGTCTTAAGA

661 AAATAACACA CTTTTTTTTT TCCTATTTGA ACAGGCAGAC GGCTAATCCA CATGGTCTTC

721 GTCCTTGACG TCGTTTTACA AGAAAACAAT GGGGCTGGTT TTGCTTCCCC GTGCATGATT

781 TACTCTTAGA GATGATTCAG AGGTCACTTC ATTTTTATTA AACAGTGAAC TTGTCTGGCT

841 TTGGCACTCT CTGCCATTCT GTGCAGGCTG CAGTGGCTCC CCTGCCCAGC CTGCTCTCCC

901 TAACCCCTTG TCCGCAAGGG GTGATGGCCG GCTGGTTGTG GGCACTGGCG GTCAAGTGTG

961 GAGGAGAGGG GTGGAGGCTG CCCCATTGAG ATCTTCCTGC TGAGTCCTTT CCAGGGGCCA

1021 ATTTTGGATG AGCATGGAGC TGTCACCTCT CAGCTGCTGG ATGACTTGAG ATGAAAAAGG

1081 AGAGACATGG AAAGGGAGAC AGCCAGGTGG CACCTGCAGC GGCTGCCCTC TGGGGCCACT

1141 TGGTAGTGTC CCCAGCCTAC CTCTCCACAA GGGGATTTTG CTGATGGGTT CTTAGAGCCT

1201 TAGCAGCCCT GGATGGTGGC CAGAAATAAA GGGACCAGCC CTTCATGGGT GGTGACGTGG

1261 TAGTCACTTG TAAGGGGAAC AGAAACATTT TTGTTCTTAT GGGGTGAGAA TATAGACAGT

1321 GCCCTTGGTG CGAGGGAAGC AATTGAAAAG GAACTTGCCC TGAGCACTCC TGGTGCAGGT

1381 CTCCACCTGC ACATTGGGTG GGGCTCCTGG GAGGGAGACT CAGCCTTCCT CCTCATCCTC

1441 CCTGACCCTG CTCCTAGCAC CCTGGAGAGT GCACATGCCC CTTGGTCCTG GCAGGGCGCC

1501 AAGTCTGGCA CCATGTTGGC CTCTTCAGGC CTGCTAGTCA CTGGAAATTG AGGTCCATGG

1561 GGGAAATCAA GGATGCTCAG TTTAAGGTAC ACTGTTTCCA TGTTATGTTT CTACACATTG

1621 CTACCTCAGT GCTCCTGGAA ACTTAGCTTT TGATGTCTCC AAGTAGTCCA CCTTCATTTA

1681 ACTCTTTGAA ACTGTATCAT CTTTGCCAAG TAAGAGTGGT GGCCTATTTC AGCTGCTTTG

1741 ACAAAATGAC TGGCTCCTGA CTTAACGTTC TATAAATGAA TGTGCTGAAG CAAAGTGCCC

1801 ATGGTGGCGG CGAAGAAGAG AAAGATGTGT TTTGTTTTGG ACTCTCTGTG GTCCCTTCCA

1861 ATGCTGTGGG TTTCCAACCA GGGGAAGGGT CCCTTTTGCA TTGCCAAGTG CCATAACCAT

1921 GAGCACTACT CTACCATGGT TCTGCCTCCT GGCCAAGCAG GCTGGTTTGC AAGAATGAAA

1981 TGAATGATTC TACAGCTAGG ACTTAACCTT GAAATGGAAA GTCTTGCAAT CCCATTTGCA

2041 GGATCCGTCT GTGCACATGC CTCTGTAGAG AGCAGCATTC CCAGGGACCT TGGAAACAGT

2101 TGGCACTGTA AGGTGCTTGC TCCCCAAGAC ACATCCTAAA AGGTGTTGTA ATGGTGAAAA

2161 CGTCTTCCTT CTTTATTGCC CCTTCTTATT TATGTGAACA ACTGTTTGTC TTTTTTTGTA

2221 TCTTTTTTAA ACTGTAAAGT TCAATTGTGA AAATGAATAT CATGCAAATA AATTATGCGA

2281 TTTTTTTTTC AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA

2341 AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAA

B: aminoacid sequence (SEQ ID NO:2) length: 120

1 MTRGTQGLPM TMGPRGRHLA QGPVLETDDP RRRRQGRREA GRAGMVSQAE GRTRTRMELG

61 NDPGVFGGCR WVRMAVQGGK GCVAGEQPGE AQTLLKRCLL CRPPHPLPAP SGAPAPPCSA

C. Nucleotide and amino acid composite sequence (SEQ ID NO:3) clone number: PP9284

Start code: 174 ATG stop coding: 534 TGA protein molecular weights: 12778.12

(annotate: what (1) provided is the position that initial sum stops first Nucleotide of coding, and (2) molecular weight unit is dalton)

1 GG GAC CTC AGA CGT ATA GTT TTC TCA GAT TTC TGT GCT TTC TGG GGC 47

48 TGG GCT ACT AGT GGA AGA AAG CAG TCT ATT CTG TCT TCT CCC AAA TCT 95

96 CCC AGA TGC CCA GTC TGT TGA AGG AGG AGC AGA ACC AGG GGG CCT TTC 143

144 CCG CTG AGG CCC GAC CTG TGT CTC CTT CAA ATG ACA CGC GGG ACT CAG 191

1 Met Thr Arg Gly Thr Gln 6

192 GGC CTT CCC ATG ACC ATG GGG CCC AGG GGG CGT CAC CTG GCC CAG GGC 239

7 Gly Leu Pro Met Thr Met Gly Pro Arg Gly Arg His Leu Ala Gln Gly 22

240 CCA GTG CTA GAA ACA GAT GAC CCC AGG AGG AGG AGG CAG GGC AGG AGG 287

23 Pro Val Leu Glu Thr Asp Asp Pro Arg Arg Arg Arg Gln Gly Arg Arg 38

288 GAA GCT GGC AGG GCT GGG ATG GTC AGC CAG GCT GAG GGG CGG ACT CGC 335

39 Glu Ala Gly Arg Ala Gly Met Val Ser Gln Ala Glu Gly Arg Thr Arg 54

336 ACC AGG ATG GAG CTA GGA AAT GAT CCA GGT GTG TTT GGC GGC TGC AGG 383

55 Thr Arg Met Glu Leu Gly Asn Asp Pro Gly Val Phe Gly Gly Cys Arg 70

384 TGG GTC CGC ATG GCT GTG CAG GGA GGG AAG GGC TGC GTG GCA GGA GAG 431

71 Trp Val Arg Met Ala Val Gln Gly Gly Lys Gly Cys Val Ala Gly Glu 86

432 CAG CCG GGG GAG GCC CAG ACT CTG CTG AAG AGA TGC CTG TTG TGC CGG 479

87 Gln Pro Gly Glu Ala Gln Thr Leu Leu Lys Arg Cys Leu Leu Cys Arg 102

480 CCT CCA CAT CCG CTG CCC GCT CCT TCC GGA GCT CCT GCC CCG CCA TGC 527

103 Pro Pro His Pro Leu Pro Ala Pro Ser Gly Ala Pro Ala Pro Pro Cys 118

528 TCA GCC TGA CTC TGA CCA ACA CGT TGG AGA GAA GAA TGA TCC CTT TGT 575

119 Ser Ala*** 121

576 GCT ATT AAG CTT GCT TAT TTG GTT TCT AAG TGC TTC ATG CGA ACC TAG 623

624 AGG AAA AAA TTA TTT TCC ACC TTT GTT TGT CTT AAG AAA ATA ACA CAC 671

672 TTT TTT TTT TCC TAT TTG AAC AGG CAG ACG GCT AAT CCA CAT GGT CTT 719

720 CGT CCT TGA CGT CGT TTT ACA AGA AAA CAA TGG GGC TGG TTT TGC TTC 767

768 CCC GTG CAT GAT TTA CTC TTA GAG ATG ATT CAG AGG TCA CTT CAT TTT 815

816 TAT TAA ACA GTG AAC TTG TCT GGC TTT GGC ACT CTC TGC CAT TCT GTG 863

864 CAG GCT GCA GTG GCT CCC CTG CCC AGC CTG CTC TCC CTA ACC CCT TGT 911

912 CCG CAA GGG GTG ATG GCC GGC TGG TTG TGG GCA CTG GCG GTC AAG TGT 959

960 GGA GGA GAG GGG TGG AGG CTG CCC CAT TGA GAT CTT CCT GCT GAG TCC 1007

1008 TTT CCA GGG GCC AAT TTT GGA TGA GCA TGG AGC TGT CAC CTC TCA GCT 1055

1056 GCT GGA TGA CTT GAG ATG AAA AAG GAG AGA CAT GGA AAG GGA GAC AGC 1103

1104 CAG GTG GCA CCT GCA GCG GCT GCC CTC TGG GGC CAC TTG GTA GTG TCC 1151

1152 CCA GCC TAC CTC TCC ACA AGG GGA TTT TGC TGA TGG GTT CTT AGA GCC 1199

1200 TTA GCA GCC CTG GAT GGT GGC CAG AAA TAA AGG GAC CAG CCC TTC ATG 1247

1248 GGT GGT GAC GTG GTA GTC ACT TGT AAG GGG AAC AGA AAC ATT TTT GTT 1295

1296 CTT ATG GGG TGA GAA TAT AGA CAG TGC CCT TGG TGC GAG GGA AGC AAT 1343

1344 TGA AAA GGA ACT TGC CCT GAG CAC TCC TGG TGC AGG TCT CCA CCT GCA 1391

1392 CAT TGG GTG GGG CTC CTG GGA GGG AGA CTC AGC CTT CCT CCT CAT CCT 1439

1440 CCC TGA CCC TGC TCC TAG CAC CCT GGA GAG TGC ACA TGC CCC TTG GTC 1487

1488 CTG GCA GGG CGC CAA GTC TGG CAC CAT GTT GGC CTC TTC AGG CCT GCT 1535

1536 AGT CAC TGG AAA TTG AGG TCC ATG GGG GAA ATC AAG GAT GCT CAG TTT 1583

1584 AAG GTA CAC TGT TTC CAT GTT ATG TTT CTA CAC ATT GCT ACC TCA GTG 1631

1632 CTC CTG GAA ACT TAG CTT TTG ATG TCT CCA AGT AGT CCA CCT TCA TTT 1679

1680 AAC TCT TTG AAA CTG TAT CAT CTT TGC CAA GTA AGA GTG GTG GCC TAT 1727

1728 TTC AGC TGC TTT GAC AAA ATG ACT GGC TCC TGA CTT AAC GTT CTA TAA 1775

1776 ATG AAT GTG CTG AAG CAA AGT GCC CAT GGT GGC GGC GAA GAA GAG AAA 1823

1824 GAT GTG TTT TGT TTT GGA CTC TCT GTG GTC CCT TCC AAT GCT GTG GGT 1871

1872 TTC CAA CCA GGG GAA GGG TCC CTT TTG CAT TGC CAA GTG CCA TAA CCA 1919

1920 TGA GCA CTA CTC TAC CAT GGT TCT GCC TCC TGG CCA AGC AGG CTG GTT 1967

1968 TGC AAG AAT GAA ATG AAT GAT TCT ACA GCT AGG ACT TAA CCT TGA AAT 2015

2016 GGA AAG TCT TGC AAT CCC ATT TGC AGG ATC CGT CTG TGC ACA TGC CTC 2063

2064 TGT AGA GAG CAG CAT TCC CAG GGA CCT TGG AAA CAG TTG GCA CTG TAA 2111

2112 GGT GCT TGC TCC CCA AGA CAC ATC CTA AAA GGT GTT GTA ATG GTG AAA 2159

2160 ACG TCT TCC TTC TTT ATT GCC CCT TCT TAT TTA TGT GAA CAA CTG TTT 2207

2208 GTC TTT TTT TGT ATC TTT TTT AAA CTG TAA AGT TCA ATT GTG AAA ATG 2255

2256 AAT ATC ATG CAA ATA AAT TAT GCG ATT TTT TTT TCA AAA AAA AAA AAA 2303

2304 AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA 2351

2352 AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA A 2394

2.PP9320

A: nucleotide sequence (SEQ ID NO:4) length: 2923

1 GCCGAGCTGA GCCGATCAAA AGGCCATGGG TAGGAGGCTT GCAGGTGTGA CTTTAGGATC

61 ATGGCTTCTC CCCACGATTT TTTGGGGGTC GAGGGAAGCA GAGCATGGTG CTCCAATCCC

121 AGAACCCAGC TGTCCTCAAG CTCAGAGGAC CAGGTCCTGG CCTGGCTGCT GCTGCTGGGA

181 CTCCTCCCTA TGGGCATCCC TGCATGTCCT GTGTGTCCCT GAGGAGGGAC ATGGGGAACT

241 CAGGGGCCAC CTCTCCTCGA ACTGCGGGGC CAGAGCAGAG AGCCCTTGCA CACCACCAGC

301 CTCTCCTCCC TGTGCCCCAG GAGTTCATCC TTTGCTGCCT GGCCCGGGAC CCTGCCCGCC

361 GGCCCTCTGC CCACAGCCTC CTCTTCCACC GCGTGCTCTT CGAGGTGCAC TCGCTGAAGC

421 TCCTGGCAGC CCACTGCTTC ATCCAGCACC AGTACCTCAT GCCTGAGAAT GTGGTGGAGG

481 AGAAGACCAA GGCCATGGAC CTGCACGCGG TCTTGGCGGA GCTTCCCCGG CCCCGCAGGC

541 CCCCGCTGCA GTGGCGGTAC TCGGAAGTCT CCTTCATGGA GCTGGACAAA TTCCTGGAGG

601 ATGTCAGGAA TGGAATCTAC CCACTGATGA ACTTTGCAGC CACTCGACCC CTGGGGCTGC

661 CCCGTGTGCT GGCCCCACCC CCGGAGGAGG TCCAAAAGGC CAAGACCCCG ACGCCAGAGC

721 CCTTTGACTC TGAGACCAGA AAGGTCATCC AGATGCAGTG CAACCTGGAG AGAAGCGAGG

781 ACAAGGCGCG CTGGCATCTC ACTCTGCTTC TGGTGCTGGA AGACCGGCTG CACCGGCAGC

841 TGACCTACGA CCTGCTCCCA ACGGACAGCG CCCAGGACCT CGCCTCGGAG CTCGTGCACT

901 ATGGCTTCCT CCACGAGGAC GACCGGATGA AGCTGGCCGC CTTCCTGGAG AGCACCTTCC

961 TCAAGTACCG TGGGACCCAG GCCTGACCCG GAGCCCCAGC CCCAGGGGAC CATGCCGGGG

1021 TGCTGCCCGG GCAGGCCATG TTGGGGAGAC TCCAGCACCG TGGGGCTGCC CTCCTCCATG

1081 CGCCTGGGAG CACAAAGGCC CCGGTAGTGA AGGAACCCCC CGTCTCCTGA GAGTGGGGCT

1141 GACCCTGCCT TGGGCGCCGA GGGGTTTGGG GGGTGGGTGT GGGGGAGCCG TTAGCCTCCC

1201 AGGTCCTTAG GATCAGGGTT GCCCCCAGAA CCCCTTCCCA TATCCTCCAT TCTCCGCCCT

1261 GAGTTCCTAC CCAGGCTGCC TGGCCGGGGC CACTGCCTCC TCAGCATGCA GGAGGCTGCC

1321 CTGTAGGGAA CCCCAGCTCT GGGGCTTGGG GGTGAGGGTC AGCCCTGGAC AGACCTCTGC

1381 CCAGGGAACT GCTCCATGGG GTCTGGGAGA GCAGCCATCC CCTGCTGGCA CCATAGACCC

1441 ACACAAGGAG CCTGCACAGC AAGCCAGCGG TGACACACCT GCAGGTGTCA GGCATGGCAC

1501 TGGGCACAAC AGGGACCTGG CAGGAGAACA GACCACAGAG AGGTCTGGAG TTGAGGCTGT

1561 TGTCAGCAAA GCCCCTGGTC CCACACAGCT CTGCCCTAGA GCCACCTCTT TGACCCTTTA

1621 CCCACCCTGA GACCAGAACT TGCAGCCCCT CTGCAGATCT CCTCTGGCCA CTGCAGCCCC

1681 TCCAATGGGC TTTTTCTCTC ATGCATTCCC TGGCCTGGAG GCGTCAGGGA CCCCACATCC

1741 TCCCTGCTCC TCAGACTCAC AGCCCCTCCA TGTTACCTCC CGCACCTCCT CCCTGGGGCA

1801 GCTGCTCCCT GGGCCTCTGA GGATGTCAGC TCCTGGCTCC CTGCCTCTCT CCCACTCCAC

1861 TCCTGGCTCA GTCTTAGAGA TTTCTATGCC CTCATGGATT CTACCCCTGC CTTCCTGGCC

1921 TCTTGATTCT TGGCTTGCCT CTCCTCCAAT TCCAAACTTA GTGAAATGGC CTTAAGCATT

1981 TTAAACTGTA TGTATACATT AGCGCATTCA TGCCTTTCTA AACGCATTTC AAATGTCAAC

2041 CAGGAAGGCA CACCACTGTA TTAGTTTTAT ACTGCCGCTG TAAAATTTAC CACAAACTTA

2101 GTGACTTAAC ACAAATTTAT TGCAATTCTG TAGGCTGGAA GTCTGACTAT GGGTCTCACT

2161 GGACTAGAAT CAAGGCTGGC AGGCTGCCTT CCTTCCTGGA GGTTCTAGGG GAGACTCTGT

2221 CTCCTGCTCC TTCAGGCTGC TGGCAGAATC CACATCCTTT CGGTGGCAGG GCCAAGGTCC

2281 CCACTTTCTT GCTGACTGTA AACTAAGGCC ACTTCCAGCT TGTAGAGGCT GCCTACATTC

2341 CTTGGCTCTT GGCCCCCTCC TCCATCTTCA GAGCTAGCAG GTTCAGTCTG TGTCACGAAC

2401 CATTTCTCTG GTTCCCTGCA GACAGGAAAG GTTGTCCCTA AGGACTCATG AGATTAGGTT

2461 GGGCCCAGCC AGATAATACA TGATAATCTC CCTCCTCAAG GTTTTTAATA TTAAACACAT

2521 CTGCAGGACA CATTTTGCCA TGTAAACTAA CATTCACTGG TTCCAGGGAT TAAGGAATGA

2581 ACCTCTTTTG TTGGGGAAGG GTGGCATTCT GCTGACCACA GCACTCCAAC CAAAAGCCAA

2641 AAACCAAAGC AAGACTTACT AACGCATATC AAATAAATTA AAGGTACAAA ATCGTGAATC

2701 TCAGTTATCT TAAATATTCC AATACTATTT ACAAAATTAT TCAAATTCTC ACGCCTTCCA

2761 ACTCAAAATT AGCAATCTAA AGTAATTTCC ATATCCTAGA TGGAAACCCT CATGCTAAAC

2821 TGTCTGATTA TGCATGGTTC TAAATGGTTT CAGTGGCAAA TACATAACAT TGTACTACTG

2881 ATTAAACTGA ACTTAAAAGC ATCAAAAAAA AAAAAAAAAA AAA

B: aminoacid sequence (SEQ ID NO:5) length: 293

1 MVLQSQNPAV LKLRGPGPGL AAAAGTPPYG HPCMSCVSLR RDMGNSGATS PRTAGPEQRA

61 LAHHQPLLPV PQEFILCCLA RDPARRPSAH SLLFHRVLFE VHSLKLLAAH CFIQHQYLMP

121 ENVVEEKTKA MDLHAVLAEL PRPRRPPLQW RYSEVSFMEL DKFLEDVRNG IYPLMNFAAT

181 RPLGLPRVLA PPPEEVQKAK TPTPEPFDSE TRKVIQMQCN LERSEDKARW HLTLLLVLED

241 RLHRQLTYDL LPTDSAQDLA SELVHYGFLH EDDPMKLAAF LESTFLKYRG TQA

C. Nucleotide and amino acid composite sequence (SEQ ID NO:6) clone number: PP9320 start code: 105 ATG stop coding: 984 TGA protein molecular weights: 33139.57

1 GC CGA GCT GAG CCG ATC AAA AGG CCA TGG GTA GGA GGC TTG CAG GTG 47

48 TGA CTT TAG GAT CAT GGC TTC TCC CCA CGA TTT TTT GGG GGT CGA GGG 95

96 AAG CAG AGC ATG GTG CTC CAA TCC CAG AAC CCA GCT GTC CTC AAG CTC 143

1 Met Val Leu Gln Ser Gln Asn Pro Ala Val Leu Lys Leu 13

144 AGA GGA CCA GGT CCT GGC CTG GCT GCT GCT GCT GGG ACT CCT CCC TAT 191

14 Arg Gly Pro Gly Pro Gly Leu Ala Ala Ala Ala Gly Thr Pro Pro Tyr 29

192 GGG CAT CCC TGC ATG TCC TGT GTG TCC CTG AGG AGG GAC ATG GGG AAC 239

30 Gly His Pro Cys Met Ser Cys Val Ser Leu Ar8 Arg Asp Met Gly Asn 45

240 TCA GGG GCC ACC TCT CCT CGA ACT GCG GGG CCA GAG GAG AGA GCC CTT 287

46 Ser Gly Ala Thr Ser Pro Arg Thr Ala Gly Pro Glu Gln Arg Ala Leu 61

288 GCA CAC CAC CAG CCT CTC CTC CCT GTG CCC CAG GAG TTC ATC CTT TGC 335

62 Ala His His Gln Pro Leu Leu Pro Val Pro Gln Glu Phe Ile Leu Cys 77

336 TGC CTG GCC CGG GAC CCT GCC CGC CGG CCC TCT GCC CAC AGC CTC CTC 383

78 Cys Leu Ala Arg Asp Pro Ala Arg Arg Pro Ser Ala His Ser Leu Leu 93

384 TTC CAC CGC GTG CTC TTC GAG GTG CAC TCG CTG AAG CTC CTG GCA GCC 431

94 Phe His Arg Val Leu Phe Glu Val His Ser Leu Lys Leu Leu Ala Ala 109

432 CAC TGC TTC ATC CAG CAC CAG TAC CTC ATG CCT GAG AAT GTG GTG GAG 479

110 His Cys Phe Ile Gln His Gln Tyr Leu Met Pro Glu Asn Val Val Glu 125

480 GAG AAG ACC AAG GCC ATG GAC CTG CAC GCG GTC TTG GCG GAG CTT CCC 527

126 Glu Lys Thr Lys Ala Met Asp Leu His Ala Val Leu Ala Glu Leu Pro 141

528 CGG CCC CGC AGG CCC CCG CTG CAG TGG CGG TAC TCG GAA GTC TCC TTC 575

142 Arg Pro Arg Arg Pro Pro Leu Gln Trp Arg Tyr Ser Glu Val Ser Phe 157

576 ATG GAG CTG GAC AAA TTC CTG GAG GAT GTC AGG AAT GGA ATC TAC CCA 623

158 Met Glu Leu Asp Lys Phe Leu Glu Asp Val Arg Asn Gly Ile Tyr Pro 173

624 CTG ATG AAC TTT GCA GCC ACT CGA CCC CTG GGG CTG CCC CGT GTG CTG 671

174 Leu Met Asn Phe Ala Ala Thr Arg Pro Leu Gly Leu Pro Arg Val Leu 189

672 GCC CCA CCC CCG GAG GAG GTC CAA AAG GCC AAG ACC CCG ACG CCA GAG 719

190 Ala Pro Pro Pro Glu Glu Val Gln Lys Ala Lys Thr Pro Thr Pro Glu 205

720 CCC TTT GAC TCT GAG ACC AGA AAG GTC ATC CAG ATG CAG TGC AAC CTG 767

206 Pro Phe Asp Ser Glu Thr Arg Lys Val Ile Gln Met Gln Cys Asn Leu 221

768 GAG AGA AGC GAG GAC AAG GCG CGC TGG CAT CTC ACT CTG CTT CTG GTG 815

222 Glu Arg Ser Glu Asp Lys Ala Arg Trp His Leu Thr Leu Leu Leu Val 237

816 CTG GAA GAC CGG CTG CAC CGG CAG CTG ACC TAC GAC CTG CTC CCA ACG 863

238 Leu Glu Asp Arg Leu His Arg Gln Leu Thr Tyr Asp Leu Leu Pro Thr 253

864 GAC AGC GCC CAG GAC CTC GCC TCG GAG CTC GTG CAC TAT GGC TTC CTC 911

254 Asp Ser Ala Gln Asp Leu Ala Ser Glu Leu Val His Tyr Gly Phe Leu 269

912 CAC GAG GAC GAC CGG ATG AAG CTG GCC GCC TTC CTG GAG AGC ACC TTC 959

270 His Glu Asp Asp Arg Met Lys Leu Ala Ala Phe Leu Glu Ser Thr Phe 285

960 CTC AAG TAC CGT GGG ACC CAG GCC TGA CCC GGA GCC CCA GCC CCA GGG 1007

286 Leu Lys Tyr Arg Gly Thr Gln Ala *** 294

1008 GAC CAT GCC GGG GTG CTG CCC GGG CAG GCC ATG TTG GGG AGA CTC CAG 1055

1056 CAC CGT GGG GCT GCC CTC CTC CAT GCG CCT GGG AGC ACA AAG GCC CCG 1103

1104 GTA GTG AAG GAA CCC CCC GTC TCC TGA GAG TGG GGC TGA CCC TGC CTT 1151

1152 GGG CGC CGA GGG GTT TGG GGG GTG GGT GTG GGG GAG CCG TTA GCC TCC 1199

1200 CAG GTC CTT AGG ATC AGG GTT GCC CCC AGA ACC CCT TCC CAT ATC CTC 1247

1248 CAT TCT CCG CCC TGA GTT CCT ACC CAG GCT GCC TGG CCG GGG CCA CTG 1295

1296 CCT CCT CAG CAT GCA GGA GGC TGC CCT GTA GGG AAC CCC AGC TCT GGG 1343

1344 GCT TGG GGG TGA GGG TCA GCC CTG GAC AGA CCT CTG CCC AGG GAA CTG 1391

1392 CTC CAT GGG GTC TGG GAG AGC AGC CAT CCC CTG CTG GCA CCA TAG ACC 1439

1440 CAC ACA AGG AGC CTG CAC AGC AAG CCA GCG GTG ACA CAC CTG CAG GTG 1487

1488 TCA GGC ATG GCA CTG GGC ACA ACA GGG ACC TGG CAG GAG AAC AGA CCA 1535

1536 CAG AGA GGT CTG GAG TTG AGG CTG TTG TCA GCA AAG CCC CTG GTC CCA 1583

1584 CAC AGC TCT GCC CTA GAG CCA CCT CTT TGA CCC TTT ACC CAC CCT GAG 1631

1632 ACC AGA ACT TGC AGC CCC TCT GCA GAT CTC CTC TGG CCA CTG CAG CCC 1679

1680 CTC CAA TGG GCT TTT TCT CTC ATG CAT TCC CTG GCC TGG AGG CGT CAG 1727

1728 GGA CCC CAC ATC CTC CCT CCT CCT CAG ACT CAC AGC CCC TCC ATG TTA 1775

1776 CCT CCC GCA CCT CCT CCC TGG GGC AGC TGC TCC CTG GGC CTC TGA GGA 1823

1824 TGT CAG CTC CTG GCT CCC TGC CTC TCT CCC ACT CCA CTC CTG GCT CAG 1871

1872 TCT TAG AGA TTT CTA TGC CCT CAT GGA TTC TAC CCC TGC CTT CCT GGC 1919

1920 CTC TTG ATT CTT GGC TTG CCT CTC CTC CAA TTC CAA ACT TAG TGA AAT 1967

1968 GGC CTT AAG CAT TTT AAA CTG TAT GTA TAC ATT AGC GCA TTC ATG CCT 2015

2016 TTC TAA ACG CAT TTC AAA TGT CAA CCA GGA AGG CAC ACC ACT GTA TTA 2063

2064 GTT TTA TAC TGC CGC TGT AAA ATT TAC CAC AAA CTT AGT GAC TTA ACA 2111

2112 CAA ATT TAT TGC AAT TCT GTA GGC TGG AAG TCT GAC TAT GGG TCT CAC 2159

2160 TGG ACT AGA ATC AAG GCT GGC AGG CTG CCT TCC TTC CTG GAG GTT CTA 2207

2208 GGG GAG ACT CTG TCT CCT GCT CCT TCA GGC TGC TGG CAG AAT CCA CAT 2255

2256 CCT TTC GGT GGC AGG GCC AAG GTC CCC ACT TTC TTG CTG ACT GTA AAC 2303

2304 TAA GGC CAC TTC CAG CTT GTA GAG GCT GCC TAC ATT CCT TGG CTC TTG 2351

2352 GCC CCC TCC TCC ATC TTC AGA GCT AGC AGG TTC AGT CTG TGT CAC GAA 2399

2400 CCA TTT CTC TGG TTC CCT GCA GAC AGG AAA GGT TGT CCC TAA GGA CTC 2447

2448 ATG AGA TTA GGT TGG GCC CAG CCA GAT AAT ACA TGA TAA TCT CCC TCC 2495

2496 TCA AGG TTT TTA ATA TTA AAC ACA TCT GCA GGA CAC ATT TTG CCA TGT 2543

2544 AAA CTA ACA TTC ACT GGT TCC AGG GAT TAA GGA ATG AAC CTC TTT TGT 2591

2592 TGG GGA AGG GTG GCA TTC TGC TGA CCA CAG CAC TCC AAC CAA AAG CCA 2639

2640 AAA ACC AAA GCA AGA CTT ACT AAC GCA TAT CAA ATA AAT TAA AGG TAC 2687

2688 AAA ATC GTG AAT CTC AGT TAT CTT AAA TAT TCC AAT ACT ATT TAC AAA 2735

2736 ATT ATT CAA ATT CTC ACG CCT TCC AAC TCA AAA TTA GCA ATC TAA AGT 2783

2784 AAT TTC CAT ATC CTA GAT GGA AAC CCT CAT GCT AAA CTG TCT GAT TAT 2831

2832 GCA TGG TTC TAA ATG GTT TCA GTG GCA AAT ACA TAA CAT TGT ACT ACT 2879

2880 GAT TAA ACT GAA CTT AAA AGC ATC AAA AAA AAA AAA AAA AAA AA 2923

3.PP10122

A: nucleotide sequence (SEQ lD NO:7) length: 1867

1 GCAAATCCAT TCTTAAACCT TGCAAGCTGA CTGCGGGAGC CCATGGATTG CAGGCCTCCC

61 CTGCAGCACT CCCTGGCTGC AGCCCCTTCC TGACCGTGCA GCTCCCTCGT GGAGCCCTGT

121 GTGGGACTCC CAGGGTGGAC TCTGGATGTG GGGTCCCAAG AATGCAGAGC CTTCTATGGG

181 TGACCCCAGG TGGTGTCCCA GTCACTTTGC CATTGAGGGA TAGGTGCTGA GGGAGCCTGT

241 CCTCTCAGAA CCTCAGTCTC CCTGTCTGTA AATTTGGGGA ACCCAGTTGG CTGCACAACC

301 CCTGCAGAAC CCTGTTGTGT GGCTCTTAGC TGGTGGTCCC TAAGTGGGTT TCTCCTGCAG

361 TCCCTCCTAA GCATCCACCC CTCCTCCCCA AGCCTCCAAC CCCCCACACC TGAGACTCCC

421 CACGTGGCCC TGCCTGGATG CCACCCACCT GTGTCCCTTC CTCTGTTCCT ACTAGTTGTT

481 GAAGACATCA ACAAACGGCG GGAACCCATT CCCAGTCTGG AGGCCATTTA TTTGCTGAGC

541 CCCACGGAGA AGGTGCCTAC ATGAGTGAGC GTGTGTGTAT GCGCGTGCAT GCGTGTACAT

601 GTGCATGTGT GTGTATGTCT GCATGCATGT GATTGCATGT GTGCATGTGT ATACGTGTGC

661 ATGTGTCCAT GTGTATGTGT GTGCATGTGT GTGTGCATCT GTGTATGCAT GTGTGTGCGT

721 TTTGCATGTG TGTCTATGTA TGTGTCTGTG TGCATGTGCA TGTGTGTGCG TCTGTGTGTG

781 CATTTGTGTG TATGTGTGTA TGCGTGTGTG TCTGTGGGTC TGTGTGTGCA TTTGTGTCTG

841 TGCATGTGTG TATGCGTGTG TATGTATGTG TGTGCATCTG TGTGCATCTG TATGTGTGTG

901 TGTGCGTCTG TCTGTGTGCA TGTGTGTATG CGTGTGTATG TATGTGTCTG CGTCTGTGTG

961 TGCGTCTGTG TGTATCTGTG TGTGCATGTG TGTATGCGTG TATATGTATG TGCATCTGTG

1021 TGCATGTGTC TATGTATGTG TGTGCATCTG TGTGTGCGTG TGTATGCGTG TGTGTATGCG

1081 TCTGTGTGCA TGTGTGTATG CGTGTGTGTG CGCATCAGTG TCTGCATGTG TGTATATGTG

1141 TGTATGTATG TGTGTGCGCG CGCATCTGTG TGTGTGCATG TGTGTATGTA TGTGTGTGCA

1201 TCTCTGTGTG TGCATGTGTG TATGTGTGTG TGCATCTGTG TGTGTGTGCA TGTGTGCATG

1261 CGTGTGTATG TGTGTGTGCG TGCGTGCATC TGTGTGTGTG CGCGTGTGCC CATGTGGGTG

1321 CGACACTAGT GTGCATTTGC ACATATACAT GTCCCCGTCC GTCCATGTTT GCACATGGTG

1381 GCAGATGGGG GGTGGCTGGG AGGCCTAGGC AGCCAATGAG CCTAGGTGTG CAGGCTCAGG

1441 CCCAGAGAGT GATCCACCTT CCCCAGTCGG TTCAGGCCCT GATCAAAGAC TTCCAGGGGA

1501 CCCCGACTTT CACCTACAAA GCGGCCCATA TCTTCTTCAC CGACACCTGC CCCGAGCCCC

1561 TGTTCAGTGA GCTAGGCCGC TCTCGTCTGG CAAAGGTGGT GAAGACGTTG AAGGAGATTC

1621 ACCTTGCCTT CCTCCCCTAC GAGGCCCAGG TACGGCCCGG GCTCATCCTG GGCAGGGGGT

1681 GGGGGTTTGT GACCAAATGT CCCCTGTTCC CTCAGAAACA GACACTGAGG CTGGGCGCAG

1741 TGGCTCATAC CTGTAATCCC AGCGCTGTGG GAGGCCAGGG CAGGAGGATC ACTTGGGGCC

1801 AGGAGTTTGA GACCAGCCTG GGTACAGAGC AAGACCCCGT CTCTTAAAAA AAAAAAAAAA

1861 AAAAAAA

B: aminoacid sequence (SEQ ID NO:8) length: 400

1 MCIRVHVSMC MCVHVCVHLC MHVCAFCMCV YVCVCVHVHV CASVCAFVCM CVCVCVCGSV

61 CAFVSVHVCM RVYVCVCICV HLYVCVCVCL CACVYACVCM CLRLCVRLCV SVCACVYACI

121 CMCICVHVSM YVCASVCACV CVCVCVCVHV CMRVCAHQCL HVCICVYVCV CARICVCACV

181 YVCVCISVCA CVYVCVHLCV CACVHACVCV CACVHLCVCA CAHVGATLVC ICTYTCPRPS

241 MFAHGGRWGV AGRPRQPMSL GVQAQAQRVI HLPQSVQALI KDFQGTPTFT YKAAHIFFTD

301 TCPEPLFSEL GRSRLAKVVK TLKEIHLAFL PYEAQVRPGL ILGRGWGFVT KCPLFPQKQT

361 LRLGAVAHTC NPSAVGGQGR RITWGQEFET SLGTEQDPVS

C. Nucleotide and amino acid composite sequence (SEQ ID NC:9) clone number: PP10122

Start code: 645 ATG stop coding: 1845 TAA protein molecular weights: 43382.43

1 GC AAA TCC ATT CTT AAA CCT TGC AAG CTG ACT GCG GGA GCC CAT GGA 47

48 TTG CAG GCC TCC CCT GCA GCA CTC CCT GGC TGC AGC CCC TTC CTG ACC 95

96 GTG CAG CTC CCT CGT GGA GCC CTG TGT GGG ACT CCC AGG GTG GAC TCT 143

144 GGA TGT GGG GTC CCA AGA ATG CAG AGC CTT CTA TGG GTG ACC CCA GGT 191

192 GGT GTC CCA GTC ACT TTG CCA TTG AGG GAT AGG TGC TGA GGG AGC CTG 239

240 TCC TCT CAG AAC CTC AGTC CTC CCT GTC TGT AAA TTT GGG GAA CCC AGT 287

288 TGG CTG CAC AAC CCC TGC AGA ACC CTG TTG TGT GGC TCT TAG CTG GTG 335

336 GTC CCT AAG TGG GTT TCT CCT GCA GTC CCT CCT AAG CAT CCA CCC CTC 383

384 CTC CCC AAG CCT CCA ACC CCC CAC ACC TGA GAC TCC CCA CGT GGC CCT 431

432 GCC TGG ATG CCA CCC ACC TGT GTC CCT TCC TCT GTT CCT ACT AGT TGT 479

480 TGA AGA CAT CAA CAA ACG GCG GGA ACC CAT TCC CAG TCT GGA GGC CAT 527

528 TTA TTT GCT GAG CCC CAC GGA GAA GGT GCC TAC ATG AGT GAG CGT GTG 575

576 TGT ATG CGC GTG CAT GCG TGT ACA TGT GCA TGT GTG TGT ATG TCT GCA 623

624 TGC ATG TGA TTG CAT GTG TGC ATG TGT ATA CGT GTG CAT GTG TCC ATG 671

1 Met Cys Ile Arg Val His Val Ser Met 9

672 TGT ATG TGT GTG CAT GTG TGT GTG CAT CTG TGT ATG CAT GTG TGT GCG 719

10 Cys Met Cys Val His Val Cys Val His Leu Cys Met His Val Cys Ala 25

720 TTT TGC ATG TGT GTC TAT GTA TGT GTC TGT GTG CAT GTG CAT GTG TGT 767

26 Phe Cys Met Cys Val Tyr Val Cys Val Cys Val His Val His Val Cys 41

768 GCG TCT GTG TGT GCA TTT GTG TGT ATG TGT GTA TGC GTG TGT GTC TGT 815

42 Ala Ser Val Cys Ala Phe Val Cys Met Cys Val Cys Val Cys Val Cys 57

816 GGG TCT GTG TGT GCA TTT GTG TCT GTG CAT GTG TGT ATG CGT GTG TAT 863

58 Gly Ser Val Cys Ala Phe Val Ser Val His Val Cys Met Arg Val Tyr 73

864 GTA TGT GTG TGC ATC TGT GTG CAT CTG TAT GTG TGT GTG TGC GTC TGT 911

74 Val Cys Val Cys Ile Cys Val His Leu Tyr Val Cys Val Cys Val Cys 89

912 CTG TGT GCA TGT GTG TAT GCG TGT GTA TGT ATG TGT CTG CGT CTG TGT 959

90 Leu Cys Ala Cys Val Tyr Ala Cys Val Cys Met Cys Leu Arg Leu Cys 105

960 GTG CGT CTG TGT GTA TCT GTG TGT GCA TGT GTG TAT GCG TGT ATA TGT 1007

106 Val Arg Leu Cys Val Ser Val Cys Ala Cys Val Tyr Ala Cys Ile Cys 121

l008 ATG TGC ATC TGT GTG CAT GTG TCT ATG TAT GTG TGT GCA TCT GTG TGT 1055

122 Met Cys Ile Cys Val His Val Ser Met Tyr Val Cys Ala Ser Val Cys 137

1056 GCG TGT GTA TGC GTG TGT GTA TGC GTC TGT GTG CAT GTG TGT ATG CGT 1103

138 Ala Cys Val Cys Val Cys Val Cys Val Cys Val His Val Cys Met Arg 153

1104 GTG TGT GCG CAT CAG TGT CTG CAT GTG TGT ATA TGT GTG TAT GTA TGT 1151

154 Val Cys Ala His Gln Cys Leu His Val Cys Ile Cys Val Tyr Val Cys 169

1152 GTG TGC GCG CGC ATC TGT GTG TGT GCA TGT GTG TAT GTA TGT GTG TGC 1199

170 Val Cys Ala Arg Ile Cys Val Cys Ala Cys Val Tyr Val Cys Val Cys 185

1200 ATC TCT GTG TGT GCA TGT GTG TAT GTG TGT GTG CAT CTG TGT GTG TGT 1247

186 Ile Ser Val Cys Ala Cys Val Tyr Val Cys Val His Leu Cys Val Cys 201

1248 GCA TGT GTG CAT GCG TGT GTA TGT GTG TGT GCG TGC GTG CAT CTG TGT 1295

202 Ala Cys Val His Ala Cys Val Cys Val Cys Ala Cys Val His Leu Cys 217

1296 GTG TGC GCG TGT GCC CAT GTG GGT GCG ACA CTA GTG TGC ATT TGC ACA 1343

218 Val Cys Ala Cys Ala His Val Gly Ala Thr Leu Val Cys Ile Cys Thr 233

1344 TAT ACA TGT CCC CGT CCG TCC ATG TTT GCA CAT GGT GGC AGA TGG GGG 1391

234 Tyr Thr Cys Pro Arg Pro Ser Met Phe Ala His Gly Gly Arg Trp Gly 249

1392 GTG GCT GGG AGG CCT AGG CAG CCA ATG AGC CTA GGT GTG CAG GCT CAG 1439

250 Val Ala Gly Arg Pro Arg Gln Pro Met Ser Leu Gly Val Gln Ala Gln 265

1440 GCC CAG AGA GTG ATC CAC CTT CCC CAG TCG GTT CAG GCC CTG ATC AAA 1487

266 Ala Gln Arg Val Ile His Leu Pro Gln Ser Val Gln Ala Leu Ile Lys 281

1488 GAC TTC CAG GGG ACC CCG ACT TTC ACC TAC AAA GCG GCC CAT ATC TTC 1535

282 Asp Phe Gln Gly Thr Pro Thr Phe Thr Tyr Lys Ala Ala His Ile Phe 297

1536 TTC ACC GAC ACC TGC CCC GAG CCC CTG TTC AGT GAG CTA GGC CGC TCT 1583

298 Phe Thr Asp Thr Cys Pro Glu Pro Leu Phe Ser Glu Leu Gly Arg Ser 313

1584 CGT CTG GCA AAG GTG GTG AAG ACG TTG AAG GAG ATT CAC CTT GCC TTC 1631

314 Arg Leu Ala Lys Val Val Lys Thr Leu Lys Glu Ile His Leu Ala Phe 329

1632 CTC CCC TAC GAG GCC CAG GTA CGG CCC GGG CTC ATC CTG GGC AGG GGG 1679

330 Leu Pro Tyr Glu Ala Gln Val Arg Pro Gly Leu Ile Leu Gly Arg Gly 345

1680 TGG GGG TTT GTG ACC AAA TGT CCC CTG TTC CCT CAG AAA CAG ACA CTG 1727

346 Trp Gly Phe Val Thr Lys Cys Pro Leu Phe Pro Gln Lys Gln Thr Leu 361

1728 AGG CTG GGC GCA GTG GCT CAT ACC TGT AAT CCC AGC GCT GTG GGA GGC 1775

362 Arg Leu Gly Ala Val Ala His Thr Cys Asn Pro Ser Ala Val Gly Gly 377

1776 CAG GGC AGG AGG ATC ACT TGG GGC CAG GAG TTT GAG ACC AGC CTG GGT 1823

378 Gln Gly Arg Arg Ile Thr Trp Gly Gln Glu Phe Glu Thr Ser Leu Gly 393

1824 ACA GAG CAA GAC CCC GTC TCT TAA AAA AAA AAA AAA AAA AAA AA 1867

394 Thr Glu Gln Asp Pro Val Ser *** 401

4.PP12744

A: nucleotide sequence (SEQ ID NO:10) length: 3094

1 GAGACACGCG GGGCTTCAGG CTGCTGCCCC ATTGGAAGAT TACTCCCCAG GCTTCCCTTG

61 CCCCAAGCAG TGAGCTGACT GGAATGGTAC CCCGGGAGGC CCCTGAGTCT GCTCAGTGCC

121 TGTGCCCTTC CCTCACCATC CCAAATGCCA AGGATGTGCT TCGGAAGAGG CACAAGAGAA

181 GGAGCCGACA GCACCAGCGG TTCATGGCCC GGAAGCCTTG CTGCAGGAGC AGGGGCTGCT

241 GAGCATGCCT CCAGAGCCAG GGTCCTCCCC ACTGCCCACC CCTTTCGGGG CAGCGACACG

301 AACTGAAGCT GCCAGCAGTG GGAAGCAGTG TCTGAGGGCT GGATCTGGCA GTGCCCCATG

361 CAGCAGAAGG CCTGCTCCCG GGAAAGCCTC AGGGCCCTTG CCCAGCAAGT GTGTGGCTAT

421 CGACTGTGAG ATGGTGGGCA CGGGACCCCG AGGCGGGTAA GCGAGCTGGC CCGCTGTTCC

481 ATTGTGAGCT ACCATGGCGA TGTCCTCTAT GACAAGTACA TCAGGCCTGA GATGCCCATC

541 GCTGACTACC GTACCCGCTG GAGTGGCATC ACTCGGCAGC ACATGCGCAA GGCTGTCCCC

601 TTCCAGGTGG CCCAGAAAGA GATCCTTAAG CTCCTGAAGG GCAAGGTGGT GGTGGGGCAC

661 GCGCTGCACA ACGACTTCCA GGCGCTCAAG TATGTCCACC CTCGGAGCCA GACCCGGGAT

721 ACCACCTATG TCCCAAACTT CCTCAGCGAG CCCGGCCTCC ACACCCGGGC CCGGGTCTCT

781 CTAAAGGACC TGGCCCTGCA GCTGCTGCAC AAGAAGATCC AGGTGGGCCA GCACGGGCAC

841 TCATCAGTAG AAGATGCCAC GACAGCCATG GAGCTCTACC GGCTGGTGGA GGTGCAGTGG

901 GAACAGCAGG AGGCCCGCAG CCTCTGGACC TGCCCCGAGG ACAGAGAACC TGACAGCAGC

961 ACAGACATGG AACAGTACAT GGAGGACCAG TACTGGCCCG ATGACCTGGC CCACGGCAGC

1021 AGAGGAGGAG CCAGGGAGGC ACAGGACAGA AGGAATTGAG AAGGGGGCGG GGCTCCCTGG

1081 CTGGGCTTCC GGTGTGGCCG GTAGGAAGTG GGGGCCAGGA GAGCAGCGGG CACTCCTTCC

1141 TGGGCAGGGT GGGGCAGGAT GCAGTGAGCC AGCCCCAGGG CCAGAGGAGT TGGGGTCATC

1201 TGTTACCTTG ACACCCTCTG CACACAGCAT AGCCCTCTCT CTCTCCAGGG CTGTTGGTTC

1261 TTTCTCCTGA CTCCTGTGGT TTTGCTAATG GCACTTTACA GACTCCATGG AGATGTCAGG

1321 TGGACCATCT TCTAGGGCCC AGCAGGAGTA GGGAATGTGC CAACAGACTG CCCAGGTTGC

1381 CGTGGCCTTC CCCACCCCCC AGATCTCCTG AGTCATCATG CTGTGCTAAT GAAAGGGATC

1441 ATATCATCCT CTCTGGGGAT GGTGGGTGGG GGGTGTCAAT ATCCTGGAGC TCCCTTACCC

1501 CAACTCAATG ACTTGGGGGT AAAGTTCTCT TCCTTTTGTT GCCTACCTCT TCCTCCACTC

1561 ATTTGGGTTC AGAATAAACA TGCCCTGAAG TTAAAGAGGA GTTAAGTCCT AAAGGAGGCA

1621 TTTCTTCCCC ACCTCCCTGA CCTGGAACTC TGGCTACAGC CATTGTAGGA ACTCCGTGCC

1681 TGGCCTGTCA GCTCCCTGCT AGGCTACAGT GGAATAGCAG AGCCCACAGG CTTCTCGTGG

1741 GGAGTTGGCT CCTTAACATT TCTTGGCAAC AGAAAGCCCC AGGCACAGCT CAGGGAGGAG

1801 GGAAGGCAGG TAAGCTTTGG ACGAGAACTG GCATATTTAT TTTGACCCAA ATCAAGGGAT

1861 TTCCCCAGTC CACCCAGTAC TGGGCTCTTA AGCAAAAGTC TGAGAAACAA GACAGTGGTT

1921 TGAATTCTGG GGCCTTTGTG TAGGATTGTG CCTGACCTTT ATTTATTTAT TAACAGCAGG

1981 GCCACTCGTC TAGGGCAGTG GAGTCTGCGT GTCTCCTGGG GCTGGGGCAG GGCATTGGCA

2041 GTTACGCAGT GGCCCTGAAC CTGGTCTGGT GCCCCCGAAC CTGGTCTGAT GCCCCCTCAG

2101 CTCTTTGACA ATCACTGTGG CTGTTGGGTT TTCTCCTATT TCTAAAAATG TTCTCTTCTT

2161 TCCTAAGTGA CAGTTTTGAA GTATTGGATA ACCAAGAGCT CAGGTCACAC AGACCTTGGA

2221 GCCCCATCTT TGCTTGCAGC TTAGCTTTGA GATACTAAGC AAGCGAGGGA CTTCACTCTT

2281 GAGCCTGTTT TTTCCTCATC TGTAAAGTGG GGATAGTGGT ACGGCCTACC TCATAGGGTT

2341 GTAATGAGCA CTAAATGTGA AGTGCTTGGC ACAGTGCCTG GCACATGGTG AGCCACAGCT

2401 ACTGTGAGTT TCTGTTTATC CCCCTTTTTT TTTTTTAAGC CCATTGTTTA TTCTTTGAGA

2461 ATTTGTTGTA ACTTCTTCAG GATAACACCT GAGTCCACAG GCTGAGCAGC TGTGGCCCAG

2521 ACAGAACTGC TCCGGCTTGG CTGTTCCAGC AGGTGGGGCG CTGGCCTCGG TGAGGGCACA

2581 GCAGCAAGGT TCACGGATAT CCGTGTGTCT TGTCTGTGGC CACCAGGCAC AGGTTTGGCT

2641 TCCGGTCAGT GTCCCGACAC TGTGCGGGAG GTGACAACAG AGCAAAGCAG CGCAGGGGTC

2701 AGGGAGGTGG AGACACTGCT GAAATCACAC TACCCCACCC TCAGCTGAAG CCCCACGTTC

2761 CACAAACTTG GGGTCATAGA TTGTCCAGTC ACTGGCTCCC TCCCTGTCAG CACAGCACAG

2821 AGGAAGGGGC TAACTGAATC TTTTACCACT TCTGGCCTGG CTCCAGAACT TTGTTCTAGA

2881 TTCCTTAAAA GTCGGTAGCT GATGTCAAAC TCAATTGAGC AGTAGCTTTG ATCCCTTGGT

2941 CTGGGGGTCG AAGGAAGATG GCGCTGTTAT CAGCGGGGAA ATGTACTATT TAAGATCAGC

3001 TTTGTTGTAA AACCATTTGT TCTAGAATAA AACTCAATTG GAAACGTGAA AAAAAAAAAA

3061 AAAAAAAAAA AAAAAAAAAC TCGAGACTAG TTCT

B: aminoacid sequence (SEQ ID NO:11) length: 175

1 MPIADYRTRW SGITRQHMRK AVPFQVAQKE ILKLLKGKVV VGHALHNDFQ ALKYVHPRSQ

61 TRDTTYVPNF LSEPGLHTRA RVSLKDLALQ LLHKKIQVGQ HGHSSVEDAT TAMELYRLVE

121 VQWEQQEARS LWTCPEDREP DSSTDMEQYM EDQYWPDDLA HGSRGGAREA QDRRN

C. Nucleotide and amino acid composite sequence (SEQ ID NO:12) clone number: PP12744 start code: 532 ATG stop coding: 1057 TGA protein molecular weights: 20287.83

1 GAG ACA CGC GGG GCT TCA GGC TGC TGC CCC ATT GGA AGA TTA CTC CCC 48

49 AGG CTT CCC TTG CCC CAA GCA GTG AGC TGA CTG GAA TGG TAC CCC GGG 96

97 AGG CCC CTG AGT CTG CTC AGT GCC TGT GCC CTT CCC TCA CCA TCC CAA 144

145 ATG CCA AGG ATG TGC TTC GGA AGA GGC ACA AGA GAA GGA GCC GAC AGC 192

193 ACC AGC GGT TCA TGG CCC GGA AGC CTT GCT GCA GGA GCA GGG GCT GCT 240

241 GAG CAT GCC TCC AGA GCC AGG GTC CTC CCC ACT GCC CAC CCC TTT CGG 288

289 GGC AGC GAC ACG AAC TGA AGC TGC CAG CAG TGG GAA GCA GTG TCT GAG 336

337 GGC TGG ATC TGG CAG TGC CCC ATG CAG CAG AAG GCC TGC TCC CGG GAA 384

385 AGC CTC AGG GCC CTT GCC CAG CAA GTG TGT GGC TAT CGA CTG TGA GAT 432

433 GGT GGG CAC GGG ACC CCG AGG CGG GTA AGC GAG CTG GCC CGC TGT TCC 480

481 ATT GTG AGC TAC CAT GGC GAT GTC CTC TAT GAC AAG TAC ATC AGG CCT 528

529 GAG ATG CCC ATC GCT GAC TAC CGT ACC CGC TGG AGT GGC ATC ACT CGG 576

1 Met Pro Ile Ala Asp Tyr Arg Thr Arg Trp Ser Gly Ile Thr Arg 15

577 CAG CAC ATG CGC AAG GCT GTC CCC TTC CAG GTG GCC CAG AAA GAG ATC 624

16 Gln His Met Arg Lys Ala Val Pro Phe Gln Val Ala Gln Lys Glu Ile 31

625 CTT AAG CTC CTG AAG GGC AAG GTG GTG GTG GGG CAC GCG CTG CAC AAC 672

32 Leu Lys Leu Leu Lys Gly Lys Val Val Val Gly His Ala Leu His Asn 47

673 GAC TTC CAG GCG CTC AAG TAT GTC CAC CCT CGG AGC CAG ACC CGG GAT 720

48 Asp Phe Gln Ala Leu Lys Tyr Val His Pro Arg Ser Gln Thr Arg Asp 63

721 ACC ACC TAT GTC CCA AAC TTC CTC AGC GAG CCC GGC CTC CAC ACC CGG 768

64 Thr Thr Tyr Val Pro Asn Phe Leu Ser Glu Pro Gly Leu His Thr Arg 79

769 GCC CGG GTC TCT CTA AAG GAC CTG GCC CTG CAG CTG CTG CAC AAG AAG 816

80 Ala Arg Val Ser Leu Lys Asp Leu Ala Leu Gln Leu Leu His Lys Lys 95

817 ATC CAG GTG GGC CAG CAC GGG CAC TCA TCA GTA GAA GAT GCC ACG ACA 864

96 Ile Gln Val Gly Gln His Gly His Ser Ser Val Glu Asp Ala Thr Thr 111

865 GCC ATG GAG CTC TAC CGG CTG GTG GAG GTG CAG TGG GAA CAG CAG GAG 912

112 Ala Met Glu Leu Tyr Arg Leu Val Glu Val Gln Trp Glu Gln Gln Glu 127

913 GCC CGC AGC CTC TGG ACC TGC CCC GAG GAC AGA GAA CCT GAC AGC AGC 960

128 Ala Arg Ser Leu Trp Thr Cys Pro Glu Asp Arg Glu Pro Asp Ser Ser 143

961 ACA GAC ATG GAA CAG TAC ATG GAG GAC CAG TAC TGG CCC GAT GAC CTG 1008

144 Thr Asp Met Glu Gln Tyr Met Glu Asp Gln Tyr Trp Pro Asp Asp Leu 159

1009 GCC CAC GGC AGC AGA GGA GGA GCC AGG GAG GCA CAG GAC AGA AGG AAT 1056

160 Ala His Gly Ser Arg Gly Gly Ala Arg Glu Ala Gln Asp Arg Arg Asn 175

1057 TGA GAA GGG GGC GGG GCT CCC TGG CTG GGC TTC CGG TGT GGC CGG TAG 1104

176 *** 176

1105 GAA GTG GGG GCC AGG AGA GCA GCG GGC ACT CCT TCC TGG GCA GGG TGG 1152

1153 GGC AGG ATG CAG TGA GCC AGC CCC AGG GCC AGA GGA GTT GGG GTC ATC 1200

1201 TGT TAC CTT GAC ACC CTC TGC ACA CAG CAT AGC CCT CTC TCT CTC CAG 1248

1249 GGC TGT TGG TTC TTT CTC CTG ACT CCT GTG GTT TTG CTA ATG GCA CTT 1296

1297 TAC AGA CTC CAT GGA GAT GTC AGG TGG ACC ATC TTC TAG GGC CCA GCA 1344

1345 GGA GTA GGG AAT GTG CCA ACA GAC TGC CCA GGT TGC CGT GGC CTT CCC 1392

1393 CAC CCC CCA GAT CTC CTG AGT CAT CAT GCT GTG CTA ATG AAA GGG ATC 1440

1441 ATA TCA TCC TCT CTG GGG ATG GTG GGT GGG GGG TGT CAA TAT CCT GGA 1488

1489 GCT CCC TTA CCC CAA CTC AAT GAC TTG GGG GTA AAG TTC TCT TCC TTT 1536

1537 TGT TGC CTA CCT CTT CCT CCA CTC ATT TGG GTT CAG AAT AAA CAT GCC 1584

1585 CTG AAG TTA AAG AGG AGT TAA GTC CTA AAG GAG GCA TTT CTT CCC CAC 1632

1633 CTC CCT GAC CTG GAA CTC TGG CTA CAG CCA TTG TAG GAA CTC CGT GCC 1680

1681 TGG CCT GTC AGC TCC CTG CTA GGC TAC AGT GGA ATA GCA GAG CCC ACA 1728

1729 GGC TTC TCG TGG GGA GTT GGC TCC TTA ACA TTT CTT GGC AAC AGA AAG 1776

1777 CCC CAG GCA CAG CTC AGG GAG GAG GGA AGG CAG GTA AGC TTT GGA CGA 1824

1825 GAA CTG GCA TAT TTA TTT TGA CCC AAA TCA AGG GAT TTC CCC AGT CCA 1872

1873 CCC AGT ACT GGG CTC TTA AGC AAA AGT CTG AGA AAC AAG ACA GTG GTT 1920

1921 TGA ATT CTG GGG CCT TTG TGT AGG ATT GTG CCT GAC CTT TAT TTA TTT 1968

1969 ATT AAC AGC AGG GCC ACCT CGT CTA GGG CAG TGGAGT CTG CGT GTC TCC 2016

2017 TGG GGC TGG GGC AGG GCA TTG GCA GTT ACG CAG TGG CCC TGA ACC TGG 2064

2065 TCT GGT GCC CCC GAA CCT GGT CTG ATG CCC CCT CAG CTC TTT GAC AAT 2112

2113 CAC TGT GGC TGT TGG GTT TTC TCC TAT TTC TAA AAA TGT TCT CTT CTT 2160

2161 TCC TAA GTG ACA GTT TTG AAG TAT TGG ATA ACC AAG AGC TCA GGT CAC 2208

2209 ACA GAC CTT GGA GCC CCA TCT TTG CTT GCA GCT TAG CTT TGA GAT ACT 2256

2257 AAG CAA GCG AGG GAC TTC ACT CTT GAG CCT GTT TTT TCC TCA TCT GTA 2304

2305 AAG TGG GGA TAG TGG TAC GGC CTA CCT CAT AGG GTT GTA ATG AGC ACT 2352

2353 AAA TGT GAA GTG CTT GGC ACA GTG CCT GGC ACA TGG TGA GCC ACA GCT 2400

2401 ACT GTG AGT TTC TGT TTA TCC CCC TTT TTT TTT TTT AAG CCC ATT GTT 2448

2449 TAT TCT TTG AGA ATT TGT TGT AAC TTC TTC AGG ATA ACA CCT GAG TCC 2496

2497 ACA GGC TGA GCA GCT GTG GCC CAG ACA GAA CTG CTC CGG CTT GGC TGT 2544

2545 TCC AGC AGG TGG GGC GCT GGC CTC GGT GAG GGC ACA GCA GCA AGG TTC 2592

2593 ACG GAT ATC CGT GTG TCT TGT CTG TGG CCA CCA GGC ACA GGT TTG GCT 2640

2641 TCC GGT CAG TGT CCC GAC ACT GTG CGG GAG GTG ACA ACA GAG CAA AGC 2688

2689 AGC GCA GGG GTC AGG GAG GTG GAG ACA CTG CTG AAA TCA CAC TAC CCC 2736

2737 ACC CTC AGC TGA AGC CCC ACG TTC CAC AAA CTT GGG GTC ATA GAT TGT 2784

2785 CCA GTC ACT GGC TCC CTC CCT GTC AGC ACA GCA CAG AGG AAG GGG CTA 2832

2833 ACT GAA TCT TTT ACC ACT TCT GGC CTG GCT CCA GAA CTT TGT TCT AGA 2880

2881 TTC CTT AAA AGT CGG TAG CTG ATG TCA AAC TCA ATT GAG CAG TAG CTT 2928

2929 TGA TCC CTT GGT CTG GGG GTC GAA GGA AGA TGG CGC TGT TAT CAG CGG 2976

2977 GGA AAT GTA CTA TTT AAG ATC AGC TTT GTT GTA AAA CCA TTT GTT CTA 3024

3025 GAA TAA AAC TCA ATT GGA AAC GTG AAA AAA AAA AAA AAA AAA AAA AAA 3072

3073 AAA AAA ACT CGA GAC TAG TTC T 3094

5.PP13624

A: nucleotide sequence (SEQ ID NO:13) length: 2140

1 GCGGAGCCGG GCTCACCAGG TCGCTGCTGC GAGGGAGTTG CTGTGCTGGG GCCTGGGTGG

61 CGGCTGGAGG CCTGAGTTGG GCTCGCGGCG GGGGTCGGCA GGGGGCCGGG TGGCGGAATG

121 ATGGAGGAGG AGGAACTGGA GTTCGTGGAG GAGCTGGAAG CCGTGCTGCA GCTCACGCCC

181 GAGGTGCAGC TGGCCATCGA GCAGGTGTTT CCAAGCCAGG ACCCTCTAGA TCGAGCAGAT

241 TTCAATGCTG TTGAGTATAT CAATACCCTG TTCCCAACCG AGCAATCTCT GGCGAACATA

301 GACGAAGTCG TGAACAAAAT TAGGCTGAAA ATAAGGAGAC TGGATGACAA TATTCGAACT

361 GTTGTAAGAG GTCAGACGAA CGTGGGGCAG GATGGACGGC AAGCGCTTGA AGAGGCTCAG

421 AAAGCTATCC AACAACTCTT TGGCAAAATC AAAGATATCA AAGACAAAGC TGAAAAATCA

481 GAGCAAATGG TGAAAGAAAT CACCCGTGAT ATTAAGCAAT TAGATCACGC CAAACGCCAC

541 CTGACCACCT CAATCACCAC ACTGAACCAC CTGCACATGC TGGCAGGAGG TGTCGACTCC

601 CTCGAAGCCA TGACCAGGCG AAGACAATAC GGAGAAGTTG CTAATCTCCT TCAGGGTGTG

661 ATGAATGTCC TGGAGCACTT CCACAAGTAT ATGGGGATTC CGCAGATCCG GCAGCTTTTCC

721 GAAAGAGTGA AGGCTGCACA GACTGAGTTA GGACAGCAAA TCCTGGCAGA TTTTGAAGAA

781 GCGTTTCCTT CCCAGGGCAC CAAGAGACCA GGAGGACCCA GCAATGTTCT ACGAGATGCA

841 TGTCTGGTTG CTAATATTCT AGATCCCAGG ATCAAACAGG AAATCATCAA AAAGTTTATT

901 AAACAGCATC TGTCAGAGTA TCTGGTACTT TTTCAAGAAA ACCAAGATGT TGCCTGGCTG

961 GACAAAATCG ACAGACGCTA TGCCTGGATA AAACGCCAGC TTGTGGACTA TGAGGAGAAA

1021 TACGGCCGCA TGTTTCCACG TGAGTGGTGC ATGGCTGAGA GGATTGCGGT GGAATTTTGC

1081 CATGTGACAA GGGCAGAACT TGCCAAGATT ATGCGTACCA GAGCGAAGGA AATTGAAGTG

1141 AAATTGCTTC TTTTTGCTAT TCAAAGAACA ACTAACTTTG AGGGGTTTCT TGCAAAACGC

1201 TTCTCCGGCT GCACCCTGAC CGATGGGACC CTGAAAAAGC TTGAGTCTCC ACCCCCATCT

1261 ACCAATCCCT TCCTGGAAGA TGAGCCAACA CCAGAGATGG AGGAACTGGC AACGGAGAAA

1321 GGAGATTTAG ATCAACCAAA GAAGCCTAAA GCCCCAGACA ATCCATTTCA TGGCATTGTT

1381 TCCAAGTGTT TTGAGCCTCA TCTCTACGTG TATATCGAAT CCCAAGACAA GAACCTCGGA

1441 GAGCTGATAG ATCGGTTTGT GGCTGATTTC AAAGCCCAGG GGCCACCTAA GCCCAACACT

1501 GATGAAGGGG GTGCCGTGCT CCCCAGCTGC GCCGACCTCT TTGTCTACTA CAAGAAGTGC

1561 ATGGTGCAAT GCTCTCAGCT CAGTACTGGG GAGCCCATGA TCGCCCTGAC CACCATTTTC

1621 CAGAAGTACC TCCGAGAATA TGCCTGGAAA ATCCTCTCTG GCAACCTGCC CAAAACCACA

1681 ACCAGCAGTG GAGGACTGAC TATCAGCAGC CTCCTCAAGG AAAAGGAGGG CTCAGAAGTA

1741 GCCAAGTTCA CTCTGGAGGA GCTCTGCCTC ATCTGTAACA TCCTGAGCAC GGCAGAGTAC

1801 TTGTCTGGCC ACCACCCAGC AGCTAGAAGA AAAACTCAAA GAAAAAGTGGA TGTAAGTCT

1861 GATTGAACGA ATCAATCTGA CTGGAGAGAT GGACACGTTC AGCACCGTCA TCTCCAGCAG

1921 TATTCAGCTG CTGGTTCAGG ATCTGGATGC TGCCTGTGAT CCTGCCCTGA CTGCCATGAG

1981 CAAGATGCAG TGGCAGAACG TGGAGCACGT TGGTGACCAG AGCCCCTACG TCACCTCTGT

2041 CATTCTGCAC ATCAAGCAGA ACGTCCCCAT CATCCGTGAC AACCTGGCCA ACATGGCAAA

2101 ATCCCATCTC TACTAAAAAT ACAAAAAAAA AAAAAAAAAA

B: aminoacid sequence (SEQ ID NO:14) length: 582

1 MMEEEELEFV EELEAVLQLT PEVQLAIEQV FPSQDPLDRA DFNAVEYINT LFPTEQSLAN

61 IDEVVNKIRL KIRRLDDNIR TVVRGQTNVG QDGRQALEEA QKAIQQLFGK IKDIKDKAEK

121 SEQMVKEITR DIKQLDHAKR HLTTSITTLN HLHMLAGGVD SLEAMTRRRQ YGEVANLLQG

181 VMNVLEHFHK YMGIPQIRQL SERVKAAQTE LGQQILADFE EAFPSQGTKR PGGPSNVLRD

241 ACLVANILDP RIKQEIIKKF IKQHLSEYLV LFQENQDVAW LDKIDRRYAW IKRQLVDYEE

301 KYGRMFPREW CMAERIAVEF CHVTRAELAK IMRTRAKEIE VKLLLFAIQR TTNFEGFLAK

361 RFSGCTLTDG TLKKLESPPP STNPFLEDEP TPEMEELATE KGDLDQPKKP KAPDNPFHGI

421 VSKCFEPHLY VYIESQDKNL GELIDRFVAD FKAQGPPKPN TDEGGAVLPS CADLFVYYKK

481 CMVQCSQLST GEPMIALTTI FQKYLREYAW KILSGNLPKT TTSSGGLTIS SLLKEKEGSE

541 VAKFTLEELC LICNILSTAE YLSGHHPAAR RKTQRKSGCK SD

C. Nucleotide and amino acid composite sequence (SEQ ID NO:15) clone number: PP13624 start code: 118 ATG stop coding: 1864 TGA protein molecular weights: 66318.71

1 GCG GAG CCG GGC TCA CCA GGT CGC TGC TGC GAG GGA GTT GCT GTG CTG 48

49 GGG CCT GGG TGG CGG CTG GAG GCC TGA GTT GGG CTC GCG GCG GGG GTC 96

97 GGC AGG GGG CCG GGT GGC GGA ATG ATG GAG GAG GAG GAA CTG GAG TTC 144

1 Met Met Glu Glu Glu Glu Leu Glu Phe 9

145 GTG GAG GAG CTG GAA GCC GTG CTG CAG CTC ACG CCC GAG GTG CAG CTG 192

10 Val Glu Glu Leu Glu Ala Val Leu Gln Leu Thr Pro Glu Val Gln Leu 25

193 GCC ATC GAG CAG GTG TTT CCA AGC CAG GAC CCT CTA GAT CGA GCA GAT 240

26 Ala Ile Glu Gln Val Phe Pro Ser Gln Asp Pro Leu Asp Arg Ala Asp 41

241 TTC AAT GCT GTT GAG TAT ATC AAT ACC CTG TTC CCA ACC GAG CAA TCT 288

42 Phe Asn Ala Val Glu Tyr Ile Asn Thr Leu Phe Pro Thr Glu Gln Ser 57

289 CTG GCG AAC ATA GAC GAA GTC GTG AAC AAA ATT AGG CTG AAA ATA AGG 336

58 Leu Ala Asn Ile Asp Glu Val Val Asn Lys Ile Arg Leu Lys Ile Arg 73

337 AGA CTG GAT GAC AAT ATT CGA ACT GTT GTA AGA GGT CAG ACG AAC GTG 384

74 Arg Leu Asp Asp Asn Ile Arg Thr Val Val Arg Gly Gln Thr Asn Val 89

385 GGG CAG GAT GGA CGG CAA GCG CTT GAA GAG GCT CAG AAA GCT ATC CAA 432

90 Gly Gln Asp Gly Arg Gln Ala Leu Glu Glu Ala Gln Lys Ala Ile Gln 105

433 CAA CTC TTT GGC AAA ATC AAA GAT ATC AAA GAC AAA GCT GAA AAA TCA 480

106 Gln Leu Phe Gly Lys Ile Lys Asp Ile Lys Asp Lys Ala Glu Lys Ser 121

481 GAG CAA ATG GTG AAA GAA ATC ACC CGT GAT ATT AAG CAA TTA GAT CAC 528

122 Glu Gln Met Val Lys Glu Ile Thr Arg Asp Ile Lys Gln Leu Asp His 137

529 GCC AAA CGC CAC CTG ACC ACC TCA ATC ACC ACA CTG AAC CAC CTG CAC 576

138 Ala Lys Arg His Leu Thr Thr Ser Ile Thr Thr Leu Asn His Leu His 153

577 ATG CTG GCA GGA GGT GTC GAC TCC CTC GAA GCC ATG ACC AGG CGA AGA 624

154 Met Leu Ala Gly Gly Val Asp Ser Leu Glu Ala Met Thr Arg Arg Arg 169

625 CAA TAC GGA GAA GTT GCT AAT CTC CTT CAG GGT GTG ATG AAT GTC CTG 672

170 Gln Tyr Gly Glu Val Ala Asn Leu Leu Gln Gly Val Met Asn Val Leu 185

673 GAG CAC TTC CAC AAG TAT ATG GGG ATT CCG CAG ATC CGG CAG CTT TCC 720

186 Glu His Phe His Lys Tyr Met Gly Ile Pro Gln Ile Arg Gln Leu Ser 201

721 GAA AGA GTG AAG GCT GCA CAG ACT GAG TTA GGA CAG CAA ATC CTG GCA 768

202 Glu Arg Val Lys Ala Ala Gln Thr Glu Leu Gly Gln Gln Ile Leu Ala 217

769 GAT TTT GAA GAA GCG TTT CCT TCC CAG GGC ACC AAG AGA CCA GGA GGA 816

218 Asp Phe Glu Glu Ala Phe Pro Ser Gln Gly Thr Lys Arg Pro Gly Gly 233

817 CCC AGC AAT GTT CTA CGA GAT GCA TGT CTG GTT GCT AAT ATT CTA GAT 864

234 Pro Ser Asn Val Leu Arg Asp Ala Cys Leu Val Ala Asn Ile Leu Asp 249

865 CCC AGG ATC AAA CAG GAA ATC ATC AAA AAG TTT ATT AAA CAG CAT CTG 912

250 Pro Arg Ile Lys Gln Glu Ile Ile Lys Lys Phe Ile Lys Gln His Leu 265

913 TCA GAG TAT CTG GTA CTT TTT CAA GAA AAC CAA GAT GTT GCC TGG CTG 960

266 Ser Glu Tyr Leu Val Leu Phe Gln Glu Asn Gln Asp Val Ala Trp Leu 281

961 GAC AAA ATC GAC AGA CGC TAT GCC TGG ATA AAA CGC CAG CTT GTG GAC 1008

282 Asp Lys Ile Asp Arg Arg Tyr Ala Trp Ile Lys Arg Gln Leu Val Asp 297

1009 TAT GAG GAG AAA TAC GGC CGC ATG TTT CCA CGT GAG TGG TGC ATG GCT 1056

298 Tyr Glu Glu Lys Tyr Gly Arg Met Phe Pro Arg Glu Trp Cys Met Ala 313

1057 GAG AGG ATT GCG GTG GAA TTT TGC CAT GTG ACA AGG GCA GAA CTT GCC 1104

314 Glu Arg Ile Ala Val Glu Phe Cys His Val Thr Arg Ala Glu Leu Ala 329

1105 AAG ATT ATG CGT ACC AGA GCG AAG GAA ATT GAA GTG AAA TTG CTT CTT 1152

330 Lys Ile Met Arg Thr Arg Ala Lys Glu Ile Glu Val Lys Leu Leu Leu 345

1153 TTT GCT ATT CAA AGA ACA ACT AAC TTT GAG GGG TTT CTT GCA AAA CGC 1200

346 Phe Ala Ile Gln Arg Thr Thr Asn Phe Glu Gly Phe Leu Ala Lys Arg 361

1201 TTC TCC GGC TGC ACC CTG ACC GAT GGG ACC CTG AAA AAG CTT GAG TCT 1248

362 Phe Ser Gly Cys Thr Leu Thr Asp Gly Thr Leu Lys Lys Leu Glu Ser 377

1249 CCA CCC CCA TCT ACC AAT CCC TTC CTG GAA GAT GAG CCA ACA CCA GAG 1296

378 Pro Pro Pro Ser Thr Asn Pro Phe Leu Glu Asp Glu Pro Thr Pro Glu 393

1297 ATG GAG GAA CTG GCA ACG GAG AAA GGA GAT TTA GAT CAA CCA AAG AAG 1344

394 Met Glu Glu Leu Ala Thr Glu Lys Gly Asp Leu Asp Gln Pro Lys Lys 409

1345 CCT AAA GCC CCA GAC AAT CCA TTT CAT GGC ATT GTT TCC AAG TGT TTT 1392

410 Pro Lys Ala Pro Asp Asn Pro Phe His Gly Ile Val Ser Lys Cys Phe 425

1393 GAG CCT CAT CTC TAC GTG TAT ATC GAA TCC CAA GAC AAG AAC CTC GGA 1440

426 Glu Pro His Leu Tyr Val Tyr Ile Glu Ser Gln Asp Lys Asn Leu Gly 441

1441 GAG CTG ATA GAT CGG TTT GTG GCT GAT TTC AAA GCC CAG GGG CCA CCT 1488

442 Glu Leu Ile Asp Arg Phe Val Ala Asp Phe Lys Ala Gln Gly Pro Pro 457

1489 AAG CCC AAC ACT GAT GAA GGG GGT GCC GTG CTC CCC AGC TGC GCC GAC 1536

458 Lys Pro Asn Thr Asp Glu Gly Gly Ala Val Leu Pro Ser Cys Ala Asp 473

1537 CTC TTT GTC TAC TAC AAG AAG TGC ATG GTG CAA TGC TCT CAG CTC AGT 1584

474 Leu Phe Val Tyr Tyr Lys Lys Cys Met Val Gln Cys Ser Gln Leu Ser 489

1585 ACT GGG GAG CCC ATG ATC GCC CTG ACC ACC ATT TTC CAG AAG TAC CTC 1632

490 Thr Gly Glu Pro Met Ile Ala Leu Thr Thr Ile Phe Gln Lys Tyr Leu 505

1633 CGA GAA TAT GCC TGG AAA ATC CTC TCT GGC AAC CTG CCC AAA ACC ACA 1680

506 Arg Glu Tyr Ala Trp Lys Ile Leu Ser Gly Asn Leu Pro Lys Thr Thr 521

1681 ACC AGC AGT GGA GGA CTG ACT ATC AGC AGC CTC CTC AAG GAA AAG GAG 1728

522 Thr Ser Ser Gly Gly Leu Thr Ile Ser Ser Leu Leu Lys Glu Lys Glu 537

1729 GGC TCA GAA GTA GCC AAG TTC ACT CTG GAG GAG CTC TGC CTC ATC TGT 1776

538 Gly Ser Glu Val Ala Lys Phe Thr Leu Glu Glu Leu Cys Leu Ile Cys 553

1777 AAC ATC CTG AGC ACG GCA GAG TAC TTG TCT GGC CAC CAC CCA GCA GCT 1824

554 Asn Ile Leu Ser Thr Ala Glu Tyr Leu Ser Gly His His Pro Ala Ala 569

1825 AGA AGA AAA ACT CAA AGA AAA AGT GGA TGT AAG TCT GAT TGA ACG AAT 1872

570 Arg Arg Lys Thr Gln Arg Lys Ser Gly Cys Lys Ser Asp *** 583

1873 CAA TCT GAC TGG AGA GAT GGA CAC GTT CAG CAC CGT CAT CTC CAG CAG 1920

1921 TAT TCA GCT GCT GGT TCA GGA TCT GGA TGC TGC CTG TGA TCC TGC CCT 1968

1969 GAC TGC CAT GAG CAA GAT GCA GTG GCA GAA CGT GGA GCA CGT TGG TGA 2016

2017 CCA GAG CCC CTA CGT CAC CTC TGT CAT TCT GCA CAT CAA GCA GAA CGT 2064

2065 CCC CAT CAT CCG TGA CAA CCT GGC CAA CAT GGC AAA ATC CCA TCT CTA 2112

2113 CTA AAA ATA CAA AAA AAA AAA AAA AAA A 2140

6.PP13671

A: nucleotide sequence (SEQ ID NO:16) length: 2986

1 GGGAGGACCC GCGACACAGC TCGGGATCCG CGCGCGCTGG GCCTTCGGCG CCGCTCGTGG

61 GGTTCGGGAG GCCGGGACCC TGCCCGGGAG ATGTGGACGC CGGGCGGACC CCCGGGGTCC

121 GCGGGCTGGG ACCGCCGTAG GTTGGGCGCG AGGTTGCGCG CGGCGTTCGC GGGGCTGCAG

181 GAGCTGCAGG GGCTGCGAGC CACGCAGCAG GAGCGGGTAC GGGGCGCCCT GGCCCTGCAG

241 CCCCCGCCCG CGCCCGCCGC GCCCTGCGGC CCCCACGGCC TCCACGGCCC CGAGCAGCAG

301 CTGGAGGCGG CGCTGGCCGC GCTGCAGGAG CAGCTGTCCC GGCTGAGACA ACAGGACATC

361 GGCCTGAAGA CCCACCTGGA CCAGCTGGAC CTGCAGATTA GCAAGCTGCA GCTGGATGTG

421 GGCACAGCCT CAGGGGAGGC CCTGGACAGC GACAGCAGGC CCAGCTCAGG CTTTTACGAG

481 ATGAGCGACG GTGGATCCTG CTCCCTGTCC ACGTCCTGTG CCTCCGTCTG CAGTGACCAC

541 ATCTCTCCCT CGCTGGGCAG TTTGTTGCCT GTGGCCCAGG CCCACAAGGC CAGGCCCAGC

601 ATGGGGGACT GGAGGCCCCG GTCGGTTGAT GAGACTACTG TGCCAGCGTG GAGACCCCAG

661 GCTACCGAGG AGGCCGCCAG GCCCCCAGGG AGCGTGGAGG ATGCAGGCCA GCCGTGGGGC

721 ACATTCTGGC CCAGGCCTGT GTCTACAGGT GATCTTGACA GAGCCCTGCC GGCGGACACG

781 GGGCTCCAGA AAGCCAGCGC GGACGCCGAG CTCCTCGGGC TCCTCTGCAG GGGGTGGATA

841 TCCCGCTGCA CGTGCCGGAC CCCAAGTATC GGCAGGACCT GGTGTCCCAG GGCGGCAGGG

901 AGGTGTACCC GTACCCCAGC CCCCTGCACG CCGTGGCTCT ACAGAGCCCC CTGTTTGTCC

961 TGACTAAGGA AACCCCACAG AGAGGTGGCC CCTCGTTCCC TAGGGAGAGC CCCAGGGGCC

1021 CCGCAGGTCT GAACACCATC CAGACTGGGC CGGTCCTCGA GGCTGGCCCG GCCAGGGCCA

1081 GAGCTTATAT CGACAGGTTG CTGCATCTGT GGGGCCGGGA GACCCCAGCA AAGGGTAGCG

1141 AGGGAGAACA GGGACCTCTA AGGCATGCAG CGTCCCCATC TCCACAGAGG CAGGGTGGCT

1201 GGAGTACAGA CGGTGGAGGG CGACTGCTGG TCTTCGCCCC AGGGAGGGAG GACGAGGGAG

1261 GGCCAGCTCA GAGCAGGGGT GCCGGCAGGG GCGGGCCCCA GCAGCAGGGA TACATGCCCC

1321 TTGAGGGTCC CCAGCAGTCT GGCAGCCTTC CAGAGGAGGG CTCCAAGCCC TCAAACAGCT

1381 GTGTCCTCAG GGAGACCATG GTGCAGGCTT CTCCCAGCTC AAAGGCCCAG CAGACACCCT

1441 CAGCTCAGGA CTATGGACGA GGCAACATCA TATCCCCATC CAGGATGCTG GACAAGAGCC

1501 CCTCACCGGC CTCTGGGCAC TTTGCCCACC CATCCTTTGC TGCCAGCCTG AAAATGGGTC

1561 CCCCCAAGAG CAAGGCTGAA AAAATCAAGA GAAGTCCCAT GGACAAGGTG CTGAGGTTTG

1621 CAAGGCAGCC GCTGCTTCTA CTGGACAGGC CTGAGGGAGC CCATGCAGCC CCCCAGCCAT

1681 CCCTGGAGTG GGACCCTGCC CACTGGCCCA CAGGGAGGGG CGGGCTCCAG CGGAGGCCAG

1741 CCCTGGCCTG GGAGGCACCC GGGCGCTCCT GTTCTGAGTC CACCCTCTAC CCCATGCCTG

1801 TCCTCGTCCC CTTGGCAGTG GCCCCGCAGG AGAGCCACCG GACCTCAGCC CAAGCCCTGT

1861 TCCCCTTTGA GGCGTCACTG CTCACCTCAG TGGCCAGGAG GAAGCATCGC CGCTGGCAGT

1921 CCACCGTGGA GATCTCGGCC CGGGCCCGCC TGGCCAGCTG TCCTGAGTCT AACCTGGGGC

1981 CCCCCAGGCC CGTGGCCAGG AGAGCAGGTG GCCCACTGGC CCGGGGCCGT CCCTCACTGG

2041 TCCGCCAGGA CGCCTACACC AGGAGCGACT CAGAGCCCTC CAAGCACTCG GCCGAGTGTG

2101 ACCCGCGGTT CCCGTCAGTC ATCCCGGAGA CCAGCGAGGG AGAGTCCAGT GACCACACCA

2161 CCAACCGATT CGGAGACCGT GAGTCCAGCA GCAGCGACGA GGAGGGCGGC GCCCAGAGCA

2221 GGGACTGTGA CCTGGCACTG GGCTATGTGG CGGCCGGGCA TGAGGAGCTG GCCTGGACCC

2281 AGGAGGCCCC GGTCAGCTCG GGGCCACTCC TGTCCCCCGT GCCCAAGCTG TGCCGTATTA

2341 AGGCCTCCAA GGCCCTGAAG AAGAAGATCC GCAGGTTCCA GCCGACGGCC CTGAAGGTCA

2401 TGACCATGGT GTGAGGTGCA GTGACTGCGT CAAGAGAAGC CTGCTGCACA CAGGGGCCCT

2461 TTCCATGCAG TGTCCTGTGC ATGTCTGGGT TTCAGTGTCG TCTTGCCAAG TCGCTTTATC

2521 TTCCGAGGCC ACCGTTTAAC AGGAGTCCCC GCAGATGGGT TCTGCCCTGT GGAGTATGGC

2581 CGTGAGTCCC CGCCCCAGCA AAGACTTCCA TGCGGAGCTC TGGTTTCAGA TGCCAGCAGC

2641 CTCCCCGGCC GACCTAGTGT CTCTTTTCAA GGTCTGCCCA GGATGCTGCT TCCCGGCATG

2701 CACCTTGTTT CCATGTTGTC ATCCTCCCAT GGCTTCCCCT GCCCTCACTC CCCTCTGGCT

2761 GGGGAAGTGT TTCCCAATCC TTTGACCATT CCTCCCCAAA AGCATTTTAA AAAGGCGGTT

2821 GCAGGACTTT GAGCTGGAAA TTGAATTTGA GTTTAAACTC CACGTTAAGC TGTCAGCATA

2881 CACAAACACC CAAATTATGC CATGATCTCA AATAAAAGGA ACATTTTTTT TCCCTCTTTT

2941 AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAA

B: aminoacid sequence (SEQ ID NO:17) length: 366

1 MPLEGPQQSG SLPEEGSKPS NSCVLRETMV QASPSSKAQQ TPSAQDYGRG NIISPSRMLD

61 KSPSPASGHF AHPSFAASLK MGPPKSKAEK IKRSPMDKVL RFARQPLLLL DRPEGAHAAP

121 QPSLEWDPAH WPTGRGGLQR RPALAWEAPG RSCSESTLYP MPVLVPLAVA PQESHRTSAQ

181 ALFPFEASLL TSVARRKHRR WQSTVEISAR ARLASCPESN LGPPRPVARR AGGPLARGRP

241 SLVRQDAYTR SDSEPSKHSA ECDPRFPSVI PETSEGESSD HTTNRFGDRE SSSSDEEGGA

301 QSRDCDLALG YVAAGHEELA WTQEAPVSSG PLLSPVPKLC RIKASKALKK KIRRFQPTAL

361 KVMTMV

C. Nucleotide and amino acid composite sequence (SEQ ID NO:18) clone number: PP13671 start code: 1314 ATG stop coding: 2412 TGA protein molecular weights: 39633.59

1 GG GAG GAC CCG CGA CAC AGC TCG GGA TCC GCG CGC GCT GGG CCTTCG 47

48 GCG CCG CTC GTG GGG TTC GGG AGG CCG GGA CCC TGC CCG GGA GAT GTG 95

96 GAC GCC GGG CGG ACC CCC GGG GTC CGC GGG CTG GGA CCG CCG TAG GTT 143

144 GGG CGC GAG GTT GCG CGC GGC GTT CGC GGG GCT GCA GGA GCT GCA GGG 191

192 GCT GCG AGC CAC GCA GCA GGA GCG GGT ACG GGG CGC CCT GGC CCT GCA 239

240 GCC CCC GCC CGC GCC CGC CGC GCC CTG CGG CCC CCA CGG CCT CCA CGG 287

288 CCC CGA GCA GCA GCT GGA GGC GGC GCT GGC CGC GCT GCA GGA GCA GCT 335

336 GTC CCG GCT GAG ACA ACA GGA CAT CGG CCT GAA GAC CCA CCT GGA CCA 383

384 GCT GGA CCT GCA GAT TAG CAA GCT GCA GCT GGA TGT GGG CAC AGC CTC 431

432 AGG GGA GGC CCT GGA CAG CGA CAG CAG GCC CAG CTC AGG CTT TTA CGA 479

480 GAT GAG CGA CGG TGG ATC CTG CTC CCT GTC CAC GTC CTG TGC CTC CGT 527

528 CTG CAG TGA CCA CAT CTC TCC CTC GCT GGG CAG TTT GTT GCC TGT GGC 575

576 CCA GGC CCA CAA GGC CAG GCC CAG CAT GGG GGA CTG GAG GCC CCG GTC 623

624 GGT TGA TGA GAC TAC TGT GCC AGC GTG GAG ACC CCA GGC TAC CGA GGA 671

672 GGG CGC CAG GCC CCC AGG GAG CGT GGA GGA TGC AGG CCA GCC GTG GGG 719

720 CAC ATT CTG GCC CAG GCC TGT GTC TAC AGG TGA TCT TGA CAG AGC CCT 767

768 GCC GGC GGA CAC GGG GCT CCA GAA AGC CAG CGC GGA CGC CGA GCT CCT 815

816 CGG GCT CCT CTG CAG GGG GTG GAT ATC CCG CTG CAC GTG CCG GAC CCC 863

864 AAG TAT CGG CAG GAC CTG GTG TCC CAG GGC GGC AGG GAG GTG TAC CCG 911

912 TAC CCC AGC CCC CTG CAC GCC GTG GCT CTA CAG AGC CCC CTG TTT GTC 959

960 CTG ACT AAG GAA ACC CCA CAG AGA GGT GGC CCC TCG TTC CCT AGG GAG 1007

1008 AGC CCC AGG GGC CCC GCA GGT CTG AAC ACC ATC CAG ACT GGG CCG GTC 1055

1056 CTC GAG CCT GGC CCG GCC AGG GCC AGA GCT TAT ATC GAC AGG TTG CTG 1103

1104 CAT CTG TGG GGC CGG GAG ACC CCA GCA AAG GGT AGC GAG GGA GAA CAG 1151

1152 GGA CCT CTA AGG CAT GCA GCG TCC CCA TCT CCA CAG AGG CAG GGT GGC 1199

1200 TGG AGT ACA GAC GGT GGA GGG CGA CTG CTG GTC TTC GCC CCA GGG AGG 1247

1248 GAG GAC GAG GGA GGG CCA GCT CAG AGC AGG GGT GCC GGC AGG GGC GGG 1295

1296 CCC CAG CAG CAG GGA TAC ATG CCC CTT GAG GGT CCC CAG CAG TCT GGC 1343

1 Met Pro Leu Glu Gly Pro Gln Gln Ser Gly 10

1344 AGC CTT CCA GAG GAG GGC TCC AAG CCC TCA AAC AGC TGT GTC CTC AGG 1391

11 Ser Leu Pro Glu Glu Gly Ser Lys Pro Ser Asn Ser Cys Val Leu Arg 26

1392 GAG ACC ATG GTG CAG GCT TCT CCC AGC TCA AAG GCC CAG CAG ACA CCC 1439

27 Glu Thr Met Val Gln Ala Ser Pro Ser Ser Lys Ala Gln Gln Thr Pro 42

1440 TCA GCT CAG GAC TAT GGA CGA GGC AAC ATC ATA TCC CCA TCC AGG ATG 1487

43 Ser Ala Gln Asp Tyr Gly Arg Gly Asn Ile Ile Ser Pro Ser Arg Met 58

1488 CTG GAC AAG AGC CCC TCA CCG GCC TCT GGG CAC TTT GCC CAC CCA TCC 1535

59 Leu Asp Lys Ser Pro Ser Pro Ala Ser Gly His Phe Ala His Pro Ser 74

1536 TTT GCT GCC AGC CTG AAA ATG GGT CCC CCC AAG AGC AAG GCT GAA AAA 1583

75 Phe Ala Ala Ser Leu Lys Met Gly Pro Pro Lys Ser Lys Ala Glu Lys 90

1584 ATC AAG AGA AGT CCC ATG GAC AAG GTG CTG AGG TTT GCA AGG CAG CCG 1631

91 Ile Lys Arg Ser Pro Met Asp Lys Val Leu Arg Phe Ala Arg Gln Pro 106

1632 CTG CTT CTA CTG GAC AGG CCT GAG GGA GCC CAT GCA GCC CCC CAG CCA 1679

107 Leu Leu Leu Leu Asp Arg Pro Glu Gly Ala His Ala Ala Pro Gln Pro 122

1680 TCC CTG GAG TGG GAC CCT GCC CAC TGG CCC ACA GGG AGG GGC GGG CTC 1727

123 Ser Leu Glu Trp Asp Pro Ala His Trp Pro Thr Gly Arg Gly Gly Leu 138

1728 CAG CGG AGG CCA GCC CTG GCC TGG GAG GCA CCC GGG CGC TCC TGT TCT 1775

139 Gln Arg Arg Pro Ala Leu Ala Trp Glu Ala Pro Gly Arg Ser Cys Ser 154

1776 GAG TCC ACC CTC TAC CCC ATG CCT GTC CTC GTC CCC TTG GCA GTG GCC 1823

155 Glu Ser Thr Leu Tyr Pro Met Pro Val Leu Val Pro Leu Ala Val Ala 170

1824 CCG CAG GAG AGC CAC CGG ACC TCA GCC CAA GCC CTG TTC CCC TTT GAG 1871

171 Pro Gln Glu Ser His Arg Thr Ser Ala Gln Ala Leu Phe Pro Phe Glu 186

1872 GCG TCA CTG CTC ACC TCA GTG GCC AGG AGG AAG CAT CGC CGC TGG CAG 1919

187 Ala Ser Leu Leu Thr Ser Val Ala Arg Arg Lys His Arg Arg Trp Gln 202

1920 TCC ACC GTG GAG ATC TCG GCC CGG GCC CGC CTG GCC AGC TGT CCT GAG 1967

203 Ser Thr Val Glu Ile Ser Ala Arg Ala Arg Leu Ala Ser Cys Pro Glu 218

1968 TCT AAC CTG GGG CCC CCC AGG CCC GTG GCC AGG AGA GCA GGT GGC CCA 2015

219 Ser Asn Leu Gly Pro Pro Arg Pro Val Ala Arg Arg Ala Gly Gly Pro 234

2016 CTG GCC CGG GGC CGT CCC TCA CTG GTC CGC CAG GAC GCC TAC ACC AGG 2063

235 Leu Ala Arg Gly Arg Pro Ser Leu Val Arg Gln Asp Ala Tyr Thr Arg 250

2064 AGC GAC TCA GAG CCC TCC AAG CAC TCG GCC GAG TGT GAC CCG CGG TTC 2111

251 Ser Asp Ser Glu Pro Ser Lys His Ser Ala Glu Cys Asp Pro Arg Phe 266

2112 CCG TCA GTC ATC CCG GAG ACC AGC GAG GGA GAG TCC AGT GAC CAC ACC 2159

267 Pro Ser Val Ile Pro Glu Thr Ser Glu Gly Glu Ser Ser Asp His Thr 282

2160 ACC AAC CGA TTC GGA GAC CGT GAG TCC AGC AGC AGC GAC GAG GAG GGC 2207

283 Thr Asn Arg Phe Gly Asp Arg Glu Ser Ser Ser Ser Asp Glu Glu Gly 298

2208 GGC GCC CAG AGC AGG GAC TGT GAC CTG GCA CTG GGC TAT GTG GCG GCC 2255

299 Gly Ala Gln Ser Arg Asp Cys Asp Leu Ala Leu Gly Tyr Val Ala Ala 314

2256 GGG CAT GAG GAG CTG GCC TGG ACC CAG GAG GCC CCG GTC AGC TCG GGG 2303

315 Gly His Glu Glu Leu Ala Trp Thr Gln Glu Ala Pro Val Ser Ser Gly 330

2304 CCA CTC CTG TCC CCC GTG CCC AAG CTG TGC CGT ATT AAG GCC TCC AAG 2351

331 Pro Leu Leu Ser Pro Val Pro Lys Leu Cys Arg Ile Lys Ala Ser Lys 346

2352 GCC CTG AAG AAG AAG ATC CGC AGG TTC CAG CCG ACG GCC CTG AAG GTC 2399

347 Ala Leu Lys Lys Lys Ile Arg Arg Phe Gln Pro Thr Ala Leu Lys Val 362

2400 ATG ACC ATG GTG TGA GGT GCA GTG ACT GCG TCA AGA GAA GCC TGC TGC 2447

363 Met Thr Met Val *** 367

2448 ACA CAG GGG CCC TTT CCA TGC AGT GTC CTG TGC ATG TCT GGG TTT CAG 2495

2496 TGT CGT CTT GCC AAG TCG CTT TAT CTT CCG AGG CCA CCG TTT AAC AGG 2543

2544 AGT CCC CGC AGA TGG GTT CTG CCC TGT GGA GTA TGG CCG TGA GTC CCC 2591

2592 GCC CCA GCA AAG ACT TCC ATG CGG AGC TCT GGT TTC AGA TGC CAG CAG 2639

2640 CCT CCC CGG CCG ACC TAG TGT CTC TTT TCA AGG TCT GCC CAG GAT GCT 2687

2688 GCT TCC CGG CAT GCA CCT TGT TTC CAT GTT GTC ATC CTC CCA TGG CTT 2735

2736 CCC CTG CCC TCA CTC CCC TCT GGC TGG GGA AGT GTT TCC CAA TCC RRR 2783

2784 GAC CAT TCC TCC CCA AAA GCA TTT TAA AAA GGC GGT TGC AGG ACT TTG 2831

2832 AGC TGG AAA TTG AAT TTG AGT TTA AAC TCC ACG TTA AGC TGT CAG CAT 2879

2880 ACA CAA ACA CCC AAA TTA TGC CAT GAT CTC AAA TAA AAG GAA CAT TTT 2927

2928 TTT TCC CTC TTT TAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA 2975

2976 AAA AAA AAA AA 2986

7.PP13759

A: nucleotide sequence (SEQ ID NO:19) length: 1581

1 GAGGCGGAGA CACAAGGCTC CGTTCCACTG GGCACGCCAG CGGTAGAGAC GGGGTTTCGC

61 CATGTTGGCC AGGCTGGTCT CAAACTCCTG AGCTCGGGCG GTCTGCCCGC CTCGGCCTCC

121 CAAAGTGCTG GGATTGCGGG CGTGAGCCAC TGCACCCGGT TCAAGCGATT CTCCTGCCTC

181 AGCCCCCTGA GTAGCTGGGA TTACAGGCAC GCGCCACCAC TCCCAGATCT TCACTTCAGG

241 TCAGCTCCAA GGAGGCTATC CTTGCCCATC TTCCTAAAAT AGAGCTCTCA AAACCTGGCT

301 GTTTTCCTTC AGAGCACTGG CCTCCAATTG CTCCGGTAGA TTGCAAATGA CCTGCTTTCT

361 TTCTGTTCCC GGGCGTTTGG ACCCCTGTCT TGGACCGCTG TCGGATAGTA AATCCCAAGT

421 AAGGTACCTG CCGTCGGCAG ATTTGAGCTT TCTTCTTGGA CACCTAATAC CCAGAGTCCT

481 CCAGGCTCCG GTAGATTGCA AATGACCTGC TTTCTTTCTG TTCCCGGGCG GCATCGGACC

541 CGTCGGAGAG TAAATCCCAA GTAAGGTACC TGCCGTTGGC AGATTTGAGC TTTCTTCTTG

601 GACACCTAAT ACCCACAGTC CTCCAGGCTC CGGTAGATTG CAAATGACCT GCTTTCTTTC

661 TGTTCCCGGG TGGCATCGAC CCGTCGGAGA GTAAATCCCA AGTAAGGTAC CTGCCGTTGG

721 CAGATTTGAG CTTTCTTCTT GGACACCTAA TACCCACAGT CCTCCAGTAA ATCCCAAGCA

781 AGGTACCTGC CGTCAGCAGA TTTGAGCTTT CTTCTTGGAC ACCTAATACC CACAGTCCTC

841 CAGGCTCCGG TAGATTGCAA ATGACCTGCT TTCTTTCTGT TCCCGGGCTG CGTTCGGACC

901 CCTGTCGGAT AGTAACTCCC AAGTAAGGTA CCTGCCGTCG GCAGATTGGA GCTTTCTTCT

961 TGGAGACCTA ATACCCACAG TCCTCCAGAA AAACAAACAA AGACATGGAT TTACTGTGCA

1021 TATTAGCAGA TCCATACTGG AAAATGCATG GAGGTTTCAT ATACACCACT TACAGTTTTC

1081 AGCTCCTCAG TAGTGACAAA GCCATACCCA TCATTGTCGA TTCGATCAAC AATCTTCCCT

1141 AGCCTCTCCT TGCTCTCGTC CGGGGTGAGC TCGTCGAAGT TCTTGGAGTC CTCCTTGCCC

1201 AGGAAGGCCT CGTGGTCGTA CTGGAAGCTC TGGTTGTCCT CAGGGGGCCG CTCGCCCAGC

1261 TCCGAGTCGG GCCGCACCAC GCGCTCTTTG CGCACCGTGG GCTTGGCCCG CAGAACCCGC

1321 GGCGCCAGCA CCAGCGCCAG CAGCAGCCCC AGGGCTAACC CCAGGCGGCC ACCGCGCGCC

1381 ATCGTCCCGA GGAGAGGGCG GCCGGGAGGG AGACGCTGAG CGAGCGACAA CAGCGGCAGC

1441 TCGGGAATGG GGGCTCGGAG CGCGGCGGCC AAGTTTTATG TTATGTATAT TTTACAAGTA

1501 AAAAAATTTT TTCACCTCAG CCTGAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA

1561 AAAAAAAAAA AAAAAAAAAA A

B: aminoacid sequence (SEQ ID NO:20) length: 123

1 MEVSYTPLTV FSSSVVTKPY PSLSIRSTIF PSLSLLSSGV SSSKFLESSL PRKASWSYWK

61 LWLSSGGRSP SSESGRTTRS LRTVGLARRT RGASTSASSS PRANPRRPPR AIVPRRGRPG

121 GRR

C. Nucleotide and amino acid composite sequence (SEQ ID NO:21) clone number: PP13759 start code: 1048 ATG stop coding: 1417 TGA protein molecular weights: 13369.38

1 GAG GCG GAG ACA CAA GGC TCC GTT CCA CTG GGC ACG CCA GCG GTA GAG 48

49 ACG GGG TTT CGC CAT GTT GGC CAG GCT GGT CTC AAA CTC CTG AGC TCG 96

97 GGC GGT CTG CCC GCC TCG GCC TCC CAA AGT GCT GGG ATT GCG GGC GTG 144

145 AGC CAC TGC ACC CGG TTC AAG CGA TTC TCC TGC CTC AGC CCC CTG AGT 192

193 AGC TGG GAT TAC AGG CAC GCG CCA CCA CTC CCA GAT CTT CAC TTC AGG 240

241 TCA GCT CCA AGG AGG CTA TCC TTG CCC ATC TTC CTA AAA TAG AGC TCT 288

289 CAA AAC CTG GCT GTT TTC CTT CAG AGC ACT GGC CTC CAA TTG CTC CGG 336

337 TAG ATT GCA AAT GAC CTG CTT TCT TTC TGT TCC CGG GCG TTT GGA CCC 384

385 CTG TCT TGG ACC GCT GTC GGA TAG TAA ATC CCA AGT AAG GTA CCT GCC 432

433 GTC GGC AGA TTT GAG CTT TCT TCT TGG ACA CCT AAT ACC CAG AGT CCT 480

481 CCA GGC TCC GGT AGA TTG CAA ATG ACC TGC TTT CTT TCT GTT CCC GGG 528

529 CGG CAT CGG ACC CGT CGG AGA GTA AAT CCC AAG TAA GGT ACC TGC CGT 576

577 TGG CAG ATT TGA GCT TTC TTC TTG GAC ACC TAA TAC CCA CAG TCC TCC 624

625 AGG CTC CGG TAG ATT GCA AAT GAC CTG CTT TCT TTC TGT TCC CGG GTG 672

673 GCA TCG ACC CGT CGG AGA GTA AAT CCC AAG TAA GGT ACC TGC CGT TGG 720

721 CAG ATT TGA GCT TTC TTC TTG GAC ACC TAA TAC CCA CAG TCC TCC AGT 768

769 AAA TCC CAA GCA AGG TAC CTG CCC TCA GCA GAT TTG AGC TTT CTT CTT 816

817 GGA CAC CTA ATA CCC ACA GTC CTC CAG GCT CCG GTA GAT TGC AAA TGA 864

865 CCT GCT TTC TTT CTG TTC CCG GGC TGC GTT CGG ACC CCT GTC GGA TAG 912

913 TAA CTC CCA AGT AAG GTA CCT GCC GTC GGC AGA TTG GAG CTT TCT TCT 960

961 TGG AGA CCT AAT ACC CAC AGT CCT CCA GAA AAA CAA ACA AAG ACA TGG 1008

1009 ATT TAC TGT GCA TAT TAG CAG ATC CAT ACT GGA AAA TGC ATG GAG GTT 1056

1 Met Glu Val 3

1057 TCA TAT ACA CCA CTT ACA GTT TTC AGC TCC TCA GTA GTG ACA AAG CCA 1104

4 Ser Tyr Thr Pro Leu Thr Val Phe Ser Ser Ser Val Val Thr Lys Pro 19

1105 TAC CCA TCA TTG TCG ATT CGA TCA ACA ATC TTC CCT AGC CTC TCC TTG 1152

20 Tyr Pro Ser Leu Ser Ile Arg Ser Thr Ile Phe Pro Ser Leu Ser Leu 35

1153 CTC TCG TCC GGG GTG AGC TCG TCG AAG TTC TTG GAG TCC TCC TTG CCC 1200

36 Leu Ser Ser Gly Val Ser Ser Ser Lys Phe Leu Glu Ser Ser Leu Pro 51

1201 AGG AAG GCC TCG TGG TCG TAC TGG AAG CTC TGG TTG TCC TCA GGG GGC 1248

52 Arg Lys Ala Ser Trp Ser Tyr Trp Lys Leu Trp Leu Ser Ser Gly Gly 67

1249 CGC TCG CCC AGC TCC GAG TCG GGC CGC ACC ACG CGC TCT TTG CGC ACC 1296

68 Arg Ser Pro Ser Ser Glu Ser Gly Arg Thr Thr Arg Ser Leu Arg Thr 83

1297 GTG GGC TTG GCC CGC AGA ACC CGC GGC GCC AGC ACC AGC GCC AGC AGC 1344

84 Val Gly Leu Ala Arg Arg Thr Arg Gly Ala Ser Thr Ser Ala Ser Ser 99

1345 AGC CCC AGG GCT AAC CCC AGG CGG CCA CCG CGC GCC ATC GTC CCG AGG 1392

100 Ser Pro Arg Ala Asn Pro Arg Arg Pro Pro Arg Ala Ile Val Pro Arg 115

1393 AGA GGG CGG CCG GGA GGG AGA CGC TGA GCG AGC GAC AAC AGC GGC AGC 1440

116 Arg Gly Arg Pro Gly Gly Arg Arg *** 124

1441 TCG GGA ATG GGG GCT CGG AGC GCG GCG GCC AAG TTT TAT GTT ATG TAT 1488

1489 ATT TTA CAA GTA AAA AAA TTT TTT CAC CTC AGC CTG AAA AAA AAA AAA 1536

1537 AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA AAA 1581

8.PP14328

A: nucleotide sequence (SEQ ID NO:22) length: 1290

1 GCGCGGGCGT TCCTGGTTCG CGCTCCCGCC CCCTCCGCCC CGCCGACTCG CCGCTTCCTC

61 CGGAGCCCCA GCGTCCCGAA CCAGGGACTG CATTTCCCGG CAGGCGCCGC GGCCCGCGGC

121 CAATGAGGGG CTGAGGATTT GGCGGCGGCG GCGCCCCGAG AGTCGGGGTG GGGGGGCTTT

181 GTGCGCGGCG GCGGCGGGAG AGGCGGCGGC GGCGGCCAGC ACGGAGGCGG AGGCCGAGGG

241 GGCTGTGCAC AGGTCGCCGC GGAGAGGCGT GCGAATTCCG AGCCGAGCGC CGAGGACCGT

301 GCTACCCAGG CCGGGCTGCC AGCCGCAGGC TCCTCTCTGG CAGCAGCGGC GGCGCGGCGA

361 CCCCCGTCCC TCGGCCTCCC CTTCCCATCC CACCTCCCGA GCCTTCCTCT TCCCGCAGCA

421 CGCCCGGCCC GGCCCGGCCG TGGCCCTCCT CAGTGCCGGC CGCCATGGCA GAGGCGTCCG

481 GCGCGGGGAA AATCTAGCCC GGGGATTTCA TGCGGCCTAG CTCGGTTCCG CCTCCTCCTC

541 GCGCGGCCCC AGCGGCTGCC CGCACCCCAG CCCCACTCCG GGCCTCCGTG TCTCTCCTGT

601 GATCGCACTG ACACGGCCGG GGGGTTAGAA TGGAACAAAC TGAAGGCCCG ATGAGAGAAA

661 GGGAAAGTTA AGGATGCTGG AGCAGAACAA TGGATTTCTC TTTCTCTTTC ATGCAAGGGA

721 TCATGGGAAA CACAATTCAG CAACCACCTC AACTCATTGA CTCCGCCAAC ATCCGTCAGG

781 AGGATGCCTT TGATAACAAC AGTGACATTG CTGAAGATGG TGGCCAGACA CCATATGAAG

841 CTACTTTGCA GCAAGGCTTT CAGTACCCAG CTACAACAGA AGATCTTCCT CCACTCACAA

901 ATGGGTATCC ATCATCAATC AGTGTGTATG AAACTCAAAC CAAATACCAG TCATATAATC

961 AGTATCCTAA TGGGTCAGCC AATGGCTTTG GTGCAGTTAG AAACTTTAGC CCCACTGACT

1021 ATTATCATTC AGAAATTCCA AACACAAGAC CACATGAAAT TCTGGAAAAA CCTTCCCCTC

1081 CACAGCCACC ACCTCCTCCT TCGGTACCAC AAACTGTGAT TCCAAAGAAG ACTGGCTCAC

1141 CTGAAATTAA ACTAAAAATA ACCAAAACTA TCCAGAATGG CAGGGAATTG TTTGAGTCTT

1201 CCCTTTGTGG AGACCTTTTA AATGAAGTAC AGGCAAGTGA GCACACGAAA TCAAAGCATG

1261 AAAGCAGAAA AAAAAAAAAA AAAAAAAAAA

B: aminoacid sequence (SEQ ID NO:23) length: 111

1 MPLITTVTLL KMVARHHMKL LCSKAFSTQL QQKIFLHSQM GIHHQSVCMK LKPNTSHIIS

61 ILMGQPMALV QLETLAPLTI IIQKFQTQDH MKFWKNLPLH SHHLLLRYHK L

C. Nucleotide and amino acid composite sequence (SEQ ID NO:24) clone number: PP14328 start code: 784 ATG stop coding: 1117 TGA protein molecular weights: 12935.10

1 GCG CGG GCG TTC CTG GTT CGC GCT CCC GCC CCC TCC GCC CCG CCG ACT 48

49 CGC CGC TTC CTC CGG AGC CCC AGC GTC CCG AAC CAG GGA CTG CAT TTC 96

97 CCG GCA GGC GCC GCG GCC CGC GGC CAA TGA GGG GCT GAG GAT TTG GCG 144

145 GCG GCG GCG CCC CGA GAG TCG GGG TGG GGG GGC TTT GTG CGC GGC GGC 192

193 GGC GGG AGA GGC GGC GGC GGC GGC CAG CAC GGA GGC GGA GGC CGA GGG 240

241 GGC TGT GCA CAG GTC GCC GCG GAG AGG CGT GCG AAT TCC GAG CCG AGC 288

289 GCC GAG GAC CGT GCT ACC CAG GCC GGG CTG CCA GCC GCA GGC TCC TCT 336

337 CTG GCA GCA GCG GCG GCG CGG CGA CCC CCC TCC CTC GGC CTC CCC TTC 384

385 CCA TCC CAC CTC CCG AGC CTT CCT CTT CCC GCA GCA CGC CCG GCC CGG 432

433 CCC GGC CGT GGC CCT CCT CAG TGC CGG CCG CCA TGG CAG AGG CGT CCG 480

481 GCG CGG GGA AAA TCT AGC CCG GGG ATT TCA TGC GGC CTA GCT CGG TTC 528

529 CGC CTC CTC CTC GCG CGG CCC CAG CGG CTG CCC GCA CCC CAG CCC CAC 576

577 TCC GGG CCT CCG TGT GTC TCC TGT GAT CGC ACT GAC ACG GCC GGG GGG 624

625 TTA GAA TGG AAC AAA CTG AAG GCC CGA TGA GAG AAA GGG AAA GTT AAG 672

673 GAT GCT GGA GCA GAA CAA TGG ATT TCT CTT TCT CTT TCA TGC AAG GGA 720

721 TCA TGG GAA ACA CAA TTC AGC AAC CAC CTC AAC TCA TTG ACT CCG CCA 768

769 ACA TCC GTC AGG AGG ATG CCT TTG ATA ACA ACA GTG ACA TTG CTG AAG 816

1 Met Pro Leu Ile Thr Thr Val Thr Leu Leu Lys 11

817 ATG GTG GCC AGA CAC CAT ATG AAG CTA CTT TGC AGC AAG GCT TTC AGT 864

12 Met Val Ala Arg His His Met Lys Leu Leu Cys Ser Lys Ala Phe Ser 27

865 ACC CAG CTA CAA CAG AAG ATC TTC CTC CAC TCA CAA ATG GGT ATC CAT 912

28 Thr Gln Leu Gln Gln Lys Ile Phe Leu His Ser Gln Met Gly Ile His 43

913 CAT CAA TCA GTG TGT ATG AAA CTC AAA CCA AAT ACC AGT CAT ATA ATC 960

44 His Gln Ser Val Cys Met Lys Leu Lys Pro Asn Thr Ser His Ile Ile 59

961 AGT ATC CTA ATG GGT CAG CCA ATG GCT TTG GTG CAG TTA GAA ACT TTA 1008

60 Ser Ile Leu Met Gly Gln Pro Met Ala Leu Val Gln Leu Glu Thr Leu 75

1009 GCC CCA CTG ACT ATT ATC ATT CAG AAA TTC CAA ACA CAA GAC CAC ATG 1056

76 Ala Pro Leu Thr Ile Ile Ile Gln Lys Phe Gln Thr Gln Asp His Met 91

1057 AAA TTC TGG AAA AAC CTT CCC CTC CAC AGC CAC CAC CTC CTC CTT CGG 1104

92 Lys Phe Trp Lys Asn Leu Pro Leu His Ser His His Leu Leu Leu Arg 107

1105 TAC CAC AAA CTG TGA TTC CAA AGA AGA CTG GCT CAC CTG AAA TTA AAC 1152

108 Tyr His Lys Leu *** 112

1153 TAA AAA TAA CCA AAA CTA TCC AGA ATG GCA GGG AAT TGT TTG AGT CTT 1200

1201 CCC TTT GTG GAG ACC TTT TAA ATG AAG TAC AGG CAA GTG AGC ACA CGA 1248

1249 AAT CAA AGC ATG AAA GCA GAA AAA AAA AAA AAA AAA AAA AAA 1290

9.PP14450

A: nucleotide sequence (SEQ ID NO:25) length: 1816

1 GAGACGGAGT CTCACTCTGT CGCCCAGGCT GGAGTACAAT GGCATGATCT CGGCTCACTG

61 CAACCTACAC CTCCCAGGTT CAAGCGATTC TCTTGCCTCA GCCTCCCAGC TCCTGCTCGC

121 CGGACGGCTC CCAGGGAGAG CAGACGCGCC AGACGCGCCA CCCTCGGGGC GCCGACGGTC

181 ACGGAGCATG GGGTCGGCCT TTGAGCGGGT AGTCCGGAGA GTGGTCCAGG AGCTGGACCA

241 TGGTGGGGAG TTCATCCCTG TGACCAGCCT GCAGAGCTCC ACTGGCTTCC AGCCCTACTG

301 CCTGGTGGTT AGGAAGCCCT CAAGCTCATG GTTCTGGAAA CCCCGTTATA AGTGTGTCAA

361 CCTGTCTATC AAGGACATCC TGGAGCCGGA TGCCGCGGAA CCAGACGTGC AGCGTGGCAG

421 GAGCTTCCAC TTCTACGATG CCATGGATGG GCAGATACAG GGCAGCGTGG AGCTGGCAGC

481 CCCAGGACAG GCAAAGATCG CAGGCGGGGC CGCGGTGTCT GACAGCTCCA GCACCTCAAT

541 GAATGTGTAC TCGCTGAGTG TGGACCCTAA CACCTGGCAG ACTCTGCTCC ATGAGAGGCA

601 CCTGCGGCAG CCAGAACACA AAGTCCTGCA GCAGCTGCGC AGCCGCGGGG ACAACGTGTA

661 CGTGGTGACT GAGGTGCTGC AGACACAGAA GGAGGTGGAA GTCACGCGCA CCCACAAGCG

721 GGAGGGCTCG GGCCGGTTTT CCCTGCCCGG AGCCACGTGC TTGCAGGGTG AGGGCCAGGG

781 CCATCTGAGC CAGAAGAAGA CGGTCACCAT CCCCTCAGGC AGCACCCTCG CATTCCGGGT

841 GGCCCAGCTG GTTATTGACT CTGACTTGGA CGTCCTTCTC TTCCCGGATA AGAAGCAGAG

901 GACCTTCCAG CCACCCGCGA CAGGCCACAA GCGTTCCACG AGCGAAGGCG CCTGGCCACA

961 GCTGCCCTCT GGCCTCTCCA TGATGAGGTG CCTCCACAAC TTCCTGACAG ATGGGGTCCC

1021 TGCGGAGGGG GCGTTCACTG AAGACTTCCA GGGCCTACGG GCAGAGGTGG AGACCATCTC

1081 CAAGGAACTG GAGCTTTTGG ACAGAGAGCT GTGCCAGCTG CTGCTGGAGG GCCTGGAGGG

1141 GGTGCTGCGG GACCAGCTGG CCCTGCGAGC CTTGGAGGAG GCGCTGGAGC AGAGCCAGAG

1201 CCTTGGGCCG GTGGAGCCCC TGGACGGTCC AGCAGGTGCT GTCCTGGAGT GCCTGGTGTT

1261 GTCCTCCGGA ATGCTGGTGC CGGAACTCGC TATCCCTGTT GTCTACCTGC TGGGGGCACT

1321 GACCATGCTG AGTGAAACGC AGCACAAGCT TGCTGGCGGA GGCGCTGGAG TCGCAGACCC

1381 TGTTGGGGCC GCTCGAGCTG GTGGGCAGCC TCTTGGAGCA GAGTGCCCCG TGGCAGGAGC

1441 GCAGCACCAT GTCCCTGCCC CCCGGGCTCC TGGGGAACAG CTGGGGCGAA GGAGCACCGG

1501 CCTGGGTCTT GCTGGACGAG TGTGGCCTAGAGCTGGGGGA GGACACTCCC CACGTGTGCT

1561 GGGAGCCGCA GGCCCAGGGC CGCATGTGTG CACTCTACGC CTCCCTGGCA CTGCTATCAG

1621 GACTGAGCCA GGAGCCCCAC TAGCCTGTGC CCGGGCATGG CCTGGCAGCT CTCCAGCAGG

1681 GCAGAGTGTT TGCCCACCAG CTGCTAGCCC TAGGAAGGCC AGGAGCCCAG TAGCCATGTG

1741 GCCAGTCTAC CATGGGGCCC AGGAGTTGGG GAAACACAAT AAAGGTGGCA TACGAAGGAA

1801 AAAAAAAAAA AAAAAA

B: aminoacid sequence (SEQ ID NO:26) length: 103

1 MGSLRRGRSL KTSRAYGQRW RPSPRNWSFW TESCASCCWR AWRGCCGTSW PCEPWRRRWS

61 RARALGRWSP WTVQQVLSWS AWCCPPECWC RNSLSLLSTC WGH

C. Nucleotide and amino acid composite sequence (SEQ ID NO:27) clone number: PP14450 start code: 1011 ATG stop coding: 1320 TGA protein molecular weights: 12272.40

1 GA GAC GGA GTC TCA CTC TGT CGC CCA GGC TGG AGT ACA ATG GCA TGA 47

48 TCT CGG CTC ACT GCA ACC TAC ACC TCC CAG GTT CAA GCG ATT CTC TTG 95

96 CCT CAG CCT CCC AGC TCC TGC TCG CCG GAC GGC TCC CAG GGA GAG CAG 143

144 ACG CGC CAG ACG CGC CAC CCT CGG GGC GCC GAC GGT CAC GGA GCA TGG 191

192 GGT CGG CCT TTG AGC GGG TAG TCC GGA GAG TGG TCC AGG AGC TGG ACC 239

240 ATG GTG GGG AGT TCA TCC CTG TGA CCA GCC TGC AGA GCT CCA CTG GCT 287

288 TCC AGC CCT ACT GCC TGG TGG TTA GGA AGC CCT CAA GCT CAT GGT TCT 335

336 GGA AAC CCC GTT ATA AGT GTG TCA ACC TGT CTA TCA AGG ACA TCC TGG 383

384 AGC CGG ATG CCG CGG AAC CAG ACG TGC AGC GTG GCA GGA GCT TCC ACT 431

432 TCT ACG ATG CCA TGG ATG GGC AGA TAC AGG GCA GCG TGG AGC TGG CAG 479

480 CCC CAG GAC AGG CAA AGA TCG CAG GCG GGG CCG CGG TGT CTG ACA GCT 527

528 CCA GCA CCT CAA TGA ATG TGT ACT CGC TGA GTG TGG ACC CTA ACA CCT 575

576 GGC AGA CTC TGC TCC ATG AGA GGC ACC TGC GGC AGC CAG AAC ACA AAG 623

624 TCC TGC AGC AGC TGC GCA GCC GCG GGG ACA ACG TGT ACG TGG TGA CTG 671

672 AGG TGC TGC AGA CAC AGA AGG AGG TGG AAG TCA CGC GCA CCC ACA AGC 719

720 GGG AGG GCT CGG GCC GGT TTT CCC TGC CCG GAG CCA CGT GCT TGC AGG 767

768 GTG AGG GCC AGG GCC ATC TGA GCC AGA AGA AGA CGG TCA CCA TCC CCT 815

816 CAG GCA GCA CCC TCG CAT TCC GGG TGG CCC AGC TGG TTA TTG ACT CTG 863

864 ACT TGG ACG TCC TTC TCT TCC CGG ATA AGA AGC AGA GGA CCT TCC AGC 911

912 CAC CCG CGA CAG GCC ACA AGC GTT CCA CGA GCG AAG GCG CCT GGC CAC 959

960 AGC TGC CCT CTG GCC TCT CCA TGA TGA GGT GCC TCC ACA ACT TCC TGA 1007

1008 CAG ATG GGG TCC CTG CGG AGG GGG CGT TCA CTG AAG ACT TCC AGG GCC 1055

1 Met Gly Ser Leu Arg Arg Gly Arg Ser Leu Lys Thr Ser Arg Ala 15

1056 TAC GGG CAG AGG TGG AGA CCA TCT CCA AGG AAC TGG AGC TTT TGG ACA 1103

16 Tyr Gly Gln Arg Trp Arg Pro Ser Pro Arg Asn Trp Ser Phe Trp Thr 31

1104 GAG AGC TGT GCC AGC TGC TGC TGG AGG GCC TGG AGG GGG TGC TGC GGG 1151

32 Glu Ser Cys Ala Ser Cys Cys Trp Arg Ala Trp Arg Gly Cys Cys Gly 47

1152 ACC AGC TGG CCC TGC GAG CCT TGG AGG AGG CGC TGG AGC AGA GCC AGA 1199

48 Thr Ser Trp Pro Cys Glu Pro Trp Arg Arg Arg Trp Ser Arg Ala Arg 63

1200 GCC TTG GGC CGG TGG AGC CCC TGG ACG GTC CAG CAG GTG CTG TCC TGG 1247

64 Ala Leu Gly Arg Trp Ser Pro Trp Thr Val Gln Gln Val Leu Ser Trp 79

1248 AGT GCC TGG TGT TGT CCT CCG GAA TGC TGG TGC CGG AAC TCG CTA TCC 1295

80 Ser Ala Trp Cys Cys Pro Pro Glu Cys Trp Cys Arg Asn Ser Leu Ser 95

1296 CTG TTG TCT ACC TGC TGG GGG CAC TGA CCA TGC TGA GTG AAA CGC AGC 1343

96 Leu Leu Ser Thr Cys Trp Gly His *** 104

1344 ACA AGC TTG CTG GCG GAG GCG CTG GAG TCG CAG ACC CTG TTG GGG CCG 1391

1392 CTC GAG CTG GTG GGC AGC CTC TTG GAG CAG AGT GCC CCG TGG CAG GAG 1439

1440 CGC AGC ACC ATG TCC CTG CCC CCC GGG CTC CTG GGG AAC AGC TGG GGC 1487

1488 GAA GGA GCA CCG GCC TGG GTC TTG CTG GAC GAG TGT GGC CTA GAG CTG 1535

1536 GGG GAG GAC ACT CCC CAC GTG TGC TGG GAG CCG CAG GCC CAG GGC CGC 1583

1584 ATG TGT GCA CTC TAC GCC TCC CTG GCA CTG CTA TCA GGA CTG AGC CAG 1631

1632 GAG CCC CAC TAG CCT GTG CCC GGG CAT GGC CTG GCA GCT CTC CAG CAG 1679

1680 GGC AGA GTG TTT GCC CAC CAG CTG CTA GCC CTA GGA AGG CCA GGA GCC 1727

1728 CAG TAG CCA TGT GGC CAG TCT ACC ATG GGG CCC AGG AGT TGG GGA AAC 1775

1776 ACA ATA AAG GTG GCA TAC GAA GGA AAA AAA AAA AAA AAA AA 1816

10.PP14733

A: nucleotide sequence (SEQ ID NO:28) length: 2638

1 GAGCCAGAAC CATGTTTTTT GGGAAATGGC TCAATAAACC TTAATTTATT GTTGCCCTTT

61 GTGAAGACTA TTAAGAGCAA TACAAAAAAA AAAAATAGTT GATGTTGCTT TGTGTAGGCT

121 ACTTTAGAAT CTCATTTTGT CTATTTGCTT ATCCTAAAAA TTAACTATAT TAAAATATTT

181 ATCATATACT TGCCCTTATT TGTGAACATT GAGAACTGAG TGCTTAACGA GCATTTATTA

241 AGAGGGAGAT GCCATAAAAG TTTGGACTAG TAGTATATAT CCACTTCAAT ATGTGGTCTG

301 TTGATGACAC AGGTAATGAG TTTAGAAGGT TAGTAATGTA GCTCGAGTAT CCTTAGTATC

361 CCTTAATTAT CTAGTATACA GTGATTATTT ATTAATATAG TCCCCTTTTT ATAAAACCTT

421 TTAAACCATC TTTAATTAGC ATCACTTAAT ATGGAACAAG CTCCTTTCTC CATTAGAATA

481 ATATTTGTTT GAAAACCACC ACTATTATCT CTTCTAGCTT CACCATAAAT ATTTTATAAT

541 TTGGCAAACA AAATTATTAT GACCATAGTT TTTATAATCA AACAACATTT TTTCTTTCTT

601 AATATACATA GAATAGAATG AAGAACAATT TTTTCCCATT ATACTGTCTT AGATGAATGT

661 CTATGACTTT ATAACATTGA ATATCTAGTT ATTCCCAAAC TGTTAAAAAG TTATTCATAC

721 TAATGATAAA ATTTTAGCAT ACCATTGTCT TAAACTCTGA CTGAAGGCCT TTTTTAAAAA

781 ATTATTTTCA GGGGCCAGGC ACAGTGGCTC ACGCCTGTAA TCCCAGCGTT TTGGGAGGCC

841 GAAGCAGGTG GATCGCCTCA GGTCAGGAGT GCGAGACCAG CCTGGCCAAC ATGGTGAAAC

901 CCCGTCTCCA CTAAAAATAC AAAAAAATTA GCTAGGTATG GTGGCGGGCA CCTGTAATTC

961 CAGCTACTTG GGAGGCTGAG GCAGGAGAAT CATTCGACCC AGGAGTCGGA GGTTGCAGTG

1021 AGCCAAGATC ACGCCACTGC ACTCCAGCCT GGGCAACAAG CACAAAACTC CGTCTCAAAA

1081 AAAAAATTAT TTTTAGGAGC ATTAGAGAAA ACCCTTGAAA TGTTTCCACT GTAACATTTA

1141 CTGGTTTCAT GAACCTCAAA TTGATGGAAA GGTCATGTCA TAGTGAAAGT AAACCTGATT

1201 CACTATTGCC TGGTAATGTC AGATATAGTT ATAAATGAAG TCAGTTTCAT TGAAAGTTAA

1261 ATGAAGGTTA GGAAAAATAA TGATGCTTAT TTACTAGACA AGAACAAAAT TAATATGGAT

1321 TGTTTCATTA GCTGTTTCTT TAAAAAGATG TTAACCACCC TCATGTTTTC ACATTCAGGT

1381 ATCCTTAGTC TGTTGGAGCA TGGAGAAGAG TACACATTTT CTCTACCCTG TGCATATGCT

1441 CGGTCAATTT TGACTGTTCC TTGGGTAGAA CTGGGTGGCA AAGTCAGTGT CAACTGTGCA

1501 AAAACTGGAT ATTCAGCCAG CATCACTTTT CATACCAAGC CATTTTATGG TGGCAAACTG

1561 CATCGGTAAG AACATTTTAA TGATTATCTA GTTCTTATTC TTCCACTTTG ATTTTGTATT

1621 ACAACTCCTT ATTCTTTTTC TGCTCTGTTC TATGTGAAGT TGGATTTGTA TTAATGTTTA

1681 TTTCTTATTT AAAATATTTC ATCTTTAAAG CATTCTGAAA GTCATGCTCT GTTTTTAAAA

1741 GTAGTAACAT TAAGATATCT ACTCTTAAAA ATTTTCCTGA TGAAGTAACT AGTGAGCTTT

1801 ATAGTAGAAT TTCTAACAAG TGAACATGCA GTCTCTGGCC CAATTCTGCC TTTAAGGGAT

1861 ACAGATTTGG ATCTGGACCT CAGTGAAGGC AGCTATAGCT ATAAGTTAGG GTGGAAATAT

1921 ATCTAATCAT GAAGAATGGT TCAAGAAGCA CAATGATTAA AGCCAGTGTA TGTGCTTCAT

1981 TAGATGCTTA GGTGGAAGCA ACTTGCAGTG ATAAATTTCT AGATCCAGTA CTTCTTATTG

2041 TCAATGATAT TGATGCATTT TTTTTTTTTG TCATTTGTTT TTTTGAGACA GAGTCTCACT

2101 CTGTCGCCTA GGCTGGAGTG CAGTGGCACA ATCTTGGCTC CTTGCAGCCG CCTCCTGGGT

2161 TCAAGCGATT TTTGTGCCTC AGCCTCCCAA GTAGCTGTGA TTACGGCATG TGCCACCATG

2221 CCTGGCTGCT TTTTGTATTT TTAGTTGAGA TGGGCTTTCA CCATGTTGGC CAGGCTGGTC

2281 TCAAACTCCT GGCCTTAAGT GATCTGCCTG CCTCAACCTC CCAAAGTGCT GGGAGCCACC

2341 ACACCTGGCT AATATTGATG TATTTCTTAG TCACATGTGA TTTTTTAGTC ATGGGTGGAT

2401 CACCTGAGGT CAGGATTTCG AGACCAGCCT AGCCAACATG ACGAGACTCC GTCTCTACTA

2461 AAAATACAAA ATTAGCTGAG TATGGTGGCG CATGCCTGTA ATCCCAGCTA TTCAGGAGGC

2521 AAGGCTGGAG GATCACTTGA ACCCAGTAGG CAGAGGTTGC AGTGAGCTGA GGTTGCACCA

2581 CTGCTCTCCA GCCGGGGTGA CAAGAGTGAA ACTCCGTCTC AAAAAAAAAA AAAAAAAA

B: aminoacid sequence (SEQ ID NO:29) length: 102

1 MKVRKNNDAY LLDKNKINMD CFISCFFKKM LTTLMFSHSG ILSLLEHGEE YTFSLPCAYA

61 RSILTVPWVE LGGKVSVNCA KTGYSASITF HTKPFYGGKL HR

C. Nucleotide and amino acid composite sequence (SEQ ID NO:30) clone number: PP14733 start code: 1261 ATG stop coding: 1567 TAA protein molecular weights: 11561.97

1 GAG CCA GAA CCA TGT TTT TTG GGA AAT GGC TCA ATA AAC CTT AAT TTA 48

49 TTG TTG CCC TTT GTG AAG ACT ATT AAG AGC AAT ACA AAA AAA AAA AAT 96

97 AGT TGA TGT TGC TTT GTG TAG GCT ACT TTA GAA TCT CAT TTT GTC TAT 144

145 TTG CTT ATC CTA AAA ATT AAC TAT ATT AAA ATA TTT ATC ATA TAC TTG 192

193 CCC TTA TTT GTG AAC ATT GAG AAC TGA GTG CTT AAC GAG CAT TTA TTA 240

241 AGA GGG AGA TGC CAT AAA AGT TTG GAC TAG TAG TAT ATA TCC ACT TCA 288

289 ATA TGT GGT CTG TTG ATG ACA CAG GTA ATG AGT TTA GAA GGT TAG TAA 336

337 TGT AGC TCG AGT ATC CTT AGT ATC CCT TAA TTA TCT AGT ATA CAG TGA 384

385 TTA TTT ATT AAT ATA GTC CCC TTT TTA TAA AAC CTT TTA AAC CAT CTT 432

433 TAA TTA GCA TCA CTT AAT ATG GAA CAA GCT CCT TTC TCC ATT AGA ATA 480

481 ATA TTT GTT TGA AAA CCA CCA CTA TTA TCT CTT CTA GCT TCA CCA TAA 528

529 ATA TIT TAT AAT TTG GCA AAC AAA ATT ATT ATG ACC ATA GTT TTT ATA 576

577 ATC AAA CAA CAT TTT TTC TTT CTT AAT ATA CAT AGA ATA GAA TGA AGA 624

625 ACA ATT TTT TCC CAT TAT ACT GTC TTA GAT GAA TGT CTA TGA CTT TAT 672

673 AAC ATT GAA TAT CTA GTT ATT CCC AAA CTG TTA AAA AGT TAT TCA TAC 720

721 TAA TGA TAA AAT TTT AGC ATA CCA TTG TCT TAA ACT CTG ACT GAA GGC 768

769 CTT TTT TAA AAA ATT ATT TTC AGG GGC CAG GCA CAG TGG CTC ACG CCT 816

817 GTA ATC CCA GCG TTT TGG GAG GCC GAA GCA GGT GGA TCG CCT CAG GTC 864

865 AGG AGT GCG AGA CCA GCC TGG CCA ACA TGG TGA AAC CCC GTC TCC ACT 912

913 AAA AAT ACA AAA AAA TTA GCT AGG TAT GGT GGC GGG CAC CTG TAA TTC 960

961 CAG CTA CTT GGG AGG CTG AGG CAG GAG AAT CAT TCG ACC CAG GAG TCG 1008

1009 GAG GTT GCA GTG AGC CAA GAT CAC GCC ACT GCA CTC CAG CCT GGG CAA 1056

1057 CAA GCA CAA AAC TCC GTC TCA AAA AAA AAA TTA TTT TTA GGA GCA TTA 1104

1105 GAG AAA ACC CTT GAA ATG TTT CCA CTG TAA CAT TTA CTG GTT TCA TGA 1152

1153 ACC TCA AAT TGA TGG AAA GGT CAT GTC ATA GTG AAA GTA AAC CTG ATT 1200

1201 CAC TAT TGC CTG GTA ATG TCA GAT ATA GTT ATA AAT GAA GTC AGT TTC 1248

1249 ATT GAA AGT TAA ATG AAG GTT AGG AAA AAT AAT GAT GCT TAT AAA CTA 1296

1 Met Lys Val Arg Lys ASn Asn Asp Ala Tyr Leu Leu 12

1297 GAC AAG AAC AAA ATT AAT ATG GAT TGT TTC ATT AGC TGT TTC TTT AAA 1344

13 Asp Lys Asn Lys Ile Asn Met Asp Cys Phe Ile Ser Cys Phe Phe Lys 28

1345 AAG ATG TTA ACC ACC CTC ATG TTT TCA CAT TCA GGT ATC CTT AGT CTG 1392

29 Lys Met Leu Thr Thr Leu Met Phs Ser His Ser Gly Ile Leu Ser Leu 44

1393 TTG GAG CAT GGA GAA GAG TAC ACA TTT TCT CTA CCC TGT GCA TAT GCT 1440

45 Leu Glu His Gly Glu Glu Tyr Thr Phe Ser Leu Pro Cys Ala Tyr Ala 60

1441 CGG TCA ATT TTG ACT GTT CCT TGG GTA GAA CTG GGT GGC AAA GTC AGT 1488

61 Arg Ser Ile Leu Thr Val Pro Trp Val Glu Leu Gly Gly Lys Val Ser 76

1489 GTC AAC TGT GCA AAA ACT GGA TAT TCA GCC AGC ATC ACT TTT CAT ACC 1536

77 Val Asn Cys Ala Lys Thr Gly Tyr Ser Ala Ser Ile Thr Phe His Thr 92

1537 AAG CCA TTT TAT GGT GGC AAA CTG CAT CGG TAA GAA CAT TTT AAT GAT 1584

93 Lys Pro Phe Tyr Gly Gly Lys Leu His Arg *** 103

1585 TAT CTA GTT CTT ATT CTT CCA CTT TGA TTT TGT ATT ACA ACT CCT TAT 1632

1633 TCT TTT TCT GCT CTG TTC TAT GTG AAG TTG GAT TTG TAT TAA TGT TTA 1680

1681 TTT CTT ATT TAA AAT ATT TCA TCT TTA AAG CAT TCT GAA AGT CAT GCT 1728

1729 CTG TTT TTA AAA GTA GTA ACA TTA AGA TAT CTA CTC TTA AAA ATT TTC 1776

1777 CTG ATG AAG TAA CTA GTG AGC TTT ATA GTA GAA TTT CTA ACA AGT GAA 1824

1825 CAT GCA GTC TCT GGC CCA ATT CTG CCT TTA AGG GAT ACA GAT TTG GAT 1872

1873 CTG GAC CTC AGT GAA GGC AGC TAT AGC TAT AAG TTA GGG TGG AAA TAT 1920

1921 ATC TAA TCA TGA AGA ATG GTT CAA GAA GCA CAA TGA TTA AAG CCA GTG 1968

1969 TAT GTG CTT CAT TAG ATG CTT AGG TGG AAG CAA CTT GCA GTG ATA AAT 2016

2017 TTC TAG ATC CAG TAC TTC AAA TTG TCA ATG ATA TTG ATG CAT TTT TTT 2064

2065 TTT TTG TCA TTT GTT TTT TTG AGA CAG AGT CTC ACT CTG TCG CCT AGG 2112

2113 CTG GAG TGC AGT GGC ACA ATC TTG GCT CCT TGC AGC CGC CTC CTG GGT 2160

2161 TCA AGC GAT TTT TGT GCC TCA GCC TCC CAA GTA GCT GTG ATT ACG GCA 2208

2209 TGT GCC ACC ATG CCT GGC TGC TTT TTG TAT TTT TAG TTG AGA TGG GCT 2256

2257 TTC ACC ATG TTG GCC AGG CTG GTC TCA AAC TCC TGG CCT TAA GTG ATC 2304

2305 TGC CTG CCT CAA CCT CCC AAA GTG CTG GGA GCC ACC ACA CCT GGC TAA 2352

2353 TAT TGA TGT ATT TCT TAG TCA CAT GTG ATT TTT TAG TCA TGG GTG GAT 2400

2401 CAC CTG AGG TCA GGA TTT CGA GAC CAG CCT AGC CAA CAT GAC GAG ACT 2448

2449 CCG TCT CTA CTA AAA ATA CAA AAT TAG CTG AGT ATG GTG GCG CAT GCC 2496

2497 TGT AAT CCC AGC TAT TCA GGA GGC AAG GCT GGA GGA TCA CTT GAA CCC 2544

2545 AGT AGG CAG AGG TTG CAG TGA GCT GAG GTT GCA CCA CTG CTC TCC AGC 2592

2593 CGG GGT GAC AAG AGT GAA ACT CCG TCT CAA AAA AAA AAA AAA AAA A 2638

11.PP14762

A: nucleotide sequence (SEQ ID NO:31) length: 2205

1 GATCTCACAG GGATTGAGTG GGCCCCAAAC GGCTGTGTGC TGGCAGTGTG GGACACCTGC

61 TTGGAGGTAT GAAGATGACC AGGTGACATG TTTGCTTTCG AGAGCTTTTC CCGGAATTTC

121 ATGCTTTCTG AATGCTGCAA TATAGTTTGC TTTATCTTAT TTCAGATAAC AAGTTGAGCT

181 TTGTTTTAAA AGACAGGGTC TTGCTCTGTC ACCCAGGCTG GAGTGCAGTG GTGTGATCAC

241 GGCCCACTGC AGCCTCGACC TCCTGGACTC AAGTGATCCT CCTACCTCAG CCTCCCAAGT

301 AGCTGGGACC ACAAGCATGC ACCACCACGC CCGGCTAATT TTTGTATTCT TTGTAGAGAT

361 GGGGTTTCAC CGTGTTGCCC AGACTGCTCT TGAACTTCTG TGTTCAAGTG ATCTGCCAGC

421 TTCGGCCTCC CAAAGTGCTG GGATTACAGG CGTGAGCCAC AGTGCCCGGC CGAGTTGAAC

481 TTTTATCAGC GAGCCATTAG GTTGACCTCC CAATTTCCCC TTTTTCCTCA TGCTCTCACT

541 GCCTCTCCGT GACTATCTCA GTACTAGCTG GCAGTTCCAG CTTTTCCACG GCCACGCGGA

601 CAGTCCTGCC AGCTTTGTGC TATCTGCACC AATGTCACTC TGCAGCACCC GCGTCTGTGG

661 TGTGTTCCTG GCGACGGGGG TGTATTCATT ATTAACTGAA ATGTCTCATC TGCAGTACAA

721 GATTCTGCTG TACTCATTGG ATGGCCGGTT GTTGTCCACG TACAGCGCTT ACGAGTGGTC

781 CTTGGGCATC AAGTCTGTGG CCTGGAGCCC CAGCAGTCAG TTCCTGGCAG TTGGGAGCCG

841 TCCCCCAGCC GCCCAACCTC CTAAGCGCTG AAGGAATTAT TTTTGGGAGT CATGACCATA

901 GCTGCCTGCT TCCCCCAACC CTCGACGACG AAAAGGACTT CGGCCCCCGG CCGGGCGGCT

961 CCGGGGGAAA AAAGAGAGAG CGACCTCCGC CCCGCGCTCA GGGCCACTCT AGAGGGAGAA

1021 GCTGCCCCGA GGCTGGCAGA GCGCCCAGCC GCGGTGGAGA CCGGAAGCCT TCTGGAGCCC

1081 AAGGCTGTGC ACGTCCCCTG TGCTGATTCT CTGCCTAGGA AAGGACCATG CAGCTGGAGA

1141 TCAAAGTAGC CCTGAACTTC ATCATCTTCT ACTTGTACAA CAAGCTGCTC TGGCGCCTCT

1201 GAAAAAGAAA TAAGAAGCCC ACTGGTACCC TGACAAACCA CTGAAGGGCT CTGGCTTCCA

1261 CACCGAGGAG ATGGTGGACC CCGTTGGGGA GCTGGCCGCT AAGCGAAGTG GCCTGACAGT

1321 GGAAGATGTG CGGGCCAATG TGCCTGAGGA GCTGAGCATA TGGATTGACC CCTTCGGGGT

1381 GTCCTACCAG ATTGGTGAGA AGGGAGCAGT GAAAGTGCTG TACCTGGATG ACAGTGACGG

1441 CTGTGGGGCC CCGGAGCTGG ACATGAAGAT CAAGAGCAGT TTCACTCCTG ACGACCAGAT

1501 GCTCTTTCTC CTCGGAAGCC AGGACAGCTC CTTGTCCAAC TCCCCGTCGC TATGCTTTGC

1561 CCATCACCCA GCCCCACCTT CATCCTCTGC CTCGCCCAGC CCATCACCTT CACCATGGAC

1621 TCCTTTGCTG CCACCAAATT AGGCTCCACT AAGATGAAGA AGAGGGGTGG GGCAACAAGT

1681 GGTAGGGGTG CAGCCAGCGG TGAAGCAGGT GGCCAGCAGC CAGTACAGCA GCCTCCACGG

1741 CCCGCTTCAA CACCAACAGC TTGTTGAAAC ACAGGAGTCT TTCTCTGTCT GTGCATTCAT

1801 TGAACTTCAT CCCAGCCAAC CGGCCTCTCA ATCCCAGCTC TCGCCCCAAG GCCACGTACA

1861 GTCTCAAGTA CAACAGTGGT GGCTTGCCCA GTTTCTTCCT TGATGGGGCC AATGGCCAGG

1921 GTAGTGACAC CCGAGCCCTC TTTGGAGGCA GTGGGACTGT CACCTGCAAC GCCAGCAGCT

1981 TCTACATGGT CTAGGTATTT GGAGGTGGTG CCACCGCCTC TTCCTGGAGA AGGCACCCTT

2041 CATGGAAGAC CTCAGCTACA ACCTGAACAC CATGCAATAT CCTAGTCAAC CGTTCCAGTC

2101 CGTGGTGCTG GCCAACTGAC CGTCTACCTG CCCTGGGGCC GGGAGCACCC AAGACCACAG

2161 AAAAGAGAAA GAAAAGGAAA GGCCAAAAAA AAAAAAAAAA AAAAA

B: aminoacid sequence (SEQ ID NO:32) length: 123

1 MVDPVGELAA KRSGLTVEDV RANVPEELSI WIDPFGVSYQ IGEKGAVKVL YLDDSDGCGA

61 PELDMKIKSS FTPDDQMLFL LGSQDSSLSN SPSLCFAHHP APPSSSASPS PSPSPWTPLL

121 PPN

C. Nucleotide and amino acid composite sequence (SEQ ID NO:33) clone number: PP14762 start code: 1271 ATG stop coding: 1640 TAG protein molecular weights: 13037.87

1 G ATC TCA CAG GGA TTG AGT GGG CCC CAA ACG GCT GTG TGC TGG CAG 46

47 TGT GGG ACA CCT GCT TGG AGG TAT GAA GAT GAC CAG GTG ACA TGT TTG 94

95 CTT TCG AGA GCT TTT CCC GGA ATT TCA TGC TTT CTG AAT GCT GCA ATA 142

143 TAG TTT GCT TTA TCT TAT TTC AGA TAA CAA GTT GAG CTT TGT TTT AAA 190

191 AGA CAG GGT CTT GCT CTG TCA CCC AGG CTG GAG TGC AGT GGT GTG ATC 238

239 ACG GCC CAC TGC AGC CTC GAC CTC CTG GAC TCA AGT GAT CCT CCT ACC 286

287 TCA GCC TCC CAA GTA GCT GGG ACC ACA AGC ATG CAC CAC CAC GCC CGG 334

335 CTA ATT TTT GTA TTC TTT GTA GAG ATG GGG TTT CAC CGT GTT GCC CAG 382

383 ACT GCT CTT GAA CTT CTG TGT TCA AGT GAT CTG CCA GCT TCG GCC TCC 430

431 CAA AGT GCT GGG ATT ACA GGC GTG AGC CAC AGT GCC CGG CCG AGT TGA 478

479 ACT TTT ATC AGC GAG CCA TTA GGT TGA CCT CCC AAT TTC CCC TTT TTC 526

527 CTC ATG CTC TCA CTG CCT CTC CGT GAC TAT CTC AGT ACT AGC TGG CAG 574

575 TTC CAG CTT TTC CAC GGC CAC GCG GAC AGT CCT GCC AGC TTT GTG CTA 622

623 TCT GCA CCA ATG TCA CTC TGC AGC ACC CGC GTC TGT GGT GTG TTC CTG 670

671 GCG ACG GGG GTG TAT TCA TTA TTA ACT GAA ATG TCT CAT CTG CAG TAC 718

719 AAG ATT CTG CTG TAC TCA TTG GAT GGC CGG TTG TTG TCC ACG TAC AGC 766

767 GCT TAC GAG TGG TCC TTG GGC ATC AAG TCT GTG GCC TGG AGC CCC AGC 814

815 AGT CAG TTC CTG GCA GTT GGG AGC CGT CCC CCA GCC GCC CAA CCT CCT 862

863 AAG CGC TGA AGG AAT TAT TTT TGG GAG TCA TGA CCA TAG CTG CCT GCT 910

911 TCC CCC AAC CCT CGA CGA CGA AAA GGA CTT CGG CCC CCG GCC GGG CGG 958

959 CTC CGG GGG AAA AAA GAG AGA GCG ACC TCC GCC CCG CGC TCA GGG CCA 1006

1007 CTC TAG AGG GAG AAG CTG CCC CGA GGC TGG CAG AGC GCC CAG CCG CGG 1054

1055 TGG AGA CCG GAA GCC TTC TGG AGC CCA AGG CTG TGC ACG TCC CCT GTG 1102

1103 CTG ATT CTC TGC CTA GGA AAG GAC CAT GCA GCT GGA GAT CAA AGT AGC 1150

1151 CCT GAA CTT CAT CAT CTT CTA CTT GTA CAA CAA GCT GCT CTG GCG CCT 1198

1199 CTG AAA AAG AAA TAA GAA GCC CAC TGG TAC CCT GAC AAA CCA CTG AAG 1246

1247 GGC TCT GGC TTC CAC ACC GAG GAG ATG GTG GAC CCC GTT GGG GAG CTG 1294

1 Met Val Asp Pro Val Gly Glu Leu 8

1295 GCC GCT AAG CGA AGT GGC CTG ACA GTG GAA GAT GTG CGG GCC AAT GTG 1342

9 Ala Ala Lys Arg Ser Gly Leu Thr Val Glu Asp Val Arg Ala Asn Val 24

1343 CCT GAG GAG CTG AGC ATA TGG ATT GAC CCC TTC GGG GTG TCC TAC CAG 1390

25 Pro Glu Glu Leu Ser Ile Trp Ile Asp Pro Phe Gly Val Ser Tyr Gln 40

1391 ATT GGT GAG AAG GGA GCA GTG AAA GTG CTG TAC CTG GAT GAC AGT GAC 1438

41 Ile Gly Glu Lys Gly Ala Val Lys Val Leu Tyr Leu Asp Asp Ser Asp 56

1439 GGC TGT GGG GCC CCG GAG CTG GAC ATG AAG ATC AAG AGC AGT TTC ACT 1486

57 Gly Cys Gly Ala Pro Glu Leu Asp Met Lys Ile Lys Ser Ser Phe Thr 72

1487 CCT GAC GAC CAG ATG CTC TTT CTC CTC GGA AGC CAG GAC AGC TCC TTG 1534

73 Pro Asp Asp Gln Met Leu Phe Leu Leu Gly Ser Gln Asp Ser Ser Leu 88

1535 TCC AAC TCC CCG TCG CTA TGC TTT GCC CAT CAC CCA GCC CCA CCT TCA 1582

89 Ser Asn Ser Pro Ser Leu Cys Phe Ala His His Pro Ala Pro Pro Ser 104

1583 TCC TCT GCC TCG CCC AGC CCA TCA CCT TCA CCA TGG ACT CCT TTG CTG 1630

105 Ser Ser Ala Ser Pro Ser Pro Ser Pro Ser Pro Trp Thr Pro Leu Leu 120

1631 CCA CCA AAT TAG GCT CCA CTA AGA TGA AGA AGA GGG GTG GGG CAA CAA 1678

121 Pro ProAsn *** 124

1679 GTG GTA GGG GTG CAG CCA GCG GTG AAG CAG GTG GCC AGC AGC CAG TAC 1726

1727 AGC AGC CTC CAC GGC CCG CTT CAA CAC CAA CAG CTT GTT GAA ACA CAG 1774

1775 GAG TCT TTC TCT GTC TGT GCA TTC ATT GAA CTT CAT CCC AGC CAA CCG 1822

1823 GCC TCT CAA TCC CAG CTC TCG CCC CAA GGC CAC GTA CAG TCT CAA GTA 1870

1871 CAA CAG TGG TGG CTT GCC CAG TTT CTT CCT TGA TGG GGC CAA TGG CCA 1918

1919 GGG TAG TGA CAC CCG AGC CCT CTT TGG AGG CAG TGG GAC TGT CAC CTG 1966

1967 CAA CGC CAG CAG CTT CTA CAT GGT CTA GGT ATT TGG AGG TGG TGC CAC 2014

2015 CGC CTC TTC CTG GAG AAG GCA CCC TTC ATG GAA GAC CTC AGC TAC AAC 2062

2063 CTG AAC ACC ATG CAA TAT CCT AGT CAA CCG TTC CAG TCC GTG GTG CTG 2110

2111 GCC AAC TGA CCG TCT ACC TGC CCT GGG GCC GGG AGC ACC CAA GAC CAC 2158

2159 AGA AAA GAG AAA GAA AAG GAA AGG CCA AAA AAA AAA AAA AAA AAA AA 2205

Claims (10)

1. isolating people's protein polypeptide with cancer suppressing function is characterized in that, it is the polypeptide with aminoacid sequence of the group of being selected from down: SEQ ID NO:2,5,8,11,14,17,20,23,26,29,32.

2. polypeptide as claimed in claim 1 is characterized in that, this amino acid sequence of polypeptide is selected from down group: SEQ ID NO:14,17,20,23,26,29,32.

3. isolating polynucleotide is characterized in that, are selected from down group:

(a) polynucleotide of polypeptide according to claim 1 of encoding;

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

4. polynucleotide as claimed in claim 3 is characterized in that, the polypeptide of this polynucleotide encoding has the aminoacid sequence of the group of being selected from down: SEQ ID NO:2,5,8,11,14,17,20,23,26,29,32.

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

SEQ ID NO:3,6,9,12,15,18,21,24,27,30,33 coding region sequence or full length sequence.

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

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

(a) host cell that transforms or transduce with the described carrier of claim 6;

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

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

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

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

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

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