CN1266457A - Mold-resistant plants and method of construction of same - Google Patents

Abstract

DNAs encoding chimeric proteins each having a domain containing at least the elicitor-binding site of an elicitor receptor and another domain containing at least the signal transduction motif of a protein capable of imparting disease resistance to plants; recombinant vectors containing these DNAs; transformed plants prepared by using these vectors or offsprings thereof; and a method for the construction of disease resistant plants characterized by transferring the above vectors into plant hosts.

Description

The method of antifungal plant and acquisition antifungal plant

Technical field

Proteic DNA, the disease-resistant plants of conferring disease resistance in plants and the method that obtains this kind of plant the present invention relates to encode.More particularly, the DNA of a kind of chimeric protein (Chimerical receptor) the present invention relates to encode, this chimeric protein comprises that two structures become: one of them structural domain contains the inducer binding site of at least one inducer (elicitor) acceptor, and another structural domain contains the signal transduction motif of the resistant gene of a plant origin; The invention still further relates to the disease resistance plant that is transferred to above-mentioned DNA; And the method that obtains this kind of plant.

Technical background

When known plants infected at the reply invasive organism, synthetic and accumulation was known as the antibiotic substance [M.Yoshikawa (1978) Nature 257:546] of phytoalexin.In plant phytophthora (Phytophthora), found to bring out the material [N.T.Keen (1975) Sccience 187:74] of this resistance reaction, and it has been called " inducer ".

Show known multiple inducer, comprise degraded product, mycetogenetic protein inducer and mycetogenetic Avr (nontoxicity) gene product of the lytic enzyme generation of plant or originated from fungus.The example of plant origin degraded product has: by the polygalacturonic acid of polygalacturonase generation.The example of originated from fungus degraded product has: chitin (the N-acetyl oligochitosan) oligosaccharides that is produced by chitinase, or the dextran that is produced by dextranase.The example of protein inducer has: what belong to the phytophthora originated from fungus brings out element (elicitin).The example of Avr gene product has: derive from the Avr4 and the Avr9 of yellow branch spore (Cladosporium fulvum), or derive from the nipl of rye beak spore (Rhynchosporium secalis).These inducers carry out specificity with the plant disease resistance genes product that comprises the inducer acceptor on the plasmalemma of plant and do mutually.By this mutual work, the invasion of identification fungi etc. also produces signal.These signals reach nucleus and react to cause multiple resistance, thereby stop the fungi invaded plants.These reactions are known as anaphylaxis, comprise necrocytosis, hydrogen peroxide the proteic expression of generation, PR, lipoxidase expression and be known as generation [W.Knogge (1996) the Plant Cell 8:1711 of the resistance material of phytoalexin; A.F.Bent (1996) Plant Cell 8:1757; K.E.Hammond-Kosack and J.D.G.Jones (1996) Plant Cell 8:1773].

Synthetic and accumulation with phytoalexin is an example, it is believed that, the biological process of induction of resistance is following from the pathogenic infection plant to plant carries out: at first, when the mycelium instruction plant cell of pathogenic agent, dextranase in the vegetable cell plays a role and decomposes the polysaccharide of pathogenic agent mycelium wall surface, thereby discharges inducer.The polysaccharide that inducer is made up of dextran.They are dextran [J.K.Sharp etc., (1984) J.Biol.Chem.259:11321 that link to each other or link to each other with β-1,3 key with β-1,6 key; M.Yoshikawa (1990) Plant CellEngineering, 1.2:695; Y.Okinaka etc., (1995) Plant Physiol.109:839].If this inducer combines with acceptor in the vegetable cell, then produce the second messenger of performance Role in Plant Signal Transduction.Sort signal transduction material is introduced in the nucleus of vegetable cell, and activates the gene transcription of those coded plant toxinicide synthetic enzyme, thereby inducing plant is antitoxic synthetic.Simultaneously, the degeneration system of phytoalexin is suppressed.Therefore, phytoalexin is accumulated in the vegetable cell effectively.For example, in soybean, the phytoalexin of bringing into play important resistance effect is known as glyceollin, and its structure has been determined [M.Yoshikawa etc., (1978) Physiol.Plant.Pathol.12:73].

So, it is believed that the dextran inducer specific receptors that derives from the big male epidemic disease tempeh microspecies of the pathogenic filamentous fungus of soybean (Phytophthora megasperma f.sp.glycinea) is a kind of receptor protein that plays a significant role in the synthetic and cumulative process of antibiotic substance glyceollin.Kakitani etc. have separated and have been purified into the specific receptors (patent announcement of Japanese unexamined 6-321995 number) of this dextran inducer from the plasma membrane component of soybean root.In addition, Umemoto etc. [N.Umemoto etc., (1997) Proc.Natl.Sci.USA 94:1029] have been cloned into the gene of this dextran inducer acceptor of coding.

The report that many resistant genes about clone plant source are arranged recently.In these genes, find partly or entirely to relate to the characteristic motif or the structural domain (for example being rich in leucic tumor-necrosis factor glycoproteins, leucine zipper, nucleotide binding site (P-Lu pounces on) and serine/threonine kinase structural domain) of signal transduction.The disease-resistant gene that contains the plant origin of this motif that participates in signal transduction or structural domain as expection, for example reported following gene: derive from the resistant gene RPS2[M.Mindrinos of Arabidopis thaliana (Arabidopsis thaliana) etc., (1994) Cell 78:1089; A.F.Bent etc., (1994) Science 265:1856], derive from the resistant gene RPM1[M.R.Grant of Arabidopis thaliana etc., (1995) Science 269:843], derive from the resistant gene N[S.Whitham of tobacco etc., (1994) Cell 78:1101], derive from the resistant gene L6[G.J.Lawrence of flax etc., (1995) Plant Cell 7:1195], derive from the resistant gene Pto[G.B.Martin of tomato etc., (1993) Science 262:1432], derive from the resistant gene Prf[J.M.Salmeron of tomato etc., (1996) Cell 86:123], derive from the resistant gene Cf-9[D.A.Jones of tomato etc., (1994) Scence 266:789], derive from the resistant gene Cf-2[M.S.Dixon of tomato etc., (1996) Cell 84:451] and derive from resistant gene Xa21[W.Y.Song of paddy rice etc., (1995) Science 270:1804].

On the other hand, with respect to the acceptor in vegetable cell source, the great majority report is based on the clone of the acceptor that derives from zooblast.Simultaneously, be the Chimerical receptor of forming about by extracellular domain and the cell intracellular domain that derives from heteroreceptor also by considerable research.For example, the extracellular domain of identification special receptor part is replaced with the extracellular domain that identification is different from other part of above-mentioned part, the latter then, promptly new extracellular domain with signal can be reached nuclear cell intracellular domain and merge mutually, prepare Chimerical receptor thus.When this acceptor is expressed in cell, it is reported the part that the new extracellular domain of this Chimerical receptor identification is discerned, thus in cell conducted signal [H.Riedel etc., (1986) Nature324:68, J.Lee etc., (1989) EMBO J.8:167; H.Lehvaslaiho etc., (1989) EMBO J.8:159, S.Lev etc., (1990) Mol.Cell.Biol.10:6064].In addition, also report is also expressed therein even the gene of the zooblast acceptor of will encoding changes in the allogenic zooblast, and this gene is still brought into play function in a similar manner; For example, it is reported when the GM-CSF acceptor that derives from the people is expressed in mouse 3T3 cell, observe the transmission [S.Watanabe etc., (1993) Mol.Cell.Biol.13:144] of promotes growth signal.

But, just known to the inventor, still do not have any report and relate to chimeric report thing in the plant.In addition, there be not the function of report this chimeric report thing of prompting in plant yet.

Specification sheets of the present invention

The characteristic motif or the characteristic structural domain of the participation signal transduction that above-mentioned dextran inducer acceptor is not found in the resistant gene of plant origin.Therefore, this hint, a kind of may be that this dextran inducer acceptor may lack the signal transduction territory.Be used for carrying out Chimerical receptor research from the acceptor of animal cell, the inventor considers following situation: obtain Chimerical receptor if will discern the structural domain fusion of the structural domain of specific ligand and the participation signal transduction that derives from different proteins (comprising acceptor), this Chimerical receptor is transferred to vegetable cell and expresses in this vegetable cell, then this part can be identified and can finish signal transduction.The inventor considers that also even the cell that Chimerical receptor is expressed does not therein belong to identical plant species with the structural domain that participates in signal transduction from its derived cell, signal transduction also can carry out in a similar fashion.In other words, the inventor considers: no matter which kind of plant species, if can in plant, synthesize and express the gene of coding Chimerical receptor, wherein in described Chimerical receptor the inducer receptors bind in the intracellular signal transduction territory of plant origin acceptor, perhaps the inducer receptors bind (for example derives from the resistant gene RPS2 or the RPM1 of Arabidopis thaliana in the resistant gene by plant origin, derive from the resistant gene N of tobacco, derive from the resistant gene L6 of flax, derive from the resistant gene Pto of tomato, derive from the resistant gene Xa21 of paddy rice) structural domain coding and expection participation intracellular signal transduction, then compare, can improve the efficient of signal transduction with the situation of inducer acceptor single expression.As a result, just might produce the plant that pathogenic fungus is had obviously strong resistance, also can improve the output of agricultural-food.In addition, will be expected to produce economic benefit from reducing to use agricultural chemicals and reduce the environmental pollution aspect.

The present invention aims to provide the DNA of coding chimeric protein, and this chimeric protein comprises the structural domain of an inducer binding site that contains at least one inducer acceptor and the structural domain of a signal transduction motif that contains the plant origin resistant gene; Wherein be transferred to the disease resistance plant of above-mentioned DNA; And the method that produces this kind of plant.

Result as the deep and broad research that addresses the above problem, the inventor is by following method, conferring disease resistance in plants successfully: the gene of composite coding Chimerical receptor, this Chimerical receptor by one from the resistant gene of plant coded and expection participates in the structural domain of signal transduction and the structural domain of an inducer binding site that contains at least one inducer acceptor is formed; This gene is changed in Arabidopis thaliana plant and the tobacco plant; And in these plants, express this gene.Thus, finish the present invention.

The present invention relates to the to encode DNA of chimeric protein, but this chimeric protein comprises the structural domain of an inducer binding site that contains at least one inducer acceptor and the structural domain of a proteic signal transduction motif that contains at least one conferring disease resistance in plants.The function of this chimeric protein performance acceptor, conferring disease resistance in plants thus.

The object lesson of above-mentioned inducer has dextran, polygalacturonic acid, N-acetyl chitose class (chitosaccharide), brings out element, from the Avr gene product of yellow branch spore or from the niple gene product of rye beak spore.The object lesson of above-mentioned inducer acceptor comprises the acceptor of the above-mentioned inducer of enumerating.About the inducer binding site of dextran inducer acceptor, the protein that can provide is: the protein that contains the aminoacid sequence shown in the SEQ ID NO:27 at least; Or the protein that contains aminoacid sequence, disappearance, displacement, the increase shown in the SEQ ID NO:27 or insert at least one amino acid and can combine with relevant dextran inducer.Contain the structural domain of signal transduction motif about this, the structural domain that can provide is: contain at least one and be selected from and be rich in leucic tumor-necrosis factor glycoproteins, leucine zipper, nucleotide binding site and Serine/the be selected from structural domain of the motif in threonine kinase territory.The object lesson of this structural domain comprises the signal transduction territory from tomato Pto gene, Prf gene, Cf-2 gene or Cf-9 expression of gene product; Signal transduction territory from paddy rice Xa21 expression of gene product; Signal transduction territory (for example structural domain of SEQ ID NO:29 representative) from Arabidopis thaliana RPS2 gene or RPM1 expression of gene product; Signal transduction territory from flax L6 expression of gene product; And from the signal transduction territory of the N expression of gene product of tobacco.

The invention still further relates to the DNA of coding chimeric protein, this chimeric protein contains the aminoacid sequence shown in the SEQ ID NO:5,7 or 9; Or contain the aminoacid sequence shown in the SEQ ID NO:5,7 or 9, lack, replace, increase or insert at least one amino acid, and conferring disease resistance in plants.The object lesson of this DNA comprises the DNA that contains the nucleotide sequence shown in the SEQ ID NO:6,8 or 10.

The invention still further relates to the recombinant vectors that contains above-mentioned DNA.

The invention still further relates to the conversion plant of above-mentioned recombinant vectors conversion or the offspring of this plant.

The invention still further relates to plant with disease resistance or the offspring of this plant, wherein this plant has above-mentioned DNA and expresses this DNA.

The invention still further relates to the method that produces the disease resistance plant, comprise above-mentioned recombinant vectors is transferred in the plant.

The invention still further relates to the offspring's who produces plant with disease resistance or this plant method, comprise above-mentioned DNA is integrated in the karyomit(e) of plant, and express this DNA.

Be detailed description of the present invention below.

The DNA that the structural domain of its coding is contained the inducer binding site of at least one inducer acceptor is connected with the DNA that the structural domain of its coding contains the proteic signal transduction motif of at least one conferring disease resistance in plants, can obtain DNA of the present invention.DNA of the present invention is known as " DNA of coding Chimerical receptor " or " chimeric DNA " sometimes.

The inducer acceptor that can specifically enumerate comprises: the acceptor that is incorporated into plant degradation product inducer (as polygalacturonic acid), or be incorporated into the acceptor of fungal cell wall degraded product inducer (as dextran, N-acetyl oligochitosan), and be combined in the acceptor of protein inducer (as the mycetogenetic element that brings out) and be incorporated into such as the Avr gene product that derives from yellow branch spore or derive from the acceptor of the niple gene product of rye beak spore.

Method described below can be used as the method for the cDNA (below be called " ERDNA ") of these inducers of clones coding report things.

In brief, active by measuring the mark inducer from the plasmalemma of plant part then earlier with above-mentioned inducer isotopic labeling with combining of this part, the inducer acceptor of purifying and this inducer specific combination.Partial amino-acid series information so that the inducer acceptor of purifying obtains designs the PCR primer.Use these primers and be that masterplate carries out PCR, thereby obtain a probe with DNA from vegetable cell.From the cDNA library, clone purpose cDNA with this probe.

On the other hand, as mentioned above, the DNA of coded signal transduction motif is known among the present invention.Therefore, this DNA can enough PCR etc. the clone.

Subsequently, the DNA that connects ERDNA and coded signal transduction motif.The method that connects these DNA is: digest these DNA with suitable Restriction Enzyme, connect with ligase enzyme then.Perhaps, can connect like this: ERDNA is connected on the DNA of coded signal transduction motif with suitable oligonucleotide.Perhaps, above-mentioned DNA is inserted in the plasmid that is fit to and connect.During connection, be not specially limited the relative position of the DNA of ERDNA and coded signal transduction motif, that is: ERDNA can be positioned at upstream or the downstream of the DNA of coded signal transduction motif.

At last, determine the nucleotide sequence of the chimeric DNA obtained with traditional method (for example dideoxy method, Maxam-Gilbert method).Usually, with full-automatic dna sequencing instrument analysis of nucleotide sequences.

Fig. 1 shows the structure iron of chimeric DNA of the present invention, and chimeric DNA of the present invention is for example by the DNA of coding dextran inducer acceptor (ER) with from the RPS2 genomic constitution of Arabidopis thaliana.In Fig. 1, CER serves as reasons corresponding to the chimeric DNA of the RPS2 gene 5 ' petiolarea of about 1/3rd (1/3) RPS2 (SEQ ID NO:29) and total length ERDNA (SEQ ID NO:2) composition.IER among Fig. 1 and ISER have the ERDNA of brachymemma.In these chimeric DNAs, ERDNA is positioned at the upstream (for example, by contrast, their place-exchange in CER) of RPS2 gene.

The inducer binding site of dextran inducer acceptor is corresponding to the partial sequence of aminoacid sequence shown in the SEQ ID NO:1 from 239 to 442, and has the aminoacid sequence shown in the SEQ ID NO:27.As long as this inducer binding site is the protein that contains aminoacid sequence shown in the SEQ ID NO:27 at least, or contain aminoacid sequence, disappearance, displacement, increase shown in the SEQ ID NO:27 or insert at least one amino acid, and can with the protein of relevant dextran receptors bind, then the length of this inducer acceptor there is no particular restriction; This inducer acceptor can be clipped form (referring to " 2-11 " among Fig. 1, " 2-16 " and " 1-5 ").As the DNA of coding, can provide the nucleotide sequence shown in the SEQ ID NO:28 by the inducer binding site aminoacid sequence of SEQ ID NO:27 representative.

The nucleotide sequence of above-mentioned chimeric DNA and by the aminoacid sequence of the chimeric protein of this dna encoding for CER, is shown in respectively in SEQ ID NO:5 and 6; For IER, be shown in respectively in SEQ ID NO:7 and 8; For ISER, be shown in respectively in SEQ ID NO:9 and 10.As long as these chimeric proteins have as the combined function of inducer acceptor and give the plant disease-resistant activity, then described aminoacid sequence (SEQ ID NO:5,7 and 8) can have such as lacking, replace, increase or insert at least one amino acid whose sudden change.Except that those encoded packets are contained in the nucleotide sequence of the aminoacid sequence in the chimeric protein of the present invention, coding phase homopolypeptide and only (be defined as that " degeneracy isomer ") is also included among the DNA of the present invention because of the discrepant DNA of degenerate codon.For example, the DNA that is changed into degenerate codon (as AAT) corresponding to the codon AAC of Asn is known as the degeneracy isomer at this.

Can finish the importing of said mutation body (for example, referring to D.F.Mark etc., Proc.Natl.Acad.Sci.USA 81:5662-5666,1984 with site-directed mutagenesis; On February 28th, 1985 disclosed PCT WO 85/00817; R.P.Wharton etc., Nature 316:601-605, on August 15th, 1985), before the application submitted to, this method was the technology that is widely known by the people.In case determine above-mentioned nucleotide sequence, DNA of the present invention can be that the hybrid method of probe obtains by chemical synthesis, PCR method or with the dna fragmentation with this nucleotide sequence just.

The encode dna sequence dna of Chimerical receptor used in the present invention preferably has at least one terminator codon (as TAG) at its 3 ' end of next-door neighbour.If desired, ' the ATG codon of initial methionine(Met) is also optionally contained in the upstream of end, and the frame of this codon is consistent with the frame of described dna sequence dna at this dna sequence dna 5.In addition, other DNA of suitable length can be arranged as non-translational region in 5 ' the end upstream or 3 ' the end downstream of this dna sequence dna.

Usually, the code book dna sequence dna of inventing used Chimerical receptor is to insert in the plasmid or to become their integral parts in the phage DNA and exist; Or in inserting plasmid, phage or genomic dna, in the integral part as them, be present in microorganism (particularly bacterium), phage particle or the plant.The object lesson of above-mentioned bacterium comprises intestinal bacteria (E.coli) and Agrobacterium (Agrobacterium).In order to make dna sequence dna stably express in plant of coding Chimerical receptor, the DNA and the terminator of promotor, coding translation initiation codon (ATG) can be added on this dna sequence dna with suitable combination.

The DNA of code book invention Chimerical receptor (below be sometimes referred to as " chimeric DNA ") can be added in the carrier that is fit to, make up recombinant vectors of the present invention.

Carrier for chimeric DNA of the present invention to be added there is no particular restriction, as long as it can duplicate in the host.For example, can adopt plasmid DNA, phage DNA and suchlike DNA.

Binary vector is a kind of of plasmid DNA, availablely prepares from intestinal bacteria or Agrobacterium such as alkali extraction method (Birnboim, H.C and Doly, J. (1979) Nucleic Acid Res.7:1513).The binary vector that can specifically enumerate comprises pBI121 and pBI101.Perhaps, can use commercially available plasmid such as pUC118 (Takara Shuzo), pUC119 (Takara Shuzo), pBluescriptSK+ (Stratagene) or pGEM-T (Promega).

The phage DNA that can specifically enumerate comprises M13mp18, M13mp19 and M13tv18.

In order to connect chimeric DNA and carrier, spendable method be with purifying chimeric DNA of the present invention with suitable Restriction Enzyme digestion, be inserted into then in the relevant limit site of suitable carrier DNA or the multiple clone site and be used for connecting.

Chimeric DNA to be expressed should be added in the carrier, the feasible function that can appear this DNA.For this purpose, except that promotor and said gene, also signal peptide gene, terminator, drug resistance gene etc. can be added in the recombinant vectors of the present invention.As can be used for signal peptide gene of the present invention, can enumerate from β-1,3 dextran of tomato (Lycopersicon seculentum) or the signal peptide gene of analogue.As can be used for enhanser of the present invention, can enumerate sequence or the similar sequence of tobacco mosaic virus (TMV) Ω.As can be used for drug resistance gene of the present invention, can enumerate kalamycin resistance gene, hygromycin gene or similar gene.

The above-mentioned promotor that can specifically enumerate comprises the coding ribulose-1,5-bisphosphate, promotor (the R.Fluhr etc. of 5-bisphosphate carboxylase small ylidene gene, Proc.Natl.Acad.Sci.USA (1986) 83:2358), the promotor (W.H.R.Langridge etc. of nopaline synthase (NOS) gene, PlantCell Rep. (1985) 4:355), produce the promotor (H.Guilley etc. of cauliflower mosaic virus 19S-RNA, Cell (1982) 30:763) and produce the promotor (J.T.Odell etc., Nature (1985) 313:810) of cauliflower mosaic virus 35S-RNA.The above-mentioned terminator that can specifically enumerate comprises the terminator [A.Depicker etc., J.Mol.Appl.Gen. (1982) 1:561] of nopaline synthase gene and the terminator [J.Gielen etc., EMBO J. (1984) 3:835] of octopine synthase gene.

Say that definitely as shown in Figure 2, cauliflower mosaic virus 35S promoter (p35S) is connected the upstream of this chimeric DNA, nopaline synthase gene terminator (NosT) is connected the downstream (this construct is known as " ER box ") of this chimeric DNA.In addition, made up kalamycin resistance gene (NPT II) is connected box (" NPT II box ") between nopaline synthase gene promotor and the terminator, hygromycin gene is connected box (" Hm box ") between p35S and the NosT.Then, NPT II box is connected the upstream of ER box, then the Hm box is connected the downstream of ER box, thereby obtains recombinant vectors of the present invention (Fig. 2).

Point out from various researchs for inducer and acceptor thereof: under the situation of for example dextran inducer and acceptor thereof, dextran inducer acceptor plays an important role in to the wide scope fungi resistance of (containing dextran in the cell walls component at them) plant.In addition, cloned the gene of coding dextran inducer acceptor, analyzed its primary sequence, the result shows that this inducer receptor deficiency participates in the structural domain of signal transduction.On the other hand, the resistant gene with the plant origin of hitherto reported is divided into following 4 classes [M.S.Dixon etc., (1996) Cell 84:451] roughly by its structure.

The first kind: the gene of this class has and is rich in leucic tumor-necrosis factor glycoproteins and nucleotide binding site.In them some also contain leucine zipper.These genes are considered to be arranged in tenuigenin.The resistant gene that belongs to this class that can specifically enumerate comprises resistant gene N from tobacco, from the resistant gene RPS2 of Arabidopis thaliana and RPM1, from the resistant gene L6 of flax with from the resistant gene Prf of tomato.

Second class: such gene has and is rich in leucic tumor-necrosis factor glycoproteins and film binding site.These genes are considered to be positioned at cell surface.Belong to such from the resistant gene Cf-2 of tomato and Cf-9 etc.

The 3rd class: such gene has the serine/threonine kinase structural domain.Belong to such from resistant gene Pto of tomato etc.

The 4th class: the gene of this class has and is rich in leucic tumor-necrosis factor glycoproteins, membrane structure territory and serine/threonine sample kinase domain.It is believed that, be rich in leucic tumor-necrosis factor glycoproteins and may discern inducer, thereby activate the serine/threonine kinase that is arranged in cell.Belong to such from resistant gene Xa-21 of paddy rice etc.

Therefore, the resistant gene of plant origin contains motif or the structural domain that one or more expections participate in signal transduction, promptly is rich in leucic tumor-necrosis factor glycoproteins, leucine zipper, nucleotide binding site and serine/threonine kinase structural domain.

So, in the present invention, the structural domain of the structural domain by connecting an inducer binding site that contains at least one inducer acceptor and the participation signal transduction of a plant origin disease resistence gene (as RPS2 gene, RPM1 gene, N gene, L6 gene, Pto gene, Xa21 gene, Cf-2 gene, Cf-9 gene, Prf gene) coding, the DNA of preparation coding chimeric protein makes its expression then.

For example, use currently known methods, the structural domain that will be contained the DNA of inducer binding site of at least one dextran inducer acceptor and its coding by the structural domain of its coding contains bright ammonia slide fastener and the chimeric DNA that DNA formed of nucleotide binding site or the fragment of this chimeric DNA from Arabidopis thaliana resistant gene (RPS2), is transferred in the higher plant and expresses therein.

As a result, compare with the situation that those dextran inducer acceptors are imported into separately and express, might give plant to fungi also will be stronger resistance.

Once proposed such theory: the fungi of those infection plants has suppressor gene usually, and has therefore obtained to suppress the ability of plant to the inherent resistance of fungi.Yet, even in these cases, also might be by changing in this plant the DNA of coding Chimerical receptor among the present invention or the fragment of this DNA and expression therein, and make this Chimerical receptor performance function, or by modifying this DNA or regulate the expression amount of this DNA, thereby produce the plant that fungi is had stronger resistance.

In addition, with DNA of the present invention or its fragment and the gene or combined the changing in the higher plant of characteristic body (for example showing antimycotic dextranase) that strengthen fungus resistant, compare with those resistances that import separately the plant of dextranases or analogue, might give plant to fungi also will be stronger resistance.

The dna sequence dna of specifiable coding dextranase, comprise the DNA that contains the following proteic nucleotide sequence of coding: comprise the albumen of aminoacid sequence shown in SEQ ID NO:11 or 13, or comprise aminoacid sequence, disappearance, displacement, increase shown in SEQ ID NO:11 or 13 or insert at least one amino acid and have the albumen of dextranase activity.Above-mentioned DNA is intended to comprise all degeneracy isomer.This isomer that can specifically enumerate comprises and contains the DNA that is shown in the nucleotide sequence in SEQ ID NO:12 or 14.

Can adopt traditional method in vegetable cell or the plant is gone in transgenosis.For example, can adopt at J.Draper etc., the method for describing in " plant genetic transforms and genetic expression, lab guide " book of Blacwell Science Press (1988).The example of gene transformation method comprises with the biological method of virus or Agrobacterium with such as the physico-chemical process of electroporation, polyoxyethylene glycol method, microinjection, particle gun and dextran method.

When plant to be transformed is dicotyledons, the preferred usually biological method that adopts Agrobacterium.When plant to be transformed is a monocotyledons, or during to the insensitive dicotyledons of agroinfection, preferred physical/chemical method (as electroporation).As the vegetable material that target DNA will be transferred to, according to described transfer method, suitable material can be selected from blade, stem, root, petal, stem tuber, protoplastis, callus, pollen, seed embryo, seedling original hase (shootprimordia) etc.

When target DNA being changed in the vegetable cell of cultivation, use protoplastis usually as material, use such as electroporation, polyoxyethylene glycol method or similarly the physical/chemical method this DNA is changed over to wherein.On the other hand, when changing over to target DNA in the plant tissue, use blade, stem, root, petal, stem tuber, protoplastis, callus, pollen, seed embryo, seedling original hase or analogue as vegetable material.Preferred blade and stem.Adopting the biological method of virus or Agrobacterium, or, this DNA is changed in this plant tissue such as particle bombardment, microinjection or similar physics ∥ chemical process.The preferred biological method that uses Agrobacterium.

For regeneration plant the plant tissue that wherein has been transferred to coding Chimerical receptor dna sequence dna from those or the vegetable cell, with those plant transformed tissues or cell cultures on the substratum that is containing suitable plant growth regulating thing such as MS.The resulting seedling that is taking root is gone to soil make it to grow up to plant.

By shift and express the dna sequence dna of coding Chimerical receptor with aforesaid method, give the resistance of plant, or strengthen the resistance of plant pathogenic fungus to pathogenic fungus.The example of this kind of plant comprises those plants to the infection sensitivity of the pathogenic fungus that contains dextran in its cell walls.Say that definitely these plants include, but are not limited to plant of Solanaceae, leguminous plants, feverfew, pinkwort and grass.Example includes but not limited to tobacco, soybean, potato, paddy rice, chrysanthemum and carnation more specifically.

As pathogenic fungus, those fungies that contain dextran in cell walls are suitable as target most.The object lesson of this pathogenic fungus includes but not limited to: phytophthora (Phytophthora), Rhizoctonia (Rhizoctonia), Pyricularia, Puccinia (Puccinia), fusarium (Fusarium), Uromyces (Uromyces), Staphlosporonites (Botrytis) and Alternaria (Alternaria).More particularly, this pathogenic fungus includes, but are not limited to: Phytophthora nicotianae (Phytophthora nicotianae), dry thread Pyrenomycetes (Rhizoctoniasolani), Pyricularia oryzae, hole handle rest fungus (Puccinia horiana), sharp sickle spore (Fusarium oxysporum), pink sickle spore (Fusarium roseum), three septal falx spores (Fusarium tricinctum), China pink monospore rest fungus (Uromyces dianthi), Botrytis cinerea (Botrytis cinerea) and Alternaria dianthicola (Alternaria dianthi).

According to the present invention, the dna sequence dna that coding is transferred to the Chimerical receptor in the plant can pass through seed heredity to the offspring.Therefore, the dna sequence dna of transfer also is present in those from the seed that pollen or the ovary of plant of the present invention form, and this hereditary property can go down to posterity.So the plant of this dna sequence dna that has wherein shifted the coding Chimerical receptor of the present invention can be by seminal propagation, and can not lose its resistance to pathogenic fungus.Plant of the present invention can also breed by a large amount of breeding methods of employing plant tissue culture or such as conventional art methods such as cuttage, press strip, grafting, plant division, and can not lose its resistance to pathogenic fungus.

Whether to fungi have resistance, can whether have the resistance reaction and confirmed when adding the dextran inducer, or check with the fungi inoculation experiments if transforming plant.The resistance reaction experiment process of carrying out that adds inducer is: dextran inducer solution is added in blade surface, or from the dorsal part of blade dextran inducer solution is penetrated into blade with syringe, after for some time, observe the browning reaction that blade surface occurs, or check the accumulation of the fluorescent substance (phytoalexin) that is inspired by UV light.In the fungi inoculation experiments, can check resistance by following inoculation method, it is divided into two groups roughly, promptly be inoculated in over-ground part and be inoculated in underground part.I. following method can be used for pathogenic agent is inoculated in over-ground part.

(1) sprays inoculation: the suspension of pathogenic fungus or its spore is sprayed onto on the plant, under the proper temperature of saturated humidity, plant was hatched one hour then, observe the degree of falling ill in inoculation tank.

(2) dusting inoculation: (writing brush) will directly spread on the plant from the spore that affected area is collected with brush, or is inoculated on the plant with little dredger.In transferring to the inoculation tank that is suitable for infecting temperature, will inoculate plant and hatch whole one day one night.Next the step of taking is identical with the sprinkling inoculation.

(3) wound inoculation: a slice mycelium of spore suspension or cultivation bunch is inoculated into an end or those parts of passing bark with brill device plug that branch is cut.

(4) pin inoculation: be used in a pin or a branch of pin scratch plant of dipping in the suspension of pathogenic fungus and be used for inoculation.

(5) cell adhesion inoculation: when using the pathogenic fungus that does not form spore on substratum, the hypha body of cultivation or sclerotium (sclerotia) stick to plant surface and inoculate.

(6) plant of damage inoculation: without the pathogenic fungus direct inoculation, and the plant of fungi damage is placed on the plant to be tested, or the leaf of fungi damage is suspended in above the plant to be tested, make by inoculating from the mycelium of the plant-growth of damaged or from the spore that leaf drops.II. following method can be used for the pathogenic agent inoculation of underground part.

(1) soaks into soil inoculation: soak into soil and inoculate with spore suspension or splitted mycelium.

(2) mixed soil inoculation: the filamentous fungus that will in such as wheat bran, grain, paddy rice bar, barley straw, cultivate and mixing with soil and inoculate.

(3) bury diseased plant inoculation: in soil, bury the residual body of diseased plant and prepare by the pathogenic fungus Contaminated soil.After plant residue rots, thorough mixing soil.Then, planting seed is transplanted this place therein or with seedling.

(4) Contaminated soil inoculation: if a kind of specific soil disease always takes place in certain district, take soil away from this district, thorough mixing is also put in the basin or in the bucket.Then, planting seed is transplanted this place therein or with seedling.

(5) soak the root inoculation: prepare spore suspension from pathogenic bacteria or filamentous fungus.The root of healthy seedling soaked in this suspension be transplanted in the basin then in 3-5 minute.

Resistant proof can carry out according to above-mentioned inoculation method.More particularly, can directly radicula byssoidea be inoculated in the plant, and observe the expansion of focus, analyze resistance phytophthora.Perhaps, resistance also can detect like this: inoculation phytophthora zoospore is also observed the variation of focus.The resistance of soil fungi outside the phytophthora is detected, can be with the fungal cell and the mixing with soil of cultivating, at this soil upper seeding wheel or allow plant-growth thereon, observe the phenomenon of dampinging off then.But, the testing method of fungus resistant is not limited to these methods.

Brief description

Fig. 1 illustrates the construct of chimeric DNA of the present invention.

Fig. 2 shows the structure sketch map of plasmid pBI (Hm)-ER.

Fig. 3 shows the structure sketch map of plasmid pBI (Hm)-LER.

Fig. 4 shows the plasmid sketch map of the DNA that contains proteins encoded RPS2 N-terminal district (corresponding to this albumen 1/3).

Fig. 5 shows the structure sketch map of plasmid pBI (Hm)-CER.

Fig. 6 shows the structure sketch map of plasmid pBI (Hm)-IER.

Fig. 7 shows the structure sketch map of plasmid pBI (Hm)-ISER.

Implement optimal mode of the present invention

Below, will the present invention be described in more detail with reference to following examples.But technical scope of the present invention is not limited to these embodiment.

In following examples, the dextran acceptor is abbreviated as " ER ".The abbreviation of using among Fig. 2-7 is represented: restriction enzyme site:

B：BamHI；Xb：XbaI；SI：SalI；RI：EcoRI；RV：EcoRV；Xh：XhoI；

Sph：SphI；Sp：SpeI；ScI：SacI；Sm：SmaI；Nsp：NspI；N：NotI；

Nsi：NsiI；Nc：NcoI；H3：HindIII

(Sm): the SmaI recognition sequence lacks owing to insert DNA in the SmaI site.

DScI, dB:SacI site and BamHI site lack respectively.The leader sequence of L: β-1,3 dextranase.The pNOS:NOS promotor; P35S: cauliflower mosaic virus 35S promoter; The Nos-T:NOS terminator.NPTII: kalamycin resistance gene; Hm: hygromycin gene.RB, the dna sequence dna of LB:Ti plasmid right margin, the dna sequence dna of Ti-plasmids left margin.

The structure of [embodiment 1] vector plasmid

Each carrier makes up with following method.Except as otherwise noted, otherwise the reagent that uses in plasmid preparation such as Restriction Enzyme, joint etc. is the product of Takara Shuzo production.For amplification in intestinal bacteria and screening, use DH5 α (BRL).(1) structure (referring to Fig. 2) of pBI (Hm)-ER

Be arranged in (1997) Proc.Natl.Acad.Sci.USA 279:141 such as plasmid pER23-1[N.Umemoto with Restriction Enzyme BamHI and SalI digestion] the BamHI site and the SalI site of polylinker, obtain to contain fragment between the total length ER gene between these two restriction sites.Separate this fragment from sepharose.On the other hand, with BamHI and SacI digestion expression of plants type double base plasmid pBI121 (Clontech); Synthetic linker DNA shown below (SEQ ID NO:15 and 16) is synthetic with full-automatic dna synthesizer (Applied Biosystems).

Make these linker DNA annealing, be connected on the pBI121 that has digested, thereby produce the pBI joint.Then, above-mentioned fragment cloning between the BamHI site and SalI site of this pBI joint, is obtained pBI-ER thus.

5’-CTAGAGGATCCGGTACCCCCGGGGTCGACGAGCT-3’(SEQ?ID?NO：15)

5’-CGTCGACCCCGGGGGTACCGGATCCT-3’(SEQ?ID?NO：16)

Subsequently, with BamHI and SacI digestion pBI-ER, obtain to contain the fragment of total length ER gene.Separate this fragment from sepharose, with by with BamHI and SacI digestion expression of plants type double base plasmid pIG121-Hm [Nakamura etc., (1991), PlantBiotechnolgy II (Modern Chemistry Suppl. the 20th volume), 123-132 page or leaf; Kenzo professor Nakamura of Japan Nagoya university delivers] and the plasmid fragment that obtains is connected, thus obtain purpose carrier pBI (Hm)-ER.

Dna sequence analysis to the gained carrier shows, has obtained the nucleotide sequence shown in the SEQ ID NO:2.The coded aminoacid sequence of nucleotide sequence of SEQ ID NO:2 is shown among the SEQ ID NO:1.

On June 15th, 1994, the bacillus coli DH 5 alpha EKB633 that is transferred to plasmid pER23-1 will be loaded with, be deposited in industrial science technical body-state-run life science and human body technical institute (Japan, 1-3, Higashi 1-chome, Tsukeba City, the Ibaraki professor), preserving number is: FERM BP-4699.(2) structure (referring to Fig. 3) of pBI (Hm)-LER

Cut two HindIII sites among the pER23-1 with the HindIII enzyme.HindIII is fixed, removes the HindIII site ER part afterwards that is arranged in ER thereby the plasmid self that obtains is connected.Then, cut two remaining NotI sites, and mend flat by the Klenow fragment with the NotI enzyme.For the plasmid that obtains, introduce the BamHI joint, produce a BamHI site thus.Digest this plasmid with BamHI and HindIII, obtain to contain the fragment that is positioned at described HindIII site ER part before.This fragment is connected with a plasmid fragment, and this plasmid fragment contains the ER part after the described HindIII site of being positioned at by obtaining with BamHI and HindIII digestion pER23-1.

Further digest resulting plasmid with XbaI and BamHI.Then, make to derive from soybean β-1,3 dextranase untranslated 5 ' end and with full-automatic dna synthesizer synthetic synthetic linker DNA (SEQ ID NO:17 and 18) annealing, and be connected on the described plasmid, prepare pLER thus through digesting.5’-CTAGACTTCTTTCCTCAACCTTCTTTCTTCTTATATATTCGAAC-3’(SEQ?ID?NO：17)5’-GATCGTTCGAATATATAAGAAGAAAGAAGGTTGAGGAAAGAAGT-3’(SEQ?ID?NO：18)

Afterwards, digest pLER, and mend flat with the Klenow fragment with SalI.Then, the SacI joint is introduced to produce a SacI site.Further with XbaI and SacI digestion, acquisition contains the fragment of the ER gene of tool homing sequence (L) to resulting plasmid.Separate this fragment from sepharose, and it is connected with the plasmid fragment that obtains with SacI digestion expression of plants type binary vector plasmid pIG121 with XbaI, thereby obtain purpose carrier pBI (Hm)-LER.

Dna sequencing result to the generation carrier shows, has obtained to be shown in the nucleotide sequence among the SEQ ID NO:4.The coded aminoacid sequence of nucleotide sequence by SEQ ID NO:4 is shown among the SEQ ID NO:3.(3) coding comes from cDNA clone's the acquisition of N-end region (corresponding to this albumen 1/3) of the RPS2 of Arabidopis thaliana

The preparation method of Arabidopis thaliana cDNA is as follows: after the ehec infection C600hfl, be coated with cDNA library (Clontech) with every dull and stereotyped 200.000 plaques on ten 15 centimetres LB flat board, and reclaim this phage from described flat board.Obtained 5 groups of phage libraries, from 2 dull and stereotyped phages of reclaiming as 1 storehouse.According to Ishida method (" gene expression test handbook ", Ishida and Ando (editor), Kodansha Scientific Co.), reclaim phage DNA from each storehouse.

Adopt following PCR primer to one of, and be masterplate with about 1 microgram phage DNA (storehouse #1-#5), purpose cDNA (using the EX-Taq test kit of Takara Shuzo) with PCR method amplification coding pRPS2 N-end region is cloned among the plasmid pBluescript SKII (+) then.

(i) sense strand primer: 5 '-TGGCATGCGATGGATTTCATCTCATCTCTT-3 ' (SEQID NO:19)

Antisense strand primer: 5 '-GGGAATTCACTCCGCGAGCCGGCGAAT-3 ' (SEQ ID NO:20)

(ii) sense strand primer:

5’-ACAAGTAAAAGAAAGAGCGAGAAATCATCGAAATG-3’(SEQ?ID?NO：20)

Antisense strand primer: 5 '-AGCCATGGCTCCTCCTAAAGTGAT-3 ' (SEQ ID NO:21)

With above primer to (i) or primer to (ii) carrying out PCR.

With the DNA phosphorylation of amplification, insert the SamI site of pBluescript SKII (+), thereby obtain to be shown in the plasmid DNA (pRPS2-6, pRPS2-14 and pRPS2-16) of Fig. 4.Confirm that through dna sequencing except that its primer part, these DNA are consistent with the sequence of being reported [M.Mindrinos etc. (1994) Cell 78:1089].(4) structure (referring to Fig. 5) of pBI (Hm)-CER

With Restriction Enzyme XbaI digestion pRPS2-14, and self connect, thus this XbaI fragment of place to go.The BamHI joint is inserted the EcoRV site of the plasmid that produces.In addition, the SacI joint is inserted the XhoI site.The plasmid that is produced BamHI and SalI enzymic digestion, and the clone advances the total length ER that downcuts from pER23-1 with BamHI and SalI.From this plasmid, purifying contains the chimeric DNA of part RPS2 and total length ER.Contact between RPS2 and the ER is carried out dna sequencing, confirm that the frame of RPS2 is consistent with the frame of ER.

On the other hand, the pSpeI joint is inserted the RcoRV site of pRPS2-6.Then, digest this plasmid with XbaI and SacI, the clone advances the dna fragmentation of above-mentioned purifying then.This plasmid contains mosaic gene, and this mosaic gene is made up of RPS2 5 ' end region and the total length ER corresponding to about 1/3 RPS2, digests this plasmid to cut out this mosaic gene with SpeI and SacI, then this mosaic gene is cloned among the plasmid pIG121-Hm.Obtain purpose carrier pBI (Hm)-CER thus.

The result who the acquisition carrier is carried out dna sequencing is to obtain being shown in the nucleotide sequence among the SEQ ID NO:6.Be shown among the SEQ ID NO:5 by the coded aminoacid sequence of nucleotide sequence among the SEQ ID NO:6.(5) structure (referring to Fig. 6) of pBI (Hm)-IER

With BamHI and NspI, from 537 amino acid whose ER cDNA fragments of pER23-1 purifying coding N-end.On the other hand, use EcoRV and SphI from plasmid pRPS2-16 purifying RPS2 cDNA fragment.These two dna fragmentations are cloned between the BamHI site and SamI site of plasmid pBluescript SKII (+).This plasmid is named as pERRPS-8.Contact between RPS2 and the ER is carried out dna sequencing, confirm that the frame of RPS2 is consistent with the frame of ER.With SpeI and SacI digestion pERRPS-8, obtain to contain the fragment of fusion gene, this fusion gene is made up of the structural domain of coding inducer land and the structural domain of encoding part length RPS2.From sepharose, separate this fragment, be connected, obtain purpose carrier pBI (Hm)-IER thus with the plasmid fragment that obtains with SacI digestion expression of plants type binary vector pIG121-Hm with XbaI.

The result who the acquisition carrier is carried out dna sequencing is to obtain being shown in the nucleotide sequence among the SEQ ID NO:8.Be shown among the SEQ ID NO:7 by the coded aminoacid sequence of nucleotide sequence among the SEQ ID NO:8.(6) structure (referring to Fig. 7) of pBI (Hm)-ISER

With NsiI and NotI digested plasmid pERRPS-8.Then, NotI-NsiI connector shown below is inserted this plasmid.The ATG frame that is arranged in this connector through the dna sequencing affirmation is consistent with the frame of ER.Digest the plasmid that is produced, resulting this RPS2/ER chimeric DNA of purifying then with EcoRV and SalI.

5’-GGCCGCGATATCATGAATGCA-3’(SEQ?ID?NO：23)

5’-TTCATGATATCGC-3’(SEQ?ID?NO：24)

The synthetic DNA that derives from β-1,3 dextranase untranslated 5 ' end shown in below the preparation, and insert in the NotI site and EcoRI site of pBluescript SKII (+), prepare plasmid pL thus.

5’-GGCCGCCTTCTTTCCTCAACCTTCTTTCTTCTTATATATTCGAAC-3’(SEQID?NO：25)

5’-AATTGTTCGAATATATAAGAAGAAAGAAGGTTGAGGAAAGAAGGC-3’(SEQID?NO：26)

With EcoRV and SalI digested plasmid pL, the RPS2/ER chimeric DNA of above-mentioned purifying is inserted between the described restriction site.Resulting plasmid is known as pSERRPS-8.With SpeI and SacI digestion pSERRPS-8, obtain to contain the fragment of fusion gene, this fusion gene is made up of the structural domain of coding inducer binding site and the structural domain of encoding part length RPS2.From sepharose, separate this fragment, be connected, obtain purpose carrier pBI (Hm)-ISER thus with the plasmid fragment that obtains with SacI digestion expression of plants type binary vector pIG121-Hm with XbaI.

The result who the acquisition carrier is carried out dna sequencing is to obtain being shown in the nucleotide sequence among the SEQ ID NO:10.Be shown among the SEQ ID NO:9 by the coded aminoacid sequence of nucleotide sequence among the SEQ ID NO:10.

The preparation of [embodiment 2] Chimerical receptor gene transformation Arabidopis thalianas (1) agroinfection liquid

Use electroporation, the conversion carrier [pBI (Hm)-ER] that will contain the conversion carrier [pBI (Hm)-CER or pBI (Hm)-ISER] of Chimerical receptor gene or contain ER gene in contrast is transferred among the agrobacterium tumefaciens EHA101, at this agrobacterium tumefaciens EHA101 of 3 milliliters of YEB inoculation of mediums, and in 28 ℃ of cultivations 16 hours.Then, centrifugal collecting cell is suspended in 10 milliliters and infects in the substratum, and preparation transforms the agroinfection liquid of usefulness.Below be YEB substratum and the composition that infects substratum:

YEB substratum: 5g/L beef extract; The 1g/L yeast extract; The 5g/L peptone; 5g/L sucrose; 2mM sal epsom.

Infect substratum: the inorganic salt and the VITAMIN of 0.5 times of concentration of used concentration in the MS substratum [Murashige and Skoog (1962) Physiol.Plant.15:473]; 15g/L sucrose; 10g/L glucose; 10mM MES (pH 5.4).(2) method of generation Arabidopis thaliana transformant

Environmental and the ecotypic Arabidopis thaliana aseptically sowing seeds of Columbia cultivated for 3 weeks on the MSHF substratum with Landsberg.Root is cut to about 5 millimeters when growing to 2-3 centimetre, be transferred on the callus inducing medium to cultivate 2 days.With the broken immersion agroinfection of undercut liquid.After inhaling the unnecessary liquid go on the root fragment with filter paper, the root fragment is transferred on the collaborative substratum of Arabidopis thaliana, in the dark cultivated 2 days.Then, the root fragment is transferred on the heavy division culture medium of Arabidopis thaliana and cultivated 2 days.Afterwards, the root fragment is gone on the heavy division culture medium of Arabidopis thaliana screening and cultivating for 1 week.Then, week about the root fragment being transferred to fresh Arabidopis thaliana heavily cultivates until obtaining the regenerated seedling on the division culture medium.

When seedling grows to about 1 centimetre, sprigging is continued to cultivate to Arabidopis thaliana root induction substratum.When root extends to 1-2 centimetre, detect in the seedling whether have transgenosis, to obtain transformant with the PCR method.Except as otherwise noted, otherwise cultivate under 8 hours in 22 ℃, 16 hours/non-illumination of illumination.The every kind of substratum that uses in the culturing process composed as follows.

MSHF substratum: inorganic salt and the VITAMIN used in the MS substratum [Murashige and Skoog (1962) Physiol.Plant.15:473]; 20g/L sucrose; The 2g/L gellan gum; 5mM MES (pH 6.2).

Callus inducing medium: inorganic salt that use in the MS substratum and VITAMIN; 20g/L sucrose; 0.5mg/L 2,4 dichlorophenoxyacetic acid (2,4-D); 0.1mg/L kinetin; The 2g/L gellan gum; 5mM MES (pH 6.2).

Arabidopis thaliana is worked in coordination with culture medium: inorganic salt that use in the MS substratum and VITAMIN; 20g/L sucrose; 0.5mg/L 2,4-D; 0.1mg/L kinetin; 0.2mM Syringylethanone; The 2g/L gellan gum; 5mM MES (pH 6.2).

The heavy division culture medium of Arabidopis thaliana: inorganic salt that use in the MS substratum and VITAMIN; 20g/L sucrose; 1mg/L 2-isopentene amine; 0.15mg/L indolylacetic acid; The 250mg/L cefotaxime; The 2g/L gellan gum; 5mM MES (pH 6.2).

Arabidopis thaliana heavily breaks up screening culture medium: inorganic salt that use in the MS substratum and VITAMIN; 20g/L sucrose; 1mg/L 2-isopentene amine; 0.15mg/L indolylacetic acid; The 2g/L gellan gum; The 50mg/L kantlex; The 250mg/L cefotaxime; 5mM MES (pH 6.2).

Arabidopis thaliana root induction substratum: inorganic salt that use in the MS substratum and VITAMIN; 20g/L sucrose; The 2mg/L naphthylacetic acid; The 2g/L gellan gum; The 250mg/L cefotaxime; 5mMMES (pH 6.2).

[embodiment 3] go into tobacco plant (1) preparation agroinfection liquid with the Chimerical receptor transgenosis

Use electroporation, the conversion carrier [pBI (Hm)-IER] that will contain the conversion carrier [pBI (Hm)-IER] of Chimerical receptor gene or contain ER gene in contrast is transferred among the agrobacterium tumefaciens EHA101, at this agrobacterium tumefaciens EHA101 of 3 milliliters of YEB inoculation of mediums, and in 28 ℃ of cultivations 16 hours.Then, centrifugal collecting cell is suspended in 10 milliliters and infects in the substratum, and preparation transforms the agroinfection liquid of usefulness.Below be YEB substratum and the composition that infects substratum:

YEB substratum: 5g/L beef extract; The 1g/L yeast extract; The 5g/L peptone; 5g/L sucrose; 2mM sal epsom.

Infect substratum: the inorganic salt and the VITAMIN of 0.5 times of concentration of used concentration in the MS substratum [Murashige and Skoog (1962) Pbysiol.Plant.15:473]; 15g/L sucrose; 10g/L glucose; 10mM MES (pH 5.4).(2) method of generation tobacco transformant

To be cut into about 1 square centimeter fragment after the sterilization of the blade of tobacco (Nicotiana tabacum L.) Cultivar Samsun, float on agroinfection liquid last 10 minute, remove unnecessary liquid with filter paper then.Afterwards, blade is transferred on the collaborative substratum of tobacco, cultivated 2 days in the dark place.Blade is transferred on the heavy division culture medium of tobacco cultivates after 1 week, transfer on the heavy division culture medium of tobacco screening and cultivated for 2 weeks.Then, every 2 weeks they being transferred on the heavy division culture medium of fresh tobacco, until obtaining the regeneration seedling.

When seedling grows to about 1 centimetre, sprigging is continued to cultivate to tobacco root induction substratum.When extending to 1-2 centimetre, root detects in seedling, whether there is transgenosis, to obtain transformant with the PCR method.Except as otherwise noted, otherwise cultivate the every kind of substratum that uses in the culturing process composed as follows under 8 hours in 25 ℃, 16 hours/non-illumination of illumination.

Tobacco is worked in coordination with culture medium: MS[Murashige and Skoog (1962) Physiol.Plant.15:473] inorganic salt and the VITAMIN used in the substratum; 30g/L sucrose; 0.1mg/L naphthylacetic acid; The 1mg/L benzyladenine; 0.2mM Syringylethanone; 8g/L agar; 5mMMES (pH5.8).

The heavy division culture medium of Arabidopis thaliana: inorganic salt that use in the MS substratum and VITAMIN; 30g/L sucrose; 0.1mg/L naphthylacetic acid; The 1mg/L benzyladenine; The 250mg/L cefotaxime; 8g/L agar; 5mM MES (pH 5.8).

Arabidopis thaliana heavily breaks up screening culture medium: inorganic salt that use in the MS substratum and VITAMIN; 30g/L sucrose; 0.1mg/L naphthylacetic acid; The 1mg/L benzyladenine; The 100mg/L kantlex; The 250mg/L cefotaxime; 8g/L agar; 5mM MES (pH 5.8).

Tobacco root induction substratum: inorganic salt that use in the MS substratum and VITAMIN; 30g/L sucrose; The 250mg/L cefotaxime; 8g/L agar; 5mM MES (pH 5.8).

The anaphylaxis test of anaphylaxis test (1) arabidopsis thaliana transformation (the Landsberg ecotype) of [embodiment 4] arabidopsis thaliana transformation

With Arabidopis thaliana transformant (CER), Arabidopis thaliana transformant (ER; SEQ ID NO:2) and non-arabidopsis thaliana transformation, Arabidopis thaliana transformant (CER) has been identified one of Chimerical receptor gene that is produced (promptly containing the gene that is shown in the nucleotide sequence among the SEQ ID NO:6) and has highly expressed therein, also confirms Arabidopis thaliana transformant (ER; SEQ ID NO:2) the ER albumen height in is expressed.

With the syringe that removes syringe needle, dextran inducer that derives from fungal cell wall (100 μ g/ml) and the independent 10mM magnesium chloride solution that is dissolved in the 10mM magnesium chloride solution penetrated into respectively in the arabidopsis thaliana blade of growing the greenhouse from vacuum side of blade.Plant is observed the variation that blade surface takes place in 25 ℃, 16 hours/dark 8 hours following cultivations 7 days of illumination.The dextran inducer that derives from fungal cell wall that adopts in this test obtains according to the method [N.Umemoto etc., (1997) Proc.Natl.Acad.Sci.USA 94:1029] of Umemoto etc.

The dextran inducer is not observed variation after being penetrated in the non-arabidopsis thaliana transformation on its blade surface.This shows that Arabidopis thaliana can not discern this dextran inducer.On the other hand, in the arabidopsis thaliana (ER) of expressing dextran inducer acceptor, there are 2 to demonstrate weak browning reaction (resistance reaction) among 6 examined clones.In the arabidopsis thaliana (CER) of expressing Chimerical receptor, there are 8 to demonstrate effective browning reaction (resistance reaction) among 12 examined clones, there is 1 clone to demonstrate weak browning reaction (table 1).

The anaphylaxis test of table 1, arabidopsis thaliana transformation (the Landsberg ecotype)

Derive from fungal cell wall

The 10mM magnesium chloride

The dextran inducer

Contrast 1--

Contrast 2--

Contrast 3--

Contrast 4--

Contrast 5--

Contrast 6--

Contrast 7--

Contrast 8--

Contrast 9--

Contrast 10--

Contrast 11--

Contrast 12--

ER1???????????????-??????????????????????-

ER2???????????????-??????????????????????-

ER3???????????????+??????????????????????-

ER4???????????????-??????????????????????-

ER5???????????????-??????????????????????-

ER6???????????????+??????????????????????-

CER1??????????????++?????????????????????-

CER2??????????????++?????????????????????-

CER3??????????????++?????????????????????-

CER4??????????????++?????????????????????-

CER5??????????????-??????????????????????-

CER6??????????????+++????????????????????-

CER7??????????????+++????????????????????-

CER8??????????????++?????????????????????-

CER9??????????????-??????????????????????-

CER10?????????????-??????????????????????-

CER11?????????????++?????????????????????-

CER12---: no change; +: slight browning reaction; ++: the moderate browning reaction; The strong browning reaction of +++:.

These results confirm, when the identification of the dextran inducer that can not discern host plant does not occur over just the ER albumen single expression in soybean source, when also occurring in the Chimerical receptor of forming by the proteic N-end structure of the RPS2 territory (expecting that it contains the signal transduction territory) in ER albumen and Arabidopis thaliana source and in Arabidopis thaliana, expressing.In addition, confirm that also the expression Chimerical receptor is more favourable for identification dextran inducer.This shows: when Chimerical receptor was expressed, with respect to the situation of ER albumen single expression, signal transduction carried out more effectively after the dextran inducer bind receptor.

The invention provides DNA and plant, contacting and/or intrusion of described DNA and the plant plant pathogenic microorganism by identification such as the fungi that contains glucan structure in its cell walls etc. can be induced the resistance reaction that is closely related with disease resistance more consumingly than single expression ER albumen.By producing this induced strong, might cultivate show the plant of strong resistance such as the plant pathogenic microorganism of fungi by the resistance reaction that the dextran inducer causes.(2) the ecotypic anaphylaxis test of arabidopsis thaliana transformation Columbia

Blade detection soybean inducer with Arabidopis thaliana transformant (ISER) and non-arabidopsis thaliana transformation (contrast) is induced anaphylactoid, and this Arabidopis thaliana transformant has been identified one of Chimerical receptor gene that is produced (promptly containing the gene that is shown in the nucleotide sequence among the SEQ ID NO:10) and has highly expressed therein.

With the syringe that removes syringe needle, dextran inducer that derives from fungal cell wall (100 μ g/ml) and independent 10mM magnesium chloride solution with being dissolved in the 10mM magnesium chloride solution penetrate into respectively in the arabidopsis thaliana blade of growing the greenhouse from vacuum side of blade.Plant is observed the variation that blade surface takes place in 22 ℃, 16 hours/dark 8 hours following cultivations 7 days of illumination.The dextran inducer that derives from fungal cell wall that adopts in this test obtains according to the method [N.Umemoto etc., (1997) Proc.Natl.Acad.Sci.USA 94:1029] of Umemoto etc.

The dextran inducer is not observed variation after being penetrated in the non-arabidopsis thaliana transformation on its blade surface.This shows that Arabidopis thaliana can not discern this dextran inducer.On the other hand, in the arabidopsis thaliana (ISER) of expressing Chimerical receptor, there are 3 to demonstrate effective browning reaction (resistance reaction) (table 2) among 5 examined clones.

The anaphylaxis test of table 2, arabidopsis thaliana transformation (the Columbia ecotype)

Derive from fungal cell wall 10mM magnesium chloride

The dextran inducer

Contrast 1--

Contrast 2--

Contrast 3--

ISER1??????????????????????+++???????????-

ISER2??????????????????????-?????????????-

ISER3??????????????????????++????????????-

ISER4??????????????????????+++???????????-

ISER5---: no change; +: slight browning reaction; ++: the moderate browning reaction; The strong browning reaction of +++:.

These results confirm, the identification of the dextran inducer that can not discern host plant takes place by expressing by lacking the Chimerical receptor of forming corresponding to the proteic N-end structure of the RPS2 territory (expecting that this structural domain contains the signal transduction territory) in the ER of the N-end region of ER albumen about 1/3 and Arabidopis thaliana source.The invention provides and to discern such as the contact of the plant pathogenic microorganism of fungi that contains glucan structure in its cell walls etc. and/or the plant of intrusion.By producing the plant of the resistance reaction that this induced strong causes by the dextran inducer, might cultivate show the plant of strong resistance such as the plant pathogenic microorganism of fungi.

The anaphylaxis test of [embodiment 5] transformation of tobacco

With tobacco transformant (IER), tobacco transformant (LER; SEQ ID NO:4) and the blade of non-transformation of tobacco (contrast) detect the soybean inducer and induce anaphylactoid, wherein said tobacco transformant has been identified one of Chimerical receptor gene that is produced (promptly containing the gene that is shown in the nucleotide sequence among the SEQ IDNO:8) and has highly expressed therein, also confirms tobacco transformant (LER; SEQ ID NO:4) the ER albumen height in is expressed.

Downcut the blade that is grown in the tobacco plant in the greenhouse in petiole portion, place the plastics casing of printing opacity.It is that 5 millimeters, length are 5 millimeters siloxanes pipe fragment that the blade upper surface is placed diameter, makes it retaining liquid.The dextran inducer (100 μ g/ml) that derives from fungal cell wall is dissolved in the 10mM magnesium chloride solution, a kind of dextran inducer of chemosynthesis (100 μ g/ml) is dissolved in same solution, with independent 10mM magnesium chloride solution in contrast, these three kinds of solution are remained in respectively in the siloxanes pipe fragment, every kind of solution is contacted with blade surface.Under too high moisture, cultivate blade with anti-drying, in illumination 16 hours/dark 8 hours, 25 ℃ following cultivations 7 days.The dextran inducer of described chemosynthesis (β-D-Portugal hexoside (glucohexaoside)) [N.Hong and T.Ogawa (1990) Tetrahedron Lett.31:3179] is delivered (Tokyo University, Physical and Chemical Inst.) by professor Ogawa.After the cultivation, remove siloxanes pipe fragment.Then, go up the antitoxic accumulation of observation tobacco plant at UV lamp (Funakoshi).

When this dextran inducer is added non-transformation of tobacco, do not observe variation.This shows that non-transformation of tobacco can not discern this dextran inducer.In the tobacco plant of expressing ER, there is 1 only to demonstrate very a spot of fluorescent substance (phytoalexin) accumulation among 5 clones that detected.In the tobacco of expressing IER, 3 fluorescent substance (phytoalexin) accumulation that demonstrate appreciable amount are arranged among 5 clones that detected, 1 clone demonstrates very a spot of fluorescent substance (phytoalexin) accumulation (table 3).

The anaphylaxis test of table 3, transformation of tobacco

	Derive from the dextran inducer of fungal cell wall	The dextran inducer of chemosynthesis	????10mM?MgCl 2
				Contrast 1	??????-	????-	??????-
Contrast 2	??????-	????-	??????-
				????LER?1	??????-	????-	??????-
????LER?2	??????-	????-	??????-
				????LER?3	??????+	????+	??????-
????LER?4	??????-	????-	??????-
				????LER?5	??????-	????-	??????-
????IER?1	??????+++	????++	??????-
				????IER?2	??????+++	????+++	??????-
????IER?3	??????++	????+	??????-
				????IER?4	??????-	????-	??????-
????IER?5	??????+	????+	??????-

-: no change; +: fluorescent substance slightly accumulates; ++: the accumulation of fluorescent substance moderate; +++: fluorescent substance accumulates in a large number.

These results show: not only when the ER albumen single expression in soybean source, and when the Chimerical receptor of being made up of the proteic N-end structure of the RPS2 territory in ER albumen and Arabidopis thaliana source is expressed, the identification of the dextran inducer that can not discern this host plant itself takes place all in the host plant of non-soybean and Arabidopis thaliana (tobacco).Also show: the expression of Chimerical receptor is more favourable for the identification of dextran inducer.Therefore show that even in the plant of non-Arabidopis thaliana, when the Chimerical receptor that contains the N-end structure territory of RPS2 when coding was expressed therein, than the situation of having only the proteic gene single expression of coding ER, signal transduction can more effectively carry out.The invention provides the DNA of coding Chimerical receptor, described Chimerical receptor can be discerned contact and/or the intrusion such as the plant pathogenic microorganism () of the fungi that has glucan structure in its cell walls, and the present invention also provides the plant with this Chimerical receptor.The result is, compared with those ER albumen situation of single expression therein, can induce the resistance reaction that is closely related with disease resistance more consumingly, as the inducing plant toxinicide.By producing the plant of the resistance reaction that this induced strong causes by the dextran inducer, might cultivate show the plant of strong resistance such as the plant pathogenic microorganism of fungi.Industrial applicability

According to the present invention, provide: the DNA of coding chimeric protein (Chimerical receptor), this chimeric protein (Chimerical receptor) comprise the structural domain of the signal transduction motif of the structural domain of an inducer binding site that contains at least one inducer acceptor and a resistant gene that comprises plant origin; Be transferred to the disease resistance plant of above-mentioned DNA; And the method that produces this kind of plant.

Chimerical receptor of the present invention can be used for illustrating antimycotic mechanism.

In addition, the DNA of the present invention that contains coding Chimerical receptor and its segmental nucleotide sequence can be used as the material of setting up the technology of cultivating antifungal plant.If that is: DNA of the present invention or its fragment are transferred to each kind of plant and expression therein, can strengthen the resistance of plant to fungi.

Sequence table

SEQ ID NO:1 sequence length: 667 sequence types: amino acid topology: linear molecule type: protein sequence is described: Val Asn Ile Gln Thr Asn Thr Ser Tyr Ile Phe Pro Gln Thr Gln Ser 15 10 15Thr Val Leu Pro Asp Pro Ser Lys Phe Phe Ser Ser Asn Leu Leu Ser

20??????????????????25??????????????????30Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn

35??????????????????40??????????????????45Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His?Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn

50??????????????????55??????????????????60Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro?Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?65??????????????????70??????????????????75??????????????????80Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp?Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly

85??????????????????90??????????????????95Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys?His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp

100?????????????????105?????????????????110Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro?Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu

115?????????????????120?????????????????125Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr?Val?Ser?Val?Thr?Gln?Pro?Thr?Pro

130?????????????????135?????????????????140Leu?Ser?Ile?Thr?Thr?Ile?His?Ser?Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp145?????????????????150?????????????????155?????????????????160Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln?Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu

165?????????????????170?????????????????175Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys?Leu?Asn?His?Thr?Leu?Ser?Glu?Ile

180?????????????????185?????????????????190Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile?Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp

195?????????????????200?????????????????205Ser?Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr

210?????????????????215?????????????????220Pro?Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr225?????????????????230?????????????????235?????????????????240Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro

245?????????????????250?????????????????255Leu?His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu

260?????????????????265?????????????????270Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val

275?????????????????280?????????????????285Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His

290?????????????????295?????????????????300Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala305?????????????????310?????????????????315?????????????????320Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr

325?????????????????330?????????????????335Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val

340?????????????????345?????????????????350Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys?Val?Arg

355?????????????????360?????????????????365Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser

370?????????????????375?????????????????380Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln385?????????????????390?????????????????395?????????????????400Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn

405?????????????????410?????????????????415Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu

420?????????????????425?????????????????430Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr

435?????????????????440?????????????????445Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn

450?????????????????455?????????????????460Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala465?????????????????470?????????????????475?????????????????480Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser

485?????????????????490?????????????????495Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr

500?????????????????505?????????????????510Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu

515?????????????????520?????????????????525Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Val?Lys?Glu?Gly?Gly?Thr?Leu

530?????????????????535?????????????????540Tyr?Glu?Lys?Glu?Phe?Thr?Gln?Glu?Asn?Arg?Val?Met?Gly?Val?Leu?Trp545?????????????????550?????????????????555?????????????????560Ser?Asn?Lys?Arg?Asp?Thr?Gly?Leu?Trp?Phe?Ala?Pro?Ala?Glu?Trp?Lys

565?????????????????570?????????????????575Glu?Cys?Arg?Leu?Gly?Ile?Gln?Leu?Leu?Pro?Leu?Ala?Pro?Ile?Ser?Glu

580?????????????????585?????????????????590Ala?Ile?Phe?Ser?Asn?Val?Asp?Phe?Val?Lys?Glu?Leu?Val?Glu?Trp?Thr

595?????????????????600?????????????????605Leu?Pro?Ala?Leu?Asp?Arg?Glu?Gly?Gly?Val?Gly?Glu?Gly?Trp?Lys?Gly

610?????????????????615?????????????????620Phe?Val?Tyr?Ala?Leu?Glu?Gly?Val?Tyr?Asp?Asn?Glu?Ser?Ala?Leu?Gln625?????????????????630?????????????????635?????????????????640Lys?Ile?Arg?Asn?Leu?Lys?Gly?Phe?Asp?Gly?Gly?Asn?Ser?Leu?Thr?Asn

645?????????????????650?????????????????655Leu?Leu?Trp?Trp?Ile?His?Ser?Arg?Ser?Asp?Glu

660 665SEQ ID NO:2 sequence lengths: 2240 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA feature

Title/keyword: CDS

Position: 29..2029 sequence description: TCGAATTAAA CCACCTTCAG CAACAATG GTT AAC ATC CAA ACC AAT ACA TCT 52

Val?Asn?Ile?Gln?Thr?Asn?Thr?Ser

1???????????????5TAC?ATC?TTC?CCT?CAA?ACA?CAA?TCC?ACT?GTT?CTT?CCT?GAT?CCC?TCC?AAA????100Tyr?Ile?Phe?Pro?Gln?Thr?Gln?Ser?Thr?Val?Leu?Pro?Asp?Pro?Ser?Lys

10??????????????????15??????????????????20TTC?TTC?TCC?TCA?AAC?CTT?CTC?TCA?AGT?CCA?CTC?CCC?ACA?AAC?TCT?TTC????148Phe?Phe?Ser?Ser?Asn?Leu?Leu?Ser?Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?25??????????????????30??????????????????35??????????????????40TTC?CAA?AAC?TTT?GTC?CTA?AAA?AAT?GGT?GAC?CAA?CAA?GAA?TAC?ATT?CAT????196Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn?Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His

45??????????????????50??????????????????55CCT?TAC?CTC?ATC?AAA?TCC?TCC?AAC?TCT?TCC?CTC?TCT?CTC?TCA?TAC?CCT????244Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn?Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro

60??????????????????65??????????????????70TCT?CGC?CAA?GCC?AGT?TCA?GCT?GTC?ATA?TTC?CAA?GTC?TTC?AAT?CCT?GAT????292Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp

75??????????????????80??????????????????85CTT?ACC?ATT?TCA?GCC?CCA?CAA?GGT?CCC?AAA?CAA?GGT?CCC?CCT?GGT?AAA????340Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly?Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys

90??????????????????95?????????????????100CAC?CTT?ATC?TCC?TCC?TAC?AGT?GAT?CTC?AGT?GTC?ACC?TTG?GAT?TTC?CCT????388His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp?Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro105?????????????????110?????????????????115?????????????????120TCT?TCC?AAT?CTG?AGC?TTC?TTC?CTT?GTT?AGG?GGA?AGC?CCC?TAT?TTG?ACT????436Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu?Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr

125?????????????????130?????????????????135GTG?TCT?GTG?ACT?CAA?CCA?ACT?CCT?CTT?TCA?ATT?ACC?ACC?ATC?CAT?TCC????484Val?Ser?Val?Thr?Gln?Pro?Thr?Pro?Leu?Ser?Ile?Thr?Thr?Ile?His?Ser

140?????????????????145?????????????????150ATT?CTC?TCA?TTC?TCT?TCA?AAT?GAC?TCC?AAC?ACC?AAG?TAC?ACC?TTT?CAG????532Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp?Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln

155?????????????????160?????????????????165TTC?AAC?AAT?GGT?CAA?ACA?TGG?CTT?CTT?TAT?GCT?ACC?TCC?CCC?ATC?AAG????580Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu?Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys

170?????????????????175?????????????????180TTG?AAC?CAC?ACC?CTT?TCT?GAG?ATA?ACT?TCT?AAT?GCA?TTT?TCT?GGC?ATA????628Leu?Asn?His?Thr?Leu?Ser?Glu?Ile?Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile185?????????????????190?????????????????195?????????????????200ATC?CGG?ATA?GCT?TTG?TTG?CCG?GAT?TCG?GAT?TCG?AAA?CAC?GAG?GCT?GTT????676Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp?Ser?Asp?Ser?Lys?His?Glu?Ala?Val

205?????????????????210?????????????????215CTT?GAC?AAG?TAT?AGT?TCT?TGT?TAC?CCC?GTG?TCA?GGT?AAA?GCT?GTG?TTC????724Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr?Pro?Val?Ser?Gly?Lys?Ala?Val?Phe

220?????????????????225?????????????????230AGA?GAA?CCT?TTC?TGT?GTG?GAA?TAT?AAC?TGG?GAG?AAG?AAA?GAT?TCA?GGG????772Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr?Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly

235?????????????????240?????????????????245GAT?TTG?CTA?CTC?TTG?GCT?CAC?CCT?CTC?CAT?GTT?CAG?CTT?CTT?CGT?AAT????820Asp?Leu?Leu?Leu?Leu?Ala?His?Pro?Leu?His?Val?Gln?Leu?Leu?Arg?Asn

250?????????????????255?????????????????260GGA?GAC?AAT?GAT?GTC?AAA?ATT?CTT?GAA?GAT?TTA?AAG?TAT?AAA?AGC?ATT????868Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile265?????????????????270?????????????????275?????????????????280GAT?GGG?GAT?CTT?GTT?GGT?GTT?GTC?GGG?GAT?TCA?TGG?GTT?TTG?AAA?ACA????916Asp?Gly?Asp?Leu?Val?Gly?Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr

285?????????????????290?????????????????295GAT?CCT?TTG?TTT?GTA?ACA?TGG?CAT?TCA?ATC?AAG?GGA?ATC?AAA?GAA?GAA????964Asp?Pro?Leu?Phe?Val?Thr?Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu

300?????????????????305?????????????????310TCC?CAT?GAT?GAG?ATT?GTC?TCA?GCC?CTT?TCT?AAA?GAT?GTT?GAG?AGC?CTA???1012Ser?His?Asp?Glu?Ile?Val?Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu

315?????????????????320?????????????????325GAT?TCA?TCA?TCA?ATA?ACT?ACA?ACA?GAG?TCA?TAT?TTT?TAT?GGG?AAG?TTG???1060Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu

330?????????????????335?????????????????340ATT?GCA?AGG?GCT?GCA?AGG?TTG?GTA?TTG?ATT?GCT?GAG?GAG?TTG?AAC?TAC???1108Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr345?????????????????350?????????????????355?????????????????360CCT?GAT?GTG?ATT?CCA?AAG?GTT?AGG?AAT?TTT?TTG?AAA?GAA?ACC?ATT?GAG???1156Pro?Asp?Val?Ile?Pro?Lys?Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu

365?????????????????370?????????????????375CCA?TGG?TTG?GAG?GGA?ACT?TTT?AGT?GGG?AAT?GGA?TTC?CTA?CAT?GAT?GAA???1204Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu

380?????????????????385?????????????????390AAA?TGG?GGT?GGC?ATT?ATT?ACC?CAA?AAG?GGG?TCC?ACT?GAT?GCT?GGT?GGT???1252Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly

395?????????????????400?????????????????405GAT?TTT?GGA?TTT?GGA?ATT?TAC?AAT?GAT?CAC?CAC?TAT?CAT?TTG?GGG?TAC???1300Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr

410?????????????????415?????????????????420TTC?ATT?TAT?GGA?ATT?GCG?GTG?CTC?ACT?AAG?CTT?GAT?CCA?GCA?TGG?GGT???1348Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly425?????????????????430?????????????????435?????????????????440AGG?AAG?TAC?AAG?CCT?CAA?GCC?TAT?TCA?ATA?GTG?CAA?GAC?TTC?TTG?AAC???1396Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr?Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn

445?????????????????450?????????????????455TTG?GAC?ACA?AAA?TTA?AAC?TCC?AAT?TAC?ACA?CGT?TTG?AGG?TGT?TTT?GAC???1444Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn?Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp

460?????????????????465?????????????????470CCT?TAT?GTG?CTT?CAC?TCT?TGG?GCT?GGA?GGG?TTA?ACT?GAG?TTC?ACA?GAT???1492Pro?Tyr?Val?Leu?His?Ser?Trp?Ala?Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp

475?????????????????480?????????????????485GGA?AGG?AAT?CAA?GAG?AGC?ACA?AGT?GAG?GCT?GTG?AGT?GCA?TAT?TAT?TCT???1540Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser?Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser

490?????????????????495?????????????????500GCT?GCT?TTG?ATG?GGA?TTA?GCA?TAT?GGT?GAT?GCA?CCT?CTT?GTT?GCA?CTT???1588Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr?Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu505?????????????????510?????????????????515?????????????????520GGA?TCA?ACA?CTC?ACA?GCA?TTG?GAA?ATT?GAA?GGG?ACT?AAA?ATG?TGG?TGG???1636Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu?Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp

525?????????????????530?????????????????535CAT?GTG?AAA?GAG?GGA?GGT?ACT?TTG?TAT?GAG?AAA?GAG?TTT?ACA?CAA?GAG???1684His?Val?Lys?Glu?Gly?Gly?Thr?Leu?Tyr?Glu?Lys?Glu?Phe?Thr?Gln?Glu

540?????????????????545?????????????????550AAT?AGG?GTG?ATG?GGT?GTT?CTA?TGG?TCT?AAC?AAG?AGG?GAC?ACT?GGA?CTT???1732Asn?Arg?Val?Met?Gly?Val?Leu?Trp?Ser?Asn?Lys?Arg?Asp?Thr?Gly?Leu

555?????????????????560?????????????????565TGG?TTT?GCT?CCT?GCT?GAG?TGG?AAA?GAG?TGT?AGG?CTT?GGC?ATT?CAG?CTC???1780Trp?Phe?Ala?Pro?Ala?Glu?Trp?Lys?Glu?Cys?Arg?Leu?Gly?Ile?Gln?Leu

570?????????????????575?????????????????580TTA?CCA?TTG?GCT?CCT?ATT?TCT?GAA?GCC?ATT?TTC?TCC?AAT?GTT?GAC?TTT???1828Leu?Pro?Leu?Ala?Pro?Ile?Ser?Glu?Ala?Ile?Phe?Ser?Asn?Val?Asp?Phe585?????????????????590?????????????????595?????????????????600GTA?AAG?GAG?CTT?GTG?GAG?TGG?ACT?TTG?CCT?GCT?TTG?GAT?AGG?GAG?GGT???1876Val?Lys?Glu?Leu?Val?Glu?Trp?Thr?Leu?Pro?Ala?Leu?Asp?Arg?Glu?Gly

605?????????????????610?????????????????615GGT?GTT?GGT?GAA?GGA?TGG?AAG?GGG?TTT?GTG?TAT?GCC?CTT?GAA?GGG?GTT???1924Gly?Val?Gly?Glu?Gly?Trp?Lys?Gly?Phe?Val?Tyr?Ala?Leu?Glu?Gly?Val

620?????????????????625?????????????????630TAT?GAC?AAT?GAA?AGT?GCA?CTG?CAG?AAG?ATA?AGA?AAC?CTG?AAA?GGT?TTT???1972Tyr?Asp?Asn?Glu?Ser?Ala?Leu?Gln?Lys?Ile?Arg?Asn?Leu?Lys?Gly?Phe

635?????????????????640?????????????????645GAT?GGT?GGA?AAC?TCT?TTG?ACC?AAT?CTC?TTG?TGG?TGG?ATT?CAT?AGC?AGA???2020Asp?Gly?Gly?Asn?Ser?Leu?Thr?Asn?Leu?Leu?Trp?Trp?Ile?His?Ser?Arg

650 655 660AGT GAT GAA TAGAATGGAT TTGGTTATTG AACATGACAA CACTGCTGAT 2069Ser Asp Glu665TTGGTTATTA TTATTATTGC TACTATTACT ATGCCAATAA AATCATCAAA TATGTCTTAC 2129ATCATAATAA AAAAATTATT ATTATGCCAA TAAGTCAATG ATTTCGATAT GTTATAGAAG 2189AAGAAAACTA TAATAAAGTT ACAACAATAT CATGATCTAT AACATGTCTG A, 2240 SEQ ID NO:3 sequence lengths: 667 sequence types: amino acid topology: linear molecule type: protein sequence is described: Val Asn Ile Gln Thr Asn Thr Ser Tyr Ile Phe Pro Gln Thr Gln Ser 15 10 15Thr Val Leu Pro Asp Pro Ser Lys Phe Phe Ser Ser Asn Leu Leu Ser

20??????????????????25??????????????????30Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn

35??????????????????40??????????????????45Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His?Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn

50??????????????????55??????????????????60Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro?Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?65??????????????????70??????????????????75??????????????????80Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp?Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly

85??????????????????90??????????????????95Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys?His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp

100?????????????????105?????????????????110Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro?Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu

115?????????????????120?????????????????125Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr?Val?Ser?Val?Thr?Gln?Pro?Thr?Pro

130?????????????????135?????????????????140Leu?Ser?Ile?Thr?Thr?Ile?His?Ser?Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp145?????????????????150?????????????????155?????????????????160Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln?Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu

165?????????????????170?????????????????175Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys?Leu?Asn?His?Thr?Leu?Ser?Glu?Ile

180?????????????????185?????????????????190Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile?Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp

195?????????????????200?????????????????205Ser?Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr

210?????????????????215?????????????????220Pro?Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr225?????????????????230?????????????????235?????????????????240Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro

245?????????????????250?????????????????255Leu?His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu

260?????????????????265?????????????????270Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val

275?????????????????280?????????????????285Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His

290?????????????????295?????????????????300Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala305?????????????????310?????????????????315?????????????????320Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr

325?????????????????330?????????????????335Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val

340?????????????????345?????????????????350Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys?Val?Arg

355?????????????????360?????????????????365Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser

370?????????????????375?????????????????380Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln385?????????????????390?????????????????395?????????????????400Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn

405?????????????????410?????????????????415Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu

420?????????????????425?????????????????430Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr

435?????????????????440?????????????????445Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn

450?????????????????455?????????????????460Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala465?????????????????470?????????????????475?????????????????480Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser

485?????????????????490?????????????????495Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr

500?????????????????505?????????????????510Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu

515?????????????????520?????????????????525Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Val?Lys?Glu?Gly?Gly?Thr?Leu

530?????????????????535?????????????????540Tyr?Glu?Lys?Glu?Phe?Thr?Gln?Glu?Asn?Arg?Val?Met?Gly?Val?Leu?Trp545?????????????????550?????????????????555?????????????????560Ser?Asn?Lys?Arg?Asp?Thr?Gly?Leu?Trp?Phe?Ala?Pro?Ala?Glu?Trp?Lys

565?????????????????570?????????????????575Glu?Cys?Arg?Leu?Gly?Ile?Gln?Leu?Leu?Pro?Leu?Ala?Pro?Ile?Ser?Glu

580?????????????????585?????????????????590Ala?Ile?Phe?Ser?Asn?Val?Asp?Phe?Val?Lys?Glu?Leu?Val?Glu?Trp?Thr

595?????????????????600?????????????????605Leu?Pro?Ala?Leu?Asp?Arg?Glu?Gly?Gly?Val?Gly?Glu?Gly?Trp?Lys?Gly

610?????????????????615?????????????????620Phe?Val?Tyr?Ala?Leu?Glu?Gly?Val?Tyr?Asp?Asn?Glu?Ser?Ala?Leu?Gln625?????????????????630?????????????????635?????????????????640Lys?Ile?Arg?Asn?Leu?Lys?Gly?Phe?Asp?Gly?Gly?Asn?Ser?Leu?Thr?Asn

645?????????????????650?????????????????655Leu?Leu?Trp?Trp?Ile?His?Ser?Arg?Ser?Asp?Glu

660 665 SEQ ID NO:4 sequence lengths: 2291 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA feature title/keyword: CDS position: 80..2080 sequence description: CTTCTTTCCT CAACCTTCTT TCTTCTTATA TATTCGAACG ATCCGGGCCG CTCGAATTAA 60ACCACCTTCA GCAACAATG GTT AAC ATC CAA ACC AAT ACA TCT TAC ATC TTC 112

Val?Asn?Ile?Gln?Thr?Asn?Thr?Ser?Tyr?Ile?Phe

1???????????????5??????????????????10CCT?CAA?ACA?CAA?TCC?ACT?GTT?CTT?CCT?GAT?CCC?TCC?AAA?TTC?TTC?TCC????160Pro?Gln?Thr?Gln?Ser?Thr?Val?Leu?Pro?Asp?Pro?Ser?Lys?Phe?Phe?Ser

15??????????????????20??????????????????25TCA?AAC?CTT?CTC?TCA?AGT?CCA?CTC?CCC?ACA?AAC?TCT?TTC?TTC?CAA?AAC????208Ser?Asn?Leu?Leu?Ser?Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?Phe?Gln?Asn

30??????????????????35??????????????????40TTT?GTC?CTA?AAA?AAT?GGT?GAC?CAA?CAA?GAA?TAC?ATT?CAT?CCT?TAC?CTC????256Phe?Val?Leu?Lys?Asn?Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His?Pro?Tyr?Leu

45??????????????????50??????????????????55ATC?AAA?TCC?TCC?AAC?TCT?TCC?CTC?TCT?CTC?TCA?TAC?CCT?TCT?CGC?CAA????304Ile?Lys?Ser?Ser?Asn?Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro?Ser?Arg?Gln?60??????????????????65??????????????????70??????????????????75GCC?AGT?TCA?GCT?GTC?ATA?TTC?CAA?GTC?TTC?AAT?CCT?GAT?CTT?ACC?ATT????352Ala?Ser?Ser?Ala?Val?Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp?Leu?Thr?Ile

80??????????????????85??????????????????90TCA?GCC?CCA?CAA?GGT?CCC?AAA?CAA?GGT?CCC?CCT?GGT?AAA?CAC?CTT?ATC????400Ser?Ala?Pro?Gln?Gly?Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys?His?Leu?Ile

95?????????????????100?????????????????105TCC?TCC?TAC?AGT?GAT?CTC?AGT?GTC?ACC?TTG?GAT?TTC?CCT?TCT?TCC?AAT????448Ser?Ser?Tyr?Ser?Asp?Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro?Ser?Ser?Asn

110?????????????????115?????????????????120CTG?AGC?TTC?TTC?CTT?GTT?AGG?GGA?AGC?CCC?TAT?TTG?ACT?GTG?TCT?GTG????496Leu?Ser?Phe?Phe?Leu?Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr?Val?Ser?Val

125?????????????????130?????????????????135ACT?CAA?CCA?ACT?CCT?CTT?TCA?ATT?ACC?ACC?ATC?CAT?TCC?ATT?CTC?TCA????544Thr?Gln?Pro?Thr?Pro?Leu?Ser?Ile?Thr?Thr?Ile?His?Ser?Ile?Leu?Ser140?????????????????145?????????????????150?????????????????155TTC?TCT?TCA?AAT?GAC?TCC?AAC?ACC?AAG?TAC?ACC?TTT?CAG?TTC?AAC?AAT????592Phe?Ser?Ser?Asn?Asp?Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln?Phe?Asn?Asn

160?????????????????165?????????????????170GGT?CAA?ACA?TGG?CTT?CTT?TAT?GCT?ACC?TCC?CCC?ATC?AAG?TTG?AAC?CAC????640Gly?Gln?Thr?Trp?Leu?Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys?Leu?Asn?His

175?????????????????180?????????????????185ACC?CTT?TCT?GAG?ATA?ACT?TCT?AAT?GCA?TTT?TCT?GGC?ATA?ATC?CGG?ATA????688Thr?Leu?Ser?Glu?Ile?Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile?Ile?Arg?Ile

190?????????????????195?????????????????200GCT?TTG?TTG?CCG?GAT?TCG?GAT?TCG?AAA?CAC?GAG?GCT?GTT?CTT?GAC?AAG????736Ala?Leu?Leu?Pro?Asp?Ser?Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys

205?????????????????210?????????????????215TAT?AGT?TCT?TGT?TAC?CCC?GTG?TCA?GGT?AAA?GCT?GTG?TTC?AGA?GAA?CCT????784Tyr?Ser?Ser?Cys?Tyr?Pro?Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro220?????????????????225?????????????????230?????????????????235TTC?TGT?GTG?GAA?TAT?AAC?TGG?GAG?AAG?AAA?GAT?TCA?GGG?GAT?TTG?CTA????832Phe?Cys?Val?Glu?Tyr?Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu

240?????????????????245?????????????????250CTC?TTG?GCT?CAC?CCT?CTC?CAT?GTT?CAG?CTT?CTT?CGT?AAT?GGA?GAC?AAT????880Leu?Leu?Ala?His?Pro?Leu?His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn

255?????????????????260?????????????????265GAT?GTC?AAA?ATT?CTT?GAA?GAT?TTA?AAG?TAT?AAA?AGC?ATT?GAT?GGG?GAT????928Asp?Val?Lys?Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp

270?????????????????275?????????????????280CTT?GTT?GGT?GTT?GTC?GGG?GAT?TCA?TGG?GTT?TTG?AAA?ACA?GAT?CCT?TTG????976Leu?Val?Gly?Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu

285?????????????????290?????????????????295TTT?GTA?ACA?TGG?CAT?TCA?ATC?AAG?GGA?ATC?AAA?GAA?GAA?TCC?CAT?GAT???1024Phe?Val?Thr?Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp300?????????????????305?????????????????310?????????????????315GAG?ATT?GTC?TCA?GCC?CTT?TCT?AAA?GAT?GTT?GAG?AGC?CTA?GAT?TCA?TCA???1072Glu?Ile?Val?Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser

320?????????????????325?????????????????330TCA?ATA?ACT?ACA?ACA?GAG?TCA?TAT?TTT?TAT?GGG?AAG?TTG?ATT?GCA?AGG???1120Ser?Ile?Thr?Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg

335?????????????????340?????????????????345GCT?GCA?AGG?TTG?GTA?TTG?ATT?GCT?GAG?GAG?TTG?AAC?TAC?CCT?GAT?GTG???1168Ala?Ala?Arg?Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val

350?????????????????355?????????????????360ATT?CCA?AAG?GTT?AGG?AAT?TTT?TTG?AAA?GAA?ACC?ATT?GAG?CCA?TGG?TTG???1216Ile?Pro?Lys?Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu

365?????????????????370?????????????????375GAG?GGA?ACT?TTT?AGT?GGG?AAT?GGA?TTC?CTA?CAT?GAT?GAA?AAA?TGG?GGT???1264Glu?Gly?Thr?Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly380?????????????????385?????????????????390?????????????????395GGC?ATT?ATT?ACC?CAA?AAG?GGG?TCC?ACT?GAT?GCT?GGT?GGT?GAT?TTT?GGA???1312Gly?Ile?Ile?Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly

400?????????????????405?????????????????410TTT?GGA?ATT?TAC?AAT?GAT?CAC?CAC?TAT?CAT?TTG?GGG?TAC?TTC?ATT?TAT???1360Phe?Gly?Ile?Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr

415?????????????????420?????????????????425GGA?ATT?GCG?GTG?CTC?ACT?AAG?CTT?GAT?CCA?GCA?TGG?GGT?AGG?AAG?TAC???1408Gly?Ile?Ala?Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr

430?????????????????435?????????????????440AAG?CCT?CAA?GCC?TAT?TCA?ATA?GTG?CAA?GAC?TTC?TTG?AAC?TTG?GAC?ACA???1456Lys?Pro?Gln?Ala?Tyr?Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr

445?????????????????450?????????????????455AAA?TTA?AAC?TCC?AAT?TAC?ACA?CGT?TTG?AGG?TGT?TTT?GAC?CCT?TAT?GTG???1504Lys?Leu?Asn?Ser?Asn?Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val460?????????????????465?????????????????470?????????????????475CTT?CAC?TCT?TGG?GCT?GGA?GGG?TTA?ACT?GAG?TTC?ACA?GAT?GGA?AGG?AAT???1552Leu?His?Ser?Trp?Ala?Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn

480?????????????????485?????????????????490CAA?GAG?AGC?ACA?AGT?GAG?GCT?GTG?AGT?GCA?TAT?TAT?TCT?GCT?GCT?TTG???1600Gln?Glu?Ser?Thr?Ser?Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu

495?????????????????500?????????????????505ATG?GGA?TTA?GCA?TAT?GGT?GAT?GCA?CCT?CTT?GTT?GCA?CTT?GGA?TCA?ACA???1648Met?Gly?Leu?Ala?Tyr?Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr

510?????????????????515?????????????????520CTC?ACA?GCA?TTG?GAA?ATT?GAA?GGG?ACT?AAA?ATG?TGG?TGG?CAT?GTG?AAA???1696Leu?Thr?Ala?Leu?Glu?Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Val?Lys

525?????????????????530?????????????????535GAG?GGA?GGT?ACT?TTG?TAT?GAG?AAA?GAG?TTT?ACA?CAA?GAG?AAT?AGG?GTG???1744Glu?Gly?Gly?Thr?Leu?Tyr?Glu?Lys?Glu?Phe?Thr?Gln?Glu?Asn?Arg?Val540?????????????????545?????????????????550?????????????????555ATG?GGT?GTT?CTA?TGG?TCT?AAC?AAG?AGG?GAC?ACT?GGA?CTT?TGG?TTT?GCT???1792Met?Gly?Val?Leu?Trp?Ser?Asn?Lys?Arg?Asp?Thr?Gly?Leu?Trp?Phe?Ala

560?????????????????565?????????????????570CCT?GCT?GAG?TGG?AAA?GAG?TGT?AGG?CTT?GGC?ATT?CAG?CTC?TTA?CCA?TTG???1840Pro?Ala?Glu?Trp?Lys?Glu?Cys?Arg?Leu?Gly?Ile?Gln?Leu?Leu?Pro?Leu

575?????????????????580?????????????????585GCT?CCT?ATT?TCT?GAA?GCC?ATT?TTC?TCC?AAT?GTT?GAC?TTT?GTA?AAG?GAG???1888Ala?Pro?Ile?Ser?Glu?Ala?Ile?Phe?Ser?Asn?Val?Asp?Phe?Val?Lys?Glu

590?????????????????595?????????????????600CTT?GTG?GAG?TGG?ACT?TTG?CCT?GCT?TTG?GAT?AGG?GAG?GGT?GGT?GTT?GGT???1936Leu?Val?Glu?Trp?Thr?Leu?Pro?Ala?Leu?Asp?Arg?Glu?Gly?Gly?Val?Gly

605?????????????????610?????????????????615GAA?GGA?TGG?AAG?GGG?TTT?GTG?TAT?GCC?CTT?GAA?GGG?GTT?TAT?GAC?AAT???1984Glu?Gly?Trp?Lys?Gly?Phe?Val?Tyr?Ala?Leu?Glu?Gly?Val?Tyr?Asp?Asn620?????????????????625?????????????????630?????????????????635GAA?AGT?GCA?CTG?CAG?AAG?ATA?AGA?AAC?CTG?AAA?GGT?TTT?GAT?GGT?GGA???2032Glu?Ser?Ala?Leu?Gln?Lys?Ile?Arg?Asn?Leu?Lys?Gly?Phe?Asp?Gly?Gly

640?????????????????645?????????????????650AAC?TCT?TTG?ACC?AAT?CTC?TTG?TGG?TGG?ATT?CAT?AGC?AGA?AGT?GAT?GAA???2080Asn?Ser?Leu?Thr?Asn?Leu?Leu?Trp?Trp?Ile?His?Ser?Arg?Ser?Asp?Glu

655?????????????????660?????????????????665TAGAATGGAT?TTGGTTATTG?AACATGACAA?CACTGCTGAT?TTGGTTATTA?TTATTATTGC?2140TACTATTACT?ATGCCAATAA?AATCATCAAA?TATGTCTTAC?ATCATAATAA?AAAAATTATT?2200ATTATGCCAA?TAAGTCAATG?ATTTCGATAT?GTTATAGAAG?AAGAAAACTA?TAATAAAGTT?2260ACAACAATAT?CATGATCTAT?AACATGTCTG?A????????????????????????????????2291

SEQ ID NO:5 sequence length: 1054 sequence types: amino acid topology: linear molecule type: protein sequence is described: Met Asp Phe Ile Ser Ser Leu Ile Val Gly Cys Ala Gln Val Leu Cys 15 10 15Glu Ser Met Asn Met Ala Glu Arg Arg Gly His Lys Thr Asp Leu Arg

20??????????????????25??????????????????30Gln?Ala?Ile?Thr?Asp?Leu?Glu?Thr?Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile

35??????????????????40??????????????????45Arg?Asp?Asp?Leu?Thr?Leu?Arg?Ile?Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg

50??????????????????55??????????????????60Ser?Cys?Ser?Asn?Arg?Ala?Arg?Glu?Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?65??????????????????70??????????????????75??????????????????80Glu?Thr?Lys?Thr?Ala?Leu?Leu?Leu?Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln

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

100?????????????????105?????????????????110Tyr?Lys?Leu?Cys?Lys?Lys?Val?Ser?Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu

115?????????????????120?????????????????125Leu?Arg?Glu?Arg?Ser?Glu?Ala?Ile?Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln

130?????????????????135?????????????????140Val?Thr?Cys?Arg?Glu?Ile?Pro?Ile?Lys?Ser?Val?Val?Gly?Asn?Thr?Thr145?????????????????150?????????????????155?????????????????160Met?Met?Glu?Gln?Val?Leu?Glu?Phe?Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly

165?????????????????170?????????????????175Ile?Ile?Gly?Val?Tyr?Gly?Pro?Gly?Gly?Val?Gly?Lys?Thr?Thr?Leu?Met

180?????????????????185?????????????????190Gln?Ser?Ile?Asn?Asn?Glu?Leu?Ile?Thr?Lys?Gly?His?Gln?Tyr?Asp?Val

195?????????????????200?????????????????205Leu?Ile?Trp?Val?Gln?Met?Ser?Arg?Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln

210?????????????????215?????????????????220Gln?Ala?Val?Gly?Ala?Arg?Leu?Gly?Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr225?????????????????230?????????????????235?????????????????240Gly?Glu?Asn?Arg?Ala?Leu?Lys?Ile?Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg

245?????????????????250?????????????????255Phe?Leu?Leu?Leu?Leu?Asp?Asp?Val?Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys

260?????????????????265?????????????????270Thr?Gly?Val?Pro?Arg?Pro?Asp?Arg?Glu?Asn?Lys?Cys?Lys?Val?Met?Phe

275?????????????????280?????????????????285Thr?Thr?Arg?Ser?Ile?Ala?Leu?Cys?Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys

290?????????????????295?????????????????300Leu?Arg?Val?Glu?Phe?Leu?Glu?Lys?Lys?His?Ala?Trp?Glu?Leu?Phe?Cys305?????????????????310?????????????????315?????????????????320Ser?Lys?Val?Trp?Arg?Lys?Asp?Leu?Leu?Glu?Ser?Ser?Ser?Ile?Arg?Arg

325?????????????????330?????????????????335Leu?Ala?Glu?Ile?Ile?Val?Ser?Lys?Cys?Gly?Gly?Leu?Pro?Leu?Ala?Leu

340?????????????????345?????????????????350Ile?Thr?Leu?Gly?Gly?Ala?Met?Ala?Gly?Leu?Gln?Glu?Phe?Asp?Pro?Gly

355?????????????????360?????????????????365Ser?Pro?Gly?Leu?Gln?Glu?Phe?Ala?Ala?Ala?Arg?Ile?Lys?Pro?Pro?Ser

370?????????????????375?????????????????380Ala?Thr?Met?Val?Asn?Ile?Gln?Thr?Asn?Thr?Ser?Tyr?Ile?Phe?Pro?Gln385?????????????????390?????????????????395?????????????????400Thr?Gln?Ser?Thr?Val?Leu?Pro?Asp?Pro?Ser?Lys?Phe?Phe?Ser?Ser?Asn

405?????????????????410?????????????????415Leu?Leu?Ser?Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?Phe?Gln?Asn?Phe?Val

420?????????????????425?????????????????430Leu?Lys?Asn?Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His?Pro?Tyr?Leu?Ile?Lys

435?????????????????440?????????????????445Ser?Ser?Asn?Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro?Ser?Arg?Gln?Ala?Ser

450?????????????????455?????????????????460Ser?Ala?Val?Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp?Leu?Thr?Ile?Ser?Ala465?????????????????470?????????????????475?????????????????480Pro?Gln?Gly?Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys?His?Leu?Ile?Ser?Ser

485?????????????????490?????????????????495Tyr?Ser?Asp?Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro?Ser?Ser?Asn?Leu?Ser

500?????????????????505?????????????????510Phe?Phe?Leu?Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr?Val?Ser?Val?Thr?Gln

515?????????????????520?????????????????525Pro?Thr?Pro?Leu?Ser?Ile?Thr?Thr?Ile?His?Ser?Ile?Leu?Ser?Phe?Ser

530?????????????????535?????????????????540Ser?Asn?Asp?Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln?Phe?Asn?Asn?Gly?Gln545?????????????????550?????????????????555?????????????????560Thr?Trp?Leu?Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys?Leu?Asn?His?Thr?Leu

565?????????????????570?????????????????575Ser?Glu?Ile?Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile?Ile?Arg?Ile?Ala?Leu

580?????????????????585?????????????????590Leu?Pro?Asp?Ser?Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser

595?????????????????600?????????????????605Ser?Cys?Tyr?Pro?Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys

610?????????????????615?????????????????620Val?Glu?Tyr?Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu625?????????????????630?????????????????635?????????????????640Ala?His?Pro?Leu?His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val

645?????????????????650?????????????????655Lys?Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val

660?????????????????665?????????????????670Gly?Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val

675?????????????????680?????????????????685Thr?Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile

690?????????????????695?????????????????700Val?Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile705?????????????????710?????????????????715?????????????????720Thr?Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala

725?????????????????730?????????????????735Arg?Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro

740?????????????????745?????????????????750Lys?Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly

755?????????????????760?????????????????765Thr?Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile

770?????????????????775?????????????????780Ile?Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly785?????????????????790?????????????????795?????????????????800Ile?Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile

805?????????????????810?????????????????815Ala?Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro

820?????????????????825?????????????????830Gln?Ala?Tyr?Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu

835?????????????????840?????????????????845Asn?Ser?Asn?Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His

850?????????????????855?????????????????860Ser?Trp?Ala?Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu865?????????????????870?????????????????875?????????????????880Ser?Thr?Ser?Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly

885?????????????????890?????????????????895Leu?Ala?Tyr?Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr

900?????????????????905?????????????????910Ala?Leu?Glu?Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Val?Lys?Glu?Gly

915?????????????????920?????????????????925Gly?Thr?Leu?Tyr?Glu?Lys?Glu?Phe?Thr?Gln?Glu?Asn?Arg?Val?Met?Gly

930?????????????????935?????????????????940Val?Leu?Trp?Ser?Asn?Lys?Arg?Asp?Thr?Gly?Leu?Trp?Phe?Ala?Pro?Ala945?????????????????950?????????????????955?????????????????960Glu?Trp?Lys?Glu?Cys?Arg?Leu?Gly?Ile?Gln?Leu?Leu?Pro?Leu?Ala?Pro

965?????????????????970?????????????????975Ile?Ser?Glu?Ala?Ile?Phe?Ser?Asn?Val?Asp?Phe?Val?Lys?Glu?Leu?Val

980?????????????????985?????????????????990Glu?Trp?Thr?Leu?Pro?Ala?Leu?Asp?Arg?Glu?Gly?Gly?Val?Gly?Glu?Gly

995?????????????????1000????????????????1005Trp?Lys?Gly?Phe?Val?Tyr?Ala?Leu?Glu?Gly?Val?Tyr?Asp?Asn?Glu?Ser

1010????????????????1015????????????????1020Ala?Leu?Gln?Lys?Ile?Arg?Asn?Leu?Lys?Gly?Phe?Asp?Gly?Gly?Asn?Ser1025????????????????1030????????????????1035????????????????1040Leu?Thr?Asn?Leu?Leu?Trp?Trp?Ile?His?Ser?Arg?Ser?Asp?Glu

1,045 1050 SEQ ID NO:6 sequence lengths: 3405 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA feature title/keyword: CDS position: 33..3194 sequence description: ACAAGTAAAA GAAAGAGCGA GAAATCATCG AA ATG GAT TTC ATC TCA TCT CTT 53

Met?Asp?Phe?Ile?Ser?Ser?Leu

1???????????????5ATC?GTT?GGC?TGT?GCT?CAG?GTG?TTG?TGT?GAA?TCT?ATG?AAT?ATG?GCG?GAG????101Ile?Val?Gly?Cys?Ala?Gln?Val?Leu?Cys?Glu?Ser?Met?Asn?Met?Ala?Glu

10??????????????????15??????????????????20AGA?AGA?GGA?CAT?AAG?ACT?GAT?CTT?AGA?CAA?GCC?ATC?ACT?GAT?CTT?GAA????149Arg?Arg?Gly?His?Lys?Thr?Asp?Leu?Arg?Gln?Ala?Ile?Thr?Asp?Leu?Glu

25??????????????????30??????????????????35ACA?GCC?ATC?GGT?GAC?TTG?AAG?GCC?ATA?CGT?GAT?GAC?CTG?ACT?TTA?CGG????197Thr?Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile?Arg?Asp?Asp?Leu?Thr?Leu?Arg?40??????????????????45??????????????????50??????????????????55ATC?CAA?CAA?GAC?GGT?CTA?GAG?GGA?CGA?AGC?TGC?TCA?AAT?CGT?GCC?AGA????245Ile?Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg?Ser?Cys?Ser?Asn?Arg?Ala?Arg

60??????????????????65??????????????????70GAG?TGG?CTT?AGT?GCG?GTG?CAA?GTA?ACG?GAG?ACT?AAA?ACA?GCC?CTA?CTT????293Glu?Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?Glu?Thr?Lys?Thr?Ala?Leu?Leu

75??????????????????80??????????????????85TTA?GTG?AGG?TTT?AGG?CGT?CGG?GAA?CAG?AGG?ACG?CGA?ATG?AGG?AGG?AGA????341Leu?Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln?Arg?Thr?Arg?Met?Arg?Arg?Arg

90??????????????????95?????????????????100TAC?CTC?AGT?TGT?TTC?GGT?TGT?GCC?GAC?TAC?AAA?CTG?TGC?AAG?AAG?GTT????389Tyr?Leu?Ser?Cys?Phe?Gly?Cys?Ala?Asp?Tyr?Lys?Leu?Cys?Lys?Lys?Val

105?????????????????110?????????????????115TCT?GCC?ATA?TTG?AAG?AGC?ATT?GGT?GAG?CTG?AGA?GAA?CGC?TCT?GAA?GCT????437Ser?Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu?Leu?Arg?Glu?Arg?Ser?Glu?Ala120?????????????????125?????????????????130?????????????????135ATC?AAA?ACA?GAT?GGC?GGG?TCA?ATT?CAA?GTA?ACT?TGT?AGA?GAG?ATA?CCC????485Ile?Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln?Val?Thr?Cys?Arg?Glu?Ile?Pro

140?????????????????145?????????????????150ATC?AAG?TCC?GTT?GTC?GGA?AAT?ACC?ACG?ATG?ATG?GAA?CAG?GTT?TTG?GAA????533Ile?Lys?Ser?Val?Val?Gly?Asn?Thr?Thr?Met?Met?Glu?Gln?Val?Leu?Glu

155?????????????????160?????????????????165TTT?CTC?AGT?GAA?GAA?GAA?GAA?AGA?GGA?ATC?ATT?GGT?GTT?TAT?GGA?CCT????581Phe?Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly?Ile?Ile?Gly?Val?Tyr?Gly?Pro

170?????????????????175?????????????????180GGT?GGG?GTT?GGG?AAG?ACA?ACG?TTA?ATG?CAG?AGC?ATT?AAC?AAC?GAG?CTG????629Gly?Gly?Val?Gly?Lys?Thr?Thr?Leu?Met?Gln?Ser?Ile?Asn?Asn?Glu?Leu

185?????????????????190?????????????????195ATC?ACA?AAA?GGA?CAT?CAG?TAT?GAT?GTA?CTG?ATT?TGG?GTT?CAA?ATG?TCC????677Ile?Thr?Lys?Gly?His?Gln?Tyr?Asp?Val?Leu?Ile?Trp?Val?Gln?Met?Ser200?????????????????205?????????????????210?????????????????215AGA?GAA?TTC?GGC?GAG?TGT?ACA?ATT?CAG?CAA?GCC?GTT?GGA?GCA?CGG?TTG????725Arg?Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln?Gln?Ala?Val?Gly?Ala?Arg?Leu

220?????????????????225?????????????????230GGT?TTA?TCT?TGG?GAC?GAG?AAG?GAG?ACC?GGC?GAA?AAC?AGA?GCT?TTG?AAG????773Gly?Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr?Gly?Glu?Asn?Arg?Ala?Leu?Lys

235?????????????????240?????????????????245ATA?TAC?AGA?GCT?TTG?AGA?CAG?AAA?CGT?TTC?TTG?TTG?TTG?CTA?GAT?GAT????821Ile?Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg?Phe?Leu?Leu?Leu?Leu?Asp?Asp

250?????????????????255?????????????????260GTC?TGG?GAA?GAG?ATA?GAC?TTG?GAG?AAA?ACT?GGA?GTT?CCT?CGA?CCT?GAC????869Val?Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys?Thr?Gly?Val?Pro?Arg?Pro?Asp

265?????????????????270?????????????????275AGG?GAA?AAC?AAA?TGC?AAG?GTG?ATG?TTC?ACG?ACA?CGG?TCT?ATA?GCA?TTA????917Arg?Glu?Asn?Lys?Cys?Lys?Val?Met?Phe?Thr?Thr?Arg?Ser?Ile?Ala?Leu280?????????????????285?????????????????290?????????????????295TGC?AAC?AAT?ATG?GGT?GCG?GAA?TAC?AAG?TTG?AGA?GTG?GAG?TTT?CTG?GAG????965Cys?Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys?Leu?Arg?Val?Glu?Phe?Leu?Glu

300?????????????????305?????????????????310AAG?AAA?CAC?GCG?TGG?GAG?CTG?TTC?TGT?AGT?AAG?GTA?TGG?AGA?AAA?GAT???1013Lys?Lys?His?Ala?Trp?Glu?Leu?Phe?Cys?Ser?Lys?Val?Trp?Arg?Lys?Asp

315?????????????????320?????????????????325CTT?TTA?GAG?TCA?TCA?TCA?ATT?CGC?CGG?CTC?GCG?GAG?ATT?ATA?GTG?AGT???1061Leu?Leu?Glu?Ser?Ser?Ser?Ile?Arg?Arg?Leu?Ala?Glu?Ile?Ile?Val?Ser

330?????????????????335?????????????????340AAA?TGT?GGA?GGA?TTG?CCA?CTA?GCG?TTG?ATC?ACT?TTA?GGA?GGA?GCC?ATG???1109Lys?Cys?Gly?Gly?Leu?Pro?Leu?Ala?Leu?Ile?Thr?Leu?Gly?Gly?Ala?Met

345?????????????????350?????????????????355GCT?GGG?CTG?CAG?GAA?TTC?GAT?CCC?GGA?TCC?CCC?GGG?CTG?CAG?GAA?TTC???1157Ala?Gly?Leu?Gln?Glu?Phe?Asp?Pro?Gly?Ser?Pro?Gly?Leu?Gln?Glu?Phe360?????????????????365?????????????????370?????????????????375GCG?GCC?GCT?CGA?ATT?AAA?CCA?CCT?TCA?GCA?ACA?ATG?GTT?AAC?ATC?CAA???1205Ala?Ala?Ala?Arg?Ile?Lys?Pro?Pro?Ser?Ala?Thr?Met?Val?Asn?Ile?Gln

380?????????????????385?????????????????390ACC?AAT?ACA?TCT?TAC?ATC?TTC?CCT?CAA?ACA?CAA?TCC?ACT?GTT?CTT?CCT???1253Thr?Asn?Thr?Ser?Tyr?Ile?Phe?Pro?Gln?Thr?Gln?Ser?Thr?Val?Leu?Pro

395?????????????????400?????????????????405GAT?CCC?TCC?AAA?TTC?TTC?TCC?TCA?AAC?CTT?CTC?TCA?AGT?CCA?CTC?CCC???1301Asp?Pro?Ser?Lys?Phe?Phe?Ser?Ser?Asn?Leu?Leu?Ser?Ser?Pro?Leu?Pro

410?????????????????415?????????????????420?ACA?AAC?TCT?TTC?TTC?CAA?AAC?TTT?GTC?CTA?AAA?AAT?GGT?GAC?CAA?CAA???1349Thr?Asn?Ser?Phe?Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn?Gly?Asp?Gln?Gln

425?????????????????430?????????????????435GAA?TAC?ATT?CAT?CCT?TAC?CTC?ATC?AAA?TCC?TCC?AAC?TCT?TCC?CTC?TCT???1397Glu?Tyr?Ile?His?Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn?Ser?Ser?Leu?Ser440?????????????????445?????????????????450?????????????????455CTC?TCA?TAC?CCT?TCT?CGC?CAA?GCC?AGT?TCA?GCT?GTC?ATA?TTC?CAA?GTC???1445Leu?Ser?Tyr?Pro?Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?Ile?Phe?Gln?Val

460?????????????????465?????????????????470TTC?AAT?CCT?GAT?CTT?ACC?ATT?TCA?GCC?CCA?CAA?GGT?CCC?AAA?CAA?GGT???1493Phe?Asn?Pro?Asp?Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly?Pro?Lys?Gln?Gly

475?????????????????480?????????????????485CCC?CCT?GGT?AAA?CAC?CTT?ATC?TCC?TCC?TAC?AGT?GAT?CTC?AGT?GTC?ACC???1541Pro?Pro?Gly?Lys?His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp?Leu?Ser?Val?Thr

490?????????????????495?????????????????500TTG?GAT?TTC?CCT?TCT?TCC?AAT?CTG?AGC?TTC?TTC?CTT?GTT?AGG?GGA?AGC???1589Leu?Asp?Phe?Pro?Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu?Val?Arg?Gly?Ser

505?????????????????510?????????????????515CCC?TAT?TTG?ACT?GTG?TCT?GTG?ACT?CAA?CCA?ACT?CCT?CTT?TCA?ATT?ACC???1637Pro?Tyr?Leu?Thr?Val?Ser?Val?Thr?Gln?Pro?Thr?Pro?Leu?Ser?Ile?Thr520?????????????????525?????????????????530?????????????????535ACC?ATC?CAT?TCC?ATT?CTC?TCA?TTC?TCT?TCA?AAT?GAC?TCC?AAC?ACC?AAG???1685Thr?Ile?His?Ser?Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp?Ser?Asn?Thr?Lys

540?????????????????545?????????????????550TAC?ACC?TTT?CAG?TTC?AAC?AAT?GGT?CAA?ACA?TGG?CTT?CTT?TAT?GCT?ACC???1733Tyr?Thr?Phe?Gln?Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu?Leu?Tyr?Ala?Thr

555?????????????????560?????????????????565TCC?CCC?ATC?AAG?TTG?AAC?CAC?ACC?CTT?TCT?GAG?ATA?ACT?TCT?AAT?GCA???1781Ser?Pro?Ile?Lys?Leu?Asn?His?Thr?Leu?Ser?Glu?Ile?Thr?Ser?Asn?Ala

570?????????????????575?????????????????580TTT?TCT?GGC?ATA?ATC?CGG?ATA?GCT?TTG?TTG?CCG?GAT?TCG?GAT?TCG?AAA???1829Phe?Ser?Gly?Ile?Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp?Ser?Asp?Ser?Lys

585?????????????????590?????????????????595CAC?GAG?GCT?GTT?CTT?GAC?AAG?TAT?AGT?TCT?TGT?TAC?CCC?GTG?TCA?GGT???1877His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr?Pro?Val?Ser?Gly600?????????????????605?????????????????610?????????????????615AAA?GCT?GTG?TTC?AGA?GAA?CCT?TTC?TGT?GTG?GAA?TAT?AAC?TGG?GAG?AAG???1925Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr?Asn?Trp?Glu?Lys

620?????????????????625?????????????????630AAA?GAT?TCA?GGG?GAT?TTG?CTA?CTC?TTG?GCT?CAC?CCT?CTC?CAT?GTT?CAG???1973Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro?Leu?His?Val?Gln

635?????????????????640?????????????????645CTT?CTT?CGT?AAT?GGA?GAC?AAT?GAT?GTC?AAA?ATT?CTT?GAA?GAT?TTA?AAG???2021Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu?Glu?Asp?Leu?Lys

650?????????????????655?????????????????660TAT?AAA?AGC?ATT?GAT?GGG?GAT?CTT?GTT?GGT?GTT?GTC?GGG?GAT?TCA?TGG???2069Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val?Gly?Asp?Ser?Trp

665?????????????????670?????????????????675GTT?TTG?AAA?ACA?GAT?CCT?TTG?TTT?GTA?ACA?TGG?CAT?TCA?ATC?AAG?GGA???2117Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His?Ser?Ile?Lys?Gly680?????????????????685?????????????????690?????????????????695ATC?AAA?GAA?GAA?TCC?CAT?GAT?GAG?ATT?GTC?TCA?GCC?CTT?TCT?AAA?GAT???2165Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala?Leu?Ser?Lys?Asp

700?????????????????705?????????????????710GTT?GAG?AGC?CTA?GAT?TCA?TCA?TCA?ATA?ACT?ACA?ACA?GAG?TCA?TAT?TTT???2213Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr?Glu?Ser?Tyr?Phe

715?????????????????720?????????????????725TAT?GGG?AAG?TTG?ATT?GCA?AGG?GCT?GCA?AGG?TTG?GTA?TTG?ATT?GCT?GAG???2261Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val?Leu?Ile?Ala?Glu

730?????????????????735?????????????????740GAG?TTG?AAC?TAC?CCT?GAT?GTG?ATT?CCA?AAG?GTT?AGG?AAT?TTT?TTG?AAA???2309Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys?Val?Arg?Asn?Phe?Leu?Lys

745?????????????????750?????????????????755GAA?ACC?ATT?GAG?CCA?TGG?TTG?GAG?GGA?ACT?TTT?AGT?GGG?AAT?GGA?TTC???2357Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser?Gly?Asn?Gly?Phe760?????????????????765?????????????????770?????????????????775CTA?CAT?GAT?GAA?AAA?TGG?GGT?GGC?ATT?ATT?ACC?CAA?AAG?GGG?TCC?ACT???2405Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln?Lys?Gly?Ser?Thr

780?????????????????785?????????????????790GAT?GCT?GGT?GGT?GAT?TTT?GGA?TTT?GGA?ATT?TAC?AAT?GAT?CAC?CAC?TAT???2453Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn?Asp?His?His?Tyr

795?????????????????800?????????????????805CAT?TTG?GGG?TAC?TTC?ATT?TAT?GGA?ATT?GCG?GTG?CTC?ACT?AAG?CTT?GAT???2501His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu?Thr?Lys?Leu?Asp

810?????????????????815?????????????????820CCA?GCA?TGG?GGT?AGG?AAG?TAC?AAG?CCT?CAA?GCC?TAT?TCA?ATA?GTG?CAA???2549Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr?Ser?Ile?Val?Gln

825?????????????????830?????????????????835GAC?TTC?TTG?AAC?TTG?GAC?ACA?AAA?TTA?AAC?TCC?AAT?TAC?ACA?CGT?TTG???2597Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn?Tyr?Thr?Arg?Leu840?????????????????845?????????????????850?????????????????855AGG?TGT?TTT?GAC?CCT?TAT?GTG?CTT?CAC?TCT?TGG?GCT?GGA?GGG?TTA?ACT???2645Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala?Gly?Gly?Leu?Thr

860?????????????????865?????????????????870GAG?TTC?ACA?GAT?GGA?AGG?AAT?CAA?GAG?AGC?ACA?AGT?GAG?GCT?GTG?AGT???2693Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser?Glu?Ala?Val?Ser

875?????????????????880?????????????????885GCA?TAT?TAT?TCT?GCT?GCT?TTG?ATG?GGA?TTA?GCA?TAT?GGT?GAT?GCA?CCT???2741Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr?Gly?Asp?Ala?Pro

890?????????????????895?????????????????900CTT?GTT?GCA?CTT?GGA?TCA?ACA?CTC?ACA?GCA?TTG?GAA?ATT?GAA?GGG?ACT???2789Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu?Ile?Glu?Gly?Thr

905?????????????????910?????????????????915AAA?ATG?TGG?TGG?CAT?GTG?AAA?GAG?GGA?GGT?ACT?TTG?TAT?GAG?AAA?GAG???2837Lys?Met?Trp?Trp?His?Val?Lys?Glu?Gly?Gly?Thr?Leu?Tyr?Glu?Lys?Glu920?????????????????925?????????????????930?????????????????935TTT?ACA?CAA?GAG?AAT?AGG?GTG?ATG?GGT?GTT?CTA?TGG?TCT?AAC?AAG?AGG???2885Phe?Thr?Gln?Glu?Asn?Arg?Val?Met?Gly?Val?Leu?Trp?Ser?Asn?Lys?Arg

940?????????????????945?????????????????950GAC?ACT?GGA?CTT?TGG?TTT?GCT?CCT?GCT?GAG?TGG?AAA?GAG?TGT?AGG?CTT???2933Asp?Thr?Gly?Leu?Trp?Phe?Ala?Pro?Ala?Glu?Trp?Lys?Glu?Cys?Arg?Leu

955?????????????????960?????????????????965GGC?ATT?CAG?CTC?TTA?CCA?TTG?GCT?CCT?ATT?TCT?GAA?GCC?ATT?TTC?TCC???2981Gly?Ile?Gln?Leu?Leu?Pro?Leu?Ala?Pro?Ile?Ser?Glu?Ala?Ile?Phe?Ser

970?????????????????975?????????????????980AAT?GTT?GAC?TTT?GTA?AAG?GAG?CTT?GTG?GAG?TGG?ACT?TTG?CCT?GCT?TTG???3029Asn?Val?Asp?Phe?Val?Lys?Glu?Leu?Val?Glu?Trp?Thr?Leu?Pro?Ala?Leu

985?????????????????990?????????????????995GAT?AGG?GAG?GGT?GGT?GTT?GGT?GAA?GGA?TGG?AAG?GGG?TTT?GTG?TAT?GCC???3077Asp?Arg?Glu?Gly?Gly?Val?Gly?Glu?Gly?Trp?Lys?Gly?Phe?Val?Tyr?Ala1000????????????????1005????????????????1010????????????????1015CTT?GAA?GGG?GTT?TAT?GAC?AAT?GAA?AGT?GCA?CTG?CAG?AAG?ATA?AGA?AAC???3125Leu?Glu?Gly?Val?Tyr?Asp?Asn?Glu?Ser?Ala?Leu?Gln?Lys?Ile?Arg?Asn

1020????????????????1025????????????????1030CTG?AAA?GGT?TTT?GAT?GGT?GGA?AAC?TCT?TTG?ACC?AAT?CTC?TTG?TGG?TGG???3173Leu?Lys?Gly?Phe?Asp?Gly?Gly?Asn?Ser?Leu?Thr?Asn?Leu?Leu?Trp?Trp

1035????????????????1040????????????????1045ATT?CAT?AGC?AGA?AGT?GAT?GAA?TAGAATGGAT?TTGGTTATTG?AACATGACAA??????3224Ile?His?Ser?Arg?Ser?Asp?Glu

1050CACTGCTGAT?TTGGTTATTA?TTATTATTGC?TACTATTACT?ATGCCAATAA?AATCATCAAA?3284TATGTCTTAC?ATCATAATAA?AAAAATTATT?ATTATGCCAA?TAAGTCAATG?ATTTCGATAT?3344GTTATAGAAG?AAGAAAACTA?TAATAAAGTT?ACAACAATAT?CATGATCTAT?AACATGTCTG?3404A?????????????????????????????????????????????????????????????????3405

SEQ ID NO:7 sequence length: 877 sequence types: amino acid topology: linear molecule type: protein sequence is described: Val Asn Ile Gln Thr Asn Thr Ser Tyr Ile Phe Pro Gln Thr Gln Ser 15 10 15Thr Val Leu Pro Asp Pro Ser Lys Phe Phe Ser Ser Asn Leu Leu Ser

20??????????????????25??????????????????30Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn

35??????????????????40??????????????????45Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His?Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn

50??????????????????55??????????????????60Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro?Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?65??????????????????70??????????????????75??????????????????80Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp?Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly

85??????????????????90??????????????????95Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys?His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp

100?????????????????105?????????????????110Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro?Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu

115?????????????????120?????????????????125Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr?Val?Ser?Val?Thr?Gln?Pro?Thr?Pro

130?????????????????135?????????????????140Leu?Ser?Ile?Thr?Thr?Ile?His?Ser?Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp145?????????????????150?????????????????155?????????????????160Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln?Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu

165?????????????????170?????????????????175Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys?Leu?Asn?His?Thr?Leu?Ser?Glu?Ile

180?????????????????185?????????????????190Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile?Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp

195?????????????????200?????????????????205Ser?Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr

210?????????????????215?????????????????220Pro?Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr225?????????????????230?????????????????235?????????????????240Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro

245?????????????????250?????????????????255Leu?His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu

260?????????????????265?????????????????270Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val

275?????????????????280?????????????????285Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His

290?????????????????295?????????????????300Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala305?????????????????310?????????????????315?????????????????320Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr

325?????????????????330?????????????????335Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val

340?????????????????345?????????????????350Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys?Val?Arg

355?????????????????360?????????????????365Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser

370?????????????????375?????????????????380Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln385?????????????????390?????????????????395?????????????????400Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn

405?????????????????410?????????????????415Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu

420?????????????????425?????????????????430Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr

435?????????????????440?????????????????445Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn

450?????????????????455?????????????????460Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala465?????????????????470?????????????????475?????????????????480Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser

485?????????????????490?????????????????495Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr

500?????????????????505?????????????????510Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu

515?????????????????520?????????????????525Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Ala?Met?Asp?Phe?Ile?Ser?Ser

530?????????????????535?????????????????540Leu?Ile?Val?Gly?Cys?Ala?Gln?Val?Leu?Cys?Glu?Ser?Met?Asn?Met?Ala545?????????????????550?????????????????555?????????????????560Glu?Arg?Arg?Gly?His?Lys?Thr?Asp?Leu?Arg?Gln?Ala?Ile?Thr?Asp?Leu

565?????????????????570?????????????????575Glu?Thr?Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile?Arg?Asp?Asp?Leu?Thr?Leu

580?????????????????585?????????????????590Arg?Ile?Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg?Ser?Cys?Ser?Asn?Arg?Ala

595?????????????????600?????????????????605Arg?Glu?Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?Glu?Thr?Lys?Thr?Ala?Leu

610?????????????????615?????????????????620Leu?Leu?Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln?Arg?Thr?Arg?Met?Arg?Arg625?????????????????630?????????????????635?????????????????640Arg?Tyr?Leu?Ser?Cys?Phe?Gly?Cys?Ala?Asp?Tyr?Lys?Leu?Cys?Lys?Lys

645?????????????????650?????????????????655Val?Ser?Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu?Leu?Arg?Glu?Arg?Ser?Glu

660??????????????????665?????????????????670Ala?Ile?Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln?Val?Thr?Cys?Arg?Glu?Ile

675?????????????????680?????????????????685Pro?Ile?Lys?Ser?Val?Val?Gly?Asn?Thr?Thr?Met?Met?Glu?Gln?Val?Leu

690?????????????????695?????????????????700Glu?Phe?Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly?Ile?Ile?Gly?Val?Tyr?Gly705?????????????????710?????????????????715?????????????????720Pro?Gly?Gly?Val?Gly?Lys?Thr?Thr?Leu?Met?Gln?Ser?Ile?Asn?Asn?Glu

725?????????????????730?????????????????735Leu?Ile?Thr?Lys?Gly?His?Gln?Tyr?Asp?Val?Leu?Ile?Trp?Val?Gln?Met

740?????????????????745?????????????????750Ser?Arg?Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln?Gln?Ala?Val?Gly?Ala?Arg

755?????????????????760?????????????????765Leu?Gly?Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr?Gly?Glu?Asn?Arg?Ala?Leu

770?????????????????775?????????????????780Lys?Ile?Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg?Phe?Leu?Leu?Leu?Leu?Asp785?????????????????790?????????????????795?????????????????800Asp?Val?Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys?Thr?Gly?Val?Pro?Arg?Pro

805?????????????????810?????????????????815Asp?Arg?Glu?Asn?Lys?Cys?Lys?Val?Met?Phe?Thr?Thr?Arg?Ser?Ile?Ala

820?????????????????825?????????????????830Leu?Cys?Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys?Leu?Arg?Val?Glu?Phe?Leu

835?????????????????840?????????????????845Glu?Lys?Lys?His?Ala?Trp?Glu?Leu?Phe?Cys?Ser?Lys?Val?Trp?Arg?Lys

850 855 860Asp Leu Leu Glu Ser Ser Ser Ile Arg Arg Leu Ala Glu865,870 875 SEQ ID NO:8 sequence lengths: 2666 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA feature title/keyword: CDS position: 29..2659 sequence description: TCGAATTAAA CCACCTTCAG CAACAATG GTT AAC ATC CAA ACC AAT ACA TCT 52

Val?Asn?Ile?Gln?Thr?Asn?Thr?Ser

1???????????????5TAC?ATC?TTC?CCT?CAA?ACA?CAA?TCC?ACT?GTT?CTT?CCT?GAT?CCC?TCC?AAA????100Tyr?Ile?Phe?Pro?Gln?Thr?Gln?Ser?Thr?Val?Leu?Pro?Asp?Pro?Ser?Lys

10??????????????????15??????????????????20TTC?TTC?TCC?TCA?AAC?CTT?CTC?TCA?AGT?CCA?CTC?CCC?ACA?AAC?TCT?TTC????148Phe?Phe?Ser?Ser?Asn?Leu?Leu?Ser?Ser?Pro?Leu?Pro?Thr?Asn?Ser?Phe?25??????????????????30??????????????????35??????????????????40TTC?CAA?AAC?TTT?GTC?CTA?AAA?AAT?GGT?GAC?CAA?CAA?GAA?TAC?ATT?CAT????196Phe?Gln?Asn?Phe?Val?Leu?Lys?Asn?Gly?Asp?Gln?Gln?Glu?Tyr?Ile?His

45??????????????????50??????????????????55CCT?TAC?CTC?ATC?AAA?TCC?TCC?AAC?TCT?TCC?CTC?TCT?CTC?TCA?TAC?CCT????244Pro?Tyr?Leu?Ile?Lys?Ser?Ser?Asn?Ser?Ser?Leu?Ser?Leu?Ser?Tyr?Pro

60??????????????????65??????????????????70TCT?CGC?CAA?GCC?AGT?TCA?GCT?GTC?ATA?TTC?CAA?GTC?TTC?AAT?CCT?GAT????292Ser?Arg?Gln?Ala?Ser?Ser?Ala?Val?Ile?Phe?Gln?Val?Phe?Asn?Pro?Asp

75??????????????????80??????????????????85CTT?ACC?ATT?TCA?GCC?CCA?CAA?GGT?CCC?AAA?CAA?GGT?CCC?CCT?GGT?AAA????340Leu?Thr?Ile?Ser?Ala?Pro?Gln?Gly?Pro?Lys?Gln?Gly?Pro?Pro?Gly?Lys

90??????????????????95?????????????????100CAC?CTT?ATC?TCC?TCC?TAC?AGT?GAT?CTC?AGT?GTC?ACC?TTG?GAT?TTC?CCT????388His?Leu?Ile?Ser?Ser?Tyr?Ser?Asp?Leu?Ser?Val?Thr?Leu?Asp?Phe?Pro105?????????????????110?????????????????115?????????????????120TCT?TCC?AAT?CTG?AGC?TTC?TTC?CTT?GTT?AGG?GGA?AGC?CCC?TAT?TTG?ACT????436Ser?Ser?Asn?Leu?Ser?Phe?Phe?Leu?Val?Arg?Gly?Ser?Pro?Tyr?Leu?Thr

125?????????????????130?????????????????135GTG?TCT?GTG?ACT?CAA?CCA?ACT?CCT?CTT?TCA?ATT?ACC?ACC?ATC?CAT?TCC????484Val?Ser?Val?Thr?Gln?Pro?Thr?Pro?Leu?Ser?Ile?Thr?Thr?Ile?His?Ser

140?????????????????145?????????????????150ATT?CTC?TCA?TTC?TCT?TCA?AAT?GAC?TCC?AAC?ACC?AAG?TAC?ACC?TTT?CAG????532Ile?Leu?Ser?Phe?Ser?Ser?Asn?Asp?Ser?Asn?Thr?Lys?Tyr?Thr?Phe?Gln

155?????????????????160?????????????????165TTC?AAC?AAT?GGT?CAA?ACA?TGG?CTT?CTT?TAT?GCT?ACC?TCC?CCC?ATC?AAG????580Phe?Asn?Asn?Gly?Gln?Thr?Trp?Leu?Leu?Tyr?Ala?Thr?Ser?Pro?Ile?Lys

170?????????????????175?????????????????180TTG?AAC?CAC?ACC?CTT?TCT?GAG?ATA?ACT?TCT?AAT?GCA?TTT?TCT?GGC?ATA????628Leu?Asn?His?Thr?Leu?Ser?Glu?Ile?Thr?Ser?Asn?Ala?Phe?Ser?Gly?Ile185?????????????????190?????????????????195?????????????????200ATC?CGG?ATA?GCT?TTG?TTG?CCG?GAT?TCG?GAT?TCG?AAA?CAC?GAG?GCT?GTT????676Ile?Arg?Ile?Ala?Leu?Leu?Pro?Asp?Ser?Asp?Ser?Lys?His?Glu?Ala?Val

205?????????????????210?????????????????215CTT?GAC?AAG?TAT?AGT?TCT?TGT?TAC?CCC?GTG?TCA?GGT?AAA?GCT?GTG?TTC????724Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr?Pro?Val?Ser?Gly?Lys?Ala?Val?Phe

220?????????????????225?????????????????230AGA?GAA?CCT?TTC?TGT?GTG?GAA?TAT?AAC?TGG?GAG?AAG?AAA?GAT?TCA?GGG????772Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr?Asn?Trp?Glu?Lys?Lys?Asp?Ser?Gly

235?????????????????240?????????????????245GAT?TTG?CTA?CTC?TTG?GCT?CAC?CCT?CTC?CAT?GTT?CAG?CTT?CTT?CGT?AAT????820Asp?Leu?Leu?Leu?Leu?Ala?His?Pro?Leu?His?Val?Gln?Leu?Leu?Arg?Asn

250?????????????????255?????????????????260GGA?GAC?AAT?GAT?GTC?AAA?ATT?CTT?GAA?GAT?TTA?AAG?TAT?AAA?AGC?ATT????868Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile265?????????????????270?????????????????275?????????????????280GAT?GGG?GAT?CTT?GTT?GGT?GTT?GTC?GGG?GAT?TCA?TGG?GTT?TTG?AAA?ACA????916Asp?Gly?Asp?Leu?Val?Gly?Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr

285?????????????????290?????????????????295GAT?CCT?TTG?TTT?GTA?ACA?TGG?CAT?TCA?ATC?AAG?GGA?ATC?AAA?GAA?GAA????964Asp?Pro?Leu?Phe?Val?Thr?Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu

300?????????????????305?????????????????310TCC?CAT?GAT?GAG?ATT?GTC?TCA?GCC?CTT?TCT?AAA?GAT?GTT?GAG?AGC?CTA???1012Ser?His?Asp?Glu?Ile?Val?Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu

315?????????????????320?????????????????325GAT?TCA?TCA?TCA?ATA?ACT?ACA?ACA?GAG?TCA?TAT?TTT?TAT?GGG?AAG?TTG???1060Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu

330?????????????????335?????????????????340ATT?GCA?AGG?GCT?GCA?AGG?TTG?GTA?TTG?ATT?GCT?GAG?GAG?TTG?AAC?TAC???1108Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr345?????????????????350?????????????????355?????????????????360CCT?GAT?GTG?ATT?CCA?AAG?GTT?AGG?AAT?TTT?TTG?AAA?GAA?ACC?ATT?GAG???1156Pro?Asp?Val?Ile?Pro?Lys?Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu

365?????????????????370?????????????????375CCA?TGG?TTG?GAG?GGA?ACT?TTT?AGT?GGG?AAT?GGA?TTC?CTA?CAT?GAT?GAA???1204Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu

380?????????????????385?????????????????390AAA?TGG?GGT?GGC?ATT?ATT?ACC?CAA?AAG?GGG?TCC?ACT?GAT?GCT?GGT?GGT???1252Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly

395?????????????????400?????????????????405GAT?TTT?GGA?TTT?GGA?ATT?TAC?AAT?GAT?CAC?CAC?TAT?CAT?TTG?GGG?TAC???1300Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr

410?????????????????415?????????????????420TTC?ATT?TAT?GGA?ATT?GCG?GTG?CTC?ACT?AAG?CTT?GAT?CCA?GCA?TGG?GGT???1348Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly425?????????????????430?????????????????435?????????????????440AGG?AAG?TAC?AAG?CCT?CAA?GCC?TAT?TCA?ATA?GTG?CAA?GAC?TTC?TTG?AAC???1396Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr?Ser?Ile?Val?Gln?Asp?Phe?Leu?Asn

445?????????????????450?????????????????455TTG?GAC?ACA?AAA?TTA?AAC?TCC?AAT?TAC?ACA?CGT?TTG?AGG?TGT?TTT?GAC???1444Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn?Tyr?Thr?Arg?Leu?Arg?Cys?Phe?Asp

460?????????????????465?????????????????470CCT?TAT?GTG?CTT?CAC?TCT?TGG?GCT?GGA?GGG?TTA?ACT?GAG?TTC?ACA?GAT???1492Pro?Tyr?Val?Leu?His?Ser?Trp?Ala?Gly?Gly?Leu?Thr?Glu?Phe?Thr?Asp

475?????????????????480?????????????????485GGA?AGG?AAT?CAA?GAG?AGC?ACA?AGT?GAG?GCT?GTG?AGT?GCA?TAT?TAT?TCT???1540Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser?Glu?Ala?Val?Ser?Ala?Tyr?Tyr?Ser

490?????????????????495?????????????????500GCT?GCT?TTG?ATG?GGA?TTA?GCA?TAT?GGT?GAT?GCA?CCT?CTT?GTT?GCA?CTT???1588Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr?Gly?Asp?Ala?Pro?Leu?Val?Ala?Leu505?????????????????510?????????????????515?????????????????520GGA?TCA?ACA?CTC?ACA?GCA?TTG?GAA?ATT?GAA?GGG?ACT?AAA?ATG?TGG?TGG???1636Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu?Ile?Glu?Gly?Thr?Lys?Met?Trp?Trp

525?????????????????530?????????????????535CAT?GCG?ATG?GAT?TTC?ATC?TCA?TCT?CTT?ATC?GTT?GGC?TGT?GCT?CAG?GTG???1684His?Ala?Met?Asp?Phe?Ile?Ser?Ser?Leu?Ile?Val?Gly?Cys?Ala?Gln?Val

540?????????????????545?????????????????550TTG?TGT?GAA?TCT?ATG?AAT?ATG?GCG?GAG?AGA?AGA?GGA?CAT?AAG?ACT?GAT???1732Leu?Cys?Glu?Ser?Met?Asn?Met?Ala?Glu?Arg?Arg?Gly?His?Lys?Thr?Asp

555?????????????????560?????????????????565CTT?AGA?CAA?GCC?ATC?ACT?GAT?CTT?GAA?ACA?GCC?ATC?GGT?GAC?TTG?AAG???1780Leu?Arg?Gln?Ala?Ile?Thr?Asp?Leu?Glu?Thr?Ala?Ile?Gly?Asp?Leu?Lys

570?????????????????575?????????????????580GCC?ATA?CGT?GAT?GAC?CTG?ACT?TTA?CGG?ATC?CAA?CAA?GAC?GGT?CTA?GAG???1828Ala?Ile?Arg?Asp?Asp?Leu?Thr?Leu?Arg?Ile?Gln?Gln?Asp?Gly?Leu?Glu585?????????????????590?????????????????595?????????????????600GGA?CGA?AGC?TGC?TCA?AAT?CGT?GCC?AGA?GAG?TGG?CTT?AGT?GCG?GTG?CAA???1876Gly?Arg?Ser?Cys?Ser?Asn?Arg?Ala?Arg?Glu?Trp?Leu?Ser?Ala?Val?Gln

605?????????????????610?????????????????615GTA?ACG?GAG?ACT?AAA?ACA?GCC?CTA?CTT?TTA?GTG?AGG?TTT?AGG?CGT?CGG???1924Val?Thr?Glu?Thr?Lys?Thr?Ala?Leu?Leu?Leu?Val?Arg?Phe?Arg?Arg?Arg

620?????????????????625?????????????????630GAA?CAG?AGG?ACG?CGA?ATG?AGG?AGG?AGA?TAC?CTC?AGT?TGT?TTC?GGT?TGT???1972Glu?Gln?Arg?Thr?Arg?Met?Arg?Arg?Arg?Tyr?Leu?Ser?Cys?Phe?Gly?Cys

635?????????????????640?????????????????645GCC?GAC?TAC?AAA?CTG?TGC?AAG?AAG?GTT?TCT?GCC?ATA?TTG?AAG?AGC?ATT???2020Ala?Asp?Tyr?Lys?Leu?Cys?Lys?Lys?Val?Ser?Ala?Ile?Leu?Lys?Ser?Ile

650?????????????????655?????????????????660GGT?GAG?CTG?AGA?GAA?CGC?TCT?GAA?GCT?ATC?AAA?ACA?GAT?GGC?GGG?TCA???2068Gly?Glu?Leu?Arg?Glu?Arg?Ser?Glu?Ala?Ile?Lys?Thr?Asp?Gly?Gly?Ser665?????????????????670?????????????????675?????????????????680ATT?CAA?GTA?ACT?TGT?AGA?GAG?ATA?CCC?ATC?AAG?TCC?GTT?GTC?GGA?AAT???2116Ile?Gln?Val?Thr?Cys?Arg?Glu?Ile?Pro?Ile?Lys?Ser?Val?Val?Gly?Asn

685?????????????????690?????????????????695ACC?ACG?ATG?ATG?GAA?CAG?GTT?TTG?GAA?TTT?CTC?AGT?GAA?GAA?GAA?GAA???2164Thr?Thr?Met?Met?Glu?Gln?Val?Leu?Glu?Phe?Leu?Ser?Glu?Glu?Glu?Glu

700?????????????????705?????????????????710AGA?GGA?ATC?ATT?GGT?GTT?TAT?GGA?CCT?GGT?GGG?GTT?GGG?AAG?ACA?ACG???2212Arg?Gly?Ile?Ile?Gly?Val?Tyr?Gly?Pro?Gly?Gly?Val?Gly?Lys?Thr?Thr

715?????????????????720?????????????????725TTA?ATG?CAG?AGC?ATT?AAC?AAC?GAG?CTG?ATC?ACA?AAA?GGA?CAT?CAG?TAT???2260Leu?Met?Gln?Ser?Ile?Asn?Asn?Glu?Leu?Ile?Thr?Lys?Gly?His?Gln?Tyr

730?????????????????735?????????????????740GAT?GTA?CTG?ATT?TGG?GTT?CAA?ATG?TCC?AGA?GAA?TTC?GGC?GAG?TGT?ACA???2308Asp?Val?Leu?Ile?Trp?Val?Gln?Met?Ser?Arg?Glu?Phe?Gly?Glu?Cys?Thr745?????????????????750?????????????????755?????????????????760ATT?CAG?CAA?GCC?GTT?GGA?GCA?CGG?TTG?GGT?TTA?TCT?TGG?GAC?GAG?AAG???2356Ile?Gln?Gln?Ala?Val?Gly?Ala?Arg?Leu?Gly?Leu?Ser?Trp?Asp?Glu?Lys

765?????????????????770?????????????????775GAG?ACC?GGC?GAA?AAC?AGA?GCT?TTG?AAG?ATA?TAC?AGA?GCT?TTG?AGA?CAG???2404Glu?Thr?Gly?Glu?Asn?Arg?Ala?Leu?Lys?Ile?Tyr?Arg?Ala?Leu?Arg?Gln

780?????????????????785?????????????????790AAA?CGT?TTC?TTG?TTG?TTG?CTA?GAT?GAT?GTC?TGG?GAA?GAG?ATA?GAC?TTG???2452Lys?Arg?Phe?Leu?Leu?Leu?Leu?Asp?Asp?Val?Trp?Glu?Glu?Ile?Asp?Leu

795?????????????????800?????????????????805GAG?AAA?ACT?GGA?GTT?CCT?CGA?CCT?GAC?AGG?GAA?AAC?AAA?TGC?AAG?GTG???2500Glu?Lys?Thr?Gly?Val?Pro?Arg?Pro?Asp?Arg?Glu?Asn?Lys?Cys?Lys?Val

810?????????????????815?????????????????820ATG?TTC?ACG?ACA?CGG?TCT?ATA?GCA?TTA?TGC?AAC?AAT?ATG?GGT?GCG?GAA???2548Met?Phe?Thr?Thr?Arg?Ser?Ile?Ala?Leu?Cys?Asn?Asn?Met?Gly?Ala?Glu825?????????????????830?????????????????835?????????????????840TAC?AAG?TTG?AGA?GTG?GAG?TTT?CTG?GAG?AAG?AAA?CAC?GCG?TGG?GAG?CTG???2596Tyr?Lys?Leu?Arg?Val?Glu?Phe?Leu?Glu?Lys?Lys?His?Ala?Trp?Glu?Leu

845?????????????????850?????????????????855TTC?TGT?AGT?AAG?GTA?TGG?AGA?AAA?GAT?CTT?TTA?GAG?TCA?TCA?TCA?ATT???2644Phe?Cys?Ser?Lys?Val?Trp?Arg?Lys?Asp?Leu?Leu?Glu?Ser?Ser?Ser?Ile

860?????????????????865?????????????????870CGC?CGG?CTC?GCG?GAG?TGAA?TTC??????????????????????????????????????2666Arg?Arg?Leu?Ala?Glu

875 SEQ ID NO:9 sequence lengths: 683 sequence types: amino acid topology: linear molecule type: protein sequence is described: Asn Ala Phe Ser Gly Ile Ile Arg Ile Ala Leu Leu Pro Asp Ser Asp 15 10 15Ser Lys His Glu Ala Val Leu Asp Lys Tyr Ser Ser Cys Tyr Pro Val

20??????????????????25??????????????????30Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr?Asn?Trp

35??????????????????40??????????????????45Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro?Leu?His

50??????????????????55??????????????????60Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu?Glu?Asp?65??????????????????70??????????????????75??????????????????80Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val?Gly?Asp

85??????????????????90??????????????????95Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His?Ser?Ile

100?????????????????105?????????????????110Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala?Leu?Ser

115?????????????????120?????????????????125Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr?Glu?Ser

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

165?????????????????170?????????????????175Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser?Gly?Asn

180?????????????????185?????????????????190Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln?Lys?Gly

195?????????????????200?????????????????205Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn?Asp?His

210?????????????????215?????????????????220His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu?Thr?Lys225?????????????????230?????????????????235?????????????????240Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr?Ser?Ile

245?????????????????250?????????????????255Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn?Tyr?Thr

260?????????????????265?????????????????270Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala?Gly?Gly

275?????????????????280?????????????????285Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser?Glu?Ala

290?????????????????295?????????????????300Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr?Gly?Asp305?????????????????310?????????????????315?????????????????320Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu?Ile?Glu

325?????????????????330?????????????????335Gly?Thr?Lys?Met?Trp?Trp?His?Ala?Met?Asp?Phe?Ile?Ser?Ser?Leu?Ile

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

355?????????????????360?????????????????365Arg?Gly?His?Lys?Thr?Asp?Leu?Arg?Gln?Ala?Ile?Thr?Asp?Leu?Glu?Thr

370?????????????????375?????????????????380Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile?Arg?Asp?Asp?Leu?Thr?Leu?Arg?Ile385?????????????????390?????????????????395?????????????????400Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg?Ser?Cys?Ser?Asn?Arg?Ala?Arg?Glu

405?????????????????410?????????????????415Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?Glu?Thr?Lys?Thr?Ala?Leu?Leu?Leu

420?????????????????425?????????????????430Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln?Arg?Thr?Arg?Met?Arg?Arg?Arg?Tyr

435?????????????????440?????????????????445Leu?Ser?Cys?Phe?Gly?Cys?Ala?Asp?Tyr?Lys?Leu?Cys?Lys?Lys?Val?Ser

450?????????????????455?????????????????460Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu?Leu?Arg?Glu?Arg?Ser?Glu?Ala?Ile465?????????????????470?????????????????475?????????????????480Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln?Val?Thr?Cys?Arg?Glu?Ile?Pro?Ile

485?????????????????490?????????????????495Lys?Ser?Val?Val?Gly?Asn?Thr?Thr?Met?Met?Glu?Gln?Val?Leu?Glu?Phe

500?????????????????505?????????????????510Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly?Ile?Ile?Gly?Val?Tyr?Gly?Pro?Gly

515?????????????????520?????????????????525Gly?Val?Gly?Lys?Thr?Thr?Leu?Met?Gln?Ser?Ile?Asn?Asn?Glu?Leu?Ile

530?????????????????535?????????????????540Thr?Lys?Gly?His?Gln?Tyr?Asp?Val?Leu?Ile?Trp?Val?Gln?Met?Ser?Arg545?????????????????550?????????????????555?????????????????560Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln?Gln?Ala?Val?Gly?Ala?Arg?Leu?Gly

565?????????????????570?????????????????575Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr?Gly?Glu?Asn?Arg?Ala?Leu?Lys?Ile

580?????????????????585?????????????????590Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg?Phe?Leu?Leu?Leu?Leu?Asp?Asp?Val

595?????????????????600?????????????????605Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys?Thr?Gly?Val?Pro?Arg?Pro?Asp?Arg

610?????????????????615?????????????????620Glu?Asn?Lys?Cys?Lys?Val?Met?Phe?Thr?Thr?Arg?Ser?Ile?Ala?Leu?Cys625?????????????????630?????????????????635?????????????????640Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys?Leu?Arg?Val?Glu?Phe?Leu?Glu?Lys

645?????????????????650?????????????????655Lys?His?Ala?Trp?Glu?Leu?Phe?Cys?Ser?Lys?Val?Trp?Arg?Lys?Asp?Leu

660?????????????????665?????????????????670Leu?Glu?Ser?Ser?Ser?Ile?Arg?Arg?Leu?Ala?Glu

675 680 SEQ ID NO:10 sequence lengths: 2117 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA feature title/keyword: CDS position: 62..2110 sequence description: GCGGCCGCCT TCTTTCCTCA ACCTTCTTTC TTCTTATATA TTCGAACAAT TCGATATCAT 60G AAT GCA TTT TCT GGC ATA ATC CGG ATA GCT TTG TTG CCG GAT TCG 106 Asn Ala Phe Ser Gly Ile Ile Arg Ile Ala Leu Leu Pro Asp Ser

1???????????????5??????????????????10??????????????????15GAT?TCG?AAA?CAC?GAG?GCT?GTT?CTT?GAC?AAG?TAT?AGT?TCT?TGT?TAC?CCC????154Asp?Ser?Lys?His?Glu?Ala?Val?Leu?Asp?Lys?Tyr?Ser?Ser?Cys?Tyr?Pro

20??????????????????25??????????????????30GTG?TCA?GGT?AAA?GCT?GTG?TTC?AGA?GAA?CCT?TTC?TGT?GTG?GAA?TAT?AAC????202Val?Ser?Gly?Lys?Ala?Val?Phe?Arg?Glu?Pro?Phe?Cys?Val?Glu?Tyr?Asn

35??????????????????40??????????????????45TGG?GAG?AAG?AAA?GAT?TCA?GGG?GAT?TTG?CTA?CTC?TTG?GCT?CAC?CCT?CTC????250Trp?Glu?Lys?Lys?Asp?Ser?Gly?Asp?Leu?Leu?Leu?Leu?Ala?His?Pro?Leu

50??????????????????55??????????????????60CAT?GTT?CAG?CTT?CTT?CGT?AAT?GGA?GAC?AAT?GAT?GTC?AAA?ATT?CTT?GAA????298His?Val?Gln?Leu?Leu?Arg?Asn?Gly?Asp?Asn?Asp?Val?Lys?Ile?Leu?Glu

65??????????????????70??????????????????75GAT?TTA?AAG?TAT?AAA?AGC?ATT?GAT?GGG?GAT?CTT?GTT?GGT?GTT?GTC?GGG????346Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly?Val?Val?Gly?80??????????????????85??????????????????90??????????????????95GAT?TCA?TGG?GTT?TTG?AAA?ACA?GAT?CCT?TTG?TTT?GTA?ACA?TGG?CAT?TCA????394Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr?Trp?His?Ser

100?????????????????105?????????????????110ATC?AAG?GGA?ATC?AAA?GAA?GAA?TCC?CAT?GAT?GAG?ATT?GTC?TCA?GCC?CTT????442Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?Ser?Ala?Leu

115?????????????????120?????????????????125TCT?AAA?GAT?GTT?GAG?AGC?CTA?GAT?TCA?TCA?TCA?ATA?ACT?ACA?ACA?GAG????490Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr?Thr?Thr?Glu

130?????????????????135?????????????????140TCA?TAT?TTT?TAT?GGG?AAG?TTG?ATT?GCA?AGG?GCT?GCA?AGG?TTG?GTA?TTG????538Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg?Leu?Val?Leu

145?????????????????150?????????????????155ATT?GCT?GAG?GAG?TTG?AAC?TAC?CCT?GAT?GTG?ATT?CCA?AAG?GTT?AGG?AAT????586Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys?Val?Arg?Asn160?????????????????165?????????????????170?????????????????175TTT?TTG?AAA?GAA?ACC?ATT?GAG?CCA?TGG?TTG?GAG?GGA?ACT?TTT?AGT?GGG????634Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr?Phe?Ser?Gly

180?????????????????185?????????????????190AAT?GGA?TTC?CTA?CAT?GAT?GAA?AAA?TGG?GGT?GGC?ATT?ATT?ACC?CAA?AAG????682Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile?Thr?Gln?Lys

195?????????????????200?????????????????205GGG?TCC?ACT?GAT?GCT?GGT?GGT?GAT?TTT?GGA?TTT?GGA?ATT?TAC?AAT?GAT????730Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile?Tyr?Asn?Asp

210?????????????????215?????????????????220CAC?CAC?TAT?CAT?TTG?GGG?TAC?TTC?ATT?TAT?GGA?ATT?GCG?GTG?CTC?ACT????778His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala?Val?Leu?Thr

225?????????????????230?????????????????235AAG?CTT?GAT?CCA?GCA?TGG?GGT?AGG?AAG?TAC?AAG?CCT?CAA?GCC?TAT?TCA????826Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys?Tyr?Lys?Pro?Gln?Ala?Tyr?Ser240?????????????????245?????????????????250?????????????????255ATA?GTG?CAA?GAC?TTC?TTG?AAC?TTG?GAC?ACA?AAA?TTA?AAC?TCC?AAT?TAC????874Ile?Val?Gln?Asp?Phe?Leu?Asn?Leu?Asp?Thr?Lys?Leu?Asn?Ser?Asn?Tyr

260?????????????????265?????????????????270ACA?CGT?TTG?AGG?TGT?TTT?GAC?CCT?TAT?GTG?CTT?CAC?TCT?TGG?GCT?GGA????922Thr?Arg?Leu?Arg?Cys?Phe?Asp?Pro?Tyr?Val?Leu?His?Ser?Trp?Ala?Gly

275?????????????????280?????????????????285GGG?TTA?ACT?GAG?TTC?ACA?GAT?GGA?AGG?AAT?CAA?GAG?AGC?ACA?AGT?GAG????970Gly?Leu?Thr?Glu?Phe?Thr?Asp?Gly?Arg?Asn?Gln?Glu?Ser?Thr?Ser?Glu

290?????????????????295?????????????????300GCT?GTG?AGT?GCA?TAT?TAT?TCT?GCT?GCT?TTG?ATG?GGA?TTA?GCA?TAT?GGT???1018Ala?Val?Ser?Ala?Tyr?Tyr?Ser?Ala?Ala?Leu?Met?Gly?Leu?Ala?Tyr?Gly

305?????????????????310?????????????????315GAT?GCA?CCT?CTT?GTT?GCA?CTT?GGA?TCA?ACA?CTC?ACA?GCA?TTG?GAA?ATT???1066Asp?Ala?Pro?Leu?Val?Ala?Leu?Gly?Ser?Thr?Leu?Thr?Ala?Leu?Glu?Ile320?????????????????325?????????????????330?????????????????335GAA?GGG?ACT?AAA?ATG?TGG?TGG?CAT?GCG?ATG?GAT?TTC?ATC?TCA?TCT?CTT???1114Glu?Gly?Thr?Lys?Met?Trp?Trp?His?Ala?Met?Asp?Phe?Ile?Ser?Ser?Leu

340?????????????????345?????????????????350ATC?GTT?GGC?TGT?GCT?CAG?GTG?TTG?TGT?GAA?TCT?ATG?AAT?ATG?GCG?GAG???1162Ile?Val?Gly?Cys?Ala?Gln?Val?Leu?Cys?Glu?Ser?Met?Asn?Met?Ala?Glu

355?????????????????360?????????????????365AGA?AGA?GGA?CAT?AAG?ACT?GAT?CTT?AGA?CAA?GCC?ATC?ACT?GAT?CTT?GAA???1210Arg?Arg?Gly?His?Lys?Thr?Asp?Leu?Arg?Gln?Ala?Ile?Thr?Asp?Leu?Glu

370?????????????????375?????????????????380ACA?GCC?ATC?GGT?GAC?TTG?AAG?GCC?ATA?CGT?GAT?GAC?CTG?ACT?TTA?CGG???1258Thr?Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile?Arg?Asp?Asp?Leu?Thr?Leu?Arg

385?????????????????390?????????????????395ATC?CAA?CAA?GAC?GGT?CTA?GAG?GGA?CGA?AGC?TGC?TCA?AAT?CGT?GCC?AGA???1306Ile?Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg?Ser?Cys?Ser?Asn?Arg?Ala?Arg400?????????????????405?????????????????410?????????????????415GAG?TGG?CTT?AGT?GCG?GTG?CAA?GTA?ACG?GAG?ACT?AAA?ACA?GCC?CTA?CTT???1354Glu?Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?Glu?Thr?Lys?Thr?Ala?Leu?Leu

420?????????????????425?????????????????430TTA?GTG?AGG?TTT?AGG?CGT?CGG?GAA?CAG?AGG?ACG?CGA?ATG?AGG?AGG?AGA???1402Leu?Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln?Arg?Thr?Arg?Met?Arg?Arg?Arg

435?????????????????440?????????????????445TAC?CTC?AGT?TGT?TTC?GGT?TGT?GCC?GAC?TAC?AAA?CTG?TGC?AAG?AAG?GTT???1450Tyr?Leu?Ser?Cys?Phe?Gly?Cys?Ala?Asp?Tyr?Lys?Leu?Cys?Lys?Lys?Val

450?????????????????455?????????????????460TCT?GCC?ATA?TTG?AAG?AGC?ATT?GGT?GAG?CTG?AGA?GAA?CGC?TCT?GAA?GCT???1498Ser?Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu?Leu?Arg?Glu?Arg?Ser?Glu?Ala

465?????????????????470?????????????????475ATC?AAA?ACA?GAT?GGC?GGG?TCA?ATT?CAA?GTA?ACT?TGT?AGA?GAG?ATA?CCC???1546Ile?Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln?Val?Thr?Cys?Arg?Glu?Ile?Pro480?????????????????485?????????????????490?????????????????495ATC?AAG?TCC?GTT?GTC?GGA?AAT?ACC?ACG?ATG?ATG?GAA?CAG?GTT?TTG?GAA???1594Ile?Lys?Ser?Val?Val?Gly?Asn?Thr?Thr?Met?Met?Glu?Gln?Val?Leu?Glu

500?????????????????505?????????????????510TTT?CTC?AGT?GAA?GAA?GAA?GAA?AGA?GGA?ATC?ATT?GGT?GTT?TAT?GGA?CCT???1642Phe?Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly?Ile?Ile?Gly?Val?Tyr?Gly?Pro

515?????????????????520?????????????????525GGT?GGG?GTT?GGG?AAG?ACA?ACG?TTA?ATG?CAG?AGC?ATT?AAC?AAC?GAG?CTG???1690Gly?Gly?Val?Gly?Lys?Thr?Thr?Leu?Met?Gln?Ser?Ile?Asn?Asn?Glu?Leu

530?????????????????535?????????????????540ATC?ACA?AAA?GGA?CAT?CAG?TAT?GAT?GTA?CTG?ATT?TGG?GTT?CAA?ATG?TCC???1738Ile?Thr?Lys?Gly?His?Gln?Tyr?Asp?Val?Leu?Ile?Trp?Val?Gln?Met?Ser

545?????????????????550?????????????????555AGA?GAA?TTC?GGC?GAG?TGT?ACA?ATT?CAG?CAA?GCC?GTT?GGA?GCA?CGG?TTG???1786Arg?Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln?Gln?Ala?Val?Gly?Ala?Arg?Leu560?????????????????565?????????????????570?????????????????575GGT?TTA?TCT?TGG?GAC?GAG?AAG?GAG?ACC?GGC?GAA?AAC?AGA?GCT?TTG?AAG???1834Gly?Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr?Gly?Glu?Asn?Arg?Ala?Leu?Lys

580?????????????????585?????????????????590ATA?TAC?AGA?GCT?TTG?AGA?CAG?AAA?CGT?TTC?TTG?TTG?TTG?CTA?GAT?GAT???1882Ile?Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg?Phe?Leu?Leu?Leu?Leu?Asp?Asp

595?????????????????600?????????????????605GTC?TGG?GAA?GAG?ATA?GAC?TTG?GAG?AAA?ACT?GGA?GTT?CCT?CGA?CCT?GAC???1930Val?Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys?Thr?Gly?Val?Pro?Arg?Pro?Asp

610?????????????????615?????????????????620AGG?GAA?AAC?AAA?TGC?AAG?GTG?ATG?TTC?ACG?ACA?CGG?TCT?ATA?GCA?TTA???1978Arg?Glu?Asn?Lys?Cys?Lys?Val?Met?Phe?Thr?Thr?Arg?Ser?Ile?Ala?Leu

625?????????????????630?????????????????635TGC?AAC?AAT?ATG?GGT?GCG?GAA?TAC?AAG?TTG?AGA?GTG?GAG?TTT?CTG?GAG???2026Cys?Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys?Leu?Arg?Val?Glu?Phe?Leu?Glu640?????????????????645?????????????????650?????????????????655AAG?AAA?CAC?GCG?TGG?GAG?CTG?TTC?TGT?AGT?AAG?GTA?TGG?AGA?AAA?GAT???2074Lys?Lys?His?Ala?Trp?Glu?Leu?Phe?Cys?Ser?Lys?Val?Trp?Arg?Lys?Asp

660?????????????????665?????????????????670CTT?TTA?GAG?TCA?TCA?TCA?ATT?CGC?CGG?CTC?GCG?GAG?TGAATTC???????????2117Leu?Leu?Glu?Ser?Ser?Ser?Ile?Arg?Arg?Leu?Ala?Glu

675 680 SEQ ID NO:11 sequence lengths: 347 sequence types: amino acid topology: linear molecule type: protein sequence is described: Met Ala Lys Tyr His Ser Ser Gly Lys Ser Ser Ser Met Thr Ala Ile 15 10 15Ala Phe Leu Phe Ile Leu Leu Ile Thr Tyr Thr Gly Thr Thr Asp Ala

20??????????????????25??????????????????30Gln?Ser?Gly?Val?Cys?Tyr?Gly?Arg?Leu?Gly?Asn?Asn?Leu?Pro?Thr?Pro

35??????????????????40??????????????????45Gln?Glu?Val?Val?Ala?Leu?Tyr?Asn?Gln?Ala?Asn?Ile?Arg?Arg?Met?Arg

50??????????????????55??????????????????60Ile?Tyr?Gly?Pro?Ser?Pro?Glu?Val?Leu?Glu?Ala?Leu?Arg?Gly?Ser?Asn?65??????????????????70??????????????????75??????????????????80Ile?Glu?Leu?Leu?Leu?Asp?Ile?Pro?Asn?Asp?Asn?Leu?Arg?Asn?Leu?Ala

85??????????????????90??????????????????95Ser?Ser?Gln?Asp?Asn?Ala?Asn?Lys?Trp?Val?Gln?Asp?Asn?Ile?Lys?Asn

100?????????????????105?????????????????110Tyr?Ala?Asn?Asn?Val?Arg?Phe?Arg?Tyr?Val?Ser?Val?Gly?Asn?Glu?Val

115?????????????????120?????????????????125Lys?Pro?Glu?His?Ser?Phe?Ala?Gln?Phe?Leu?Val?Pro?Ala?Leu?Glu?Asn

130?????????????????135?????????????????140Ile?Gln?Arg?Ala?Ile?Ser?Asn?Ala?Gly?Leu?Gly?Asn?Gln?Val?Lys?Val145?????????????????150?????????????????155?????????????????160Ser?Thr?Ala?Ile?Asp?Thr?Gly?Ala?Leu?Ala?Glu?Ser?Phe?Pro?Pro?Ser

165?????????????????170?????????????????175Lys?Gly?Ser?Phe?Lys?Ser?Asp?Tyr?Arg?Gly?Ala?Tyr?Leu?Asp?Gly?Val

180?????????????????185?????????????????190Ile?Arg?Phe?Leu?Val?Asn?Asn?Asn?Ala?Pro?Leu?Met?Val?Asn?Val?Tyr

195?????????????????200?????????????????205Ser?Tyr?Phe?Ala?Tyr?Thr?Ala?Asn?Pro?Lys?Asp?Ile?Ser?Leu?Asp?Tyr

210?????????????????215?????????????????220Ala?Leu?Phe?Arg?Ser?Pro?Ser?Val?Val?Val?Gln?Asp?Gly?Ser?Leu?Gly225?????????????????230?????????????????235?????????????????240Tyr?Arg?Asn?Leu?Phe?Asp?Ala?Ser?Val?Asp?Ala?Val?Tyr?Ala?Ala?Leu

245?????????????????250?????????????????255Glu?Lys?Ala?Gly?Gly?Gly?Ser?Leu?Asn?Ile?Val?Val?Ser?Glu?Ser?Gly

260?????????????????265?????????????????270Trp?Pro?Ser?Ser?Gly?Gly?Thr?Ala?Thr?Ser?Leu?Asp?Asn?Ala?Arg?Thr

275?????????????????280?????????????????285Tyr?Asn?Thr?Asn?Leu?Val?Arg?Asn?Val?Lys?Gln?Gly?Thr?Pro?Lys?Arg

290?????????????????295?????????????????300Pro?Gly?Ala?Pro?Leu?Glu?Thr?Tyr?Val?Phe?Ala?Met?Phe?Asp?Glu?Asn305?????????????????310?????????????????315?????????????????320Gln?Lys?Gln?Pro?Glu?Phe?Glu?Lys?Phe?Trp?Gly?Leu?Phe?Ser?Pro?Ile

325?????????????????330?????????????????335Thr?Lys?Gln?Pro?Lys?Tyr?Ser?Ile?Asn?Phe?Asn

340 345 SEQ ID NO:12 sequence lengths: 1044 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA sequence description: ATG GCT AAG TAT CAT TCA AGT GGG AAA AGC TCT TCC ATG ACT GCT ATA 48Met Ala Lys Tyr His Ser Ser Gly Lys Ser Ser Ser Met Thr Ala Ile 15 10 15GCC TTC CTG TTT ATC CTT CTA ATC ACT TAT ACA GGC ACA ACA GAT GCA 96Ala Phe Leu Phe Ile Leu Leu Ile Thr Tyr Thr Gly Thr Thr Asp Ala

20??????????????????25??????????????????30CAA?TCC?GGG?GTA?TGT?TAT?GGA?AGA?CTT?GGC?AAC?AAC?TTA?CCA?ACC?CCT????144Gln?Ser?Gly?Val?Cys?Tyr?Gly?Arg?Leu?Gly?Asn?Asn?Leu?Pro?Thr?Pro

35??????????????????40??????????????????45CAA?GAA?GTT?GTG?GCC?CTC?TAC?AAT?CAA?GCC?AAC?ATT?CGC?AGG?ATG?CGA????192Gln?Glu?Val?Val?Ala?Leu?Tyr?Asn?Gln?Ala?Asn?Ile?Arg?Arg?Met?Arg

50??????????????????55??????????????????60ATC?TAC?GGT?CCA?AGC?CCA?GAA?GTC?CTC?GAA?GCA?CTA?AGA?GGT?TCC?AAC????240Ile?Tyr?Gly?Pro?Ser?Pro?Glu?Val?Leu?Glu?Ala?Leu?Arg?Gly?Ser?Asn?65??????????????????70??????????????????75??????????????????80ATT?GAG?CTT?TTG?CTA?GAC?ATT?CCA?AAT?GAC?AAC?CTC?AGA?AAC?CTA?GCA????288Ile?Glu?Leu?Leu?Leu?Asp?Ile?Pro?Asn?Asp?Asn?Leu?Arg?Asn?Leu?Ala

85??????????????????90??????????????????95TCT?AGC?CAA?GAC?AAT?GCA?AAC?AAA?TGG?GTG?CAA?GAC?AAC?ATC?AAA?AAC????336Ser?Ser?Gln?Asp?Asn?Ala?Asn?Lys?Trp?Val?Gln?Asp?Asn?Ile?Lys?Asn

100?????????????????105?????????????????110TAT?GCC?AAC?AAT?GTC?AGA?TTC?AGA?TAC?GTT?TCA?GTG?GGA?AAT?GAA?GTG????384Tyr?Ala?Asn?Asn?Val?Arg?Phe?Arg?Tyr?Val?Ser?Val?Gly?Asn?Glu?Val

115?????????????????120?????????????????125AAA?CCC?GAA?CAC?TCA?TTT?GCA?CAA?TTT?CTA?GTG?CCT?GCA?TTG?GAA?AAC????432Lys?Pro?Glu?His?Ser?Phe?Ala?Gln?Phe?Leu?Val?Pro?Ala?Leu?Glu?Asn

130?????????????????135?????????????????140ATT?CAG?AGG?GCC?ATT?TCT?AAT?GCT?GGC?CTT?GGA?AAC?CAA?GTA?AAA?GTT????480Ile?Gln?Arg?Ala?Ile?Ser?Asn?Ala?Gly?Leu?Gly?Asn?Gln?Val?Lys?Val145?????????????????150?????????????????155?????????????????160TCC?ACT?GCC?ATT?GAT?ACT?GGT?GCC?TTG?GCA?GAA?TCA?TTC?CCA?CCA?TCA????528Ser?Thr?Ala?Ile?Asp?Thr?Gly?Ala?Leu?Ala?Glu?Ser?Phe?Pro?Pro?Ser

165?????????????????170?????????????????175AAG?GGT?TCC?TTC?AAA?TCT?GAT?TAT?AGA?GGA?GCA?TAT?CTT?GAT?GGT?GTC????576Lys?Gly?Ser?Phe?Lys?Ser?Asp?Tyr?Arg?Gly?Ala?Tyr?Leu?Asp?Gly?Val

180?????????????????185?????????????????190ATC?AGA?TTT?CTA?GTG?AAC?AAT?AAT?GCC?CCA?TTA?ATG?GTT?AAT?GTG?TAC????624Ile?Arg?Phe?Leu?Val?Asn?Asn?Asn?Ala?Pro?Leu?Met?Val?Asn?Val?Tyr

195?????????????????200?????????????????205TCT?TAC?TTC?GCT?TAC?ACT?GCA?AAC?CCT?AAG?GAC?ATT?AGT?CTT?GAC?TAT????672Ser?Tyr?Phe?Ala?Tyr?Thr?Ala?Asn?Pro?Lys?Asp?Ile?Ser?Leu?Asp?Tyr

210?????????????????215?????????????????220GCA?CTT?TTT?AGG?TCT?CCT?TCG?GTG?GTA?GTG?CAA?GAT?GGT?TCA?CTT?GGT????720Ala?Leu?Phe?Arg?Ser?Pro?Ser?Val?Val?Val?Gln?Asp?Gly?Ser?Leu?Gly225?????????????????230?????????????????235?????????????????240TAC?CGT?AAC?CTC?TTT?GAT?GCT?TCG?GTT?GAT?GCT?GTT?TAT?GCT?GCA?TTG????768Tyr?Arg?Asn?Leu?Phe?Asp?Ala?Ser?Val?Asp?Ala?Val?Tyr?Ala?Ala?Leu

245?????????????????250?????????????????255GAG?AAA?GCA?GGA?GGA?GGG?TCA?TTG?AAC?ATA?GTT?GTG?TCT?GAG?AGT?GGA????816Glu?Lys?Ala?Gly?Gly?Gly?Ser?Leu?Asn?Ile?Val?Val?Ser?Glu?Ser?Gly

260?????????????????265?????????????????270TGG?CCT?TCT?TCT?GGT?GGA?ACT?GCA?ACT?TCA?CTT?GAT?AAT?GCA?AGA?ACT????864Trp?Pro?Ser?Ser?Gly?Gly?Thr?Ala?Thr?Ser?Leu?Asp?Asn?Ala?Arg?Thr

275?????????????????280?????????????????285TAC?AAC?ACA?AAC?TTG?GTT?CGG?AAT?GTG?AAG?CAA?GGA?ACC?CCT?AAA?AGG????912Tyr?Asn?Thr?Asn?Leu?Val?Arg?Asn?Val?Lys?Gln?Gly?Thr?Pro?Lys?Arg

290?????????????????295?????????????????300CCT?GGT?GCA?CCC?CTT?GAA?ACT?TAT?GTG?TTT?GCC?ATG?TTT?GAT?GAA?AAT????960Pro?Gly?Ala?Pro?Leu?Glu?Thr?Tyr?Val?Phe?Ala?Met?Phe?Asp?Glu?Asn305?????????????????310?????????????????315?????????????????320CAG?AAG?CAG?CCA?GAG?TTT?GAA?AAA?TTT?TGG?GGG?CTC?TTT?TCT?CCT?ATA???1008Gln?Lys?Gln?Pro?Glu?Phe?Glu?Lys?Phe?Trp?Gly?Leu?Phe?Ser?Pro?Ile

325?????????????????330?????????????????335ACT?AAG?CAG?CCC?AAA?TAC?TCG?ATT?AAT?TTC?AAT?TAA???????????????????1044Thr?Lys?Gln?Pro?Lys?Tyr?Ser?Ile?Asn?Phe?Asn

340 345 SEQ ID NO:13 sequence lengths: 331 sequence types: amino acid topology: linear molecule type: protein sequence is described: Met Ser Ala Leu Leu Leu Leu Leu Gly Val Leu Ser Ser Thr Gly Val 15 10 15Leu Leu Thr Gly Val Glu Ser Val Gly Val Cys Tyr Gly Gly Asn Gly

20??????????????????25??????????????????30Asn?Asn?Leu?Pro?Thr?Lys?Gln?Ala?Val?Val?Asn?Leu?Tyr?Lys?Ser?Asn

35??????????????????40??????????????????45Gly?Ile?Gly?Lys?Ile?Arg?Leu?Tyr?Tyr?Pro?Asp?Glu?Gly?Ala?Leu?Gln

50??????????????????55??????????????????60Ala?Leu?Arg?Gly?Ser?Asn?Ile?Glu?Val?Ile?Leu?Ala?Val?Pro?Asn?Asp?65??????????????????70??????????????????75??????????????????80Gln?Leu?Gln?Ser?Val?Ser?Asn?Asn?Gly?Gly?Ala?Thr?Asn?Trp?Val?Asn

85??????????????????90??????????????????95Lys?Tyr?Val?Lys?Pro?Tyr?Ala?Gly?Asn?Val?Lys?Leu?Lys?Tyr?Ile?Ala

100?????????????????105?????????????????110Val?Gly?Asn?Glu?Val?His?Pro?Gly?Asp?Ala?Leu?Ala?Gly?Ser?Val?Leu

115?????????????????120?????????????????125Pro?Ala?Leu?Gln?Ser?Ile?Gln?Asn?Ala?Ile?Ser?Ala?Ala?Asn?Leu?Gln

130?????????????????135?????????????????140Arg?Gln?Ile?Lys?Val?Ser?Thr?Ala?Ile?Asp?Thr?Thr?Leu?Leu?Gly?Asn145?????????????????150?????????????????155?????????????????160Ser?Tyr?Pro?Pro?Lys?Asp?Gly?Val?Phe?Ser?Asn?Ser?Ala?Ser?Ser?Tyr

165?????????????????170?????????????????175Ile?Thr?Pro?Ile?Ile?Asn?Phe?Leu?Ala?Lys?Asn?Gly?Ala?Pro?Leu?Leu

180?????????????????185?????????????????190Ala?Asn?Val?Tyr?Pro?Tyr?Phe?Ala?Tyr?Val?Asn?Asn?Gln?Gln?Asn?Ile

195?????????????????200?????????????????205Gly?Leu?Asp?Tyr?Ala?Leu?Phe?Thr?Lys?Gln?Gly?Asn?Asn?Glu?Val?Gly

210?????????????????215?????????????????220Tyr?Gln?Asn?Leu?Phe?Asp?Ala?Leu?Val?Asp?Ser?Leu?Tyr?Ala?Ala?Leu225?????????????????230?????????????????235?????????????????240Glu?Lys?Val?Gly?Ala?Ser?Asn?Val?Lys?Val?Val?Val?Ser?Glu?Ser?Gly

245?????????????????250?????????????????255Trp?Pro?Ser?Gln?Gly?Gly?Val?Gly?Ala?Thr?Val?Gln?Asn?Ala?Gly?Thr

260?????????????????265?????????????????270Tyr?Tyr?Arg?Asn?Leu?Ile?Lys?His?Val?Lys?Gly?Gly?Thr?Pro?Lys?Arg

275?????????????????280?????????????????285Pro?Asn?Gly?Pro?Ile?Glu?Thr?Tyr?Leu?Phe?Ala?Met?Phe?Asp?Glu?Asn

290?????????????????295?????????????????300Gln?Lys?Gly?Gly?Ala?Glu?Thr?Glu?Lys?His?Phe?Gly?Leu?Phe?Arg?Pro305?????????????????310?????????????????315?????????????????320Asp?Lys?Ser?Pro?Lys?Tyr?Gln?Leu?Ser?Phe?Asn

325 330 SEQ ID NO:14 sequence lengths: 993 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA sequence description: ATG TCT GCC TTA TTG CTG CTT CTT GGA GTA TTA TCT TCC ACT GGA GTA 48Met Ser Ala Leu Leu Leu Leu Leu Gly Val Leu Ser Ser Thr Gly Val 15 10 15CTG CTT ACT GGG GTA GAA TCT GTG GGT GTG TGT TAT GGA GGA AAT GGA 96Leu Leu Thr Gly Val Glu Ser Val Gly Val Cys Tyr Gly Gly Asn Gly

20??????????????????25??????????????????30AAC?AAT?CTA?CCA?ACA?AAG?CAA?GCA?GTG?GTG?AAT?CTC?TAC?AAA?TCA?AAC????144Asn?Asn?Leu?Pro?Thr?Lys?Gln?Ala?Val?Val?Asn?Leu?Tyr?Lys?Ser?Asn

35??????????????????40??????????????????45GGA?ATT?GGC?AAA?ATC?CGT?TTA?TAC?TAT?CCA?GAT?GAA?GGT?GCC?CTT?CAA????192Gly?Ile?Gly?Lys?Ile?Arg?Leu?Tyr?Tyr?Pro?Asp?Glu?Gly?Ala?Leu?Gln

50??????????????????55??????????????????60GCC?GTC?AGA?GGT?TCA?AAC?ATA?GAA?GTG?ATA?CTT?GCT?GTT?CCT?AAT?GAT????240Ala?Leu?Arg?Gly?Ser?Asn?Ile?Glu?Val?Ile?Leu?Ala?Val?Pro?Asn?Asp?65??????????????????70??????????????????75??????????????????80CAA?CTT?CAA?TCT?GTC?TCC?AAC?AAT?GGA?GGT?GCA?ACA?AAT?TGG?GTC?AAC????288Gln?Leu?Gln?Ser?Val?Ser?Asn?Asn?Gly?Gly?Ala?Thr?Asn?Trp?Val?Asn

85??????????????????90??????????????????95AAG?TAC?GTG?AAA?CCC?TAT?GCA?GGA?AAC?GTG?AAA?TTG?AAG?TAC?ATT?GCA????336Lys?Tyr?Val?Lys?Pro?Tyr?Ala?Gly?Asn?Val?Lys?Leu?Lys?Tyr?Ile?Ala

100?????????????????105?????????????????110GTT?GGC?AAC?GAA?GTT?CAC?CCT?GGT?GAT?GCT?CTA?GCA?GGC?TCA?GTT?CTT????384Val?Gly?Asn?Glu?Val?His?Pro?Gly?Asp?Ala?Leu?Ala?Gly?Ser?Val?Leu

115?????????????????120?????????????????125CCA?GCA?CTT?CAA?AGC?ATT?CAG?AAC?GCA?ATT?TCT?GCA?GCA?AAT?TTG?CAA????432Pro?Ala?Leu?Gln?Ser?Ile?Gln?Asn?Ala?Ile?Ser?Ala?Ala?Asn?Leu?Gln

130?????????????????135?????????????????140CGC?CAA?ATC?AAA?GTC?TCC?ACA?GCA?ATA?GAC?ACC?ACT?CTA?CTG?GGC?AAC????480Arg?Gln?Ile?Lys?Val?Ser?Thr?Ala?Ile?Asp?Thr?Thr?Leu?Leu?Gly?Asn145?????????????????150?????????????????155?????????????????160TCT?TAC?CCA?CCA?AAA?GAT?GGC?GTT?TTC?AGC?AAC?AGT?GCA?AGT?TCA?TAC????528Ser?Tyr?Pro?Pro?Lys?Asp?Gly?Val?Phe?Ser?Asn?Ser?Ala?Ser?Ser?Tyr

165?????????????????170?????????????????175ATA?ACT?CCA?ATC?ATA?AAC?TTT?TTA?GCC?AAA?AAC?GGT?GCC?CCA?CTT?CTT????576Ile?Thr?Pro?Ile?Ile?Asn?Phe?Leu?Ala?Lys?Asn?Gly?Ala?Pro?Leu?Leu

180?????????????????185?????????????????190GCA?AAC?GTG?TAC?CCT?TAC?TTC?GCC?TAC?GTT?AAC?AAT?CAA?CAA?AAC?ATT????624Ala?Asn?Val?Tyr?Pro?Tyr?Phe?Ala?Tyr?Val?Asn?Asn?Gln?Gln?Asn?Ile

195?????????????????200?????????????????205GGT?CTT?GAT?TAT?GCC?TTG?TTT?ACC?AAA?CAA?GGC?AAC?AAC?GAA?GTT?GGG????672Gly?Leu?Asp?Tyr?Ala?Leu?Phe?Thr?Lys?Gln?Gly?Asn?Asn?Glu?Val?Gly

210?????????????????215?????????????????220TAC?CAA?AAC?CTG?TTT?GAT?GCA?TTG?GTG?GAT?TCT?CTG?TAC?GCA?GCT?CTT????720Tyr?Gln?Asn?Leu?Phe?Asp?Ala?Leu?Val?Asp?Ser?Leu?Tyr?Ala?Ala?Leu225?????????????????230?????????????????235?????????????????240GAG?AAA?GTG?GGA?GCA?TCA?AAT?GTG?AAG?GTT?GTT?GTG?TCT?GAG?AGT?GGG????768Glu?Lys?Val?Gly?Ala?Ser?Asn?Val?Lys?Val?Val?Val?Ser?Glu?Ser?Gly

245?????????????????250?????????????????255TGG?CCA?TCA?CAA?GGT?GGA?GTT?GGA?GCC?ACT?GTT?CAA?AAC?GCA?GGA?ACG????816Trp?Pro?Ser?Gln?Gly?Gly?Val?Gly?Ala?Thr?Val?Gln?Asn?Ala?Gly?Thr

260?????????????????265?????????????????270TAT?TAC?AGG?AAT?TTG?ATC?AAA?CAT?GTT?AAG?GGT?GGC?ACC?CCA?AAG?AGG????864Tyr?Tyr?Arg?Asn?Leu?Ile?Lys?His?Val?Lys?Gly?Gly?Thr?Pro?Lys?Arg

275?????????????????280?????????????????285CCT?AAT?GGA?CCC?ATA?GAG?ACT?TAC?CTC?TTT?GCC?ATG?TTT?GAT?GAA?AAC????912Pro?Asn?Gly?Pro?Ile?Glu?Thr?Tyr?Leu?Phe?Ala?Met?Phe?Asp?Glu?Asn

290?????????????????295?????????????????300CAG?AAG?GGT?GGT?GCA?GAA?ACT?GAG?AAA?CAC?TTT?GGT?CTC?TTC?AGG?CCT????960Gln?Lys?Gly?Gly?Ala?Glu?Thr?Glu?Lys?His?Phe?Gly?Leu?Phe?Arg?Pro305?????????????????310?????????????????315?????????????????320GAT?AAA?TCA?CCA?AAA?TAC?CAA?CTC?AGT?TTC?AAT????????????????????????993Asp?Lys?Ser?Pro?Lys?Tyr?Gln?Leu?Ser?Phe?Asn

325 330 SEQ ID NO：15：34：：：： ( DNA ) ：CTAGAGGATC CGGTACCCCC GGGGTCGACG AGCT 34 SEQ ID NO：16：26：：：： ( DNA ) ：CGTCGACCCC GGGGGTACCG GATCCT 26 SEQ ID NO：17：44：：：： ( DNA ) ：CTAGACTTCT TTCCTCAACC TTCTTTCTTC TTATATATTC GAAC 44 SEQ ID NO：18：44：：：： ( DNA ) ：GATCGTTCGA ATATATAAGA AGAAAGAAGG TTGAGGAAAG AAGT 44 SEQ ID NO：19：30：：：： ( DNA ) ：TGGCATGCGA TGGATTTCAT CTCATCTCTT 30 SEQ ID NO：20：27：：：： ( DNA ) ：GGGAATTCAC TCCGCGAGCC GGCGAAT 27 SEQ ID NO：21：35：：：： ( DNA ) ：ACAAGTAAAA GAAAGAGCGA GAAATCATCG AAATG 35 SEQ ID NO：22：24：：：： ( DNA ) ：AGCCATGGCT CCTCCTAAAG TGAT 24 SEQ ID NO：23：21：：：： ( DNA ) ：GGCCGCGATA TCATGAATGC A 21 SEQ ID NO：24：13：：：： ( DNA ) ：TTCATGATAT CGC 13 SEQ ID NO：25：45：：：： ( DNA ) ：GGCCGCCTTC TTTCCTCAAC CTTCTTTCTT CTTATATATT CGAAC 45 SEQ ID NO：26：45：：：： ( DNA ) ：AATTGTTCGA ATATATAAGA AGAAAGAAGG TTGAGGAAAG AAGGC 45 SEQ ID NO：27：204：：：：Glu Tyr Asn Trp Glu Lys Lys Asp Ser Gly Asp Leu Leu Leu Leu Ala 1 5 10 15His Pro Leu His Val Gln Leu Leu Arg Asn Gly Asp Asn Asp Val Lys

20??????????????????25??????????????????30Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly

35??????????????????40??????????????????45Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr

50??????????????????55??????????????????60Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?65??????????????????70??????????????????75??????????????????80Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr

85??????????????????90??????????????????95Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg

100?????????????????105?????????????????110Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys

115?????????????????120?????????????????125Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr

130?????????????????135?????????????????140Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile145?????????????????150?????????????????155?????????????????160Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile

165?????????????????170?????????????????175Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala

180?????????????????185?????????????????190Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys

195 200 SEQ ID NO:28 sequence lengths: 612 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA sequence description: GAA TAT AAC TGG GAG AAG AAA GAT TCA GGG GAT TTG CTA CTC TTG GCT 48Glu Tyr Asn Trp Glu Lys Lys Asp Ser Gly Asp Leu Leu Leu Leu Ala 15 10 15CAC CCT CTC CAT GTT CAG CTT CTT CGT AAT GGA GAC AAT GAT GTC AAA 96His Pro Leu His Val Gln Leu Leu Arg Asn Gly Asp Asn Asp Val Lys

20??????????????????25??????????????????30ATT?CTT?GAA?GAT?TTA?AAG?TAT?AAA?AGC?ATT?GAT?GGG?GAT?CTT?GTT?GGT????144Ile?Leu?Glu?Asp?Leu?Lys?Tyr?Lys?Ser?Ile?Asp?Gly?Asp?Leu?Val?Gly

35??????????????????40??????????????????45GTT?GTC?GGG?GAT?TCA?TGG?GTT?TTG?AAA?ACA?GAT?CCT?TTG?TTT?GTA?ACA????192Val?Val?Gly?Asp?Ser?Trp?Val?Leu?Lys?Thr?Asp?Pro?Leu?Phe?Val?Thr

50??????????????????55??????????????????60TGG?CAT?TCA?ATC?AAG?GGA?ATC?AAA?GAA?GAA?TCC?CAT?GAT?GAG?ATT?GTC????240Trp?His?Ser?Ile?Lys?Gly?Ile?Lys?Glu?Glu?Ser?His?Asp?Glu?Ile?Val?65??????????????????70??????????????????75??????????????????80TCA?GCC?CTT?TCT?AAA?GAT?GTT?GAG?AGC?CTA?GAT?TCA?TCA?TCA?ATA?ACT????288Ser?Ala?Leu?Ser?Lys?Asp?Val?Glu?Ser?Leu?Asp?Ser?Ser?Ser?Ile?Thr

85??????????????????90??????????????????95ACA?ACA?GAG?TCA?TAT?TTT?TAT?GGG?AAG?TTG?ATT?GCA?AGG?GCT?GCA?AGG????336Thr?Thr?Glu?Ser?Tyr?Phe?Tyr?Gly?Lys?Leu?Ile?Ala?Arg?Ala?Ala?Arg

100?????????????????105?????????????????110TTG?GTA?TTG?ATT?GCT?GAG?GAG?TTG?AAC?TAC?CCT?GAT?GTG?ATT?CCA?AAG????384Leu?Val?Leu?Ile?Ala?Glu?Glu?Leu?Asn?Tyr?Pro?Asp?Val?Ile?Pro?Lys

115?????????????????120?????????????????125GTT?AGG?AAT?TTT?TTG?AAA?GAA?ACC?ATT?GAG?CCA?TGG?TTG?GAG?GGA?ACT????432Val?Arg?Asn?Phe?Leu?Lys?Glu?Thr?Ile?Glu?Pro?Trp?Leu?Glu?Gly?Thr

130?????????????????135?????????????????140TTT?AGT?GGG?AAT?GGA?TTC?CTA?CAT?GAT?GAA?AAA?TGG?GGT?GGC?ATT?ATT????480Phe?Ser?Gly?Asn?Gly?Phe?Leu?His?Asp?Glu?Lys?Trp?Gly?Gly?Ile?Ile145?????????????????150?????????????????155?????????????????160ACC?CAA?AAG?GGG?TCC?ACT?GAT?GCT?GGT?GGT?GAT?TTT?GGA?TTT?GGA?ATT????528Thr?Gln?Lys?Gly?Ser?Thr?Asp?Ala?Gly?Gly?Asp?Phe?Gly?Phe?Gly?Ile

165?????????????????170?????????????????175TAC?AAT?GAT?CAC?CAC?TAT?CAT?TTG?GGG?TAC?TTC?ATT?TAT?GGA?ATT?GCG????576Tyr?Asn?Asp?His?His?Tyr?His?Leu?Gly?Tyr?Phe?Ile?Tyr?Gly?Ile?Ala

180?????????????????185?????????????????190GTG?CTC?ACT?AAG?CTT?GAT?CCA?GCA?TGG?GGT?AGG?AAG????????????????????612Val?Leu?Thr?Lys?Leu?Asp?Pro?Ala?Trp?Gly?Arg?Lys

195 200 SEQ ID NO:29 sequence lengths: 1080 sequence types: nucleic acid chain: double-stranded topology: linear molecule type: cDNA to mRNA sequence description: ATG GAT TTC ATC TCA TCT CTT ATC GTT GGC TGT GCT CAG GTG TTG TGT 48Met Asp Phe Ile Ser Ser Leu Ile Val Gly Cys Ala Gln Val Leu Cys 15 10 15GAA TCT ATG AAT ATG GCG GAG AGA AGA GGA CAT AAG ACT GAT CTT AGA 96Glu Ser Met Asn Met Ala Glu Arg Arg Gly His Lys Thr Asp Leu Arg

20??????????????????25??????????????????30CAA?GCC?ATC?ACT?GAT?CTT?GAA?ACA?GCC?ATC?GGT?GAC?TTG?AAG?GCC?ATA????144Gln?Ala?Ile?Thr?Asp?Leu?Glu?Thr?Ala?Ile?Gly?Asp?Leu?Lys?Ala?Ile

35??????????????????40??????????????????45CGT?GAT?GAC?CTG?ACT?TTA?CGG?ATC?CAA?CAA?GAC?GGT?CTA?GAG?GGA?CGA????192Arg?Asp?Asp?Leu?Thr?Leu?Arg?Ile?Gln?Gln?Asp?Gly?Leu?Glu?Gly?Arg

50??????????????????55??????????????????60AGC?TGC?TCA?AAT?CGT?GCC?AGA?GAG?TGG?CTT?AGT?GCG?GTG?CAA?GTA?ACG????240Ser?Cys?Ser?Asn?Arg?Ala?Arg?Glu?Trp?Leu?Ser?Ala?Val?Gln?Val?Thr?65??????????????????70??????????????????75??????????????????80GAG?ACT?AAA?ACA?GCC?CTA?CTT?TTA?GTG?AGG?TTT?AGG?CGT?CGG?GAA?CAG????288Glu?Thr?Lys?Thr?Ala?Leu?Leu?Leu?Val?Arg?Phe?Arg?Arg?Arg?Glu?Gln

85??????????????????90??????????????????95AGG?ACG?CGA?ATG?AGG?AGG?AGA?TAC?CTC?AGT?TGT?TTC?GGT?TGT?GCC?GAC????336Arg?Thr?Arg?Met?Arg?Arg?Arg?Tyr?Leu?Ser?Cys?Phe?Gly?Cys?Ala?Asp

100?????????????????105?????????????????110TAC?AAA?CTG?TGC?AAG?AAG?GTT?TCT?GCC?ATA?TTG?AAG?AGC?ATT?GGT?GAG????384Tyr?Lys?Leu?Cys?Lys?Lys?Val?Ser?Ala?Ile?Leu?Lys?Ser?Ile?Gly?Glu

115??????????????????120?????????????????125CTG?AGA?GAA?CGC?TCT?GAA?GCT?ATC?AAA?ACA?GAT?GGC?GGG?TCA?ATT?CAA????432Leu?Arg?Glu?Arg?Ser?Glu?Ala?Ile?Lys?Thr?Asp?Gly?Gly?Ser?Ile?Gln

130?????????????????135?????????????????140GTA?ACT?TGT?AGA?GAG?ATA?CCC?ATC?AAG?TCC?GTT?GTC?GGA?AAT?ACC?ACG????480Val?Thr?Cys?Arg?Glu?Ile?Pro?Ile?Lys?Ser?Val?Val?Gly?Asn?Thr?Thr145?????????????????150?????????????????155?????????????????160ATG?ATG?GAA?CAG?GTT?TTG?GAA?TTT?CTC?AGT?GAA?GAA?GAA?GAA?AGA?GGA????528Met?Met?Glu?Gln?Val?Leu?Glu?Phe?Leu?Ser?Glu?Glu?Glu?Glu?Arg?Gly

165?????????????????170?????????????????175ATC?ATT?GGT?GTT?TAT?GGA?CCT?GGT?GGG?GTT?GGG?AAG?ACA?ACG?TTA?ATG????576Ile?Ile?Gly?Val?Tyr?Gly?Pro?Gly?Gly?Val?Gly?Lys?Thr?Thr?Leu?Met

180?????????????????185?????????????????190CAG?AGC?ATT?AAC?AAC?GAG?CTG?ATC?ACA?AAA?GGA?CAT?CAG?TAT?GAT?GTA????624Gln?Ser?Ile?Asn?Asn?Glu?Leu?Ile?Thr?Lys?Gly?His?Gln?Tyr?Asp?Val

195?????????????????200?????????????????205CTG?ATT?TGG?GTT?CAA?ATG?TCC?AGA?GAA?TTC?GGC?GAG?TGT?ACA?ATT?CAG????672Leu?Ile?Trp?Val?Gln?Met?Ser?Arg?Glu?Phe?Gly?Glu?Cys?Thr?Ile?Gln

210?????????????????215?????????????????220CAA?GCC?GTT?GGA?GCA?CGG?TTG?GGT?TTA?TCT?TGG?GAC?GAG?AAG?GAG?ACC????720Gln?Ala?Val?Gly?Ala?Arg?Leu?Gly?Leu?Ser?Trp?Asp?Glu?Lys?Glu?Thr225?????????????????230?????????????????235?????????????????240GGC?GAA?AAC?AGA?GCT?TTG?AAG?ATA?TAC?AGA?GCT?TTG?AGA?CAG?AAA?CGT????768Gly?Glu?Asn?Arg?Ala?Leu?Lys?Ile?Tyr?Arg?Ala?Leu?Arg?Gln?Lys?Arg

245?????????????????250?????????????????255TTC?TTG?TTG?TTG?CTA?GAT?GAT?GTC?TGG?GAA?GAG?ATA?GAC?TTG?GAG?AAA????816Phe?Leu?Leu?Leu?Leu?Asp?Asp?Val?Trp?Glu?Glu?Ile?Asp?Leu?Glu?Lys

260?????????????????265?????????????????270ACT?GGA?GTT?CCT?CGA?CCT?GAC?AGG?GAA?AAC?AAA?TGC?AAG?GTG?ATG?TTC????864Thr?Gly?Val?Pro?Arg?Pro?Asp?Arg?Glu?Asn?Lys?Cys?Lys?Val?Met?Phe

275?????????????????280?????????????????285ACG?ACA?CGG?TCT?ATA?GCA?TTA?TGC?AAC?AAT?ATG?GGT?GCG?GAA?TAC?AAG????912Thr?Thr?Arg?Ser?Ile?Ala?Leu?Cys?Asn?Asn?Met?Gly?Ala?Glu?Tyr?Lys

290?????????????????295?????????????????300TTG?AGA?GTG?GAG?TTT?CTG?GAG?AAG?AAA?CAC?GCG?TGG?GAG?CTG?TTC?TGT????960Leu?Arg?Val?Glu?Phe?Leu?Glu?Lys?Lys?His?Ala?Trp?Glu?Leu?Phe?Cys305?????????????????310?????????????????315?????????????????320AGT?AAG?GTA?TGG?AGA?AAA?GAT?CTT?TTA?GAG?TCA?TCA?TCA?ATT?CGC?CGG???1008Ser?Lys?Val?Trp?Arg?Lys?Asp?Leu?Leu?Glu?Ser?Ser?Ser?Ile?Arg?Arg

325?????????????????330?????????????????335CTC?GCG?GAG?ATT?ATA?GTG?AGT?AAA?TGT?GGA?GGA?TTG?CCA?CTA?GCG?TTG???1056Leu?Ala?Glu?Ile?Ile?Val?Ser?Lys?Cys?Gly?Gly?Leu?Pro?Leu?Ala?Leu

340?????????????????345?????????????????350ATC?ACT?TTA?GGA?GGA?GCC?ATG?GCT???????????????????????????????????1080Ile?Thr?Leu?Gly?Gly?Ala?Met?Ala

355?????????????????360

Claims (13)

1. the DNA of coding chimeric protein, described chimeric protein comprises the structural domain of an inducer binding site that contains at least one inducer acceptor and the structural domain of a proteic signal transduction motif that contains at least one conferring disease resistance in plants.

2. the DNA of claim 1, wherein said inducer be dextran, polygalacturonic acid, N-acetyl oligochitosan, bring out element, derive from the Avr gene product of yellow branch spore or derive from the nipl gene product of rye beak spore.

3. the DNA of claim 1, wherein said inducer binding site comprises following recombinant protein (a) or recombinant protein (b):

(a) comprise the albumen of the aminoacid sequence shown in the SEQ ID NO:27

(b) comprise aminoacid sequence, disappearance, displacement, the increase shown in the SEQ ID NO:27 or insert at least one amino acid whose albumen, described albumen can combine with the dextran inducer.

4. each DNA in the claim 1 to 3, the structural domain that wherein contains the signal transduction motif comprises at least one and is selected from following motif: be rich in leucic tumor-necrosis factor glycoproteins, leucine zipper, nucleotide binding site and serine/threonine kinase territory.

5. each DNA in the claim 1 to 4, the structural domain that wherein contains the signal transduction motif are the signal transduction territories of Pto, the Prf, Cf-2 or the Cf-9 expression of gene product that derive from tomato; Derive from the signal transduction territory of the Xa21 expression of gene product of paddy rice; Derive from the signal transduction territory of the RPS2 gene or the RPM1 expression of gene product of Arabidopis thaliana; Derive from the signal transduction territory of the L6 expression of gene product of flax; Or derive from the signal transduction territory of the N expression of gene product of tobacco.

6. the DNA of claim 5, wherein the RPS2 gene comprises the nucleotide sequence that is shown among the SEQ ID NO:29.

7. the DNA of coding following albumen (c) or albumen (d):

(c) contain the chimeric protein that is shown in the aminoacid sequence among the SEQ ID NO:5,7 or 9;

(d) contain and be shown in aminoacid sequence, disappearance, displacement, the increase among the SEQ ID NO:5,7 or 9 or insert at least one amino acid whose chimeric protein, described albumen conferring disease resistance in plants.

8. the DNA of chimeric protein of coding conferring disease resistance in plants, described DNA contains the nucleotide sequence that is shown among the SEQ ID NO:6,8 or 10.

9. the recombinant vectors that contains each DNA in the claim 1 to 8.

10. conversion plant that transforms with the recombinant vectors of claim 9 or the offspring of described plant.

11. produce the method for disease resistance plant, comprise that the recombinant vectors with claim 9 is transferred in the plant.

12. have the offspring of the plant or the described plant of disease resistance of plant, described plant has been transferred in the claim 1 to 8 each DNA and has expressed described DNA.

13. produce the offspring's of plant with disease resistance of plant or described plant method, comprise being integrated into each DNA in the claim 1 to 8 in the plant chromosome and expressing described DNA.

Images